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Nov.14.2022

Levonorgestrel

Indications/Dosage

Labeled

  • contraception
  • menorrhagia
  • postcoital contraception

Off-Label

  • endometriosis
† Off-label indication

For routine contraception

Intrauterine dosage (Mirena IUD only)

Adults and Adolescents

Insert 1 IUD into the uterus as per device instructions. IUD delivers 21 mcg/day of levonorgestrel; the rate is reduced to about 11 mcg/day after 5 years and 7 mcg/day after 8 years. Provides efficacy for up to 8 years, then remove and replace. Never reinsert a removed system. Wait at least 6-weeks postpartum or until uterine involution occurs before inserting the IUD.[48254]

Intrauterine dosage (Skyla IUD only)

Adults and Adolescents

Insert 1 IUD into the uterus as per device instructions. IUD delivers approximately 14 mcg/day of levonorgestrel after 24 days. This rate decreases progressively to approximately 6 mcg/day after 1 year and to 5 mcg/day after 3 years. The average in vivo release rate of LNG is approximately 8 mcg/day over the first year of use and 6 mcg/day over a period of 3 years. Remove device at the end of third year, replace with new device if continued contraception is desired. Wait at least 6-weeks postpartum or until uterine involution occurs before inserting the IUD.[52878]

Intrauterine dosage (Liletta IUD only)

Adults and Adolescents

Insert 1 IUD into the uterus as per device instructions. IUD delivers approximately 20 mcg/day of levonorgestrel over a period of 8 years. Remove device at the end of eighth year, replace with new device if continued contraception is desired. Wait at least 4-weeks postpartum or until uterine involution occurs before inserting the IUD.[58928]

Intrauterine dosage (Kyleena IUD only)

Adults and Adolescents

Insert 1 IUD into the uterus as per device instructions. IUD delivers approximately 9 mcg/day of levonorgestrel over a period of 5 years. Provides efficacy for up to 5 years, then remove and replace. Never reinsert a removed system. Wait at least 6-weeks postpartum or until uterine involution occurs before inserting the IUD.[61277]

For postcoital contraception after unprotected intercourse or known or suspected contraceptive failure

Oral dosage (e.g., Plan B One-Step or equivalent generic/branded-generic products, 1.5 mg levonorgestrel tablets)

Any female of child-bearing age

Give 1 tablet (1.5 mg levonorgestrel) PO as soon as possible after intercourse (no later than 72 hours after the event). Although the manufacturer states levonorgestrel should be administered no later than 72 hours, studies suggest that efficacy lasts for up to 5 days after the event.[66716] [66717] Consider repeating the dose if vomiting occurs within 2 hours of administration.[62899] The single-dose regimen is similarly effective to the 2-dose, FDA-approved regimen.[32604] NOTE: Plan B One-Step and equivalent generic brands are approved for non-prescription use in all females of childbearing potential regardless of age.[55077]

Oral dosage (e.g., Plan B or equivalent generic/branded-generic products, 0.75 mg levonorgestrel tablets)

Adult and Adolescent females

Give 1 tablet (750 mcg levonorgestrel) PO as a first dose as soon as possible after intercourse (i.e., preferably within 12 to 24 hours after the event). Although the manufacturer states levonorgestrel should be administered no later than 72 hours, studies suggest that efficacy lasts for up to 5 days after the event.[66716] [66717] MUST give a second dose 12 hours after the initial dose. If patient vomits within 1 hour of the initial (first) dose, repeat the dose. Though rare, an antiemetic may be needed, as progestin-only emergency contraception regimens induce vomiting much less than traditional Yuzpe methods. NOTE: This 2-dose regimen is FDA-approved for non-prescription (OTC) use in women 17 years of age and older. In females less than 17 years of age, the 2-dose regimen is available only as a prescription.

non-FDA approved alternative dosage regimens for emergency contraception†

Oral dosage (e.g., Plan B tablets and other levonorgestrel 0.75 mg tablets - ALTERNATIVE, non-FDA-approved regimen)†

Adult and Adolescent females

Give 1 tablet (750 mcg levonorgestrel) PO as a first dose as soon as possible after intercourse (i.e., preferably within 12 to 24 hours after the event). Although the manufacturer states levonorgestrel should be administered no later than 72 hours, studies suggest that efficacy lasts for up to 5 days after the event.[66716] [66717] MUST give a second dose 24 hours after the initial dose.[32605] [33117] If patient vomits within 1 hour of the initial (first) dose, repeat the dose. Though rare, an antiemetic may be needed. The alternative regimen goal is to increase patient compliance.[32606] Further data are needed, particularly under circumstances of repeat use. Most data come from non-U.S. based populations.[32605] [32606] [32607]

For the treatment of menorrhagia in persons who choose to use intrauterine contraception as their method of contraception

Intrauterine dosage (Mirena)

Adults

52 mg intrauterine device (IUD) inserted into the uterus. Remove and replace the IUD after 5 years if continued treatment is needed.[48254]

For the treatment of endometriosis† in females with no contraindications to hormonal contraceptives, who have achieved menarche and desire contraception

Intrauterine dosage (Mirena IUD only)

Adult and adolescent females

Follow administration as for routine contraception. Insert 1 IUD into the uterus as per device instructions. IUD delivers 20 mcg/day of levonorgestrel. Provides efficacy for up to 5 years, then remove and replace. Never reinsert a removed system. Wait at least 6-weeks postpartum or until uterine involution occurs before inserting the IUD.[48254] Guidelines state that a levonorgestrel-releasing intrauterine device (IUD) may be considered as 1 of the options to reduce endometriosis-associated pain.[57749]

Therapeutic Drug Monitoring

Maximum Dosage Limits

    Patients with Hepatic Impairment Dosing

    Routine contraception: Avoid use of the levonorgestrel intrauterine systems if significant hepatic disease is present.[48254][58928][52878][61277]

    Emergency contraception: Levonorgestrel emergency contraceptive products have not been studied in hepatic disease. Guidelines recommend that emergency contraception may be used with caution, since the limited dosing poses less risk than traditional routine contraception.[52930][55077][48201]

    Patients with Renal Impairment Dosing

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.[48254][58928][52878][61277][52930][55077][48201]

    † Off-label indication
    Revision Date: 11/14/2022, 11:22:06 AM

    References

    32604 - Cheng L, Gulmezoglu AM, Piaggio G, et al. Interventions for emergency contraception. Cochrane Database Syst Rev 2007;(2):CD001324.32605 - Ngai SW, Fan S, Li S, et al. A randomized trial to compare 24 h versus 12 h double dose regimen of levonorgestrel for emergency contraception. Hum Reprod 2005;20:307-11.32606 - von Hertzen H, Piaggio G, Ding J, et al. WHO Research Group on Post-ovulatory Methods of Fertility Regulation. Low dose mifepristone and two regimens of levonorgestrel for emergency contraception: a WHO multicentre randomised trial. Lancet 2002;360:1803-10.32607 - Arowojolu AO, Okewole IA, Adekunle AO. Comparative evaluation of the effectiveness and safety of two regimens of levonorgestrel for emergency contraception in Nigerians. Contraception 2002;66:269-73. Erratum in: Contraception 2003;67:165.33117 - Hansen LB, Saseen JJ, Teal SB. Levonorgestrel-only dosing strategies for emergency contraception. Pharmacotherapy 2007;27:278-84.48201 - US Department of Health and Human Services/Centers for Disease Control and Prevention. U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. MMWR Recomm Rep. 2016;65:1-103.48254 - Mirena (levonorgestrel-releasing intrauterine system) package insert. Wayne, NJ: Bayer HealthCare Pharmaceuticals Inc.; Aug 2022.52878 - Skyla (levonorgestrel-releasing intrauterine system) package insert. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2021 July.52930 - Plan B (levonorgestrel) package insert. Pomona, NY: Duramed Pharmaceuticals Inc.; 2017 Sept.55077 - Food and Drug Administration (US FDA) News Release. FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential. Retrieved June 21, 2013. Available on the World Wide Web at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm358082.htm.57749 - Dunselman GA, Vermeulen N, Becker C, et al. ESHRE guideline: management of women with endometriosis. Hum Reprod 2014;29:400-12.58928 - Liletta (levonorgestrel-releasing intrauterine system) package insert. Irvine, CA: Allergan USA, Inc.; Nov 2022.61277 - Kyleena (levonorgestrel-releasing intrauterine system) package insert. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; July 2021.62899 - Plan B One-Step (levonorgestrel 1.5 mg) emergency contraceptive regimen consumer product label. Teva Women’s Health, Inc. 2022 Dec.66716 - Committee on Practice Bulletins-Gynecology Practice bulletin no 152:emergency contraception Obstet Gynecol 2015;126(3):1– 1166717 - Center for Disease Control and Prevention website Emergency contraception Updated November 2, 2018 Accessed June 7, 2021 https://www.cdc.gov/reproductivehealth/contraception/mmwr/spr/emergency.html

    How Supplied

    Levonorgestrel Implant

    Norplant System Kit Intradermal Implant (00008-2564) (Wyeth Pharmaceuticals Inc, a subsidiary of Pfizer Inc) (off market)

    Levonorgestrel Oral tablet [Emergency Contraception]

    Levonorgestrel 0.75mg Tablet (45802-0840) (Perrigo Pharmaceuticals Company) (off market)Levonorgestrel 0.75mg Tablet package photo

    Levonorgestrel Oral tablet [Emergency Contraception]

    Next Choice 0.75mg Tablet (52544-0475) (Teva/Actavis US) (off market)

    Levonorgestrel Oral tablet [Emergency Contraception]

    Next Choice 0.75mg Tablet (52544-0275) (Teva/Actavis US) (off market)Next Choice 0.75mg Tablet package photo

    Levonorgestrel Oral tablet [Emergency Contraception]

    Plan B 0.75mg Tablet (51285-0038) (Teva Pharmaceuticals USA) nullPlan B 0.75mg Tablet package photo

    Levonorgestrel Oral tablet [Emergency Contraception]

    Plan B 0.75mg Tablet (51285-0769) (Teva Pharmaceuticals USA) nullPlan B 0.75mg Tablet package photo

    Levonorgestrel Oral tablet [Emergency Contraception]

    Plan B 0.75mg Tablet (64836-0000) (Womens Capital Corp) (off market)Plan B 0.75mg Tablet package photo

    Levonorgestrel Oral tablet [Emergency Contraception]

    Plan B 0.75mg Tablet Clinic Pack (51285-0038) (Teva Pharmaceuticals USA) null

    Levonorgestrel Oral tablet [Emergency Contraception]

    AfterPill 1.5mg Tablet (null) (Syzygy Healthcare Solutions LLC) null

    Levonorgestrel Oral tablet [Emergency Contraception]

    AfterPill 1.5mg Tablet (null) (Syzygy Healthcare Solutions LLC) null

    Levonorgestrel Oral tablet [Emergency Contraception]

    EContra EZ 1.5mg Tablet (50102-0111) (Afaxys, Inc. ) null

    Levonorgestrel Oral tablet [Emergency Contraception]

    EContra One-Step 1.5mg Tablet (50102-0211) (Afaxys, Inc. ) nullEContra One-Step 1.5mg Tablet package photo

    Levonorgestrel Oral tablet [Emergency Contraception]

    Fallback Solo 1.5mg Tablet (68180-0853) (Lupin Pharmaceuticals, Inc.) (off market)

    Levonorgestrel Oral tablet [Emergency Contraception]

    Her Style 1.5mg Tablet (50742-0352) (Ingenus Pharmaceuticals, LLC) null

    Levonorgestrel Oral tablet [Emergency Contraception]

    Levonorgestrel 1.5mg Tablet (73358-0911) (Curae Pharma360 Inc.) null

    Levonorgestrel Oral tablet [Emergency Contraception]

    Levonorgestrel 1.5mg Tablet (68462-0123) (Glenmark Pharmaceuticals) (off market)

    Levonorgestrel Oral tablet [Emergency Contraception]

    Levonorgestrel 1.5mg Tablet (63704-0009) (Pharmacist Pharmacy) (off market)

    Levonorgestrel Oral tablet [Emergency Contraception]

    Levonorgestrel 1.5mg Tablet (63704-0010) (Pharmacist Pharmacy) null

    Levonorgestrel Oral tablet [Emergency Contraception]

    Levonorgestrel 1.5mg Tablet (00536-1142) (Rugby Laboratories a Division of The Harvard Drug Group, LLC) nullLevonorgestrel 1.5mg Tablet package photo

    Levonorgestrel Oral tablet [Emergency Contraception]

    Levonorgestrel 1.5mg Tablet (70700-0164) (Xiromed LLC a Division of the Chemo Group) null

    Levonorgestrel Oral tablet [Emergency Contraception]

    My Choice 1.5mg Tablet (62756-0720) (Sun Pharmaceutical Industries, Inc.) nullMy Choice 1.5mg Tablet package photo

    Levonorgestrel Oral tablet [Emergency Contraception]

    My Way 1.5mg Tablet (43386-0622) (Gavis Pharmaceuticals, LLC, wholly owned subsidiary of Lupin) (off market)

    Levonorgestrel Oral tablet [Emergency Contraception]

    My Way 1.5mg Tablet (43386-0620) (Gavis Pharmaceuticals, LLC, wholly owned subsidiary of Lupin) (off market)

    Levonorgestrel Oral tablet [Emergency Contraception]

    My Way 1.5mg Tablet (68180-0852) (Lupin Pharmaceuticals, Inc.) null

    Levonorgestrel Oral tablet [Emergency Contraception]

    New Day 1.5mg Tablet (16714-0809) (NorthStar Rx LLC) null

    Levonorgestrel Oral tablet [Emergency Contraception]

    Next Choice One Dose 1.5mg Tablet (52544-0287) (Teva/Actavis US) (off market)Next Choice One Dose 1.5mg Tablet package photo

    Levonorgestrel Oral tablet [Emergency Contraception]

    Next Choice One Dose 1.5mg Tablet (52544-0065) (Teva/Actavis US) (off market)Next Choice One Dose 1.5mg Tablet package photo

    Levonorgestrel Oral tablet [Emergency Contraception]

    Opcicon One-Step 1.5mg Tablet (62756-0718) (Sun Pharmaceutical Industries, Inc.) null

    Levonorgestrel Oral tablet [Emergency Contraception]

    Plan B One-Step 1.5mg Tablet (69536-0146) (Foundation Consumer Healthcare, LLC) null

    Levonorgestrel Oral tablet [Emergency Contraception]

    Plan B One-Step 1.5mg Tablet (51285-0088) (Teva Pharmaceuticals USA) (off market)

    Levonorgestrel Oral tablet [Emergency Contraception]

    Plan B One-Step 1.5mg Tablet (51285-0943) (Teva Women's Health, Inc.) null

    Levonorgestrel Oral tablet [Emergency Contraception]

    Plan B One-Step 1.5mg Tablet (51285-0942) (Teva Women's Health, Inc.) nullPlan B One-Step 1.5mg Tablet package photo

    Levonorgestrel Oral tablet [Emergency Contraception]

    Plan B One-Step 1.5mg Tablet (51285-0162) (Teva Women's Health, Inc.) nullPlan B One-Step 1.5mg Tablet package photo

    Levonorgestrel Oral tablet [Emergency Contraception]

    Plan B One-Step 1.5mg Tablet Clinic Pack (51285-0146) (Teva Women's Health, Inc.) null

    Levonorgestrel Oral tablet [Emergency Contraception]

    Preventeza 1.5mg Tablet (11509-0067) (Combe Inc) null

    Levonorgestrel Oral tablet [Emergency Contraception]

    React 1.5mg Tablet (64679-0050) (Wockhardt USA, LLC) null

    Levonorgestrel Oral tablet [Emergency Contraception]

    Take Action 1.5mg Tablet (51285-0100) (Teva Women's Health, Inc.) null

    Levonorgestrel Vaginal insert

    Skyla Intrauterine System (50419-0422) (Bayer HealthCare Pharmaceuticals) null

    Levonorgestrel Vaginal insert

    Kyleena Intrauterine Device (50419-0424) (Bayer HealthCare Pharmaceuticals) null

    Levonorgestrel Vaginal insert

    Liletta Intrauterine Device (52544-0035) (Allergan USA, Inc.) (off market)

    Levonorgestrel Vaginal insert

    Liletta Intrauterine Device (00023-5858) (Allergan USA, Inc.) nullLiletta Intrauterine Device package photo

    Levonorgestrel Vaginal insert

    Mirena Intrauterine Device (50419-0421) (Bayer HealthCare Pharmaceuticals) null

    Levonorgestrel Vaginal insert

    Mirena Intrauterine Device (50419-0423) (Bayer HealthCare Pharmaceuticals) null

    Levonorgestrel Vaginal insert

    Mirena Intrauterine Device (50419-0421) (Berlex Laboratories Inc) (off market)

    Description/Classification

    Description

    Levonorgestrel is a synthetic progestin. Levonorgestrel is used for the routine prevention of pregnancy as various intrauterine devices (IUDs) such as Mirena, Skyla, Liletta, and Kyleena. Each IUD brand has different durations of use. The Mirena IUD is indicated for contraception for up to 8 years of use; Mirena is additionally used for the treatment of menorrhagia for up to 5 years in women additionally desiring an IUD for contraception.[48254] The Liletta IUD is indicated for up to 8 years of use.[58928] The Kyleena IUD releases a low amount of levonorgestrel continuously over a 5-year period.[61277] The Skyla IUD is indicated for up to 3 years of use.[52878] Levonorgestrel is also commonly used as an emergency post-coital oral contraceptive (Plan B, Plan B One-Step, and others). A 2-dose levonorgestrel-only emergency oral contraceptive regimen (e.g., Plan-B, others) is available non-prescription (OTC) for women age 17 years and older, is very effective at preventing pregnancy when ingested within 72 hours of unprotected sex. The regimen causes less post-dose nausea than oral combination estrogen-progestin postcoital (Yuzpe) regimens.[52930] Plan B One-Step (a 1 tablet, single-dose emergency oral contraceptive), is approved for non-prescription (OTC) use in all females of childbearing potential regardless of age; many other marketed products are available besides this brand.[55077] A levonorgestrel implantable device (Norplant) was used historically for continuous routine contraception, but is no longer marketed.

    Classifications

    • Genito-urinary System and Sex Hormones
      • Other Gynecologicals
        • Intrauterine devices
          • Progestogen containing intrauterine devices
      • Sex Hormones and Modulators of the Genital System
        • Hormonal Contraceptives
          • Emergency Contraceptives and Abortifacients
          • Progestogen Only Contraceptives
        • Progestogens
    Revision Date: 11/14/2022, 04:24:12 PM

    References

    48254 - Mirena (levonorgestrel-releasing intrauterine system) package insert. Wayne, NJ: Bayer HealthCare Pharmaceuticals Inc.; Aug 2022.52878 - Skyla (levonorgestrel-releasing intrauterine system) package insert. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2021 July.52930 - Plan B (levonorgestrel) package insert. Pomona, NY: Duramed Pharmaceuticals Inc.; 2017 Sept.55077 - Food and Drug Administration (US FDA) News Release. FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential. Retrieved June 21, 2013. Available on the World Wide Web at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm358082.htm.58928 - Liletta (levonorgestrel-releasing intrauterine system) package insert. Irvine, CA: Allergan USA, Inc.; Nov 2022.61277 - Kyleena (levonorgestrel-releasing intrauterine system) package insert. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; July 2021.

    Administration Information

    General Administration Information

    For storage information, see the specific product information within the How Supplied section.

    Hazardous Drugs Classification

    • NIOSH 2016 List: Group 2 [63664]
    • NIOSH (Draft) 2020 List: Table 2
    • Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
    • ORAL TABLETS/CAPSULES/ORAL LIQUID: Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure and require additional protective equipment. Eye/face and respiratory protection may be needed during preparation and administration.
    • TOPICAL/TRANSDERMAL/VAGINAL: Use double chemotherapy gloves and protective gown. Eye/face and respiratory protection may be needed during preparation and administration.[63664][67506][67507]

    Route-Specific Administration

    Oral Administration

    • For emergency contraception, administer as soon as possible within the 72 to 120 hours (3 to 5 days) following unprotected intercourse. Although FDA-approved for up to 72 hours, data have demonstrated efficacy for up to 5 days after unprotected intercourse.[66716][66717]
    • Follow the directions of the product label for the specific product chosen.
    • If a patient vomits within 2 hours after taking a dose of the medication, they should call their health care professional to see if they need to repeat a dose.[52930][62899]

    Other Administration Route(s)

    Intrauterine device (IUD) Administration (Kyleena, Liletta, Mirena, Skyla)

    • IUD is for insertion into the uterus and should only be administered by physicians specifically trained in administering levonorgestrel by this route.
    • The expiration date of the IUD should be verified prior to insertion of the IUD.
    • Follow all instructions for the specific IUD device regarding preparation of the device prior to insertion and insertion technique.
    • Timing of IUD insertion based on clinical status:
      • Starting the IUD in patients not currently using hormonal or intrauterine contraception: The IUD system can be inserted any time the provider can be reasonably certain the patient is not pregnant. Consider the possibility of ovulation and conception prior to initiation of this product. If the IUD is inserted during the first 7 days of the menstrual cycle or immediately after first-trimester abortion, back up contraception is not needed. If the IUD is not inserted during the first 7 days of the menstrual cycle, the patient should use a barrier method of contraception or should abstain from vaginal intercourse for 7 days to prevent pregnancy.
      • Switching to the IUD from an oral, transdermal, or vaginal hormonal contraceptive: The IUD may be inserted at any time, including during the hormone-free interval of the previous method. If inserted during active use of the previous method, continue that method for 7 days after the IUD insertion or until the end of the current treatment cycle. If the patient was using continuous hormonal contraception, discontinue that method 7 days after IUD insertion.
      • Switching to the IUD from an injectable progestin contraceptive: The IUD may be inserted at any time; a back-up method of contraception (such as condoms or spermicide) should also be used for 7 days if IUD is inserted more than 3 months (13 weeks) after the last injection.
      • Switching to the IUD from a contraceptive implant or use of another IUD: Insert the IUD on the same day the implant or IUD is removed.
      • Inserting the IUD after abortion, miscarriage, childbirth, or postpartum following the complete involution of the uterus: Review the manufacturer recommendations regarding timing of insertion and the need for a back-up method of contraception.
    • The retrieval threads should be visible after insertion.
    • Placement can be checked with ultrasound.
    • Patients should be reexamined and evaluated 4 to 12 weeks after insertion and once a year thereafter, or more frequently if clinically indicated.
    • The Skyla IUD should not remain in the uterus after 3 years.
    • The Kyleena IUD should not remain in the uterus after 5 years.
    • The Liletta IUD should not remain in the uterus after 8 years.
    • The Mirena IUD should not remain in the uterus after 8 years for routine contraception or after 5 years for heavy menstrual bleeding in patients who desire an IUD for birth control.
    • IUD REMOVAL: Remove the IUD by applying gentle traction on the threads with forceps. The arms of the system will fold upward as it is withdrawn from the uterus. Never reinsert a removed system. A new IUD may be inserted immediately following removal.[48254][52878][58928][61277] Removal may be associated with breakage or embedment of the IUD in the myometrium that can make removal difficult. Analgesia, paracervical anesthesia, cervical dilation, alligator forceps or other grasping instrument, or hysteroscopy may be used to assist in removal.[48254]

    Clinical Pharmaceutics Information

    From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database
      Revision Date: 11/14/2022, 11:20:41 AM

      References

      48254 - Mirena (levonorgestrel-releasing intrauterine system) package insert. Wayne, NJ: Bayer HealthCare Pharmaceuticals Inc.; Aug 2022.52878 - Skyla (levonorgestrel-releasing intrauterine system) package insert. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2021 July.52930 - Plan B (levonorgestrel) package insert. Pomona, NY: Duramed Pharmaceuticals Inc.; 2017 Sept.58928 - Liletta (levonorgestrel-releasing intrauterine system) package insert. Irvine, CA: Allergan USA, Inc.; Nov 2022.61277 - Kyleena (levonorgestrel-releasing intrauterine system) package insert. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; July 2021.62899 - Plan B One-Step (levonorgestrel 1.5 mg) emergency contraceptive regimen consumer product label. Teva Women’s Health, Inc. 2022 Dec.63664 - CDC National Institute for Occupational Safety and Health (NIOSH). NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2016. DHHS (NIOSH) Publication Number 2016-161, September 2016. Available on the World Wide Web at https://www.cdc.gov/niosh/docs/2016-161/pdfs/2016-161.pdf?id=10.26616/NIOSHPUB201616166716 - Committee on Practice Bulletins-Gynecology Practice bulletin no 152:emergency contraception Obstet Gynecol 2015;126(3):1– 1166717 - Center for Disease Control and Prevention website Emergency contraception Updated November 2, 2018 Accessed June 7, 2021 https://www.cdc.gov/reproductivehealth/contraception/mmwr/spr/emergency.html67506 - American Society of Health-System Pharmacists. ASHP guidelines on handling hazardous drugs. Am J Health-Syst Pharm. 2018; 75:1996-2031.67507 - NIOSH [2016]. NIOSH Alert: Preventing Occupational Exposures to Antineoplastics and Other Hazardous Drugs in Health Care Settings. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2016-161.

      Adverse Reactions

      Mild

      • abdominal pain
      • acne vulgaris
      • alopecia
      • amenorrhea
      • anxiety
      • back pain
      • breakthrough bleeding
      • chills
      • dizziness
      • dysmenorrhea
      • emotional lability
      • fatigue
      • fever
      • headache
      • hirsutism
      • infection
      • leukorrhea
      • libido decrease
      • mastalgia
      • menorrhagia
      • menstrual irregularity
      • nausea
      • oligomenorrhea
      • pelvic pain
      • rash
      • seborrhea
      • syncope
      • urticaria
      • vaginal discharge
      • vomiting
      • weight gain

      Moderate

      • anemia
      • cholestasis
      • depression
      • dyspareunia
      • fluid retention
      • hyperglycemia
      • hypertension
      • jaundice
      • migraine
      • ovarian enlargement
      • uterine contractions
      • vaginitis

      Severe

      • angioedema
      • bradycardia
      • ectopic pregnancy
      • endometritis
      • hepatoma
      • myocardial infarction
      • pulmonary embolism
      • retinal thrombosis
      • stroke
      • thromboembolism
      • thrombosis
      • uterine perforation
      • visual impairment

      Common adverse reactions associated with levonorgestrel used orally as an emergency contraceptive (e.g., Plan-B) are usually self-limited to the treatment period. Nausea occurs in 13% to 23% and vomiting in 5.6% of patients versus 51% and 19%, respectively, of those who take estrogen-progestin oral emergency contraceptives (e.g., the Yuzpe methods). Other common side effects include abdominal pain (13% to 18%), fatigue (13% to 17%), and dizziness (9% to 11%). Serious side effects are not common.[33117] [52930] In Mirena levonorgestrel intrauterine device (IUD) trials, adverse events reported in Mirena users included abdominal pain (5%), nausea (5%), and vomiting (less than 5%). Weight gain was reported in 9% of Mirena users in a study of women who have used Mirena for more than 5 years; it is unknown if the weight gain was attributed to Mirena use.[48254] In Skyla levonorgestrel IUD trials, abdominal pain (18.9%) and nausea (5.5%) were reported.[52878] In Liletta levonorgestrel IUD trials, nausea or vomiting (10.5%), abdominal discomfort or pain (10%), and weight gain (6.1%) were reported.[58928] In Kyleena levonorgestrel IUD trials, abdominal pain was reported in 13.3 to 21% of patients and was the cause for study discontinuation in 4.2% of patients. Nausea was reported in 4.7% of Kyleena IUD users.[61277] Any patient using a levonorgestrel IUD should report continued or severe pelvic or abdominal pain or nausea/vomiting, as these may be symptoms of pregnancy, infectious processes, device embedment, or a cyst that may need medical evaluation or treatment.

      Because levonorgestrel in the intrauterine device (IUD) system is released just within the uterus, very few systemic side effects are expected to occur. Serious, but rare, adverse events associated with the device include IUD system embedment causing cervical or uterine perforation. The incidence of uterine perforation during clinical trials of the various levonorgestrel IUDs, which excluded breast-feeding women, was less than 0.1%.[48254] [52878] [58928] [61277] Data from a large postmarketing safety study suggest an increased risk of uterine perforation in lactating women; the incidence of uterine perforation was reported as 6.3 per 1,000 insertions for lactating women, compared to 1 per 1,000 insertions for non-lactating women.[61655] [61656] In a large retrospective cohort study, women who were breast-feeding at the time of IUD insertion were at a 33% higher risk of uterine perforation compared to women who were not breast-feeding at the time of insertion. The risk of perforation was highest with IUD insertion in the period up to 6 weeks postpartum. Progressively lower risk of uterine perforation was observed in the postpartum insertion time window beyond 6 weeks.[48254] [52878] [61277] The risk may be increased if an IUD is inserted when the uterus is fixed retroverted or not completely involuted. Most manufacturers recommend waiting a minimum of 6 weeks postpartum for uterine involution to minimize the risk; some experts state anytime 4 weeks or more postpartum may be acceptable but specific device recommendations should be consulted.[48201] [48254] [52878] [58928] [61277] Penetration of the uterine wall or cervix may also occur during any IUD insertion procedure, although the perforation may not be detected immediately. If embedment occurs, the IUD should be removed as contraceptive efficacy is decreased; surgery may be required. If perforation occurs, pregnancy may occur; the IUD must be removed as soon as possible and surgery may be required. Delayed identification of uterine perforation may lead to migration of the IUD outside of the uterine cavity, adhesions, peritonitis, intestinal perforations, intestinal obstruction, and abscesses and erosion of adjacent viscera. Device breakage has also been reported during postmarketing experience with the various levonorgestrel IUDs and requires removal of the broken device.[48254] [52878] [58928] [61277] There is also a risk for IUD expulsion during use. Partial or complete expulsion of a levonorgestrel IUD may occur, resulting in the loss of contraceptive protection. IUD expulsion may be associated with symptoms of bleeding or pain, or it may be asymptomatic and go unnoticed. An increase in menstrual blood flow during use of a levonorgestrel IUD may also be indicative of device expulsion, since the levonorgestrel IUDs typically cause menstrual bleeding to decrease over time after insertion. Consider further diagnostic imaging, such as x-ray, if IUD expulsion is suspected based on ultrasound. If IUD threads are not visible, consider the possibility of retraction or expulsion. In clinical trials for the Mirena levonorgestrel IUD, a 4.5% expulsion rate was reported over the 5-year study duration. In clinical trials for Skyla levonorgestrel IUD, a 3-year expulsion rate of 3.2% (54 out of 1,665 subjects) was reported. In the clinical trial with Liletta levonorgestrel IUD, an overall expulsion rate of 4.1% was reported, with a rate of 2.4% in nulliparous women and 6.4% in parous women. In Kyleena levonorgestrel IUD trials, a 5-year expulsion rate of 3.5% (59 out of 1,690 subjects) was reported and was the cause for study discontinuation in 3.1% of patients. If expulsion occurs, levonorgestrel IUDs may be replaced any time the provider can be reasonably certain the woman is not pregnant.[48254] [52878] [58928] [61277] Data from a large postmarketing safety study suggest risk of IUD expulsion was variable over the postpartum interval through 52 weeks. Patients who were breast-feeding were at a 28% lower risk of IUD expulsion compared to those who were not breast-feeding at the time of insertion.[48254] [52878] [61277]

      In levonorgestrel intrauterine device (IUD) trials, ectopic pregnancy was reported among serious adverse reactions. The incidence of ectopic pregnancy in clinical trials with levonorgestrel IUDs was approximately 0.1% to 0.2% per year. In patients without risk factors, ectopic pregnancy is an infrequent complication of levonorgestrel IUD users (rate of 1 per 1,000 users per year). However, up to 50% of pregnancies that occur when an IUD is already in place may be ectopic. The risk of an ectopic pregnancy in women who have a history of ectopic pregnancy is not known; clinical trials excluded patients with a history of ectopic pregnancy, and use in this population is not recommended.[48254] [52878] [58928] [61277]

      Common adverse reactions associated with levonorgestrel used orally as an emergency contraceptive (e.g., Plan-B) include menstrual changes [heavier (13% to 30%) or lighter bleeding (13%)], and breast tenderness (8% to 11%). A pregnancy test is indicated if menstrual bleeding does not occur within 21 days of taking the emergency oral levonorgestrel regimen; serious side effects are not common.[52930] In Mirena levonorgestrel intrauterine device (IUD) trials, adverse events reported in 5% of Mirena users include: dysmenorrhea (6.4%); mastalgia (8.5%); leukorrhea; libido decrease. Vulvo-vaginitis was reported in 10.5%.[48254] In Skyla levonorgestrel IUD trials, common adverse reactions (occurring in at least 5% of users) included: increased menstrual bleeding or menorrhagia (7.8%); vulvo-vaginitis (20.2%); dysmenorrhea (8.6%); breast pain/discomfort (mastalgia) (8.6%).[52878] In Liletta levonorgestrel IUD trials, common reported adverse reactions (occurring in at least 5% of users) included: breast tenderness or pain (mastalgia) (10.1%) and dysmenorrhea (7.3%).[58928] Increased menstrual bleeding (menorrhagia) was reported in 8% of women using Kyleena and was the cause for discontinuation in 4.5 % of patients. Dysmenorrhea (8% to 10%) and uterine spasm (2.4% to 10%) were reported in Kyleena users and were rarely cause for discontinuation. Mastalgia (7.1% to 10%) or breast discomfort (3.5% to 10%), and vulvo-vaginitis (24%) were also reported with Kyleena.[61277] It is common/expected for levonorgestrel IUDs to alter the menstrual bleeding pattern and result in menstrual irregularity, spotting or breakthrough bleeding, heavy bleeding, oligomenorrhea, and amenorrhea. During the first 3 to 6 months of IUD use, the number of bleeding and spotting days may be increased and bleeding patterns may be irregular. After that, the number of bleeding and spotting days usually decreases, but bleeding may remain irregular. If bleeding irregularities develop during prolonged treatment, appropriate diagnostic measures should be taken to rule out endometrial pathology. Amenorrhea develops in approximately 20% of Mirena users by end of year 1. By the end of year 8, amenorrhea and infrequent bleeding occur in 34% and 26% of patients, respectively; irregular bleeding occurs in 10%, frequent bleeding in 3%, and prolonged bleeding in 3% of users.[48254] Amenorrhea develops in approximately 6% of Skyla users by the end of year 1 and 12% by the end of year 2.[52878] Amenorrhea developed in approximately 19% of Liletta users by the end of year 1, in 27% by the end of year 2, in 37% of users by the end of year 3, 37% by the end of year 4, 40% by the end of years 5 and 6, and 39% by the end of years 7 and 8.[58928] Amenorrhea developed in approximately 12% of Kyleena users by the end of year 1, in 20% by the end of year 2, and in approximately 23% of users by the end of year 5.[61277] The possibility of pregnancy should be considered if menstruation does not occur within 6 weeks of the onset of previous menstruation in a woman with any of these IUDs. Once pregnancy has been excluded, repeated pregnancy tests are generally not necessary in amenorrheic women unless indicated, for example, by other signs of pregnancy/ectopic pregnancy. A levonorgestrel IUD should be removed for menorrhagia and/or metrorrhagia that produces anemia. In levonorgestrel IUD clinical trials, adverse events reported in 5% or less of patients included anemia.[48254] [52878] [58928] [61277]

      Genital or vaginal discharge occurred in the following percentages of patients receiving the various levonorgestrel intrauterine devices (IUDs): Mirena 14.9%, Kyleena, 4.5%, Liletta 5.8%, and Skyla 4.2%. Dyspareunia was reported in less than 5% of patients (Mirena), in 9.6% of patients (Liletta), and was not specifically reported for Skyla or Kyleena but estimated at less than 1%. Pelvic pain has been reported in users of levonorgestrel IUDs in clinical trials: 22.6% for Mirena, 8.7% for Liletta, 6.2% to 18.9% for Skyla, and 8.2% to 21% for Kyleena.[48254] [52878] [58928] [61277] Uterine contractions, cramps, or spasms may occur in roughly 0.6% to 10% of levonorgestrel IUD users and are common upon device insertion; continuing uterine spasm can lead to IUD discontinuation in some patients. Abdominal pain, pelvic pain, or dyspareunia in any user of a levonorgestrel intrauterine device (IUD) may need to prompt a clinical evaluation, to exclude infectious processes (e.g., sexually transmitted disease, endometritis or pelvic inflammatory disease), ovarian cysts, pregnancy, or other serious medical issues. An odorous vaginal discharge, or discharge accompanied by other symptoms, may indicate a need to rule out an infectious process.[48254] [52878] [58928] [61277] Since the contraceptive effect of the levonorgestrel IUD is mainly due to its local effect, ovulatory cycles with follicular rupture usually occur in women of fertile age, and sometimes atresia of the follicle is delayed and the follicle may continue to grow. Enlarged follicles (which may cause ovarian enlargement due to the size of the cyst) have been diagnosed sometime during IUD use in approximately 12% of those using Mirena IUD, 14% using Skyla IUD, and 22% using Kyleena IUD, and infrequently (less than 1%) in those using Liletta IUD. Ovarian cysts were reported as adverse events in 13.2% of women using Skyla IUD if they were abnormal, non-functional cysts and/or had a diameter more than 3 cm on ultrasound examination; 0.3% of women discontinued because of an ovarian cyst.[52878] Symptomatic ovarian cysts occurred in 4.7% of participants using Liletta IUD over the course of 8 years, and 0.3% of patients discontinued use because of an ovarian cyst.[58928] Most of these follicles are asymptomatic, although some may be accompanied by dyspareunia. In most cases the enlarged follicles disappear spontaneously during the first 2 to 3 months observation. Surgical intervention is not usually required. Ovarian cysts can cause clinical symptoms including pelvic pain, abdominal pain or dyspareunia and a patient should contact her healthcare provider if she experiences these symptoms.[48254] [52878] [58928] [61277] In Liletta IUD clinical trials, vaginal bacterial infections (19.2%) and vulvovaginal mycotic infections (20.2%) were reported. Pelvic infection (0.2% to 3.5% of levonoregestrel IUD users) may occur and such upper genital tract infections may be serious. Endometritis (estimated incidence 0.2% to 2.1%) is an infection that may occur soon after IUD insertion. Severe infection or sepsis, including Group A streptococcal sepsis (GAS), have been reported immediately following insertion of levonorgestrel IUDs. In some cases, severe pelvic pain occurs within hours of insertion followed by sepsis within days. Because death from GAS is more likely if treatment is delayed, it is important to be aware of this rare but serious infection. Aseptic technique during IUD insertion is essential. Pelvic inflammatory disease (PID) has been reported with all IUD devices and the risk of subsequent infection is increased in those patients with a history of PID. The incidence of pelvic inflammatory disease is rare to infrequent, but is estimated from levonorgestrel IUD clinical trial data to be approximately 0.4% to 0.6% and most often occurs within the first year of use and often within the first month of insertion.[48254] [52878] [58928] [61277] Pelvic infections can cause tubal damage leading to ectopic pregnancy or infertility, or infrequently can necessitate hysterectomy, or cause death. Teach patients to recognize and report to their healthcare provider promptly any symptoms of pelvic infection. These symptoms include development of menstrual disorders (prolonged or heavy bleeding), unusual or odorous vaginal discharge, abdominal or pelvic pain or tenderness, dyspareunia, chills, and fever. A levonorgestrel IUD should be removed for any of the following medical reasons: AIDS or other sexually transmitted disease, pelvic infection, endometritis, genital actinomycosis, intractable pelvic or uterine pain, severe dyspareunia, or uterine or cervical perforation.[48254] [52878] [58928] [61277]

      Headache (9.8% to 17%) is a common side effect associated with levonorgestrel used orally as an emergency contraceptive (e.g., Plan-B) but is usually self-limited to the time around the treatment period.[33117] [52930] Headache and migraine are also reported in users of levonorgestrel intrauterine devices (IUDs). In Mirena IUD trials, headache/migraine was reported in 16.3% of Mirena users. In Skyla IUD trials headache was reported in 12.4%, migraine was reported in 2.3%. In Liletta IUD clinical trials, headache/migraine was reported in 10.1%. In Kyleena IUD trials headache (12.9% to 15%) and migraine (3.3% to 15%) were reported. As with all hormonal contraceptives, headache patterns may change during levonorgestrel use. Consider IUD removal if migraine headaches or exceptionally severe headaches occur, especially if the migraine is focal in nature with asymmetrical visual impairment or other symptoms that may suggest transient cerebral ischemia and risk for cerebrovascular accident (CVA).[48254] [52878] [58928] [61277]

      Fluid retention may occur in patients receiving chronic therapy with progestins, including levonorgestrel intrauterine devices (IUDs), but has not been specifically reported with use. In Mirena levonorgestrel IUD trials, increased blood pressure was reported as an adverse event in 5% of users and was reported during postmarket experience with Kyleena. During use, if marked increased blood pressure or hypertension occurs, consider IUD discontinuation.[48254] [52930] [52878] [61277] Rare cases of arterial and venous thromboembolism, including cases of pulmonary embolism, deep vein thrombosis and stroke, have occurred during postmarket use of levonorgestrel IUDs.[48254] [52930] [52878] [61277] Progestin-only contraceptives are generally the hormonal contraceptives of choice in patients with a potential risk for thrombosis when reliable contraception must be ensured and the risks of hormonal therapy are acceptable; advantages of these methods usually outweigh potential risks.[41608] When multiple thrombosis risk factors exist, the risk of thromboembolic disease may increase. The increase in the risk of thrombosis from newer progestin-only contraceptives (e.g., levonorgestrel IUD) is still substantially less than with combined oral contraceptives containing both estrogen and progestin.[41608] For women who are at an increased risk of thromboembolism and have multiple-risk factors for thrombosis (e.g., tobacco smoking woman age 35 and older, diabetes, hypercoagulopathy, severe hypertension, etc.), consider an IUD or other estrogen-free contraceptive if appropriate.[41608] A provider should be alert to the earliest manifestations of thrombotic disorder (thrombophlebitis, cerebrovascular disease, cardiac disease, myocardial infarction, pulmonary embolism, severe hypertension, stroke, valvular heart disease, and retinal thrombosis). Should any of these thrombotic-type events occur or be suspected, or if new risk factors warrant, consider removal of the levonorgestrel IUD.[48254] [52930] [52878] [61277] Patients using oral levonorgestrel are not expected to be at significant/clinical risk of thromboembolic complications due to short duration of use; the advantages of the emergency contraceptive usually outweigh any theoretical risks.[41608] [52930] [55077]

      Dermatologic and allergic reactions have been reported in levonorgestrel intrauterine device (IUD) users. Acne vulgaris was reported in 6.8% of Mirena IUD users. Less than 5% of patients receiving Mirena IUD reported hirsutism and alopecia (partial and complete).[48254] In Liletta levonorgestrel IUD trials, acne vulgaris was reported in 15.5%.[58928] In Skyla IUD trials, acne vulgaris was reported in 13.6% and seborrhea in 1.4%.[52878] In Kyleena IUD trials, acne was reported in 14.1%, seborrhea in 1.8%, and alopecia was reported in 1%. Hypersensitivity reactions, including rash (unspecified), urticaria, and angioedema have been reported during postmarketing experience with the various levonorgestrel IUDs.[48254] [52878] [58928] [61277]

      Patients receiving levonorgestrel intrauterine device (IUD) contraceptives can experience emotional lability. In Mirena IUD trials, depression or depressive mood were reported in 6.4%.[48254] In Liletta levonorgestrel IUD trials, anxiety (9.6%), depression or depressed mood (9.1%), and mood changes (6.5%) were reported. In Skyla IUD trials, depression (3.8%) and depressed mood (0.5%) were reported. In Kyleena IUD trials, depression (4.4%) and depressed mood (0.2%) were reported.[61277] Rarely serious psychiatric adverse reactions have been reported such as suicidality and exacerbations of depression and bipolar disorder.[58928]

      Syncope, bradycardia, or other neurovascular episodes may occur during insertion or removal of the levonorgestrel intrauterine device (IUD), especially in patients predisposed to these conditions or with cervical stenosis. These side effects are due to the device procedures involved and not due to the drug itself. If decreased pulse, diaphoresis, or pallor is observed, the patient should remain supine until these signs have disappeared.[48254] [52930] [58928] [61277]

      In levonorgestrel intrauterine device (IUD) clinical trials, back pain was reported in 0% to 7.9% of patients.[48254] [52878] [58928] [61277]

      Rare adverse reactions that may occur with chronic administration of progestins such as levonorgestrel include hepatoma (benign or other tumor), elevated bilirubin levels, cholestasis, jaundice, and hyperglycemia.[51292] The appearance of jaundice may indicate the need to evaluate for hepatic disease and is a reason to consider levonorgestrel intrauterine device (IUD) discontinuation.[48254] [52930] [52878] [61277]

      Revision Date: 11/14/2022, 01:29:31 PM

      References

      33117 - Hansen LB, Saseen JJ, Teal SB. Levonorgestrel-only dosing strategies for emergency contraception. Pharmacotherapy 2007;27:278-84.41608 - US Department of Health and Human Services/Centers for Disease Control and Prevention. U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. MMWR Recomm Rep. 2016;65:1-103.48201 - US Department of Health and Human Services/Centers for Disease Control and Prevention. U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. MMWR Recomm Rep. 2016;65:1-103.48254 - Mirena (levonorgestrel-releasing intrauterine system) package insert. Wayne, NJ: Bayer HealthCare Pharmaceuticals Inc.; Aug 2022.51292 - Levin ER, Hammes SR. Chapter 40. Estrogens and Progestins. In: Chabner BA, Brunton LL, Knollman BC, eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 12th ed. New York, NY: McGraw-Hill; 2011. ISBN 978-0-07-162442-8 Available at: http://accesspharmacy.mhmedical.com.proxy.lib.umich.edu/book.aspx?bookid=1613. Accessed October 13, 2016.52878 - Skyla (levonorgestrel-releasing intrauterine system) package insert. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2021 July.52930 - Plan B (levonorgestrel) package insert. Pomona, NY: Duramed Pharmaceuticals Inc.; 2017 Sept.55077 - Food and Drug Administration (US FDA) News Release. FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential. Retrieved June 21, 2013. Available on the World Wide Web at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm358082.htm.58928 - Liletta (levonorgestrel-releasing intrauterine system) package insert. Irvine, CA: Allergan USA, Inc.; Nov 2022.61277 - Kyleena (levonorgestrel-releasing intrauterine system) package insert. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; July 2021.61655 - Berry-Bibee EN, Tepper NK, Jatlaoui TC, et al. The safety of intrauterine devices in breastfeeding women: a systematic review. Contraception 2016;94:725—738.61656 - Heinemann K, Reed S, Moehner S, et al. Risk of uterine perforation with levonorgestrel-releasing and copper intrauterine devices in the European Active Surveillance Study on Intrauterine Devices. Contraception 2015;91:274—9.

      Contraindications/Precautions

      Absolute contraindications are italicized.

      • breast cancer
      • cervical cancer
      • cervicitis
      • ectopic pregnancy
      • hepatic disease
      • hepatocellular cancer
      • incomplete abortion
      • jaundice
      • pregnancy
      • uterine cancer
      • uterine leiomyomata
      • vaginal bleeding
      • vaginitis
      • acquired immunodeficiency syndrome (AIDS)
      • anticoagulant therapy
      • Asian patients
      • bradycardia
      • breast-feeding
      • cerebrovascular disease
      • children
      • coagulopathy
      • diabetes mellitus
      • endometritis
      • headache
      • human immunodeficiency virus (HIV) infection
      • hypertension
      • infection
      • intrauterine fetal death
      • leukemia
      • magnetic resonance imaging (MRI)
      • menstrual irregularity
      • migraine
      • myocardial infarction
      • obesity
      • obstetric delivery
      • ovarian cyst
      • pregnancy testing
      • renal disease
      • requires an experienced clinician
      • seizure disorder
      • sexually transmitted disease
      • stroke
      • syncope
      • thromboembolic disease
      • thrombophlebitis
      • tobacco smoking
      • vaginal discharge
      • valvular heart disease
      • visual disturbance

      In addition to the other listed contraindications for levonorgestrel in general, levonorgestrel should not be used in patients hypersensitive to levonorgestrel or any component of the products or devices. Levonorgestrel intrauterine device (IUD) systems are contraindicated in anyone hypersensitive to the IUD components, which may include silicone and polyethylene.[41608][48254][52878][58928][61277]

       

      Levonorgestrel tablets for emergency contraception, like Plan-B and Plan B One-Step, are not intended to be used as a routine contraceptive. It is unknown if all precautions that apply with the use of other progestin-only oral contraceptives for routine contraception also apply to the intermittent use of levonorgestrel emergency contraception. Levonorgestrel IUD systems are contraindicated for use as postcoital contraception (emergency contraception).[41608]

      The oral postcoital emergency contraceptive products (e.g., Plan B and others) are not to be used by females who suspect or know that they are pregnant.[52930] [55077] Plan B and Plan B One-Step are not effective for termination of an existing pregnancy. In the use of levonorgestrel for emergency contraception, the patient should be instructed to see her health care provider if there is a delay in the expected onset of menses beyond 1 week as a pregnancy test may be needed.[52930] [55077] Levonorgestrel intrauterine devices (IUDs) are contraindicated for use during pregnancy or suspected pregnancy.[48254] [52878] [58928] [61277] Prior to IUD insertion, exclude pregnancy (via pregnancy testing or other confirmation) and confirm that there are no other contraindications to the IUD insertion. Should an intrauterine pregnancy occur while an IUD is in place, the prescriber should refer to the specific IUD literature that states considerations during such events and the patient should be informed of the potential reproductive risks.[48254] [52878] [58928] [61277] The majority of recent studies do not indicate a teratogenic effect of progestin-only contraceptive IUDs when inadvertently used during early pregnancy; however, the IUD should be discontinued as soon as pregnancy is suspected or detected. When pregnancy continues with the IUD in place, long-term effects on the offspring are unknown. If an intrauterine pregnancy occurs while a levonorgestrel IUD is in place, it should be removed, which may result in pregnancy loss. The patient should be informed of the possibility of intrauterine fetal death or miscarriage. If the patient refuses to have the IUD removed, or if it can not be removed, the patient should be closely monitored and advised to report fever/chills, vaginal discharge or fluid leakage immediately; the risks for miscarriage, premature labor/delivery, and sepsis are increased if the IUD is left in place. Congenital anomalies in live births have occurred infrequently. No clear trend towards disorders of any kind has been observed. Because of the intrauterine administration of levonorgestrel and local exposure of the fetus to the hormone, the possibility of teratogenicity following exposure to the IUD cannot be completely excluded. Observational data support a small increased risk of masculinization of the external genitalia of females after exposure to progestins at doses greater than those currently used for oral contraception. Women using levonorgestrel IUD should be informed of isolated reports of virilization of the female fetus following local exposure to levonorgestrel during pregnancy with a levonorgestrel IUD in place.[48254] [52878] [61277] Levonorgestrel, especially an IUD, should not be used if there is a suspicion of current ectopic pregnancy. A levonorgestrel IUD is contraindicated in patients with a history of ectopic pregnancy or condition that would predispose to ectopic pregnancy. The IUD-form should not be inserted if a history of ectopic pregnancy exists, but such a history does not contraindicate oral levonorgestrel use. Health care providers should be alert to the possibility of ectopic pregnancy in women who become pregnant or complain of lower abdominal pain while on any levonorgestrel product. Up to 10% of pregnancies reported in the routine use of progestin-only oral contraceptives are ectopic; however, up to 50% of pregnancies are ectopic in women who become pregnant while an IUD is in place.[48254] [52878] [58928] [61277]

      Small amounts of levonorgestrel are excreted into breast-milk during routine oral contraceptive use, resulting in infant plasma levels that are 1% to 6% of those found in maternal plasma. However, no adverse effects due to progestin-only emergency contraceptive pills have been observed in breast-feeding infants, and experts have stated that emergency oral contraception with levonorgestrel is acceptable for the woman who is breast-feeding.[52930] [48201] Experts generally consider the use of other progestin-only routine contraceptives such as levonorgestrel intrauterine device (IUDs) to be compatible with breast-feeding.[27500] [48201] No adverse effects on the growth or development of infants have been reported; however there have been isolated cases of decreased milk production in women using levonorgestrel intrauterine device (IUDs).[48254] [52878] [58928] [61277] There is an increased risk of uterine perforation after IUD insertion in breast-feeding women during the early postpartum period. In a large 1-year postmarketing safety study of levonorgestrel IUD users, the incidence of uterine perforation was reported as 6.3 per 1,000 insertions for lactating women, compared to 1 per 1,000 insertions for non-lactating women.[61655] [61656] Delay IUD insertion a minimum of 6 weeks postpartum in order to minimize the risk for uterine perforation.[41608] [48254] [58928] [52878] [61277] [48201]

      Levonorgestrel is absolutely contraindicated in undiagnosed abnormal vaginal bleeding or incomplete abortion. Levonorgestrel is contraindicated in patients with known or suspected cancers of reproductive organs, such as cervical cancer or uterine cancer, except as palliative therapy in selected patients. Because irregular bleeding/spotting is common during the first months of levonorgestrel IUD use, exclude endometrial pathology (polyps or cancer) prior to the insertion of levonorgestrel IUD in women with persistent or uncharacteristic bleeding.[48254] [52878] [58928] [61277]

      Levonorgestrel is contraindicated in patients with known or suspected breast cancer. A meta-analysis from 54 epidemiological studies reported that there is a slightly increased relative risk (RR = 1.24) of having breast cancer diagnosed in women who are currently using combination oral contraceptives compared to never-users. The increased risk gradually disappears during the course of the 10 years after cessation of combination oral contraceptive use. These studies do not provide evidence for causation. The observed pattern of increased risk of breast cancer diagnosis may be due to earlier detection of breast cancer in combination oral contraceptive users, the biological effects of combination oral contraceptives, or a combination of both. Because breast cancer is rare in women less than 40 years of age, the excess number of breast cancer diagnoses in current and recent combination oral contraceptive users is small in relation to the lifetime risk of breast cancer. Breast cancers diagnosed in ever-users tend to be less advanced clinically than the cancers diagnosed in never-users. Although the results were broadly similar for progestin-only oral contraceptives, the data are based on much smaller numbers of progestin-only oral contraceptive users and therefore are less conclusive than for combination oral contraceptives.

      Some women may experience spotting a few days after taking a levonorgestrel emergency contraceptive. Menstrual irregularity is common among women using progestin-only postcoital and emergency contraception. If there is a delay in the onset of expected menses beyond 1 week, consider the possibility of pregnancy.[52930] With levonorgestrel intrauterine device (IUD) contraceptives, there can be alterations in menstrual bleeding patterns, including amenorrhea. Some of these changes may be expected during the early months of treatment. Patients should be instructed that menstrual irregularity may occur and to notify their prescriber of any persistent changes in bleeding patterns; these may require medical evaluation. Because the contraceptive effect of the levonorgestrel IUD is mainly due to its local effects within the uterus, ovulatory cycles with follicular rupture usually occur in women of fertile age during IUD use. Sometime atresia of the follicle is delayed and the follicle may continue to grow. Ovarian cyst formation has been reported. Most ovarian cysts are asymptomatic, although some may be accompanied by pelvic pain or dyspareunia. In most cases an ovarian cyst will disappear spontaneously during 2 to 3 months observation. Evaluate persistent ovarian cysts. Surgical intervention is not usually required.[48254] [52878] [58928] [61277]

      Levonorgestrel should be used cautiously in patients with diabetes mellitus. Although the effects appear to be minimal during therapy with progestins, altered glucose tolerance secondary to decreased insulin sensitivity has been reported during hormonal contraceptive therapy.

      The safety and efficacy of levonorgestrel products have only been established in females of reproductive age. Safety and efficacy of levonorgestrel is expected to be the same for postpubertal children under the age of 16 and for users 16 years of age and older. Use of levonorgestrel products in female children before menarche is not indicated.

      Levonorgestrel contraceptive intrauterine devices (IUDs) and other products intended for routine contraception are contraindicated in patients with significant hepatic disease, jaundice, or hepatic tumors (benign or hepatocellular cancer).[48254] [52878] [58928] [61277] Levonorgestrel emergency contraceptive products have not been studied in hepatic disease. Guidelines recommend that emergency contraception may be used with caution, since the limited dosing poses less risk than traditional routine contraception.[52930] [55077] [48201]

      No formal studies have evaluated the effect of race on the efficacy of oral levonorgestrel emergency contraceptive regimens. Asian patients, specifically Chinese women, have demonstrated a higher pregnancy rate in clinical trials with Plan B, Plan B One-Step, and Yuzpe emergency contraceptive regimens. The reason for the apparent increase in pregnancy rates is not known.

      It is recommended that insertion of the levonorgestrel intrauterine device (IUD) system, be delayed until at least 6 weeks after obstetric delivery until uterine involution is complete to decrease the risk of uterine or cervical perforation. If uterine involution is delayed, consider waiting until 12 weeks postpartum before inserting the IUD. Inserting the IUD immediately after first trimester abortion is not known to increase the risk of perforation, but insertion after second trimester abortion should be delayed until uterine involution is complete.[41608] [48254] [52878] [58928] [61277]

      The insertion of an intrauterine device (IUD) requires an experienced clinician who is trained in IUD insertion using aseptic technique. Health care professionals should be thoroughly familiar with insertion procedures, the specific product educational materials, product insertion instructions, prescribing information, and patient labeling before inserting the IUD.[41608] The insertion of an IUD is a simple office procedure that really only takes a couple of minutes; very effective birth control can last for up to 8 years for Mirena, 5 years for Kyleena, 3 years for Skyla, and 8 years for Liletta. Mirena is recommended for use in patients who have had at least 1 child (i.e., not nulliparous) and who is in a mutually monogamous relationship.[48254] Skyla, Liletta, and Kyleena can be used whether the patient has previously had a child or not.[52878] [58928] [61277] Insertion of a levonorgestrel IUD is contraindicated in patients with a congenital or acquired uterine anomaly, including uterine leiomyomata (fibroids), if such conditions distort the uterine cavity. Sonography may be indicated in some patients to ensure appropriate anatomical conditions for IUD placement.[41608] [48254] [52878] [58928] [61277]

      The insertion of a levonorgestrel intrauterine device (IUD) is contraindicated in patients with acute pelvic inflammatory disease (PID) infection or a history of PID unless there has been a subsequent intrauterine pregnancy. IUDs increase the risk for PID. Both PID and endometritis are often associated with a sexually transmitted disease (STD), and the levonorgestrel IUDs do not protect against STDs. The risk of PID or endometritis is greater for women who have multiple sexual partners, and also for women whose sexual partner(s) have multiple sexual partners (women who are not in monogamous relationships). Women who have had PID or endometritis are at increased risk for a recurrence or re-infection. In particular, ascertain whether the woman is at increased risk of infection (e.g., leukemia, acquired immunodeficiency syndrome (AIDS) , or intravenous substance abuse). The IUDs are also contraindicated in patients with a history of postpartum endometritis or infected abortion in the past 3 months, untreated acute cervicitis or vaginitis (including bacterial vaginosis), known chlamydial or gonococcal cervical infection, genital actinomycosis, or other lower genital tract infections until the infection is controlled. The levonorgestrel IUD is contraindicated in patients with conditions associated with an increased risk for pelvic infections. The highest risk of PID occurs shortly after insertion (usually within the first 20 days), but PID may present at any time. Endometritis is more common in the first 40 days after insertion. Counsel women who receive the IUD to notify a healthcare provider if they have complaints of lower abdominal or pelvic pain, odorous vaginal discharge, unexplained bleeding, fever, or genital lesions or sores. The IUD should be removed if a patient has a pelvic infection or endometritis.[48254] [52878] [58928] [61277]

      Like all hormonal contraceptives, levonorgestrel contraceptive intrauterine device (IUD) or emergency oral contraceptive use does not protect against the transmission of human immunodeficiency virus (HIV) infection or other sexually transmitted disease (STD).[52930] For patients using a levonorgestrel IUD, if the patient's relationship should cease to be mutually monogamous, or should she or her partner become HIV positive or acquire a sexually transmitted disease, the patient should be instructed to report this change to her clinician immediately; the removal of the IUD may be recommended. IUD use is contraindicated in patients with active untreated sexually transmitted disease (STD) such as acute cervicitis or vaginitis (including bacterial vaginosis), known chlamydial or gonococcal cervical infection, genital actinomycosis, or other lower genital tract infections until the infection is controlled. The use of a barrier method as a partial protection against acquiring sexually transmitted diseases should be strongly recommended. Removal of the IUD should be considered.[48254] [52878] [58928] [61277]

      Syncope, bradycardia, or other neurovascular episodes may occur during insertion or removal of the levonorgestrel intrauterine device (IUD), especially in patients predisposed to these conditions or those with cervical stenosis. If decreased pulse, diaphoresis, or pallor is observed, the patient should remain supine until these signs have disappeared.[48254] [52878] [58928] [61277] Patients with a seizure disorder or epilepsy may also experience seizures during insertion. Consider administering analgesics prior to insertion.[48254]

      The effect of obesity on emergency contraceptive efficacy has been assessed in clinical studies, rather than pharmacokinetic analyses alone. Pregnancy rates with use of levonorgestrel 1.5 mg as a single dose for emergency contraception were low at less than 3% across different weight and BMI categories. Pooled analyses of 4 large studies, many conducted by the World Health Organization (WHO) have showed an increase in pregnancy rates among obese women with a body mass index (BMI) more than 30 kg/m2 compared to women with normal BMI levels, but the data were influenced by pregnancies reported from one study site in Nigeria.[27235] [56551] [61312] [61313] The four studies were not originally intended to be stratified in the randomization according to weight or BMI of patients.[61313] Results of the meta-analyses indicate that levonorgestrel emergency contraceptive products should still be promoted to women who need them, and not be restricted in any weight or BMI category, with additional attention for counseling and advice for obese women.[61313] The most important factor affecting how well emergency contraception works is how quickly it is taken after unprotected sex.[52930] [61315] The FDA has completed a review of available scientific data concerning the effectiveness of levonorgestrel emergency contraceptives in women who weigh more than 165 pounds (75 kg) or have a body mass index (BMI) above 25 kg/m2. The data are conflicting and too limited to reach a definitive conclusion as to whether effectiveness is reduced in this group. The FDA continues to state that all women, regardless of BMI, can use levonorgestrel emergency contraceptive products to prevent unintended pregnancy following unprotected sexual intercourse or contraceptive failure; no changes have been made to the levonorgestrel emergency contraceptive labeling with regard to weight. Continued research is needed to determine if a high BMI provides a risk factor for emergency contraceptive failure.[61315]

      Because of the potential for uterine injury from the levonorgestrel intrauterine devices (IUDs), insert and use the IUDs with caution in patients on anticoagulant therapy or with a coagulopathy. Consider removal of the IUD should these conditions arise during use.[48254] [52878] [58928] [61277]

      Levonorgestrel intrauterine device (IUD) is recommended to be used cautiously and with careful consideration in patients with active thromboembolic disease or a history of thrombophlebitis or thromboembolic disease.[41608] Although thromboembolic disease is believed to be an estrogen-related effect, studies have shown that patients receiving hormonal combined contraceptives or hormonal replacement therapy (HRT) regimens containing progestins may have a higher risk of venous thromboembolic (VTE) disease. Because of the higher risk of thromboembolic disease in tobacco smoking women, women should be advised not to smoke, particularly if they are over the age of 35 years. Despite the caution against use in patients with known thrombotic disease, progestin-only contraceptives are generally the hormonal contraceptives of choice in patients with a potential risk for thrombosis when reliable contraception must be ensured and the risks of hormonal therapy are acceptable; advantages of these methods usually outweigh proven or theoretical risks.[41608] When multiple thrombosis risk factors exist, the risk of thromboembolic disease may increase; determine risk vs. benefit for use of the progestin-only contraceptive. The increase in the risk of thrombosis from newer progestin-only contraceptives (e.g., levonorgestrel IUD) is still substantially less than with combined oral contraceptives containing both estrogen and progestin.[41608] For women who are at an increased risk of thromboembolism and have multiple-risk factors for thrombosis (e.g., tobacco smoking woman age 35 and older, diabetes, hypercoagulopathy, severe hypertension, etc.), consider an IUD or other estrogen-free contraceptive if appropriate.[41608] During use of the levonorgestrel IUD in patients without a history of thrombosis, the provider should be alert to the earliest manifestations of thrombotic disorder (thrombophlebitis, cerebrovascular disease, cardiac disease, myocardial infarction, pulmonary embolism, severe hypertension, stroke, valvular heart disease, and retinal thrombosis). Should any of these thrombotic-type events occur or be suspected, or if new risk factors warrant, consider removal of the levonorgestrel IUD.[48254] [61277] Patients using oral levonorgestrel for emergency contraception would be expected to experience less of a clinical impact on the risk of thromboembolic complications due to shorter duration of use; advantages of the emergency contraceptive usually outweigh the theoretical risk; no specific precautions apply to emergency contraceptive use in patients with thromboembolic disease risk factors.[41608] [52930] [55077]

      Use levonorgestrel intrauterine devices (IUDs) with caution in a patient with a history of migraine. During IUD use, a migraine that is accompanied by focal neurological symptoms (e.g., aura); the exacerbation of migraine, or the development of headache with a new pattern which is recurrent, persistent or severe requires evaluation of the cause. Sudden onset of severe headache or a sever migraine, focal migraine with asymmetrical visual loss or other symptoms may indicate transient cerebral ischemia or stroke and should prompt the consideration for removal of the IUD.[48254] Consistent with potential thrombotic effects, any change in vision or visual acuity should be examined by an ophthalmologist. Patients developing any unexplained visual disturbance require evaluation. If retinal vascular occlusion occurs, consider removal of the IUD.[48254] [52878] [58928] [61277]

      No studies have been performed with any levonorgestrel contraceptive intrauterine device (IUD) or emergency contraceptive to determine the effect of renal disease or renal impairment on the disposition of the drug in these products.[52930] [48254] [52878] [58928] [61277]

      Should a patient with an intrauterine device (IUD) need to have an examination that involves magnetic resonance imaging (MRI), the patient should inform her healthcare provider and scan technician that a levonorgestrel IUD is in place prior to the procedure. Some of the IUDs are MRI conditional, meaning, that the IUD can be safely scanned only under specific conditions. Refer to the specific information for the particular IUD used prior to scheduling a MRI procedure.[48254] [52878] [58928] [61277]

      Revision Date: 11/14/2022, 11:27:14 AM

      References

      27235 - Holt VL, et al. Body weight and risk of oral contraceptive failure. Obstet Gynecol 2002;99:820-827.27500 - American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108(3):776-789.41608 - US Department of Health and Human Services/Centers for Disease Control and Prevention. U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. MMWR Recomm Rep. 2016;65:1-103.48201 - US Department of Health and Human Services/Centers for Disease Control and Prevention. U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. MMWR Recomm Rep. 2016;65:1-103.48254 - Mirena (levonorgestrel-releasing intrauterine system) package insert. Wayne, NJ: Bayer HealthCare Pharmaceuticals Inc.; Aug 2022.52878 - Skyla (levonorgestrel-releasing intrauterine system) package insert. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2021 July.52930 - Plan B (levonorgestrel) package insert. Pomona, NY: Duramed Pharmaceuticals Inc.; 2017 Sept.55077 - Food and Drug Administration (US FDA) News Release. FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential. Retrieved June 21, 2013. Available on the World Wide Web at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm358082.htm.56551 - Glasier A, Cameron ST, Blithe D, et al. Can we identify women at risk of pregnancy despite using emergency contraception? Data from randomized trials of ulipristal acetate and levonorgestrel. Contraception 2011;84:363-7.58928 - Liletta (levonorgestrel-releasing intrauterine system) package insert. Irvine, CA: Allergan USA, Inc.; Nov 2022.61277 - Kyleena (levonorgestrel-releasing intrauterine system) package insert. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; July 2021.61312 - Kapp N, Abitbol JL, Mathe H, et al. Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception. Contraception. 2015;91:97-104.61313 - Festin MP, Peregoudov A, Seuc A, et al. Effect of BMI and body weight on pregnancy rates with LNG as emergency contraception: analysis of four WHO HRP studies. Contraception. 2016 Aug 12. Available at: http://www.sciencedirect.com/science/article/pii/S0010782416303572 [Epub ahead of print] Accessed October 14, 2016.61315 - U.S. Food and Drug Administration. Plan B and Plan B One-Step information. FDA communication on levonorgestrel emergency contraceptive effectiveness and weight. Updated May 24, 2016. Available at: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm109775.htm Accessed: October 14, 2016.61655 - Berry-Bibee EN, Tepper NK, Jatlaoui TC, et al. The safety of intrauterine devices in breastfeeding women: a systematic review. Contraception 2016;94:725—738.61656 - Heinemann K, Reed S, Moehner S, et al. Risk of uterine perforation with levonorgestrel-releasing and copper intrauterine devices in the European Active Surveillance Study on Intrauterine Devices. Contraception 2015;91:274—9.

      Mechanism of Action

      The primary contraceptive effect of progestins involves the suppression of the midcycle surge of luteinizing hormone (LH). The exact mechanism of action, however, is unknown. At the cellular level, progestins diffuse freely into target cells and bind to the progesterone receptor. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Once bound to the receptor, progestins slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH surge, thereby preventing follicular maturation and ovulation. Additional mechanisms may be involved. Other actions of progestins include alterations in the endometrium that can impair implantation and an increase in cervical mucus viscosity which inhibits sperm migration into the uterus.[51292]

       

      • Emergency oral contraception: Clinical data supports an effect on inhibiting or delaying ovulation and the midcycle hormonal changes. Evidence also supports the conclusion that there is no direct effect on postovulatory processes, such as fertilization or implantation. Levonorgestrel emergency contraception is not effective if pregnancy has already occurred.[62899][68389]
      • Intrauterine device (IUD) contraception: A levonorgestrel IUD has mainly local progestogen effects in the uterine cavity. Morphological changes of the endometrium are observed, including stromal pseudodecidualization, glandular atrophy, leukocytic infiltration, and a decrease in glandular and stromal mitoses. The local mechanism by which continuously released levonorgestrel in an IUD provides contraception has not been conclusively demonstrated. Studies suggest several mechanisms for pregnancy prevention: 1) prevention of fertilization due to the thickening of the cervical mucus, which inhibits sperm passage through the cervix, and 2) inhibition of sperm mobility and function (capacitation), and 3) alteration of the endometrium. Because the contraceptive effect of a levonorgestrel IUD is mainly due to its local effects within the uterus, ovulatory cycles with follicular rupture usually occur in women of fertile age. In clinical contraception studies with Mirena, the reported 12-month pregnancy rates were less than or equal to 0.2 per 100 women (0.2%) and the cumulative 5-year pregnancy rate was approximately 0.7 per 100 women (0.7%). The pregnancy rate (calculated as the Pearl Index) at the end of Year 6 was 0.34; one pregnancy occurred during Year 6 within 7 days after Mirena removal. The indication for the 8th year of use is based on a Pearl Index (PI) of no pregnancies occurring during Year 8 and within 7 days after Mirena removal or expulsion.[48254] In clinical contraception studies with Skyla, the cumulative 3-year pregnancy rate, based on 10 pregnancies, estimated by the Kaplan-Meier method was 0.9 per 100 women or 0.9%, with a 95% upper confidence limit of 1.7%.[52878] In clinical contraceptive studies with Liletta, the pregnancy rate calculated as the Pearl Index (PI) at year-1 was based on 2 pregnancies and was approximately 0.15%, and the cumulative 8-year pregnancy rate was based on a total of 11 pregnancies that occurred and was 1.37%.[58928] In clinical contraception studies with Kyleena, the cumulative 5-year pregnancy rate, based on 13 pregnancies, estimated by the Kaplan-Meier method was 1.45, with a 95% upper confidence interval of 0.82 to 2.53.[61277] Once a levonorgestrel IUD is removed, fertility usually returns rapidly. Approximately 80% of women who want to become pregnant and who have no other fertility issues will become pregnant in the first year after the IUD is removed. For example, about 71% of 163 women who desired pregnancy after study discontinuation and provided follow-up information, conceived within 12 months after removal of Kyleena.[61277]
      Revision Date: 12/28/2022, 02:45:00 PM

      References

      48254 - Mirena (levonorgestrel-releasing intrauterine system) package insert. Wayne, NJ: Bayer HealthCare Pharmaceuticals Inc.; Aug 2022.51292 - Levin ER, Hammes SR. Chapter 40. Estrogens and Progestins. In: Chabner BA, Brunton LL, Knollman BC, eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 12th ed. New York, NY: McGraw-Hill; 2011. ISBN 978-0-07-162442-8 Available at: http://accesspharmacy.mhmedical.com.proxy.lib.umich.edu/book.aspx?bookid=1613. Accessed October 13, 2016.52878 - Skyla (levonorgestrel-releasing intrauterine system) package insert. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2021 July.58928 - Liletta (levonorgestrel-releasing intrauterine system) package insert. Irvine, CA: Allergan USA, Inc.; Nov 2022.61277 - Kyleena (levonorgestrel-releasing intrauterine system) package insert. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; July 2021.62899 - Plan B One-Step (levonorgestrel 1.5 mg) emergency contraceptive regimen consumer product label. Teva Women’s Health, Inc. 2022 Dec.68389 - Foundation Consumer Healthcare, LLC. Levonorgestrel 1.5 mg Tablet Emergency Contraceptive Labeling Supplement for Update to Mechanism of Action Information. Retrieved December 28, 2022. Available on the World Wide Web at https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/021998Orig1s005SumR.pdf

      Pharmacokinetics

      Levonorgestrel is administered orally as a single agent for post-coital emergency contraception or is administered in progestin-only intrauterine devices (IUDs). Levonorgestrel is bound non-specifically to serum albumin and specifically to sex hormone binding globulin (SHBG); thus, changes in SHBG serum concentrations result in changes of the total levonorgestrel concentration in serum. Less than 2% of circulating levonorgestrel is present as free steroid. Levonorgestrel is not subject to first-pass hepatic metabolism. Levonorgestrel is extensively metabolized to inactive metabolites. Oxidative metabolism of levonorgestrel is catalyzed by hepatic cytochrome P450 isoenzymes, especially CYP3A4. Approximately 45% of levonorgestrel and its metabolites are excreted in the urine and about 32% are excreted in feces, mostly as glucuronide conjugates. No entero-hepatic recycling occurs. The elimination half-life following a single oral dose of 0.75 mg levonorgestrel is roughly 17 to 24 hours.[52930] The elimination half-life of levonorgestrel after daily oral doses or parenteral administration is approximately 17 hours and 20 hours, respectively.[48254][52878][58928][61277]

       

      Affected cytochrome P450 (CYP450) enzymes and drug transporters: CYP3A4

      Drugs or herbal products that induce enzymes, including CYP3A4, that metabolize progestins may decrease the serum concentrations of progestins; in some cases these interactions might reduce contraceptive efficacy.[52930][48254][52878][58928][61277] CYP3A4 inhibitors may increase plasma hormone levels; no formal drug-drug interaction studies have been performed with intrauterine administration of levonorgestrel.[48254][52878][58928][61277]

      Route-Specific Pharmacokinetics

      Oral Route

      The literature indicates that levonorgestrel oral tablets are rapidly and completely absorbed after oral administration, with bioavailability approaching 100%.[52930]

      Intravenous Route

      Following intravenous (IV) administration of 0.09 mg levonorgestrel to healthy volunteers, the total clearance of levonorgestrel is approximately 1 mL/minute/kg and the elimination half-life is approximately 20 hours. Metabolic clearance rates may differ among individuals by several-fold, and this may account in part for wide individual variations in concentrations seen in individuals using levonorgestrel–containing contraceptive products.[52878]

      Other Route(s)

      Intrauterine Route

      • Mirena intrauterine device (IUD): Following IUD insertion, the initial release of levonorgestrel into the uterine cavity is approximately 21 mcg/day. The release rate is reduced to about 11 mcg/day after 5 years and 7 mcg/day after 8 years. After insertion, levonorgestrel is detectable in serum/plasma after 1 hour and the maximum concentration is reached within 2 weeks after insertion and is about 180 ng/L. Levonorgestrel concentrations after long-term use of 12, 36, 60 months (5 years), and 96 months (8 years) were 159 ng/L, 139 ng/L, 123 ng/L, and 100 ng/L respectively. The mean endometrial tissue concentrations achieved with levonorgestrel IUDs are roughly 808 ng/gram wet tissue weight, much higher than the endometrial tissue levels following oral levonorgestrel (i.e., roughly 3.5 ng/gram).[48254]
      • Skyla intrauterine device (IUD): Following IUD insertion, the release rate of levonorgestrel is approximately 14 mcg/day after 24 days. After 60 days, the rate is reduced to approximately 10 mcg/day and then decreases progressively to approximately 6 mcg/day for 3 years, and then 5 mcg/day after 3 years. The average levonorgestrel release rate is approximately 8 mcg/day the first year, and then 6 mcg/day over the period of 3 years. Maximum levonorgestrel plasma levels, 192 +/- 105 pg/mL, occur 2 days (median) after IUD insertion. Thereafter, serum concentrations decrease after long-term use of 12, 24, and 36 months to concentrations of 77 +/- 21 pg/mL, 62 +/- 38 pg/mL, and 72 +/- 29 pg/mL, respectively.[52878]
      • Liletta intrauterine device (IUD): Following IUD insertion, the initial release rate of levonorgestrel is approximately 20.4 mcg/day. The rate is progressively reduced to approximately 17.7 mcg/day at year 1, 15.3 mcg/day at year 2, 13.3 mcg/day at year 3, 11.5 mcg/day at year 4, 10 mcg/day at year 5, 8.7 mcg/day at year 6, 7.5 mcg/day at year 7, and 6.5 mcg/day at 8 years. The average release rate of levonorgestrel is approximately 13.5 mcg/day over the 8-year period. Initial plasma levonorgestrel concentrations 7 days following IUD insertion are 252+/-123 pg/mL and decrease over time to concentrations of 195 +/- 68 pg/mL, 168 +/- 51 pg/mL, 150 +/- 47 pg/mL, 132 +/- 54 pg/mL, 114 +/- 52 pg/mL, 101 +/- 42 pg/mL, 92 +/- 43 pg/mL, 90 +/- 38 pg/mL, 88 +/- 37 pg/mL at 6, 12, 24, 36, 48, 60 months, 72 months, 84 months, and 96 months, respectively.[58928]
      • Kyleena intrauterine device (IUD): Following IUD insertion, the initial release rate of levonorgestrel is approximately 17.5 mcg/day after 24 days and is reduced to approximately 15.3 mcg/day after 60 days and to 9.8 mcg/day after 1 year. The rate is progressively reduced to approximately 7.9 mcg/day after 3 years and 7.4 mcg/day after 5 years. The average levonorgestrel in vivo release rate is approximately 9 mcg/day over the period of 5 years. Initial plasma levonorgestrel concentrations 7.5 days following IUD insertion are 302 +/- 170 pg/mL and decrease over time to concentrations of 199 +/- 171 pg/mL, 120 +/- 57 pg/mL, 122 +/- 65 pg/mL, 79 +/- 12 pg/mL, 65 +/- 15 pg/mL at Year 1, 2, 3, 4 and 5, respectively. A population pharmacokinetic evaluation based on a broader database (more than 1,000 patients) showed a similar declining concentration profile, with 175 +/- 74 pg/mL at 7 days after placement, 125 +/- 50 pg/mL at 1 year, 99 +/- 41 pg/mL after 3 years, and 90 +/- 35 pg/mL after 5 years.[61277]

      Special Populations

      Hepatic Impairment

      No pharmacokinetic studies have been performed on levonorgestrel oral emergency contraceptives or intrauterine devices in patients with hepatic impairment.[52930][48254][52878][58928][61277]

      Renal Impairment

      No pharmacokinetic studies have been conducted regarding the use of oral or intrauterine levonorgestrel in patients with renal impairment.[52930][48254][52878][58928][61277]

      Pediatrics

      No pharmacokinetic studies have been conducted in children less than 12 years of age; levonorgestrel products are not indicated before the age of menarche. In a 1-year study in post-menarchal female adolescents (mean age 16.2, range 12 to 18 years) using Skyla levonorgestrel IUD, the population pharmacokinetic analysis of 278 adolescents showed mean estimated levonorgestrel serum concentrations slightly higher (approximately 10%) in adolescent females compared to prior data in adult females. This correlates to the generally lower body weight in adolescents. The ranges estimated for adolescents are within the ranges estimated for adults.[52878]

      Geriatric

      No pharmacokinetic studies of levonorgestrel have been performed in adults greater than 65 years of age, as the drug is not indicated for use in post-menopausal females.

      Ethnic Differences

      During levonorgestrel IUD (Liletta) clinical trials, no differences in levonorgestrel concentrations were apparent in Black subjects or Hispanic subjects.[58928] A population pharmacokinetic analysis of Asian (Chinese) women receiving the levonorgestrel IUD (Skyla) showed that mean estimated levonorgestrel serum concentrations in Asian women were slightly higher (approximately 4 to 16%) than those in another phase 3 study which was performed in mainly White women (79.7%). This slightly higher exposure might be explained by the lower body weight of Asian women.[52878] No studies have evaluated the effect of race on pharmacokinetics of other levonorgestrel IUDs, including Mirena or Kyleena.

      Obesity

      • Oral emergency contraceptive use in obesity or those with increased Body Mass Index (BMI): The effect of obesity on emergency contraceptive efficacy has been assessed in clinical studies, rather than pharmacokinetic analyses alone. Pregnancy rates with use of levonorgestrel 1.5mg as a single dose for emergency contraception were low at less than 3% across different weight and BMI categories. Pooled analyses of 4 large studies, many conducted by the World Health Organization (WHO) have showed an increase in pregnancy rates among obese women (BMI more than 30 kg/m2) compared to women with normal BMI levels, but the data were influenced by pregnancies reported from 1 study site.[61312][61313] The FDA continues to state that all women, regardless of BMI, can use these products to prevent unintended pregnancy following unprotected sexual intercourse or contraceptive failure. The most important factor affecting how well emergency contraception works is how quickly it is taken after unprotected sex.
      • Intrauterine Device (IUD) obesity data: In levonorgestrel IUD (Liletta) clinical trials, overweight (24%), obese (24%), and morbidly obese (5%) women were included. Levonorgestrel systemic exposure decreased with increasing body weight; however, there was no apparent effect of body mass index (BMI) or body weight on contraceptive efficacy.[58928] No studies have evaluated the effect of BMI on pharmacokinetics of other levonorgestrel IUDs, including Mirena, Skyla or Kyleena.
      Revision Date: 11/14/2022, 04:34:20 PM

      References

      48254 - Mirena (levonorgestrel-releasing intrauterine system) package insert. Wayne, NJ: Bayer HealthCare Pharmaceuticals Inc.; Aug 2022.52878 - Skyla (levonorgestrel-releasing intrauterine system) package insert. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2021 July.52930 - Plan B (levonorgestrel) package insert. Pomona, NY: Duramed Pharmaceuticals Inc.; 2017 Sept.58928 - Liletta (levonorgestrel-releasing intrauterine system) package insert. Irvine, CA: Allergan USA, Inc.; Nov 2022.61277 - Kyleena (levonorgestrel-releasing intrauterine system) package insert. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; July 2021.61312 - Kapp N, Abitbol JL, Mathe H, et al. Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception. Contraception. 2015;91:97-104.61313 - Festin MP, Peregoudov A, Seuc A, et al. Effect of BMI and body weight on pregnancy rates with LNG as emergency contraception: analysis of four WHO HRP studies. Contraception. 2016 Aug 12. Available at: http://www.sciencedirect.com/science/article/pii/S0010782416303572 [Epub ahead of print] Accessed October 14, 2016.

      Pregnancy/Breast-feeding

      ectopic pregnancy, intrauterine fetal death, pregnancy, pregnancy testing

      The oral postcoital emergency contraceptive products (e.g., Plan B and others) are not to be used by females who suspect or know that they are pregnant.[52930] [55077] Plan B and Plan B One-Step are not effective for termination of an existing pregnancy. In the use of levonorgestrel for emergency contraception, the patient should be instructed to see her health care provider if there is a delay in the expected onset of menses beyond 1 week as a pregnancy test may be needed.[52930] [55077] Levonorgestrel intrauterine devices (IUDs) are contraindicated for use during pregnancy or suspected pregnancy.[48254] [52878] [58928] [61277] Prior to IUD insertion, exclude pregnancy (via pregnancy testing or other confirmation) and confirm that there are no other contraindications to the IUD insertion. Should an intrauterine pregnancy occur while an IUD is in place, the prescriber should refer to the specific IUD literature that states considerations during such events and the patient should be informed of the potential reproductive risks.[48254] [52878] [58928] [61277] The majority of recent studies do not indicate a teratogenic effect of progestin-only contraceptive IUDs when inadvertently used during early pregnancy; however, the IUD should be discontinued as soon as pregnancy is suspected or detected. When pregnancy continues with the IUD in place, long-term effects on the offspring are unknown. If an intrauterine pregnancy occurs while a levonorgestrel IUD is in place, it should be removed, which may result in pregnancy loss. The patient should be informed of the possibility of intrauterine fetal death or miscarriage. If the patient refuses to have the IUD removed, or if it can not be removed, the patient should be closely monitored and advised to report fever/chills, vaginal discharge or fluid leakage immediately; the risks for miscarriage, premature labor/delivery, and sepsis are increased if the IUD is left in place. Congenital anomalies in live births have occurred infrequently. No clear trend towards disorders of any kind has been observed. Because of the intrauterine administration of levonorgestrel and local exposure of the fetus to the hormone, the possibility of teratogenicity following exposure to the IUD cannot be completely excluded. Observational data support a small increased risk of masculinization of the external genitalia of females after exposure to progestins at doses greater than those currently used for oral contraception. Women using levonorgestrel IUD should be informed of isolated reports of virilization of the female fetus following local exposure to levonorgestrel during pregnancy with a levonorgestrel IUD in place.[48254] [52878] [61277] Levonorgestrel, especially an IUD, should not be used if there is a suspicion of current ectopic pregnancy. A levonorgestrel IUD is contraindicated in patients with a history of ectopic pregnancy or condition that would predispose to ectopic pregnancy. The IUD-form should not be inserted if a history of ectopic pregnancy exists, but such a history does not contraindicate oral levonorgestrel use. Health care providers should be alert to the possibility of ectopic pregnancy in women who become pregnant or complain of lower abdominal pain while on any levonorgestrel product. Up to 10% of pregnancies reported in the routine use of progestin-only oral contraceptives are ectopic; however, up to 50% of pregnancies are ectopic in women who become pregnant while an IUD is in place.[48254] [52878] [58928] [61277]

      breast-feeding

      Small amounts of levonorgestrel are excreted into breast-milk during routine oral contraceptive use, resulting in infant plasma levels that are 1% to 6% of those found in maternal plasma. However, no adverse effects due to progestin-only emergency contraceptive pills have been observed in breast-feeding infants, and experts have stated that emergency oral contraception with levonorgestrel is acceptable for the woman who is breast-feeding.[52930] [48201] Experts generally consider the use of other progestin-only routine contraceptives such as levonorgestrel intrauterine device (IUDs) to be compatible with breast-feeding.[27500] [48201] No adverse effects on the growth or development of infants have been reported; however there have been isolated cases of decreased milk production in women using levonorgestrel intrauterine device (IUDs).[48254] [52878] [58928] [61277] There is an increased risk of uterine perforation after IUD insertion in breast-feeding women during the early postpartum period. In a large 1-year postmarketing safety study of levonorgestrel IUD users, the incidence of uterine perforation was reported as 6.3 per 1,000 insertions for lactating women, compared to 1 per 1,000 insertions for non-lactating women.[61655] [61656] Delay IUD insertion a minimum of 6 weeks postpartum in order to minimize the risk for uterine perforation.[41608] [48254] [58928] [52878] [61277] [48201]

      Revision Date: 06/15/2021, 12:54:56 PM

      References

      27500 - American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108(3):776-789.41608 - US Department of Health and Human Services/Centers for Disease Control and Prevention. U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. MMWR Recomm Rep. 2016;65:1-103.48201 - US Department of Health and Human Services/Centers for Disease Control and Prevention. U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. MMWR Recomm Rep. 2016;65:1-103.48254 - Mirena (levonorgestrel-releasing intrauterine system) package insert. Wayne, NJ: Bayer HealthCare Pharmaceuticals Inc.; Aug 2022.52878 - Skyla (levonorgestrel-releasing intrauterine system) package insert. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2021 July.52930 - Plan B (levonorgestrel) package insert. Pomona, NY: Duramed Pharmaceuticals Inc.; 2017 Sept.55077 - Food and Drug Administration (US FDA) News Release. FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential. Retrieved June 21, 2013. Available on the World Wide Web at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm358082.htm.58928 - Liletta (levonorgestrel-releasing intrauterine system) package insert. Irvine, CA: Allergan USA, Inc.; Nov 2022.61277 - Kyleena (levonorgestrel-releasing intrauterine system) package insert. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; July 2021.61655 - Berry-Bibee EN, Tepper NK, Jatlaoui TC, et al. The safety of intrauterine devices in breastfeeding women: a systematic review. Contraception 2016;94:725—738.61656 - Heinemann K, Reed S, Moehner S, et al. Risk of uterine perforation with levonorgestrel-releasing and copper intrauterine devices in the European Active Surveillance Study on Intrauterine Devices. Contraception 2015;91:274—9.

      Interactions

      Level 2 (Major)

      • Acitretin
      • Apalutamide
      • Aprepitant, Fosaprepitant
      • Armodafinil
      • Artemether; Lumefantrine
      • Atazanavir
      • Atazanavir; Cobicistat
      • Belzutifan
      • Bexarotene
      • Bosentan
      • Calaspargase pegol
      • Carbamazepine
      • Cenobamate
      • Charcoal
      • Clobazam
      • Cobicistat
      • Dabrafenib
      • Darunavir
      • Darunavir; Cobicistat
      • Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide
      • Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir
      • Efavirenz
      • Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate
      • Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate
      • Elagolix
      • Elagolix; Estradiol; Norethindrone acetate
      • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide
      • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate
      • Encorafenib
      • Enzalutamide
      • Eslicarbazepine
      • Etravirine
      • Felbamate
      • Fosamprenavir
      • Griseofulvin
      • Hydantoins
      • Isoniazid, INH; Pyrazinamide, PZA; Rifampin
      • Isoniazid, INH; Rifampin
      • Ivosidenib
      • Lesinurad
      • Lesinurad; Allopurinol
      • Lomitapide
      • Lopinavir; Ritonavir
      • Lorlatinib
      • Lumacaftor; Ivacaftor
      • Mifepristone
      • Mitotane
      • Mobocertinib
      • Modafinil
      • Nelfinavir
      • Nirmatrelvir; Ritonavir
      • Ombitasvir; Paritaprevir; Ritonavir
      • Oxcarbazepine
      • Pegaspargase
      • Perampanel
      • Pexidartinib
      • Pitolisant
      • Pretomanid
      • Rifampin
      • Rifapentine
      • Ritonavir
      • Rufinamide
      • St. John's Wort, Hypericum perforatum
      • Sugammadex
      • Tazemetostat
      • Tipranavir
      • Tirzepatide
      • Tizanidine
      • Ulipristal

      Level 3 (Moderate)

      • Adagrasib
      • Amikacin
      • Aminoglycosides
      • Amobarbital
      • Amoxicillin
      • Amoxicillin; Clarithromycin; Omeprazole
      • Amoxicillin; Clavulanic Acid
      • Ampicillin
      • Ampicillin; Sulbactam
      • Aspirin, ASA; Butalbital; Caffeine
      • Aspirin, ASA; Butalbital; Caffeine; Codeine
      • Azithromycin
      • Aztreonam
      • Bacitracin
      • Barbiturates
      • Bismuth Subcitrate Potassium; Metronidazole; Tetracycline
      • Bismuth Subsalicylate; Metronidazole; Tetracycline
      • Butabarbital
      • Butalbital; Acetaminophen
      • Butalbital; Acetaminophen; Caffeine
      • Butalbital; Acetaminophen; Caffeine; Codeine
      • Carbapenems
      • Cefaclor
      • Cefadroxil
      • Cefazolin
      • Cefdinir
      • Cefditoren
      • Cefepime
      • Cefiderocol
      • Cefixime
      • Cefotaxime
      • Cefotetan
      • Cefoxitin
      • Cefpodoxime
      • Cefprozil
      • Ceftaroline
      • Ceftazidime
      • Ceftazidime; Avibactam
      • Ceftibuten
      • Ceftizoxime
      • Ceftolozane; Tazobactam
      • Ceftriaxone
      • Cefuroxime
      • Cephalexin
      • Chloramphenicol
      • Ciprofloxacin
      • Clarithromycin
      • Clindamycin
      • Colistimethate, Colistin, Polymyxin E
      • Colistin
      • Dalbavancin
      • Daptomycin
      • Deferasirox
      • Delafloxacin
      • Demeclocycline
      • Dicloxacillin
      • Doripenem
      • Doxycycline
      • Eravacycline
      • Ertapenem
      • Erythromycin
      • Exenatide
      • Fidaxomicin
      • Flibanserin
      • Gemifloxacin
      • Gentamicin
      • Glycylcyclines
      • Idelalisib
      • Imipenem; Cilastatin
      • Imipenem; Cilastatin; Relebactam
      • Indinavir
      • Insulin Glargine; Lixisenatide
      • Kanamycin
      • Lamotrigine
      • Lansoprazole; Amoxicillin; Clarithromycin
      • Lefamulin
      • Leflunomide
      • Levofloxacin
      • Lincomycin
      • Lincosamides
      • Linezolid
      • Lixisenatide
      • Mafenide
      • Meropenem
      • Meropenem; Vaborbactam
      • Methohexital
      • Metronidazole
      • Miltefosine
      • Minocycline
      • Mivacurium
      • Morphine
      • Morphine; Naltrexone
      • Moxifloxacin
      • Nafcillin
      • Neomycin
      • Nevirapine
      • Nitrofurantoin
      • Ofloxacin
      • Omadacycline
      • Omeprazole; Amoxicillin; Rifabutin
      • Oritavancin
      • Oxacillin
      • Paromomycin
      • Penicillin G
      • Penicillin G Benzathine
      • Penicillin G Benzathine; Penicillin G Procaine
      • Penicillin G Procaine
      • Penicillin V
      • Pentobarbital
      • Phenobarbital
      • Phenobarbital; Hyoscyamine; Atropine; Scopolamine
      • Phentermine; Topiramate
      • Piperacillin
      • Piperacillin; Tazobactam
      • Plazomicin
      • Polymyxin B
      • Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements)
      • Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved)
      • Primidone
      • Riluzole
      • Roflumilast
      • Sarilumab
      • Secobarbital
      • Siltuximab
      • Streptogramins
      • Streptomycin
      • Succinylcholine
      • Sulfadiazine
      • Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole
      • Sulfasalazine
      • Sulfonamides
      • Tedizolid
      • Telavancin
      • Teriflunomide
      • Tetracycline
      • Thalidomide
      • Tigecycline
      • Tinidazole
      • Tobramycin
      • Tocilizumab
      • Topiramate
      • Trimethoprim
      • Vancomycin
      • Vonoprazan; Amoxicillin
      • Vonoprazan; Amoxicillin; Clarithromycin

      Level 4 (Minor)

      • Acetohexamide
      • Alogliptin
      • Alogliptin; Metformin
      • Alogliptin; Pioglitazone
      • Alpha-glucosidase Inhibitors
      • Bromocriptine
      • Canagliflozin
      • Canagliflozin; Metformin
      • Chenodiol
      • Chlorpropamide
      • Dapagliflozin
      • Dapagliflozin; Metformin
      • Dapagliflozin; Saxagliptin
      • Empagliflozin
      • Empagliflozin; Linagliptin
      • Empagliflozin; Linagliptin; Metformin
      • Empagliflozin; Metformin
      • Ertugliflozin
      • Ertugliflozin; Metformin
      • Ertugliflozin; Sitagliptin
      • Glimepiride
      • Glimepiride; Rosiglitazone
      • Glipizide
      • Glipizide; Metformin
      • Glyburide
      • Glyburide; Metformin
      • Insulins
      • Linagliptin
      • Linagliptin; Metformin
      • Meglitinides
      • Metformin
      • Metformin; Repaglinide
      • Metformin; Rosiglitazone
      • Metformin; Saxagliptin
      • Metformin; Sitagliptin
      • Pioglitazone
      • Pioglitazone; Glimepiride
      • Pioglitazone; Metformin
      • Pramlintide
      • Rosiglitazone
      • Saquinavir
      • Saxagliptin
      • Simvastatin; Sitagliptin
      • Sitagliptin
      • Sulfonylureas
      • Thiazolidinediones
      • Tolazamide
      • Tolbutamide
      Acetohexamide: (Minor) Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. [6266] Acitretin: (Major) Acitretin interferes with the contraceptive effect of microdose progestins ('minipill' contraceptive preparations), and may possibly interfere with the effecitivenss of emergency contraceptives like levonorgestrel (e.g., Plan B, Plan B OneStep). It is not known if acitretin also interacts with other progestational contraceptives, such as levonorgestrel implants or IUDs or if these methods are adequate methods of contraception during acitretin therapy. However, female patients should be advised of the possibility that any contraceptive method can fail. Since Acitretin may cause serious birth defects, the patient should use 2 forms of reliable contraception at the same time for at least 1 month before beginning acitretin therapy, during acitretin therapy, and must continue to use them for at least 3 years after acitretin treatment has stopped. It is recommended that the patient either abstain from sexual intercourse or use 2 reliable kinds of birth control at the same time to prevent unwanted pregnancy. [5225] Adagrasib: (Moderate) Use caution if coadministration of adagrasib with progestins is necessary, as the systemic exposure of progestins may be increased resulting in an increase in treatment-related adverse reactions. Progestins are metabolized primarily by hydroxylation via a CYP3A; adagrasib is a strong CYP3A inhibitor. [63694] [68325] Alogliptin: (Minor) Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. [7347] Alogliptin; Metformin: (Minor) Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. [7347] (Minor) Patients receiving antidiabetic agents like metformin should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. Progestins can impair glucose tolerance. [28550] [30585] [62853] Alogliptin; Pioglitazone: (Minor) Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. [7347] (Minor) Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. [30585] [62853] Alpha-glucosidase Inhibitors: (Minor) Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. [4995] Amikacin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Aminoglycosides: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Amobarbital: (Moderate) Barbiturates can accelerate the hepatic clearance of progestins. For hormonal contraceptives, this interaction could result in unintended pregnancy or breakthrough bleeding. For patients regularly taking a barbiturate, an alternative or back-up method of contraception may be advisable to ensure contraceptive reliability during the use of the barbiturate, and for 1 month following the discontinuation of barbiturate use. The exception is the use of levonorgestrel progestin IUDs, which have not been reported to interact and appear to maintain reliable efficacy. Pregnancy has been reported during therapy with both estrogen- and/or progestin-based oral contraceptives in patients receiving barbiturates (e.g., phenobarbital). For patients taking progestins for other indications, like hormone replacement, monitor the patient for signs and symptoms of reduced therapeutic efficacy or need for dosage adjustment. [22005] [28502] [29653] [29821] [30802] [30858] [30890] [33322] [42126] [46375] [48201] [48254] [49996] [57048] [57271] [57649] [59800] [62899] Amoxicillin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Amoxicillin; Clarithromycin; Omeprazole: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include clarithromycin. [28238] [28482] [28509] [31698] [34329] Amoxicillin; Clavulanic Acid: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Ampicillin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Ampicillin; Sulbactam: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Apalutamide: (Major) Progestins are susceptible to drug interactions with hepatic enzyme inducing drugs such as apalutamide. Concurrent administration of apalutamide with progestins, oral contraceptives, or non-oral combination contraceptives may reduce hormonal concentrations. Progestins are CYP3A4 substrates and apalutamide is a strong CYP3A4 inducer. If the hormone is used for contraception, an alternate or additional form of contraception should be considered. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of apalutamide. Monitor hormonal replacement therapy for loss of efficacy while on apalutamide, with dose adjustments as needed. Women taking hormonal replacement and apalutamide should report breakthrough bleeding to their prescribers. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin). [62874] [63694] Aprepitant, Fosaprepitant: (Major) If aprepitant, fosaprepitant is coadministered with hormonal contraceptives, including hormonal contraceptive devices (skin patches, implants, and hormonal IUDs), use an alternative or back-up non-hormonal method of contraception (e.g., condoms, spermicides) during treatment and for at least 1 month following the last dose of aprepitant, fosaprepitant. The efficacy of progestins may be reduced when coadministered with aprepitant, fosaprepitant and for 28 days after the last dose. The exact mechanism for this interaction has not been described. Progestins are CYP3A4 substrates and aprepitant, fosaprepitant is a CYP3A4 inducer; however, aprepitant, fosaprepitant is also a dose-dependent weak-to-moderate CYP3A4 inhibitor. When administered as an oral 3-day regimen (125mg/80mg/80mg) in combination with ondansetron and dexamethasone, aprepitant decreased trough concentrations of ethinyl estradiol and norethindrone by up to 64% for 3 weeks post-treatment. When ethinyl estradiol and norgestimate were administered on days 1 to 21 and aprepitant (40mg) give as a single dose on day 8, the AUC of ethinyl estradiol decreased by 4% on day 8 and by 29% on day 12; the AUC of norelgestromin increased by 18% on day 8, and decreased by 10% on day 12. Trough concentrations of both ethinyl estradiol and norelgestromin were generally lower after coadministration of aprepitant (40mg) on day 8 compared to administration without aprepitant. Specific studies have not been done with other hormonal contraceptives (e.g., progestins, non-oral combination contraceptives), an alternative or additional non-hormonal method of birth control during treatment and for 28 days after treatment is prudent to avoid potential for contraceptive failure. The clinical significance of this is not known since aprepitant, fosaprepitant is only used intermittently. [30676] [40617] [47343] [57085] Armodafinil: (Major) Armodafinil may cause failure of oral contraceptives or hormonal contraceptive-containing implants or devices due to induction of CYP3A4 isoenzyme metabolism of estrogens and/or the progestins in these products. Female patients of child-bearing potential should be advised to discuss contraceptive options with their health care provider to prevent unintended pregnancies. An alternative method or an additional method of contraception should be utilized during armodafinil therapy and continued for one month after armodafinil discontinuation. [33467] Artemether; Lumefantrine: (Major) Although no formal drug interaction studies have been performed, the manufacturer states that artemether; lumefantrine may reduce the effectiveness of hormonal contraceptives, including progestin contraceptives (i.e. levonorgestrel). Additional use of a non-hormonal method of birth control is recommended. [35401] [4744] Aspirin, ASA; Butalbital; Caffeine: (Moderate) Barbiturates can accelerate the hepatic clearance of progestins. For hormonal contraceptives, this interaction could result in unintended pregnancy or breakthrough bleeding. For patients regularly taking a barbiturate, an alternative or back-up method of contraception may be advisable to ensure contraceptive reliability during the use of the barbiturate, and for 1 month following the discontinuation of barbiturate use. The exception is the use of levonorgestrel progestin IUDs, which have not been reported to interact and appear to maintain reliable efficacy. Pregnancy has been reported during therapy with both estrogen- and/or progestin-based oral contraceptives in patients receiving barbiturates (e.g., phenobarbital). For patients taking progestins for other indications, like hormone replacement, monitor the patient for signs and symptoms of reduced therapeutic efficacy or need for dosage adjustment. [22005] [28502] [29653] [29821] [30802] [30858] [30890] [33322] [42126] [46375] [48201] [48254] [49996] [57048] [57271] [57649] [59800] [62899] Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Barbiturates can accelerate the hepatic clearance of progestins. For hormonal contraceptives, this interaction could result in unintended pregnancy or breakthrough bleeding. For patients regularly taking a barbiturate, an alternative or back-up method of contraception may be advisable to ensure contraceptive reliability during the use of the barbiturate, and for 1 month following the discontinuation of barbiturate use. The exception is the use of levonorgestrel progestin IUDs, which have not been reported to interact and appear to maintain reliable efficacy. Pregnancy has been reported during therapy with both estrogen- and/or progestin-based oral contraceptives in patients receiving barbiturates (e.g., phenobarbital). For patients taking progestins for other indications, like hormone replacement, monitor the patient for signs and symptoms of reduced therapeutic efficacy or need for dosage adjustment. [22005] [28502] [29653] [29821] [30802] [30858] [30890] [33322] [42126] [46375] [48201] [48254] [49996] [57048] [57271] [57649] [59800] [62899] Atazanavir: (Major) Studies evaluating use of atazanavir with levonorgestrel have not been conducted; therefore, an alternative method of contraception is recommended. Taking these drugs together may alter the exposure and serum concentrations of levonorgestrel. If the drugs must be used together, instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms. [28142] Atazanavir; Cobicistat: (Major) Consider the benefits and risk of administering antiretroviral regimens containing cobicistat with levonorgestrel. Insufficient data are available to make dosage recommendations, particularly when cobicistat is combined in other antiviral regimens. It is not clear how cobicistat alters various progestin-only agents used for contraception, fertility or luteal support, or for hormone replacement therapy (HRT). Instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. There is a potential for altered efficacy for combined hormonal contraceptives. Consider alternative methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS. When progestins are used for other purposes, monitor for altered clinical response to hormonal therapy. [51664] [58000] (Major) Studies evaluating use of atazanavir with levonorgestrel have not been conducted; therefore, an alternative method of contraception is recommended. Taking these drugs together may alter the exposure and serum concentrations of levonorgestrel. If the drugs must be used together, instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. It may be prudent for women who receive hormonal contraceptives with atazanavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms. [28142] Azithromycin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Aztreonam: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Bacitracin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Barbiturates: (Moderate) Barbiturates can accelerate the hepatic clearance of progestins. For hormonal contraceptives, this interaction could result in unintended pregnancy or breakthrough bleeding. For patients regularly taking a barbiturate, an alternative or back-up method of contraception may be advisable to ensure contraceptive reliability during the use of the barbiturate, and for 1 month following the discontinuation of barbiturate use. The exception is the use of levonorgestrel progestin IUDs, which have not been reported to interact and appear to maintain reliable efficacy. Pregnancy has been reported during therapy with both estrogen- and/or progestin-based oral contraceptives in patients receiving barbiturates (e.g., phenobarbital). For patients taking progestins for other indications, like hormone replacement, monitor the patient for signs and symptoms of reduced therapeutic efficacy or need for dosage adjustment. [22005] [28502] [29653] [29821] [30802] [30858] [30890] [33322] [42126] [46375] [48201] [48254] [49996] [57048] [57271] [57649] [59800] [62899] Belzutifan: (Major) Women taking both progestins and belzutifan should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed belzutifan. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of belzutifan. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and belzutifan is a weak CYP3A4 inducer. [33322] [57648] [66875] Bexarotene: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy. [4791] [4792] Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Bosentan: (Major) Hormonal contraceptives should not be used as the sole method to prevent pregnancy in patients receiving bosentan. There is a possibility of contraceptive failure when bosentan is coadministered with products containing estrogens and/or progestins. Bosentan is teratogenic. To prevent pregnancy, females of reproductive potential must use 2 acceptable contraception methods during treatment and for 1 month after discontinuation of bosentan therapy. The patient may choose 1 highly effective contraceptive form, including an intrauterine device (IUD) or tubal sterilization, a combination of a hormonal contraceptive with a barrier method, or 2 barrier methods. If a male partner's vasectomy is chosen as a method of contraception, a hormonal or barrier method must still be used by the female patient. Hormonal contraceptives, including oral contraceptives or non-oral combination contraceptives (injectable, transdermal, and implantable contraceptives) may not be reliably effective in the presence of bosentan, since many contraceptive drugs are metabolized by CYP3A4 isoenzymes and bosentan is a significant inducer of CYP3A enzymes. Decreases in hormonal exposure have been documented in drug interaction studies of bosentan with hormonal contraception. Additionally, estrogens and progestins used for hormone replacement therapy (HRT) may also be less effective; patients should be monitored for changes in efficacy such as breakthrough bleeding or an increase in hot flashes. Dosage adjustments may be necessary. [28496] Bromocriptine: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Progestins can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended; an alternate form of contraception is recommended during bromocriptine therapy. [5066] Butabarbital: (Moderate) Barbiturates can accelerate the hepatic clearance of progestins. For hormonal contraceptives, this interaction could result in unintended pregnancy or breakthrough bleeding. For patients regularly taking a barbiturate, an alternative or back-up method of contraception may be advisable to ensure contraceptive reliability during the use of the barbiturate, and for 1 month following the discontinuation of barbiturate use. The exception is the use of levonorgestrel progestin IUDs, which have not been reported to interact and appear to maintain reliable efficacy. Pregnancy has been reported during therapy with both estrogen- and/or progestin-based oral contraceptives in patients receiving barbiturates (e.g., phenobarbital). For patients taking progestins for other indications, like hormone replacement, monitor the patient for signs and symptoms of reduced therapeutic efficacy or need for dosage adjustment. [22005] [28502] [29653] [29821] [30802] [30858] [30890] [33322] [42126] [46375] [48201] [48254] [49996] [57048] [57271] [57649] [59800] [62899] Butalbital; Acetaminophen: (Moderate) Barbiturates can accelerate the hepatic clearance of progestins. For hormonal contraceptives, this interaction could result in unintended pregnancy or breakthrough bleeding. For patients regularly taking a barbiturate, an alternative or back-up method of contraception may be advisable to ensure contraceptive reliability during the use of the barbiturate, and for 1 month following the discontinuation of barbiturate use. The exception is the use of levonorgestrel progestin IUDs, which have not been reported to interact and appear to maintain reliable efficacy. Pregnancy has been reported during therapy with both estrogen- and/or progestin-based oral contraceptives in patients receiving barbiturates (e.g., phenobarbital). For patients taking progestins for other indications, like hormone replacement, monitor the patient for signs and symptoms of reduced therapeutic efficacy or need for dosage adjustment. [22005] [28502] [29653] [29821] [30802] [30858] [30890] [33322] [42126] [46375] [48201] [48254] [49996] [57048] [57271] [57649] [59800] [62899] Butalbital; Acetaminophen; Caffeine: (Moderate) Barbiturates can accelerate the hepatic clearance of progestins. For hormonal contraceptives, this interaction could result in unintended pregnancy or breakthrough bleeding. For patients regularly taking a barbiturate, an alternative or back-up method of contraception may be advisable to ensure contraceptive reliability during the use of the barbiturate, and for 1 month following the discontinuation of barbiturate use. The exception is the use of levonorgestrel progestin IUDs, which have not been reported to interact and appear to maintain reliable efficacy. Pregnancy has been reported during therapy with both estrogen- and/or progestin-based oral contraceptives in patients receiving barbiturates (e.g., phenobarbital). For patients taking progestins for other indications, like hormone replacement, monitor the patient for signs and symptoms of reduced therapeutic efficacy or need for dosage adjustment. [22005] [28502] [29653] [29821] [30802] [30858] [30890] [33322] [42126] [46375] [48201] [48254] [49996] [57048] [57271] [57649] [59800] [62899] Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Barbiturates can accelerate the hepatic clearance of progestins. For hormonal contraceptives, this interaction could result in unintended pregnancy or breakthrough bleeding. For patients regularly taking a barbiturate, an alternative or back-up method of contraception may be advisable to ensure contraceptive reliability during the use of the barbiturate, and for 1 month following the discontinuation of barbiturate use. The exception is the use of levonorgestrel progestin IUDs, which have not been reported to interact and appear to maintain reliable efficacy. Pregnancy has been reported during therapy with both estrogen- and/or progestin-based oral contraceptives in patients receiving barbiturates (e.g., phenobarbital). For patients taking progestins for other indications, like hormone replacement, monitor the patient for signs and symptoms of reduced therapeutic efficacy or need for dosage adjustment. [22005] [28502] [29653] [29821] [30802] [30858] [30890] [33322] [42126] [46375] [48201] [48254] [49996] [57048] [57271] [57649] [59800] [62899] Calaspargase pegol: (Major) The concomitant use of calaspargase pegol and oral contraceptives may reduce the efficacy of oral contraceptives. Women of reproductive potential should use a non-hormonal method of birth control during therapy and for at least 3 months after the last calaspargase pegol dose due to the risk of fetal harm. [63842] Canagliflozin: (Minor) Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. [30585] [62853] Canagliflozin; Metformin: (Minor) Patients receiving antidiabetic agents like metformin should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. Progestins can impair glucose tolerance. [28550] [30585] [62853] (Minor) Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. [30585] [62853] Carbamazepine: (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin). [28024] [30675] [33322] [41237] [42126] [48201] [57036] [57588] [57648] [63694] Carbapenems: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Cefaclor: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Cefadroxil: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Cefazolin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Cefdinir: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Cefditoren: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Cefepime: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Cefiderocol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Cefixime: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Cefotaxime: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Cefotetan: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Cefoxitin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Cefpodoxime: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Cefprozil: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Ceftaroline: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Ceftazidime: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Ceftazidime; Avibactam: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Ceftibuten: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Ceftizoxime: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Ceftolozane; Tazobactam: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Ceftriaxone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Cefuroxime: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Cenobamate: (Major) Women taking both progestins and cenobamate should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed cenobamate. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of cenobamate. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on cenobamate, with dose adjustments made based on clinical efficacy. Progestins are CYP3A4 substrates and cenobamate is a moderate CYP3A4 inducer. Concurrent administration may increase progestin elimination. [33322] [57648] [64768] Cephalexin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Charcoal: (Major) Note that charcoal exerts a nonspecific effect, and many medications can be adsorbed by activated charcoal; repeat doses may decrease the enterohepatic recycling of some drugs. Activated charcoal dietary supplements may have the potential to reduce the effectiveness of oral contraceptives. Data clearly demonstrating this interaction are not available. Ovulatory potential was studied during the use of two monophasic oral contraceptive pill preparations, after repeated mid-cycle administration of activated charcoal to treat diarrhea in women. None of eleven women ovulated. Repeated charcoal treatment, when administered 3 hours after but at least 12 hours before pill intake, did not alter oral contraceptive efficacy. [6833] [6834] Chenodiol: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol. [37102] Chloramphenicol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include chloramphenicol. [28482] [28509] [29624] [31698] Chlorpropamide: (Minor) Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. [6266] Ciprofloxacin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Clarithromycin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include clarithromycin. [28238] [28482] [28509] [31698] [34329] Clindamycin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Clobazam: (Major) Clobazam induces CYP3A4, which may reduce the concentrations of estrogen and progestin hormones. Hormonal contraceptives may not be reliable when coadministered with clobazam. Females taking hormonal-based birth control should use additional non-hormonal methods and not rely solely on hormonal contraceptive methods when taking clobazam. The additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Hormonal contraceptives include combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins and includes oral, injectable, transdermal, vaginal inserts, and implantable forms of hormonal birth control. Clobazam may also reduce the effectiveness of other estrogens or progestins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on clobazam, with adjustments made based on clinical efficacy. [46370] Cobicistat: (Major) Consider the benefits and risk of administering antiretroviral regimens containing cobicistat with levonorgestrel. Insufficient data are available to make dosage recommendations, particularly when cobicistat is combined in other antiviral regimens. It is not clear how cobicistat alters various progestin-only agents used for contraception, fertility or luteal support, or for hormone replacement therapy (HRT). Instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. There is a potential for altered efficacy for combined hormonal contraceptives. Consider alternative methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS. When progestins are used for other purposes, monitor for altered clinical response to hormonal therapy. [51664] [58000] Colistimethate, Colistin, Polymyxin E: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Colistin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Dabrafenib: (Major) Avoid concomitant use of dabrafenib and hormonal contraceptives; decreased hormonal contraceptive concentrations and loss of efficacy may occur. Use of an alternative non-hormonal contraceptive method of birth control is recommended during treatment for 2 weeks after the last dose of dabrafenib. Dabrafenib is a moderate CYP3A4 inducer and many hormonal contraceptive are CYP3A4 substrates. [54802] Dalbavancin: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Dapagliflozin: (Minor) Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. [7347] Dapagliflozin; Metformin: (Minor) Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. [7347] (Minor) Patients receiving antidiabetic agents like metformin should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. Progestins can impair glucose tolerance. [28550] [30585] [62853] Dapagliflozin; Saxagliptin: (Minor) Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. [7347] (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. [7347] Daptomycin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Darunavir: (Major) Studies evaluating use of darunavir (boosted with either ritonavir or cobicistat) with levonorgestrel have not been conducted; therefore, an alternative (non-hormonal) method of contraception is recommended. Taking these drugs together may alter the exposure and serum concentrations of levonorgestrel. If the drugs must be used together, instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. It may be prudent for women who receive hormonal contraceptives with darunavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms. [32432] [58763] Darunavir; Cobicistat: (Major) Consider the benefits and risk of administering antiretroviral regimens containing cobicistat with levonorgestrel. Insufficient data are available to make dosage recommendations, particularly when cobicistat is combined in other antiviral regimens. It is not clear how cobicistat alters various progestin-only agents used for contraception, fertility or luteal support, or for hormone replacement therapy (HRT). Instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. There is a potential for altered efficacy for combined hormonal contraceptives. Consider alternative methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS. When progestins are used for other purposes, monitor for altered clinical response to hormonal therapy. [51664] [58000] (Major) Studies evaluating use of darunavir (boosted with either ritonavir or cobicistat) with levonorgestrel have not been conducted; therefore, an alternative (non-hormonal) method of contraception is recommended. Taking these drugs together may alter the exposure and serum concentrations of levonorgestrel. If the drugs must be used together, instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. It may be prudent for women who receive hormonal contraceptives with darunavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms. [32432] [58763] Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Consider the benefits and risk of administering antiretroviral regimens containing cobicistat with levonorgestrel. Insufficient data are available to make dosage recommendations, particularly when cobicistat is combined in other antiviral regimens. It is not clear how cobicistat alters various progestin-only agents used for contraception, fertility or luteal support, or for hormone replacement therapy (HRT). Instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. There is a potential for altered efficacy for combined hormonal contraceptives. Consider alternative methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS. When progestins are used for other purposes, monitor for altered clinical response to hormonal therapy. [51664] [58000] (Major) Studies evaluating use of darunavir (boosted with either ritonavir or cobicistat) with levonorgestrel have not been conducted; therefore, an alternative (non-hormonal) method of contraception is recommended. Taking these drugs together may alter the exposure and serum concentrations of levonorgestrel. If the drugs must be used together, instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. It may be prudent for women who receive hormonal contraceptives with darunavir boosted with ritonavir or cobicistat to use an additional method of contraception to protect against unwanted pregnancy. Further, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, HIV-infected women should use an additional barrier method of contraception such as condoms. [32432] [58763] Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) Data on the effects that protease inhibitors have on the serum concentrations of estrogens and progestins are complex. Some protease inhibitors increase (i.e., ritonavir, lopinavir; ritonavir, nelfinavir, tipranavir) and others decrease (i.e., atazanavir, indinavir) the metabolism of hormonal contraceptives. The safety and efficacy of hormonal contraceptives may be affected if coadministered with protease inhibitors. Women receiving hormonal contraceptives and anti-retroviral protease inhibitors concurrently should be instructed to report any breakthrough bleeding or other adverse effects to their prescribers. It may be prudent for women who receive hormonal contraceptives concurrently with protease inhibitors to use an additional method of contraception to protect against unwanted pregnancy, unless other drug-specific recommendations are made by the manufacturer of the protease inhibitor. Furthermore, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, women who receive hormonal contraceptives concurrently with protease inhibitors should use an additional barrier method of contraception such as condoms. [46638] [5044] Deferasirox: (Moderate) Counsel patients to use non-hormonal methods of contraception during treatment with deferasirox. Deferasirox may induce the CYP3A4 metabolism of hormonal contraceptives; thereby decreasing their effectiveness. [31807] [52930] Delafloxacin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Demeclocycline: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Dicloxacillin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Doripenem: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Doxycycline: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Efavirenz: (Major) Patients should be advised to use a reliable method of barrier contraception in addition to oral contraceptives or non-oral combination contraceptives, including implantable etonogestrel, while using efavirenz. Efavirenz has no effect on ethinyl estradiol concentrations, but levels of progestins (norelgestromin and levonorgestrel) can be markedly decreased. Norelgestromin Cmax and AUC decreased by 46% and 64%, respectively. Levonorgestrel Cmax and AUC decreased bu 80% and 83%, respectively. There have been post-marketing reports of contraceptive failure with implantable etonogestrel in efavirenz-exposed patients. Decreased exposure of etonogestrel may be expected. There are no effects of ethinyl estradiol/norgestimate on efavirenz plasma concentrations. [28442] [46638] Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Patients should be advised to use a reliable method of barrier contraception in addition to oral contraceptives or non-oral combination contraceptives, including implantable etonogestrel, while using efavirenz. Efavirenz has no effect on ethinyl estradiol concentrations, but levels of progestins (norelgestromin and levonorgestrel) can be markedly decreased. Norelgestromin Cmax and AUC decreased by 46% and 64%, respectively. Levonorgestrel Cmax and AUC decreased bu 80% and 83%, respectively. There have been post-marketing reports of contraceptive failure with implantable etonogestrel in efavirenz-exposed patients. Decreased exposure of etonogestrel may be expected. There are no effects of ethinyl estradiol/norgestimate on efavirenz plasma concentrations. [28442] [46638] Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Patients should be advised to use a reliable method of barrier contraception in addition to oral contraceptives or non-oral combination contraceptives, including implantable etonogestrel, while using efavirenz. Efavirenz has no effect on ethinyl estradiol concentrations, but levels of progestins (norelgestromin and levonorgestrel) can be markedly decreased. Norelgestromin Cmax and AUC decreased by 46% and 64%, respectively. Levonorgestrel Cmax and AUC decreased bu 80% and 83%, respectively. There have been post-marketing reports of contraceptive failure with implantable etonogestrel in efavirenz-exposed patients. Decreased exposure of etonogestrel may be expected. There are no effects of ethinyl estradiol/norgestimate on efavirenz plasma concentrations. [28442] [46638] Elagolix: (Major) During use of elagolix, females of childbearing potential should use non-hormonal methods of contraception for the duration of treatment and for 28 days following the discontinuation of therapy. Estrogen-containing injectable, implantable, transdermal, vaginal or oral contraceptives are expected to reduce the efficacy of elagolix. The effect of progestin-only contraceptives on elagolix is not known. However, elagolix is a weak to moderate inducer of CYP3A4, and many estrogens and progestins are metabolized via this enzyme. Thus, elagolix may decrease plasma concentrations of hormonal contraceptives. Coadministration of elagolix 200 mg twice daily and a combined oral contraceptive (COC) containing 0.1 mg levonorgestrel decreases the plasma concentrations of levonorgestrel by 27%, potentially affecting contraceptive efficacy. Coadministration of elagolix with COCs containing norethindrone acetate did not show reduction in plasma concentrations of norethindrone. Elagolix may also increase contraceptive concentrations. Coadministration of a COC (containing 20 mcg ethinyl estradiol/0.1 mg levonorgestrel) following administration of elagolix 200 mg twice daily for 14 days increases the plasma ethinyl estradiol concentration by 2.2-fold compared to this COC alone; this may lead to increased risk of ethinyl estradiol-related adverse events including thromboembolic disorders and vascular events. [63387] Elagolix; Estradiol; Norethindrone acetate: (Major) During use of elagolix, females of childbearing potential should use non-hormonal methods of contraception for the duration of treatment and for 28 days following the discontinuation of therapy. Estrogen-containing injectable, implantable, transdermal, vaginal or oral contraceptives are expected to reduce the efficacy of elagolix. The effect of progestin-only contraceptives on elagolix is not known. However, elagolix is a weak to moderate inducer of CYP3A4, and many estrogens and progestins are metabolized via this enzyme. Thus, elagolix may decrease plasma concentrations of hormonal contraceptives. Coadministration of elagolix 200 mg twice daily and a combined oral contraceptive (COC) containing 0.1 mg levonorgestrel decreases the plasma concentrations of levonorgestrel by 27%, potentially affecting contraceptive efficacy. Coadministration of elagolix with COCs containing norethindrone acetate did not show reduction in plasma concentrations of norethindrone. Elagolix may also increase contraceptive concentrations. Coadministration of a COC (containing 20 mcg ethinyl estradiol/0.1 mg levonorgestrel) following administration of elagolix 200 mg twice daily for 14 days increases the plasma ethinyl estradiol concentration by 2.2-fold compared to this COC alone; this may lead to increased risk of ethinyl estradiol-related adverse events including thromboembolic disorders and vascular events. [63387] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Consider the benefits and risk of administering antiretroviral regimens containing cobicistat with levonorgestrel. Insufficient data are available to make dosage recommendations, particularly when cobicistat is combined in other antiviral regimens. It is not clear how cobicistat alters various progestin-only agents used for contraception, fertility or luteal support, or for hormone replacement therapy (HRT). Instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. There is a potential for altered efficacy for combined hormonal contraceptives. Consider alternative methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS. When progestins are used for other purposes, monitor for altered clinical response to hormonal therapy. [51664] [58000] (Moderate) Consider the benefits and risk of administering elvitegravir with ethinyl estradiol; norgestimate and other combination oral contraceptives. Concurrent use may result in elevated norgestimate and reduced ethinyl estradiol serum concentrations. Risk associated with these altered concentrations may include increased insulin resistance, dyslipidemia, acne, and venous thrombosis. Consider alternative non-hormonal methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS. [46638] [58001] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Consider the benefits and risk of administering antiretroviral regimens containing cobicistat with levonorgestrel. Insufficient data are available to make dosage recommendations, particularly when cobicistat is combined in other antiviral regimens. It is not clear how cobicistat alters various progestin-only agents used for contraception, fertility or luteal support, or for hormone replacement therapy (HRT). Instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. There is a potential for altered efficacy for combined hormonal contraceptives. Consider alternative methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS. When progestins are used for other purposes, monitor for altered clinical response to hormonal therapy. [51664] [58000] (Moderate) Consider the benefits and risk of administering elvitegravir with ethinyl estradiol; norgestimate and other combination oral contraceptives. Concurrent use may result in elevated norgestimate and reduced ethinyl estradiol serum concentrations. Risk associated with these altered concentrations may include increased insulin resistance, dyslipidemia, acne, and venous thrombosis. Consider alternative non-hormonal methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS. [46638] [58001] Empagliflozin: (Minor) Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. [60134] Empagliflozin; Linagliptin: (Minor) Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. [60134] (Minor) Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Patients receiving antidiabetic agents, such as linagliptin, should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. [7347] Empagliflozin; Linagliptin; Metformin: (Minor) Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. [60134] (Minor) Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Patients receiving antidiabetic agents, such as linagliptin, should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. [7347] (Minor) Patients receiving antidiabetic agents like metformin should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. Progestins can impair glucose tolerance. [28550] [30585] [62853] Empagliflozin; Metformin: (Minor) Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. [60134] (Minor) Patients receiving antidiabetic agents like metformin should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. Progestins can impair glucose tolerance. [28550] [30585] [62853] Encorafenib: (Major) Avoid coadministration of encorafenib and hormonal contraceptives due to the potential for loss of contraceptive efficacy. Advise females of reproductive potential to use an effective, non-hormonal method of contraception during treatment and for 2 weeks after the final dose of encorafenib. Encorafenib can cause fetal harm when administered during pregnancy. [63317] Enzalutamide: (Major) Avoid coadministration of enzalutamide with progestins if used for contraception; consider an alternate or additional form of contraception. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of enzalutamide. Patients taking hormonal replacement therapy may need to be monitored for reduced clinical effect while on enzalutamide, with dose adjustments made based on clinical efficacy. Higher-dose hormonal regimens may be indicated where acceptable or applicable. Women taking hormonal replacement and enzalutamide should report breakthrough bleeding, hot flashes, or other symptoms to their prescribers. Progestins are substrates of CYP3A4 and enzalutamide is a strong CYP3A4 inducer. Concurrent administration of enzalutamide with progestins, oral contraceptives, or non-oral combination contraceptives may reduce hormonal concentrations. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin). [51727] [63694] Eravacycline: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Ertapenem: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Ertugliflozin: (Minor) Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. [30585] [62853] Ertugliflozin; Metformin: (Minor) Patients receiving antidiabetic agents like metformin should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. Progestins can impair glucose tolerance. [28550] [30585] [62853] (Minor) Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. [30585] [62853] Ertugliflozin; Sitagliptin: (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. [7347] (Minor) Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. [30585] [62853] Erythromycin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Eslicarbazepine: (Major) Coadministration of eslicarbazepine with oral contraceptives may result in contraceptive failure. Coadministration of eslicarbazepine and ethinyl estradiol and levonorgestrel has resulted in decreased plasma concentrations of these hormones. Instruct females of child-bearing potential to use additional or non-hormonal contraception during therapy with eslicarbazepine and after treatment has been discontinued for at least one menstrual cycle. [56436] Etravirine: (Major) Women taking both progestins and etravirine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed etravirine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of etravirine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and etravirine is a strong CYP3A4 inducer. [33322] [33718] [57648] [63694] Exenatide: (Moderate) Separate the administration times of exenatide and estrogen and progestin containing oral contraceptives. Advise patients to take estrogen and progestin containing oral contraceptives at least 1 hour before exenatide. Exenatide slows gastric emptying and simultaneous coadministration may reduce the rate and extent of estrogen and progestin oral absorption which may reduce efficacy. Additionally, estrogens can impair glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day. [30585] [44456] [48491] [62853] Felbamate: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary. [7006] [7241] Fidaxomicin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Flibanserin: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including oral contraceptives, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the risks of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient. In one study of 24 healthy women, the effect of 100 mg flibanserin once daily for 2 weeks on the pharmacokinetics of a single dose of ethinyl estradiol 30 mcg/levonorgestrel 150 mcg was evaluated. Flibanserin increased the AUC and Cmax of ethinyl estradiol by 1.09-fold and 1.1-fold, respectively. Flibanserin decreased the levonorgestrel AUC by 1.06-fold. During pre-marketing evaluation of flibanserin, patients who reported using oral contraceptives had a greater incidence of CNS effects than flibenserin-treated patients who did not report oral contraceptive use, including dizziness (13.4% vs. 9.9%), somnolence (12.3% vs. 10.6%), and fatigue (11.4% vs. 7.5%). [60099] Fosamprenavir: (Major) Avoid concurrent use of contraceptives and hormone replacement therapies (HRT) containing progestins with fosamprenavir. Alternative methods of non-hormonal contraception are recommended. Concomitant use may decrease the efficacy of both the progestin and fosamprenavir, which could lead to loss of virologic response and possible viral resistance. Additionally, there is an increased risk of transaminase elevations during concurrent use of progestins and fosamprenavir boosted with ritonavir. [29012] [68183] Gemifloxacin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used with antibiotics. Oral contraceptives (estrogen/progesterone) reduced the AUC and Cmax of gemifloxacin by 19% and 12%, respectively. These reductions are considered to be clinically insignificant. Gemifloxacin did not affect the pharmacokinetics of an ethinyl estradiol/levonorgestrel oral contraceptive product in healthy females. It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28424] [28482] [28509] Gentamicin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Glimepiride: (Minor) Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. [6266] Glimepiride; Rosiglitazone: (Minor) Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. [30585] [62853] (Minor) Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. [6266] Glipizide: (Minor) Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. [6266] Glipizide; Metformin: (Minor) Patients receiving antidiabetic agents like metformin should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. Progestins can impair glucose tolerance. [28550] [30585] [62853] (Minor) Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. [6266] Glyburide: (Minor) Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. [6266] Glyburide; Metformin: (Minor) Patients receiving antidiabetic agents like metformin should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. Progestins can impair glucose tolerance. [28550] [30585] [62853] (Minor) Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. [6266] Glycylcyclines: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Griseofulvin: (Major) The concurrent use of griseofulvin and oral contraceptives can reduce contraceptive efficacy and result in an unintended pregnancy and/or breakthrough bleeding. This risk is particularly serious because griseofulvin is contraindicated during pregnancy due to the risk of teratogenic and abortifacient effects. An alternate or additional form of contraception should be used during concomitant treatment and continued for 1 month after griseofulvin discontinuation. If these drugs are used together, counsel the patient about the risk of pregnancy and teratogenic effects, and instruct the patient to notify the prescriber if they experience breakthrough bleeding while receiving these drugs together. Additionally, patients taking non-oral combination contraceptives or progestins for hormone replacement therapy may also experience reduced clinical efficacy. [28509] [45723] [58441] [59800] Hydantoins: (Major) Women taking both progestins and hydantoins should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of non-hormonal contraception should be considered in patients prescribed hydantoins. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of hydantoins. Patients taking progestins for other indications may need to be monitored for reduced clinical effect while on hydantoins, with dose adjustments made based on clinical efficacy. Hydantoins are strong hepatic CYP450 inducers. Concurrent administration may increase progestin elimination This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin). [28535] [28771] [42126] [48201] [57036] [57588] [57648] [63694] Idelalisib: (Moderate) Idelalisib is a strong CYP3A inhibitor, and ethinyl estradiol (EE) is a CYP3A substrate. Use caution in dose selection, as the hormonal side effects of ethinyl estradiol may be increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Females of reproductive potential should avoid becoming pregnant during idelalisib therapy, using effective contraception during treatment and for at least 1 month after the last dose. Thus, use idelalisib with caution in combination with any combination oral contraceptives, most of which contain EE or mestranol (which is converted to EE). In addiiton, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. [31698] [47343] [4744] [57675] Imipenem; Cilastatin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Imipenem; Cilastatin; Relebactam: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Indinavir: (Moderate) Indinavir decreases the metabolism of oral contraceptives and non-oral combination contraceptives; the AUC for ethinyl estradiol and norethindrone increased by 24+/-17% and 26+/-14%, respectively, when coadministered with indinavir. Women receiving hormonal contraceptives and anti-retroviral protease inhibitors (PIs), such as indinavir, should be instructed to report any breakthrough bleeding or other adverse effects to their prescribers. Because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, women who receive hormonal contraceptives with PIs should use an additional barrier method of contraception such as condoms. [28731] [46638] Insulin Glargine; Lixisenatide: (Moderate) Separate the administration times of lixisenatide and estrogen and progestin containing oral contraceptives. Advise patients to take estrogen and progestin containing oral contraceptives at least 1 hour before or 11 hours after lixisenatide. Lixisenatide slows gastric emptying and simultaneous coadministration may reduce the rate and extent of estrogen and progestin oral absorption which may reduce efficacy. Additionally, estrogens can impair glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day. [30585] [48491] [61024] [62853] Insulins: (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. [60172] Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer. [30314] [33322] [57648] Isoniazid, INH; Rifampin: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer. [30314] [33322] [57648] Ivosidenib: (Major) Consider alternative methods of contraception in patients receiving ivosidenib. Coadministration may decrease the concentrations of hormonal contraceptives. [63368] Kanamycin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Lamotrigine: (Moderate) Patients taking progestin hormones for contraception may consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month after discontinuation of lamotrigine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lamotrigine with dose adjustments made based on clinical efficacy. The AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively, among 16 volunteers during concurrent use with lamotrigine 300 mg/day. Serum progesterone concentrations did not suggest ovulation, however, serum FSH, LH, and estradiol concentrations suggested some loss of suppression of the hypothalamic-pituitary-ovarian axis. [28451] [44123] [48201] Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include clarithromycin. [28238] [28482] [28509] [31698] [34329] Lefamulin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Leflunomide: (Moderate) Carefully consider the type and dose of oral contraceptives in patients taking leflunomide.Leflunomide may increase the effects of oral contraceptives. Following oral administration, leflunomide is metabolized to an active metabolite, teriflunomide, which is responsible for essentially all of leflunomide's in vivo activity. Following repeated teriflunomide doses, mean ethinyl estradiol Cmax and AUC increased 1.58- and 1.54-fold, respectively. Levonorgestrel Cmax increased 1.33-fold and AUC 1.41-fold during coadministration. [49634] Lesinurad: (Major) Lesinurad induces CYP3A4, which may reduce the concentrations of estrogen and progestin hormones. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females taking hormonal-based birth control should use additional non-hormonal methods and not rely solely on hormonal contraceptive methods when taking lesinurad. Hormonal contraceptives include combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins and includes oral, injectable, transdermal, vaginal inserts, and implantable forms of hormonal birth control. Lesinurad may also reduce the effectiveness of other estrogens or progestins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lesinurad, with adjustments made based on clinical efficacy. [60473] Lesinurad; Allopurinol: (Major) Lesinurad induces CYP3A4, which may reduce the concentrations of estrogen and progestin hormones. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females taking hormonal-based birth control should use additional non-hormonal methods and not rely solely on hormonal contraceptive methods when taking lesinurad. Hormonal contraceptives include combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins and includes oral, injectable, transdermal, vaginal inserts, and implantable forms of hormonal birth control. Lesinurad may also reduce the effectiveness of other estrogens or progestins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lesinurad, with adjustments made based on clinical efficacy. [60473] Levofloxacin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Linagliptin: (Minor) Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Patients receiving antidiabetic agents, such as linagliptin, should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. [7347] Linagliptin; Metformin: (Minor) Estrogens, progestins, or oral contraceptives can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving > 50 mcg of ethinyl estradiol per day. The presence or absence of a concomitant progestin may influence the significance of this effect. Patients receiving antidiabetic agents, such as linagliptin, should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. [7347] (Minor) Patients receiving antidiabetic agents like metformin should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. Progestins can impair glucose tolerance. [28550] [30585] [62853] Lincomycin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Lincosamides: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Linezolid: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Lixisenatide: (Moderate) Separate the administration times of lixisenatide and estrogen and progestin containing oral contraceptives. Advise patients to take estrogen and progestin containing oral contraceptives at least 1 hour before or 11 hours after lixisenatide. Lixisenatide slows gastric emptying and simultaneous coadministration may reduce the rate and extent of estrogen and progestin oral absorption which may reduce efficacy. Additionally, estrogens can impair glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day. [30585] [48491] [61024] [62853] Lomitapide: (Major) Concomitant use of lomitapide and oral contraceptives may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Oral Contraceptives are weak CYP3A4 inhibitors; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. In addition, females of reproductive potential must use effective contraception during lomitapide therapy. Because vomiting and diarrhea have been frequently reported during lomitapide therapy and hormone absorption from oral contraceptives may be incomplete in the presence of vomiting or diarrhea, warn patients that the use of additional contraceptive methods is warranted if vomiting or diarrhea occur. [52698] Lopinavir; Ritonavir: (Major) Data on the effects that protease inhibitors have on the serum concentrations of estrogens and progestins are complex. Some protease inhibitors increase (i.e., ritonavir, lopinavir; ritonavir, nelfinavir, tipranavir) and others decrease (i.e., atazanavir, indinavir) the metabolism of hormonal contraceptives. The safety and efficacy of hormonal contraceptives may be affected if coadministered with protease inhibitors. Women receiving hormonal contraceptives and anti-retroviral protease inhibitors concurrently should be instructed to report any breakthrough bleeding or other adverse effects to their prescribers. It may be prudent for women who receive hormonal contraceptives concurrently with protease inhibitors to use an additional method of contraception to protect against unwanted pregnancy, unless other drug-specific recommendations are made by the manufacturer of the protease inhibitor. Furthermore, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, women who receive hormonal contraceptives concurrently with protease inhibitors should use an additional barrier method of contraception such as condoms. [46638] [5044] Lorlatinib: (Major) Women taking both progestins and lorlatinib should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed lorlatinib. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of lorlatinib. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and lorlatinib is a moderate CYP3A4 inducer. [33322] [57648] [63732] Lumacaftor; Ivacaftor: (Major) Avoid concomitant use of hormonal contraceptives and lumacaftor; ivacaftor, unless the benefits outweigh the risks. Lumacaftor; ivacaftor may decrease hormonal contraceptive exposure, reducing efficacy. When coadministered with lumacaftor; ivacaftor, hormonal contraceptives are not a reliable method of effective contraception; instruct patients on alternative methods of birth control. In addition, concomitant use may increase the incidence of menstruation-associated adverse reactions (e.g., amenorrhea, dysmenorrhea, menorrhagia). [59891] Mafenide: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Meglitinides: (Minor) Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. [7053] Meropenem: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Meropenem; Vaborbactam: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Metformin: (Minor) Patients receiving antidiabetic agents like metformin should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. Progestins can impair glucose tolerance. [28550] [30585] [62853] Metformin; Repaglinide: (Minor) Patients receiving antidiabetic agents like metformin should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. Progestins can impair glucose tolerance. [28550] [30585] [62853] Metformin; Rosiglitazone: (Minor) Patients receiving antidiabetic agents like metformin should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. Progestins can impair glucose tolerance. [28550] [30585] [62853] (Minor) Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. [30585] [62853] Metformin; Saxagliptin: (Minor) Patients receiving antidiabetic agents like metformin should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. Progestins can impair glucose tolerance. [28550] [30585] [62853] (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. [7347] Metformin; Sitagliptin: (Minor) Patients receiving antidiabetic agents like metformin should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. Progestins can impair glucose tolerance. [28550] [30585] [62853] (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. [7347] Methohexital: (Moderate) Barbiturates can accelerate the hepatic clearance of progestins. For hormonal contraceptives, this interaction could result in unintended pregnancy or breakthrough bleeding. For patients regularly taking a barbiturate, an alternative or back-up method of contraception may be advisable to ensure contraceptive reliability during the use of the barbiturate, and for 1 month following the discontinuation of barbiturate use. The exception is the use of levonorgestrel progestin IUDs, which have not been reported to interact and appear to maintain reliable efficacy. Pregnancy has been reported during therapy with both estrogen- and/or progestin-based oral contraceptives in patients receiving barbiturates (e.g., phenobarbital). For patients taking progestins for other indications, like hormone replacement, monitor the patient for signs and symptoms of reduced therapeutic efficacy or need for dosage adjustment. [22005] [28502] [29653] [29821] [30802] [30858] [30890] [33322] [42126] [46375] [48201] [48254] [49996] [57048] [57271] [57649] [59800] [62899] Metronidazole: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Mifepristone: (Major) Mifepristone is a progesterone-receptor antagonist and will interfere with the effectiveness of hormonal contraceptives. Therefore, non-hormonal contraceptive methods should be used in Cushing's patients taking mifepristone. [48697] Miltefosine: (Moderate) Miltefosine-induced vomiting and/or diarrhea may affect absorption of oral contraceptives and compromise their efficacy. If vomiting or diarrhea occur during miltefosine therapy, advise females to use an additional non-oral method of effective contraception. [56867] Minocycline: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Mitotane: (Major) Levonorgestrel is not recommended for women who require chronic use of drugs that are potent inducers of hepatic enzymes, including mitotane, because contraception efficacy is likely to be reduced. Consider additional or alternative forms of contraception. Mitotane is a strong CYP3A4 inducer and progestins like levonorgestrel are CYP3A4 substrates. Coadministration may result in decreased plasma concentrations of oral and other hormonal combination contraceptives. [41934] Mivacurium: (Moderate) Plasma cholinesterase activity may be diminished by chronic administration of oral contraceptives; consider the possibility of prolonged neuromuscular block after administration of mivacurium in patients with reduced plasma cholinesterase activity. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration. [42613] [65534] Mobocertinib: (Major) Women taking both progestins and mobocertinib should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed mobocertinib. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of mobocertinib. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A substrates and mobocertinib is a weak CYP3A inducer. [33322] [57648] [63694] [66990] Modafinil: (Major) Modafinil may cause failure of oral contraceptives or hormonal contraceptive-containing implants or devices due to induction of CYP3A4 isoenzyme metabolism of the progestins in these products. An alternative method or an additional method of contraception should be utilized during modafinil therapy and continued for one month after modafinil discontinuation. If these drugs are used together, monitor patients for a decrease in clinical effects; patients should report breakthrough bleeding to their prescriber. Dosage adjustments may be necessary. [4718] [4744] [5259] Morphine: (Moderate) Combination oral contraceptives have been shown to decrease plasma concentrations of morphine, due to induction of conjugation. Monitor for decreased efficacy of morphine. [43307] [58441] Morphine; Naltrexone: (Moderate) Combination oral contraceptives have been shown to decrease plasma concentrations of morphine, due to induction of conjugation. Monitor for decreased efficacy of morphine. [43307] [58441] Moxifloxacin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28423] [28482] [28509] Nafcillin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Nelfinavir: (Major) Nelfinavir increases the metabolism of oral contraceptives and non-oral combination contraceptives; coadministration with ethinyl estradiol; norethindrone results in a 47% decrease in ethinyl estradiol plasma concentrations and an 18% decrease in norethindrone plasma concentrations. Women receiving hormonal contraceptives and anti-retroviral protease inhibitors (PIs), such as nelfinavir, should be instructed to report any breakthrough bleeding or other adverse effects to their prescribers. It may be prudent for women who receive hormonal contraceptives concurrently with PIs to use an additional method of contraception to protect against unwanted pregnancy. Additionally, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, women who receive hormonal contraceptives concurrently with PIs should use an additional barrier method of contraception such as condoms. [28839] Neomycin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Nevirapine: (Moderate) Nevirapine may decrease plasma concentrations of oral contraceptives and non-oral combination contraceptives (i.e., ethinyl estradiol and norethindrone). However despite lower exposures, literature suggests that use of nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. Thus, the manufacturer states that no dose adjustments are needed when these drugs are used for contraception in combination with nevirapine. When these oral contraceptives are used for hormone replacement and given with nevirapine, the therapeutic effect of the hormonal therapy should be monitored. [42456] Nirmatrelvir; Ritonavir: (Major) Data on the effects that protease inhibitors have on the serum concentrations of estrogens and progestins are complex. Some protease inhibitors increase (i.e., ritonavir, lopinavir; ritonavir, nelfinavir, tipranavir) and others decrease (i.e., atazanavir, indinavir) the metabolism of hormonal contraceptives. The safety and efficacy of hormonal contraceptives may be affected if coadministered with protease inhibitors. Women receiving hormonal contraceptives and anti-retroviral protease inhibitors concurrently should be instructed to report any breakthrough bleeding or other adverse effects to their prescribers. It may be prudent for women who receive hormonal contraceptives concurrently with protease inhibitors to use an additional method of contraception to protect against unwanted pregnancy, unless other drug-specific recommendations are made by the manufacturer of the protease inhibitor. Furthermore, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, women who receive hormonal contraceptives concurrently with protease inhibitors should use an additional barrier method of contraception such as condoms. [46638] [5044] Nitrofurantoin: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Ofloxacin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Omadacycline: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Ombitasvir; Paritaprevir; Ritonavir: (Major) Data on the effects that protease inhibitors have on the serum concentrations of estrogens and progestins are complex. Some protease inhibitors increase (i.e., ritonavir, lopinavir; ritonavir, nelfinavir, tipranavir) and others decrease (i.e., atazanavir, indinavir) the metabolism of hormonal contraceptives. The safety and efficacy of hormonal contraceptives may be affected if coadministered with protease inhibitors. Women receiving hormonal contraceptives and anti-retroviral protease inhibitors concurrently should be instructed to report any breakthrough bleeding or other adverse effects to their prescribers. It may be prudent for women who receive hormonal contraceptives concurrently with protease inhibitors to use an additional method of contraception to protect against unwanted pregnancy, unless other drug-specific recommendations are made by the manufacturer of the protease inhibitor. Furthermore, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, women who receive hormonal contraceptives concurrently with protease inhibitors should use an additional barrier method of contraception such as condoms. [46638] [5044] Omeprazole; Amoxicillin; Rifabutin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Oritavancin: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Oxacillin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Oxcarbazepine: (Major) Progestins are susceptible to drug interactions with hepatic enzyme inducing drugs such as oxcarbazepine. Concurrent administration of oxcarbazepine progestins may increase the hormone's elimination. A high percentage of breakthrough bleeding has been reported in the literature from the combined use of oxcarbazepine and oral contraceptives; the results of one study demonstrated that the mean AUC of ethinyl estradiol/levonorgestrel was decreased by 52% when coadministered with oxcarbazepine. Women taking both hormones and hepatic enzyme-inducing drugs should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed hepatic enzyme inducing drugs, or higher-dose hormonal regimens may be indicated where acceptable or applicable as pregnancy has been reported in patients taking the hepatic enzyme inducing drug phenytoin concurrently with hormonal contraceptives. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Additionally, epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism; if oral contraceptive failure occurs, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on oxcarbazepine, with dose adjustments made based on clinical efficacy. [22005] [5307] [55436] [57046] [57048] [5749] [57648] [6300] Paromomycin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Pegaspargase: (Major) Avoid the concomitant use of pegaspargase and oral hormonal contraceptives due to the potential for decreased contraceptive efficacy and risk of fetal harm from pegaspargase. Women of reproductive potential should use an effective non-hormonal method of birth control during therapy and for at least 3 months after the last pegaspargase dose. [61310] Penicillin G Benzathine: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Penicillin G Benzathine; Penicillin G Procaine: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Penicillin G Procaine: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Penicillin G: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Penicillin V: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillins and their derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use (i.e., amoxicillin, chloramphenicol, neomycin, nitrofurantoin, sulfonamides, etc.) may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Pentobarbital: (Moderate) Barbiturates can accelerate the hepatic clearance of progestins. For hormonal contraceptives, this interaction could result in unintended pregnancy or breakthrough bleeding. For patients regularly taking a barbiturate, an alternative or back-up method of contraception may be advisable to ensure contraceptive reliability during the use of the barbiturate, and for 1 month following the discontinuation of barbiturate use. The exception is the use of levonorgestrel progestin IUDs, which have not been reported to interact and appear to maintain reliable efficacy. Pregnancy has been reported during therapy with both estrogen- and/or progestin-based oral contraceptives in patients receiving barbiturates (e.g., phenobarbital). For patients taking progestins for other indications, like hormone replacement, monitor the patient for signs and symptoms of reduced therapeutic efficacy or need for dosage adjustment. [22005] [28502] [29653] [29821] [30802] [30858] [30890] [33322] [42126] [46375] [48201] [48254] [49996] [57048] [57271] [57649] [59800] [62899] Perampanel: (Major) Perampanel may reduce the efficacy of hormonal contraceptives containing levonorgestrel. Advise women taking perampanel and a levonorgesterol-containing contraceptive to use additional non-hormonal contraception while using perampanel and for a month after discontinuation. With concomitant use, perampanel 12 mg/day decreased the Cmax and AUC of levonorgestrel by 42% and 40%, respectively. No significant effect on oral contraception exposure was noted when lower perampanel dosing regimens (4 to 8 mg/day) were used. [52140] Pexidartinib: (Major) Avoid the concomitant use of pexidartinib and hormone-containing contraceptives; the effectiveness of hormonal contraceptives may be decreased resulting in contraceptive failure. Females of reproductive potential should avoid pregnancy during and for 1 month after treatment with pexidartinib. Advise these patients to use an effective, non-hormonal method of contraception. Pexidartinib is a moderate CYP3A inducer and many oral contraceptives are metabolized by CYP3A. [64535] Phenobarbital: (Moderate) Barbiturates can accelerate the hepatic clearance of progestins. For hormonal contraceptives, this interaction could result in unintended pregnancy or breakthrough bleeding. For patients regularly taking a barbiturate, an alternative or back-up method of contraception may be advisable to ensure contraceptive reliability during the use of the barbiturate, and for 1 month following the discontinuation of barbiturate use. The exception is the use of levonorgestrel progestin IUDs, which have not been reported to interact and appear to maintain reliable efficacy. Pregnancy has been reported during therapy with both estrogen- and/or progestin-based oral contraceptives in patients receiving barbiturates (e.g., phenobarbital). For patients taking progestins for other indications, like hormone replacement, monitor the patient for signs and symptoms of reduced therapeutic efficacy or need for dosage adjustment. [22005] [28502] [29653] [29821] [30802] [30858] [30890] [33322] [42126] [46375] [48201] [48254] [49996] [57048] [57271] [57649] [59800] [62899] Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Barbiturates can accelerate the hepatic clearance of progestins. For hormonal contraceptives, this interaction could result in unintended pregnancy or breakthrough bleeding. For patients regularly taking a barbiturate, an alternative or back-up method of contraception may be advisable to ensure contraceptive reliability during the use of the barbiturate, and for 1 month following the discontinuation of barbiturate use. The exception is the use of levonorgestrel progestin IUDs, which have not been reported to interact and appear to maintain reliable efficacy. Pregnancy has been reported during therapy with both estrogen- and/or progestin-based oral contraceptives in patients receiving barbiturates (e.g., phenobarbital). For patients taking progestins for other indications, like hormone replacement, monitor the patient for signs and symptoms of reduced therapeutic efficacy or need for dosage adjustment. [22005] [28502] [29653] [29821] [30802] [30858] [30890] [33322] [42126] [46375] [48201] [48254] [49996] [57048] [57271] [57649] [59800] [62899] Phentermine; Topiramate: (Moderate) Topiramate may reduce the efficacy of progestins used in contraception or hormone replacement therapies. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception (e.g., non-hormonal contraceptives) may also be needed. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. Pregnancy has been reported in patients who are using hormonal-containing contraceptives and hepatic enzyme inducers. [22005] [28378] [33941] [48201] [57046] [57048] [57588] [57648] Pioglitazone: (Minor) Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. [30585] [62853] Pioglitazone; Glimepiride: (Minor) Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. [30585] [62853] (Minor) Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. [6266] Pioglitazone; Metformin: (Minor) Patients receiving antidiabetic agents like metformin should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. Progestins can impair glucose tolerance. [28550] [30585] [62853] (Minor) Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. [30585] [62853] Piperacillin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Piperacillin; Tazobactam: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Pitolisant: (Major) Advise patients to use an alternative, non-hormonal contraceptive during and for at least 21 days after discontinuation of pitolisant. Pitolisant is a weak CYP3A4 inducer and may decrease the plasma exposure of hormonal contraceptives resulting in decreased efficacy. [64562] Plazomicin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Polymyxin B: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Pramlintide: (Minor) Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. [7053] Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements): (Moderate) Either additive or antagonistic effects could potentially occur if prasterone is combined with progestins. [2455] Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved): (Moderate) Either additive or antagonistic effects could potentially occur if prasterone is combined with progestins. [2455] Pretomanid: (Major) Avoid coadministration of pretomanid with oral contraceptives, especially in patients with impaired hepatic function, due to increased risk for hepatotoxicity. Monitor for evidence of hepatotoxicity if coadministration is necessary. If new or worsening hepatic dysfunction occurs, discontinue hepatotoxic medications. [63549] [64561] Primidone: (Moderate) Barbiturates can accelerate the hepatic clearance of progestins. For hormonal contraceptives, this interaction could result in unintended pregnancy or breakthrough bleeding. For patients regularly taking a barbiturate, an alternative or back-up method of contraception may be advisable to ensure contraceptive reliability during the use of the barbiturate, and for 1 month following the discontinuation of barbiturate use. The exception is the use of levonorgestrel progestin IUDs, which have not been reported to interact and appear to maintain reliable efficacy. Pregnancy has been reported during therapy with both estrogen- and/or progestin-based oral contraceptives in patients receiving barbiturates (e.g., phenobarbital). For patients taking progestins for other indications, like hormone replacement, monitor the patient for signs and symptoms of reduced therapeutic efficacy or need for dosage adjustment. [22005] [28502] [29653] [29821] [30802] [30858] [30890] [33322] [42126] [46375] [48201] [48254] [49996] [57048] [57271] [57649] [59800] [62899] Rifampin: (Major) Women taking both progestins and rifampin should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifampin. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifampin. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifampin is a strong CYP3A4 inducer. [30314] [33322] [57648] Rifapentine: (Major) Women taking both progestins and rifapentine should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed rifapentine. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of rifapentine. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and rifapentine is a strong CYP3A4 inducer. [33322] [57648] [65685] Riluzole: (Moderate) Monitor patients for increased riluzole-related adverse events, such as gastrointestinal symptoms and elevated hepatic enzymes, when hormonal contraceptives are prescribed concurrently. Serum concentrations of riluzole, a CYP1A2 substrate, may increase when oral contraceptives, moderate CYP1A2 inhibitors, are used concurrently. In vitro findings suggest an increase in riluzole exposure is likely when a CYP1A2 inhibitor is given. [29747] [57048] Ritonavir: (Major) Data on the effects that protease inhibitors have on the serum concentrations of estrogens and progestins are complex. Some protease inhibitors increase (i.e., ritonavir, lopinavir; ritonavir, nelfinavir, tipranavir) and others decrease (i.e., atazanavir, indinavir) the metabolism of hormonal contraceptives. The safety and efficacy of hormonal contraceptives may be affected if coadministered with protease inhibitors. Women receiving hormonal contraceptives and anti-retroviral protease inhibitors concurrently should be instructed to report any breakthrough bleeding or other adverse effects to their prescribers. It may be prudent for women who receive hormonal contraceptives concurrently with protease inhibitors to use an additional method of contraception to protect against unwanted pregnancy, unless other drug-specific recommendations are made by the manufacturer of the protease inhibitor. Furthermore, because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, women who receive hormonal contraceptives concurrently with protease inhibitors should use an additional barrier method of contraception such as condoms. [46638] [5044] Roflumilast: (Moderate) Coadminister oral contraceptives containing gestodene and ethinyl estradiol and roflumilast cautiously, as the combination has resulted in increased drug exposure to roflumilast in pharmacokinetic study. In an open-label crossover study in 20 healthy adult volunteers, coadministration of a single dose of oral roflumilast 500 mcg with repeated doses of a fixed combination oral contraceptive containing 0.075 mg gestodene and 0.03 mg ethinyl estradiol to steady state resulted in a 38% increase in Cmax of roflumilast and a 12% decrease in Cmax of the active metabolite roflumilast N-oxide. Roflumilast and roflumilast N-oxide AUCs were increased by 51% and 14%, respectively. A similar interaction is expected with oral contraceptives and ethinyl estradiol; etonogestrel. [43551] Rosiglitazone: (Minor) Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. [30585] [62853] Rufinamide: (Major) Coadministration of hormonal contraceptives with rufinamide may reduce hormone concentrations and therefore reduce the clinical efficacy of hormonal contraceptives. If coadministration is necessary, recommend patients use additional non-hormonal forms of contraception. Hormonal contraceptives are metabolized by CYP3A4 and rufinamide is a weak CYP3A4 inducer. [34590] Saquinavir: (Minor) Coadministration of levonorgestrel with a strong CYP3A4 inhibitor such as saquinavir may increase the serum concentration of levonorgestrel. The oxidative metabolism of levonorgestrel is catalyzed by hepatic cytochrome P450 isoenzymes, especially CYP3A4. [28995] [39863] [39864] Sarilumab: (Moderate) Utilize caution with concomitant use of sarilumab and CYP3A4 substrate drugs, such as combined hormonal oral contraceptives, where a decrease in effectiveness is undesirable. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. [61976] Saxagliptin: (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. [7347] Secobarbital: (Moderate) Barbiturates can accelerate the hepatic clearance of progestins. For hormonal contraceptives, this interaction could result in unintended pregnancy or breakthrough bleeding. For patients regularly taking a barbiturate, an alternative or back-up method of contraception may be advisable to ensure contraceptive reliability during the use of the barbiturate, and for 1 month following the discontinuation of barbiturate use. The exception is the use of levonorgestrel progestin IUDs, which have not been reported to interact and appear to maintain reliable efficacy. Pregnancy has been reported during therapy with both estrogen- and/or progestin-based oral contraceptives in patients receiving barbiturates (e.g., phenobarbital). For patients taking progestins for other indications, like hormone replacement, monitor the patient for signs and symptoms of reduced therapeutic efficacy or need for dosage adjustment. [22005] [28502] [29653] [29821] [30802] [30858] [30890] [33322] [42126] [46375] [48201] [48254] [49996] [57048] [57271] [57649] [59800] [62899] Siltuximab: (Moderate) Caution is warranted when siltuximab is used in patients taking CYP3A4 substrates, such as oral contraceptives, in which a decreased effect would be undesirable. Cytochrome P450s in the liver are down regulated by infection and inflammation stimuli, including cytokines such as interleukin-6 (IL-6). Inhibition of IL-6 signaling by siltuximab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. The effect of siltuximab on CYP450 enzyme activity can persist for several weeks after stopping therapy. [57062] Simvastatin; Sitagliptin: (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. [7347] Sitagliptin: (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued. [7347] St. John's Wort, Hypericum perforatum: (Major) As with other CYP3A4 inducers, St. John's wort may reduce the therapeutic efficacy of progestin-only contraceptives or other progestin-based hormonal therapies. Patients should report irregular menstrual bleeding or other hormone-related symptoms to their health care providers if they are taking St. John's wort concurrently with their hormones. Avoidance of St. John's wort is recommended. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin). [42126] [48201] [57202] [57588] [57648] [63694] Streptogramins: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. Additionally, dalfopristin; quinupristin is a major inhibitor of cytochrome P450 3A4 and may decrease the elimination of drugs metabolized by this enzyme including ethinyl estradiol and norethindrone. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. [28482] [28509] [31698] Streptomycin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Succinylcholine: (Moderate) Plasma cholinesterase activity may be diminished by chronic administration of oral contraceptives; consider the possibility of prolonged neuromuscular block after administration of succinylcholine in patients with reduced plasma cholinesterase activity. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration. [42039] [65534] Sugammadex: (Major) If an oral contraceptive is taken the same day sugammadex is administered, the patient must use an additional, non-hormonal contraceptive method or back-up method of contraception for the next 7 days. Sugammadex may bind to progestogen, resulting in a decrease in progestogen exposure. The administration of a bolus dose of sugammadex results in actions that are essentially equivalent to missing one or more doses of contraceptives containing estrogen or progestogen, including combination oral contraceptives, non-oral combination contraceptives, or progestins. [60450] Sulfadiazine: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Sulfasalazine: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Sulfonamides: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Sulfonylureas: (Minor) Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. [6266] Tazemetostat: (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer. [33322] [57648] [64952] Tedizolid: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances.Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Telavancin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Teriflunomide: (Moderate) Teriflunomide may increase the effects of oral contraceptives. Following consecutive teriflunomide doses, mean ethinyl estradiol Cmax and AUC increased 1.58- and 1.54-fold, respectively, during coadministration. Levonorgestrel Cmax increased 1.33-fold and AUC 1.41-fold during coadministration. Use caution when selecting the type and dose of oral contraceptives in patients taking teriflunomide. [51794] Tetracycline: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Thalidomide: (Moderate) Thalidomide and hormone contraceptives should be used cautiously due an increased risk of thromboembolism. The pharmacokinetic parameters of norethindrone/estradiol were not affected when a single dose of norethindrone 1 mg/estradiol 75 micrograms was administered in 10 healthy women who were receiving thalidomide 200 mg/day (at steady state levels). [49713] Thiazolidinediones: (Minor) Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. [30585] [62853] Tigecycline: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Tinidazole: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Tipranavir: (Major) Tipranavir increases the metabolism of hormonal contraceptives, including combined oral contraceptives and non-oral combination contraceptives; concentrations of ethinyl estradiol decrease by 50% when coadministered. Additionally, in one drug interaction trial in healthy female volunteers administered a single dose of ethinyl estradiol followed by tipranavir with ritonavir, 33% of subjects developed a rash. Women receiving combined hormonal contraceptives and anti-retroviral protease inhibitors (PIs), such as tipranavir, should be instructed to report any breakthrough bleeding or other adverse effects to their prescribers. Alternate methods of non-hormonal contraception should be used in patients receiving tipranavir. Because hormonal contraceptives do not protect against the transmission of HIV/AIDS and other sexually transmitted diseases, women who receive hormonal contraceptives concurrently with PIs should use an additional barrier method of contraception such as condoms. [46638] [8102] Tirzepatide: (Major) Advise patients receiving tirzepatide and oral contraceptives to switch to a non-oral contraceptive method or to add a barrier method of contraception for 4 weeks after initiation and for 4 weeks after each dose escalation of tirzepatide. Tirzepatide delays gastric emptying and may reduce the rate and extent of estrogen and progestin absorption which may reduce efficacy. Gastric emptying delays are greatest after the first dose of tirzepatide and diminish over time. Hormonal contraceptives that are not administered orally should not be affected. Additionally, estrogens can impair glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day. [30585] [48491] [62853] [67631] Tizanidine: (Major) Avoid concomitant use of tizanidine and oral contraceptives as increased tizanidine exposure may occur. If use together is necessary, initiate tizanidine with a single 2 mg dose and increase by 2 to 4 mg/day based on clinical response. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occurs. A retrospective analysis of population pharmacokinetic data found that the clearance of tizanidine was 50% lower in females taking oral contraceptives compared to those not on oral contraceptives. [52430] Tobramycin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Tocilizumab: (Moderate) Utilize caution with concomitant use of tocilizumab and CYP3A4 substrate drugs, such as combined hormonal oral contraceptives, where a decrease in effectiveness is undesirable. Inhibition of IL-6 signaling by tocilizumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping tocilizumab. In vitro, tocilizumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. [38283] Tolazamide: (Minor) Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. [6266] Tolbutamide: (Minor) Progestins can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued. [6266] Topiramate: (Moderate) Topiramate may reduce the efficacy of progestins used in contraception or hormone replacement therapies. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception (e.g., non-hormonal contraceptives) may also be needed. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. Pregnancy has been reported in patients who are using hormonal-containing contraceptives and hepatic enzyme inducers. [22005] [28378] [33941] [48201] [57046] [57048] [57588] [57648] Trimethoprim: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Ulipristal: (Major) Avoid concurrent use of ulipristal and progestin-containing hormonal contraceptives or other progestins. Hormonal contraceptives may be started or resumed no sooner than 5 days after ulipristal treatment. Also, a reliable barrier method of contraception should be used during the same menstrual cycle in which ulipristal was administered (until the next menstrual period). Progestin-containing contraceptives may impair the ability of ulipristal to delay ovulation. Ulipristal may reduce the effectiveness of progestin-containing hormonal contraceptives by competitively binding at the progesterone receptor. [41569] [50623] Vancomycin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Vonoprazan; Amoxicillin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] Vonoprazan; Amoxicillin; Clarithromycin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. [28482] [28509] (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. Strong CYP3A4 inhibitors include clarithromycin. [28238] [28482] [28509] [31698] [34329]
      Revision Date: 02/02/2023, 02:26:00 AM

      References

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      Monitoring Parameters

      • pap smear
      • pelvic exam
      • pelvic ultrasound
      • pregnancy testing

      US Drug Names

      • AfterPill
      • EContra EZ
      • EContra One-Step
      • Fallback Solo
      • Kyleena
      • LILETTA
      • Mirena
      • My Choice
      • My Way
      • Next Choice
      • Next Choice One Dose
      • Norplant
      • Opcicon One-Step
      • Plan B
      • Plan B One-Step
      • Preventeza
      • React
      • Skyla
      • Take Action
      ;