Elsevier Logo

English

ThisiscontentfromElsevier'sDrugInformation

TRANSFORM HOW YOU USE DRUG INFORMATION

Learn more about Elsevier's Drug Information today! Get the drug data and decision support you need, including TRUE Daily Updates™ including every day including weekends and holidays.

Feb.19.2021

Metformin

Indications/Dosage

Labeled

  • type 2 diabetes mellitus

Off-Label

  • drug-induced obesity
  • gestational diabetes
  • infertility
  • insulin resistance
  • polycystic ovary syndrome
  • precocious puberty
  • prediabetes
  • prolongation of pubertal growth
† Off-label indication

For treatment of type 2 diabetes mellitus

For the adjunct treatment of patients with hyperinsulinemia secondary to polycystic ovary syndrome† (PCOS), including the treatment of infertility† in these patients

Oral dosage (regular-release tablets)

Adult females

500 mg PO 3 times per day. After roughly 1 month, 33% of females with PCOS will ovulate compared to 4% with placebo. When metformin is added to clomiphene therapy for PCOS with infertility, roughly 86% of patients ovulate in comparison to roughly 8% on clomiphene alone.[26676] Worldwide data of metformin use in PCOS to regulate menstrual cycles and decrease ovarian steroidogenesis are relatively extensive. Metformin-failure may occur in severely obese patients, so weight loss and dietary control are also recommended.

For the delay of clinical puberty and early menarche in females with precocious puberty†

Oral dosage

Female children older than 6 years

Limited data indicate that 425 mg PO once daily with dinner may be effective. Thirty-eight females with precocious puberty (average age at study initiation 7.9 +/- 0.2 years, average age at diagnosis of precocious puberty 6.8 +/- 0.2 years), low birth weight (less than 2.9 kg for term birth or -1SD for gestational age at preterm birth), and prepuberty (Tanner breast stage 1) were randomized to 425 mg of metformin at bedtime (n = 19) or no therapy (n = 19) in an open-label fashion; patients did not have a history of diabetes mellitus, adrenal hyperplasia, or thyroid abnormalities. After 24 months, patients treated with metformin experienced statistically significant improvements in metabolic abnormalities (i.e., insulin resistance, androgen excess, atherogenic lipid profile, and adipose body composition) as well as a 0.4 year delay in the clinical onset of puberty (defined as Tanner breast stage 2); additionally, metformin treatment was associated with a 1-year delay in the puberty-associated insulin-like growth factor-I rise. Preliminary 3-year data indicate that metformin treatment is associated with a delay in menarche (5/19 patients in the no treatment group have undergone menarche compared to 0/19 patients in the metformin-treated group, p = 0.016). Furthermore, the patients treated with metformin maintained gains in height and lean mass.[32892]

For the prolongation of pubertal growth† and to prevent the delay of early menarche in low birth weight females with early-normal onset of puberty

Oral dosage

Female children with onset of puberty between 8 and 9 years of age

Limited data indicate that 825 mg PO once daily with dinner may be effective. Twenty-two females with onset of puberty (defined as Tanner breast stage 2) between 8 and 9 years of age (average age at onset 8.6 +/- 0.1 years) and low birth weight (2.8 kg or less for term birth or -1.5 SD for gestational age) were randomized to 850 mg metformin once daily (n = 10) or no treatment (n = 12) in an open-label fashion for 36 months. At enrollment, these patients had a height greater than or equal to 1 SD above midparenteral height for chronological age and bone age of greater than 1 year above chronological age; in addition, all patients had central and progressive puberty. Treatment with metformin resulted in a delay of menarche by a median of 1 year (p < 0.01) and increases in near-adult height (height gain over 42 months of treatment was 16 cm for the untreated group vs. 19.5 cm for the metformin-treated group, p <= 0.05). In addition, patients are still being followed and height has ceased in almost all of the patients in the untreated group, while 4/10 patients in the metformin-treated group continue to grow at a rate of greater than 2 cm/year. In addition, those patients receiving metformin had a leaner body composition and demonstrated lower levels of insulin resistance with improved lipid profiles.[32893]

For the treatment of gestational diabetes† in pregnant women not controlled by diet-therapy alone

Oral dosage (immediate-release dosage forms)

Adult females

500 mg PO once nightly for 1 week, then titrate to 500 mg PO twice daily. Further titration of the daily dose by 500 mg every 1 to 2 weeks to attain glycemic targets is used. Max: If needed, up to 2.5 to 3 grams/day PO, given in 2 or 3 divided doses, has been studied in gestational diabetes mellitus (GDM).[62358] Metformin is not recommended for routine use during pregnancy.[28550]Many studies and analyses of metformin in use in pregnancy have been published.[46201] The American College of Obstetricians and Gynecologists (ACOG) and the American Diabetes Association (ADA) continue to recommend human insulin as the standard of care in women with GDM requiring medical therapy. Per ACOG, metformin is a preferred second-line choice for women who decline insulin therapy or are unable to safely administer insulin. Per the ADA, metformin may be used to treat GDM as a treatment option; however, metformin does cross the placenta. While no teratogenic effects have been associated with metformin, no long-term safety data are available. Metformin may cause a lower risk of neonatal hypoglycemia and less maternal weight gain than insulin; however, some data suggest that metformin may slightly increase the risk of prematurity. The ADA notes that in some clinical studies, nearly 50% of GDM patients initially treated with metformin have needed the addition of insulin in order to achieve acceptable glucose control.[64926] [62358]

For the treatment of prediabetes†, including patients with insulin resistance†

Oral dosage (regular-release tablets)

Adults

850 mg PO once daily for 1 month, then increase to 850 mg PO twice daily, unless GI adverse effects necessitate a longer titration period.[19237] [64081] [64082] According to the American Diabestes Association (ADA) Standards of Care, metformin should be considered in those with prediabetes, especially for those with a BMI of 35 kg/m2 and greater, those less than 60 years of age, and women with prior gestational diabetes mellitus.[64926]

For the treatment of drug-induced obesity† and adverse metabolic effects secondary to antipsychotic medications†

Oral dosage (regular-release tablets)

Adults

750 mg to 2 g PO daily in 2 to 3 divided doses has been studied in clinical trials. Doses up to 2.55 g/day have also been used. To minimize GI adverse effects, most trials initiated therapy with 250 mg or 500 mg PO twice daily or 850 mg PO once daily, and increased the dose gradually based on tolerability.[64084] [64085] [64086] [64087] [64088] [64089] [64090] The AACE/ACE guidelines for patients with obesity provide a strong recommendation with strong evidence for the use of metformin in promoting modest weight loss and metabolic improvement in patients who are taking antipsychotic medications.[62881]

Oral dosage (extended-release tablets)

Adults

1 g to 2 g PO once daily was the maintenance dose range in clinical trials. To minimize GI adverse effects, trials initiated therapy with 500 mg PO once daily and titrated dosage upwards in 500 mg increments every 2 to 6 weeks based on tolerability.[64091] [64092] The AACE/ACE guidelines for patients with obesity provide a strong recommendation with strong evidence for the use of metformin in promoting modest weight loss and metabolic improvement in patients who are taking antipsychotic medications.[62881]

Therapeutic Drug Monitoring

  • Individualize glycemic goals based on a risk-benefit assessment.
  • Use higher goals in patients with persistent hypoglycemia.
  • Monitor post-prandial glucose concentrations if there is any inconsistency between pre-prandial glucose and A1C concentrations and to help assess basal-bolus regimens.[64926]

 

Blood glucose goals for adults with type 1 or type 2 diabetes [64926]:

  • Pre-prandial = 80 to 130 mg/dL
  • Peak post-prandial = less than 180 mg/dL

 

A1C goals for adults with type 1 or type 2 diabetes [64926]:

  • Assess A1C at least 2 times a year in patients who are meeting treatment goals (and who have stable glycemic control). Perform the A1C test quarterly in patients whose therapy has changed or who are not meeting glycemic goals.
  • In general, an A1C target is less than 7% in nonpregnant adults.[50321][64926][64933]
    • A more stringent goal of less than 6.5% may be appropriate for selected individual patients if this can be achieved without significant hypoglycemia or other adverse effects.[60608]
    • Less stringent goals (e.g., A1C less than 8%) may be appropriate for patients with a history of severe hypoglycemia, limited life expectancy, advanced microvascular/macrovascular complications, or extensive comorbid conditions.[64926]

 

A1C goals for children and adolescents with type 2 diabetes [64926]:

  • Assess A1C every 3 months in most patients or more frequently as clinically indicated.
  • In general, the A1C target is less than 7% when treatment is with oral agents alone. A lower goal of less than 6.5% is reasonable if it can be achieved without excessive hypoglycemia or adverse effects of treatment. A less stringent A1C goal of less than 7.5% may be appropriate for patients with an increased risk of hypoglycemia.

Maximum Dosage Limits

  • Adults

    2,550 mg/day PO for regular-release tablets and oral solution; 2,000 to 2,500 mg/day PO for extended-release tablets depending on product used; 2,000 mg/day PO for extended-release suspension.

  • Geriatric

    Use more than 1,000 mg/day PO with caution in older adult. Adult Max: 2,550 mg/day PO for regular-release tablets and oral solution; 2,000 to 2,500 mg/day PO for extended-release tablets depending on product used; 2,000 mg/day PO for extended-release suspension.

  • Adolescents

    2,000 mg/day PO for regular-release tablets, oral solution, and extended-release suspension; safe and effective use has not been established for extended-release tablets.

  • Children

    10 years and older: 2,000 mg/day PO for regular-release tablets, oral solution, and extended-release suspension; safe and effective use has not been established for extended-release tablets.

    Less than 10 years: Safety and efficacy have not been established.

  • Infants

    Safety and efficacy have not been established.

Patients with Hepatic Impairment Dosing

Generally avoid metformin use in hepatic impairment; hepatic disease increases the risk of metformin-associated lactic acidosis.

Patients with Renal Impairment Dosing

eGFR more than 45 mL/minute/1.73 m2: No dosage adjustment needed. Obtain an eGFR at least annually in all patients taking metformin.[60699]

eGFR 30 to 45 mL/minute/1.73 m2: Initiation of metformin is not recommended. Obtain an eGFR at least annually in all patients taking metformin. In patients whose eGFR is initially greater than 45 mL/minute/1.73 m2, and then later falls below 45 mL/minute/1.73 m2, assess the benefits and risks of continuing treatment. Discontinue metformin if the patient's eGFR later falls below 30 mL/minute/1.73 m2.[60699] The ADA and others suggest it is reasonable to decrease the dose by 50% (or use one-half the maximum recommended dose) and monitor renal function every 3 months in those with an eGFR less than 45 mL/minute/1.73 m2. Do not initiate the drug in patients at this stage. Additional caution is required in patients with anticipated significant fluctuations in renal status or those at risk for abrupt deterioration in kidney function, based on previous history, other comorbidities, albuminuria, and medication regimen (e.g., potent diuretics or nephrotoxic agents).[50321][50322]

eGFR less than 30 mL/minute/1.73 m2: Use is contraindicated.[60699]

 

Intermittent hemodialysis

Metformin use is contraindicated. Metformin is dialyzable; hemodialysis will efficiently remove accumulated metformin in the case of drug-induced lactic acidosis, provided metformin is halted.

† Off-label indication
Revision Date: 02/19/2021, 12:36:35 PM

References

19237 - Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:393-40326676 - Nestler JE, Jakubowicz DJ, Evans WS, et al. Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. N Engl J Med 1998;338:1876-1880.28550 - Glucophage and Glucophage XR (metformin HCl tablets and extended-release tablets) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2018 May.32892 - Ibanez L, Ong K, Valls C, et al. Metformin treatment to prevent early puberty in girls with precocious puberty. J Clin Endocrinol Metab 2006;91:2888-91.32893 - Ibanez L, Valls C, Ong K, et al. Metformin therapy during puberty delays menarche, prolongs puberal growth, and augments adult height: a randomized study in low-birth-weight girls with early-normal onset of puberty. J Clin Endocrinol Metab 2006;0:2068-73.46201 - Dhulkotia JS, Ola B, Fraser R, et al. Oral hypoglycemic agents vs insulin in management of gestational diabetes: a systematic review and metaanalysis. Am J Obstet Gynecol 2010;203:457.50229 - Nathan DM, Buse JB, Davidson MB, et al; American Diabetes Association; European Association for Study of Diabetes. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes Care 2009;32:193-203.50321 - Davies MJ, D'Alessio DA, Fradkin J, et al. Management of hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2018;41:2669-2701.50322 - Lipska KJ, Bailey CJ, Inzucchi SE. Use of metformin in the setting of mild-to-moderate renal insufficiency. Diabetes Care 2011;34:1432-1437.60608 - Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus Statement by The American Association of Clinical Endocrinologists and American College of Endocrinology on the Comprehensive Type 2 Diabetes Management Algorithm 2019 Executive Summary. Endocrine Pract 2019;25:69-100.60699 - US Food and Drug Administration (FDA) MedWatch for Metformin-containing Drugs: Revised Warnings for Certain Patients With Reduced Kidney Function. Retrieved April 8, 2016. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm494829.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery60711 - Fortamet (metformin extended-release film-coated tablets) package insert. Ft. Lauderdale, FL: Watson Laboratories-Florida; 2017 April.60714 - Glumetza (metformin hydrochloride film-coated modified-release tablet) package insert. Menlo Park, CA: Depomed, Inc.; 2017 April.60715 - Riomet (metformin hydrochloride) oral solution package insert. Jacksonville FL: Ranbaxy Laboratories Inc.; 2018 Nov.62358 - American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins-Obstetrics. Practice Bulletin No. 190: Gestational Diabetes Mellitus. Obstet Gynecol. 2018;131:e49-e64. Reaffirmed 2019.62881 - Garvey WT, Mechanick JI, Brett EM, et al; Reviewers of the AACE/ACE Obesity Clinical Practice Guidelines. American Association of Clinical Endocrinologists and American College of Endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity. Endocr Pract. 2016;22 Suppl 3:1-203.64081 - Knowler WC, Fowler SE, Hamman RF, et al. Diabetes Prevention Program Research Group. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet. 2009;374:1677-86.64082 - Apolzan JW, Venditti EM, Edelstein SL, et al. Long-Term Weight Loss With Metformin or Lifestyle Intervention in the Diabetes Prevention Program Outcomes Study. Ann Intern Med 2019. Epub ahead of print, doi: 10.7326/M18-1605.64084 - Baptista T, Rangel N, Fernandez V, et al. Metformin as an adjunctive treatment to control body weight and metabolic dysfunction during olanzapine administration: a multicentric, double-blind, placebo-controlled trial. Schizophr Res 2007;93:99-108.64085 - Zheng W, Li XB, Tang YL, Xiang YQ, Wang CY, de Leon J. Metformin for weight gain and metabolic abnormalities associated with antipsychotic treatment: meta-analysis or randomized placebo-controlled trials. J Clin Psychopharmacol 2015;35:499-509.64086 - De Silva VA, Suraweera C, Ratnatunga SS, Dayabandara M, Wanniarachchi N, Hanwella R. Metformin in prevention and treatment of antipsychotic induced weight gain: a systematic review and meta-analysis. BMC Psychiatry 2016;16:341.64087 - Wang M, Tong JH, Zhu G, Liang GM, Yan HF, Wang XZ. Metformin for treatment of antipsychotic-induced weight gain: a randomized, placebo-controlled study. Schizophr Res 2012;138:54-57.64088 - Das C, Mendez G, Jagasia S, Labbate LA. Second-generation antipsychotic use in schizophrenia and associated weight gain: a critical review and meta-analysis of behavioral and pharmacologic treatments. Ann Clin Psychiatry 2012;24:225-239.64089 - Chen CH, Huang MC, Kao CF, et al. Effects of adjunctive metformin on metabolic traits in nondiabetic clozapine-treated patients with schizophrenia and the effect of metformin discontinuation on body weight: a 24-week, randomized, double-blind, placebo-controlled study. J Clin Psychiatry 2013;74:e424-e430.64090 - Jarskog LF, Hamer RM, Catellier DJ, et al; METS Investigators. Metformin for weight loss and metabolic control in overweight outpatients with schizophrenia and schizoaffective disorder. Am J Psychiatry 2013;170:1032-1040.64091 - Rado J, von Ammon Cavanaugh S. A naturalistic randomized placebo-controlled trial of extended-release metformin to prevent weight gain associated with olanzapine in a US community-dwelling population. J Clin Psychopharmacol 2016;36:163-168.64092 - Carrizo E, Fernandez V, Connell L, et al. Extended release metformin for metabolic control assistance during prolonged clozapine administration: a 14 week, double-blind, parallel group, placebo-controlled study. Schizophr Res 2009;113:19-26.64593 - Riomet XR (metformin extended-release suspension) package insert. Cranbury, NJ: Sun Pharmaceutical Industries, Inc.; 2019 Aug.64926 - American Diabetes Association. Standards of Medical Care in Diabetes - 2021. Diabetes Care. 2021; 44(Suppl 1):S1-S232. Available at: https://care.diabetesjournals.org/content/44/Supplement_164933 - Buse JB, Wexler DJ, Tsapas A, et al. 2019 Update to: Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2019. Epub ahead of print, doi: 10.2337/dci19-0066.66433 - Bansal N, Dhaliwal R, Weinstock RS. Management of diabetes in the elderly. Med Clin North Am 2015;99:351-77.

How Supplied

Metformin Hydrochloride Oral solution

Metformin Hydrochloride 500mg/5mL Solution (71800-0008) (Innovida Pharmaceutique Corporation) null

Metformin Hydrochloride Oral solution

Metformin Hydrochloride 500mg/5mL Solution (42571-0360) (Micro Labs USA Inc. ) null

Metformin Hydrochloride Oral solution

Riomet 500mg/5mL Solution (10631-0206) (Ranbaxy Laboratories, a Sun Pharma Company) nullRiomet 500mg/5mL Solution package photo

Metformin Hydrochloride Oral solution

Riomet 500mg/5mL Solution (10631-0238) (Ranbaxy Laboratories, a Sun Pharma Company) null

Metformin Hydrochloride Oral solution

Riomet 500mg/5mL Solution (63304-0206) (Sun Pharmaceutical Industries, Inc.) (off market)

Metformin Hydrochloride Oral suspension, Metformin Hydrochloride Powder for oral suspension, extended release

RIOMET ER 500mg/5mL Extended-Release Suspension (10631-0019) (Ranbaxy Laboratories, a Sun Pharma Company) null

Metformin Hydrochloride Oral tablet

Glucophage 500mg Tablet (00087-6060) (Bristol Myers Squibb Co) (off market)

Metformin Hydrochloride Oral tablet

Glucophage 500mg Tablet (55289-0211) (PD-Rx Pharmaceuticals, Inc.) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (71093-0132) (ACI Healthcare USA, Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (62584-0259) (American Health Packaging) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (60687-0155) (American Health Packaging) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (53746-0218) (Amneal Pharmaceuticals) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (65162-0218) (Amneal Pharmaceuticals LLC) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (65162-0175) (Amneal Pharmaceuticals LLC) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (60505-0190) (Apotex Corp) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (67877-0217) (Ascend Laboratories, LLC a Subsidiary of Alkem Laboratories Ltd) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (67877-0217) (Ascend Laboratories, LLC a Subsidiary of Alkem Laboratories Ltd) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (67877-0561) (Ascend Laboratories, LLC a Subsidiary of Alkem Laboratories Ltd) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (65862-0008) (Aurobindo Pharma USA Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (23155-0102) (Avet Pharmaceuticals Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (23155-0102) (Avet Pharmaceuticals Inc.) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (42291-0605) (AvKARE, Inc.) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (10544-0254) (Blenheim Pharmacal, Inc.) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (24658-0290) (Blu Pharmaceuticals, LLC) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (51991-0805) (Breckenridge Inc) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (70882-0124) (Cambridge Therapeutics Technologies, LLC) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (61442-0361) (Carlsbad Technology Inc) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (42806-0313) (Epic Pharma LLC) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (42806-0213) (Epic Pharma LLC) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (68462-0159) (Glenmark Pharmaceuticals) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (60429-0111) (Golden State Medical Supply, Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (70010-0063) (Granules Pharmaceuticals Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (59762-4320) (Greenstone Ltd) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (50742-0154) (Ingenus Pharmaceuticals, LLC) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (42385-0904) (Laurus Labs Private Limited) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (68645-0290) (Legacy Pharmaceutical Packaging, LLC) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (68645-0539) (Legacy Pharmaceutical Packaging, LLC) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (68645-0582) (Legacy Pharmaceutical Packaging, LLC) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (68645-0544) (Legacy Pharmaceutical Packaging, LLC) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (00904-5601) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (00904-5601) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (00904-5849) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (00904-5601) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (00904-6090) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (00904-6343) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (00904-7162) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (00904-5634) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (00904-6326) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (00904-6689) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) nullMetformin Hydrochloride 500mg Tablet package photo

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (00904-6343) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (10135-0617) (Marlex Pharmaceuticals) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (63739-0640) (McKesson Packaging) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (63739-0299) (McKesson Packaging Inc) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (71717-0104) (Megalith Pharmaceuticals) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (71709-0110) (Metcure Pharmaceuticals, Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (58657-0640) (Method Pharmaceuticals) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (51079-0172) (Mylan Institutional LLC ) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (65162-0218) (Mylan Institutional LLC ) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (51079-0972) (Mylan Institutional LLC ) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (00378-0234) (Mylan Pharmaceuticals Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (00378-7185) (Mylan Pharmaceuticals Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (58517-0040) (New Horizon Rx Group, LLC) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (49884-0739) (Par Pharmaceuticals, an Endo Company) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (49884-0736) (Par Pharmaceuticals, an Endo Company) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (00603-4467) (Par Pharmaceuticals, an Endo Company) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (55289-0615) (PD-Rx Pharmaceuticals, Inc.) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (43063-0527) (PD-Rx Pharmaceuticals, Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (43063-0012) (PD-Rx Pharmaceuticals, Inc.) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (43063-0539) (PD-Rx Pharmaceuticals, Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (43063-0012) (PD-Rx Pharmaceuticals, Inc.) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (72789-0192) (PD-Rx Pharmaceuticals, Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (43063-0898) (PD-Rx Pharmaceuticals, Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (00781-5050) (Sandoz Inc. a Novartis Company) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (00185-0213) (Sandoz Inc. a Novartis Company) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (50228-0105) (ScieGen Pharmaceuticals, Inc) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (43547-0320) (Solco Healthcare US LLC) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (43547-0320) (Solco Healthcare US LLC) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (43547-0357) (Solco Healthcare US LLC) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (43547-0248) (Solco Healthcare US LLC) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (53489-0467) (Sun Pharmaceutical Industries, Inc.) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (57664-0397) (Sun Pharmaceutical Industries, Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (51224-0020) (TAGI Pharma, Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (00093-1048) (Teva Pharmaceuticals USA) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (00555-0385) (Teva Pharmaceuticals USA) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (00172-4331) (Teva Pharmaceuticals USA) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (00093-1048) (Teva Pharmaceuticals USA) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (00093-1048) (Teva Pharmaceuticals USA) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (00228-2657) (Teva/Actavis US) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (00591-2713) (Teva/Actavis US) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (62037-0674) (Teva/Actavis US) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (62037-0674) (Teva/Actavis US) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (49483-0622) (Time Cap Laboratories Inc) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (69367-0180) (Westminster Pharmaceuticals, LLC) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (64679-0528) (Wockhardt USA, LLC) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (68382-0028) (Zydus Pharmaceuticals (USA) Inc.) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (68382-0758) (Zydus Pharmaceuticals (USA) Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 500mg Tablet (00406-2028) (Zypharma Pharmaceuticals) (off market)

Metformin Hydrochloride Oral tablet

Glucophage 850mg Tablet (00087-6070) (Bristol Myers Squibb Co) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (71093-0133) (ACI Healthcare USA, Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (62584-0332) (American Health Packaging) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (60687-0143) (American Health Packaging) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (53746-0219) (Amneal Pharmaceuticals) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (65162-0219) (Amneal Pharmaceuticals LLC) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (65162-0174) (Amneal Pharmaceuticals LLC) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (60505-0191) (Apotex Corp) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (67877-0218) (Ascend Laboratories, LLC a Subsidiary of Alkem Laboratories Ltd) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (67877-0218) (Ascend Laboratories, LLC a Subsidiary of Alkem Laboratories Ltd) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (67877-0562) (Ascend Laboratories, LLC a Subsidiary of Alkem Laboratories Ltd) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (65862-0009) (Aurobindo Pharma USA Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (23155-0103) (Avet Pharmaceuticals Inc.) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (23155-0103) (Avet Pharmaceuticals Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (42291-0606) (AvKARE, Inc.) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (10544-0255) (Blenheim Pharmacal, Inc.) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (10544-0589) (Blenheim Pharmacal, Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (51991-0806) (Breckenridge Inc) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (70882-0125) (Cambridge Therapeutics Technologies, LLC) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (61442-0362) (Carlsbad Technology Inc) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (42806-0215) (Epic Pharma LLC) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (42806-0314) (Epic Pharma LLC) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (68462-0160) (Glenmark Pharmaceuticals) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (60429-0112) (Golden State Medical Supply, Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (70010-0064) (Granules Pharmaceuticals Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (59762-4321) (Greenstone Ltd) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (50742-0155) (Ingenus Pharmaceuticals, LLC) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (68645-0548) (Legacy Pharmaceutical Packaging, LLC) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (68645-0549) (Legacy Pharmaceutical Packaging, LLC) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (68645-0583) (Legacy Pharmaceutical Packaging, LLC) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (68645-0547) (Legacy Pharmaceutical Packaging, LLC) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (00904-5602) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (00904-6327) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (00904-5635) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (00904-6091) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (00904-5602) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (00904-6344) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (00904-6690) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)Metformin Hydrochloride 850mg Tablet package photo

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (00904-7163) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (00904-5602) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (00904-5850) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (10135-0618) (Marlex Pharmaceuticals) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (63739-0702) (McKesson Packaging) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (63739-0300) (McKesson Packaging Inc) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (71717-0105) (Megalith Pharmaceuticals) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (71709-0111) (Metcure Pharmaceuticals, Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (58657-0641) (Method Pharmaceuticals) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (51079-0173) (Mylan Institutional LLC ) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (51079-0973) (Mylan Institutional LLC ) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (00378-0240) (Mylan Pharmaceuticals Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (00378-7186) (Mylan Pharmaceuticals Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (49884-0737) (Par Pharmaceuticals, an Endo Company) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (49884-0740) (Par Pharmaceuticals, an Endo Company) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (00603-4468) (Par Pharmaceuticals, an Endo Company) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (55289-0934) (PD-Rx Pharmaceuticals, Inc.) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (43063-0429) (PD-Rx Pharmaceuticals, Inc.) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (43063-0507) (PD-Rx Pharmaceuticals, Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (00185-0215) (Sandoz Inc. a Novartis Company) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (00781-5051) (Sandoz Inc. a Novartis Company) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (50228-0106) (ScieGen Pharmaceuticals, Inc) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (43547-0321) (Solco Healthcare US LLC) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (43547-0249) (Solco Healthcare US LLC) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (43547-0321) (Solco Healthcare US LLC) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (43547-0358) (Solco Healthcare US LLC) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (57664-0435) (Sun Pharmaceutical Industries, Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (53489-0468) (Sun Pharmaceutical Industries, Inc.) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (51224-0120) (TAGI Pharma, Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (00093-1049) (Teva Pharmaceuticals USA) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (00172-4330) (Teva Pharmaceuticals USA) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (00093-1049) (Teva Pharmaceuticals USA) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (00555-0386) (Teva Pharmaceuticals USA) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (00093-1049) (Teva Pharmaceuticals USA) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (00228-2715) (Teva/Actavis US) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (00591-2775) (Teva/Actavis US) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (62037-0675) (Teva/Actavis US) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (62037-0675) (Teva/Actavis US) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (49483-0621) (Time Cap Laboratories Inc) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (69367-0181) (Westminster Pharmaceuticals, LLC) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (64679-0529) (Wockhardt USA, LLC) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (68382-0029) (Zydus Pharmaceuticals (USA) Inc.) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (68382-0759) (Zydus Pharmaceuticals (USA) Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 850mg Tablet (00406-2029) (Zypharma Pharmaceuticals) (off market)

Metformin Hydrochloride Oral tablet

Glucophage 1000mg Tablet (00087-6071) (Bristol Myers Squibb Co) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (71093-0134) (ACI Healthcare USA, Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (62584-0452) (American Health Packaging) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (60687-0162) (American Health Packaging) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (53746-0220) (Amneal Pharmaceuticals) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (65162-0220) (Amneal Pharmaceuticals LLC) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (65162-0177) (Amneal Pharmaceuticals LLC) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (60505-0192) (Apotex Corp) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (67877-0563) (Ascend Laboratories, LLC a Subsidiary of Alkem Laboratories Ltd) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (67877-0221) (Ascend Laboratories, LLC a Subsidiary of Alkem Laboratories Ltd) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (67877-0221) (Ascend Laboratories, LLC a Subsidiary of Alkem Laboratories Ltd) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (65862-0010) (Aurobindo Pharma USA Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (23155-0104) (Avet Pharmaceuticals Inc.) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (23155-0104) (Avet Pharmaceuticals Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (42291-0607) (AvKARE, Inc.) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (10544-0947) (Blenheim Pharmacal, Inc.) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (10544-0630) (Blenheim Pharmacal, Inc.) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (10544-0058) (Blenheim Pharmacal, Inc.) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (10544-0253) (Blenheim Pharmacal, Inc.) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (24658-0292) (Blu Pharmaceuticals, LLC) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (51991-0807) (Breckenridge Inc) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (61442-0363) (Carlsbad Technology Inc) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (42806-0221) (Epic Pharma LLC) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (42806-0315) (Epic Pharma LLC) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (68462-0161) (Glenmark Pharmaceuticals) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (60429-0113) (Golden State Medical Supply, Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (70010-0065) (Granules Pharmaceuticals Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (59762-4322) (Greenstone Ltd) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (50742-0156) (Ingenus Pharmaceuticals, LLC) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (42385-0902) (Laurus Labs Private Limited) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (68645-0546) (Legacy Pharmaceutical Packaging, LLC) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (68645-0584) (Legacy Pharmaceutical Packaging, LLC) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (68645-0545) (Legacy Pharmaceutical Packaging, LLC) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (68645-0300) (Legacy Pharmaceutical Packaging, LLC) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (00904-5636) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (00904-5603) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (00904-5603) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (00904-6345) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (00904-5603) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (00904-6691) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) nullMetformin Hydrochloride 1000mg Tablet package photo

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (00904-5851) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (00904-6328) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (00904-6092) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (10135-0619) (Marlex Pharmaceuticals) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (71717-0106) (Megalith Pharmaceuticals) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (71709-0112) (Metcure Pharmaceuticals, Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (58657-0642) (Method Pharmaceuticals) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (51079-0995) (Mylan Institutional LLC ) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (51079-0174) (Mylan Institutional LLC ) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (00378-0244) (Mylan Pharmaceuticals Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (00378-7187) (Mylan Pharmaceuticals Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (49884-0738) (Par Pharmaceuticals, an Endo Company) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (00603-4469) (Par Pharmaceuticals, an Endo Company) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (49884-0741) (Par Pharmaceuticals, an Endo Company) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (55289-0919) (PD-Rx Pharmaceuticals, Inc.) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (43063-0544) (PD-Rx Pharmaceuticals, Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (43063-0889) (PD-Rx Pharmaceuticals, Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (43063-0430) (PD-Rx Pharmaceuticals, Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (72789-0189) (PD-Rx Pharmaceuticals, Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (65084-0416) (Rx Pak Div of Mckesson Corp) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (00781-5052) (Sandoz Inc. a Novartis Company) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (00185-0221) (Sandoz Inc. a Novartis Company) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (50228-0107) (ScieGen Pharmaceuticals, Inc) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (43547-0322) (Solco Healthcare US LLC) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (43547-0250) (Solco Healthcare US LLC) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (43547-0359) (Solco Healthcare US LLC) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (43547-0322) (Solco Healthcare US LLC) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (53489-0469) (Sun Pharmaceutical Industries, Inc.) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (57664-0474) (Sun Pharmaceutical Industries, Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (51224-0220) (TAGI Pharma, Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (00093-7214) (Teva Pharmaceuticals USA) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (00093-7214) (Teva Pharmaceuticals USA) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (00555-0387) (Teva Pharmaceuticals USA) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (00093-7214) (Teva Pharmaceuticals USA) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (00172-4432) (Teva Pharmaceuticals USA) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (00228-2718) (Teva/Actavis US) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (00591-2455) (Teva/Actavis US) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (62037-0676) (Teva/Actavis US) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (62037-0676) (Teva/Actavis US) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (49483-0620) (Time Cap Laboratories Inc) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (69367-0182) (Westminster Pharmaceuticals, LLC) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (64679-0530) (Wockhardt USA, LLC) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (68382-0030) (Zydus Pharmaceuticals (USA) Inc.) (off market)

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (68382-0760) (Zydus Pharmaceuticals (USA) Inc.) null

Metformin Hydrochloride Oral tablet

Metformin Hydrochloride 1000mg Tablet (00406-2030) (Zypharma Pharmaceuticals) (off market)

Metformin Hydrochloride Oral tablet, extended release

Glucophage XR 500mg Extended-Release Tablet (00087-6063) (Bristol Myers Squibb Co) null

Metformin Hydrochloride Oral tablet, extended release

Glucophage XR 500mg Extended-Release Tablet (58864-0507) (PD-Rx Pharmaceuticals, Inc.) (off market)

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (27241-0188) (Ajanta Pharma USA Inc) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (68084-0072) (American Health Packaging) (off market)

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (60687-0640) (American Health Packaging) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (53746-0178) (Amneal Pharmaceuticals) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (65162-0178) (Amneal Pharmaceuticals LLC) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (15338-0400) (Apace Packaging LLC) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (60505-0260) (Apotex Corp) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (67877-0159) (Ascend Laboratories, LLC a Subsidiary of Alkem Laboratories Ltd) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (67877-0413) (Ascend Laboratories, LLC a Subsidiary of Alkem Laboratories Ltd) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (67877-0413) (Ascend Laboratories, LLC a Subsidiary of Alkem Laboratories Ltd) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (65862-0291) (Aurobindo Pharma USA Inc.) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (42291-0610) (AvKARE, Inc.) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (50268-0531) (AvPAK; a Division of AvKARE Inc) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (76385-0128) (Bayshore Pharmaceuticals) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (10544-0944) (Blenheim Pharmacal, Inc.) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (10544-0248) (Blenheim Pharmacal, Inc.) (off market)

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (42806-0632) (Epic Pharma LLC) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (70010-0491) (Granules Pharmaceuticals Inc.) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (53746-0178) (Interpharm Inc) (off market)

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (68645-0120) (Legacy Pharmaceutical Packaging, LLC) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (33342-0239) (MacLeods Pharma) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (00904-6107) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (00904-5794) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (00904-5794) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (51079-0626) (Mylan Institutional LLC ) (off market)

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (00378-0352) (Mylan Pharmaceuticals Inc.) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (75834-0500) (Nivagen Pharmaceuticals) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (29033-0018) (Nostrum Laboratories, Inc.) (off market)

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (29033-0055) (Nostrum Laboratories, Inc.) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (49884-0921) (Par Pharmaceuticals, an Endo Company) (off market)

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (55289-0384) (PD-Rx Pharmaceuticals, Inc.) (off market)

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (72789-0009) (PD-Rx Pharmaceuticals, Inc.) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (72789-0059) (PD-Rx Pharmaceuticals, Inc.) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (43063-0428) (PD-Rx Pharmaceuticals, Inc.) (off market)

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (72789-0105) (PD-Rx Pharmaceuticals, Inc.) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (43063-0428) (PD-Rx Pharmaceuticals, Inc.) (off market)

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (43063-0428) (PD-Rx Pharmaceuticals, Inc.) (off market)

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (00185-4416) (Sandoz Inc. a Novartis Company) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (00781-5055) (Sandoz Inc. a Novartis Company) (off market)

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (00781-5503) (Sandoz Inc. a Novartis Company) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (63304-0860) (Sun Pharmaceutical Industries, Inc.) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (62756-0142) (Sun Pharmaceutical Industries, Inc.) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (51224-0007) (TAGI Pharma, Inc.) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (00172-4435) (Teva Pharmaceuticals USA) (off market)

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (00093-7267) (Teva Pharmaceuticals USA) (off market)

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (62037-0571) (Teva/Actavis US) (off market)

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (62037-0571) (Teva/Actavis US) (off market)

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (00228-2740) (Teva/Actavis US) (off market)

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (49483-0623) (Time Cap Laboratories Inc) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (29300-0389) (Unichem Pharmaceuticals USA, Inc) nullMetformin Hydrochloride 500mg Extended-Release Tablet package photo

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 500mg Extended-Release Tablet (68382-0027) (Zydus Pharmaceuticals (USA) Inc.) (off market)

Metformin Hydrochloride Oral tablet, extended release

Glucophage XR 750mg Extended-Release Tablet (00087-6064) (Bristol Myers Squibb Co) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 750mg Extended-Release Tablet (53746-0179) (Amneal Pharmaceuticals) (off market)

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 750mg Extended-Release Tablet (65162-0179) (Amneal Pharmaceuticals LLC) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 750mg Extended-Release Tablet (60505-1329) (Apotex Corp) (off market)

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 750mg Extended-Release Tablet (67877-0414) (Ascend Laboratories, LLC a Subsidiary of Alkem Laboratories Ltd) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 750mg Extended-Release Tablet (65862-0292) (Aurobindo Pharma USA Inc.) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 750mg Extended-Release Tablet (42291-0611) (AvKARE, Inc.) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 750mg Extended-Release Tablet (50268-0532) (AvPAK; a Division of AvKARE Inc) (off market)

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 750mg Extended-Release Tablet (76385-0129) (Bayshore Pharmaceuticals) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 750mg Extended-Release Tablet (10544-0521) (Blenheim Pharmacal, Inc.) (off market)

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 750mg Extended-Release Tablet (42806-0633) (Epic Pharma LLC) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 750mg Extended-Release Tablet (70010-0492) (Granules Pharmaceuticals Inc.) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 750mg Extended-Release Tablet (53746-0179) (Interpharm Inc) (off market)

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 750mg Extended-Release Tablet (33342-0240) (MacLeods Pharma) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 750mg Extended-Release Tablet (00904-6108) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 750mg Extended-Release Tablet (00904-5795) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 750mg Extended-Release Tablet (00378-0350) (Mylan Pharmaceuticals Inc.) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 750mg Extended-Release Tablet (29033-0056) (Nostrum Laboratories, Inc.) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 750mg Extended-Release Tablet (29033-0021) (Nostrum Laboratories, Inc.) (off market)

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 750mg Extended-Release Tablet (43063-0902) (PD-Rx Pharmaceuticals, Inc.) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 750mg Extended-Release Tablet (43063-0372) (PD-Rx Pharmaceuticals, Inc.) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 750mg Extended-Release Tablet (72789-0097) (PD-Rx Pharmaceuticals, Inc.) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 750mg Extended-Release Tablet (72789-0106) (PD-Rx Pharmaceuticals, Inc.) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 750mg Extended-Release Tablet (63304-0767) (Sun Pharmaceutical Industries, Inc.) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 750mg Extended-Release Tablet (62756-0143) (Sun Pharmaceutical Industries, Inc.) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 750mg Extended-Release Tablet (51224-0107) (TAGI Pharma, Inc.) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 750mg Extended-Release Tablet (00555-0107) (Teva Pharmaceuticals USA) (off market)

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 750mg Extended-Release Tablet (00093-7212) (Teva Pharmaceuticals USA) (off market)

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 750mg Extended-Release Tablet (62037-0577) (Teva/Actavis US) (off market)

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 750mg Extended-Release Tablet (00228-2728) (Teva/Actavis US) (off market)

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 750mg Extended-Release Tablet (00228-2728) (Teva/Actavis US) (off market)

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 750mg Extended-Release Tablet (62037-0577) (Teva/Actavis US) (off market)

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 750mg Extended-Release Tablet (49483-0624) (Time Cap Laboratories Inc) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 750mg Extended-Release Tablet (29300-0399) (Unichem Pharmaceuticals USA, Inc) nullMetformin Hydrochloride 750mg Extended-Release Tablet package photo

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 750mg Extended-Release Tablet (72578-0036) (Viona Pharmaceuticals Inc.) null

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 750mg Extended-Release Tablet (68382-0039) (Zydus Pharmaceuticals (USA) Inc.) (off market)

Metformin Hydrochloride Oral tablet, extended release

Metformin Hydrochloride 1000mg Extended-Release Tablet (27241-0241) (Ajanta Pharma USA Inc) null

Metformin Hydrochloride Oral tablet, modified release

Glumetza 500mg Extended-Release Tablet (13913-0002) (Assertio Therapeutics, Inc) (off market)

Metformin Hydrochloride Oral tablet, modified release

Glumetza 500mg Extended-Release Tablet (68012-0002) (Bausch Health US, LCC) (off market)

Metformin Hydrochloride Oral tablet, modified release

Glumetza 500mg Extended-Release Tablet (68012-0004) (Bausch Health US, LCC) null

Metformin Hydrochloride Oral tablet, modified release

Metformin Hydrochloride 500mg Extended-Release Tablet (27241-0240) (Ajanta Pharma USA Inc) null

Metformin Hydrochloride Oral tablet, modified release

Metformin Hydrochloride 500mg Extended-Release Tablet (42291-0558) (AvKARE, Inc.) null

Metformin Hydrochloride Oral tablet, modified release

Metformin Hydrochloride 500mg Extended-Release Tablet (68682-0017) (Bausch Health US, LLC) (off market)

Metformin Hydrochloride Oral tablet, modified release

Metformin Hydrochloride 500mg Extended-Release Tablet (68682-0021) (Bausch Health US, LLC) null

Metformin Hydrochloride Oral tablet, modified release

Metformin Hydrochloride 500mg Extended-Release Tablet (68462-0520) (Glenmark Pharmaceuticals) null

Metformin Hydrochloride Oral tablet, modified release

Metformin Hydrochloride 500mg Extended-Release Tablet (68180-0338) (Lupin Pharmaceuticals, Inc.) null

Metformin Hydrochloride Oral tablet, modified release

Metformin Hydrochloride 500mg Extended-Release Tablet (16714-0938) (Northstar Rx LLC) null

Metformin Hydrochloride Oral tablet, modified release

Metformin Hydrochloride 500mg Extended-Release Tablet (50228-0445) (ScieGen Pharmaceuticals, Inc) null

Metformin Hydrochloride Oral tablet, modified release

Metformin Hydrochloride 500mg Extended-Release Tablet (47335-0305) (Sun Pharmaceutical Industries, Inc.) null

Metformin Hydrochloride Oral tablet, modified release

Metformin Hydrochloride 500mg Extended-Release Tablet (00591-2411) (Teva/Actavis US) null

Metformin Hydrochloride Oral tablet, modified release

Metformin Hydrochloride 500mg Extended-ReleaseTablet (70010-0496) (Granules Pharmaceuticals Inc.) null

Metformin Hydrochloride Oral tablet, modified release

Glumetza 1000mg Extended-Release Tablet (13913-0003) (Assertio Therapeutics, Inc) (off market)

Metformin Hydrochloride Oral tablet, modified release

Glumetza 1000mg Extended-Release Tablet (68012-0003) (Bausch Health US, LCC) null

Metformin Hydrochloride Oral tablet, modified release

Metformin Hydrochloride 1000mg Extended-Release Tablet (42291-0559) (AvKARE, Inc.) null

Metformin Hydrochloride Oral tablet, modified release

Metformin Hydrochloride 1000mg Extended-Release Tablet (68682-0018) (Bausch Health US, LLC) null

Metformin Hydrochloride Oral tablet, modified release

Metformin Hydrochloride 1000mg Extended-Release Tablet (68462-0521) (Glenmark Pharmaceuticals) null

Metformin Hydrochloride Oral tablet, modified release

Metformin Hydrochloride 1000mg Extended-Release Tablet (70010-0497) (Granules Pharmaceuticals Inc.) null

Metformin Hydrochloride Oral tablet, modified release

Metformin Hydrochloride 1000mg Extended-Release Tablet (68180-0339) (Lupin Pharmaceuticals, Inc.) null

Metformin Hydrochloride Oral tablet, modified release

Metformin Hydrochloride 1000mg Extended-Release Tablet (16714-0939) (Northstar Rx LLC) null

Metformin Hydrochloride Oral tablet, modified release

Metformin Hydrochloride 1000mg Extended-Release Tablet (50228-0446) (ScieGen Pharmaceuticals, Inc) null

Metformin Hydrochloride Oral tablet, modified release

Metformin Hydrochloride 1000mg Extended-Release Tablet (47335-0306) (Sun Pharmaceutical Industries, Inc.) null

Metformin Hydrochloride Oral tablet, modified release

Metformin Hydrochloride 1000mg Extended-Release Tablet (00591-2412) (Teva/Actavis US) null

Metformin Hydrochloride Oral tablet, osmotic laser drilled

Fortamet 500mg Extended-Release Tablet (62022-0574) (Shionogi USA, Inc.) (off market)

Metformin Hydrochloride Oral tablet, osmotic laser drilled

Fortamet 500mg Extended-Release Tablet (59630-0574) (Shionogi USA, Inc.) (off market)

Metformin Hydrochloride Oral tablet, osmotic laser drilled

Metformin Hydrochloride 500mg Extended-Release Tablet (11788-0037) (AiPing Pharmaceiticals, Inc.) null

Metformin Hydrochloride Oral tablet, osmotic laser drilled

Metformin Hydrochloride 500mg Extended-Release Tablet (42291-0582) (AvKARE, Inc.) null

Metformin Hydrochloride Oral tablet, osmotic laser drilled

Metformin Hydrochloride 500mg Extended-Release Tablet (42291-0592) (AvKARE, Inc.) (off market)

Metformin Hydrochloride Oral tablet, osmotic laser drilled

Metformin Hydrochloride 500mg Extended-Release Tablet (42806-0405) (Epic Pharma LLC) null

Metformin Hydrochloride Oral tablet, osmotic laser drilled

Metformin Hydrochloride 500mg Extended-Release Tablet (51407-0058) (Golden State Medical Supply, Inc.) null

Metformin Hydrochloride Oral tablet, osmotic laser drilled

Metformin Hydrochloride 500mg Extended-Release Tablet (50742-0633) (Ingenus Pharmaceuticals, LLC) null

Metformin Hydrochloride Oral tablet, osmotic laser drilled

Metformin Hydrochloride 500mg Extended-Release Tablet (68180-0336) (Lupin Pharmaceuticals, Inc.) null

Metformin Hydrochloride Oral tablet, osmotic laser drilled

Metformin Hydrochloride 500mg Extended-Release Tablet (00378-6002) (Mylan Pharmaceuticals Inc.) null

Metformin Hydrochloride Oral tablet, osmotic laser drilled

Metformin Hydrochloride 500mg Extended-Release Tablet (29033-0031) (Nostrum Laboratories, Inc.) null

Metformin Hydrochloride Oral tablet, osmotic laser drilled

Metformin Hydrochloride 500mg Extended-Release Tablet (00591-2719) (Teva/Actavis US) null

Metformin Hydrochloride Oral tablet, osmotic laser drilled

Fortamet 1000mg Extended-Release Tablet (62022-0575) (Shionogi USA, Inc.) (off market)

Metformin Hydrochloride Oral tablet, osmotic laser drilled

Fortamet 1000mg Extended-Release Tablet (59630-0575) (Shionogi USA, Inc.) (off market)

Metformin Hydrochloride Oral tablet, osmotic laser drilled

Metformin Hydrochloride 1000mg Extended-Release Tablet (11788-0038) (AiPing Pharmaceiticals, Inc.) null

Metformin Hydrochloride Oral tablet, osmotic laser drilled

Metformin Hydrochloride 1000mg Extended-Release Tablet (27241-0189) (Ajanta Pharma USA Inc) null

Metformin Hydrochloride Oral tablet, osmotic laser drilled

Metformin Hydrochloride 1000mg Extended-Release Tablet (68084-0819) (American Health Packaging) (off market)

Metformin Hydrochloride Oral tablet, osmotic laser drilled

Metformin Hydrochloride 1000mg Extended-Release Tablet (42291-0593) (AvKARE, Inc.) (off market)

Metformin Hydrochloride Oral tablet, osmotic laser drilled

Metformin Hydrochloride 1000mg Extended-Release Tablet (42291-0583) (AvKARE, Inc.) null

Metformin Hydrochloride Oral tablet, osmotic laser drilled

Metformin Hydrochloride 1000mg Extended-Release Tablet (42806-0406) (Epic Pharma LLC) null

Metformin Hydrochloride Oral tablet, osmotic laser drilled

Metformin Hydrochloride 1000mg Extended-Release Tablet (51407-0059) (Golden State Medical Supply, Inc.) null

Metformin Hydrochloride Oral tablet, osmotic laser drilled

Metformin Hydrochloride 1000mg Extended-Release Tablet (50742-0634) (Ingenus Pharmaceuticals, LLC) null

Metformin Hydrochloride Oral tablet, osmotic laser drilled

Metformin Hydrochloride 1000mg Extended-Release Tablet (68180-0337) (Lupin Pharmaceuticals, Inc.) null

Metformin Hydrochloride Oral tablet, osmotic laser drilled

Metformin Hydrochloride 1000mg Extended-Release Tablet (00378-6001) (Mylan Pharmaceuticals Inc.) null

Metformin Hydrochloride Oral tablet, osmotic laser drilled

Metformin Hydrochloride 1000mg Extended-Release Tablet (29033-0032) (Nostrum Laboratories, Inc.) null

Metformin Hydrochloride Oral tablet, osmotic laser drilled

Metformin Hydrochloride 1000mg Extended-Release Tablet (00591-2720) (Teva/Actavis US) null

Description/Classification

Description

Metformin is an oral biguanide used to improve glycemic control in adult and pediatric patients 10 years and older with type 2 diabetes mellitus (DM). The actions of metformin differ from, yet complement, those of other antidiabetic therapies. Metformin is first-line in the treatment of type 2 DM. The combination of metformin with lifestyle interventions should be initiated in most patients at the time of diagnosis of type 2 DM. Metformin was chosen as the initial drug therapy based on its efficacy, safety, and cost. While metformin carries a low risk for lactic acidosis as outlined in the prescribing information and boxed warning of all metformin-containing products, care in prescribing and monitoring can reduce this risk. In patients with established cardiovascular (CV) disease, heart failure (HF), or chronic kidney disease (CKD), a sodium-glucose co-transporter 2 (SGLT2) inhibitor or glucagon-like peptide-1 receptor agonist (GLP-1 RA) with proven CV benefit and reduction of CKD progression is recommended for add-on therapy, independent of baseline A1C or individualized A1C target.[50321][64933][60608][64926] In a follow-up study to the UKPDS, researchers found that after 10-years of resuming typical care, patients originally randomized to metformin therapy had a 33% relative reduction in the risk of myocardial infarction and a 27% relative reduction in the risk of death from any cause as compared to patients receiving conventional therapy; the reductions in cardiovascular risk persisted even though A1C concentrations were similar in the 2 groups after 1 year of follow-up.[34541] In patients with prediabetes, metformin reduces the risk of future diabetes by 25% to 30% and may confer cardiovascular benefit.[60608] Metformin has been found useful in the off-label treatment of polycystic ovary syndrome (PCOS); it lowers serum androgens and restores normal menstrual cycles and ovulation, and may improve pregnancy rates.[27528] Additionally, limited data indicate that it may delay puberty onset in females with precocious puberty and delay menarche onset in females with early-normal onset of puberty.[32892][32893]

 

NOTE: Globally, as well as in the U.S., some metformin ER products have been recalled from the market because they may contain unacceptable levels of N-nitrosodimethylamine (NDMA), a probable human carcinogen. FDA testing has not shown NDMA in IR metformin products. NDMA has been linked with cancers of the digestive tract, bladder, kidney, and others. The FDA has required testing of manufactured products. If testing shows NDMA above the acceptable daily intake limit, the manufacturer must inform the FDA and should not release the lot for consumer use. Patients taking prescription metformin ER who wish to stop taking these products should talk to their health care professional about other treatment/product options first and should not stop taking their metformin product on their own.

Classifications

  • Alimentary Tract and Metabolism
    • Antidiabetic Agents
      • Blood Glucose Lowering Agents, excluding Insulins
        • Biguanide Antidiabetics
Revision Date: 05/29/2020, 11:18:49 AM

References

27528 - Kosasa TS. Making a Case for Metformin. OB/GYN 2003;48:69-80.32892 - Ibanez L, Ong K, Valls C, et al. Metformin treatment to prevent early puberty in girls with precocious puberty. J Clin Endocrinol Metab 2006;91:2888-91.32893 - Ibanez L, Valls C, Ong K, et al. Metformin therapy during puberty delays menarche, prolongs puberal growth, and augments adult height: a randomized study in low-birth-weight girls with early-normal onset of puberty. J Clin Endocrinol Metab 2006;0:2068-73.34541 - Holman RR, Paul SK, Bethel MA, et al. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008;359:1577-89.50321 - Davies MJ, D'Alessio DA, Fradkin J, et al. Management of hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2018;41:2669-2701.60608 - Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus Statement by The American Association of Clinical Endocrinologists and American College of Endocrinology on the Comprehensive Type 2 Diabetes Management Algorithm 2019 Executive Summary. Endocrine Pract 2019;25:69-100.64926 - American Diabetes Association. Standards of Medical Care in Diabetes - 2021. Diabetes Care. 2021; 44(Suppl 1):S1-S232. Available at: https://care.diabetesjournals.org/content/44/Supplement_164933 - Buse JB, Wexler DJ, Tsapas A, et al. 2019 Update to: Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2019. Epub ahead of print, doi: 10.2337/dci19-0066.

Administration Information

General Administration Information

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

Route-Specific Administration

Oral Administration

Oral Solid Formulations

Regular-release tablets:

  • Administer orally with meals.[28550]

 

Extended-release tablets:

  • Do not crush or chew; have patient swallow whole.
  • Usually administered once-daily with the evening meal.
  • The inactive ingredients may occasionally be eliminated in the feces as a soft mass that may resemble the original tablet.[28550]

Oral Liquid Formulations

Oral Solution (e.g., Riomet oral solution)

  • For accurate dosing, use a calibrated spoon, oral syringe, or container to measure the oral solution.
  • Administer orally with meals.[60715]

 

Oral extended-release Suspension (e.g., Riomet ER suspension)

  • Shake well for at least 10 seconds prior to each administration.
  • Measure dosage with the manufacturer provided dosing cup to ensure accurate dosing.
  • Administer once daily with the evening meal.[64593]

 

Reconstitution method for oral extended-release suspension (prior to dispensing):

  • Metformin ER suspension is supplied as a powder for oral suspension which must be reconstituted with the accompanying diluent prior to dispensing; both the powder and diluent contain metformin.
  • Remove the bottles containing drug pellets and drug diluent along with the measuring cup from the box.
  • Remove the child-resistant cap (push down and turn) from the bottle containing drug pellets and the drug diluent bottle. Keep the child-resistant cap.
  • Pour the contents of the bottle containing the drug pellets into the diluent bottle and discard the empty pellet bottle.
  • Close the drug diluent bottle with the child-resistant cap.
  • Shake continuously in an up and down direction for at least 2 full minutes; this is important for the product to mix evenly.
  • The concentration of the reconstituted suspension is metformin 500 mg/5mL.
  • Storage after reconstitution: Store reconstituted suspension in the original bottle at room temperature between 20 and 25 degrees C (68 and 77 degrees F). Do not repackage. Label to discard any unused portion after 100 days.[64593]

Clinical Pharmaceutics Information

From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database
Revision Date: 01/29/2020, 01:16:56 PMCopyright 2004-2021 by Lawrence A. Trissel. All Rights Reserved.

References

28550 - Glucophage and Glucophage XR (metformin HCl tablets and extended-release tablets) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2018 May.60715 - Riomet (metformin hydrochloride) oral solution package insert. Jacksonville FL: Ranbaxy Laboratories Inc.; 2018 Nov.64593 - Riomet XR (metformin extended-release suspension) package insert. Cranbury, NJ: Sun Pharmaceutical Industries, Inc.; 2019 Aug.

Adverse Reactions

Mild

  • abdominal pain
  • anorexia
  • chills
  • diarrhea
  • dizziness
  • dysgeusia
  • dyspepsia
  • flatulence
  • flushing
  • headache
  • hyperhidrosis
  • infection
  • malaise
  • metallic taste
  • myalgia
  • nausea
  • rash
  • vomiting
  • weight loss

Moderate

  • chest pain (unspecified)
  • cholestasis
  • elevated hepatic enzymes
  • folate deficiency
  • hepatitis
  • hypoglycemia
  • metabolic acidosis
  • palpitations
  • vitamin B12 deficiency

Severe

  • lactic acidosis
  • megaloblastic anemia
  • rhabdomyolysis

Gastrointestinal (GI) adverse effects are the most common side effects experienced by patients taking metformin. In clinical trials, diarrhea was experienced by 53.2% of patients receiving immediate-release metformin monotherapy, and was a reason for drug discontinuation in 6%. Extended-release formulations cause diarrhea in roughly 9.6% of patients. Nausea and vomiting are reported in 6.5% to 25.5% of all patients taking metformin; with the lower incidences seen in patients receiving extended-release products. Other common GI effects include flatulence (1% to 12.1%), indigestion or dyspepsia (1% to 7.1%), and abdominal pain or discomfort (1% to 6.4%). GI effects occurring in 1% to 5% of patients included anorexia, dysgeusia (metallic taste or other taste disturbance), and a change in stool appearance. Frequent side effects tend to decline with continued use and can be minimized by initiating therapy with low doses of metformin, and extended-release formulas lower GI side effect incidences. In pediatric patients with diabetes mellitus type 2 treated with metformin, the adverse event profiles and incidences are similar to those seen in adults.[28550] [60711] [60715] [64593]

The risk of hypoglycemia is not common with metformin monotherapy; hypoglycemia was reported in 1% to 5% of patients during clinical trials.[24568] [28550] [60711] [60715] [64593] Other studies have reported varying incidences of hypoglycemia. In a nested case-control analysis (n = more than 50,000 subjects with type 2 diabetes mellitus), the rate of hypoglycemia due to metformin yielded a crude incidence rate of 3.3 cases among 100,000 person-years compared vs. 4.8 cases among sulfonylurea users per 100,000 person-years.[34580] In a separate systematic review, the rates for hypoglycemia with metformin monotherapy varied in the studies reviewed between 0% to 21%, with the risk of major hypoglycemic episodes due to metformin reported to be rare.[43853] Hypoglycemia is more common when metformin is coadministered with other oral hypoglycemic agents (especially sulfonylureas), when ethanol has been ingested, or when there is deficient caloric intake or strenuous exercise not compensated by caloric supplementation. Since metformin reverses insulin resistance and subsequently causes a decrease in insulin concentrations, metformin-induced hypoglycemia is usually mild and does not necessitate the discontinuation of therapy. In overdose, hypoglycemia is noted in roughly 10% of patients, but a causal association with metformin is not established. Patients should be aware of the common, early symptoms and signs of low blood sugar, such as feeling anxious, dizzy, or irritable, impaired concentration, increased hunger, unusually weak or tired, sweating, shakiness, headache, blurry vision, or a fast heartbeat. Headache has also been reported as a side effect with metformin therapy, in the absence of hypoglycemia. During clinical trials, the incidence of headache with metformin immediate-release therapy was 5.7%.[28550] [60711] [60715] [64593]

Metformin decreases the absorption of vitamin B12; asymptomatic vitamin B12 deficiency was reported with metformin monotherapy in 7% of patients during clinical trials. The decrease is possibly due to interference with B12 absorption from the B12-intrinsic factor complex; however, it is only very rarely associated with anemia and appears to be rapidly reversible with discontinuation of metformin treatment or vitamin B12 (cyanocobalamin) supplementation. Metformin may also decrease folate concentrations leading to folate deficiency. During clinical trials, serum folic acid concentrations did not decrease significantly. Measurement of hematologic parameters on an annual basis is advised. Certain individuals (those with inadequate vitamin B12, folic acid, or calcium intake or absorption) appear to be predisposed to developing subnormal vitamin B12 levels. In these patients, routine serum vitamin B12 measurements at 2- to 3-year intervals may be useful. Rare cases of megaloblastic anemia have been reported with metformin (none in the U.S.); incidence rates are expected to be less than 1% for symptomatic deficiency.[28550] [60711] [60715] [64593] [63388]

Mild weight loss may occur during therapy with metformin, perhaps as a result of its ability to cause anorexia. Such weight loss can be expected in almost any patient with type 2 diabetes receiving metformin monotherapy; however, weight loss may attenuate when metformin is combined with other treatments. A mean weight loss of 1 to 8.4 lbs was reported in clinical trials of adults receiving metformin immediate-release products as monotherapy; a mean weight loss of 2 to 3 lbs was reported in pediatric studies. When extended-release tablets were used, the weight loss was not clinically significant in adults and mean reductions ranged from 0.7 to 2.2 lbs.[28550] [60711] [60715] [64593]

Lactic acidosis is a rare but serious form of metabolic acidosis that can occur if metformin accumulates during treatment; when it occurs, it is fatal in approximately 50% of cases. The onset of lactic acidosis often is subtle, and accompanied only by early nonspecific symptoms such as malaise and myalgia (1 to 5% of patients), and quickly followed by respiratory distress (dyspnea 1 to 5%), increasing somnolence, and nonspecific abdominal distress. Lactic acidosis is a medical emergency that must be treated in a hospital setting; metformin should be discontinued immediately, and general supportive measures promptly instituted. Prompt hemodialysis is recommended to correct the acidosis and remove the accumulated metformin. Such management often results in prompt reversal of symptoms and recovery.[28550] [60711] [60715] [64593] Lactic acidosis is characterized by elevated blood lactate levels (more than 5 mmol/L), decreased blood pH, electrolyte disturbances with an increased anion gap, and an increased lactate/pyruvate ratio. When metformin is implicated as the cause of lactic acidosis, metformin plasma levels greater than 5 mcg/mL are generally present. More marked lactic acidosis/metabolic acidosis may be associated with hypothermia, hypotension, and resistant bradyarrhythmias. The reported incidence of lactic acidosis in patients receiving metformin is very low (approximately 0.03 cases/1,000 patient-years); of nearly 20,000 patients in clinical trials, there were no reports of lactic acidosis. A nested case-control study of 50,048 patients with type 2 diabetes mellitus demonstrated that during concurrent use of oral diabetes drugs, there were 6 identified cases of lactic acidosis; all of the subjects had relevant comorbidities known to be risk factors for lactic acidosis.[34580] The incidence of lactic acidosis in metformin recipients without comorbid conditions appears to be no different than in recipients of other antidiabetic agents. Risk factors include significant renal insufficiency, the presence of multiple concomitant medical/surgical problems (e.g., liver disease, alcoholism, cardiorespiratory insufficiency, or other conditions associated with tissue hypoperfusion or hypoxemia), and exposure to multiple concomitant medications known to increase risks. The risk of lactic acidosis increases with the degree of renal impairment and the patient's age. Lactic acidosis is less likely to occur with metformin than with other biguanide agents (e.g., phenformin), because metformin is not metabolized, does not bind to liver or plasma proteins, and is excreted by active tubular processes. Regular monitoring of renal function and by use of the minimum effective dose of metformin may reduce the risk of this adverse reaction. Patients should be informed to discontinue metformin should symptoms suggestive of lactic acidosis appear and promptly report the symptoms to their physician.[43853] [28550] [60711] [60715] [64593]

The following miscellaneous adverse reactions were reported in 1% to 5% of patients treated with metformin and occurred more commonly than in patients treated with placebo: lightheaded (dizziness), nail disorder, rash (unspecified), hyperhidrosis (sweating increased), chest pain (unspecified) or chest discomfort, chills, flu syndrome or upper respiratory infection, flushing, and palpitations.[28550] [60711] [60715] [64593]

Liver function test abnormalities (elevated hepatic enzymes) or hepatitis have been reported very rarely in patients taking metformin and have resolved upon metformin discontinuation. During postmarketing experience with metformin, cholestasis and hepatocellular or mixed hepatocellular liver injury have been reported.[28550] [60711] [60715] [64593]

In an ISMP safety report, metformin was noted as 1 of the 25 drugs having the strongest signals for rhabdomyolysis with 20 cases reported over 1 year to the FDA Adverse Event Reporting System (FAERS).[63529]

Revision Date: 01/28/2020, 07:58:07 PM

References

24568 - Bailey CJ, Turner RC. Metformin. N Engl J Med 1996;334:574-9.28550 - Glucophage and Glucophage XR (metformin HCl tablets and extended-release tablets) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2018 May.34580 - Bodmer M, Meier C, Krahenbuhl S, et al. Metformin, sulfonylureas, or other antidiabetes drugs and the risk of lactic acidosis or hypoglycemia. Diabetes Care 2008;31:2086-91.43853 - Bolen S, Feldman L, Vassy J, et al. Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus. Ann Intern Med 2007;147:386–99.60711 - Fortamet (metformin extended-release film-coated tablets) package insert. Ft. Lauderdale, FL: Watson Laboratories-Florida; 2017 April.60715 - Riomet (metformin hydrochloride) oral solution package insert. Jacksonville FL: Ranbaxy Laboratories Inc.; 2018 Nov.63388 - Nutrient-Drug Interactions and Drug-Induced Nutrient Depletions. In: Stargrove MB, Treasure J, McKee DL. Herb, Nutrient, and Drug Interactions: Clinical Implications and Therapeutic Strategies. St. Louis: Mosby Elsevier; 2008:173-831.63529 - Institute for Safe Medication Practices (ISMP). Acute Care ISMP Medication Safety Alert 2018;23:1-2.64593 - Riomet XR (metformin extended-release suspension) package insert. Cranbury, NJ: Sun Pharmaceutical Industries, Inc.; 2019 Aug.

Contraindications/Precautions

Absolute contraindications are italicized.

  • diabetic ketoacidosis
  • lactic acidosis
  • metabolic acidosis
  • renal failure
  • acidemia
  • acute heart failure
  • acute myocardial infarction
  • adrenal insufficiency
  • alcoholism
  • breast-feeding
  • burns
  • cardiac disease
  • cardiogenic shock
  • children
  • dehydration
  • diarrhea
  • ethanol ingestion
  • ethanol intoxication
  • fever
  • gastroparesis
  • geriatric
  • GI obstruction
  • heart failure
  • hepatic disease
  • hypercortisolism
  • hyperglycemia
  • hyperthyroidism
  • hypoglycemia
  • hypothyroidism
  • hypoxemia
  • ileus
  • infection
  • malnutrition
  • pernicious anemia
  • pituitary insufficiency
  • polycystic ovary syndrome
  • pregnancy
  • radiographic contrast administration
  • renal disease
  • renal impairment
  • sepsis
  • surgery
  • trauma
  • type 1 diabetes mellitus
  • vomiting

Do not use metformin in patients who have a known metformin hypersensitivity.

Metformin should not be used for Type 1 diabetes mellitus. Metformin is not an effective treatment of and use is contraindicated in diabetic ketoacidosis (DKA). DKA, with or without coma; DKA should be treated with insulin.

Metformin is contraindicated in patients with metabolic acidosis. Metformin is associated with a risk for lactic acidosis and therefore should not be used in patients with lactic acidosis, a form of metabolic acidosis. Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonemia). Lactic acidosis is a rare but serious complication that can occur due to metformin accumulation; when it occurs, it is fatal in approximately 50% of cases. Lactic acidosis may also occur in association with a number of pathophysiologic conditions, including diabetes mellitus, and whenever there is significant tissue hypoperfusion and hypoxemia or significant renal dysfunction.[28550] [60711] [60714] [60715] Certain medications used concomitantly with metformin may also increase the risk of lactic acidosis. Lactic acidosis is characterized by elevated blood lactate levels, acidemia, electrolyte disturbances, an increased anion gap, and an increased lactate/pyruvate ratio. When metformin is implicated as the cause of lactic acidosis, metformin plasma levels more than 5 mcg/mL are generally found. The reported incidence of lactic acidosis in patients receiving metformin is very low; in more than 20,000 patient-years exposure to metformin in clinical trials, there have been no reports of lactic acidosis and approximately 0.03 cases/1,000 patient-years have been estimated with post-marketing surveillance. A nested case-control study of 50,048 patients with type 2 diabetes mellitus demonstrated that during concurrent use of oral diabetes drugs, there were 6 identified cases of lactic acidosis. The crude incidence rate was 3.3 cases per 100,000 person-years in patients treated with metformin; it should be noted that all of the subjects had relevant comorbidities known to be risk factors for lactic acidosis.[34580] The onset of lactic acidosis often is subtle, and accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress. There may be associated hypothermia, hypotension, and resistant bradycardia with more marked acidemia. The patient and the prescriber must be aware of such symptoms and the patient should be instructed to notify the physician immediately if they occur. Metformin should be withdrawn until the situation is clarified. Serum electrolytes, ketones, blood glucose, and if indicated, blood pH, lactate levels, and even blood metformin levels may be useful.[28550]

Gastrointestinal (GI) side effects are common during metformin initiation. However, once a patient is stabilized on any dose of metformin, GI symptoms are unlikely to be drug related. Later occurrence of GI symptoms may be due to a change in clinical status and may increase the risk of lactic acidosis or other serious disease. Patients stable on metformin therapy who complain of an increase in GI symptoms should undergo laboratory investigation to determine the etiology of the GI symptoms. These include, but are not limited to, diarrhea and nausea/vomiting. Furthermore, withholding metformin therapy until the cause of the GI symptoms is known may be necessary. Finally, diarrhea and nausea/vomiting may alter gastric emptying and caloric intake, which could all affect blood glucose control, especially increasing the risk of low blood glucose. Patients should be advised to contact their prescriber if an increase in gastrointestinal symptoms occurs while taking metformin; patients should also be advised to monitor their blood glucose concentrations more frequently.

Metformin is substantially eliminated by the kidney and the risk of lactic acidosis increases with the degree of intrinsic renal disease or impairment. Certain medications that are eliminated via the kidney when used concomitantly with metformin may also increase the risk of lactic acidosis. Prior to initiating treatment in any patient, obtain an estimated glomerular filtration rate (eGFR) to assess renal function.[28550] Metformin is contraindicated for use in patients with renal failure or severe renal impairment (defined as eGFR below 30 mL/minute/1.73 m2). Initiating metformin in patients with an eGFR between 30 to 45 mL/minute/1.73 m2 is not recommended. Obtain an eGFR at least annually in all patients taking metformin. In those patients at increased risk for the development of renal impairment such as the elderly, renal function should be assessed more frequently. In patients taking metformin whose eGFR later falls below 45 mL/minute/1.73 m2, assess the benefits and risks of continuing treatment. Discontinue metformin if the patient’s eGFR later falls below 30 mL/minute/1.73 m2. Based on the results of a comprehensive FDA safety review, the FDA concluded that metformin can be used safely in patients with mild renal impairment, and in some patients with moderate renal impairment. The measure of kidney function used to determine whether a patient can receive metformin has been changed from serum creatinine to the eGFR; this is because in addition to serum creatinine concentration, the eGFR takes into account additional parameters that are important, such as the patient’s age, gender, race and/or weight.[60699] [50321] [50322]

According to the manufacturer, metformin should be used with caution in patients with congestive heart failure requiring pharmacologic treatment. However, a systematic review evaluating antidiabetic agents and outcomes in patients with heart failure and diabetes concluded that metformin is not associated with any measurable harm in patients with heart failure; in this analysis, metformin was associated with reduced mortality.[34437] It should be noted that in acute congestive heart failure characterized by acute hypoxia, lactic acidosis has occurred in patients taking metformin. To reduce the risk of lactic acidosis, metformin should be promptly withheld in the presence of any condition associated with hypoxemia. Acute hypoxia and acute cardiac disease (e.g., acute heart failure, cardiogenic shock, or acute myocardial infarction) and other conditions characterized by acute hypoxia have been associated with the development of lactic acidosis and may cause prerenal azotemia. If such events occur, discontinue metformin.

Metformin administration increases the risk for lactic acidosis. Since the liver is important for clearing accumulated lactic acid, metformin is not recommended in patients with clinical or laboratory evidence of hepatic disease as the risk of lactic acidosis may be increased. Hepatic disease also causes altered gluconeogenesis, which may affect glycemic control. Alcohol is known to potentiate the effect of metformin on lactate metabolism. Patients should be warned against excessive ethanol ingestion (ethanol intoxication) while taking metformin due to the increased risk for lactic acidosis. Those with ethanol intoxication are also particularly susceptible to hypoglycemic effects of oral antidiabetic agents. Metformin use should be avoided by those patients with alcoholism.[28550]

Discontinue metformin at the time of or before radiographic contrast administration in patients with an estimated glomerular filtration rate (eGFR) between 30 and 60 mL/minute/1.73 m2; in patients with a history of hepatic disease, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR the 48 hours after the imaging procedure; restart metformin if renal function is stable.[60699] [28550]

To reduce the risk of lactic acidosis, metformin should be promptly withheld in the presence of any condition associated with hypoxemia, dehydration, or sepsis. Metformin therapy should be temporarily suspended for any surgery, except for minor procedures where intake of fluids and food is not restricted. Do not restart this drug until oral intake is resumed and renal function has been evaluated as normal. Temporary use of insulin in place of oral antidiabetic agents may be necessary during periods of physiologic stress (e.g., burns, systemic infection, trauma, surgery, or fever). Any change in clinical status, including diarrhea or vomiting, may also increase the risk of lactic acidosis and may require laboratory evaluation in patients on metformin and may require the drug be withheld.

Delayed stomach emptying may alter blood glucose control; monitor patients with diarrhea, gastroparesis, GI obstruction, ileus, or vomiting carefully. Conditions that predispose patients to developing hypoglycemia or hyperglycemia may alter antidiabetic agent efficacy. Hyperglycemia related conditions include drug interactions, female hormonal changes, high fever, severe psychological stress, and uncontrolled hypercortisolism or hyperthyroidism. Metformin causes hypoglycemia infrequently in the absence of risk factors as monotherapy. Conditions associated with an increased risk for hypoglycemia include debilitated physical condition, drug interactions, malnutrition, uncontrolled adrenal insufficiency, pituitary insufficiency or hypothyroidism. More frequent blood glucose monitoring may be necessary in patients with these conditions while receiving metformin. There is also an increased risk of hypoglycemia when metformin is combined with insulin or an insulin secretagogue (e.g., sulfonylureas). Therefore, a lower dose of insulin or an insulin secretagogue may be required to minimize the risk of hypoglycemia when used in combination with metformin. Monitor blood glucose.[28550]

Metformin may result in suboptimal vitamin B12 absorption, possibly due to interference with the B12-intrinsic factor complex. The interaction very rarely results in a pernicious anemia that appears reversible with discontinuation of metformin or with cyanocobalamin supplementation. Certain individuals may be predisposed to this type of anemia; a nested case-control study of 465 patients taking metformin (155 with vitamin B12 deficiency and 310 without) demonstrated that dose and duration of metformin use may be associated with an increased odds of vitamin B12 deficiency. Each 1 gram/day increment in dose significantly increased the odds of vitamin B12 deficiency (OR 2.88, 95% CI 2.15 to3.87) as did taking metformin for 3 years or more (OR 2.39, 95% CI 1.46 to 3.91).[32890] Regular measurement of hematologic parameters is recommended in all patients on chronic metformin treatment.[28550]

Controlled clinical studies of metformin did not include sufficient numbers of older patients to determine whether they respond differently from younger patients, although other reported clinical experience has not identified differences in responses between geriatric and younger adult patients. Use metformin with caution in geriatric patients. Metformin is substantially excreted by the kidney and the risk of adverse reactions (including lactic acidosis) is greater in patients with reduced renal function. Because aging is associated with renal function decline, care should be taken with dose selection and titration. Obtain an estimated glomerular filtration rate (eGFR) at least annually in all patients taking metformin. In patients at increased risk for the development of renal impairment such as geriatric patients, renal function should be assessed more frequently.[60699] Unless estimated renal function via the eGFR is determined to be normal, do not use metformin in geriatric patients 80 years of age and older. Generally, elderly or debilitated patients should not be titrated up to maximum metformin dosages. Elderly, debilitated, or malnourished patients are also particularly susceptible to hypoglycemic effects of antidiabetic agents; monitor blood glucose frequently.[28550] The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to OBRA, the use of antidiabetic medications should include monitoring (e.g., periodic blood glucose) for effectiveness based on desired goals for that individual and to identify complications of treatment such as hypoglycemia or impaired renal function. Metformin has been associated with lactic acidosis, which is more likely to occur under the following conditions: serum creatinine of 1.5 mg/dL or higher in males or 1.4 mg/dL or higher in females, abnormal creatinine clearance from any cause, age of 80 years or older unless measurement of creatinine clearance verifies normal renal function, radiologic studies in which intravascular iodinated contrast materials are given, congestive heart failure requiring pharmacologic management, or acute/chronic metabolic acidosis with or without coma (including diabetic ketoacidosis).[60742]

Premenopausal anovulatory females with insulin resistance (i.e., those with polycystic ovary syndrome (PCOS)) may resume ovulation as a result of metformin therapy; patients may be at risk of conception if adequate contraception is not used in those not desiring to become pregnant. In some cases, metformin is used as an adjunct in PCOS patients to regulate menstrual cycles or to enhance fertility. Metformin is not recommended for routine use during pregnancy.[28550] Metformin does pass through the placenta and the fetus is likely exposed to therapeutic concentrations of metformin.[31404] The American College of Obstetricians and Gynecologists (ACOG) and the American Diabetes Association (ADA) continue to recommend human insulin as the standard of care in women with diabetes mellitus or gestational diabetes mellitus (GDM) requiring medical therapy.[64926] [62358] Per ACOG, in women who decline insulin therapy or are unable to safely administer insulin, metformin is the preferred second-line choice. Per the ADA, metformin may be used to treat GDM as a treatment option; however, no long term safety data are available for any oral agent. Metformin may cause a lower risk of neonatal hypoglycemia and less maternal weight gain than insulin; however, some data suggest that metformin may slightly increase the risk of prematurity. The ADA notes that in some clinical studies, nearly 50% of GDM patients initially treated with metformin have needed the addition of insulin in order to achieve acceptable glucose control.[64926] [62358] Many studies and analyses of metformin use in pregnancy have been published. The data suggest no increase in the rates of expected birth defects or other adverse outcomes in exposed infants and studies comparing metformin to insulin in the treatment of gestational diabetes have generally found no significant differences in glycemic control or pregnancy outcomes.[46193] [46201] [46203]

Small studies indicate that metformin is excreted in human breast milk. Infant hypoglycemia or other side effects are a possibility; however, adverse effects on infant plasma glucose have not been reported in human studies. Animal data show that metformin is excreted into breast milk and reaches levels similar to those in plasma.[31407] [31408] [31409] Furthermore, the use of metformin 2550 mg/day by mothers breast-feeding their infants for 6 months does not affect growth, motor, or social development; the effects beyond 6 months are not known.[32459] In all of these studies, the estimated weight-adjusted infant exposure to metformin ranged from 0.11% to 1.08% of the mother's dose. While the manufacturers of metformin recommend that a decision should be made to discontinue breast-feeding or discontinue the drug, the results of these studies indicate that maternal ingestion of metformin during breast-feeding is probably safe to the infant. However, a risk and benefit analysis should be made for each mother and her infant; if patients elect to continue metformin while breast-feeding, the mother should be aware of the potential risks to the infant. If metformin is discontinued and blood glucose is not controlled on diet and exercise alone, insulin therapy should be considered. Because acarbose has limited systemic absorption, which results in minimal maternal plasma concentrations, clinically significant exposure via breast milk is not expected [46303]; therefore, this agent may represent a reasonable alternative for some patients. Tolbutamide is usually considered compatible with breast-feeding.[27500] Glyburide may be a suitable alternative since it was not detected in the breast milk of lactating women who received single and multiple doses of glyburide.[31568] If any oral hypoglycemics are used during breast feeding, the nursing infant should be monitored for signs of hypoglycemia, such as increased fussiness or somnolence.[46104]

Metformin has been shown to effectively lower glucose levels in children (ages 10 to 16 years) with type 2 diabetes. Metformin has not been adequately studied in children less than 10 years of age.[28550] [60715]

Revision Date: 02/25/2021, 03:11:21 PM

References

27500 - American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108(3):776-789.28550 - Glucophage and Glucophage XR (metformin HCl tablets and extended-release tablets) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2018 May.31404 - Vanky E, Zahlsen K, Spigset O, et al. Placental passage of metformin in women with polycystic ovary syndrome. Fertil Steril 2005;83:1575-8.31407 - Hale TW, Kristensen JH, Hackett LP, et al. Transfer of metformin into human milk. Diabetologia 2002;45:1509-14.31408 - Gardiner SJ, Kirkpatrick CMJ, Begg EJ, et al. Transfer of metformin into human milk. Clin Pharmacol Ther 2003;73:71-7.31409 - Briggs GG, Ambrose PJ, Nageotte MP, et al. Excretion of metformin into breast milk and the effect on nursing infants. Obstet Gynecol 2005;105:1437-41.31568 - Feig DS, Donat DJ, Briggs GG, et al. Transfer of glyburide and glipizide into breast milk. Diabetes Care 2005;28:1851-5.32459 - Glueck CJ, Salehi M, Sieve L, et al. Growth, motor, and social development in breast- and formula- fed infants of metformin-treated women with polycystic ovary syndrome. J Pediatr 2006;148:628-32.32890 - Ting RZ, Szeto CC, Chan MH, et al. Risk factors of vitamin B12 deficiency in patients receiving metformin. Arch Intern Med 2006;166:1975-9.34437 - Eurich DT, McAlister FA, Blackburn DF, et al. Benefits and harms of antidiabetic agents in patients with diabetes and heart failure: systematic review. BMJ 2007;335(7618):497 Epub 2007 Aug 3034580 - Bodmer M, Meier C, Krahenbuhl S, et al. Metformin, sulfonylureas, or other antidiabetes drugs and the risk of lactic acidosis or hypoglycemia. Diabetes Care 2008;31:2086-91.46104 - Spencer JP, Gonzalez LS, Barnhart DJ. Medications in the breast-feeding mother. Am Fam Physician 2001; 64:119-126.46193 - Glueck CJ, Goldenberg N, Pranikoff J, et al. Height, weight, and motor-social development during the first 18 months of life in 126 infants born to 109 mothers with polycystic ovary syndrome who conceived on and continued metformin through pregnancy. Hum Reprod 2004;19:1323-30.46201 - Dhulkotia JS, Ola B, Fraser R, et al. Oral hypoglycemic agents vs insulin in management of gestational diabetes: a systematic review and metaanalysis. Am J Obstet Gynecol 2010;203:457.46203 - Balani J, Hyer SL, Rodin DA, et al. Pregnancy outcomes in women with gestational diabetes treated with metformin or insulin: a case-control study. Diabet Med 2009;26:798-802.46303 - Everett J. Use of oral antidiabetic agents during breastfeeding. J Hum Lact 1997;13:319-21.50321 - Davies MJ, D'Alessio DA, Fradkin J, et al. Management of hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2018;41:2669-2701.50322 - Lipska KJ, Bailey CJ, Inzucchi SE. Use of metformin in the setting of mild-to-moderate renal insufficiency. Diabetes Care 2011;34:1432-1437.60699 - US Food and Drug Administration (FDA) MedWatch for Metformin-containing Drugs: Revised Warnings for Certain Patients With Reduced Kidney Function. Retrieved April 8, 2016. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm494829.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery60711 - Fortamet (metformin extended-release film-coated tablets) package insert. Ft. Lauderdale, FL: Watson Laboratories-Florida; 2017 April.60714 - Glumetza (metformin hydrochloride film-coated modified-release tablet) package insert. Menlo Park, CA: Depomed, Inc.; 2017 April.60715 - Riomet (metformin hydrochloride) oral solution package insert. Jacksonville FL: Ranbaxy Laboratories Inc.; 2018 Nov.60742 - Health Care Financing Administration. Interpretive Guidelines for Long-term Care Facilities. Title 42 CFR 483.25(l) F329: Unnecessary Drugs. Revised 2015.62358 - American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins-Obstetrics. Practice Bulletin No. 190: Gestational Diabetes Mellitus. Obstet Gynecol. 2018;131:e49-e64. Reaffirmed 2019.64926 - American Diabetes Association. Standards of Medical Care in Diabetes - 2021. Diabetes Care. 2021; 44(Suppl 1):S1-S232. Available at: https://care.diabetesjournals.org/content/44/Supplement_1

Mechanism of Action

Metformin is an antihyperglycemic agent that improves glucose tolerance, lowering both basal and postprandial plasma glucose with mechanisms different from other classes of oral antidiabetic agents. Metformin decreases hepatic gluconeogenesis production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. With metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may actually decrease. Metformin improve glucose utilization in skeletal muscle and adipose tissue by increasing cell membrane glucose transport. This effect may be due to improved binding of insulin to insulin receptors since metformin is not effective in diabetics without some residual functioning pancreatic islet cells.[24568] Unlike the sulfonylureas, metformin rarely causes hypoglycemia since it does not significantly change insulin concentrations. An important distinction is that sulfonylureas increase insulin secretion thus making them useful in non-obese patients with type 2 diabetes mellitus (DM) while metformin improves insulin resistance, a common pathophysiologic finding in obese patients with type 2 DM.[24568] Metformin causes a 10% to 20% decrease in fatty-acid oxidation and a slight increase in glucose oxidation. Unlike phenformin, metformin does not inhibit the mitochondrial oxidation of lactate unless plasma concentrations of metformin become excessive (i.e., in patients with renal failure) and/or hypoxia is present.[24438]

 

Clinically, metformin lowers fasting and postprandial hyperglycemia. The decrease in fasting plasma glucose is approximately 25% to 30%. Unlike oral sulfonylureas, metformin rarely causes hypoglycemia. Thus, metformin demonstrates more of an antihyperglycemic action than a hypoglycemic action. Metformin does not cause weight gain and in fact, may cause a modest weight loss due to drug-induced anorexia. Metformin also decreases plasma VLDL triglycerides resulting in modest decreases in plasma triglycerides and total cholesterol. Patients receiving metformin show a significant improvement in A1C, and a tendency toward improvement in the lipid profile, especially when baseline values are abnormally elevated.

 

Insulin resistance is a primary cause of polycystic ovarian syndrome (PCOS). In PCOS patients, metformin reduces insulin resistance and lowers insulin levels, which lowers serum androgen concentrations, restores normal menstrual cycles and ovulation, and may help to resolve PCOS-associated infertility. Metformin, when administered to lean, overweight, and moderately obese women with PCOS, has been found to significantly reduce serum leuteinizing hormone (LH) and increase follicle stimulating hormone (FSH) and sex hormone binding globulin (SHBG). Serum testosterone concentrations were also found to decrease by approximately 50%.[27528]

Revision Date: 02/20/2019, 05:28:54 PM

References

24438 - Lalau JD, Lacroix C, Compagnon P, et al. Role of metformin accumulation in metformin-associated lactic acidosis. Diabetes Care 1995;18:779-84.24568 - Bailey CJ, Turner RC. Metformin. N Engl J Med 1996;334:574-9.27528 - Kosasa TS. Making a Case for Metformin. OB/GYN 2003;48:69-80.

Pharmacokinetics

Metformin is administered orally. The drug is distributed rapidly into peripheral body tissues and fluids and appears to distribute slowly into erythrocytes and to a deep tissue compartment (most likely GI tissues). The highest concentrations are found in the GI tract (10 times the concentrations in the plasma) and lower concentrations in the kidney, liver, and salivary gland tissue. Metformin is negligibly bound to plasma proteins. Metformin is not metabolized by the liver and this fact may explain why the risk of lactic acidosis is much less for metformin than for phenformin (i.e., approximately 10% of patients have an inherited defect in the ability to metabolize phenformin).[24568] The drug is excreted by the kidneys, largely unchanged, through an active tubular process. Tubular secretion may be altered by many cationic drugs. Approximately 10% of an oral dose is excreted in the feces, presumably as unabsorbed metformin and about 90% of a dose is excreted by the kidneys within 24 hours. Although the average elimination half-life in the plasma is 6.2 hours in patients with normal renal function, metformin is distributed to and accumulates in red blood cells, which leads to a much longer elimination half-life in the blood (17.6 hours).[28550][42826]

 

Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: Organic cationic transporter-2 (OCT2), multidrug and toxin extrusion (MATE1 and MATE2k)

Drugs that interfere with common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2]/multidrug and toxin extrusion [MATE1 and MATE2k] inhibitors such as ranolazine, vandetanib, dolutegravir, and cimetidine) increase systemic exposure to metformin. Careful patient monitoring and dose adjustment of metformin and/or the potentially interfering drug is recommended with concurrent use.[28550]

Route-Specific Pharmacokinetics

Oral Route

  • Metformin Solution (Riomet): The rate and extent of absorption are comparable to regular-release tablets. Peak plasma concentrations are achieved at approximately 2.2 hours. The extent of absorption from the oral solution increases when given with food, and while there is a negligible decrease in Cmax, the Tmax increases from 2.5 to approximately 4 hours. Studies indicate that dose proportionality is lacking with increasing doses due to a decrease in the absorption at higher doses.[60715]
  • Metformin Regular-release tablets: The bioavailability of 500 mg tablets is 50% to 60% with peak plasma concentrations achieved at approximately 2.5 hours. Food decreases the extent and slightly delays the absorption. Studies indicate that dose proportionality is lacking with increasing doses due to a decrease in the oral absorption at higher doses.[28550]
  • Metformin Extended-release tablets (Glucophage XR): Using a dual hydrophilic polymer system, metformin is released slowly by diffusion through a gel matrix, allowing for once-daily administration. Peak plasma concentrations are achieved at approximately 7 hours (range, 4 to 8 hours). While peak plasma concentrations are approximately 20% lower for extended-release tablets versus the same dose of regular-release tablets, the extent of absorption from 2,000 mg once-daily of extended-release tablets is similar to the same total daily dose administered as 1,000 mg twice-daily of regular-release tablets. Food increases the extent of absorption of extended-release tablets (as per AUC) by approximately 50%, although Cmax and Tmax are unaltered.[28550]
  • Metformin Extended-release tablets (Fortamet): Using single-composition osmotic technology (SCOT), metformin is released at a constant rate from an osmotically active tablet core surrounded by a semi-permeable membrane. Peak plasma concentrations are achieved at approximately 6 hours (range 3 to 10 hours). While peak concentrations are higher with Fortamet, the bioavailability of Fortamet 2,000 mg once daily in the evening (as per AUC) is similar to the same total daily dose administered as regular-release tablets 1,000 mg twice daily. When administered with food, the extent of absorption is increased by approximately 60%; also, Cmax is increased by 30%, and Tmax is prolonged (6.1 hours vs. 4 hours). There is a dose-proportional increase in exposure following administration of 1,000 to 2,500 mg.[60711]
  • Metformin Extended-release tablets (Glumetza): Using gastric-retentive (GR) technology, tablets are designed to remain in the stomach and deliver metformin to the upper GI tract to enhance absorption over an extended period, thus allowing for once-daily dosing. Glumetza tablets must be administered directly after a meal to maximize therapeutic benefit. Peak plasma concentrations from Glumetza 1,000 mg after a meal are achieved in 7 to 8 hours. At usual clinical doses of metformin, steady-state plasma concentrations are reached within 24 to 48 hours and are generally less than 1 mcg/mL. In single and multiple dose studies, once daily Glumetza 1,000 mg provides equivalent systemic exposure (as per AUC), and up to 35% higher Cmax concentrations, when compared to 500 mg twice daily regular-release tablets. Low-fat and high-fat meals increase systemic exposure (as per AUC) by 38% and 73%, respectively, relative to fasting. Both meal types prolong Tmax by approximately 3 hours, but Cmax is not affected.[60714]
  • Metformin Extended-release suspension (Riomet XR): The mean Cmax is 815 ng/mL and the AUC0-t is 7694 ng/hr/mL following a single oral dose of 750 mg metformin ER suspension taken with high-fat meal, in healthy adult male subjects. The Tmax is achieved with a median value of 4.5 hours and a range of 3.5 to 6.5 hours. In the same study, the administration of metformin ER suspension following a standardized high-fat, high-calorie breakfast (containing approximately 150 kcal from protein, 250 kcal from carbohydrates and 500 kcal from fat) had minimal effect on the AUC of metformin; however, Cmax is decreased by approximately 20% when compared to dosing under fasting condition. The median Tmax is delayed by 1 hour under fed condition compared to fasting condition. The observed elimination half-life (t1/2) is similar under both fasting and fed conditions.[64593]

Special Populations

Hepatic Impairment

Specific pharmacokinetic studies have not been performed in patients with hepatic dysfunction receiving metformin, but hepatic impairment may increase the risk of lactic acidosis.

Renal Impairment

Metformin will accumulate in patients with moderate to severe renal dysfunction. Increasing renal dysfunction is associated with an increased risk of lactic acidosis. In patients with decreased renal function (based on measured creatinine clearance, CrCl), the plasma and blood half-life of metformin is prolonged and the renal clearance is decreased in proportion to the decrease in creatinine clearance. In patients with severe renal impairment (CrCl less than 30 mL/minute), the steady-state metformin exposure was approximately 40% higher than that of patients with normal renal function (AUC increase of 42% and Cmax increase of 35%). Metformin is removed by hemodialysis.[24568][28550]

Pediatrics

After administration of metformin 500 mg regular-release tablet PO as a single dose with food, the geometric mean metformin maximum concentration (Cmax) and exposure (AUC) differed less than 5% between pediatric type 2 diabetic patients (12 to 16 years of age) and gender- and weight-matched healthy adults (20 to 45 years of age), all with normal renal function.[28550]

Geriatric

The elderly, due to age-related decreased renal function, may accumulate metformin.

Gender Differences

Gender does not appear to affect metformin pharmacokinetics.

Ethnic Differences

Race does not appear to affect metformin pharmacokinetics.

Revision Date: 05/26/2021, 08:13:18 PM

References

24568 - Bailey CJ, Turner RC. Metformin. N Engl J Med 1996;334:574-9.28550 - Glucophage and Glucophage XR (metformin HCl tablets and extended-release tablets) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2018 May.42826 - Robert F, Fendri S, Hary L,et al. Kinetics of plasma and erythrocyte metformin after acute administration in healthy subjects. Diabetes Metab 2003;29:279–83.60711 - Fortamet (metformin extended-release film-coated tablets) package insert. Ft. Lauderdale, FL: Watson Laboratories-Florida; 2017 April.60714 - Glumetza (metformin hydrochloride film-coated modified-release tablet) package insert. Menlo Park, CA: Depomed, Inc.; 2017 April.60715 - Riomet (metformin hydrochloride) oral solution package insert. Jacksonville FL: Ranbaxy Laboratories Inc.; 2018 Nov.64593 - Riomet XR (metformin extended-release suspension) package insert. Cranbury, NJ: Sun Pharmaceutical Industries, Inc.; 2019 Aug.

Pregnancy/Breast-feeding

polycystic ovary syndrome, pregnancy

Premenopausal anovulatory females with insulin resistance (i.e., those with polycystic ovary syndrome (PCOS)) may resume ovulation as a result of metformin therapy; patients may be at risk of conception if adequate contraception is not used in those not desiring to become pregnant. In some cases, metformin is used as an adjunct in PCOS patients to regulate menstrual cycles or to enhance fertility. Metformin is not recommended for routine use during pregnancy.[28550] Metformin does pass through the placenta and the fetus is likely exposed to therapeutic concentrations of metformin.[31404] The American College of Obstetricians and Gynecologists (ACOG) and the American Diabetes Association (ADA) continue to recommend human insulin as the standard of care in women with diabetes mellitus or gestational diabetes mellitus (GDM) requiring medical therapy.[64926] [62358] Per ACOG, in women who decline insulin therapy or are unable to safely administer insulin, metformin is the preferred second-line choice. Per the ADA, metformin may be used to treat GDM as a treatment option; however, no long term safety data are available for any oral agent. Metformin may cause a lower risk of neonatal hypoglycemia and less maternal weight gain than insulin; however, some data suggest that metformin may slightly increase the risk of prematurity. The ADA notes that in some clinical studies, nearly 50% of GDM patients initially treated with metformin have needed the addition of insulin in order to achieve acceptable glucose control.[64926] [62358] Many studies and analyses of metformin use in pregnancy have been published. The data suggest no increase in the rates of expected birth defects or other adverse outcomes in exposed infants and studies comparing metformin to insulin in the treatment of gestational diabetes have generally found no significant differences in glycemic control or pregnancy outcomes.[46193] [46201] [46203]

breast-feeding

Small studies indicate that metformin is excreted in human breast milk. Infant hypoglycemia or other side effects are a possibility; however, adverse effects on infant plasma glucose have not been reported in human studies. Animal data show that metformin is excreted into breast milk and reaches levels similar to those in plasma.[31407] [31408] [31409] Furthermore, the use of metformin 2550 mg/day by mothers breast-feeding their infants for 6 months does not affect growth, motor, or social development; the effects beyond 6 months are not known.[32459] In all of these studies, the estimated weight-adjusted infant exposure to metformin ranged from 0.11% to 1.08% of the mother's dose. While the manufacturers of metformin recommend that a decision should be made to discontinue breast-feeding or discontinue the drug, the results of these studies indicate that maternal ingestion of metformin during breast-feeding is probably safe to the infant. However, a risk and benefit analysis should be made for each mother and her infant; if patients elect to continue metformin while breast-feeding, the mother should be aware of the potential risks to the infant. If metformin is discontinued and blood glucose is not controlled on diet and exercise alone, insulin therapy should be considered. Because acarbose has limited systemic absorption, which results in minimal maternal plasma concentrations, clinically significant exposure via breast milk is not expected [46303]; therefore, this agent may represent a reasonable alternative for some patients. Tolbutamide is usually considered compatible with breast-feeding.[27500] Glyburide may be a suitable alternative since it was not detected in the breast milk of lactating women who received single and multiple doses of glyburide.[31568] If any oral hypoglycemics are used during breast feeding, the nursing infant should be monitored for signs of hypoglycemia, such as increased fussiness or somnolence.[46104]

Revision Date: 04/03/2020, 03:45:49 PM

References

27500 - American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108(3):776-789.28550 - Glucophage and Glucophage XR (metformin HCl tablets and extended-release tablets) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2018 May.31404 - Vanky E, Zahlsen K, Spigset O, et al. Placental passage of metformin in women with polycystic ovary syndrome. Fertil Steril 2005;83:1575-8.31407 - Hale TW, Kristensen JH, Hackett LP, et al. Transfer of metformin into human milk. Diabetologia 2002;45:1509-14.31408 - Gardiner SJ, Kirkpatrick CMJ, Begg EJ, et al. Transfer of metformin into human milk. Clin Pharmacol Ther 2003;73:71-7.31409 - Briggs GG, Ambrose PJ, Nageotte MP, et al. Excretion of metformin into breast milk and the effect on nursing infants. Obstet Gynecol 2005;105:1437-41.31568 - Feig DS, Donat DJ, Briggs GG, et al. Transfer of glyburide and glipizide into breast milk. Diabetes Care 2005;28:1851-5.32459 - Glueck CJ, Salehi M, Sieve L, et al. Growth, motor, and social development in breast- and formula- fed infants of metformin-treated women with polycystic ovary syndrome. J Pediatr 2006;148:628-32.46104 - Spencer JP, Gonzalez LS, Barnhart DJ. Medications in the breast-feeding mother. Am Fam Physician 2001; 64:119-126.46193 - Glueck CJ, Goldenberg N, Pranikoff J, et al. Height, weight, and motor-social development during the first 18 months of life in 126 infants born to 109 mothers with polycystic ovary syndrome who conceived on and continued metformin through pregnancy. Hum Reprod 2004;19:1323-30.46201 - Dhulkotia JS, Ola B, Fraser R, et al. Oral hypoglycemic agents vs insulin in management of gestational diabetes: a systematic review and metaanalysis. Am J Obstet Gynecol 2010;203:457.46203 - Balani J, Hyer SL, Rodin DA, et al. Pregnancy outcomes in women with gestational diabetes treated with metformin or insulin: a case-control study. Diabet Med 2009;26:798-802.46303 - Everett J. Use of oral antidiabetic agents during breastfeeding. J Hum Lact 1997;13:319-21.62358 - American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins-Obstetrics. Practice Bulletin No. 190: Gestational Diabetes Mellitus. Obstet Gynecol. 2018;131:e49-e64. Reaffirmed 2019.64926 - American Diabetes Association. Standards of Medical Care in Diabetes - 2021. Diabetes Care. 2021; 44(Suppl 1):S1-S232. Available at: https://care.diabetesjournals.org/content/44/Supplement_1

Interactions

Level 1 (Severe)

  • Iodipamide Meglumine
  • Ionic Contrast Media
  • Ioxaglate Meglumine; Ioxaglate Sodium

Level 2 (Major)

  • Abacavir; Dolutegravir; Lamivudine
  • Chloroquine
  • Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir
  • Dofetilide
  • Dolutegravir
  • Dolutegravir; Lamivudine
  • Dolutegravir; Rilpivirine
  • Non-Ionic Contrast Media
  • Ombitasvir; Paritaprevir; Ritonavir
  • Phentermine; Topiramate
  • Ranolazine
  • Topiramate

Level 3 (Moderate)

  • Abacavir; Lamivudine, 3TC
  • Abacavir; Lamivudine, 3TC; Zidovudine, ZDV
  • Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine
  • Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine
  • Acetaminophen; Chlorpheniramine; Phenylephrine
  • Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine
  • Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine
  • Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine
  • Acetaminophen; Dextromethorphan; Phenylephrine
  • Acetaminophen; Dextromethorphan; Pseudoephedrine
  • Acetaminophen; Guaifenesin; Phenylephrine
  • Acetaminophen; Propoxyphene
  • Acetaminophen; Pseudoephedrine
  • Acetazolamide
  • Acetohexamide
  • Acrivastine; Pseudoephedrine
  • Adefovir
  • Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ
  • Aliskiren; Hydrochlorothiazide, HCTZ
  • Aliskiren; Valsartan
  • Amiloride; Hydrochlorothiazide, HCTZ
  • Amlodipine; Benazepril
  • Amlodipine; Olmesartan
  • Amlodipine; Valsartan
  • Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ
  • Amoxicillin; Clarithromycin; Omeprazole
  • Amphetamine
  • Amphetamine; Dextroamphetamine
  • Amphetamines
  • Androgens
  • Angiotensin II receptor antagonists
  • Angiotensin-converting enzyme inhibitors
  • Atazanavir; Cobicistat
  • Atenolol; Chlorthalidone
  • atypical antipsychotic
  • Azilsartan
  • Azilsartan; Chlorthalidone
  • Benazepril
  • Benazepril; Hydrochlorothiazide, HCTZ
  • Bendroflumethiazide; Nadolol
  • Benzphetamine
  • Beta-blockers
  • Bictegravir; Emtricitabine; Tenofovir Alafenamide
  • Bisoprolol; Hydrochlorothiazide, HCTZ
  • Bortezomib
  • Brigatinib
  • Brompheniramine; Carbetapentane; Phenylephrine
  • Brompheniramine; Dextromethorphan; Phenylephrine
  • Brompheniramine; Hydrocodone; Pseudoephedrine
  • Brompheniramine; Phenylephrine
  • Brompheniramine; Pseudoephedrine
  • Brompheniramine; Pseudoephedrine; Dextromethorphan
  • Budesonide; Glycopyrrolate; Formoterol
  • Candesartan
  • Candesartan; Hydrochlorothiazide, HCTZ
  • Capmatinib
  • Captopril
  • Captopril; Hydrochlorothiazide, HCTZ
  • Carbetapentane; Chlorpheniramine; Phenylephrine
  • Carbetapentane; Diphenhydramine; Phenylephrine
  • Carbetapentane; Guaifenesin; Phenylephrine
  • Carbetapentane; Phenylephrine
  • Carbetapentane; Phenylephrine; Pyrilamine
  • Carbetapentane; Pseudoephedrine
  • Carbinoxamine; Dextromethorphan; Pseudoephedrine
  • Carbinoxamine; Hydrocodone; Phenylephrine
  • Carbinoxamine; Hydrocodone; Pseudoephedrine
  • Carbinoxamine; Phenylephrine
  • Carbinoxamine; Pseudoephedrine
  • Cephalexin
  • Cetirizine; Pseudoephedrine
  • Chlophedianol; Dexchlorpheniramine; Pseudoephedrine
  • Chlophedianol; Guaifenesin; Phenylephrine
  • Chlorothiazide
  • Chlorpheniramine; Dextromethorphan; Phenylephrine
  • Chlorpheniramine; Dextromethorphan; Pseudoephedrine
  • Chlorpheniramine; Dihydrocodeine; Phenylephrine
  • Chlorpheniramine; Dihydrocodeine; Pseudoephedrine
  • Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine
  • Chlorpheniramine; Hydrocodone; Phenylephrine
  • Chlorpheniramine; Hydrocodone; Pseudoephedrine
  • Chlorpheniramine; Ibuprofen; Pseudoephedrine
  • Chlorpheniramine; Phenylephrine
  • Chlorpheniramine; Pseudoephedrine
  • Chlorpropamide
  • Chlorthalidone
  • Chlorthalidone; Clonidine
  • Chromium
  • Cimetidine
  • Cisapride
  • Clarithromycin
  • Clofarabine
  • Cobicistat
  • Codeine; Guaifenesin; Pseudoephedrine
  • Codeine; Phenylephrine; Promethazine
  • Colesevelam
  • Corticosteroids
  • Cyclosporine
  • Daclatasvir
  • Danazol
  • Darunavir; Cobicistat
  • Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide
  • Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir
  • Desloratadine; Pseudoephedrine
  • Dexbrompheniramine; Pseudoephedrine
  • Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine
  • Dextroamphetamine
  • Dextromethorphan; Diphenhydramine; Phenylephrine
  • Dextromethorphan; Guaifenesin; Phenylephrine
  • Dextromethorphan; Guaifenesin; Pseudoephedrine
  • Dichlorphenamide
  • Digoxin
  • Dihydrocodeine; Guaifenesin; Pseudoephedrine
  • Diphenhydramine; Hydrocodone; Phenylephrine
  • Diphenhydramine; Phenylephrine
  • Disopyramide
  • Donepezil; Memantine
  • Doravirine; Lamivudine; Tenofovir disoproxil fumarate
  • Efavirenz; Emtricitabine; Tenofovir
  • Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate
  • Elbasvir; Grazoprevir
  • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide
  • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate
  • Emtricitabine
  • Emtricitabine; Rilpivirine; Tenofovir alafenamide
  • Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate
  • Emtricitabine; Tenofovir alafenamide
  • Emtricitabine; Tenofovir disoproxil fumarate
  • Enalapril, Enalaprilat
  • Enalapril; Felodipine
  • Enalapril; Hydrochlorothiazide, HCTZ
  • Entecavir
  • Ephedrine
  • Ephedrine; Guaifenesin
  • Eprosartan
  • Eprosartan; Hydrochlorothiazide, HCTZ
  • Erdafitinib
  • Erythromycin; Sulfisoxazole
  • Esterified Estrogens; Methyltestosterone
  • Ethacrynic Acid
  • Ethanol
  • Fenofibrate
  • Fenofibric Acid
  • Fexofenadine; Pseudoephedrine
  • Fibric acid derivatives
  • Fluoxetine
  • Fluoxymesterone
  • Fosinopril
  • Fosinopril; Hydrochlorothiazide, HCTZ
  • Garlic, Allium sativum
  • Gemfibrozil
  • Glecaprevir; Pibrentasvir
  • Glimepiride
  • Glimepiride; Rosiglitazone
  • Glipizide
  • Glipizide; Metformin
  • Glyburide
  • Glyburide; Metformin
  • Glycopyrrolate
  • Glycopyrrolate; Formoterol
  • Green Tea
  • Guaifenesin; Hydrocodone; Pseudoephedrine
  • Guaifenesin; Phenylephrine
  • Guaifenesin; Pseudoephedrine
  • Hydralazine; Hydrochlorothiazide, HCTZ
  • Hydrochlorothiazide, HCTZ
  • Hydrochlorothiazide, HCTZ; Methyldopa
  • Hydrochlorothiazide, HCTZ; Moexipril
  • Hydrocodone; Phenylephrine
  • Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine
  • Hydrocodone; Pseudoephedrine
  • Hydroxychloroquine
  • Ibuprofen; Pseudoephedrine
  • Indacaterol; Glycopyrrolate
  • Indapamide
  • Insulin Aspart
  • Insulin Aspart; Insulin Aspart Protamine
  • Insulin Degludec
  • Insulin Degludec; Liraglutide
  • Insulin Detemir
  • Insulin Glargine
  • Insulin Glargine; Lixisenatide
  • Insulin Glulisine
  • Insulin Lispro
  • Insulin Lispro; Insulin Lispro Protamine
  • Insulin, Inhaled
  • Insulins
  • Irbesartan
  • Irbesartan; Hydrochlorothiazide, HCTZ
  • Isophane Insulin (NPH)
  • Lamivudine, 3TC
  • Lamivudine, 3TC; Zidovudine, ZDV
  • Lamivudine; Tenofovir Disoproxil Fumarate
  • Lamotrigine
  • Lanreotide
  • Lansoprazole; Amoxicillin; Clarithromycin
  • Ledipasvir; Sofosbuvir
  • Lente Insulin
  • Linezolid
  • Lisdexamfetamine
  • Lisinopril
  • Lisinopril; Hydrochlorothiazide, HCTZ
  • Lithium
  • Loratadine; Pseudoephedrine
  • Lorcaserin
  • Losartan
  • Losartan; Hydrochlorothiazide, HCTZ
  • Lovastatin; Niacin
  • Mecasermin rinfabate
  • Mecasermin, Recombinant, rh-IGF-1
  • Meglitinides
  • Memantine
  • Metformin; Repaglinide
  • Methamphetamine
  • Methazolamide
  • Methyclothiazide
  • Methyltestosterone
  • Metolazone
  • Metoprolol; Hydrochlorothiazide, HCTZ
  • Metyrapone
  • Midodrine
  • Moexipril
  • Monoamine oxidase inhibitors
  • Nandrolone Decanoate
  • Naproxen; Pseudoephedrine
  • Nateglinide
  • Nebivolol; Valsartan
  • Niacin, Niacinamide
  • Niacin; Simvastatin
  • Octreotide
  • Olanzapine; Fluoxetine
  • Olmesartan
  • Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ
  • Olmesartan; Hydrochlorothiazide, HCTZ
  • Oxandrolone
  • Oxymetholone
  • Pasireotide
  • Pegvisomant
  • Pentamidine
  • Pentoxifylline
  • Perindopril
  • Perindopril; Amlodipine
  • Phenylephrine
  • Pioglitazone; Glimepiride
  • Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements)
  • Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved)
  • Promethazine; Phenylephrine
  • Propantheline
  • Propoxyphene
  • Propranolol; Hydrochlorothiazide, HCTZ
  • Protease inhibitors
  • Pseudoephedrine
  • Pseudoephedrine; Triprolidine
  • Pyrimethamine; Sulfadoxine
  • Quinapril
  • Quinapril; Hydrochlorothiazide, HCTZ
  • Quinolones
  • Ramipril
  • Regular Insulin
  • Regular Insulin; Isophane Insulin (NPH)
  • Repaglinide
  • Reserpine
  • Risdiplam
  • Sacubitril; Valsartan
  • Salicylates
  • Sofosbuvir
  • Sofosbuvir; Velpatasvir
  • Sofosbuvir; Velpatasvir; Voxilaprevir
  • Somatropin, rh-GH
  • Spironolactone; Hydrochlorothiazide, HCTZ
  • Sulfadiazine
  • Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole
  • Sulfasalazine
  • Sulfisoxazole
  • Sulfonamides
  • Sulfonylureas
  • Tacrolimus
  • Tafenoquine
  • Tegaserod
  • Telmisartan
  • Telmisartan; Amlodipine
  • Telmisartan; Hydrochlorothiazide, HCTZ
  • Tenofovir Alafenamide
  • Tenofovir, PMPA
  • Testolactone
  • Testosterone
  • Thiazide diuretics
  • tobacco
  • Tolazamide
  • Tolbutamide
  • Trandolapril
  • Trandolapril; Verapamil
  • Triamterene; Hydrochlorothiazide, HCTZ
  • Trilaciclib
  • Trospium
  • Ultralente Insulin
  • Valsartan
  • Valsartan; Hydrochlorothiazide, HCTZ
  • Vandetanib
  • Zonisamide

Level 4 (Minor)

  • Bumetanide
  • Calcium Carbonate; Famotidine; Magnesium Hydroxide
  • Clonidine
  • Conjugated Estrogens
  • Conjugated Estrogens; Bazedoxifene
  • Conjugated Estrogens; Medroxyprogesterone
  • Cyanocobalamin, Vitamin B12
  • Desogestrel; Ethinyl Estradiol
  • Diazoxide
  • Dienogest; Estradiol valerate
  • Diethylstilbestrol, DES
  • Drospirenone
  • Drospirenone; Estetrol
  • Drospirenone; Estradiol
  • Drospirenone; Ethinyl Estradiol
  • Drospirenone; Ethinyl Estradiol; Levomefolate
  • Elagolix; Estradiol; Norethindrone acetate
  • Esterified Estrogens
  • Estradiol
  • Estradiol Cypionate; Medroxyprogesterone
  • Estradiol; Levonorgestrel
  • Estradiol; Norethindrone
  • Estradiol; Norgestimate
  • Estradiol; Progesterone
  • Estramustine
  • Estrogens
  • Estropipate
  • Ethinyl Estradiol
  • Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate
  • Ethinyl Estradiol; Norelgestromin
  • Ethinyl Estradiol; Norethindrone Acetate
  • Ethinyl Estradiol; Norgestrel
  • Ethotoin
  • Ethynodiol Diacetate; Ethinyl Estradiol
  • Etonogestrel
  • Etonogestrel; Ethinyl Estradiol
  • Famotidine
  • Famotidine; Ibuprofen
  • Fosphenytoin
  • Furosemide
  • Hydroxyprogesterone
  • Leuprolide; Norethindrone
  • Levomefolate
  • Levonorgestrel
  • Levonorgestrel; Ethinyl Estradiol
  • Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate
  • Levothyroxine
  • Levothyroxine; Liothyronine (Porcine)
  • Levothyroxine; Liothyronine (Synthetic)
  • Liothyronine
  • Medroxyprogesterone
  • Mestranol; Norethindrone
  • Nicotine
  • Nifedipine
  • Norethindrone
  • Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate
  • Norethindrone; Ethinyl Estradiol
  • Norethindrone; Ethinyl Estradiol; Ferrous fumarate
  • Norgestimate; Ethinyl Estradiol
  • Norgestrel
  • Orlistat
  • Phenothiazines
  • Phenytoin
  • Progesterone
  • Progestins
  • Relugolix; Estradiol; Norethindrone acetate
  • Segesterone Acetate; Ethinyl Estradiol
  • Thyroid hormones
  • Torsemide
Abacavir; Dolutegravir; Lamivudine: (Major) If these drugs are used in combination, the total daily dose of metformin must not exceed 1,000 mg/day. Dolutegravir may increase exposure to metformin. Increased exposure to metformin may increase the risk for hypoglycemia, gastrointestinal side effects, and potentially increase the risk for lactic acidosis. Consider the benefits and risks of concomitant use of dolutegravir with metformin. Close monitoring of blood glucose and patient clinical status (gastrointestinal side effects, renal function, electrolytes and acid-base balance) is recommended. When stopping dolutegravir, the metformin dose may need to be adjusted. In drug interaction studies, dolutegravir increased both the Cmax and AUC of metformin when metformin 500 mg PO twice daily was coadministered. Dolutegravir inhibits common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2]/multidrug and toxin extrusion [MATE1 and MATE2k]). [28550] [55594] (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems. [28550] [29240] Abacavir; Lamivudine, 3TC: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems. [28550] [29240] Abacavir; Lamivudine, 3TC; Zidovudine, ZDV: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems. [28550] [29240] Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Acetaminophen; Propoxyphene: (Moderate) Propoxyphene may enhance the hypoglycemic action of antidiabetic agents. Patients should be closely monitored for changes in glycemic control while receiving propoxyphene in combination with antidiabetic agents. [7224] Acetaminophen; Pseudoephedrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Acetazolamide: (Moderate) Carbonic anhydrase inhibitors such as acetazolamide frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of acetazolamide with metformin may increase the risk for lactic acidosis; consider more frequent monitoring. Carbonic anhydrase inhibitors may also alter blood sugar; both hyperglycemia and hypoglycemia have been described. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction. [28267] [28550] [57357] Acetohexamide: (Moderate) Use of metformin with a sulfonylurea may increase the risk of hypoglycemia. Sulfonylureas are known to cause hypoglycemia. To manage hypoglycemic risk, lower doses of the sulfonylurea may be needed. Monitor blood sugar. [28550] Acrivastine; Pseudoephedrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Adefovir: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion (e.g., adefovir) may decrease metformin elimination by competing for common renal tubular transport systems. Although such interactions remain theoretical, careful patient monitoring and dose adjustment of metformin and/or the interfering cationic drug are recommended. [28550] [28784] Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Aliskiren; Valsartan: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Amlodipine; Benazepril: (Moderate) Angiotensin-converting enzyme (ACE) inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. ACE inhibitors may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [29403] [30585] [33489] [42591] Amlodipine; Olmesartan: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] Amlodipine; Valsartan: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Amoxicillin; Clarithromycin; Omeprazole: (Moderate) The concomitant use of clarithromycin and antidiabetic agents can result in significant hypoglycemia. Careful monitoring of blood glucose is recommended. [28238] Amphetamine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Amphetamine; Dextroamphetamine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Amphetamines: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Androgens: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together. [33919] [33920] [33921] [33922] [33923] [33924] Angiotensin II receptor antagonists: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] Angiotensin-converting enzyme inhibitors: (Moderate) Angiotensin-converting enzyme (ACE) inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. ACE inhibitors may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [29403] [30585] [33489] [42591] Atazanavir; Cobicistat: (Moderate) Concurrent administration of metformin and cobicistat may increase the risk of lactic acidosis. Cobicistat is a potent inhibitor of the human multidrug and toxic extrusion 1 (MATE1) on proximal renal tubular cells; metformin is a MATE1 substrate. Inhibition of MATE1 by cobicistat may decrease metformin eliminiation by blocking renal tubular secretion. If these drugs are given together, closely monitor for signs of metformin toxicity; metformin dose adjustments may be needed. [28550] [51664] [58763] Atenolol; Chlorthalidone: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] atypical antipsychotic: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. [28915] [30575] Azilsartan: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] Azilsartan; Chlorthalidone: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Benazepril: (Moderate) Angiotensin-converting enzyme (ACE) inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. ACE inhibitors may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [29403] [30585] [33489] [42591] Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Angiotensin-converting enzyme (ACE) inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. ACE inhibitors may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [29403] [30585] [33489] [42591] (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Bendroflumethiazide; Nadolol: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Benzphetamine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Beta-blockers: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present. [28618] [29403] [30489] [30575] [32916] [53617] [62853] Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Caution is advised when administering bictegravir with metformin, as coadministration may increase exposure to metformin and increase the risk for hypoglycemia, gastrointestinal side effects, and potentially increase the risk for lactic acidosis. Close monitoring of blood glucose and patient clinical status is recommended. In drug interaction studies, bictegravir increased both the Cmax and AUC of metformin at a metformin dose of 500 mg PO twice daily. Bictegravir inhibits common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2]/multidrug and toxin extrusion [MATE1]). [28550] [62852] (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Drugs that are eliminated by renal tubular secretion, such as emtricitabine, may decrease metformin elimination by competing for common renal tubular transport systems. Although such interactions remain theoretical, careful patient monitoring and dose adjustment of metformin and/or the interfering cationic drug are recommended. [28550] Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Bortezomib: (Moderate) During clinical trials of bortezomib, hypoglycemia and hyperglycemia were reported in diabetic patients receiving antidiabetic agents. Patients taking antidiabetic agents and receiving bortezomib treatment may require close monitoring of their blood glucose levels and dosage adjustment of their medication. [28383] Brigatinib: (Moderate) Consider the benefits and risks of concomitant therapy of brigatinib with metformin. Concomitant use of drugs that interfere with common renal tubular transport systems involved in the renal elimination of metformin (e.g., MATE inhibitors) could increase systemic exposure to metformin and increase the risk for lactic acidosis. Brigatinib inhibits MATE1 and MATE2K in vitro and may have the potential to increase concentrations of coadministered substrates of these transporters. [28550] [61909] Brompheniramine; Carbetapentane; Phenylephrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Brompheniramine; Phenylephrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Brompheniramine; Pseudoephedrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Budesonide; Glycopyrrolate; Formoterol: (Moderate) Coadministration of glycopyrrolate with metformin my increase metformin plasma concentrations, which may lead to increased metformin effects and possible adverse events. If coadministration is necessary, monitor clinical response to metformin and adjust metformin dose accordingly. [41489] Bumetanide: (Minor) Bumetanide has been associated with hyperglycemia, possibly due to potassium depletion, and, glycosuria has been reported. Because of this, a potential pharmacodynamic interaction exists between bumetanide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely. [5351] Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Minor) Famotidine may decrease the renal clearance of metformin secondary to competition for renal tubular transport systems. Such an interaction has been observed when cimetidine was administered with metformin. The decrease in renal excretion led to a 40% increase in metformin AUC. Although interactions with cationic drugs remain theoretical (except for cimetidine), caution is warranted when famotidine and metformin are prescribed concurrently. Famotidine may be less likely to interact with metformin versus cimetidine or ranitidine because of less tubular excretion. [7775] Candesartan: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Capmatinib: (Moderate) Monitor for an increased risk of metformin-related adverse reactions including lactic acidosis if coadministration with capmatinib is necessary; consider the benefits and risks of concomitant use. Metformin is a substrate of multidrug and toxin extrusion (MATE) and capmatinib is a MATE1 and MATE2K inhibitor. Coadministration may interfere with the renal elimination of metformin and increase metformin exposure. [28550] [65377] Captopril: (Moderate) Angiotensin-converting enzyme (ACE) inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. ACE inhibitors may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [29403] [30585] [33489] [42591] Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Angiotensin-converting enzyme (ACE) inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. ACE inhibitors may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [29403] [30585] [33489] [42591] (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Carbetapentane; Chlorpheniramine; Phenylephrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Carbetapentane; Guaifenesin; Phenylephrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Carbetapentane; Phenylephrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Carbetapentane; Phenylephrine; Pyrilamine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Carbetapentane; Pseudoephedrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Carbinoxamine; Phenylephrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Carbinoxamine; Pseudoephedrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Cephalexin: (Moderate) In healthy subjects given single 500 mg doses of cephalexin and metformin, plasma metformin Cmax and AUC increased by an average of 34% and 24%, respectively; metformin renal clearance decreased by an average of 14%. No information is available about the interaction of cephalexin and metformin following multiple dose administration. [29922] [29923] Cetirizine; Pseudoephedrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Chlophedianol; Guaifenesin; Phenylephrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Chloroquine: (Major) Careful monitoring of blood glucose is recommended when chloroquine and antidiabetic agents, including metformin, are coadministered. A decreased dose of the antidiabetic agent may be necessary as severe hypoglycemia has been reported in patients treated concomitantly with chloroquine and an antidiabetic agent. [29758] Chlorothiazide: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Chlorpheniramine; Phenylephrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Chlorpheniramine; Pseudoephedrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Chlorpropamide: (Moderate) Use of metformin with a sulfonylurea may increase the risk of hypoglycemia. Sulfonylureas are known to cause hypoglycemia. To manage hypoglycemic risk, lower doses of the sulfonylurea may be needed. Monitor blood sugar. [28550] Chlorthalidone: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Chlorthalidone; Clonidine: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients. [29533] [30585] [44086] Chromium: (Moderate) Chromium dietary supplements may lower blood glucose. As part of the glucose tolerance factor molecule, chromium appears to facilitate the binding of insulin to insulin receptors in tissues and to aid in glucose metabolism. Because blood glucose may be lowered by the use of chromium, patients who are on antidiabetic agents may need dose adjustments. Close monitoring of blood glucose is recommended. [25731] [25732] Cimetidine: (Moderate) Use with caution, as cimetidine inhibits renal elimination of metformin. Consider alternatives to cimetidine. Increased metformin exposure due to use of cimetidine may lead to gastrointestinal complaints, altered glycemic control, and a potential for an increased risk for lactic acidosis. If it is medically necessary to use cimetidine, carefully monitor. Metformin dose reduction may be needed. An interaction between metformin and oral cimetidine has been observed in normal healthy volunteers in both single- and multiple-dose drug interaction studies. Cimetidine caused a 60% increase in peak metformin concentrations and a 40% increase in metformin exposure (AUC). Cimetidine inhibits common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2]/multidrug and toxin extrusion [MATE1 and MATE2k]). [28550] [56579] Cisapride: (Moderate) Because cisapride can enhance gastric emptying in diabetic patients, blood glucose can be affected, which, in turn, may affect the clinical response to antidiabetic agents. Monitor blood glucose and adjust if cliniically indicated. [47221] Clarithromycin: (Moderate) The concomitant use of clarithromycin and antidiabetic agents can result in significant hypoglycemia. Careful monitoring of blood glucose is recommended. [28238] Clofarabine: (Moderate) Concomitant use of clofarabine and metformin may result in altered clofarabine levels because both agents are a substrate of OCT1. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 substrates. [51834] [54578] Clonidine: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients. [29533] [30585] [44086] Cobicistat: (Moderate) Concurrent administration of metformin and cobicistat may increase the risk of lactic acidosis. Cobicistat is a potent inhibitor of the human multidrug and toxic extrusion 1 (MATE1) on proximal renal tubular cells; metformin is a MATE1 substrate. Inhibition of MATE1 by cobicistat may decrease metformin eliminiation by blocking renal tubular secretion. If these drugs are given together, closely monitor for signs of metformin toxicity; metformin dose adjustments may be needed. [28550] [51664] [58763] Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Codeine; Phenylephrine; Promethazine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Colesevelam: (Moderate) The clinical response to metformin extended-release (metformin ER) should be monitored in patients receiving concomitant therapy with colesevelam. Be alert for changes in glycemic control, increased metformin side effects, such as gastrointestinal disturbances and a risk for lactic acidosis. Colesevelam increases the Cmax and AUC of metformin ER by approximately 8% and 44%, respectively. The mechanism of the interaction is not known. Colesevelam has no significant effect on the bioavailability of immediate-release metformin. [30812] Conjugated Estrogens: (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] Conjugated Estrogens; Bazedoxifene: (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] Conjugated Estrogens; Medroxyprogesterone: (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] (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] Corticosteroids: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] Cyanocobalamin, Vitamin B12: (Minor) Metformin may result in suboptimal oral vitamin B12 absorption by competitively blocking the calcium-dependent binding of the intrinsic factor-vitamin B12 complex to its receptor. Regular measurement of hematologic parameters is recommended in all patients on chronic metformin treatment; abnormalities should be investigated. [5280] Cyclosporine: (Moderate) Patients should be monitored for worsening glycemic control if therapy with cyclosporine is initiated in patients receiving antidiabetic agents. Cyclosporine has been reported to cause hyperglycemia or exacerbate diabetes mellitus; this effect appears to be dose-related and caused by direct beta-cell toxicity. Also, any drug that deteriorates the renal status of the patient is likely to alter metformin concentrations in the body, so renal function should be carefully monitored during the use of cyclosporine and metformin together. [30585] [62853] Daclatasvir: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir. [60001] Danazol: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together. [33919] [33920] [33921] [33922] [33923] [33924] Darunavir; Cobicistat: (Moderate) Concurrent administration of metformin and cobicistat may increase the risk of lactic acidosis. Cobicistat is a potent inhibitor of the human multidrug and toxic extrusion 1 (MATE1) on proximal renal tubular cells; metformin is a MATE1 substrate. Inhibition of MATE1 by cobicistat may decrease metformin eliminiation by blocking renal tubular secretion. If these drugs are given together, closely monitor for signs of metformin toxicity; metformin dose adjustments may be needed. [28550] [51664] [58763] Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Drugs that are eliminated by renal tubular secretion, such as emtricitabine, may decrease metformin elimination by competing for common renal tubular transport systems. Although such interactions remain theoretical, careful patient monitoring and dose adjustment of metformin and/or the interfering cationic drug are recommended. [28550] (Moderate) Concurrent administration of metformin and cobicistat may increase the risk of lactic acidosis. Cobicistat is a potent inhibitor of the human multidrug and toxic extrusion 1 (MATE1) on proximal renal tubular cells; metformin is a MATE1 substrate. Inhibition of MATE1 by cobicistat may decrease metformin eliminiation by blocking renal tubular secretion. If these drugs are given together, closely monitor for signs of metformin toxicity; metformin dose adjustments may be needed. [28550] [51664] [58763] Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir : (Moderate) Closely monitor blood glucose levels if dasabuvir; ombitasvir; paritaprevir; ritonavir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as dasabuvir; ombitasvir; paritaprevir; ritonavir. [58664] [60002] [61023] Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) While no dosage adjustment of metformin is recommended in patients with normal hepatic or renal function, careful patient monitoring and dose adjustment of metformin and/or the potentially interfering drug is recommended with concurrent use. Monitor for signs of onset of lactic acidosis such as respiratory distress, somnolence, and non-specific abdominal distress or worsening renal function. Do not use metformin with paritaprevir in patients with renal insufficiency or hepatic impairment. Drugs that interfere with common renal tubular transport systems involved in the renal elimination of metformin could increase systemic exposure to metformin and may increase the risk for lactic acidosis. Paritaprevir is an inhibitor of the organic anion transporters OATP1B1 and OATP1B3. While initial drug-drug interaction studies of paritaprevir-containing hepatitis treatments have not noted an effect on metformin concentrations, more study is needed. [28550] [58664] [60002] [61023] Desloratadine; Pseudoephedrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Desogestrel; Ethinyl Estradiol: (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] (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] Dexbrompheniramine; Pseudoephedrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Dextroamphetamine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Diazoxide: (Minor) Diazoxide, when administered intravenously or orally, produces a prompt dose-related increase in blood glucose level, due primarily to an inhibition of insulin release from the pancreas, and also to an extrapancreatic effect. The hyperglycemic effect begins within an hour and generally lasts no more than 8 hours in the presence of normal renal function. The hyperglycemic effect of diazoxide is expected to be antagonized by certain antidiabetic agents (e.g., insulin or a sulfonylurea). Blood glucose should be closely monitored. [49068] Dichlorphenamide: (Moderate) Carbonic anhydrase inhibitors such as dichlorphenamide frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of dichlorphenamide with metformin may increase the risk for lactic acidosis; consider more frequent monitoring. Carbonic anhydrase inhibitors may also alter blood sugar; both hyperglycemia and hypoglycemia have been described. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction. [28550] [60122] Dienogest; Estradiol valerate: (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] (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] Diethylstilbestrol, DES: (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] Digoxin: (Moderate) Metformin may increase digoxin concentrations, but the magnitude is unclear. Measure serum digoxin concentrations before initiating metformin, and periodically after that. Monitor heart rate and other clinical parameters. Adjust digoxin dose as necessary. [28272] Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Diphenhydramine; Phenylephrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Disopyramide: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving disopyramide concomitantly with antidiabetic agents should be monitored for changes in glycemic control. [28228] Dofetilide: (Major) Dofetilide should be co-administered with metformin with caution since both drugs are actively secreted via cationic secretion and could compete for common renal tubular transport systems. This results in a possible increase in plasma concentrations of either drug. Reduced clearance of metformin may increase the risk for lactic acidosis; increased concentrations of dofetilide may increase the risk for side effects including proarrhythmia. Careful patient monitoring and dose adjustment of metformin and dofetilide is recommended. [28221] [28550] Dolutegravir: (Major) If these drugs are used in combination, the total daily dose of metformin must not exceed 1,000 mg/day. Dolutegravir may increase exposure to metformin. Increased exposure to metformin may increase the risk for hypoglycemia, gastrointestinal side effects, and potentially increase the risk for lactic acidosis. Consider the benefits and risks of concomitant use of dolutegravir with metformin. Close monitoring of blood glucose and patient clinical status (gastrointestinal side effects, renal function, electrolytes and acid-base balance) is recommended. When stopping dolutegravir, the metformin dose may need to be adjusted. In drug interaction studies, dolutegravir increased both the Cmax and AUC of metformin when metformin 500 mg PO twice daily was coadministered. Dolutegravir inhibits common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2]/multidrug and toxin extrusion [MATE1 and MATE2k]). [28550] [55594] Dolutegravir; Lamivudine: (Major) If these drugs are used in combination, the total daily dose of metformin must not exceed 1,000 mg/day. Dolutegravir may increase exposure to metformin. Increased exposure to metformin may increase the risk for hypoglycemia, gastrointestinal side effects, and potentially increase the risk for lactic acidosis. Consider the benefits and risks of concomitant use of dolutegravir with metformin. Close monitoring of blood glucose and patient clinical status (gastrointestinal side effects, renal function, electrolytes and acid-base balance) is recommended. When stopping dolutegravir, the metformin dose may need to be adjusted. In drug interaction studies, dolutegravir increased both the Cmax and AUC of metformin when metformin 500 mg PO twice daily was coadministered. Dolutegravir inhibits common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2]/multidrug and toxin extrusion [MATE1 and MATE2k]). [28550] [55594] (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems. [28550] [29240] Dolutegravir; Rilpivirine: (Major) If these drugs are used in combination, the total daily dose of metformin must not exceed 1,000 mg/day. Dolutegravir may increase exposure to metformin. Increased exposure to metformin may increase the risk for hypoglycemia, gastrointestinal side effects, and potentially increase the risk for lactic acidosis. Consider the benefits and risks of concomitant use of dolutegravir with metformin. Close monitoring of blood glucose and patient clinical status (gastrointestinal side effects, renal function, electrolytes and acid-base balance) is recommended. When stopping dolutegravir, the metformin dose may need to be adjusted. In drug interaction studies, dolutegravir increased both the Cmax and AUC of metformin when metformin 500 mg PO twice daily was coadministered. Dolutegravir inhibits common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2]/multidrug and toxin extrusion [MATE1 and MATE2k]). [28550] [55594] Donepezil; Memantine: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Drugs that are eliminated by renal tubular secretion (e.g., memantine) may decrease metformin elimination by competing for common renal tubular transport systems. It should be noted that in a pharmacokinetic study in which memantine and glyburide; metformin (Glucovance) were coadministered, the pharmacokinetics of memantine, metformin, or glyburide were not altered. Regardless, careful patient monitoring is recommended. [31418] [5280] Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems. [28550] [29240] (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Drugs that are eliminated by renal tubular secretion, such as tenofovir, PMPA may decrease metformin elimination by competing for common renal tubular transport systems. Although such interactions remain theoretical, careful patient monitoring and dose adjustment of metformin and/or the interfering cationic drug are recommended. [28193] [28550] Drospirenone: (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] Drospirenone; Estetrol: (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] (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] Drospirenone; Estradiol: (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] (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] Drospirenone; Ethinyl Estradiol: (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] (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] Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) Levomefolate and metformin should be used together cautiously. Plasma concentrations of levomefolate may be reduced during treatment of type 2 diabetes with metformin. Monitor patients for decreased efficacy of levomefolate if these agents are used together. [35581] (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] (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] Efavirenz; Emtricitabine; Tenofovir: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Drugs that are eliminated by renal tubular secretion, such as emtricitabine, may decrease metformin elimination by competing for common renal tubular transport systems. Although such interactions remain theoretical, careful patient monitoring and dose adjustment of metformin and/or the interfering cationic drug are recommended. [28550] (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Drugs that are eliminated by renal tubular secretion, such as tenofovir, PMPA may decrease metformin elimination by competing for common renal tubular transport systems. Although such interactions remain theoretical, careful patient monitoring and dose adjustment of metformin and/or the interfering cationic drug are recommended. [28193] [28550] Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems. [28550] [29240] (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Drugs that are eliminated by renal tubular secretion, such as tenofovir, PMPA may decrease metformin elimination by competing for common renal tubular transport systems. Although such interactions remain theoretical, careful patient monitoring and dose adjustment of metformin and/or the interfering cationic drug are recommended. [28193] [28550] Elagolix; Estradiol; Norethindrone acetate: (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] (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] Elbasvir; Grazoprevir: (Moderate) Closely monitor blood glucose levels if elbasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as elbasvir. [60523] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Drugs that are eliminated by renal tubular secretion, such as emtricitabine, may decrease metformin elimination by competing for common renal tubular transport systems. Although such interactions remain theoretical, careful patient monitoring and dose adjustment of metformin and/or the interfering cationic drug are recommended. [28550] (Moderate) Concurrent administration of metformin and cobicistat may increase the risk of lactic acidosis. Cobicistat is a potent inhibitor of the human multidrug and toxic extrusion 1 (MATE1) on proximal renal tubular cells; metformin is a MATE1 substrate. Inhibition of MATE1 by cobicistat may decrease metformin eliminiation by blocking renal tubular secretion. If these drugs are given together, closely monitor for signs of metformin toxicity; metformin dose adjustments may be needed. [28550] [51664] [58763] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Drugs that are eliminated by renal tubular secretion, such as emtricitabine, may decrease metformin elimination by competing for common renal tubular transport systems. Although such interactions remain theoretical, careful patient monitoring and dose adjustment of metformin and/or the interfering cationic drug are recommended. [28550] (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Drugs that are eliminated by renal tubular secretion, such as tenofovir, PMPA may decrease metformin elimination by competing for common renal tubular transport systems. Although such interactions remain theoretical, careful patient monitoring and dose adjustment of metformin and/or the interfering cationic drug are recommended. [28193] [28550] (Moderate) Concurrent administration of metformin and cobicistat may increase the risk of lactic acidosis. Cobicistat is a potent inhibitor of the human multidrug and toxic extrusion 1 (MATE1) on proximal renal tubular cells; metformin is a MATE1 substrate. Inhibition of MATE1 by cobicistat may decrease metformin eliminiation by blocking renal tubular secretion. If these drugs are given together, closely monitor for signs of metformin toxicity; metformin dose adjustments may be needed. [28550] [51664] [58763] Emtricitabine: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Drugs that are eliminated by renal tubular secretion, such as emtricitabine, may decrease metformin elimination by competing for common renal tubular transport systems. Although such interactions remain theoretical, careful patient monitoring and dose adjustment of metformin and/or the interfering cationic drug are recommended. [28550] Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Drugs that are eliminated by renal tubular secretion, such as emtricitabine, may decrease metformin elimination by competing for common renal tubular transport systems. Although such interactions remain theoretical, careful patient monitoring and dose adjustment of metformin and/or the interfering cationic drug are recommended. [28550] Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Drugs that are eliminated by renal tubular secretion, such as emtricitabine, may decrease metformin elimination by competing for common renal tubular transport systems. Although such interactions remain theoretical, careful patient monitoring and dose adjustment of metformin and/or the interfering cationic drug are recommended. [28550] (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Drugs that are eliminated by renal tubular secretion, such as tenofovir, PMPA may decrease metformin elimination by competing for common renal tubular transport systems. Although such interactions remain theoretical, careful patient monitoring and dose adjustment of metformin and/or the interfering cationic drug are recommended. [28193] [28550] Emtricitabine; Tenofovir alafenamide: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Drugs that are eliminated by renal tubular secretion, such as emtricitabine, may decrease metformin elimination by competing for common renal tubular transport systems. Although such interactions remain theoretical, careful patient monitoring and dose adjustment of metformin and/or the interfering cationic drug are recommended. [28550] Emtricitabine; Tenofovir disoproxil fumarate: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Drugs that are eliminated by renal tubular secretion, such as emtricitabine, may decrease metformin elimination by competing for common renal tubular transport systems. Although such interactions remain theoretical, careful patient monitoring and dose adjustment of metformin and/or the interfering cationic drug are recommended. [28550] (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Drugs that are eliminated by renal tubular secretion, such as tenofovir, PMPA may decrease metformin elimination by competing for common renal tubular transport systems. Although such interactions remain theoretical, careful patient monitoring and dose adjustment of metformin and/or the interfering cationic drug are recommended. [28193] [28550] Enalapril, Enalaprilat: (Moderate) Angiotensin-converting enzyme (ACE) inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. ACE inhibitors may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [29403] [30585] [33489] [42591] Enalapril; Felodipine: (Moderate) Angiotensin-converting enzyme (ACE) inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. ACE inhibitors may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [29403] [30585] [33489] [42591] Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Angiotensin-converting enzyme (ACE) inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. ACE inhibitors may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [29403] [30585] [33489] [42591] (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Entecavir: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion (e.g., entecavir) may decrease metformin elimination by competing for common renal tubular transport systems. Although such interactions remain theoretical, careful patient monitoring and dose adjustment of metformin and/or the interfering cationic drug are recommended. [28550] [31230] Ephedrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Ephedrine; Guaifenesin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Eprosartan: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Erdafitinib: (Moderate) Consider the benefits and risks of concomitant treatment with metformin and erdafitinib. Metformin is a substrate of organic cationic transporter-2 (OCT2). Erdafitinib is an OCT2 inhibitor. Coadministration with OCT2 inhibitors could increase systemic exposure to metformin and increase the risk for lactic acidosis. [28550] [56579] [64064] Erythromycin; Sulfisoxazole: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. Patients at risk include those with compromised renal function, those fasting for prolonged periods, those that are malnourished, and those receiving high or excessive doses of sulfonamides. [29536] [30585] [30623] [32166] Esterified Estrogens: (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] Esterified Estrogens; Methyltestosterone: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together. [33919] [33920] [33921] [33922] [33923] [33924] (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] Estradiol Cypionate; Medroxyprogesterone: (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] (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] Estradiol: (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] Estradiol; Levonorgestrel: (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] (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] Estradiol; Norethindrone: (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] (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] Estradiol; Norgestimate: (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] (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] Estradiol; Progesterone: (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] (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] Estramustine: (Minor) Estramustine should be used cautiously in patients receiving metformin. Patients should routinely monitor their blood glucose as indicated. Estramustine may decrease glucose tolerance leading to hyperglycemia. [28072] Estrogens: (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] Estropipate: (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] Ethacrynic Acid: (Moderate) Loop diuretics can decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations.Patients receiving antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. [28429] [28620] [40390] Ethanol: (Moderate) Patients taking metformin should be advised to limit their use of alcohol. Blood lactate concentrations and the lactate to pyruvate ratio are increased during excessive (acute or chronic) intake of alcohol with metformin. Elevated lactic acid concentrations are associated with increased morbidity rates as the risk for lactic acidosis is increased. In patients with diabetes, alcohol intake can also cause hypoglycemia or worsen glycemic control as it provides a source of additional calories. Many non-prescription drug products may be formulated with alcohol; have patients scrutinize product labels prior to consumption. [28550] [30488] [62853] Ethinyl Estradiol: (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Minor) Levomefolate and metformin should be used together cautiously. Plasma concentrations of levomefolate may be reduced during treatment of type 2 diabetes with metformin. Monitor patients for decreased efficacy of levomefolate if these agents are used together. [35581] (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] (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] Ethinyl Estradiol; Norelgestromin: (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] (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] Ethinyl Estradiol; Norethindrone Acetate: (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] (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] Ethinyl Estradiol; Norgestrel: (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] (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] Ethotoin: (Minor) Ethotoin and other hydantoins have the potential to increase blood glucose and thus interact with antidiabetic agents pharmacodynamically. Monitor blood glucose for changes in glycemic control. Dosage adjustments may be necessary in some patients. [23813] [28550] Ethynodiol Diacetate; Ethinyl Estradiol: (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] (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] Etonogestrel: (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] Etonogestrel; Ethinyl Estradiol: (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] (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] Famotidine: (Minor) Famotidine may decrease the renal clearance of metformin secondary to competition for renal tubular transport systems. Such an interaction has been observed when cimetidine was administered with metformin. The decrease in renal excretion led to a 40% increase in metformin AUC. Although interactions with cationic drugs remain theoretical (except for cimetidine), caution is warranted when famotidine and metformin are prescribed concurrently. Famotidine may be less likely to interact with metformin versus cimetidine or ranitidine because of less tubular excretion. [7775] Famotidine; Ibuprofen: (Minor) Famotidine may decrease the renal clearance of metformin secondary to competition for renal tubular transport systems. Such an interaction has been observed when cimetidine was administered with metformin. The decrease in renal excretion led to a 40% increase in metformin AUC. Although interactions with cationic drugs remain theoretical (except for cimetidine), caution is warranted when famotidine and metformin are prescribed concurrently. Famotidine may be less likely to interact with metformin versus cimetidine or ranitidine because of less tubular excretion. [7775] Fenofibrate: (Moderate) Dose reductions and increased frequency of glucose monitoring may be required when antidiabetic agents are administered with fibric acid derivatives (e.g., clofibrate, fenofibric acid, fenofibrate, gemfibrozil). Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. [30585] [62853] Fenofibric Acid: (Moderate) Dose reductions and increased frequency of glucose monitoring may be required when antidiabetic agents are administered with fibric acid derivatives (e.g., clofibrate, fenofibric acid, fenofibrate, gemfibrozil). Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. [30585] [62853] Fexofenadine; Pseudoephedrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Fibric acid derivatives: (Moderate) Dose reductions and increased frequency of glucose monitoring may be required when antidiabetic agents are administered with fibric acid derivatives (e.g., clofibrate, fenofibric acid, fenofibrate, gemfibrozil). Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. [30585] [62853] Fluoxetine: (Moderate) In patients with diabetes mellitus, fluoxetine may alter glycemic control. Hypoglycemia has occurred during fluoxetine therapy. Hyperglycemia has developed in patients with diabetes mellitus following discontinuation of the drug. The dosage of insulin and/or other antidiabetic agents may need to be adjusted when therapy with fluoxetine is instituted or discontinued. [30585] [32127] [44058] [44059] Fluoxymesterone: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together. [33919] [33920] [33921] [33922] [33923] [33924] Fosinopril: (Moderate) Angiotensin-converting enzyme (ACE) inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. ACE inhibitors may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [29403] [30585] [33489] [42591] Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Angiotensin-converting enzyme (ACE) inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. ACE inhibitors may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [29403] [30585] [33489] [42591] (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Fosphenytoin: (Minor) Fosphenytoin and other hydantoins have the potential to increase blood glucose and thus interact with antidiabetic agents pharmacodynamically. Monitor blood glucose for changes in glycemic control. Dosage adjustments may be necessary in some patients. [23813] [28550] Furosemide: (Minor) Furosemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. [28429] [28550] Garlic, Allium sativum: (Moderate) Patients receiving antidiabetic agents should use dietary supplements of Garlic, Allium sativum with caution. Constituents in garlic might have some antidiabetic activity, and may increase serum insulin levels and increase glycogen storage in the liver. Monitor blood glucose and glycemic control. Patients with diabetes should inform their health care professionals of their intent to ingest garlic dietary supplements. Some patients may require adjustment to their hypoglycemic medications over time. One study stated that additional garlic supplementation (0.05 to 1.5 grams PO per day) contributed to improved blood glucose control in patients with type 2 diabetes mellitus within 1 to 2 weeks, and had positive effects on total cholesterol and high/low density lipoprotein regulation over time. It is unclear if hemoglobin A1C is improved or if improvements are sustained with continued treatment beyond 24 weeks. Other reviews suggest that garlic may provide modest improvements in blood lipids, but few studies demonstrate decreases in blood glucose in diabetic and non-diabetic patients. More controlled trials are needed to discern if garlic has an effect on blood glucose in patients with diabetes. When garlic is used in foods or as a seasoning, or at doses of 50 mg/day or less, it is unlikely that blood glucose levels are affected to any clinically significant degree. [28464] [28465] [28466] [57571] [63042] [63043] Gemfibrozil: (Moderate) Dose reductions and increased frequency of glucose monitoring may be required when antidiabetic agents are administered with fibric acid derivatives (e.g., clofibrate, fenofibric acid, fenofibrate, gemfibrozil). Fibric acid derivatives may enhance the hypoglycemic effects of antidiabetic agents through increased insulin sensitivity and decreased glucagon secretion. [30585] [62853] Glecaprevir; Pibrentasvir: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. [62201] (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir. [62201] Glimepiride: (Moderate) Use of metformin with a sulfonylurea may increase the risk of hypoglycemia. Sulfonylureas are known to cause hypoglycemia. To manage hypoglycemic risk, lower doses of the sulfonylurea may be needed. Monitor blood sugar. [28550] Glimepiride; Rosiglitazone: (Moderate) Use of metformin with a sulfonylurea may increase the risk of hypoglycemia. Sulfonylureas are known to cause hypoglycemia. To manage hypoglycemic risk, lower doses of the sulfonylurea may be needed. Monitor blood sugar. [28550] Glipizide: (Moderate) Use of metformin with a sulfonylurea may increase the risk of hypoglycemia. Sulfonylureas are known to cause hypoglycemia. To manage hypoglycemic risk, lower doses of the sulfonylurea may be needed. Monitor blood sugar. [28550] Glipizide; Metformin: (Moderate) Use of metformin with a sulfonylurea may increase the risk of hypoglycemia. Sulfonylureas are known to cause hypoglycemia. To manage hypoglycemic risk, lower doses of the sulfonylurea may be needed. Monitor blood sugar. [28550] Glyburide: (Moderate) Use of metformin with a sulfonylurea may increase the risk of hypoglycemia. Sulfonylureas are known to cause hypoglycemia. To manage hypoglycemic risk, lower doses of the sulfonylurea may be needed. Monitor blood sugar. [28550] Glyburide; Metformin: (Moderate) Use of metformin with a sulfonylurea may increase the risk of hypoglycemia. Sulfonylureas are known to cause hypoglycemia. To manage hypoglycemic risk, lower doses of the sulfonylurea may be needed. Monitor blood sugar. [28550] Glycopyrrolate: (Moderate) Coadministration of glycopyrrolate with metformin my increase metformin plasma concentrations, which may lead to increased metformin effects and possible adverse events. If coadministration is necessary, monitor clinical response to metformin and adjust metformin dose accordingly. [41489] Glycopyrrolate; Formoterol: (Moderate) Coadministration of glycopyrrolate with metformin my increase metformin plasma concentrations, which may lead to increased metformin effects and possible adverse events. If coadministration is necessary, monitor clinical response to metformin and adjust metformin dose accordingly. [41489] Green Tea: (Moderate) Green tea catechins have been shown to decrease serum glucose concentrations in vitro. Patients with diabetes mellitus taking antidiabetic agents should be monitored closely for hypoglycemia if consuming green tea products. [29904] [29905] Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Guaifenesin; Phenylephrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Hydralazine; Hydrochlorothiazide, HCTZ: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Hydrochlorothiazide, HCTZ: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Angiotensin-converting enzyme (ACE) inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. ACE inhibitors may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [29403] [30585] [33489] [42591] (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Hydrocodone; Phenylephrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Hydrocodone; Pseudoephedrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Hydroxychloroquine: (Moderate) Careful monitoring of blood glucose is recommended when hydroxychloroquine and antidiabetic agents, including metformin, are coadministered. A decreased dose of the antidiabetic agent may be necessary as severe hypoglycemia has been reported in patients treated concomitantly with hydroxychloroquine and an antidiabetic agent. [41806] Hydroxyprogesterone: (Minor) Progestins, like hydroxyprogesterone, 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] [43316] [62853] [62893] Ibuprofen; Pseudoephedrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Indacaterol; Glycopyrrolate: (Moderate) Coadministration of glycopyrrolate with metformin my increase metformin plasma concentrations, which may lead to increased metformin effects and possible adverse events. If coadministration is necessary, monitor clinical response to metformin and adjust metformin dose accordingly. [41489] Indapamide: (Moderate) A potential pharmacodynamic interaction exists between indapamide and antidiabetic agents, like metformin. Indapamide can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. [29403] [48959] Insulin Aspart: (Moderate) Coadministration of metformin with an insulin may increase the risk of hypoglycemia. Insulins are known to cause hypoglycemia. To manage hypoglycemic risk, lower doses of insulin may be needed. Monitor blood sugar and adjust insulin dosage as clinically indicated. [28550] Insulin Aspart; Insulin Aspart Protamine: (Moderate) Coadministration of metformin with an insulin may increase the risk of hypoglycemia. Insulins are known to cause hypoglycemia. To manage hypoglycemic risk, lower doses of insulin may be needed. Monitor blood sugar and adjust insulin dosage as clinically indicated. [28550] Insulin Degludec: (Moderate) Coadministration of metformin with an insulin may increase the risk of hypoglycemia. Insulins are known to cause hypoglycemia. To manage hypoglycemic risk, lower doses of insulin may be needed. Monitor blood sugar and adjust insulin dosage as clinically indicated. [28550] Insulin Degludec; Liraglutide: (Moderate) Coadministration of metformin with an insulin may increase the risk of hypoglycemia. Insulins are known to cause hypoglycemia. To manage hypoglycemic risk, lower doses of insulin may be needed. Monitor blood sugar and adjust insulin dosage as clinically indicated. [28550] Insulin Detemir: (Moderate) Coadministration of metformin with an insulin may increase the risk of hypoglycemia. Insulins are known to cause hypoglycemia. To manage hypoglycemic risk, lower doses of insulin may be needed. Monitor blood sugar and adjust insulin dosage as clinically indicated. [28550] Insulin Glargine: (Moderate) Coadministration of metformin with an insulin may increase the risk of hypoglycemia. Insulins are known to cause hypoglycemia. To manage hypoglycemic risk, lower doses of insulin may be needed. Monitor blood sugar and adjust insulin dosage as clinically indicated. [28550] Insulin Glargine; Lixisenatide: (Moderate) Coadministration of metformin with an insulin may increase the risk of hypoglycemia. Insulins are known to cause hypoglycemia. To manage hypoglycemic risk, lower doses of insulin may be needed. Monitor blood sugar and adjust insulin dosage as clinically indicated. [28550] Insulin Glulisine: (Moderate) Coadministration of metformin with an insulin may increase the risk of hypoglycemia. Insulins are known to cause hypoglycemia. To manage hypoglycemic risk, lower doses of insulin may be needed. Monitor blood sugar and adjust insulin dosage as clinically indicated. [28550] Insulin Lispro: (Moderate) Coadministration of metformin with an insulin may increase the risk of hypoglycemia. Insulins are known to cause hypoglycemia. To manage hypoglycemic risk, lower doses of insulin may be needed. Monitor blood sugar and adjust insulin dosage as clinically indicated. [28550] Insulin Lispro; Insulin Lispro Protamine: (Moderate) Coadministration of metformin with an insulin may increase the risk of hypoglycemia. Insulins are known to cause hypoglycemia. To manage hypoglycemic risk, lower doses of insulin may be needed. Monitor blood sugar and adjust insulin dosage as clinically indicated. [28550] Insulin, Inhaled: (Moderate) Coadministration of metformin with an insulin may increase the risk of hypoglycemia. Insulins are known to cause hypoglycemia. To manage hypoglycemic risk, lower doses of insulin may be needed. Monitor blood sugar and adjust insulin dosage as clinically indicated. [28550] Insulins: (Moderate) Coadministration of metformin with an insulin may increase the risk of hypoglycemia. Insulins are known to cause hypoglycemia. To manage hypoglycemic risk, lower doses of insulin may be needed. Monitor blood sugar and adjust insulin dosage as clinically indicated. [28550] Iodipamide Meglumine: (Contraindicated) Metformin and combination products containing metformin should be temporarily discontinued prior to the administration of iodinated contrast media. Metformin should be held for at least 48 hours after contrast administration and not restarted until renal function returns to normal post-procedure. Lactic acidosis has been reported in patients taking metformin that experience nephrotoxicity after use of iodinated contrast media. [28550] Ionic Contrast Media: (Contraindicated) Metformin and combination products containing metformin should be temporarily discontinued prior to the administration of iodinated contrast media. Metformin should be held for at least 48 hours after contrast administration and not restarted until renal function returns to normal post-procedure. Lactic acidosis has been reported in patients taking metformin that experience nephrotoxicity after use of iodinated contrast media. [28550] Ioxaglate Meglumine; Ioxaglate Sodium: (Contraindicated) Metformin and combination products containing metformin should be temporarily discontinued prior to the administration of iodinated contrast media. Metformin should be held for at least 48 hours after contrast administration and not restarted until renal function returns to normal post-procedure. Lactic acidosis has been reported in patients taking metformin that experience nephrotoxicity after use of iodinated contrast media. [28550] Irbesartan: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Isophane Insulin (NPH): (Moderate) Coadministration of metformin with an insulin may increase the risk of hypoglycemia. Insulins are known to cause hypoglycemia. To manage hypoglycemic risk, lower doses of insulin may be needed. Monitor blood sugar and adjust insulin dosage as clinically indicated. [28550] Lamivudine, 3TC: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems. [28550] [29240] Lamivudine, 3TC; Zidovudine, ZDV: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems. [28550] [29240] Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems. [28550] [29240] (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Drugs that are eliminated by renal tubular secretion, such as tenofovir, PMPA may decrease metformin elimination by competing for common renal tubular transport systems. Although such interactions remain theoretical, careful patient monitoring and dose adjustment of metformin and/or the interfering cationic drug are recommended. [28193] [28550] Lamotrigine: (Moderate) Coadministration of metformin and lamotrigine may decrease metformin clearance, resulting in increased plasma concentrations and the potential for adverse events, including a risk for lactic acidosis. Lamotrigine is an inhibitor of renal tubular secretion via organic cationic transporter 2 (OCT2) proteins, and metformin is excreted via this route. [28451] [28550] [56579] Lanreotide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia. [33519] Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) The concomitant use of clarithromycin and antidiabetic agents can result in significant hypoglycemia. Careful monitoring of blood glucose is recommended. [28238] Ledipasvir; Sofosbuvir: (Moderate) Closely monitor blood glucose levels if ledipasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agent(s) may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as ledipasvir. [56528] [58167] (Moderate) Closely monitor blood glucose levels if sofosbuvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as sofosbuvir. [56528] Lente Insulin: (Moderate) Coadministration of metformin with an insulin may increase the risk of hypoglycemia. Insulins are known to cause hypoglycemia. To manage hypoglycemic risk, lower doses of insulin may be needed. Monitor blood sugar and adjust insulin dosage as clinically indicated. [28550] Leuprolide; Norethindrone: (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] Levomefolate: (Minor) Levomefolate and metformin should be used together cautiously. Plasma concentrations of levomefolate may be reduced during treatment of type 2 diabetes with metformin. Monitor patients for decreased efficacy of levomefolate if these agents are used together. [35581] Levonorgestrel: (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] Levonorgestrel; Ethinyl Estradiol: (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] (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] Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] (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] Levothyroxine: (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin. [28550] [30585] Levothyroxine; Liothyronine (Porcine): (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin. [28550] [30585] Levothyroxine; Liothyronine (Synthetic): (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin. [28550] [30585] Linezolid: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents. [28599] Liothyronine: (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin. [28550] [30585] Lisdexamfetamine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Lisinopril: (Moderate) Angiotensin-converting enzyme (ACE) inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. ACE inhibitors may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [29403] [30585] [33489] [42591] Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Angiotensin-converting enzyme (ACE) inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. ACE inhibitors may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [29403] [30585] [33489] [42591] (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Lithium: (Moderate) Lithium may cause variable effects on glycemic control when used in patients receiving antidiabetic agents. Monitor blood glucose concentrations closely if lithium is coadministered with antidiabetic agents. Dosage adjustments of antidiabetic agents may be necessary. [29403] [30466] [30585] Loratadine; Pseudoephedrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Lorcaserin: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin. [51065] Losartan: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Lovastatin; Niacin: (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary. [28550] [43933] Mecasermin rinfabate: (Moderate) Use caution in combining mecasermin, recombinant, rh-IGF-1 or mecasermin rinfabate (rh-IGF-1/rh-IGFBP-3) with antidiabetic agents. Patients should be advised to eat within 20 minutes of mecasermin administration. Glucose monitoring is important when initializing or adjusting mecasermin therapies, when adjusting concomitant antidiabetic therapy, and in the event of hypoglycemic symptoms. An increased risk for hypoglycemia is possible. The hypoglycemic effect induced by IGF-1 activity may be exacerbated. The amino acid sequence of mecasermin (rh-IGF-1) is approximately 50 percent homologous to insulin and cross binding with either receptor is possible. Treatment with mecasermin has been shown to improve insulin sensitivity and to improve glycemic control in patients with either Type 1 or Type 2 diabetes mellitus when used alone or in conjunction with insulins. [31516] [31524] [31821] Mecasermin, Recombinant, rh-IGF-1: (Moderate) Use caution in combining mecasermin, recombinant, rh-IGF-1 or mecasermin rinfabate (rh-IGF-1/rh-IGFBP-3) with antidiabetic agents. Patients should be advised to eat within 20 minutes of mecasermin administration. Glucose monitoring is important when initializing or adjusting mecasermin therapies, when adjusting concomitant antidiabetic therapy, and in the event of hypoglycemic symptoms. An increased risk for hypoglycemia is possible. The hypoglycemic effect induced by IGF-1 activity may be exacerbated. The amino acid sequence of mecasermin (rh-IGF-1) is approximately 50 percent homologous to insulin and cross binding with either receptor is possible. Treatment with mecasermin has been shown to improve insulin sensitivity and to improve glycemic control in patients with either Type 1 or Type 2 diabetes mellitus when used alone or in conjunction with insulins. [31516] [31524] [31821] Medroxyprogesterone: (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] Meglitinides: (Moderate) Use of metformin with a meglitinide ("glinide") may increase the risk of hypoglycemia. Meglitinides are insulin secretagogues and are known to cause hypoglycemia. To manage hypoglycemic risk, lower doses of the meglitinide may be needed. Monitor blood sugar. [28550] Memantine: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Drugs that are eliminated by renal tubular secretion (e.g., memantine) may decrease metformin elimination by competing for common renal tubular transport systems. It should be noted that in a pharmacokinetic study in which memantine and glyburide; metformin (Glucovance) were coadministered, the pharmacokinetics of memantine, metformin, or glyburide were not altered. Regardless, careful patient monitoring is recommended. [31418] [5280] Mestranol; Norethindrone: (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] (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: (Moderate) Use of metformin with a meglitinide ("glinide") may increase the risk of hypoglycemia. Meglitinides are insulin secretagogues and are known to cause hypoglycemia. To manage hypoglycemic risk, lower doses of the meglitinide may be needed. Monitor blood sugar. [28550] Methamphetamine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Methazolamide: (Moderate) Carbonic anhydrase inhibitors such as methazolamide frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of methazolamide with metformin may increase the risk for lactic acidosis; consider more frequent monitoring. Carbonic anhydrase inhibitors may also alter blood sugar; both hyperglycemia and hypoglycemia have been described. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction. [28294] [28550] Methyclothiazide: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Methyltestosterone: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together. [33919] [33920] [33921] [33922] [33923] [33924] Metolazone: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Metyrapone: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified. [33528] Midodrine: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, like midodrine, may decrease metformin elimination by competing for common renal tubular transport systems. Careful patient monitoring and dose adjustment of metformin and/or midodrine is recommended. [29241] Moexipril: (Moderate) Angiotensin-converting enzyme (ACE) inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. ACE inhibitors may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [29403] [30585] [33489] [42591] Monoamine oxidase inhibitors: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including metformin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents. [30585] [59433] Nandrolone Decanoate: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together. [33919] [33920] [33921] [33922] [33923] [33924] Naproxen; Pseudoephedrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Nateglinide: (Moderate) Use of metformin with a meglitinide ("glinide") may increase the risk of hypoglycemia. Meglitinides are insulin secretagogues and are known to cause hypoglycemia. To manage hypoglycemic risk, lower doses of the meglitinide may be needed. Monitor blood sugar. [28550] Nebivolol; Valsartan: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] Niacin, Niacinamide: (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary. [28550] [43933] Niacin; Simvastatin: (Moderate) Niacin interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin is added or deleted to the medication regimen. Dosage adjustments may be necessary. [28550] [43933] Nicotine: (Minor) Blood glucose concentrations should be monitored more closely whenever a change in either nicotine intake or smoking status occurs; dosage adjustments of metformin may be needed. Nicotine may increase plasma glucose; tobacco smoking is known to aggravate insulin resistance. The cessation of nicotine therapy or tobacco smoking may result in a decrease in blood glucose. [29535] Nifedipine: (Minor) Nifedipine may increase the plasma metformin Cmax and AUC and increase the amount of metformin excreted in the urine. Metformin half-life is unaffected. Nifedipine appears to enhance the absorption of metformin. [5280] Non-Ionic Contrast Media: (Major) Discontinue metformin at the time of, or before, administration of non-ionic contrast media to patients with an eGFR of 30 to 60 mL/minute/1.73 m2, history of liver disease, alcoholism, or heart failure, or who will be administered intra-arterial iodinated contrast. Reevaluate eGFR 48 hours after the imaging procedure; restart metformin if renal function is stable. Iodinated contrast agents appear to increase the risk of metformin-induced lactic acidosis, possibly as a result of worsening renal function. [28550] [28963] [49612] Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] (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] Norethindrone: (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] Norethindrone; Ethinyl Estradiol: (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] (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] Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] (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] Norgestimate; Ethinyl Estradiol: (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] (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] Norgestrel: (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] Octreotide: (Moderate) Monitor patients receiving octreotide concomitantly with insulin or other antidiabetic agents for changes in glycemic control and adjust doses of these medications accordingly. Octreotide alters the balance between the counter-regulatory hormones of insulin, glucagon, and growth hormone, which may result in hypoglycemia or hyperglycemia. The hypoglycemia or hyperglycemia which occurs during octreotide acetate therapy is usually mild but may result in overt diabetes mellitus or necessitate dose changes in insulin or other hypoglycemic agents. In patients with concomitant type1 diabetes mellitus, octreotide is likely to affect glucose regulation, and insulin requirements may be reduced. Symptomatic hypoglycemia, which may be severe, has been reported in type 1 diabetic patients. In Type 2 diabetes patients with partially intact insulin reserves, octreotide administration may result in decreases in plasma insulin levels and hyperglycemia. [29113] [51310] Olanzapine; Fluoxetine: (Moderate) In patients with diabetes mellitus, fluoxetine may alter glycemic control. Hypoglycemia has occurred during fluoxetine therapy. Hyperglycemia has developed in patients with diabetes mellitus following discontinuation of the drug. The dosage of insulin and/or other antidiabetic agents may need to be adjusted when therapy with fluoxetine is instituted or discontinued. [30585] [32127] [44058] [44059] Olmesartan: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Ombitasvir; Paritaprevir; Ritonavir: (Major) While no dosage adjustment of metformin is recommended in patients with normal hepatic or renal function, careful patient monitoring and dose adjustment of metformin and/or the potentially interfering drug is recommended with concurrent use. Monitor for signs of onset of lactic acidosis such as respiratory distress, somnolence, and non-specific abdominal distress or worsening renal function. Do not use metformin with paritaprevir in patients with renal insufficiency or hepatic impairment. Drugs that interfere with common renal tubular transport systems involved in the renal elimination of metformin could increase systemic exposure to metformin and may increase the risk for lactic acidosis. Paritaprevir is an inhibitor of the organic anion transporters OATP1B1 and OATP1B3. While initial drug-drug interaction studies of paritaprevir-containing hepatitis treatments have not noted an effect on metformin concentrations, more study is needed. [28550] [58664] [60002] [61023] Orlistat: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated. [25616] [27971] [60877] [62881] Oxandrolone: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together. [33919] [33920] [33921] [33922] [33923] [33924] Oxymetholone: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together. [33919] [33920] [33921] [33922] [33923] [33924] Pasireotide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia. [52611] [58639] Pegvisomant: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pegvisomant treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pegvisomant increases sensitivity to insulin by lowering the activity of growth hormone, and in some patients glucose tolerance improves with treatment. Patients with diabetes treated with pegvisomant and antidiabetic agents may be more likely to experience hypoglycemia. [51250] Pentamidine: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine. [28879] Pentoxifylline: (Moderate) Pentoxiphylline has been used concurrently with antidiabetic agents without observed problems, but it may enhance the hypoglycemic action of antidiabetic agents. Patients should be monitored for changes in glycemic control while receiving pentoxifylline in combination with antidiabetic agents. [6316] [7238] Perindopril: (Moderate) Angiotensin-converting enzyme (ACE) inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. ACE inhibitors may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [29403] [30585] [33489] [42591] Perindopril; Amlodipine: (Moderate) Angiotensin-converting enzyme (ACE) inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. ACE inhibitors may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [29403] [30585] [33489] [42591] Phenothiazines: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. When such drugs are administered to a patient receiving metformin, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin, observe the patient closely for hypoglycemia. [28550] [28915] [30575] Phentermine; Topiramate: (Major) Extended-release topiramate is contraindicated in patients with metabolic acidosis who are taking concomitant metformin because topiramate can frequently cause metabolic acidosis, a condition for which metformin use is contraindicated. Consider more frequent monitoring of patients taking immediate-release topiramate with metformin. In healthy volunteers, metformin Cmax and AUC increased by 17% and 25%, respectively, when topiramate was added, and oral plasma clearance of topiramate appears to be reduced when administered with metformin. However, the clinical significance of these pharmacokinetic effects is unclear. [28378] [28550] [55675] Phenylephrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Phenytoin: (Minor) Phenytoin and other hydantoins have the potential to increase blood glucose and thus interact with antidiabetic agents pharmacodynamically. Monitor blood glucose for changes in glycemic control. Dosage adjustments may be necessary in some patients. [23813] [28550] Pioglitazone; Glimepiride: (Moderate) Use of metformin with a sulfonylurea may increase the risk of hypoglycemia. Sulfonylureas are known to cause hypoglycemia. To manage hypoglycemic risk, lower doses of the sulfonylurea may be needed. Monitor blood sugar. [28550] Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements): (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together. [33919] [33920] [33921] [33922] [33923] [33924] Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved): (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together. [33919] [33920] [33921] [33922] [33923] [33924] Progesterone: (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] Progestins: (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] Promethazine; Phenylephrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Propantheline: (Moderate) Propantheline slows GI motility, which may increase the absorption of metformin from the small intestine. A 19% increase in metformin AUC has been reported in studies of this interaction in healthy volunteers. However, no serious side effects resulted. [29539] Propoxyphene: (Moderate) Propoxyphene may enhance the hypoglycemic action of antidiabetic agents. Patients should be closely monitored for changes in glycemic control while receiving propoxyphene in combination with antidiabetic agents. [7224] Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Protease inhibitors: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Another possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients taking antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. [30480] [30575] Pseudoephedrine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Pseudoephedrine; Triprolidine: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Pyrimethamine; Sulfadoxine: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. Patients at risk include those with compromised renal function, those fasting for prolonged periods, those that are malnourished, and those receiving high or excessive doses of sulfonamides. [29536] [30585] [30623] [32166] Quinapril: (Moderate) Angiotensin-converting enzyme (ACE) inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. ACE inhibitors may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [29403] [30585] [33489] [42591] Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Angiotensin-converting enzyme (ACE) inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. ACE inhibitors may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [29403] [30585] [33489] [42591] (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Quinolones: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including metformin, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur. [28423] [28424] [43411] [62028] [65562] Ramipril: (Moderate) Angiotensin-converting enzyme (ACE) inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. ACE inhibitors may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [29403] [30585] [33489] [42591] Ranolazine: (Major) Limit the dose of metformin to 1,700 mg/day in adults if coadministered with ranolazine 1,000 mg twice daily. Coadministration of metformin with ranolazine 1,000 mg twice daily results in increased exposure to metformin. There is potential for an increased risk for lactic acidosis, which is associated with high metformin concentrations. Doses of metformin do not require reduction if coadministered with ranolazine 500 mg twice daily, as metformin exposure was not significantly increased with this lower dose of ranolazine. Ranolazine inhibits common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2]/multidrug and toxin extrusion [MATE1 and MATE2k]). Consider the benefits and risks of concomitant use of ranolazine with metformin. Monitor blood sugar and for gastrointestinal side effects, and increase monitoring for a risk for lactic acidosis, including renal function and electrolytes/acid-base balance. [28550] [31938] Regular Insulin: (Moderate) Coadministration of metformin with an insulin may increase the risk of hypoglycemia. Insulins are known to cause hypoglycemia. To manage hypoglycemic risk, lower doses of insulin may be needed. Monitor blood sugar and adjust insulin dosage as clinically indicated. [28550] Regular Insulin; Isophane Insulin (NPH): (Moderate) Coadministration of metformin with an insulin may increase the risk of hypoglycemia. Insulins are known to cause hypoglycemia. To manage hypoglycemic risk, lower doses of insulin may be needed. Monitor blood sugar and adjust insulin dosage as clinically indicated. [28550] Relugolix; Estradiol; Norethindrone acetate: (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] (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] Repaglinide: (Moderate) Use of metformin with a meglitinide ("glinide") may increase the risk of hypoglycemia. Meglitinides are insulin secretagogues and are known to cause hypoglycemia. To manage hypoglycemic risk, lower doses of the meglitinide may be needed. Monitor blood sugar. [28550] Reserpine: (Moderate) Reserpine may mask the signs and symptoms of hypoglycemia. Patients receiving these drugs concomitantly should be monitored for changes in glycemic control. [30466] Risdiplam: (Moderate) Concomitant administration of metformin and risdiplam may increase metformin exposure and increase the risk for lactic acidosis. If these drugs are given together, monitor for signs of metformin toxicity; metformin dose adjustments may be needed. Metformin is a human multidrug and toxic extrusion 1 (MATE1) substrate and risdiplam is a an MATE1/2-K inhibitor. MATE inhibitors may decrease metformin elimination by blocking renal tubular secretion. [28550] [65815] Sacubitril; Valsartan: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] Salicylates: (Moderate) Large doses of salicylates may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis. If these agents are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. [29403] Segesterone Acetate; Ethinyl Estradiol: (Minor) Monitor blood glucose periodically in patients on metformin for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. [28550] [30585] [62853] (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] Sofosbuvir: (Moderate) Closely monitor blood glucose levels if sofosbuvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as sofosbuvir. [56528] Sofosbuvir; Velpatasvir: (Moderate) Closely monitor blood glucose levels if sofosbuvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as sofosbuvir. [56528] (Moderate) Closely monitor blood glucose levels if velpatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as velpatasvir. [56528] [60911] Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Closely monitor blood glucose levels if sofosbuvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as sofosbuvir. [56528] (Moderate) Closely monitor blood glucose levels if velpatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as velpatasvir. [56528] [60911] (Moderate) Closely monitor blood glucose levels if voxilaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as voxilaprevir. [62131] Somatropin, rh-GH: (Moderate) Patients with diabetes mellitus should be monitored closely during somatropin (recombinant rhGH) therapy. Antidiabetic drugs (e.g., insulin or oral agents) may require adjustment when somatropin therapy is instituted in these patients. Growth hormones, such as somatropin, may decrease insulin sensitivity, leading to glucose intolerance and loss of blood glucose control. Therefore, glucose levels should be monitored periodically in all patients treated with somatropin, especially in those with risk factors for diabetes mellitus. [30059] [33527] [45044] [45045] [49770] [56647] [56648] [56649] [56650] [56651] [58095] [58096] [59579] [60682] Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Sulfadiazine: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. Patients at risk include those with compromised renal function, those fasting for prolonged periods, those that are malnourished, and those receiving high or excessive doses of sulfonamides. [29536] [30585] [30623] [32166] Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. Patients at risk include those with compromised renal function, those fasting for prolonged periods, those that are malnourished, and those receiving high or excessive doses of sulfonamides. [29536] [30585] [30623] [32166] Sulfasalazine: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. Patients at risk include those with compromised renal function, those fasting for prolonged periods, those that are malnourished, and those receiving high or excessive doses of sulfonamides. [29536] [30585] [30623] [32166] Sulfisoxazole: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. Patients at risk include those with compromised renal function, those fasting for prolonged periods, those that are malnourished, and those receiving high or excessive doses of sulfonamides. [29536] [30585] [30623] [32166] Sulfonamides: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. Patients at risk include those with compromised renal function, those fasting for prolonged periods, those that are malnourished, and those receiving high or excessive doses of sulfonamides. [29536] [30585] [30623] [32166] Sulfonylureas: (Moderate) Use of metformin with a sulfonylurea may increase the risk of hypoglycemia. Sulfonylureas are known to cause hypoglycemia. To manage hypoglycemic risk, lower doses of the sulfonylurea may be needed. Monitor blood sugar. [28550] Tacrolimus: (Moderate) Tacrolimus has been reported to cause hyperglycemia. Furthermore, tacrolimus has been implicated in causing insulin-dependent diabetes mellitus in patients after renal transplantation. Tacrolimus may have direct beta-cell toxicity. Patients should be monitored for worsening of glycemic control if Tacrolimus is initiated in patients receiving antidiabetic agents. [30576] [30585] Tafenoquine: (Moderate) Consider the benefits and risks of coadministration of tafenoquine and metformin due to the potential for increased metformin concentrations and lactic acidosis. If coadministration cannot be avoided, monitor for metformin-related toxicities, and consider metformin dosage reduction, if needed. The effect of coadministration of tafenoquine on the pharmacokinetics of OCT2 and MATE substrates, like metformin, in humans is unknown; however, in vitro observations suggest the potential for increased concentrations of OCT2 and MATE substrates. Tafenoquine may interfere with these common renal tubular transport systems involved in the renal elimination of metformin. [28550] [56579] [63373] Tegaserod: (Moderate) Because tegaserod can enhance gastric emptying in diabetic patients, blood glucose can be affected, which, in turn, may affect the clinical response to antidiabetic agents. The dosing of antidiabetic agents may require adjustment in patients who receive GI prokinetic agents concomitantly. [28956] Telmisartan: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] Telmisartan; Amlodipine: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Tenofovir Alafenamide: (Moderate) According to the manufacturer, interactions are not expected when metformin is administered with tenofovir alafenamide; however, because tenofovir and metformin can compete for elimination through the kidneys, use of these medications together may increase the risk for side effects, such as lactic acidosis. Drugs that are eliminated by renal tubular secretion, such as tenofovir alafenamide, may decrease metformin elimination by competing for common renal tubular transport systems. Although such interactions remain theoretical, careful patient monitoring and dose adjustment of metformin and/or the interfering cationic drug are recommended. [28550] [60614] [60688] Tenofovir, PMPA: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Drugs that are eliminated by renal tubular secretion, such as tenofovir, PMPA may decrease metformin elimination by competing for common renal tubular transport systems. Although such interactions remain theoretical, careful patient monitoring and dose adjustment of metformin and/or the interfering cationic drug are recommended. [28193] [28550] Testolactone: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together. [33919] [33920] [33921] [33922] [33923] [33924] Testosterone: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together. [33919] [33920] [33921] [33922] [33923] [33924] Thiazide diuretics: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Thyroid hormones: (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin. [28550] [30585] Tobacco: (Moderate) Tobacco smoking is known to aggravate insulin resistance. The cessation of tobacco smoking may result in a decrease in blood glucose. Blood glucose concentrations should be monitored more closely whenever a change in either smoking status occurs; dosage adjustments in antidiabetic agents may be needed. [29535] Tolazamide: (Moderate) Use of metformin with a sulfonylurea may increase the risk of hypoglycemia. Sulfonylureas are known to cause hypoglycemia. To manage hypoglycemic risk, lower doses of the sulfonylurea may be needed. Monitor blood sugar. [28550] Tolbutamide: (Moderate) Use of metformin with a sulfonylurea may increase the risk of hypoglycemia. Sulfonylureas are known to cause hypoglycemia. To manage hypoglycemic risk, lower doses of the sulfonylurea may be needed. Monitor blood sugar. [28550] Topiramate: (Major) Extended-release topiramate is contraindicated in patients with metabolic acidosis who are taking concomitant metformin because topiramate can frequently cause metabolic acidosis, a condition for which metformin use is contraindicated. Consider more frequent monitoring of patients taking immediate-release topiramate with metformin. In healthy volunteers, metformin Cmax and AUC increased by 17% and 25%, respectively, when topiramate was added, and oral plasma clearance of topiramate appears to be reduced when administered with metformin. However, the clinical significance of these pharmacokinetic effects is unclear. [28378] [28550] [55675] Torsemide: (Minor) Hyperglycemia has been detected during torsemide therapy, but the incidence is low. Because of this, a potential pharmacodynamic interaction exists between torsemide and all antidiabetic agents, including metformin. Monitor blood glucose. [29353] Trandolapril: (Moderate) Angiotensin-converting enzyme (ACE) inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. ACE inhibitors may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [29403] [30585] [33489] [42591] Trandolapril; Verapamil: (Moderate) Angiotensin-converting enzyme (ACE) inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving antidiabetic agents can become hypoglycemic if ACE inhibitors are administered concomitantly. ACE inhibitors may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [29403] [30585] [33489] [42591] Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Trilaciclib: (Moderate) Concomitant administration of metformin and trilaciclib may increase metformin exposure and increase the risk for lactic acidosis. If these drugs are given together, monitor for signs of metformin toxicity; metformin dose adjustments may be needed. Metformin is an OCT2 and MATE substrate; trilaciclib is an OCT2 and MATE inhibitor that may decrease metformin elimination by blocking renal tubular secretion. [28550] [66411] Trospium: (Moderate) Trospium, if used concomitantly with metformin, may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion like trospium may decrease metformin elimination by competing for common renal tubular transport systems. [28550] [29236] Ultralente Insulin: (Moderate) Coadministration of metformin with an insulin may increase the risk of hypoglycemia. Insulins are known to cause hypoglycemia. To manage hypoglycemic risk, lower doses of insulin may be needed. Monitor blood sugar and adjust insulin dosage as clinically indicated. [28550] Valsartan: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Vandetanib: (Moderate) Vandetanib could increase systemic exposure to metformin and may increase the risk for lactic acidosis. Vandetanib increased the plasma concentrations of metformin, which is transported by the renal organic cation transporter type 2 (OCT2). Use caution and closely monitor for toxicities when administering vendetanib with metformin. [28550] [43901] Zonisamide: (Moderate) Carbonic anhydrase inhibitors such as zonisamide frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Use of zonisamide with metformin may increase the risk for lactic acidosis; consider more frequent monitoring. Carbonic anhydrase inhibitors may also alter blood sugar; both hyperglycemia and hypoglycemia have been described. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction. [28550] [28843]
Revision Date: 09/17/2021, 02:35:00 AM

References

5280 - Glucophage and Glucophage XR (metformin HCl tablets and extended-release tablets) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2018 May.5351 - Bumex (bumetanide) package insert. Parsippany, NJ: Validus Pharmaceuticals LLC; 2018 Aug.6316 - Trental (pentoxifylline) package insert. Bridgewater, NJ: Sanofi-Aventis Pharmaceuticals Inc.; 2010 Jun.7224 - NovoLog (Insulin aspart) package insert. Princeton, NJ: Novo Nordisk Pharmaceuticals, Inc.; 2007 Jan.7238 - Apidra (Insulin glulisine) package insert. Kansas City, MO: Aventis Pharmaceuticals, Inc.; 2004 Apr.7775 - Somogyi A, Stockley C, Keal J, Rolan P et al. Reduction of metformin renal tubular secretion by cimetidine in man. Br J Clin Pharmacol 1987;23:545-51.23813 - Carter BL, Small RE, Mandel MD, et al. Phenytoin-induced hyperglycemia. Am J Hosp Pharm 1981;38:1508-12.25616 - Hollander PA, Elbein SC, Hirsch IB, et al. Role of orlistat in the treatment of obese patients with type 2 diabetes. A 1-year randomized double-blind study. Diabetes Care 1998;21:1288-94.25731 - Anderson RA, Cheng N, Bryden NA, et al. Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetes. Diabetes 1997;46:1786-1791.25732 - Ravina A, Slezak L, Mirsky N, et al. Reversal of corticosteroid induced diabetes mellitus with supplemental chromium. Diabet Med 1999;16:164-167.27971 - Xenical (orlistat) package insert. South San Francisco, CA: Genentech USA, Inc.; 2016 Jun.28032 - McMahon M, Gerich J, Rizza R. Effects of glucocorticoids on carbohydrate metabolism. Diabetes Metab Rev 1988;4:17-30.28072 - Emcyt (estramustine) package insert. Kalamazoo, MI: Pharmacia and Upjohn Company;2003 Mar.28193 - Viread (tenofovir disoproxil fumarate) package insert. Foster City, CA: Gilead Sciences, Inc; 2019 Apr.28221 - Tikosyn (dofetilide) package insert. New York, NY: Pfizer Labs; 2019 Aug.28228 - Norpace and Norpace CR (disopyramide) package insert. Chicago, IL: G.D. Searle LLC division of Pfizer Inc; 2016 Aug.28238 - Biaxin (clarithromycin) package insert. North Chicago, IL: AbbVie, Inc.; 2019 Sep.28267 - Acetazolamide package insert. Mahwah, NJ: Lifestar Pharma LLC; 2020 Mar.28272 - Lanoxin (digoxin) tablets package insert. St. Michael, Barbados: Concordia Pharmaceuticals Inc.; 2020 Apr..28294 - Methazolamide tablet package insert. Basking Ridge, NJ: Micro Labs USA, Inc.; 2019 Nov.28378 - Topamax (topiramate) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2021 Jun.28383 - Velcade (bortezomib) injection package insert. Cambridge, MA: Millennium Pharmaceuticals, Inc.; 2019 Apr.28423 - Avelox (moxifloxacin) package insert. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2020 May.28424 - Factive (gemifloxacin mesylate) package insert. Toronto, ON: Merus Labs International, Inc.; 2019 May.28429 - Lasix (furosemide) package insert. Bridgewater, NJ: Aventis Pharmaceuticals; 2018 Aug.28451 - Lamictal (lamotrigine) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Mar.28464 - Sheela CG, Kumud K, Augusti KT. Anti-diabetic effects of onion and garlic sulfoxide amino acids in rats. Planta Med 1995;61:356-7.28465 - Ryan EA, Pick ME, Marceau C. Use of alternative medicines in diabetes mellitus. Diabet Med 2001;18:242-5.28466 - Bordia A, Verma SK, Srivastava KC. Effect of garlic (Allium sativum) on blood lipids, blood sugar, fibrinogen and fibrinolytic activity in patients with coronary artery disease. Prostaglandins Leukot Essent Fatty Acids 1998;58:257-63.28550 - Glucophage and Glucophage XR (metformin HCl tablets and extended-release tablets) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2018 May.28599 - Zyvox (linezolid) package insert. New York, NY: Pharmacia and Upjohn Company; 2021 Sep.28618 - Tenormin (atenolol) package insert. Morristown, NJ: Almatica Pharma, Inc.; 2019 Apr28620 - Bumex (bumetanide) package insert. Parsippany, NJ: Validus Pharmaceuticals LLC; 2018 Aug.28784 - Hepsera (adefovir dipivoxil) package insert. Foster City, CA: Gilead Sciences, Inc.; 2018 Dec.28843 - Zonegran (zonisamide) package insert. Dublin, Ireland: Concordia Pharmaceuticals, Inc.; 2020 Apr.28879 - Pentamidine isethionate injection package insert. East Brunswick, NJ: Avet Pharmaceuticals Inc.; 2021 Jan.28915 - Lindenmayer JP, Czobor P, Volavka J, et al. Changes in glucose and cholesterol levels in patients with schizophrenia treated with typical or atypical antipsychotics. Am J Psych 2003;160:290-96.28956 - Zelnorm (tegaserod maleate) package insert. Louisville, KY: US WorldMeds, LLC; 2019 Mar.28963 - Omnipaque (iohexol) package insert. Marlborough, MA: GE Healthcare, Inc.; 2021 Aug.29113 - Sandostatin (octreotide) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2021 May.29236 - Sanctura (trospium tablets) package insert. Irvine, CA: Allergan, Inc.; 2012 July.29240 - Epivir (lamivudine) package insert. Research Triangle Park, NC: Viiv Healthcare; 2019 May.29241 - ProAmatine (midodrine) package insert. Austria, GmbH: Nycomed; 2003 Oct.29353 - Demadex (torsemide) package insert. Nutley, NJ: Roche Laboratories; 2003 Apr.29403 - Gilbert RE, Cooper ME, Krum H. Drug Administration in Patients with Diabetes Mellitus, Safety Considerations. Drug Safety 1998;18:441-55.29533 - McKenney JM, Goodman RP, Wright JT. Use of antihypertensive agents in patients with glucose intolerance. Clin Pharm 1985;4:649-56.29535 - Madsbad S, McNair P, Christensen MS, et al. Influence of smoking on insulin requirement and metbolic status in diabetes mellitus. Diabetes Care 1980;3:41-3.29536 - Chan JC, Cockram CS, Critchley JA. Drug-induced disorders of glucose metabolism. Mechanisms and management. Drug Saf 1996;15:135-57.29539 - Marathe PH, Wen Y, Norton J, et al. Effect of altered gastric emptying and gastrointestinal motility on metformin absorption. Br J Clin Pharmacol 2000;50:325-32.29758 - Aralen (chloroquine) package insert. Bridgewater, NJ: Sanofi-aventis U.S. LLC.; 2018 Oct.29904 - Shimizu M, Kobayashi Y, Suzuki M, et al. Regulation of intestinal glucose transport by tea catechins. Biofactors 2000;13:61-5.29905 - Sabu MC, Smitha K, Ramadassan K. Anti-diabetic activity of green tea polyphenols and their role in reducing oxidative stress in experimental diabetes. J Ethnopharmacol 2002;83:109-16.29922 - Keflex (cephalexin capsules) package insert. Locust Valley, NY: Pragma Pharmaceuticals, LLC; 2018 Dec.29923 - Jayasagar G, Krishna Kumar M, Chandrasekhar K, et al. Effect of cephalexin on the pharmacokinetics of metformin in healthy human volunteers. Drug Metabol Drug Interact 2002;19:41-8.30059 - Humatrope (somatropin) package insert. Indianapolis, IN: Eli Lilly and Company; 2019 Oct.30466 - NovoLog (Insulin aspart) package insert. Princeton, NJ: Novo Nordisk Pharmaceuticals, Inc.; 2007 Jan.30480 - Apidra (Insulin glulisine) package insert. Kansas City, MO: Aventis Pharmaceuticals, Inc.; 2004 Apr.30488 - Cryer PE, Davis SN, Shamoon H. Hypoglycemia in diabetes. Diabetes Care 2003;26:1902-12.30489 - Chobanian AV, Bakris GL, Black HR. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 Report. JAMA 2003;289:2560-71.30575 - Luna B, Feinglos MN. Drug-induced hyperglycemia. JAMA 2001;286:1945-8.30576 - Manske CL. Hyperglycemia and intensive glycemic control in diabetic patients with chronic renal disease. Am J Kidney Dis 1998;32 (Suppl 3):S157-S171.30585 - Pandit MK, Burke J, Gustafson AB, et al. Drug-induced disorders of glucose tolerance. Ann Intern Med 1993;118:529-39.30623 - Lee AJ, Maddix DS. Trimethoprim/sulfamethoxazole-induced hypoglycemia in a patient with acute renal failure. Ann Pharmacother 1997;31:727-32.30812 - Welchol (colesevelam) package insert. Basking Ridge, NJ: Daiichi Sankyo 2020 Jul.31230 - Baraclude (entecavir) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2019 Nov.31418 - Namenda (memantine) immediate-release package insert. Madison, NJ: Allergan, USA, Inc.; 2018 Nov.31516 - Ranke MB. Insulin-like growth factor-1 treatment of growth disorders, diabetes mellitus, and insulin resistance. Trends Endocrinol Metab 2005;16:190-7.31524 - Burroughs KD, Dunn SE, Barrett JC, et al. Insulin-like growth factor-1: a key regulator of human cancer risk?. J Natl Cancer Inst 1999;91:579-8131821 - IPLEX (mecasermin rinfabate) package insert. Glen Allen, VA: Insmed Incorporated; 2005 Dec.31938 - Ranexa (ranolazine extended-release tablets) package insert. Foster City, CA: Gilead Sciences, Inc. 2019 Oct.32127 - Prozac (fluoxetine hydrochloride) package insert. Indianapolis, IN: Eli Lilly and Company; 2020 Apr.32166 - Strevel EL, Kuper A, Gold WL. Severe and protracted hypoglycemia associated with co-trimoxazole [sulfamethoxazole; trimethoprim] use. Lancet Infect Dis 2006;6:178-82.32916 - Lopressor (metoprolol tartrate) tablets and injection. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2012 Dec.33489 - Ostergren J. Renin-angiotensin-system blockade in the prevention of diabetes. Diabetes Res Clin Pract 2007;76S:S13-S21.33519 - Somatuline Depot (lanreotide) package insert. Signes, France: Ipsen Pharma Biotech; 2018 Dec.33527 - Serostim (somatropin) package insert. Rockland, MA: EMD Serono, Inc.; 2017 May.33528 - Metopirone (metyrapone) capsule package insert. Farmingdale, NJ: Direct Success, Inc; 2020 Feb.33919 - Boyanov MA, Boneva Z, Christov VG. Testosterone supplementation in men with type 2 diabetes, visceral obesity, and partial androgen deficiency. Aging Male 2003;6:1-7.33920 - Kapoor D, Goodwin E, Channer KS, et al. Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity, and hypercholesterolaemia in hypogonadal men with type 2 diabetes. Eur J Clin Endocrinol 2006; 154:899-906.33921 - Hobbs CJ, Jones RE, Plymate SR. Nandrolone, a 19-nortestosterone, enhances insulin-independent glucose uptake in normal men. J Clin Endocrinol Metab 1996; 81:1582-5.33922 - Corrales JJ, Burgo RM, Garcia-Berrocal B, et al. Partial androgen deficiency in aging type 2 diabetic men and its relationship to glycemic control. Metabolism 2004;53:666-72.33923 - Lee CH, Kuo SW, Hung YJ, et al. The effect of testosterone supplement on insulin sensitivity, glucose effectiveness, and acute insulin response after glucose load in male type 2 diabetics. Endocrine Res 2005;31:139-148.33924 - Cohen JC, Hickman R. Insulin resistance and diminished glucose tolerance in powerlifters ingesting anabolic steroids. J Clin Endocrinol Metab 1987;64:960-3.35581 - Deplin (L-methylfolate) capsules package insert. Covington, LA: Alfasigma USA, Inc; 2017 Feb.40390 - Demadex (Torsemide) package insert. Somerset, NJ: Meda Pharmaceuticals; 2017 Feb.41489 - Cuvposa (glycopyrrolate oral solution) package insert. Atlanta, GA: Mikart, Inc.; 2018 Feb.41806 - Plaquenil (hydroxychloroquine) package insert. St. Michael, Barbados: Concordia Pharmaceuticals, Inc.; 2021 May.42591 - Scheen AJ. Drug Interactions of Clinical Importance with Antihyperglycemic Agents. Drug Saf 2005;28:601-631.43316 - Makena (hydroxyprogesterone caproate injection) package insert. McPherson, KS: Hospira, Inc.; 2018 Feb.43411 - Cipro (ciprofloxacin tablet; suspension) package insert. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2021 Mar.43901 - Caprelsa (vandetanib) package insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020 June.43933 - Niaspan (niacin extended-release) tablet package insert. North Chicago, IL: AbbVie Inc.; 2020 Sept.44058 - Prozac Weekly (fluoxetine hydrochloride delayed-release capsules) package insert. Indianapolis, IN: Lilly USA, LLC; 2017 Mar.44059 - Sarafem (fluoxetine hydrochloride) package insert. Irvine, CA: Allergan USA, Inc; 2021 Sept.44086 - Lantus (insulin glargine [rDNA origin] injection) solution for subcutaneous injection package insert. Bridgewater, NJ: Sanofi-Aventis U.S. LLC; 2019 Nov.44662 - Condit FS, Campbell RK, White JR. Diabetes. In: Handbook of Nonprescription Drugs. 12th ed. Washington, DC: American Pharmaceutical Association 2000;285:315-359.45044 - Omnitrope (somatropin) package insert. Princeton, NJ: Sandoz, Inc.; 2016 Dec.45045 - Genotropin (somatropin) package insert. New York, NY: Pharmacia & Upjohn Company; 2016 Dec.47221 - Propulsid (cisapride) package insert. Titusville, NJ; Janssen Pharmaceutica; 2006 Oct. NOTE: As of May 2000; Propulsid has only been available in the United States via an investigational limited access program to ensure proper patient screening and prescribing.48959 - Indapamide package insert. Baudette, MN: ANI Pharmaceuticals, Inc.; 2021 Apr.49068 - Proglycem (diazoxide) package insert. Horsham, PA: Teva Pharmaceuticals USA; 2015 Sep.49612 - Visipaque (iodixanol) package insert. Malborough, MA: GE Healthcare, Inc.; 2020 Jul.49770 - Nutropin (somatropin) package insert. San Francisco, CA: Genentech; 2016 Dec.51002 - Chan JC, Cockram CS, Critchley JA. Drug-induced disorders of glucose metabolism. Mechanisms and management. Drug Saf 1996;15:135—57.51065 - Belviq and Belviq XR (lorcaserin hydrochloride) package insert. Woodcliff Lake, NJ: Eisai Inc.; 2016 Nov.51250 - Somavert (pegvisomant) package insert. Dublin, Ireland: Pfizer Ireland Pharmaceuticals; 2012 June.51310 - Sandostatin LAR Depot (octreotide acetate) injection package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2021 Mar.51664 - Stribild (elvitegravir; cobicistat; emtricitabine; tenofovir disoproxil fumarate) package insert. Foster City, CA: Gilead Sciences, Inc; 2021 Sept.51834 - Food and Drug Administration (FDA): Drug development and drug interactions. Retrieved Sep 19, 2012. Available on the World Wide Web http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm#transporter.52611 - Signifor (pasireotide diaspartate) package insert. Stein, Switzerland: Novartis Pharma Stein AG; 2020 Jan.53617 - Inderal LA (propranol sustained-release) capsules. Baudette, MN: ANI Pharmaceuticals, Inc. 2019 Aug.54578 - Clolar (clofarabine) injection package insert. Cambridge, MA: Genzyme Corporation; 2019 Dec.55594 - Tivicay (dolutegravir) package insert. Research Triangle Park, NC: ViiV Healthcare; 2021 Jul.55675 - Trokendi XR (topiramate extended-release capsules) package insert. Rockville, MD: Supernus Pharmaceuticals; 2020 Nov.56528 - Sovaldi (sofosbuvir) tablet and oral pellets package insert. Foster City, CA: Gilead Sciences, Inc; 2020 Mar.56579 - Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers. Updated Mar 10, 2020. Retrieved from the World Wide Web at www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm56647 - Nutropin AQ (somatropin) package insert. San Francisco, CA: Genentech; 2016 Dec.56648 - Nutropin Depot (somatropin) package insert. San Francisco, CA: Genentech; 2004 Oct.56649 - Saizen (somatropin) package insert. Rockland, MA: EMD Serono Inc; 2017 May.56650 - Tev-Tropin (somatropin) package insert. Horsham, PA: Teva Select Brands; 2015 Feb.56651 - Valtropin (somatropin) package insert. Seoul, Korea: LG Life Sciences; 2007 Sept.57357 - Acetazolamide injection package insert. Big Flats, NY: X-GEN Pharmaceuticals, Inc.; 2013 Mar.57571 - Ackermann RT, Mulrow CD, Ramirez G, et al. Garlic shows promise for improving some cardiovascular risk factors. Arch Intern Med 2001;161:813-24.58095 - Norditropin (somatropin) package insert. Plainsboro, NJ: Novo Nordisk; 2017 Feb.58167 - Harvoni (ledipasvir; sofosbuvir) tablet and oral pellets package insert. Foster City, CA: Gilead Sciences, Inc; 2020 Mar.58639 - Signifor LAR (pasireotide) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2020 Jun.58664 - Viekira Pak (ombitasvir; paritaprevir; ritonavir; dasabuvir) tablet package insert. North Chicago, IL: AbbVie, Inc; 2019 Dec.58763 - Prezcobix (darunavir and cobicistat) tablets package insert. Titusville, NJ: Janssen Therapeutics; 2021 Jul.59433 - D'Arcy PF, Griffin JF. Interactions with drugs used in the treatment of depressive illness. Adverse Drug React Toxicol Rev. 1995;4:211-31.59579 - Zomacton (somatropin) package insert. Parsippany, NJ: Ferring Pharmaceuticals, Inc; 2018 July.60001 - Daklinza (daclatasvir) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2019 Oct.60002 - Technivie (ombitasvir; paritaprevir; ritonavir) tablet package insert. North Chicago, IL: AbbVie, Inc; 2019 Dec.60122 - Keveyis (dichlorphenamide) tablets package insert. Trevose, PA: Strongbridge US Inc.; 2019 Nov.60523 - Zepatier (elbasvir; grazoprevir) tablet package insert. Whitehouse Station, NJ: Merck, Inc; 2019 Dec.60614 - Odefsey (emtricitabine; rilpivirine; tenofovir alafenamide) package insert. Foster City, CA: Gilead Sciences, Inc.; 2021 Sept.60682 - Zorbtive (somatropin) injection package insert. Rockland, MA: EMD Serono, Inc.; 2017 May.60688 - Descovy (emtricitabine; tenofovir alafenamide) package insert. Foster City, CA: Gilead Sciences, Inc.; 2021 Sept.60877 - Alli (orlistat) capsules. Warren, NJ: GSK Consumer Healthcare; 2016 May.60911 - Epclusa (sofosbuvir; velpatasvir) tablet package insert. Foster City, CA: Gilead Sciences, Inc; 2021 Jun.61023 - Viekira XR (ombitasvir; paritaprevir; ritonavir; dasabuvir) extended-release tablet package insert. North Chicago, IL: AbbVie, Inc; 2019 Dec.61909 - Alunbrig (brigatinib) tablet package insert. Cambridge, MA: Ariad Pharmaceuticals Inc.; 2020 May.62028 - Baxdela (delafloxacin) package insert. Lincolnshire, IL: Melinta Therapeutics, Inc.; 2019 Oct.62131 - Vosevi (sofosbuvir; velpatasvir; voxilaprevir) tablet package insert. Foster City, CA: Gilead Sciences, Inc; 2019 Nov.62201 - Mavyret (glecaprevir; pibrentasvir) tablets package insert. North Chicago, IL: AbbVie Inc.; 2021 Jun.62852 - Biktarvy (bictegravir; emtricitabine; tenofovir alafenamide) tablets package insert. Foster City, CA: Gilead Sciences, Inc.; 2021 Sept.62853 - Amin M, Suksomboon N. Pharmacotherapy of type 2 diabetes mellitus: an update on drug-drug interactions. Drug Saf. 2014;37:903-919.62881 - Garvey WT, Mechanick JI, Brett EM, et al; Reviewers of the AACE/ACE Obesity Clinical Practice Guidelines. American Association of Clinical Endocrinologists and American College of Endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity. Endocr Pract. 2016;22 Suppl 3:1-203.62893 - Hydroxyprogesterone caproate injection 1.25 gram/5 mL package insert. Baudette, MN; ANI Pharmaceuticals, Inc.: 2016 June.63042 - Wang J, Zhang X, Lan H, et al. Effect of garlic supplement in the management of type 2 diabetes mellitus (T2DM): a meta-analysis of randomized controlled trials. Food Nutr Res. 2017;61:1377571. eCollection 2017.63043 - Tattelman E. Health effects of garlic. Am Fam Physician. 2005;72:103-106. Review.63373 - Krintafel (tafenoquine) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2020 Nov.64064 - Balversa (erdafitinib) tablets package insert. Horsham, PA: Janssen Products, LP; 2019 April.65377 - Tabrecta (capmatinib) tablets package insert. Novartis Pharmaceuticals Corporation;East Hanover, NJ:2020 May.65562 - Levofloxacin tablets package insert. Livonia, MI; Major Pharmaceuticals: 2019 Nov.65815 - Evrysdi (risdiplam) oral solution package insert. South San Francisco, CA: Genentech, Inc. 2021 April.66411 - Cosela (trilaciclib) injection package insert. Durham, NC:G1 Therapeutics, Inc; 2021 Feb.

Monitoring Parameters

  • blood glucose
  • CBC
  • glycosylated hemoglobin A1c (HbA1c)
  • LFTs
  • serum creatinine/BUN

US Drug Names

  • Fortamet
  • Glucophage
  • Glucophage XR
  • Glumetza
  • Riomet
  • RIOMET ER
;