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Apr.17.2022

Medroxyprogesterone

Indications/Dosage

Labeled

  • amenorrhea
  • contraception
  • dysfunctional uterine bleeding
  • endometriosis
  • estrogen replacement therapy

Off-Label

  • andropause
  • hot flashes
  • hyperparathyroidism
  • menopause
  • paraphilia
  • Pickwickian syndrome
† Off-label indication

For the treatment of secondary amenorrhea

Oral dosage

Adult and Adolescent females

5 to 10 mg PO once daily for 5 to 10 days, starting anytime during the cycle; but usually started during the latter half of the cycle (days 16 to 21). If the endometrium has been primed with estrogens, administer 10 mg PO once daily for 10 days starting on the 16th day of the cycle. Progestin withdrawal bleeding usually occurs 3 to 7 days after discontinuation of therapy.[59800]

For the treatment of dysfunctional uterine bleeding due to hormonal imbalance, in the absence of organic pathology such as fibroids or uterine cancer

Oral dosage

Adult and Adolescent females

5 to 10 mg PO once daily for 5 to 10 days during the latter half of the cycle (days 16 to 21). If the endometrium has been primed with estrogens, administer 10 mg PO once daily for 10 days starting on the 16th day of the cycle. Progestin withdrawal bleeding usually occurs 3 to 7 days after discontinuation of therapy.[59800]

For routine contraception

Intramuscular dosage (e.g., medroxyprogesterone acetate contraceptive injection 150 mg/mL, Depo-Provera)

Adults

150 mg IM every 13 weeks. Treatment for longer than 2 years is not recommended unless other options are inadequate, due to the impact of long-term treatment on bone mineral density (BMD).[42126]

Adolescents

150 mg IM every 13 weeks. Treatment for longer than 2 years is not recommended unless other options are inadequate, due to the impact of long-term treatment on bone mineral density (BMD).[42126]

Subcutaneous dosage (e.g., medroxyprogesterone acetate 104 mg/0.65 mL depot injection, Depo-SubQ Provera)

Adults

104 mg subcutaneously every 12 to 14 weeks. Treatment for longer than 2 years is not recommended unless other options are inadequate, due to the impact of long-term treatment on bone mineral density (BMD).[57649]

Adolescents

104 mg subcutaneously every 12 to 14 weeks. Treatment for longer than 2 years is not recommended unless other options are inadequate, due to the impact of long-term treatment on bone mineral density (BMD).[57649]

For the treatment of endometriosis-associated pain

Subcutaneous dosage (e.g., medroxyprogesterone acetate 104 mg/0.65 mL injection, Depo-subQ Provera 104 Injection)

Adult and Adolescent females

104 mg (using 104 mg/0.65 mL prefilled syringe) subcutaneously every 3 months. Initial dose is given within 5 days of the onset of menses and during or after the sixth postpartum week in breast-feeding women. For subsequent doses, if more than 14 weeks have passed, determine the patient is not pregnant before dosing. Treatment for longer than 2 years is not recommended, due to the impact on peak bone mass in adolescents and bone mineral density (BMD) in women of all ages. If symptoms of endometriosis recur upon discontinuation, evaluate BMD before considering retreatment.[57649] Endometriosis treatment guidelines recommend progestins, including medroxyprogesterone, as options for reducing endometriosis-associated pain.[57749]

Oral dosage†

Adult and Adolescent females

10 mg PO once daily for 10 days a month (e.g., from day 16 to 25 of the menstrual cycle) for 3 months.[57763] Treatment guidelines recommend progestogens, including medroxyprogesterone, as options for reducing endometriosis-associated pain.[57749] Although many oral progestogen regimens have been studied, current practice is to use regimens with a lower dose and for a shorter duration.[57763] [57764]

For the treatment of hypoventilation due to obesity-hypoventilation syndrome† (Pickwickian syndrome†)

Oral dosage

Adults

Dosage not established. 20 mg PO 3 times per day is a commonly reported dosage. The results of treatment have been contradictory; some studies have reported improvements in oxygenation and ventilation, others have not. Randomized controlled trials are needed to define efficacy and safety, since medroxyprogesterone can increase the risk for thromboembolism in at-risk patients.[61351]

For the prevention of endometrial hyperplasia associated with estrogen replacement therapy in postmenopausal women with an intact uterus

Oral dosage

Adult females with an intact uterus

5 to 10 mg PO once daily for 10 to 14 or more days each month for females with an intact uterus in whom estrogen is given in a sequential manner (e.g., withdrawal bleeding is expected). Alternatively, if estrogens are administered continuously each day, take 2.5 to 5 mg PO once daily (when withdrawal bleeding not desirable).[59800]

For the treatment of hot flashes† due to menopause†

Oral dosage

Adult females

Various doses have been reported; a common dose is 10 mg or 20 mg PO once daily. Several clinical trials have demonstrated the effectiveness of medroxyprogesterone in significantly reducing the number of daily hot flashes in postmenopausal women. The North American Menopause Society (NAMS) Guidelines recommend the short-term use of progestin monotherapy in women who do not want to use or who have contraindications to the use of estrogens and do not have contraindications to progestin therapy and find the potential risks of progestin therapy acceptable. No long term studies have addressed the safety of progestin-only treatment on menopause symptoms.[50638]

Intramuscular dosage (depot suspension injection)

Adult females

Various doses have been reported. 150 mg IM once every month reduced hot flashes by 90% compared to baseline compared to 25% with placebo.[50638] In another study, a single 400 mg IM injection of medroxyprogesterone was compared to venlafaxine 75 mg/day PO. Hot flash scores were reduced by 79% in the medroxyprogesterone arm compared to 55% in the venlafaxine arm after 6 weeks (p less than 0.0001). In addition, significantly more patients receiving medroxyprogesterone had a decrease in hot flashes by 50% compared to baseline (74% for medroxyprogesterone vs. 46% for venlafaxine, p less than 0.0001). Of note, 61% of the women in this trial had a history of breast cancer.[32281] Lower doses (e.g., 150 mg) administered IM once every 3 months have also been shown to be effective.[50638] The North American Menopause Society (NAMS) Guidelines recommend the short-term use of progestin monotherapy in women who do not want to use or who have contraindications to the use of estrogens and do not have contraindications to progestin therapy and find the potential risks of progestin therapy acceptable. No long term studies have addressed the safety of progestin-only treatment on menopause symptoms.[50638]

For use to reduce the rate of decline in bone mineral density and to control biochemical indices of mild primary hyperparathyroidism† in postmenopausal women

Oral dosage

Adult females with an intact uterus

In one study of 42 postmenopausal women with mild primary hyperparathyroidism, conjugated estrogens 0.625 mg with medroxyprogesterone 5 mg PO once daily for 2 years improved bone mineral density and biochemical markers of bone turnover compared to placebo.[24685]

For the management of paraphilia† (atypical or extreme compulsive sexual behaviors†) in men

Intramuscular dosage

Adult males†

Dosage is not established. The evidence for effective dosing is lacking due to the lack of controlled trials and need for individualization of dose to response. Secondary outcomes are often reported in the small trials available, such as reduction in sexual fantasy or other compulsive behavior, rather than reduction in sexual offending. Initial doses are usually given once weekly. Maintenance doses range from 200 to 600 mg IM weekly, biweekly, or monthly and are usually adjusted based on patient sexual response, tolerance, and/or plasma testosterone levels.[61348] In one open-label study, male patients with long-standing histories of deviant sexual behavior (n = 48) received weekly medroxyprogesterone acetate IM (dose individualized) along with therapy for up to 12 months. Forty subjects responded positively, all within 3 weeks, with diminished frequency of sexual fantasies and arousal, decreased desire for deviant sexual behavior, increased control over sexual urges, and improvement in psychosocial functioning.[61350]

For the treatment of hot flashes† due to prostate cancer† and associated induced androgen deficiency† ("andropause†") in men who have had surgical or medication induced castration

Intramuscular dosage

Adult males

Dosage is not established. 150 mg or 400 mg IM as needed (once monthly or for a longer duration between doses) based on patient-reported symptoms has been used. In a retrospective review, 91% of 48 patients that received either 150 mg IM or 400 mg IM reported an improvement in hot flashes, with 46% reporting elimination of hot flashes. Patients received additional injections based on symptoms; in general, patients received a median of 4 injections over a 43 month period. Statistical differences between the 2 dosages were not noted; however, the power for detecting a difference between the 2 groups was small because only 8 patients received the 150 mg dose. Only those patients receiving 400 mg IM reported a complete response.[32284]

Therapeutic Drug Monitoring

Maximum Dosage Limits

  • Adults

    Dependent on product used and indication for therapy.

  • Elderly

    Dependent on product used and indication for therapy.

  • Adolescents

    Dependent on product used and indication for therapy.

  • Children

    Not indicated in prepubescent children.

Patients with Hepatic Impairment Dosing

Elimination of medroxyprogesterone is reduced in patients with alcoholic cirrhosis; the oral dose may need to be lowered in patients with significant hepatic impairment. No guidelines are available for the injectable formulations. In general, progestins such as medroxyprogesterone should be avoided in patients with hepatic dysfunction.

Patients with Renal Impairment Dosing

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

† Off-label indication
Revision Date: 04/17/2022, 10:32:37 AM

References

24685 - Grey AB, Stapleton JP, Evans MC, et al. Effect of hormone replacement therapy on bone mineral density in postmenopausal women with mild primary hyperparathyroidism. Ann Intern Med 1996;125:360-8.32281 - Loprinzi CL, Levitt R, Barton D, et al. Phase III comparison of depomedroxyprogesterone acetate to venlafaxine for managing hot flashes: north central cancer treatment group trial N99C7. J Clin Oncol 2006;24:1409-14.32284 - Langenstroer P, Kramer B, Cutting B, et al. Parenteral medroxyprogesterone for the management of luteinizing hormone releasing hormone induced hot flashes in men with advanced prostate cancer. J Urol 2005;174:642-5.42126 - Depo-Provera Contraceptive Injection (Depo-Provera CI) (medroxyprogesterone acetate 150 mg/mL) injection suspension package insert. New York, NY: Pharmacia & Upjohn Company; 2020 Dec.50638 - The 2022 hormone therapy position statement of The North American Menopause Society. Menopause. 2022 July. [Epub aheadof print]57649 - Depo-SubQ Provera 104 (medroxyprogesterone acetate 104 mg/ 0.65 mL contraceptive injection suspension) package insert. New York, NY: Pharmacia & Upjohn Company; 2020 Dec.57749 - Dunselman GA, Vermeulen N, Becker C, et al. ESHRE guideline: management of women with endometriosis. Hum Reprod 2014;29:400-12.57763 - Ismail MT, Fahmy DM, Elshmaa NS, et al. Efficacy of levonorgestrel-releasing intrauterine system versus oral progestins in treatment of simple endometrial hyperplasia without atypia. Reprod Sci 2013;20:45-50.57764 - Gallos ID, Shehmar M, Thangaratinam S, et al. Oral progestogens vs levonorgestrel-releasing intrauterine system for endometrial hyperplasia: a systematic review and metaanalysis. Am J Obstet Gynecol 2010;203:547.59800 - Provera (medroxyprogesterone acetate) tablet package insert. New York, NY: Pharmacia & Upjohn Company; 2015 May.61348 - Codispoti VL. Pharmacology of sexually compulsive behavior. Psychiatr Clin North Am. 2008;31:671-679. Review.61350 - Gagne P. Treatment of sex offenders with medroxyprogesterone acetate. Am J Psychiatry. 1981;138:644-646.61351 - Mokhlesi B, Tulaimat A. Recent advances in obesity hypoventilation syndrome. Chest. 2007;132:1322-1336. Review.

How Supplied

Medroxyprogesterone Acetate Oral tablet

Medroxyprogesterone Acetate 2.5mg Tablet (59762-3740) (Greenstone Ltd) (off market)

Medroxyprogesterone Acetate Oral tablet

Medroxyprogesterone Acetate 2.5mg Tablet (59762-0055) (Greenstone Ltd) null

Medroxyprogesterone Acetate Oral tablet

Medroxyprogesterone Acetate 2.5mg Tablet (00904-5227) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Medroxyprogesterone Acetate Oral tablet

Medroxyprogesterone Acetate 2.5mg Tablet (72789-0043) (PD-Rx Pharmaceuticals, Inc.) null

Medroxyprogesterone Acetate Oral tablet

Medroxyprogesterone Acetate 2.5mg Tablet (55289-0816) (PD-Rx Pharmaceuticals, Inc.) (off market)

Medroxyprogesterone Acetate Oral tablet

Medroxyprogesterone Acetate 2.5mg Tablet (00677-1617) (Sun Pharmaceutical Industries, Inc.) (off market)

Medroxyprogesterone Acetate Oral tablet

Medroxyprogesterone Acetate 2.5mg Tablet (00555-0872) (Teva Pharmaceuticals USA) null

Medroxyprogesterone Acetate Oral tablet

Provera 2.5mg Tablet (55289-0121) (PD-Rx Pharmaceuticals, Inc.) (off market)

Medroxyprogesterone Acetate Oral tablet

Provera 2.5mg Tablet (00009-0064) (Pfizer Inc.) null

Medroxyprogesterone Acetate Oral tablet

Provera 2.5mg Tablet (00009-0065) (Pfizer Inc.) null

Medroxyprogesterone Acetate Oral tablet

Medroxyprogesterone Acetate 5mg Tablet (10544-0001) (Blenheim Pharmacal, Inc.) (off market)

Medroxyprogesterone Acetate Oral tablet

Medroxyprogesterone Acetate 5mg Tablet (59762-0058) (Greenstone Ltd) null

Medroxyprogesterone Acetate Oral tablet

Medroxyprogesterone Acetate 5mg Tablet (59762-0058) (Greenstone Ltd) null

Medroxyprogesterone Acetate Oral tablet

Medroxyprogesterone Acetate 5mg Tablet (59762-3741) (Greenstone Ltd) (off market)

Medroxyprogesterone Acetate Oral tablet

Medroxyprogesterone Acetate 5mg Tablet (00904-5228) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Medroxyprogesterone Acetate Oral tablet

Medroxyprogesterone Acetate 5mg Tablet (55289-0908) (PD-Rx Pharmaceuticals, Inc.) (off market)

Medroxyprogesterone Acetate Oral tablet

Medroxyprogesterone Acetate 5mg Tablet (00677-1618) (Sun Pharmaceutical Industries, Inc.) (off market)

Medroxyprogesterone Acetate Oral tablet

Medroxyprogesterone Acetate 5mg Tablet (00555-0873) (Teva Pharmaceuticals USA) null

Medroxyprogesterone Acetate Oral tablet

Provera 5mg Tablet (00009-0286) (Pfizer Inc.) (off market)

Medroxyprogesterone Acetate Oral tablet

Provera 5mg Tablet (00009-0287) (Pfizer Inc.) null

Medroxyprogesterone Acetate Oral tablet

Amen 10mg Tablet (00086-0049) (Carnrick Laboratories Inc Div GW Carnrick Co) (off market)

Medroxyprogesterone Acetate Oral tablet

Medroxyprogesterone Acetate 10mg Tablet (60687-0105) (American Health Packaging) null

Medroxyprogesterone Acetate Oral tablet

Medroxyprogesterone Acetate 10mg Tablet (10544-0062) (Blenheim Pharmacal, Inc.) (off market)

Medroxyprogesterone Acetate Oral tablet

Medroxyprogesterone Acetate 10mg Tablet (59762-3742) (Greenstone Ltd) (off market)

Medroxyprogesterone Acetate Oral tablet

Medroxyprogesterone Acetate 10mg Tablet (59762-0056) (Greenstone Ltd) null

Medroxyprogesterone Acetate Oral tablet

Medroxyprogesterone Acetate 10mg Tablet (00904-2690) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Medroxyprogesterone Acetate Oral tablet

Medroxyprogesterone Acetate 10mg Tablet (52555-0463) (Martec Pharmaceuticals Inc) (off market)

Medroxyprogesterone Acetate Oral tablet

Medroxyprogesterone Acetate 10mg Tablet (55289-0160) (PD-Rx Pharmaceuticals, Inc.) null

Medroxyprogesterone Acetate Oral tablet

Medroxyprogesterone Acetate 10mg Tablet (43063-0438) (PD-Rx Pharmaceuticals, Inc.) (off market)

Medroxyprogesterone Acetate Oral tablet

Medroxyprogesterone Acetate 10mg Tablet (43063-0438) (PD-Rx Pharmaceuticals, Inc.) (off market)

Medroxyprogesterone Acetate Oral tablet

Medroxyprogesterone Acetate 10mg Tablet (54807-0550) (Rid Inc) (off market)

Medroxyprogesterone Acetate Oral tablet

Medroxyprogesterone Acetate 10mg Tablet (00677-0803) (Sun Pharmaceutical Industries, Inc.) (off market)

Medroxyprogesterone Acetate Oral tablet

Medroxyprogesterone Acetate 10mg Tablet (00677-1619) (Sun Pharmaceutical Industries, Inc.) (off market)

Medroxyprogesterone Acetate Oral tablet

Medroxyprogesterone Acetate 10mg Tablet (00555-0779) (Teva Pharmaceuticals USA) null

Medroxyprogesterone Acetate Oral tablet

Medroxyprogesterone Acetate 10mg Tablet (00832-0087) (Upsher-Smith Laboratories, LLC) (off market)

Medroxyprogesterone Acetate Oral tablet

Provera 10mg Tablet (55289-0034) (PD-Rx Pharmaceuticals, Inc.) (off market)

Medroxyprogesterone Acetate Oral tablet

Provera 10mg Tablet (00009-0050) (Pfizer Inc.) null

Medroxyprogesterone Acetate Oral tablet

Provera 10mg Tablet (00009-0051) (Pfizer Inc.) null

Medroxyprogesterone Acetate Suspension for injection [Contraception]

Depo-subQ Provera 104 Suspension for Injection (00009-4709) (Pfizer Inc.) (off market)Depo-subQ Provera 104 Suspension for Injection package photo

Medroxyprogesterone Acetate Suspension for injection [Contraception]

Depo-subQ Provera 104 Suspension for Injection (00009-4709) (Pfizer Inc.) nullDepo-subQ Provera 104 Suspension for Injection package photo

Medroxyprogesterone Acetate Suspension for injection [Contraception]

Depo-Provera Contraceptive 150mg/ml Suspension for Injection (00009-0746) (Pfizer Inc.) nullDepo-Provera Contraceptive 150mg/ml Suspension for Injection package photo

Medroxyprogesterone Acetate Suspension for injection [Contraception]

Depo-Provera Contraceptive 150mg/ml Suspension for Injection (00009-7376) (Pfizer Inc.) (off market)Depo-Provera Contraceptive 150mg/ml Suspension for Injection package photo

Medroxyprogesterone Acetate Suspension for injection [Contraception]

Depo-Provera Contraceptive 150mg/ml Suspension for Injection (00009-7376) (Pfizer Inc.) (off market)

Medroxyprogesterone Acetate Suspension for injection [Contraception]

Depo-Provera Contraceptive 150mg/ml Suspension for Injection (00009-7376) (Pfizer Injectables) nullDepo-Provera Contraceptive 150mg/ml Suspension for Injection package photo

Medroxyprogesterone Acetate Suspension for injection [Contraception]

Medroxyprogesterone Acetate 150mg/ml Suspension for Injection (55150-0330) (Eugia US LLC fka AuroMedics Pharma LLC) null

Medroxyprogesterone Acetate Suspension for injection [Contraception]

Medroxyprogesterone Acetate 150mg/ml Suspension for Injection (59762-4537) (Greenstone Ltd) nullMedroxyprogesterone Acetate 150mg/ml Suspension for Injection package photo

Medroxyprogesterone Acetate Suspension for injection [Contraception]

Medroxyprogesterone Acetate 150mg/ml Suspension for Injection (59762-4538) (Greenstone Ltd) (off market)Medroxyprogesterone Acetate 150mg/ml Suspension for Injection package photo

Medroxyprogesterone Acetate Suspension for injection [Contraception]

Medroxyprogesterone Acetate 150mg/ml Suspension for Injection (59762-4538) (Greenstone Ltd) (off market)Medroxyprogesterone Acetate 150mg/ml Suspension for Injection package photo

Medroxyprogesterone Acetate Suspension for injection [Contraception]

Medroxyprogesterone Acetate 150mg/ml Suspension for Injection (66993-0371) (Prasco Laboratories) null

Medroxyprogesterone Acetate Suspension for injection [Contraception]

Medroxyprogesterone Acetate 150mg/ml Suspension for Injection (00703-6801) (Teva Pharmaceuticals USA) (off market)Medroxyprogesterone Acetate 150mg/ml Suspension for Injection package photo

Medroxyprogesterone Acetate Suspension for injection [Contraception]

Medroxyprogesterone Acetate 150mg/ml Suspension for Injection (00703-6811) (Teva Pharmaceuticals USA) (off market)Medroxyprogesterone Acetate 150mg/ml Suspension for Injection package photo

Medroxyprogesterone Acetate Suspension for injection [Contraception]

Medroxyprogesterone Acetate 150mg/mL Suspension for Injection (50102-0591) (Afaxys, Inc. ) nullMedroxyprogesterone Acetate 150mg/mL Suspension for Injection package photo

Medroxyprogesterone Acetate Suspension for injection [Contraception]

Medroxyprogesterone Acetate 150mg/mL Suspension for Injection (00548-5701) (Amphastar Pharmaceuticals, Inc) nullMedroxyprogesterone Acetate 150mg/mL Suspension for Injection package photo

Medroxyprogesterone Acetate Suspension for injection [Contraception]

Medroxyprogesterone Acetate 150mg/mL Suspension for Injection (00548-5401) (Amphastar Pharmaceuticals, Inc) null

Medroxyprogesterone Acetate Suspension for injection [Contraception]

Medroxyprogesterone Acetate 150mg/mL Suspension for Injection (00548-5400) (Amphastar Pharmaceuticals, Inc) nullMedroxyprogesterone Acetate 150mg/mL Suspension for Injection package photo

Medroxyprogesterone Acetate Suspension for injection [Contraception]

Medroxyprogesterone Acetate 150mg/mL Suspension for Injection (55150-0329) (Eugia US LLC fka AuroMedics Pharma LLC) null

Medroxyprogesterone Acetate Suspension for injection [Contraception]

Medroxyprogesterone Acetate 150mg/mL Suspension for Injection (59762-4538) (Greenstone Ltd) nullMedroxyprogesterone Acetate 150mg/mL Suspension for Injection package photo

Medroxyprogesterone Acetate Suspension for injection [Contraception]

Medroxyprogesterone Acetate 150mg/mL Suspension for Injection (67457-0887) (Mylan Institutional LLC ) nullMedroxyprogesterone Acetate 150mg/mL Suspension for Injection package photo

Medroxyprogesterone Acetate Suspension for injection [Contraception]

Medroxyprogesterone Acetate 150mg/mL Suspension for Injection (16714-0999) (NorthStar Rx LLC) nullMedroxyprogesterone Acetate 150mg/mL Suspension for Injection package photo

Medroxyprogesterone Acetate Suspension for injection [Contraception]

Medroxyprogesterone Acetate 150mg/mL Suspension for Injection (16714-0981) (NorthStar Rx LLC) null

Medroxyprogesterone Acetate Suspension for injection [Contraception]

Medroxyprogesterone Acetate 150mg/mL Suspension for Injection (16714-0028) (NorthStar Rx LLC) (off market)

Medroxyprogesterone Acetate Suspension for injection [Contraception]

Medroxyprogesterone Acetate 150mg/mL Suspension for Injection (66993-0370) (Prasco Laboratories) null

Medroxyprogesterone Acetate Suspension for injection [Contraception]

Medroxyprogesterone Acetate 150mg/mL Suspension for Injection (62756-0090) (Sun Pharmaceutical Industries, Inc.) null

Medroxyprogesterone Acetate Suspension for injection [Contraception]

Medroxyprogesterone Acetate 150mg/mL Suspension for Injection (62756-0091) (Sun Pharmaceutical Industries, Inc.) null

Medroxyprogesterone Acetate Suspension for injection [Contraception]

Medroxyprogesterone Acetate 150mg/mL Suspension for Injection (00703-6801) (Teva Pharmaceuticals USA) nullMedroxyprogesterone Acetate 150mg/mL Suspension for Injection package photo

Medroxyprogesterone Acetate Suspension for injection [Contraception]

Medroxyprogesterone Acetate 150mg/mL Suspension for Injection (NOVAPLUS) (00548-5410) (Amphastar Pharmaceuticals, Inc) null

Medroxyprogesterone Acetate Suspension for injection [Contraception]

Medroxyprogesterone Acetate 150mg/mL Suspension for Injection (NOVAPLUS) (00548-5711) (Amphastar Pharmaceuticals, Inc) null

Medroxyprogesterone Acetate Suspension for injection [Malignancy]

Depo-Provera 400mg/ml Suspension for Injection (00009-0626) (Pfizer Inc.) (off market)Depo-Provera 400mg/ml Suspension for Injection package photo

Description/Classification

Description

Medroxyprogesterone is an oral and parenteral synthetic progestin that is 15 times more potent than progesterone. Medroxyprogesterone can be used for the treatment of amenorrhea, abnormal uterine bleeding, hot flashes, and endometriosis secondary to hormonal imbalances. Medroxyprogesterone may be useful as respiratory stimulants in certain pulmonary disorders such as chronic obstructive pulmonary disease (COPD), Pickwickian syndrome, and other hypercapnic pulmonary conditions. Investigational agents containing medroxyprogesterone are also under development. InKine Pharmaceutical Co. is developing Colirest, a proprietary form of medroxyprogesterone, as a treatment for patients with Crohn's disease, ulcerative colitis, and other inflammatory bowel disorders. The drug may have applicability in these diseases because medroxyprogesterone inhibits pro-inflammatory mediators such as interleukin-6 and tumour necrosis factor (TNF), and thus offers an alternative to steroids and other available treatments. A phase 3 placebo-controlled trial is underway for the treatment of Crohn's disease; other studies are in progress for ulcerative colitis. Medroxyprogesterone was originally approved by the FDA in 1959.

Classifications

  • Antineoplastic and Immunomodulating Agents
    • Cytostatic Hormone Therapy
      • Cytostatic Hormone Agonists
        • Cytostatic Progestogens
  • Genito-urinary System and Sex Hormones
    • Sex Hormones and Modulators of the Genital System
      • Hormonal Contraceptives
        • Progestogen Only Contraceptives
      • Progestogens
Revision Date: 01/21/2022, 04:27:27 PM

References

Administration Information

General Administration Information

For storage information, see 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.
  • INJECTABLES: Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.[63664][67506][67507]
  • ORAL TABLETS/CAPSULES/ORAL LIQUID: Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure and require additional protective equipment. Oral liquid drugs require double chemotherapy gloves and protective gown; may require eye/face protection.[63664][67506][67507]

Route-Specific Administration

Oral Administration

Oral Solid Formulations

  • Medroxyprogesterone tablets may be administered without regard to meals.
  • When needed, tablets may be administered sublingually†; absorption is adequate by this route.

Injectable Administration

  • Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Intramuscular Administration

Depo-Provera Contraceptive injection suspension:

  • For IM administration only, NEVER administer intravenously (IV). For administration by a health care provider.
  • Instruct patient on risks and warnings associated with hormonal contraceptives.
  • To ensure the patient is not pregnant at the time of the first injection, only administer the first injection during the first 5 days of a normal menstrual period; only within the first 5 days postpartum if not breast-feeding; and if exclusively breast-feeding, only at the sixth postpartum week.
  • Do not dilute.
  • Shake vigorously immediately before administration.
  • Inject deeply into the gluteal or deltoid muscle.
  • Missed dose: If the time interval between injections is more than 13 weeks, determine that the patient is not pregnant before administering the drug.[42126]

 

Depo-Provera Sterile Aqueous Suspension injection, preserved:

  • For IM administration only, NEVER administer intravenously (IV).
  • Instruct patient on risks and warnings associated with progestin use (see Patient Information in the package insert).
  • Do not dilute.
  • Shake vigorously immediately before administration.
  • When multi-dose vials are used, special care to prevent contamination of the contents is essential.
  • Inject medroxyprogesterone deeply into the gluteal or deltoid muscle.[57648][57329]

Subcutaneous Administration

Depo-SubQ Provera 104 Contraceptive injection suspension:

  • For subcutaneous administration only, NEVER administer intramuscularly (IM) or intravenously (IV).
  • Instruct patient on risks and warnings associated with hormonal contraceptives.
  • To ensure the patient is not pregnant at the time of the first injection, only administer the first injection during the first 5 days of a normal menstrual period for women who are sexually active and who have regular menses and only during or after the sixth postpartum week if breast-feeding.
  • Do not dilute.
  • Shake vigorously for at least 1 minute immediately before administration.
  • Inject the entire contents of the prefilled medroxyprogesterone syringe subcutaneously into the anterior thigh or abdomen, avoiding bony areas and the umbilicus. Gently grasp and squeeze a large area of skin in the chosen injection area ensuring that the skin is pulled away from the body. Insert the needle at a 45-degree angle. Inject the medication until the syringe is empty; this usually requires 5 to 7 seconds. Following administration, press lightly on the injection site with a clean cotton pad for a few seconds; do not rub the area.
  • Missed dose: If the time interval between injections is more than 14 weeks, determine that the patient is not pregnant before administering the drug.[57649]

Clinical Pharmaceutics Information

From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database
    Revision Date: 04/21/2022, 12:00:10 PM

    References

    42126 - Depo-Provera Contraceptive Injection (Depo-Provera CI) (medroxyprogesterone acetate 150 mg/mL) injection suspension package insert. New York, NY: Pharmacia & Upjohn Company; 2020 Dec.57329 - Medroxyprogesterone Acetate- medroxyprogesterone acetate injection [package insert]. Sellersville, PA: Teva Pharmaceuticals; 10/201157648 - Depo-Provera (medroxyprogesterone acetate 400 mg/ml) injection suspension package insert. New York, NY: Pharmacia & Upjohn Company; 2017 Apr.57649 - Depo-SubQ Provera 104 (medroxyprogesterone acetate 104 mg/ 0.65 mL contraceptive injection suspension) package insert. New York, NY: Pharmacia & Upjohn Company; 2020 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/NIOSHPUB201616167506 - 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
    • appetite stimulation
    • arthralgia
    • asthenia
    • back pain
    • breakthrough bleeding
    • breast discharge
    • breast enlargement
    • chills
    • diarrhea
    • dizziness
    • drowsiness
    • dysmenorrhea
    • emotional lability
    • fatigue
    • fever
    • headache
    • hirsutism
    • hyperhidrosis
    • injection site reaction
    • insomnia
    • irritability
    • leukorrhea
    • libido decrease
    • libido increase
    • malaise
    • mastalgia
    • melasma
    • menorrhagia
    • menstrual irregularity
    • muscle cramps
    • nausea
    • oligomenorrhea
    • paresthesias
    • pelvic pain
    • polydipsia
    • pruritus
    • rash
    • skin discoloration
    • syncope
    • urticaria
    • weight gain
    • weight loss
    • xerosis

    Moderate

    • anemia
    • anovulation
    • cervical dysplasia
    • cholestasis
    • cystitis
    • depression
    • dyspareunia
    • edema
    • endometrial hyperplasia
    • euphoria
    • fluid retention
    • galactorrhea
    • hot flashes
    • hyperbilirubinemia
    • hypercalcemia
    • hyperglycemia
    • impaired cognition
    • impotence (erectile dysfunction)
    • infertility
    • jaundice
    • lipodystrophy
    • migraine
    • osteopenia
    • osteoporosis
    • phlebitis
    • postmenopausal bleeding
    • sinus tachycardia
    • vaginal bleeding
    • vaginitis

    Severe

    • anaphylactic shock
    • anaphylactoid reactions
    • angioedema
    • bone fractures
    • breast cancer
    • dementia
    • endometrial cancer
    • GI bleeding
    • myocardial infarction
    • new primary malignancy
    • optic neuritis
    • ovarian cancer
    • porphyria
    • pulmonary embolism
    • retinal thrombosis
    • seizures
    • skin atrophy
    • stroke
    • thromboembolism
    • thrombosis

    The types of adverse events that are experienced during medroxyprogesterone use are dependent on the indication for use, and the gender of the recipient. Some of the more common events involve the female genitourinary (GU) system. For the use of medroxyprogesterone depot contraceptive injections, menstrual irregularity predominates, with 57.3% of patients reporting irregular menses during the first 12 months and 32.1% after 24 months of use, respectively. Intermenstrual bleeding was reported in roughly 7% of patients during clinical trials for the subcutaneous contraceptive injection, and amenorrhea in approximately 6%. Amenorrhea is even more common with continued contraceptive injection use (55% at 12 months, 68% at 24 months).[42126] [57649] Other GU events reported with contraceptive injection use in 1% to 5% of women include leukorrhea (2.9%), vaginitis (1.2%), abnormal cervical smears, dysmenorrhea, menometrorrhagia, menorrhagia, uterine hemorrhage, and vaginal hemorrhage.[42126] [57649] Postmarketing, the following events have been reported with the medroxyprogesterone contraceptive injections: oligomenorrhea, delayed return to fertility, prolonged anovulation (temporary infertility), unexpected pregnancy, uterine hyperplasia, genitourinary infections, and vaginal cysts.[42126] [57649] The following GU effects have been reported in the use of medroxyprogesterone tablets as monotherapy (e.g., without estrogens) in females for hormone replacement therapy (HRT): change in menstrual flow; breakthrough bleeding or spotting; changes in cervical erosion; and changes in cervical secretions.[59800] The incidence of amenorrhea during estrogen-medroxyprogesterone HRT in postmenopausal women is determined by the regimens chosen. Amenorrhea accompanies continuous use of combined HRT in many menopausal women; cyclic administration produces amenorrhea in roughly 5%.[59848] When medroxyprogesterone tablets have been used along with estrogens in women for combined hormone replacement therapy (HRT), abnormal uterine postmenopausal bleeding/spotting/flow; breakthrough bleeding or spotting; dysmenorrhea or pelvic pain; increase in size of uterine leiomyomata; vaginitis, including vaginal candidiasis; changes in amount of cervical secretion; changes in cervical ectropion or cervical dysplasia; endometrial growth, and female-related cancers have been reported. The following adverse reactions have also been observed in females receiving estrogen; progestin combination drugs: premenstrual syndrome, cystitis-like syndrome.[57648] [59800]

    The types of adverse events that are experienced during medroxyprogesterone use are dependent on the indication for use, and the gender of the recipient. Changes in the breasts and in sexual function have been reported in both females and males. For the use of medroxyprogesterone depot contraceptive injections in females, breast pain (mastalgia) was reported in 2.8%, and libido decrease in up to 5.5%. Breast lumps, changes in breast size, nipple bleeding, galactorrhea, dyspareunia, and libido increase have been reported in post-market reports with contraceptive depot injection use. Lactation suppression is not common with progestin-only contraception, and depot contraceptive medroxyprogesterone injections are often a hormonal agent of choice in the early weeks postpartum [66564]; however, lactation prevention has been reported postmarketing.[42126] [57649] The following breast changes have been reported in the use of medroxyprogesterone tablets as monotherapy (e.g., without estrogens) in females for hormone replacement therapy (HRT): breast tenderness, mastodynia or mastalgia, or galactorrhea.[59800] When medroxyprogesterone tablets have been used along with estrogens in women in combined HRT regimens, breast tenderness, breast enlargement, pain (mastalgia), nipple breast discharge, galactorrhea; fibrocystic breast changes; and breast cancer have been reported.[59800] Changes in libido (decrease or increase) have been reported with the use of medroxyprogesterone-estrogen HRT regimens and with medroxyprogesterone 400 mg/mL depot injection as well.[57648] In males receiving medroxyprogesterone depot injections for palliative reasons or for paraphilia, impotence (erectile dysfunction) may occur when plasma testosterone levels decreased by 25% (one-quarter) or more of the pretreatment concentration.[57648]

    Dermatologic, vascular, and allergic reactions may occur with medroxyprogesterone therapy. Angioedema, anaphylactoid reactions, and anaphylactic shock have been reported with the use of medroxyprogesterone. The following common skin reactions occurred in 1—5% of women receiving medroxyprogesterone depot contraceptive injections: hot flashes or flushes and acne vulgaris; increased acne can be a common reason for contraceptive injection discontinuation. No hair growth or alopecia has been reported in approximately 1.1% of contraceptive injection recipients. The following skin disorders have been reported in patients receiving medroxyprogesterone depot contraceptive injections post-marketing: angioedema, dry skin (xerosis), increased body odor and axillary sweating (hyperhidrosis), axillary swelling, melasma, scleroderma, pruritus, rash (unspecified), and urticaria.[42126] [57649] With the use of medroxyprogesterone 400 mg/mL depot injections and medroxyprogesterone tablets as monotherapy (without estrogens), hypersensitivity reactions (anaphylaxis and anaphylactoid reactions, angioedema), urticaria or rash (allergic) with and without pruritus, acne, loss of scalp hair, alopecia, hot flushes, and hirsutism have been reported.[57648] [59800] The following adverse skin reactions have been observed in women receiving combination hormonal therapy (estrogen along with medroxyprogesterone tablets) for hormone replacement therapy (HRT) regimens: chloasma or melasma that may persist when drug is discontinued, erythema multiforme, erythema nodosum, and hemorrhagic eruption, loss of scalp hair, alopecia.[57648] [59800]

    Central nervous system (CNS) reactions, including emotional lability, may occur with medroxyprogesterone therapy. Dizziness (less than 5.6%), insomnia (1% to 5%), nervousness (10.8%), depression (1% to 5%), and headache (9% to 16.5%) have been reported in women receiving medroxyprogesterone depot contraceptive injections [42126] [57649]; women receiving medroxyprogesterone monotherapy for other indications have also reported these adverse events, but the incidence is not known.[59800] Changes in headache or migraine pattern during contraceptive or hormonal therapy use may occur; if a headache or migraine has focal features consistent with cerebral ischemia or a potential thrombotic cause, discontinuation of medroxyprogesterone is recommended.[48201] Anxiety and irritability have been reported in 1% to 5% of women receiving medroxyprogesterone depot contraceptive injections.[57649] Drowsiness/somnolence has been reported during postmarketing experience with medroxyprogesterone depot contraceptive injection and with the use of other medroxyprogesterone formulations for various indications.[42126] [57648] [57649] [59800] Other CNS effects reported postmarketing with the contraceptive injections have included facial palsy, fainting, paralysis, and paresthesias.[42126] [57649] Euphoria has been reported in patients receiving medroxyprogesterone depot injection for malignancy.[57648] Patients with a history of seizure disorder should use medroxyprogesterone cautiously since progestins may exacerbate their condition; seizures have been reported in patients receiving medroxyprogesterone for various indications.[42126] [57648] [57649] [59800] Chorea and mood disturbances have been reported in women receiving combined estrogen plus progestin therapy for hormone replacement.[59800]

    Gastrointestinal (GI) effects are fairly common with medroxyprogesterone therapy. Abdominal pain/discomfort (11.2%), nausea (3.3%), and bloating (2.3%) are the most common GI effects with medroxyprogesterone IM depot contraceptive injection; abdominal distention, abdominal pain, diarrhea, nausea occurred in approximately 1% to 5% of those receiving depot subcutaneous contraceptive injections in clinical trials. GI side effects reported postmarketing with contraceptive depot injection use include general GI disturbances, jaundice, excessive thirst (polydipsia) and rectal GI bleeding.[42126] [57649] The following adverse reactions have been reported in women taking medroxyprogesterone tablets as monotherapy (without concomitant estrogens): nausea and cholestatic jaundice (jaundice due to cholestasis).[59800] These effects have also been reported in the use of medroxyprogesterone depot injections for other indications; cholestatic jaundice has included neonatal jaundice and hyperbilirubinemia.[57648] Additional adverse events reported in women receiving combined estrogen and progestin treatment include: nausea, vomiting; abdominal pain, cramps, bloating; cholestatic jaundice; increased incidence of gallbladder disease; pancreatitis; and enlargement of hepatic hemangiomas.[59800]

    Changes in appetite may occur during medroxyprogesterone treatment. Appetite stimulation may occur. Weight gain iis a common side effects for medroxyprogesterone contraceptive injections in females; increased weight (defined as a more than 10 pound weight gain at 24 months occurs in 37.7% of patients receiving the IM depot contraceptive injection and 6% of those receiving the subcutaneous contraceptive depot injection. Weight gain one of the primary reasons women discontinue the contraceptive (2% or more discontinue due to weight gain).[42126] [57649] A slight amount of weight gain may be due to fluid retention. Edema is reported in 2.2% of contraceptive depot injection recipients.[42126] [57649] Weight gain or weight loss, fluid retention, and/or edema have been reported for medroxyprogesterone tablets for hormone replacement (HRT) in females or in the use of medroxyprogesterone in men or women for palliation of cancer or other indications.[57648] [59800]

    During use of medroxyprogesterone, the provider should be alert to possible thrombotic disorders (e.g., cerebrovascular disorder or migraine or headache with focal symptoms that suggest cerebral ischemia, pulmonary embolism or thromboembolism, thromboembolism, heart attack, or unexplained visual disturbance with ocular pain, which might indicate retinal thrombosis). Should any of these occur or be suspected, medroxyprogesterone therapy should be discontinued immediately; with depot-injections, the effects of the hormone may persist for some time after discontinuation.[59800] [57648] [42126] [57649] [48201] HORMONE REPLACEMENT THERAPY: Hormone replacement therapy (HRT) with estrogens and progestins in combination presents a risk for thromboembolism and cardiovascular events in postmenopausal women; these risks are highlighted in the boxed warnings for oral medroxyprogesterone. The Women's Health Initiative (WHI) estrogen plus progestin substudy reported an increased risk of thromboembolism, including deep vein thrombosis (DVT), pulmonary embolism (PE), stroke and myocardial infarction (MI) in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral conjugated estrogens [0.625 mg] combined with medroxyprogesterone acetate oral tablets (MPA) [2.5 mg], relative to placebo. In the absence of comparable data, the risk of such events should be assumed to be similar for other doses of conjugated estrogens/medroxyprogesterone or other estrogen/progestin combinations in postmenopausal women. Should any of these cardiovascular or thrombotic events occur or be suspected, estrogen plus progestin HRT should be discontinued immediately.[27272] [59800] PROGESTIN ONLY CONTRACEPTION: Active thrombophlebitis, or current or past history of thromboembolic disorders, or cerebral vascular disease are contraindications to medroxyprogesterone contraceptive injections. Syncope, sinus tachycardia, chest pain (unspecified), thromboembolism, DVT, PE, thrombo-phlebitis, and varicose veins are cardiovascular effects that have been reported in postmarketing reports from the use of medroxyprogesterone depot contraceptive injections. Although MPA has not been causally associated with the induction of thrombotic or thromboembolic disorders, there have been rare reports of serious thrombotic events in women using MPA contraceptive injections. Any patient who develops thrombosis during contraceptive use should discontinue treatment unless she has no other acceptable options for birth control.[42126] [57649] The use of progestin-only contraception may be acceptable in women without a previous or active history of thromboembolic events, but with certain risk factors for thrombosis, when hormonal contraception is desired. Guidances have been published based on expert review of the literature that can help guide contraceptive product selection in patients with risk factors for thrombosis. 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; risk versus benefit must be considered individually. 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, etc.), consider an intra-uterine device (IUD) or other estrogen-free contraceptive if appropriate.[48201] OTHER USES: During clinical use of medroxyprogesterone monotherapy for various indications, effects such as pulmonary embolism (PE) and retinal thrombosis have been rarely reported; when combined with estrogens, various types of thromboembolic events have been reported.[57648]

    An injection site reaction can occur with both intramuscular and subcutaneous injections of medroxyprogesterone. Adverse local reactions include residual lump, skin discoloration, pain, tenderness, persistent atrophy, indentation, dimpling, lipodystrophy, and sterile abscess.[42126] [57648] [57649] In women receiving medroxyprogesterone depot contraceptive, injection site reaction was reported in 5% of patients, and 1% had persistent skin changes, typically described as small areas of skin induration or skin atrophy.[57649]

    The following adverse reactions have been reported in women taking medroxyprogesterone tablets, without concomitant estrogens treatment: neuro-ocular lesions (e.g., retinal thrombosis) and optic neuritis. The following adverse reactions have been reported with estrogen plus progestin therapy: retinal vascular thrombosis and intolerance to contact lenses. Should retinal thrombosis occur or be suspected, estrogen plus progestin therapy should be discontinued immediately.[59800]

    MEDROXYPROGESTERONE CONTRACEPTIVE INJECTIONS: Women using medroxyprogesterone contraceptive injections may lose significant bone mineral density. Bone loss (osteopenia) is greater with increasing duration of use and may not be completely reversible. It is unknown if use of these contraceptive injections during adolescence or early adulthood, a critical period of bone accretion, will reduce peak bone mass and increase the risk for osteoporotic fracture in later life. There have been postmarketing reports of osteopenia and loss of bone mineral density as well as osteoporosis, including osteoporotic bone fractures, in patients using medroxyprogesterone depot contraceptive injections. Women should not use medroxyprogesterone injections as a long-term birth control method (i.e., longer than 2 years) unless other birth control methods are considered inadequate.[42126] [57329] In a controlled clinical study, adult women using medroxyprogesterone depot-injections for up to 5 years showed a 5% to 6% mean decrease in spine and hip bone mineral density (BMD), compared to no significant change in BMD in the control group. The decline in BMD was more pronounced during the first 2 years of use, with smaller declines reported in subsequent years. Observed mean changes in lumbar spine BMD of -2.86%, -4.11%, -4.89%, -4.93%, and -5.38% after 1, 2, 3, 4, and 5 years, respectively. A partial recovery of BMD toward baseline values during a 2-year post-therapy period was seen following the cessation of medroxyprogesterone depot injections; longer duration of treatment was associated with less complete BMD recovery during this 2-year post-treatment period. An open-label, non-randomized, clinical study was preformed to evaluate the impact of treatment for up to 4.6 years in adolescent females (12 to 18 years). Results showed that medroxyprogesterone depot injections were associated with a significant decline in BMD from baseline. The decline in BMD was greater with longer duration of use, with a mean decreases in BMD at 4.6 years of -6.4% at total hip, -5.4% at femoral neck, and -2.1% at lumbar spine. In addition, the extent of BMD recovery was evaluated during post-treatment follow-up for up to 60 months. Data revealed that adolescents treated for more than 2 years did not recover baseline BMD at femoral neck or total hip, but did recover baseline BMD at lumbar spine after treatment discontinuation. In comparison, adolescents in the untreated group gained BMD throughout the trial period. The evidence suggests that the increase in bone density that is normally seen during the period of growth following menarche may be impaired by medroxyprogesterone depot injection use.[42126] [57329] OTHER USES: It is possible that osteoporosis may occur with medroxyprogesterone depot injections used chronically for other purposes. An evaluation of bone mineral density may be appropriate in some patients who use higher doses of medroxyprogesterone acetate depot injection for long-term treatment of cancer.[57648]

    Decreased glucose tolerance has been reported with medroxyprogesterone monotherapy, and may occur in either gender and during use of the hormone for a variety of indications. Hyperglycemia may occur, and patients with diabetes should be carefully monitored for changes in blood glucose control during medroxyprogesterone treatment.[57648] [42126] [57649] [59800]

    Hypercalcemia has been reported in patients receiving medroxyprogesterone depot injection for malignancy.[57648] Hypocalcemia has been reported in patients receiving estrogen plus progestin therapy, and is due to estrogen-induced hypocalcemia.[59800]

    Musculoskeletal adverse reactions reported in >= 1% and < 5% of patients receiving depot medroxyprogesterone for contraception (intramuscularly or subcutaneously) include leg muscle cramps (approximately 3.7%), arthralgia (1%), back pain and limb pain.[42126] [57649] Backache and arthralgia have been reported in those receiving estrogen-progestin combined hormonal therapy.[57648] [59800]

    Asthenia and/or fatigue (4.2%) occur in > 1% and < 5% of patients receiving medroxyprogesterone contraceptive injections. Post marketing, fever, chills, asthenia have been reported.[42126] [57649] General adverse reactions reported with hormonal therapy with medroxyprogesterone for cancer or hormone replacement include edema, pyrexia, fatigue, malaise.[57648] [59800]

    Anemia and blood dyscrasia reported during post-marketing experience with medroxyprogesterone contraceptive injections.[42126] [57649] Aggravation of porphyria has been reported in the use of medroxyprogesterone for cancer or hormone replacement therapy.[57648] [59800]

    Estrogen/progestin combination hormonal replacement therapy (HRT) does not prevent mild impaired cognition (memory loss) and has been found to increase the risk of dementia in women 65 years and older. The WHIMS study, an ancillary study of the WHI trial to assess the effects of estrogen/progestin therapy on cognitive function in geriatric women (65 years of age or older), reported similar rates of developing mild cognitive impairment in those receiving active treatment vs. placebo. Also, patients receiving estrogen/progestin combination therapy were more likely than patients receiving placebo to be diagnosed with dementia. The applicability of this finding to women who use estrogen alone or to the typical user of HRT (i.e., younger, symptomatic adult women taking hormone replacement therapy to relieve menopausal symptoms) is unclear. Administration of estrogen/progestin combination therapy should be avoided in women 65 years of age and older and estrogen/progestin combination therapy should not be used to prevent or treat dementia or preserve cognition (memory).[27451] [59800]

    The issue of hormonal influences on the development of cancers (new primary malignancy) has been widely researched for many decades. The risks of various cancers for progestin-only hormonal contraceptive use differ from the risks associated with postmenopausal hormone replacement therapy (HRT) or other hormonal uses. Undiagnosed vaginal bleeding should be evaluated in any patient using medroxyprogesterone as is clinically appropriate, since female genital cancers may be influenced by hormonal therapy. HORMONE REPLACEMENT THERAPY POSTMENOPAUSE: Numerous epidemiologic studies have examined the effects of estrogen and estrogen-progestin hormone replacement therapy (HRT) on the development of new primary malignancy (e.g., breast cancer, endometrial cancer, ovarian cancer) in postmenopausal women. The Women's Health Initiative (WHI) estrogen plus progestin study reported increased risks of invasive breast cancer in patients taking combined estrogen-progestin HRT vs. placebo. The potential risk of breast cancer may increase with longer duration of use. Due to breast cancer and other cancer risks, combined HRT should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.[59800] [27272] [32125] [27273] [50638] There is an association of unopposed estrogen therapy and endometrial cancer in women with an intact uterus. Adding a progestin, such as medroxyprogesterone, to estrogen therapy has been shown to reduce, but not eliminate, the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Clinical surveillance of all women using estrogen-alone or estrogen plus progestin therapy is important. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal vaginal bleeding. The reported endometrial cancer risk among unopposed estrogen users is about 2- to 12-times greater than in non-users, and appears dependent on duration of treatment and on estrogen dose. Most studies show no significant increased risk associated with use of estrogens for less than 1 year. The greatest risk appears associated with prolonged use, with increased risks of 15- to 24-fold for 5 to 10 years or more, and this risk has been shown to persist for at least 8 to 15 years after estrogen therapy is discontinued. There is no evidence that the use of natural estrogens results in a different endometrial risk profile than synthetic estrogens of equivalent estrogen dose. Among combined estrogen/progestin HRT users, roughly 10% will have some endometrial thickening. Postmarketing reports of endometrial hyperplasia have been reported in women receiving combined estrogen/progestin HRT; however, the incidence of endometrial hyperplasia is estimated to be 1% or less in these patients.[59800] [50638] [23505] [27272] Women who used HRT for menopausal symptoms also had an increased risk for ovarian cancer, but data are still uncertain if risk is associated with a specific duration of use. The contraindications and precautions sections for progesterone HRT product labels more fully discuss the data and what is known about HRT use with respect to risks for various cancers.[59800] [27272] [32125] [27273] [50638] MEDROXYPROGESTERONE CONTRACEPTIVE INJECTIONS: The relative risk of developing breast cancer in patients receiving depot medroxyprogesterone for contraception has been investigated in a number of trials. Among 5 epidemiologic studies assessing the associated risk, 3 of the studies suggested a slightly increased risk of breast cancer in the overall population of users. Data from one study (n = 1,028) of women 20 to 44 years of age, receiving medroxyprogesterone contraceptive injections, showed that recent use (last use within the previous 5 years) for 12 months or longer was associated with a 2.2-fold (95% CI: 1.2 to 4.2) increased risk of invasive breast cancer.[42126] [57649] [58771]

    Revision Date: 03/31/2021, 03:06:41 PM

    References

    23505 - Grady D, Rubin SM, Petitti DB, et al. Hormone therapy to prevent disease and prolong life in postmenopausal women. Ann Intern Med 1992;117:1016-37.27272 - Rossouw JE, Anderson GL, Prentice RL, et al. The Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 2002;288:321-333.27273 - Lacey JV, Mink PJ, Lubin JH, et al. Menopausal hormone replacement therapy and risk of ovarian cancer. JAMA 2002;288:334-341.27451 - Shumaker SA, Legault C, Rapp SR, et al. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women. The Women's Health Initiative Memory Study: A randomized controlled trial (WHIMS). JAMA 2003;289:2651-62.32125 - Stefanick ML, Anderson GL, Margolis KL, et al. Effects of conjugated equine estrogens on breast cancer and mammography screening in postmenopausal women with hysterectomy. JAMA 2006;295:1647-57.42126 - Depo-Provera Contraceptive Injection (Depo-Provera CI) (medroxyprogesterone acetate 150 mg/mL) injection suspension package insert. New York, NY: Pharmacia & Upjohn Company; 2020 Dec.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;65:1-103.50638 - The 2022 hormone therapy position statement of The North American Menopause Society. Menopause. 2022 July. [Epub aheadof print]57329 - Medroxyprogesterone Acetate- medroxyprogesterone acetate injection [package insert]. Sellersville, PA: Teva Pharmaceuticals; 10/201157648 - Depo-Provera (medroxyprogesterone acetate 400 mg/ml) injection suspension package insert. New York, NY: Pharmacia & Upjohn Company; 2017 Apr.57649 - Depo-SubQ Provera 104 (medroxyprogesterone acetate 104 mg/ 0.65 mL contraceptive injection suspension) package insert. New York, NY: Pharmacia & Upjohn Company; 2020 Dec.58771 - Li CI, Beaber EF, Tang MT, et al. Effect of depo-medroxyprogesterone acetate on breast cancer risk among women 20 to 44 years of age. Cancer research 2012.15;72:2028-35.59800 - Provera (medroxyprogesterone acetate) tablet package insert. New York, NY: Pharmacia & Upjohn Company; 2015 May.59848 - Archer DF, Pickar JH, Bottiglioni F. Bleeding patterns in postmenopausal women taking continuous combined or sequential regimens of conjugated estrogens with medroxyprogesterone acetate. Menopause Study Group. Obstet Gynecol. 1994;83:686-692.66564 - American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins-Gynecology. ACOG Practice Bulletin No. 206: Use of Hormonal Contraception in Women With Coexisting Medical Conditions. Obstet Gynecol. 2019;133:e128-e150. Erratum in: Obstet Gynecol. 2019;133:1288. Reaffirmed 2020.

    Contraindications/Precautions

    Absolute contraindications are italicized.

    • breast cancer
    • cerebrovascular disease
    • cervical cancer
    • endometrial cancer
    • hepatic disease
    • history of angioedema
    • incomplete abortion
    • myocardial infarction
    • ovarian cancer
    • pregnancy
    • stroke
    • thromboembolic disease
    • thromboembolism
    • thrombophlebitis
    • uterine cancer
    • vaginal cancer
    • acquired immunodeficiency syndrome (AIDS)
    • alcoholism
    • anorexia nervosa
    • asthma
    • breast-feeding
    • children
    • cholestasis
    • coronary artery disease
    • corticosteroid therapy
    • dementia
    • depression
    • diabetes mellitus
    • ectopic pregnancy
    • endometrial hyperplasia
    • geriatric
    • human immunodeficiency virus (HIV) infection
    • hypercholesterolemia
    • hyperlipidemia
    • hypertension
    • hypocalcemia
    • infants
    • infertility
    • intravenous administration
    • jaundice
    • menstrual irregularity
    • migraine
    • neonates
    • new primary malignancy
    • obesity
    • osteopenia
    • osteoporosis
    • porphyria
    • renal disease
    • seizure disorder
    • sexually transmitted disease
    • systemic lupus erythematosus (SLE)
    • tobacco smoking
    • vaginal bleeding
    • visual disturbance

    Medroxyprogesterone acetate products are contraindicated in patients with a known hypersensitivity to medroxyprogesterone acetate or any of the product ingredients, including history of anaphylaxis or history of angioedema to medroxyprogesterone acetate. Cases of both anaphylactic reactions and angioedema have been reported in patients receiving medroxyprogesterone acetate.[59800] [57648] [57649] [42126]

    Medroxyprogesterone acetate depot injections are suspensions that are either administered intramuscularly or subcutaneously depending on the formulation. Never administer via intravenous administration; intravenous administration may result in serious adverse reactions.

    Medroxyprogesterone contraceptive injections and oral tablets are contraindicated in patients with pre-existing breast cancer.[59800] [42126] [57649] The oral tablets are contraindicated in any other known or suspected estrogen- or progestin-dependent neoplasia, including cervical cancer, endometrial cancer, uterine cancer, or vaginal cancer.[59800] Medroxyprogesterone depot injection suspension for the treatment of endometrial or renal cancer should generally not be used in women with a history of breast cancer, as breast cancer may be hormonally sensitive. Women with a strong family history of breast cancer should be monitored with particular care.[57648] Do not use medroxyprogesterone products in patients with undiagnosed abnormal genital or vaginal bleeding.[59800] [42126] [57649] [57648] HORMONE REPLACEMENT THERAPY (HRT): The WHI estrogen plus progestin substudy demonstrated an increased risk of invasive breast cancer (new primary malignancy of the breast) in postmenopausal women receiving HRT. The use of estrogen-alone and estrogen plus progestin has been reported to result in an increase in abnormal mammograms, requiring further evaluation. All women taking estrogen with or without a progestin should receive an annual clinical breast examination, perform monthly self-examinations, and have regular mammograms as recommended by their health care professional based on patient age, risk factors, and prior mammogram results.[59800] The most important randomized clinical trial providing information about breast cancer in patients taking combined estrogen-progestin HRT regimens is the WHI substudy of CE (0.625 mg/day) plus MPA (2.5 mg/day).[27530] [27272] After a mean follow-up of 5.6 years, the WHI estrogen plus progestin substudy reported an increased risk of invasive breast cancer in women who took daily CE plus MPA vs. placebo. In this substudy, prior use of estrogen-alone or estrogen plus progestin therapy was reported by 26% of the women. The relative risk of invasive breast cancer was 1.24, and the absolute risk was 41 versus 33 cases per 10,000 women-years, for CE plus MPA compared with placebo. Among women who reported prior use of hormone therapy, the relative risk of invasive breast cancer was 1.86, and the absolute risk was 46 vs. 25 cases per 10,000 women-years for CE plus MPA compared with placebo. Among women who reported no prior use of hormone therapy, the relative risk of invasive breast cancer was 1.09, and the absolute risk was 40 vs. 36 cases per 10,000 women-years for CE plus MPA compared with placebo. In the same WHI substudy, invasive breast cancers were larger, were more likely to be node positive, and were diagnosed at a more advanced stage in the combined HRT group compared with the placebo group. Metastatic disease was rare, with no apparent difference between the 2 groups. Other prognostic factors, such as histologic subtype, grade and hormone receptor status did not differ between the 2 groups.[27530] Consistent with the WHI clinical trial, observational studies have also reported an increased risk of breast cancer for estrogen plus progestin therapy, and a smaller increased risk for estrogen-alone therapy, after several years of use. The risk increased with duration of use, and appeared to return to baseline over about 5 years after stopping treatment (only the observational studies have substantial data on risk after stopping). Observational studies also suggest that the risk of breast cancer was greater, and became apparent earlier, with combined HRT as compared to estrogen-alone therapy. However, these studies have not found significant variation in the risk of breast cancer among different estrogen plus progestin combinations, doses, or routes of administration.[59800] Adding a progestin such as medroxyprogesterone to estrogen therapy has been shown to reduce, but not completely eliminate, the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Clinical surveillance of all women using estrogen plus progestin therapy is important. Adequate diagnostic measures, including endometrial sampling when indicated, should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal vaginal bleeding.[59800] The WHI estrogen plus progestin substudy reported a statistically non-significant increased risk of ovarian cancer. After an average follow-up of 5.6 years, the relative risk for ovarian cancer for CE plus MPA versus placebo was 1.58 (95% CI, 0.77 to 3.24). The absolute risk for CE plus MPA was 4 versus 3 cases per 10,000 women-years. In some epidemiologic studies, the use of estrogen plus progestin and estrogen-only products, in particular for 5 or more years, has been associated with increased risk of ovarian cancer. However, the duration of exposure associated with increased risk is not consistent across all epidemiologic studies and some report no association.[59800] MEDROXYPROGESTERONE CONTRACEPTIVE INJECTIONS: The relative risk of developing breast cancer in patients receiving depot medroxyprogesterone for contraception has been investigated in a number of trials. Among 5 epidemiologic studies assessing the associated risk, three of the studies suggested a slightly increased risk of breast cancer in the overall population of users. Data from one study (n = 1028) of women 20 to 44 years of age, receiving depo-medroxyprogesterone acetate, showed that recent use (last use within the previous 5 years) for 12 months or longer was associated with a 2.2-fold (95% CI: 1.2 to 4.2) increased risk of invasive breast cancer.[42126] [57649] [58771]

    Medroxyprogesterone 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 contraception and during hormonal replacement therapy (HRT). Monitor blood glucose routinely, and manage risk factors for heart disease to help reduce cardiovascular risks in patients with diabetes receiving hormonal therapy.

    Medroxyprogesterone injections are contraindicated in patients with active or a history of thrombophlebitis. Medroxyprogesterone oral and injectable dose forms are contraindicated in patients with active arterial or venous thromboembolic disease (e.g., thromboembolism, deep venous thrombosis, pulmonary embolism, myocardial infarction (MI), cerebrovascular disease and stroke) or a history of these conditions.[59800] [57648] [42126] [57649] Patients with risk factors for heart disease, arterial vascular disease, thromboembolism, and stroke (e.g., hypertension, diabetes mellitus, tobacco smoking, hypercholesterolemia, obesity, etc.) should be monitored closely and managed appropriately. During use of medroxyprogesterone in patients without a history of thrombosis, the provider should be alert to the earliest manifestations of thrombotic disorder (thrombophlebitis, heart attack, cerebrovascular disorder such as stroke or focal headache with symptoms consistent with cerebral ischemia, pulmonary embolism, or unexplained visual disturbance with ocular pain, which might indicate retinal thrombosis). Should any of these occur or be suspected, medroxyprogesterone therapy should be discontinued immediately; with depot-injections, the effects of the hormone may persist for some time after discontinuation.[59800] [57648] [42126] [57649] HORMONAL REPLACEMENT THERAPY: Medroxyprogesterone, when used with estrogen therapy for postmenopausal hormone replacement, is associated with cardiovascular and thromboembolic risks. The Women's Health Initiative (WHI) estrogen plus progestin substudy reported an increased risk of deep vein thrombosis (DVT), pulmonary embolism (PE), stroke and myocardial infarction (MI) in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral conjugated estrogens (CE) [0.625 mg] combined with medroxyprogesterone acetate (MPA) [2.5 mg], relative to placebo.[59800] In the WHI estrogen plus progestin substudy, a statistically significant 2-fold greater rate of VTE was reported in women receiving estrogen (conjugated estrogens) plus progestin (medroxyprogesterone) HRT compared to women receiving placebo (35 vs. 17 per 10,000 women-years). Statistically significant increases in risk for both DVT (26 vs. 13 per 10,000 women-years) and PE (18 vs. 8 per 10,000 women-years) were also demonstrated. The increase in VTE risk was demonstrated during the first year and persisted.[17825] [27272] Estrogens with or without a progestin such as medroxyprogesterone should not be used for the prevention of cardiac disease or cardiovascular disease (e.g., coronary artery disease) in postmenopausal women. In the WHI estrogen plus progestin substudy, there was a statistically non-significant increased risk of CHD events reported in women receiving daily estrogen plus progestin compared to women receiving placebo (41 vs. 34 per 10,000 women-years). An increase in relative risk was demonstrated in year 1, and a trend toward decreasing relative risk was reported in years 2 through 5.[27272] [17808] Studies have also shown no cardiovascular benefit to the use of estrogen-progestin therapy for secondary prevention in women with documented cardiac disease or CHD.[25473] [27270] In the WHI estrogen plus progestin substudy, a statistically significant increased risk of stroke was reported in women 50 to 79 years of age receiving estrogen plus progestin HRT compared to women in the same age group receiving placebo (33 vs. 25 per 10,000 women-years). The increase in risk was demonstrated after the first year and persisted. Women over the age of 65 years were at increased risk for non-fatal stroke.[38488] [27272] [59800] MEDROXYPROGESTERONE CONTRACEPTIVE INJECTIONS: Despite the contraindication against use of medroxyprogesterone injection in patients with known active or history of 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.[48201] 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., etonorgestrel implants) is still substantially less than with combined oral contraceptives containing both estrogen and progestin.[48201] For women who are at an increased risk of thromboembolism and have multiple-risk factors for thrombosis, consider an IUD or other estrogen-free contraceptive if appropriate. Use with caution in patients with pre-existing hypertension. A woman who is taking a hormonal contraceptive should have a yearly visit with her healthcare provider for a blood pressure check and for other indicated healthcare.[48201] [42126] [57649]

    Medroxyprogesterone should be used cautiously in patients with hyperlipidemia. Although hyperlipidemia is associated with estrogen-progestin combinations, the effects of progestin-only oral contraceptives on serum lipids have not been studied. Serum lipoproteins (HDL and LDL) should be monitored during therapy with medroxyprogesterone.

    Medroxyprogesterone is contraindicated for use during known pregnancy or suspected pregnancy. Although the drug should not be used during pregnancy, there appears to be little or no increased risk of birth defects in women who have inadvertently been exposed to medroxyprogesterone acetate contraceptive injections in early pregnancy. Newborns exposed to medroxyprogesterone acetate in-utero and followed to adolescence showed no evidence of any adverse effects on their health including their physical, intellectual, sexual or social development.[42126] [57649] There may be an increased risk of minor birth defects in pediatric patients whose mothers are exposed to medroxyprogesterone tablets during the first 4 months of pregnancy, such as hypospadias, clitoral enlargement and labial fusion; however a clear association between these conditions and the use of the drug has not been established.[59800] It is not known whether other forms of medroxyprogesterone acetate (such as the injection dose used for cancer) can cause fetal harm when administered to a pregnant woman; use this cancer treatment during pregnancy only if clearly needed and the benefits to the mother outweigh potential fetal risks.[57648] Be alert to the possibility of an ectopic pregnancy among women using medroxyprogesterone contraceptive injections who complain of severe abdominal pain or become pregnant during use.[42126] [57649] Medroxyprogesterone contraceptive injections should not be used if there is a history of ectopic pregnancy or in diagnostic tests for pregnancy.[42126] [57649] When used in high doses, medroxyprogesterone acetate depot suspension injection is an anti-fertility drug in females, inducing temporary infertility, and a return to ovulation and baseline fertility may be delayed after stopping treatment.[42126] [57648] [57649] [59800] Available surveillance data suggest that the median time to conception for those who do conceive is 10 months following the last medroxyprogesterone contraceptive injection with a range of 4 to 31 months, and is unrelated to the duration of use.[42126]

    Medroxyprogesterone tablets are contraindicated in incomplete abortion. Medroxyprogesterone contraceptive injections can cause irregular menstrual bleeding in most women. In general, these irregularities diminish with continuing use. Women should be counseled regarding menstrual irregularity.

    Combination estrogen-progestin oral contraceptives are classified as carcinogenic to humans in the development of hepatic cancer by the World Health Organization, International Agency for Research on Cancer (WHO IARC). Because of this association, medroxyprogesterone is contraindicated in patients with hepatic dysfunction or hepatic disease; specifically, the injectable medroxyprogesterone acetate (Depot-Provera) for contraception, is contraindicated for use in patients with severe hepatic disease.[42126] Medroxyprogesterone for palliative care should not be used by women with significant liver disease and should be discontinued if jaundice or disturbances of liver function occur.[57648] Use medroxyprogesterone with caution in patients with a past history of cholestasis and jaundice associated with past estrogen use or with pregnancy. If hepatic adverse events recur following medroxyprogesterone administration, consider discontinuation.[42126] [43702] 

    Medroxyprogesterone contraceptive injections may be used safely during breast-feeding. Detectable amounts of drug have been identified in the milk of mothers receiving contraceptive injections of medroxyprogesterone. However, in nursing mothers, milk composition, quality, and amount are not adversely affected. Neonates and infants exposed to medroxyprogesterone from breast milk have been studied for developmental and behavioral effects through puberty. No adverse effects have been identified.[42126] [57649] [48201] Alternatives include other progestin-only contraceptives, such as norethindrone oral contraceptive pills.[48201] Other dosage forms, such as the medroxyprogesterone suspension injection for cancer treatment, or medroxyprogesterone tablets, are recommended to be avoided during lactation.[57648] [59800]

    Medroxyprogesterone should be prescribed cautiously in patients with asthma, congestive heart failure, nephrotic syndrome or other renal disease, or cardiac disease. Hormonal contraceptives can cause fluid retention and may exacerbate any of the above conditions.

    Medroxyprogesterone should be used cautiously in patients with a history of major depression, migraine, or seizure disorder. Progestins may exacerbate these conditions in some patients.[51292] If a patient receiving medroxyprogesterone develops changes in migraine patterns, or a focal migraine with symptoms consistent with cerebral ischemia, or a severe headache pattern that may indicate a cerebrovascular disorder, consider discontinuation of the drug.[41608]

    Patients should be counseled that medroxyprogesterone contraceptive injections do not protect against human immunodeficiency virus (HIV) infection or other sexually transmitted disease. Conversely, patients with known HIV infection or acquired immunodeficiency syndrome (AIDS) should be aware that the use of medroxyprogesterone depot-injection will not prevent the transmission of HIV or other diseases to their partner(s).[42126]

    Estrogen/progestin combination therapy does not prevent mild cognitive impairment (memory loss) and has been found to increase the risk of dementia in women 65 years and older. The WHIMS study, an ancillary study of the WHI trial to assess the effects of estrogen/progestin therapy on cognitive function in geriatric women (65 years of age or older), reported similar rates of developing mild cognitive impairment in those receiving active treatment vs. placebo. Also, patients receiving estrogen/progestin combination therapy were more likely than patients receiving placebo to be diagnosed with dementia. The applicability of this finding to women who use estrogen alone or to the typical user of HRT (i.e., younger, symptomatic adult women taking hormone replacement therapy to relieve menopausal symptoms) is unclear. Administration of estrogen/progestin combination therapy should be avoided in women 65 years of age and older and estrogen/progestin combination therapy should not be used to prevent or treat dementia or preserve cognition (memory).[27451]

    Estrogen plus progestin therapy should be used with caution in individuals with severe hypocalcemia. In addition, combination hormonal therapy may cause an exacerbation of porphyria and systemic lupus erythematosus (SLE) and should be used with caution in women with these conditions.[43702]

    Medroxyprogesterone contraceptive depot-injections carry a boxed warning regarding bone mineral density reductions (osteopenia) in pre-menopausal women. Women using medroxyprogesterone contraceptive injections may lose significant bone mineral density. Bone loss is greater with increasing duration of use and may not be completely reversible. It is unknown if use of these contraceptive injections during adolescence or early adulthood, a critical period of bone accretion, will reduce peak bone mass and increase the risk for osteoporosis and osteoporotic fracture in later life. Women should not use medroxyprogesterone injections as a long-term birth control method (i.e., longer than 2 years) unless other birth control methods are considered inadequate.[42126] [57329] Consider alternative methods of contraception in women with osteoporosis risk factors (e.g., metabolic bone disease, chronic alcohol use, alcoholism, anorexia nervosa, strong family history of osteoporosis, tobacco smoking, or chronic use of drugs that can reduce bone mass, such as anticonvulsants or chronic corticosteroid therapy). While there are no studies available which address the usefulness of calcium and vitamin D to lessen BMD loss in women using medroxyprogesterone depot-injections, all patients should have adequate calcium and vitamin D intake.[42126] [57649] [48201] OTHER USES: BMD evaluation may also be appropriate in patients who use higher doses of depot medroxyprogesterone injections for long-term treatment of endometrial or renal cancers, due to a potential risk for loss of bone mineral density.[57648]

    The safety and efficacy of medroxyprogesterone in children below age 12 years have not been established; there is no known use of the hormone in infants or neonates. The safety and efficacy of hormonal contraceptive products have only been established in females of reproductive age. Safety and efficacy of hormonal birth control is expected to be the same for postpubertal children under the age of 16 and for users 16 years of age and older; medroxyprogesterone depot-contraceptive injection and other depot-injections are associated with a significant loss of bone mineral density, which is of particular concern during the critical period of bone accretion: adolescence and early adulthood. It is unknown if use of medroxyprogesterone depot-injections by young menarchal women will reduce peak bone mass and increase the risk of osteoporotic fractures in later life.[57648] [42126] Use of hormonal contraceptive products in female children before menarche is not indicated.

    Revision Date: 03/20/2018, 10:48:57 AM

    References

    17808 - Hsia J, Langer RD, Manson JE, et al. Conjugated equine estrogens and coronary heart disease. The Women's Health Initiative. Arch Intern Med. 2006;166:357-365.17825 - Cushman M, Kuller LH, Prentice R, et al. Estrogen plus progestin and risk of venous thrombosis. JAMA. 2004;292:1573-1580.25473 - The Heart and Estrogen/progestin Replacement Study (HERS) Research Group. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA 1998;280:605-13.27270 - Grady D, Herrington D, Bittner V, et al. Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). JAMA 2002;288:49-57.27272 - Rossouw JE, Anderson GL, Prentice RL, et al. The Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 2002;288:321-333.27451 - Shumaker SA, Legault C, Rapp SR, et al. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women. The Women's Health Initiative Memory Study: A randomized controlled trial (WHIMS). JAMA 2003;289:2651-62.27530 - Chlebowski RT, Hendrix SL, Langer RD, et al. Influence of Estrogen Plus Progestin on Breast Cancer and Mammography in Healthy Postmenopausal Women: The Women's Health Initiative Randomized Trial. JAMA 2003;289:3243-53.38488 - Rossoun JE, Prentice RL, Manson JE. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA. 2007;297:1465-1477.41608 - 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;65:1-103.42126 - Depo-Provera Contraceptive Injection (Depo-Provera CI) (medroxyprogesterone acetate 150 mg/mL) injection suspension package insert. New York, NY: Pharmacia & Upjohn Company; 2020 Dec.43702 - Medroxyprogesterone acetate tablet package insert. Columbus, OH: American Health; 2013 Apr.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;65:1-103.51292 - 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, 2016.57329 - Medroxyprogesterone Acetate- medroxyprogesterone acetate injection [package insert]. Sellersville, PA: Teva Pharmaceuticals; 10/201157648 - Depo-Provera (medroxyprogesterone acetate 400 mg/ml) injection suspension package insert. New York, NY: Pharmacia & Upjohn Company; 2017 Apr.57649 - Depo-SubQ Provera 104 (medroxyprogesterone acetate 104 mg/ 0.65 mL contraceptive injection suspension) package insert. New York, NY: Pharmacia & Upjohn Company; 2020 Dec.58771 - Li CI, Beaber EF, Tang MT, et al. Effect of depo-medroxyprogesterone acetate on breast cancer risk among women 20 to 44 years of age. Cancer research 2012.15;72:2028-35.59800 - Provera (medroxyprogesterone acetate) tablet package insert. New York, NY: Pharmacia & Upjohn Company; 2015 May.

    Mechanism of Action

    The primary contraceptive effect of progestins involves the inhibition of gonadotropin secretion (suppression of the midcycle surge of luteinizing hormone, or LH), which prevents follicular maturation and ovulation. 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 progesterone 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 contraceptive 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. In five clinical contraception studies, the 12-month failure rate for the group of women treated with medroxyprogesterone-contraceptive depot injection was zero (no pregnancies reported) to 0.7 by Life-Table method.[42126]

     

    Medroxyprogesterone converts a proliferative endometrium into a secretory one in women with adequate endogenous estrogen. Restoring adequate progesterone can help pre-menopausal women with secondary amenorrhea or dysfunctional uterine bleeding to re-establish normal menstrual patterns. The drug reduces endometrial growth in menopausal and postmenopausal women with an intact uterus who are receiving estrogen therapy, thus adding a protective effect against endometrial hyperplasia. Medroxyprogesterone decreases endometriosis related pain by suppressing serum estradiol concentrations and possibly by having a direct action on the lesions of endometriosis. Androgenic and anabolic effects have been noted, but the drug is apparently devoid of significant estrogenic activity. The route and dosage of the drug determine pharmacologic effects. While parenterally administered medroxyprogesterone inhibits gonadotropin production and thus prevents follicular maturation and ovulation, available data indicate that this does not occur when the usually recommended oral dosage is given as single daily doses.[57648][59800]

     

    Progestins are mild, direct stimulants of the respiratory center. During pregnancy and the luteal phase of the menstrual cycle, women can hyperventilate and become hypocapnic due to elevated concentrations of endogenous progestins. Therapeutically, medroxyprogesterone has been used successfully in patients with COPD and hypercapnia, in patients with Pickwickian syndrome, and in patients with sleep apnea.

    Revision Date: 01/21/2022, 04:28:52 PM

    References

    42126 - Depo-Provera Contraceptive Injection (Depo-Provera CI) (medroxyprogesterone acetate 150 mg/mL) injection suspension package insert. New York, NY: Pharmacia & Upjohn Company; 2020 Dec.57648 - Depo-Provera (medroxyprogesterone acetate 400 mg/ml) injection suspension package insert. New York, NY: Pharmacia & Upjohn Company; 2017 Apr.59800 - Provera (medroxyprogesterone acetate) tablet package insert. New York, NY: Pharmacia & Upjohn Company; 2015 May.

    Pharmacokinetics

    Medroxyprogesterone is administered orally or injected intramuscularly or subcutaneously as a depot injection. Greater than 90% of the absorbed drug is protein bound. Medroxyprogesterone acetate is extensively metabolized in the liver via hydroxylation, with subsequent conjugation and elimination in the urine. Most metabolites are excreted in the urine as glucuronide conjugates with only minor amounts excreted as sulfates.[59800]

     

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

    CYP3A4 is the principal enzyme responsible for the overall metabolism of medroxyprogesterone.[61948]

    Route-Specific Pharmacokinetics

    Oral Route

    Peak serum concentrations after oral administration of medroxyprogesterone occur within 2 to 4 hours. The half-life following oral administration of 10 mg for 7 days is variable, but is approximately 16.6 hours to 30 hours. Administration with food increases bioavailability. A 10 mg dose, taken immediately before or after a meal, increased maximum concentration (50 to 70%) and AUC (18 to 33%). The half-life of medroxyprogesterone acetate was not changed with food.[59800]

    Intramuscular Route

    Peak serum concentrations of medroxyprogesterone occur within 3 weeks after a single IM depot suspension dose. Once peak concentrations are achieved with the IM injection, serum concentrations then begin to decrease exponentially to undetectable levels at 120 to 200 days following the injection. The half-life is roughly 50 days following IM depot administration.[42126][57648]

    Subcutaneous Route

    Peak serum concentrations of medroxyprogesterone are reached within approximately 1 week after a single subcutaneous depot dose. Following subcutaneous administration, serum concentrations at 12 to 14 weeks are generally below 0.5 ng/mL. The half-life is roughly 40 days following subcutaneous depot administration.[57649]

    Revision Date: 05/23/2017, 03:37:23 PM

    References

    42126 - Depo-Provera Contraceptive Injection (Depo-Provera CI) (medroxyprogesterone acetate 150 mg/mL) injection suspension package insert. New York, NY: Pharmacia & Upjohn Company; 2020 Dec.57648 - Depo-Provera (medroxyprogesterone acetate 400 mg/ml) injection suspension package insert. New York, NY: Pharmacia & Upjohn Company; 2017 Apr.57649 - Depo-SubQ Provera 104 (medroxyprogesterone acetate 104 mg/ 0.65 mL contraceptive injection suspension) package insert. New York, NY: Pharmacia & Upjohn Company; 2020 Dec.59800 - Provera (medroxyprogesterone acetate) tablet package insert. New York, NY: Pharmacia & Upjohn Company; 2015 May.61948 - Kobayashi K, Mimura N, Fujii H, et al. Role of human cytochrome P450 3A4 in metabolism of medroxyprogesterone acetate. Clin Cancer Res 2000;6:3297-303.

    Pregnancy/Breast-feeding

    ectopic pregnancy, infertility, pregnancy

    Medroxyprogesterone is contraindicated for use during known pregnancy or suspected pregnancy. Although the drug should not be used during pregnancy, there appears to be little or no increased risk of birth defects in women who have inadvertently been exposed to medroxyprogesterone acetate contraceptive injections in early pregnancy. Newborns exposed to medroxyprogesterone acetate in-utero and followed to adolescence showed no evidence of any adverse effects on their health including their physical, intellectual, sexual or social development.[42126] [57649] There may be an increased risk of minor birth defects in pediatric patients whose mothers are exposed to medroxyprogesterone tablets during the first 4 months of pregnancy, such as hypospadias, clitoral enlargement and labial fusion; however a clear association between these conditions and the use of the drug has not been established.[59800] It is not known whether other forms of medroxyprogesterone acetate (such as the injection dose used for cancer) can cause fetal harm when administered to a pregnant woman; use this cancer treatment during pregnancy only if clearly needed and the benefits to the mother outweigh potential fetal risks.[57648] Be alert to the possibility of an ectopic pregnancy among women using medroxyprogesterone contraceptive injections who complain of severe abdominal pain or become pregnant during use.[42126] [57649] Medroxyprogesterone contraceptive injections should not be used if there is a history of ectopic pregnancy or in diagnostic tests for pregnancy.[42126] [57649] When used in high doses, medroxyprogesterone acetate depot suspension injection is an anti-fertility drug in females, inducing temporary infertility, and a return to ovulation and baseline fertility may be delayed after stopping treatment.[42126] [57648] [57649] [59800] Available surveillance data suggest that the median time to conception for those who do conceive is 10 months following the last medroxyprogesterone contraceptive injection with a range of 4 to 31 months, and is unrelated to the duration of use.[42126]

    breast-feeding

    Medroxyprogesterone contraceptive injections may be used safely during breast-feeding. Detectable amounts of drug have been identified in the milk of mothers receiving contraceptive injections of medroxyprogesterone. However, in nursing mothers, milk composition, quality, and amount are not adversely affected. Neonates and infants exposed to medroxyprogesterone from breast milk have been studied for developmental and behavioral effects through puberty. No adverse effects have been identified.[42126] [57649] [48201] Alternatives include other progestin-only contraceptives, such as norethindrone oral contraceptive pills.[48201] Other dosage forms, such as the medroxyprogesterone suspension injection for cancer treatment, or medroxyprogesterone tablets, are recommended to be avoided during lactation.[57648] [59800]

    Revision Date: 01/10/2017, 01:37:31 PM

    References

    42126 - Depo-Provera Contraceptive Injection (Depo-Provera CI) (medroxyprogesterone acetate 150 mg/mL) injection suspension package insert. New York, NY: Pharmacia & Upjohn Company; 2020 Dec.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;65:1-103.57648 - Depo-Provera (medroxyprogesterone acetate 400 mg/ml) injection suspension package insert. New York, NY: Pharmacia & Upjohn Company; 2017 Apr.57649 - Depo-SubQ Provera 104 (medroxyprogesterone acetate 104 mg/ 0.65 mL contraceptive injection suspension) package insert. New York, NY: Pharmacia & Upjohn Company; 2020 Dec.59800 - Provera (medroxyprogesterone acetate) tablet package insert. New York, NY: Pharmacia & Upjohn Company; 2015 May.

    Interactions

    Level 2 (Major)

    • Acitretin
    • Apalutamide
    • Aprepitant, Fosaprepitant
    • Armodafinil
    • Artemether; Lumefantrine
    • Atazanavir
    • Atazanavir; Cobicistat
    • Belzutifan
    • Bexarotene
    • Bosentan
    • Carbamazepine
    • Cenobamate
    • Clobazam
    • Cobicistat
    • Darunavir; Cobicistat
    • Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide
    • Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir
    • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide
    • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate
    • Enzalutamide
    • Etravirine
    • Felbamate
    • Fosamprenavir
    • grapefruit juice
    • Griseofulvin
    • Hydantoins
    • Idelalisib
    • Indinavir
    • Isoniazid, INH; Pyrazinamide, PZA; Rifampin
    • Isoniazid, INH; Rifampin
    • Itraconazole
    • Ivosidenib
    • Lesinurad
    • Lesinurad; Allopurinol
    • Lopinavir; Ritonavir
    • Lorlatinib
    • Lumacaftor; Ivacaftor
    • Mitotane
    • Mobocertinib
    • Modafinil
    • Nefazodone
    • Nelfinavir
    • Nirmatrelvir; Ritonavir
    • Ombitasvir; Paritaprevir; Ritonavir
    • Oxcarbazepine
    • Pegvaliase
    • Posaconazole
    • Ribociclib
    • Ribociclib; Letrozole
    • Rifampin
    • Rifapentine
    • Ritonavir
    • St. John's Wort, Hypericum perforatum
    • Sugammadex
    • Tazemetostat
    • Tipranavir
    • Ulipristal
    • Voriconazole

    Level 3 (Moderate)

    • Adagrasib
    • Amobarbital
    • Aspirin, ASA; Butalbital; Caffeine
    • Aspirin, ASA; Butalbital; Caffeine; Codeine
    • Barbiturates
    • Berotralstat
    • Butabarbital
    • Butalbital; Acetaminophen
    • Butalbital; Acetaminophen; Caffeine
    • Butalbital; Acetaminophen; Caffeine; Codeine
    • Ceritinib
    • Conivaptan
    • Crizotinib
    • Elbasvir; Grazoprevir
    • Fedratinib
    • Fluvoxamine
    • Ketoconazole
    • Lamotrigine
    • Lefamulin
    • Lenacapavir
    • Letermovir
    • Levoketoconazole
    • Lonafarnib
    • Methohexital
    • Nevirapine
    • Pentobarbital
    • Phenobarbital
    • Phenobarbital; Hyoscyamine; Atropine; Scopolamine
    • Phentermine; Topiramate
    • Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements)
    • Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved)
    • Primidone
    • Secobarbital
    • Topiramate
    • Tucatinib
    • Voxelotor

    Level 4 (Minor)

    • Acetohexamide
    • Alogliptin
    • Alogliptin; Metformin
    • Alogliptin; Pioglitazone
    • Alpha-glucosidase Inhibitors
    • Bromocriptine
    • Canagliflozin
    • Canagliflozin; Metformin
    • 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
    • Tamoxifen
    • 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). It is not known if acitretin also interacts with other progestational contraceptives, such as medroxyprogesterone injectables, or if this method is an adequate method 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] 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] 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. medroxyprogesterone). This may be due to a CYP3A4 interaction. 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) Coadministration of medroxyprogesterone, a CYP3A substrate with atazanavir, a strong CYP3A inhibitor should be avoided since it is expected to increase concentrations of medroxyprogesterone acetate. Formal drug interaction studies have not been conducted; however, medroxyprogesterone is metabolized primarily by hydroxylation via the CYP3A4 in vitro. [28142] [57648] Atazanavir; Cobicistat: (Major) Coadministration of medroxyprogesterone, a CYP3A substrate with atazanavir, a strong CYP3A inhibitor should be avoided since it is expected to increase concentrations of medroxyprogesterone acetate. Formal drug interaction studies have not been conducted; however, medroxyprogesterone is metabolized primarily by hydroxylation via the CYP3A4 in vitro. [28142] [57648] (Major) Consider the benefits and risk of administering antiretroviral regimens containing cobicistat with medroxyprogesterone. 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] 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] Berotralstat: (Moderate) Use caution if coadministration of berotralstat with medroxyprogesterone is necessary, as the systemic exposure of medroxyprogesterone may be increased resulting in an increase in treatment-related adverse reactions. Medroxyprogesterone is metabolized primarily by hydroxylation via CYP3A4 and berotralstat is a moderate CYP3A4 inhibitor. [57648] [66159] 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] 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] 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] 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] Ceritinib: (Moderate) Use caution if coadministration of ceritinib with medroxyprogesterone is necessary, as the systemic exposure of medroxyprogesterone may be increased resulting in an increase in treatment-related adverse reactions. Ceritinib is a strong CYP3A4 inhibitor. Medroxyprogesterone is metabolized primarily by hydroxylation via a CYP3A4. [57094] [57648] 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] Clobazam: (Major) The addition of non-hormonal forms of contraception are recommended during concurrent use of clobazam and hormonal contraceptives. Concurrent administration of clobazam, a weak CYP3A4 inducer, with progestins may increase the elimination of these hormones. The additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Patients taking these hormones for indications other than contraception may need to be monitored for reduced clinical effect while on clobazam, with dose adjustments made based on clinical efficacy. [46370] [6300] Cobicistat: (Major) Consider the benefits and risk of administering antiretroviral regimens containing cobicistat with medroxyprogesterone. 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] Conivaptan: (Moderate) Use caution if coadministration of conivaptan with medroxyprogesterone is necessary, as the systemic exposure of medroxyprogesterone may be increased resulting in an increase in treatment-related adverse reactions. Conivaptan is a moderate CYP3A inhibitor. Medroxyprogesterone is metabolized primarily by hydroxylation via a CYP3A. [31764] [57648] Crizotinib: (Moderate) Use caution if concomitant of crizotinib and medroxyprogesterone is necessary, as the systemic exposure of medroxyprogesterone may be increased resulting in an increase in treatment-related adverse reactions. Crizotinib is a moderate CYP3A4 inhibitor. Medroxyprogesterone is metabolized primarily by hydroxylation via a CYP3A4. [45458] [57648] 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] Darunavir; Cobicistat: (Major) Consider the benefits and risk of administering antiretroviral regimens containing cobicistat with medroxyprogesterone. 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] Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Consider the benefits and risk of administering antiretroviral regimens containing cobicistat with medroxyprogesterone. 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] Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) Coadministration of medroxyprogesterone, a CYP3A substrate with ritonavir, a strong CYP3A inhibitor should be avoided since it is expected to increase concentrations of medroxyprogesterone acetate. Formal drug interaction studies have not been conducted; however, medroxyprogesterone is metabolized primarily by hydroxylation via the CYP3A4 in vitro. [28380] [34557] [47165] [57648] Elbasvir; Grazoprevir: (Moderate) Administering medroxyprogesterone with elbasvir; grazoprevir may result in elevated medroxyprogesterone plasma concentrations. Medroxyprogesterone is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events. [57648] [60523] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Consider the benefits and risk of administering antiretroviral regimens containing cobicistat with medroxyprogesterone. 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] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Consider the benefits and risk of administering antiretroviral regimens containing cobicistat with medroxyprogesterone. 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] 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] 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] 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] 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] Fedratinib: (Moderate) Use caution if coadministration of fedratinib with medroxyprogesterone is necessary, as the systemic exposure of medroxyprogesterone may be increased resulting in an increase in treatment-related adverse reactions. Medroxyprogesterone is metabolized primarily by hydroxylation via a CYP3A4. Fedratinib is a moderate CYP3A4 inhibitor. [57648] [64568] 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] Fluvoxamine: (Moderate) Coadministration of medroxyprogesterone, a CYP3A substrate, with fluvoxamine, a moderate CYP3A inhibitor, may result in an increase in concentrations of medroxyprogesterone. Formal drug interaction studies have not been conducted; however, medroxyprogesterone is metabolized primarily by hydroxylation via CYP3A4 in vitro. [47184] [54631] [54632] [57648] 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] 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] Grapefruit juice: (Major) Coadministration of medroxyprogesterone, a CYP3A substrate with grapefruit juice, a strong CYP3A inhibitor should be avoided since it is expected to increase concentrations of medroxyprogesterone acetate. Formal drug interaction studies have not been conducted; however, medroxyprogesterone is metabolized primarily by hydroxylation via the CYP3A4 in vitro. [29087] [57648] [58104] 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: (Major) Coadministration of medroxyprogesterone, a CYP3A substrate with idelalisib, a strong CYP3A inhibitor should be avoided since it is expected to increase concentrations of medroxyprogesterone acetate. Formal drug interaction studies have not been conducted; however, medroxyprogesterone is metabolized primarily by hydroxylation via the CYP3A4 in vitro. [57648] [57675] Indinavir: (Major) Coadministration of medroxyprogesterone, a CYP3A substrate with indinavir, a strong CYP3A inhibitor should be avoided since it is expected to increase concentrations of medroxyprogesterone acetate. Formal drug interaction studies have not been conducted; however, medroxyprogesterone is metabolized primarily by hydroxylation via the CYP3A4 in vitro. Indinavir also 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] [34557] [46638] [57648] 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] Itraconazole: (Major) Coadministration of medroxyprogesterone, a CYP3A substrate with itraconazole, a strong CYP3A inhibitor should be avoided since it is expected to increase concentrations of medroxyprogesterone acetate. Formal drug interaction studies have not been conducted; however, medroxyprogesterone is metabolized primarily by hydroxylation via the CYP3A4 in vitro. [27983] [29036] [57648] Ivosidenib: (Major) Consider alternative methods of contraception in patients receiving ivosidenib. Coadministration may decrease the concentrations of hormonal contraceptives. [63368] Ketoconazole: (Moderate) Use caution if coadministration of ketoconazole with medroxyprogesterone is necessary, as the systemic exposure of medroxyprogesterone may be increased resulting in an increase in treatment-related adverse reactions. Medroxyprogesterone is metabolized primarily by hydroxylation via a CYP3A4 and ketoconazole is a strong CYP3A4 inhibitor. [27982] [57648] [67231] 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] Lefamulin: (Moderate) Use caution if coadministration of oral lefamulin with medroxyprogesterone is necessary, as the systemic exposure of medroxyprogesterone may be increased resulting in an increase in treatment-related adverse reactions. Oral lefamulin is a moderate CYP3A4 inhibitor; an interaction is not expected with intravenous lefamulin. Medroxyprogesterone is metabolized primarily by hydroxylation via a CYP3A4. [57648] [64576] Lenacapavir: (Moderate) Use caution if coadministration of lenacapavir with medroxyprogesterone is necessary, as the systemic exposure of medroxyprogesterone may be increased resulting in an increase in treatment-related adverse reactions. Medroxyprogesterone is metabolized primarily by hydroxylation via a CYP3A; lenacapavir is a moderate CYP3A inhibitor. [57648] [68383] Lesinurad: (Major) Hormonal contraceptives, including combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins. This includes injectable, transdermal, and implantable forms. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females should use additional, non-hormonal methods of contraception and not rely solely on hormonal contraceptive methods when taking lesinurad. [60473] Lesinurad; Allopurinol: (Major) Hormonal contraceptives, including combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins. This includes injectable, transdermal, and implantable forms. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females should use additional, non-hormonal methods of contraception and not rely solely on hormonal contraceptive methods when taking lesinurad. [60473] Letermovir: (Moderate) An increase in the plasma concentration of medroxyprogesterone may occur if given with letermovir. In patients who are also receiving treatment with cyclosporine, the magnitude of this interaction may be amplified. Avoid coadministration of medroxyprogesterone in patient receiving both letermovir and cyclosporine as this may increase the risk for adverse reactions. Medroxyprogesterone is primarily metabolized by CYP3A4. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. [57648] [62611] Levoketoconazole: (Moderate) Use caution if coadministration of ketoconazole with medroxyprogesterone is necessary, as the systemic exposure of medroxyprogesterone may be increased resulting in an increase in treatment-related adverse reactions. Medroxyprogesterone is metabolized primarily by hydroxylation via a CYP3A4 and ketoconazole is a strong CYP3A4 inhibitor. [27982] [57648] [67231] 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] Lonafarnib: (Moderate) Use caution if coadministration of lonafarnib with medroxyprogesterone is necessary, as the systemic exposure of medroxyprogesterone may be increased resulting in an increase in treatment-related adverse reactions. Medroxyprogesterone is metabolized primarily by hydroxylation via a CYP3A4; lonafarnib is a strong CYP3A4 inhibitor. [57648] [66129] Lopinavir; Ritonavir: (Major) Coadministration of medroxyprogesterone, a CYP3A substrate with ritonavir, a strong CYP3A inhibitor should be avoided since it is expected to increase concentrations of medroxyprogesterone acetate. Formal drug interaction studies have not been conducted; however, medroxyprogesterone is metabolized primarily by hydroxylation via the CYP3A4 in vitro. [28380] [34557] [47165] [57648] 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 medroxyprogesterone and lumacaftor; ivacaftor, unless the benefits outweigh the risks. Lumacaftor; ivacaftor may decrease medroxyprogesterone, reducing efficacy. When coadministered with lumacaftor; ivacaftor, hormonal contraceptives are not a reliable method of effective contraception; instruct patients on alternative and/or additional methods of birth control. In addition, concomitant use of hormonal contraceptives and lumacaftor; ivacaftor may increase the incidence of menstruation-associated adverse reactions (e.g., amenorrhea, dysmenorrhea, menorrhagia). Patients taking medroxyprogesterone for other indications should be monitored for clinical efficacy of the progestin. Medroxyprogesterone is primarily metabolized in vitro via CYP3A4. Lumacaftor is a strong CYP3A inducer. [57648] [59891] 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] 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] Mitotane: (Major) Use caution if mitotane and medroxyprogesterone are used concomitantly, and monitor for decreased medroxyprogesterone efficacy. Since the dosage of medroxyprogesterone injections for contraception cannot be modified, an alternate or additional form of contraception should be considered in patients requiring therapy with mitotane. The alternative or additional contraceptive agent may need to be continued for one month after discontinuation of mitotane. Mitotane is a strong CYP3A4 inducer and medroxyprogesterone is a CYP3A4 substrate in vitro; coadministration may result in decreased plasma concentrations of medroxyprogesterone. Pregnancies have been reported during therapy with progestin contraceptives in patients receiving other strong CYP3A inducers. [41934] [57648] 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] Nefazodone: (Major) Coadministration of medroxyprogesterone, a CYP3A substrate with nefazodone, a strong CYP3A inhibitor should be avoided since it is expected to increase concentrations of medroxyprogesterone acetate. Formal drug interaction studies have not been conducted; however, medroxyprogesterone is metabolized primarily by hydroxylation via the CYP3A4 in vitro. [28683] [54634] [57648] 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. In addition, coadministration of medroxyprogesterone, a CYP3A substrate with nelfinavir, a strong CYP3A inhibitor should be avoided since it is expected to increase concentrations of medroxyprogesterone acetate. Formal drug interaction studies have not been conducted; however, medroxyprogesterone is metabolized primarily by hydroxylation via the CYP3A4 in vitro. [28839] [34558] [34559] [57648] 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) Coadministration of medroxyprogesterone, a CYP3A substrate with ritonavir, a strong CYP3A inhibitor should be avoided since it is expected to increase concentrations of medroxyprogesterone acetate. Formal drug interaction studies have not been conducted; however, medroxyprogesterone is metabolized primarily by hydroxylation via the CYP3A4 in vitro. [28380] [34557] [47165] [57648] Ombitasvir; Paritaprevir; Ritonavir: (Major) Coadministration of medroxyprogesterone, a CYP3A substrate with ritonavir, a strong CYP3A inhibitor should be avoided since it is expected to increase concentrations of medroxyprogesterone acetate. Formal drug interaction studies have not been conducted; however, medroxyprogesterone is metabolized primarily by hydroxylation via the CYP3A4 in vitro. [28380] [34557] [47165] [57648] 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] Pegvaliase: (Major) The use of medroxyprogesterone acetate suspension injection (a formulation containing PEG 3350) may increase the risk for serious hypersensitivity reactions and anaphylaxis when given with pegvaliase. Make sure any patient receiving pegvaliase has an emergency supply of epinephrine and knows how to use it in the case of a serious allergic reaction or anaphylaxis. In a single dose study of pegvaliase in adult patients with PKU, 2 patients receiving medroxyprogesterone acetate suspension injection (a formulation containing PEG 3350) experienced hypersensitivity reactions. One of the 2 patients experienced a hypersensitivity reaction on day 15 after a single pegvaliase dose of 0.67 mg within 15 minutes following medroxyprogesterone acetate injectable suspension, and subsequently experienced anaphylaxis on day 89 within 30 minutes after the next dose of medroxyprogesterone acetate injectable suspension. The other patient experienced a hypersensitivity reaction on day 40 after a single pegvaliase dosage of 0.08 mg within 10 minutes following medroxyprogesterone acetate injectable suspension. Both patients had high anti-PEG IgG antibody titers at or around the time of the hypersensitivity reactions. Most pegvaliase-treated patients developed anti-PEG IgM and IgG antibodies after treatment with the drug. The clinical effects of concomitant treatment with different PEGylated products is unknown. Monitor patients treated with pegvaliase and concomitantly with other PEGylated products for hypersensitivity reactions including anaphylaxis. [63190] 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] 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] Posaconazole: (Major) Coadministration of medroxyprogesterone, a CYP3A substrate with posaconazole, a strong CYP3A inhibitor should be avoided since it is expected to increase concentrations of medroxyprogesterone acetate. Formal drug interaction studies have not been conducted; however, medroxyprogesterone is metabolized primarily by hydroxylation via the CYP3A4 in vitro. [32723] [34464] [34465] [57648] 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] 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] Ribociclib: (Major) Avoid coadministration of medroxyprogesterone with ribociclib due to increased plasma concentrations of medroxyprogesterone. Medroxyprogesterone is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. Though no formal drug interaction trials have been conducted, concomitant administration of strong CYP3A4 inhibitors is expected to increase medroxyprogesterone exposure. [57648] [61816] Ribociclib; Letrozole: (Major) Avoid coadministration of medroxyprogesterone with ribociclib due to increased plasma concentrations of medroxyprogesterone. Medroxyprogesterone is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. Though no formal drug interaction trials have been conducted, concomitant administration of strong CYP3A4 inhibitors is expected to increase medroxyprogesterone exposure. [57648] [61816] 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] Ritonavir: (Major) Coadministration of medroxyprogesterone, a CYP3A substrate with ritonavir, a strong CYP3A inhibitor should be avoided since it is expected to increase concentrations of medroxyprogesterone acetate. Formal drug interaction studies have not been conducted; however, medroxyprogesterone is metabolized primarily by hydroxylation via the CYP3A4 in vitro. [28380] [34557] [47165] [57648] 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] Saquinavir: (Minor) Coadministration of medroxyprogesterone, a CYP3A substrate with saquinavir, a strong CYP3A inhibitor should be avoided since it is expected to increase concentrations of medroxyprogesterone acetate. Formal drug interaction studies have not been conducted; however, medroxyprogesterone is metabolized primarily by hydroxylation via the CYP3A4 in vitro. [28995] [39863] [39864] [57648] 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] 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] 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] 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] Tamoxifen: (Minor) Medroxyprogesterone reduces plasma concentrations of N-dimethyltamoxifen, the metabolite of tamoxifen, but not tamoxifen. [63589] 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] 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] 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. In addition, coadministration of medroxyprogesterone, a CYP3A substrate with tipranavir, a strong CYP3A inhibitor should be avoided since it is expected to increase concentrations of medroxyprogesterone acetate. Formal drug interaction studies have not been conducted; however, medroxyprogesterone is metabolized primarily by hydroxylation via the CYP3A4 in vitro. [31320] [46638] [57648] [58679] [8102] 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] Tucatinib: (Moderate) Use caution if coadministration of tucatinib with medroxyprogesterone is necessary, as the systemic exposure of medroxyprogesterone may be increased resulting in an increase in treatment-related adverse reactions. Tucatinib is a strong CYP3A4 inhibitor. Medroxyprogesterone is metabolized primarily by hydroxylation via a CYP3A4. [57648] [65295] 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] Voriconazole: (Major) Coadministration of medroxyprogesterone, a CYP3A substrate with voriconazole, a strong CYP3A inhibitor should be avoided since it is expected to increase concentrations of medroxyprogesterone acetate. Formal drug interaction studies have not been conducted; however, medroxyprogesterone is metabolized primarily by hydroxylation via the CYP3A4 in vitro. [57648] Voxelotor: (Moderate) Use caution if coadministration of voxelotor with medroxyprogesterone is necessary, as the systemic exposure of medroxyprogesterone may be increased resulting in an increase in treatment-related adverse reactions. Voxelotor is a moderate CYP3A inhibitor. Medroxyprogesterone is metabolized primarily by hydroxylation via a CYP3A. [57648] [64778]
    Revision Date: 02/02/2023, 02:26:00 AM

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    Monitoring Parameters

    • pap smear
    • pelvic exam

    US Drug Names

    • Amen
    • Depo-Provera
    • Depo-subQ Provera 104
    • Provera
    ;