metformin (Rx)

Type 2 Diabetes Mellitus

Adjunctive therapy to diet and exercise to improve glycemic control in adults with type 2 diabetes

Monotherapy or with sulfonylurea

Immediate-release tablet or solution

• Initial: 500 mg PO q12hr or 850 mg PO qDay with meals; increase dose in increments of 500 mg/week or 850 mg q2Weeks on the basis of glycemic control and tolerability
• Maintenance: 1500-2550 mg/day PO divided q8-12hr with meal
• Not to exceed 2550 mg/day

Extended-release tablet or suspension

• 500 mg PO qDay with dinner; titrate by 500 mg/day qWeek; not to exceed 2000 mg/day

Type 2 Diabetes Prevention (Off-label)

850 mg PO qDay

Target dosing: 850 mg PO q12hr

Dosage Modifications

Hepatic impairment: Avoid use; risk of lactic acidosis

Renal impairment

• Obtain eGFR before starting metformin
• eGFR <30 mL/min/1.73 m²: Contraindicated
• eGFR 30-45 mL/min/1.73 m²: Not recommended to initiate treatment
• Monitor eGFR at least annually or more often for those at risk for renal impairment (eg, elderly)
• If eGFR falls below 45mL/min/1.73 m² while taking metformin, risks and benefits of continuing therapy should be evaluated
• If eGFR falls below 30 mL/min/1.73 m² while taking metformin, discontinue drug

Discontinuation for iodinated contrast imaging procedures

• Discontinue metformin HCl at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR between 30 and 60 mL/min/1.73 m² ; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinated contrast
• Re-evaluate eGFR 48 hr after imaging procedure; restart metformin HCl if renal function is stable

Dosing Consideration

Switching from metformin immediate-release to metformin extended-release

• Patients receiving metformin HCl may be switched to metformin extended-release at the same total daily dose, up to 2,000 mg/day

Polycystic Ovary Syndrome (Orphan)

Orphan designation for treatment of pediatric polycystic ovary syndrome

Sponsor

• EffRx Pharmaceuticals SA; Wolleraustrass 41 B; 8807 Freienbach (SZ); SWITZERLAND

Myoclonus Epilepsy (Orphan)

Orphan designation for treatment of progressive myoclonus epilepsy type 2 (Lafora disease)

Sponsor

• Consorcio Centro de Investigación Biomédica en Red, M.P. (CIBER); Monforte de Lemos, 3-5 Pabellon 11; Madrid, Spain

Type 2 Diabetes Mellitus

Indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients (≥10 years) with type 2 diabetes mellitus.

10 to <17 years

• Immediate-release

  • Initial: 500 mg PO q12hr
  • Maintenance: Titrate qWeek by 500 mg; no more than 2000 mg/day in divided doses

• Extended-release

  • 500 mg PO qDay with dinner; increase the dose in increments of 500 mg (5 mL) weekly, up to a maximum dose of 2,000 mg (20 mL) once daily, with the evening meal

Dosage Modifications

Renal impairment

• Obtain eGFR before initiating metformin
• eGFR <30 mL/min/1.73 m²: Contraindicated
• eGFR 30-45 mL/min/1.73 m²: Initiating not recommended
• Obtain GFR at least annually in all patients taking metformin; assess eGFR more frequently in patients at increased risk for renal impairment (eg, elderly)
• If eGFR falls to <45 mL/min/1.73 m² during treatment: Assess the benefits and risks of continuing treatment
• If eGFR falls to <30 mL/min/1.73 m² during treatment: Discontinue

Elderly patients are more likely to have decreased renal function; contraindicated in patients with renal impairment, carefully monitor renal function in the elderly and use with caution as age increases

Not for use in patients >80 years unless normal renal function establishedInitial and maintenance dosing of metformin should be conservative in patients with advanced age due to the potential for decreased renal function in this population

Controlled clinical studies of metformin did not include sufficient numbers of elderly patients to determine whether they respond differently from younger patients

Contraindicated (0)

Serious - Use Alternative (13)

• contrast media (iodinated)

  contrast media (iodinated) increases levels of metformin by decreasing renal clearance. Contraindicated. Acute renal failure or lactic acidosis may result. D/c metformin 48 hr before and after imaging study.

• ethanol

  ethanol increases toxicity of metformin by Other (see comment). Contraindicated. Comment: Excessive EtOH consumption may alter glycemic control. Some sulfonylureas may produce a disulfiram like rxn; alcohol may potentiate the risk of lactic acidosis.

• ioversol

  ioversol increases levels of metformin by decreasing renal clearance. Contraindicated. Acute renal failure or lactic acidosis may result. D/c metformin 48 hr before and after imaging study.

• methylene blue

  methylene blue will increase the level or effect of metformin by unspecified interaction mechanism. Avoid or Use Alternate Drug.

• pacritinib

  pacritinib will increase the level or effect of metformin by Other (see comment). Avoid or Use Alternate Drug. Concomitant administration of pacritinib (OCT1 inhibitor) with OCT1 substrates may increase the plasma concentrations of these substrates.

• ranolazine

  ranolazine will increase the level or effect of metformin by decreasing elimination. Avoid or Use Alternate Drug. Limit metformin dose to 1700 mg/day when used together with ranolazine 1000 mg twice daily; monitor closelly for signs or symptoms of metformin toxicity

• risdiplam

  risdiplam will increase the level or effect of metformin by decreasing elimination. Avoid or Use Alternate Drug. Risdiplam inhibits MATE1 and MATE2-K. If unable to avoid coadministration with MATE substrates, consider dosage reduction of MATE substrate.

• selegiline

  selegiline will increase the level or effect of metformin by unspecified interaction mechanism. Avoid or Use Alternate Drug.

• selegiline transdermal

  selegiline transdermal will increase the level or effect of metformin by unspecified interaction mechanism. Avoid or Use Alternate Drug.

• tafenoquine

  tafenoquine will increase the level or effect of metformin by Other (see comment). Avoid or Use Alternate Drug. Tafenoquine inhibits organic cation transporter-2 (OCT2) and multidrug and toxin extrusion (MATE) transporters in vitro. Avoid coadministration with OCT2 or MATE substrates. If coadministration cannot be avoided, monitor for substrate-related toxicities and consider dosage reduction if needed based on product labeling of the coadministered drug.

• tedizolid

  tedizolid will increase the level or effect of metformin by unspecified interaction mechanism. Avoid or Use Alternate Drug.

• tranylcypromine

  tranylcypromine will increase the level or effect of metformin by unspecified interaction mechanism. Avoid or Use Alternate Drug.

• trilaciclib

  trilaciclib will decrease the level or effect of metformin by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of trilaciclib (OCT2, MATE1, and MATE-2K inhibitor) with substrates where minimal increased concentration in kidney or blood may lead to serious or life-threatening toxicities.

Monitor Closely (195)

• acetazolamide

  acetazolamide increases toxicity of metformin by Other (see comment). Use Caution/Monitor. Comment: Decreases serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis.

• albiglutide

  albiglutide, metformin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.

• amiodarone

  amiodarone will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

• amlodipine

  amlodipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• aripiprazole

  aripiprazole, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• asenapine

  asenapine, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• atazanavir

  atazanavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• benazepril

  benazepril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• benzphetamine

  benzphetamine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• betamethasone

  betamethasone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• bictegravir

  bictegravir will increase the level or effect of metformin by decreasing renal clearance. Modify Therapy/Monitor Closely. Bictegravir inhibits organic cation transporter 2 (OCT2) and multidrug and toxin extrusion transporter 1 (MATE1) in vitro. Coadministration with OCT2 and MATE1 substrates may increase their plasma concentrations. Metformin dose reduction may be required.

• bitter melon

  bitter melon increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypoglycemia.

• brexpiprazole

  brexpiprazole decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• bumetanide

  bumetanide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• bupropion

  bupropion increases levels of metformin by Other (see comment). Use Caution/Monitor. Comment: Bupropion may inhibit OCT2 mediated renal excretion of metformin.

• captopril

  captopril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• cariprazine

  cariprazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• cephalexin

  cephalexin increases toxicity of metformin by decreasing renal clearance. Use Caution/Monitor. particularly in patients who may have other risk factors for metformin toxicity. .

• ceritinib

  ceritinib decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• chlorpromazine

  chlorpromazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• cimetidine

  cimetidine will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

• cinnamon

  cinnamon increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Potential for hypoglycemia.

• ciprofloxacin

  ciprofloxacin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Hyper and hypoglycemia have been reported in patients treated concomitantly with quinolones and antidiabetic agents. Careful monitoring of blood glucose is recommended.

• citalopram

  citalopram increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• clevidipine

  clevidipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• clozapine

  clozapine, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• colesevelam

  colesevelam increases levels of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• conjugated estrogens

  conjugated estrogens decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• corticotropin

  corticotropin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• dabrafenib

  dabrafenib decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• dalfampridine

  metformin, dalfampridine. Either increases levels of the other by Other (see comment). Use Caution/Monitor. Comment: Metformin and dalfampridine are organic cation transporter 2 (OCT2) substrates; both drugs may compete for renal tubular uptake and could potentially increase systemic exposure of either drug when administered concomitantly.

• darunavir

  darunavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• desogestrel

  desogestrel decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• diatrizoate

  diatrizoate increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• diatrizoate meglumine/diatrizoate sodium

  diatrizoate meglumine/diatrizoate sodium increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• diazoxide

  diazoxide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• dichlorphenamide

  dichlorphenamide, metformin. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Both drugs can cause metabolic acidosis.

• dienogest/estradiol valerate

  dienogest/estradiol valerate decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• diethylpropion

  diethylpropion decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• digoxin

  digoxin, metformin. Either increases levels of the other by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor. Measure serum digoxin concentrations before initiating metformin. Monitor patients who take both metformin and digoxin for possible digoxin toxicity and lactic acidosis. Reduce the digoxin and/or metformin dose as necessary.

• diltiazem

  diltiazem decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• dofetilide

  dofetilide will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

• dolutegravir

  dolutegravir will increase the level or effect of metformin by decreasing renal clearance. Modify Therapy/Monitor Closely. Dolutegravir inhibits the renal organic cation transporter, OCT2; when used with metformin, limit total daily dose of metformin to 1,000 mg either when starting metformin or dolutegravir; when stopping dolutegravir, adjustment of metformin dose may be necessary; monitor blood glucose when initiating concomitant use and after withdrawal of dolutegravir

• drospirenone

  drospirenone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• dulaglutide

  dulaglutide, metformin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• enalapril

  enalapril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• entecavir

  entecavir, metformin. Either increases levels of the other by Other (see comment). Use Caution/Monitor. Comment: Coadministration of entecavir with metformin may increase the risk of lactic acidosis.

• erdafitinib

  metformin increases levels of erdafitinib by decreasing renal clearance. Modify Therapy/Monitor Closely. Consider alternatives that are not OCT2 substrates or consider reducing the dose of OCT2 substrates based on tolerability.

• escitalopram

  escitalopram increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• estradiol

  estradiol decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• estrogens conjugated synthetic

  estrogens conjugated synthetic decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• estropipate

  estropipate decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• ethacrynic acid

  ethacrynic acid decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• ethinylestradiol

  ethinylestradiol decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• ethiodized oil

  ethiodized oil increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• etonogestrel

  etonogestrel decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• everolimus

  everolimus decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• exenatide injectable solution

  exenatide injectable solution, metformin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.

• exenatide injectable suspension

  exenatide injectable suspension, metformin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.

• felodipine

  felodipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• fleroxacin

  fleroxacin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.

• fluoxetine

  fluoxetine increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• fluphenazine

  fluphenazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• fluvoxamine

  fluvoxamine increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• fosamprenavir

  fosamprenavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• fosinopril

  fosinopril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• fosphenytoin

  fosphenytoin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• gemifloxacin

  gemifloxacin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.

• glucagon intranasal

  glucagon intranasal decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• glycopyrrolate

  glycopyrrolate increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. May require a dose reduction.

• goserelin

  goserelin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• histrelin

  histrelin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• hydroxyprogesterone caproate

  hydroxyprogesterone caproate decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• iloperidone

  iloperidone, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• imidapril

  imidapril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• indinavir

  indinavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• insulin aspart

  metformin, insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin aspart protamine/insulin aspart

  metformin, insulin aspart protamine/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin degludec

  metformin, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin degludec/insulin aspart

  metformin, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin detemir

  metformin, insulin detemir. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin glargine

  metformin, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin glulisine

  metformin, insulin glulisine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin inhaled

  metformin, insulin inhaled. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin isophane human/insulin regular human

  metformin, insulin isophane human/insulin regular human. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin lispro

  metformin, insulin lispro. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin lispro protamine/insulin lispro

  metformin, insulin lispro protamine/insulin lispro. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin NPH

  metformin, insulin NPH. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin regular human

  metformin, insulin regular human. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• iodixanol

  iodixanol increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• ioflupane I 123

  ioflupane I 123 increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• iohexol

  iohexol increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• iopamidol

  iopamidol increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• iopromide

  iopromide increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• ioversol

  ioversol increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• ioxilan

  ioxilan increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• isocarboxazid

  isocarboxazid will increase the level or effect of metformin by unspecified interaction mechanism. Use Caution/Monitor.

• isoniazid

  isoniazid decreases effects of metformin by unspecified interaction mechanism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• isradipine

  isradipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• ketotifen, ophthalmic

  ketotifen, ophthalmic, metformin. Other (see comment). Use Caution/Monitor. Comment: Combination may result in thrombocytopenia (rare). Monitor CBC.

• lanreotide

  lanreotide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• leuprolide

  leuprolide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• levofloxacin

  levofloxacin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.

• levonorgestrel intrauterine

  levonorgestrel intrauterine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• levonorgestrel oral

  levonorgestrel oral decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• levothyroxine

  levothyroxine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• linezolid

  linezolid will increase the level or effect of metformin by unspecified interaction mechanism. Use Caution/Monitor.

• liothyronine

  liothyronine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• liotrix

  liotrix decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• liraglutide

  liraglutide, metformin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.

• lisinopril

  lisinopril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• lithium

  metformin decreases levels of lithium by Other (see comment). Use Caution/Monitor. Comment: SGLT2 inhibitors with lithium may decrease serum lithium concentrations; monitor serum lithium concentration more frequently during therapy initiation and dosage changes.

• lonapegsomatropin

  lonapegsomatropin decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Closely monitor blood glucose when treated with antidiabetic agents. Lonapegsomatropin may decrease insulin sensitivity, particularly at higher doses. Patients with diabetes mellitus may require adjustment of their doses of insulin and/or other antihyperglycemic agents.

• lopinavir

  lopinavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• lurasidone

  lurasidone, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• marijuana

  marijuana decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• mecasermin

  mecasermin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Additive hypoglycemic effects.

• medroxyprogesterone

  medroxyprogesterone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• methamphetamine

  methamphetamine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• methazolamide

  methazolamide increases toxicity of metformin by Other (see comment). Use Caution/Monitor. Comment: Decreases serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis.

• moexipril

  moexipril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• moxifloxacin

  moxifloxacin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.

• nelfinavir

  nelfinavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• niacin

  niacin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• nicardipine

  nicardipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• nifedipine

  nifedipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• nilotinib

  nilotinib decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• nimodipine

  nimodipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• nisoldipine

  nisoldipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• nizatidine

  nizatidine will increase the level or effect of metformin by decreasing renal clearance. Modify Therapy/Monitor Closely.

• norelgestromin

  norelgestromin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• norethindrone

  norethindrone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• norgestimate

  norgestimate decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• octreotide

  octreotide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• ofloxacin

  ofloxacin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.

• olanzapine

  olanzapine, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• omacetaxine

  omacetaxine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

  ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Monitor for signs of onset of lactic acidosis such as respiratory distress, somnolence, and non-specific abdominal distress or worsening renal function; concomitant metformin use in patients with renal insufficiency or hepatic impairment not recommended.

• ondansetron

  ondansetron increases levels of metformin by Other (see comment). Use Caution/Monitor. Comment: Ondansetron inhibition of transporters (MATE or OCTs), which are responsible for active renal secretion of metformin may play a role.

• opuntia ficus indica

  opuntia ficus indica increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• paliperidone

  paliperidone, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• paroxetine

  paroxetine increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• pasireotide

  pasireotide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• patiromer

  patiromer will decrease the level or effect of metformin by drug binding in GI tract. Modify Therapy/Monitor Closely. Separate administration by at least 3 hr from patiromer

• pentamidine

  pentamidine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• perindopril

  perindopril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• perphenazine

  perphenazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• phendimetrazine

  phendimetrazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• phenelzine

  phenelzine will increase the level or effect of metformin by unspecified interaction mechanism. Use Caution/Monitor.

• phentermine

  phentermine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• phenytoin

  phenytoin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• procainamide

  metformin will increase the level or effect of procainamide by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

• procarbazine

  procarbazine will increase the level or effect of metformin by unspecified interaction mechanism. Use Caution/Monitor.

• prochlorperazine

  prochlorperazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• progesterone intravaginal gel

  progesterone intravaginal gel decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• progesterone micronized

  progesterone micronized decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• progesterone, natural

  progesterone, natural decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• promethazine

  promethazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• quetiapine

  quetiapine, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• quinapril

  quinapril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• quinidine

  quinidine will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

• ramipril

  ramipril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• rasagiline

  rasagiline will increase the level or effect of metformin by unspecified interaction mechanism. Use Caution/Monitor.

• risperidone

  risperidone, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• ritonavir

  ritonavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• saquinavir

  saquinavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• sertraline

  sertraline increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• shark cartilage

  shark cartilage increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Theoretical interaction.

• sirolimus

  sirolimus decreases levels of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• somapacitan

  somapacitan decreases effects of metformin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone products may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating somapacitan. .

• somatropin

  somatropin decreases levels of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• sulfamethoxypyridazine

  sulfamethoxypyridazine increases effects of metformin by unspecified interaction mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• tacrolimus

  tacrolimus decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• temsirolimus

  temsirolimus decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• tenofovir DF

  tenofovir DF increases levels of metformin by decreasing renal clearance. Use Caution/Monitor. Increased risk of lactic acidosis.

• thioridazine

  thioridazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• thyroid desiccated

  thyroid desiccated decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• tibolone

  tibolone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• tipranavir

  tipranavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• topiramate

  topiramate increases toxicity of metformin by Other (see comment). Use Caution/Monitor. Comment: Decreases serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis.

• torsemide

  torsemide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• trandolapril

  trandolapril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• triamcinolone acetonide injectable suspension

  triamcinolone acetonide injectable suspension decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Corticosteroids may diminish hypoglycemic effect of antidiabetic agents. Monitor blood glucose levels carefully.

• trifluoperazine

  trifluoperazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• trimethoprim

  trimethoprim increases levels of metformin by Other (see comment). Use Caution/Monitor. Comment: Trimethoprim may inhibit active renal tubular secretion of metformin (eg, via OCT2, MATE1); dose adjustments may be necessary.

• triptorelin

  triptorelin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• trospium chloride

  metformin will decrease the level or effect of trospium chloride by increasing renal clearance. Use Caution/Monitor. Coadministration reduced steady state trospium systemic exposure (decreased AUC and Cmax) by competing for renal tubular secretion

• vandetanib

  vandetanib increases levels of metformin by Other (see comment). Modify Therapy/Monitor Closely. Comment: Vandetanib inhibits the uptake of substrates of organic cation transporter type 2 (OCT2).

• verapamil

  verapamil decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Verapamil may inhibit hepatic uptake of metformin by OCT1 and/or other transporters.

• vilazodone

  vilazodone increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• vorinostat

  vorinostat decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• vortioxetine

  vortioxetine increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• xipamide

  xipamide decreases levels of metformin by increasing renal clearance. Use Caution/Monitor.

• ziprasidone

  ziprasidone, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• zonisamide

  zonisamide increases toxicity of metformin by Other (see comment). Use Caution/Monitor. Comment: Decreases serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis.

Minor (82)

• agrimony

  agrimony increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• American ginseng

  American ginseng increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• amitriptyline

  amitriptyline increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• amoxapine

  amoxapine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• anamu

  anamu increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Theoretical interaction.

• bendroflumethiazide

  bendroflumethiazide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• budesonide

  budesonide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.

• chlorothiazide

  chlorothiazide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• chlorthalidone

  chlorthalidone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• chromium

  chromium increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• clomipramine

  clomipramine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• clonidine

  clonidine decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  clonidine, metformin. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

• cornsilk

  cornsilk increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).

• cortisone

  cortisone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.

• cyanocobalamin

  metformin decreases levels of cyanocobalamin by unspecified interaction mechanism. Minor/Significance Unknown. It may take several years of metformin therapy to develop vitamin B12 deficiency.

• cyclopenthiazide

  cyclopenthiazide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• damiana

  damiana decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Theoretical interaction.

• danazol

  danazol increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• deflazacort

  deflazacort decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.

• desipramine

  desipramine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• devil's claw

  devil's claw increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• dexamethasone

  dexamethasone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.

• diltiazem

  diltiazem will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• doxepin

  doxepin increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• elderberry

  elderberry increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (in vitro research).

• eucalyptus

  eucalyptus increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Theoretical interaction.

• famotidine

  famotidine increases levels of metformin by decreasing renal clearance. Minor/Significance Unknown.

• fludrocortisone

  fludrocortisone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.

• fluoxymesterone

  fluoxymesterone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• fo-ti

  fo-ti increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• folic acid

  metformin decreases levels of folic acid by unspecified interaction mechanism. Minor/Significance Unknown.

• forskolin

  forskolin increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Colenol, a compound found in Coleus root, may stimulate insulin release.

• furosemide

  metformin decreases levels of furosemide by unspecified interaction mechanism. Minor/Significance Unknown.
  
  furosemide increases levels of metformin by unspecified interaction mechanism. Minor/Significance Unknown. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• gotu kola

  gotu kola increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction).

• guanfacine

  guanfacine decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  guanfacine, metformin. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

• gymnema

  gymnema increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• horse chestnut seed

  horse chestnut seed increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• hydrochlorothiazide

  hydrochlorothiazide will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  hydrochlorothiazide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• hydrocortisone

  hydrocortisone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.

• ibuprofen/famotidine

  ibuprofen/famotidine increases levels of metformin by decreasing renal clearance. Minor/Significance Unknown.

• imipramine

  imipramine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• indapamide

  indapamide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• juniper

  juniper increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).

• L-methylfolate

  metformin decreases levels of L-methylfolate by unspecified interaction mechanism. Minor/Significance Unknown.

• lofepramine

  lofepramine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• lycopus

  lycopus increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).

• maitake

  maitake increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (animal research).

• maprotiline

  maprotiline increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• memantine

  memantine will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• mesterolone

  mesterolone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• methyclothiazide

  methyclothiazide will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  methyclothiazide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• methylprednisolone

  methylprednisolone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.

• methyltestosterone

  methyltestosterone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• metolazone

  metolazone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• midodrine

  metformin will increase the level or effect of midodrine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• nettle

  nettle increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction).

• nifedipine

  nifedipine increases levels of metformin by enhancing GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• nortriptyline

  nortriptyline increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• ofloxacin

  metformin will increase the level or effect of ofloxacin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  ofloxacin, metformin. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Potential dysglycemia.

• oxandrolone

  oxandrolone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• oxymetholone

  oxymetholone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• pegvisomant

  pegvisomant increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• potassium acid phosphate

  potassium acid phosphate increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia.

• potassium chloride

  potassium chloride increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia.

• potassium citrate

  potassium citrate increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia.

• prednisolone

  prednisolone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.

• prednisone

  prednisone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.

• protriptyline

  protriptyline increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• quinine

  metformin will increase the level or effect of quinine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• sage

  sage increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• stevia

  stevia increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• sulfamethoxazole

  sulfamethoxazole will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• testosterone

  testosterone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• testosterone buccal system

  testosterone buccal system increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• testosterone topical

  testosterone topical increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• tongkat ali

  tongkat ali increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypoglycemia.

• trazodone

  trazodone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• triamterene

  metformin will increase the level or effect of triamterene by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• trimethoprim

  metformin will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• trimipramine

  trimipramine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• vanadium

  vanadium increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• verapamil

  metformin will increase the level or effect of verapamil by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• acetazolamide

  Monitor Closely (1)acetazolamide increases toxicity of metformin by Other (see comment). Use Caution/Monitor. Comment: Decreases serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis.

• agrimony

  Minor (1)agrimony increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• albiglutide

  Monitor Closely (1)albiglutide, metformin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.

• American ginseng

  Minor (1)American ginseng increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• amiodarone

  Monitor Closely (1)amiodarone will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

• amitriptyline

  Minor (1)amitriptyline increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• amlodipine

  Monitor Closely (1)amlodipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• amoxapine

  Minor (1)amoxapine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• anamu

  Minor (1)anamu increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Theoretical interaction.

• aripiprazole

  Monitor Closely (1)aripiprazole, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• asenapine

  Monitor Closely (1)asenapine, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• atazanavir

  Monitor Closely (1)atazanavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• benazepril

  Monitor Closely (1)benazepril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• bendroflumethiazide

  Minor (1)bendroflumethiazide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• benzphetamine

  Monitor Closely (1)benzphetamine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• betamethasone

  Monitor Closely (1)betamethasone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• bictegravir

  Monitor Closely (1)bictegravir will increase the level or effect of metformin by decreasing renal clearance. Modify Therapy/Monitor Closely. Bictegravir inhibits organic cation transporter 2 (OCT2) and multidrug and toxin extrusion transporter 1 (MATE1) in vitro. Coadministration with OCT2 and MATE1 substrates may increase their plasma concentrations. Metformin dose reduction may be required.

• bitter melon

  Monitor Closely (1)bitter melon increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypoglycemia.

• brexpiprazole

  Monitor Closely (1)brexpiprazole decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• budesonide

  Minor (1)budesonide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.

• bumetanide

  Monitor Closely (1)bumetanide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• bupropion

  Monitor Closely (1)bupropion increases levels of metformin by Other (see comment). Use Caution/Monitor. Comment: Bupropion may inhibit OCT2 mediated renal excretion of metformin.

• captopril

  Monitor Closely (1)captopril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• cariprazine

  Monitor Closely (1)cariprazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• cephalexin

  Monitor Closely (1)cephalexin increases toxicity of metformin by decreasing renal clearance. Use Caution/Monitor. particularly in patients who may have other risk factors for metformin toxicity. .

• ceritinib

  Monitor Closely (1)ceritinib decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• chlorothiazide

  Minor (1)chlorothiazide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• chlorpromazine

  Monitor Closely (1)chlorpromazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• chlorthalidone

  Minor (1)chlorthalidone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• chromium

  Minor (1)chromium increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• cimetidine

  Monitor Closely (1)cimetidine will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

• cinnamon

  Monitor Closely (1)cinnamon increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Potential for hypoglycemia.

• ciprofloxacin

  Monitor Closely (1)ciprofloxacin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Hyper and hypoglycemia have been reported in patients treated concomitantly with quinolones and antidiabetic agents. Careful monitoring of blood glucose is recommended.

• citalopram

  Monitor Closely (1)citalopram increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• clevidipine

  Monitor Closely (1)clevidipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• clomipramine

  Minor (1)clomipramine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• clonidine

  Minor (2)clonidine decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  clonidine, metformin. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

• clozapine

  Monitor Closely (1)clozapine, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• colesevelam

  Monitor Closely (1)colesevelam increases levels of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• conjugated estrogens

  Monitor Closely (1)conjugated estrogens decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• contrast media (iodinated)

  Serious - Use Alternative (1)contrast media (iodinated) increases levels of metformin by decreasing renal clearance. Contraindicated. Acute renal failure or lactic acidosis may result. D/c metformin 48 hr before and after imaging study.

• cornsilk

  Minor (1)cornsilk increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).

• corticotropin

  Monitor Closely (1)corticotropin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• cortisone

  Minor (1)cortisone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.

• cyanocobalamin

  Minor (1)metformin decreases levels of cyanocobalamin by unspecified interaction mechanism. Minor/Significance Unknown. It may take several years of metformin therapy to develop vitamin B12 deficiency.

• cyclopenthiazide

  Minor (1)cyclopenthiazide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• dabrafenib

  Monitor Closely (1)dabrafenib decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• dalfampridine

  Monitor Closely (1)metformin, dalfampridine. Either increases levels of the other by Other (see comment). Use Caution/Monitor. Comment: Metformin and dalfampridine are organic cation transporter 2 (OCT2) substrates; both drugs may compete for renal tubular uptake and could potentially increase systemic exposure of either drug when administered concomitantly.

• damiana

  Minor (1)damiana decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Theoretical interaction.

• danazol

  Minor (1)danazol increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• darunavir

  Monitor Closely (1)darunavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• deflazacort

  Minor (1)deflazacort decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.

• desipramine

  Minor (1)desipramine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• desogestrel

  Monitor Closely (1)desogestrel decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• devil's claw

  Minor (1)devil's claw increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• dexamethasone

  Minor (1)dexamethasone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.

• diatrizoate

  Monitor Closely (1)diatrizoate increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• diatrizoate meglumine/diatrizoate sodium

  Monitor Closely (1)diatrizoate meglumine/diatrizoate sodium increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• diazoxide

  Monitor Closely (1)diazoxide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• dichlorphenamide

  Monitor Closely (1)dichlorphenamide, metformin. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Both drugs can cause metabolic acidosis.

• dienogest/estradiol valerate

  Monitor Closely (1)dienogest/estradiol valerate decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• diethylpropion

  Monitor Closely (1)diethylpropion decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• digoxin

  Monitor Closely (1)digoxin, metformin. Either increases levels of the other by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor. Measure serum digoxin concentrations before initiating metformin. Monitor patients who take both metformin and digoxin for possible digoxin toxicity and lactic acidosis. Reduce the digoxin and/or metformin dose as necessary.

• diltiazem

  Monitor Closely (1)diltiazem decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.Minor (1)diltiazem will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• dofetilide

  Monitor Closely (1)dofetilide will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

• dolutegravir

  Monitor Closely (1)dolutegravir will increase the level or effect of metformin by decreasing renal clearance. Modify Therapy/Monitor Closely. Dolutegravir inhibits the renal organic cation transporter, OCT2; when used with metformin, limit total daily dose of metformin to 1,000 mg either when starting metformin or dolutegravir; when stopping dolutegravir, adjustment of metformin dose may be necessary; monitor blood glucose when initiating concomitant use and after withdrawal of dolutegravir

• doxepin

  Minor (1)doxepin increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• drospirenone

  Monitor Closely (1)drospirenone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• dulaglutide

  Monitor Closely (1)dulaglutide, metformin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• elderberry

  Minor (1)elderberry increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (in vitro research).

• enalapril

  Monitor Closely (1)enalapril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• entecavir

  Monitor Closely (1)entecavir, metformin. Either increases levels of the other by Other (see comment). Use Caution/Monitor. Comment: Coadministration of entecavir with metformin may increase the risk of lactic acidosis.

• erdafitinib

  Monitor Closely (1)metformin increases levels of erdafitinib by decreasing renal clearance. Modify Therapy/Monitor Closely. Consider alternatives that are not OCT2 substrates or consider reducing the dose of OCT2 substrates based on tolerability.

• escitalopram

  Monitor Closely (1)escitalopram increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• estradiol

  Monitor Closely (1)estradiol decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• estrogens conjugated synthetic

  Monitor Closely (1)estrogens conjugated synthetic decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• estropipate

  Monitor Closely (1)estropipate decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• ethacrynic acid

  Monitor Closely (1)ethacrynic acid decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• ethanol

  Serious - Use Alternative (1)ethanol increases toxicity of metformin by Other (see comment). Contraindicated. Comment: Excessive EtOH consumption may alter glycemic control. Some sulfonylureas may produce a disulfiram like rxn; alcohol may potentiate the risk of lactic acidosis.

• ethinylestradiol

  Monitor Closely (1)ethinylestradiol decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• ethiodized oil

  Monitor Closely (1)ethiodized oil increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• etonogestrel

  Monitor Closely (1)etonogestrel decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• eucalyptus

  Minor (1)eucalyptus increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Theoretical interaction.

• everolimus

  Monitor Closely (1)everolimus decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• exenatide injectable solution

  Monitor Closely (1)exenatide injectable solution, metformin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.

• exenatide injectable suspension

  Monitor Closely (1)exenatide injectable suspension, metformin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.

• famotidine

  Minor (1)famotidine increases levels of metformin by decreasing renal clearance. Minor/Significance Unknown.

• felodipine

  Monitor Closely (1)felodipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• fleroxacin

  Monitor Closely (1)fleroxacin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.

• fludrocortisone

  Minor (1)fludrocortisone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.

• fluoxetine

  Monitor Closely (1)fluoxetine increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• fluoxymesterone

  Minor (1)fluoxymesterone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• fluphenazine

  Monitor Closely (1)fluphenazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• fluvoxamine

  Monitor Closely (1)fluvoxamine increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• fo-ti

  Minor (1)fo-ti increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• folic acid

  Minor (1)metformin decreases levels of folic acid by unspecified interaction mechanism. Minor/Significance Unknown.

• forskolin

  Minor (1)forskolin increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Colenol, a compound found in Coleus root, may stimulate insulin release.

• fosamprenavir

  Monitor Closely (1)fosamprenavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• fosinopril

  Monitor Closely (1)fosinopril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• fosphenytoin

  Monitor Closely (1)fosphenytoin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• furosemide

  Minor (2)metformin decreases levels of furosemide by unspecified interaction mechanism. Minor/Significance Unknown.
  
  furosemide increases levels of metformin by unspecified interaction mechanism. Minor/Significance Unknown. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• gemifloxacin

  Monitor Closely (1)gemifloxacin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.

• glucagon intranasal

  Monitor Closely (1)glucagon intranasal decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• glycopyrrolate

  Monitor Closely (1)glycopyrrolate increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. May require a dose reduction.

• goserelin

  Monitor Closely (1)goserelin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• gotu kola

  Minor (1)gotu kola increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction).

• guanfacine

  Minor (2)guanfacine decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  guanfacine, metformin. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

• gymnema

  Minor (1)gymnema increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• histrelin

  Monitor Closely (1)histrelin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• horse chestnut seed

  Minor (1)horse chestnut seed increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• hydrochlorothiazide

  Minor (2)hydrochlorothiazide will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  hydrochlorothiazide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• hydrocortisone

  Minor (1)hydrocortisone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.

• hydroxyprogesterone caproate

  Monitor Closely (1)hydroxyprogesterone caproate decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• ibuprofen/famotidine

  Minor (1)ibuprofen/famotidine increases levels of metformin by decreasing renal clearance. Minor/Significance Unknown.

• iloperidone

  Monitor Closely (1)iloperidone, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• imidapril

  Monitor Closely (1)imidapril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• imipramine

  Minor (1)imipramine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• indapamide

  Minor (1)indapamide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• indinavir

  Monitor Closely (1)indinavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• insulin aspart

  Monitor Closely (1)metformin, insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin aspart protamine/insulin aspart

  Monitor Closely (1)metformin, insulin aspart protamine/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin degludec

  Monitor Closely (1)metformin, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin degludec/insulin aspart

  Monitor Closely (1)metformin, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin detemir

  Monitor Closely (1)metformin, insulin detemir. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin glargine

  Monitor Closely (1)metformin, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin glulisine

  Monitor Closely (1)metformin, insulin glulisine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin inhaled

  Monitor Closely (1)metformin, insulin inhaled. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin isophane human/insulin regular human

  Monitor Closely (1)metformin, insulin isophane human/insulin regular human. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin lispro

  Monitor Closely (1)metformin, insulin lispro. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin lispro protamine/insulin lispro

  Monitor Closely (1)metformin, insulin lispro protamine/insulin lispro. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin NPH

  Monitor Closely (1)metformin, insulin NPH. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin regular human

  Monitor Closely (1)metformin, insulin regular human. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• iodixanol

  Monitor Closely (1)iodixanol increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• ioflupane I 123

  Monitor Closely (1)ioflupane I 123 increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• iohexol

  Monitor Closely (1)iohexol increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• iopamidol

  Monitor Closely (1)iopamidol increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• iopromide

  Monitor Closely (1)iopromide increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• ioversol

  Monitor Closely (1)ioversol increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .Serious - Use Alternative (1)ioversol increases levels of metformin by decreasing renal clearance. Contraindicated. Acute renal failure or lactic acidosis may result. D/c metformin 48 hr before and after imaging study.

• ioxilan

  Monitor Closely (1)ioxilan increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• isocarboxazid

  Monitor Closely (1)isocarboxazid will increase the level or effect of metformin by unspecified interaction mechanism. Use Caution/Monitor.

• isoniazid

  Monitor Closely (1)isoniazid decreases effects of metformin by unspecified interaction mechanism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• isradipine

  Monitor Closely (1)isradipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• juniper

  Minor (1)juniper increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).

• ketotifen, ophthalmic

  Monitor Closely (1)ketotifen, ophthalmic, metformin. Other (see comment). Use Caution/Monitor. Comment: Combination may result in thrombocytopenia (rare). Monitor CBC.

• L-methylfolate

  Minor (1)metformin decreases levels of L-methylfolate by unspecified interaction mechanism. Minor/Significance Unknown.

• lanreotide

  Monitor Closely (1)lanreotide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• leuprolide

  Monitor Closely (1)leuprolide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• levofloxacin

  Monitor Closely (1)levofloxacin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.

• levonorgestrel intrauterine

  Monitor Closely (1)levonorgestrel intrauterine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• levonorgestrel oral

  Monitor Closely (1)levonorgestrel oral decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• levothyroxine

  Monitor Closely (1)levothyroxine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• linezolid

  Monitor Closely (1)linezolid will increase the level or effect of metformin by unspecified interaction mechanism. Use Caution/Monitor.

• liothyronine

  Monitor Closely (1)liothyronine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• liotrix

  Monitor Closely (1)liotrix decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• liraglutide

  Monitor Closely (1)liraglutide, metformin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.

• lisinopril

  Monitor Closely (1)lisinopril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• lithium

  Monitor Closely (1)metformin decreases levels of lithium by Other (see comment). Use Caution/Monitor. Comment: SGLT2 inhibitors with lithium may decrease serum lithium concentrations; monitor serum lithium concentration more frequently during therapy initiation and dosage changes.

• lofepramine

  Minor (1)lofepramine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• lonapegsomatropin

  Monitor Closely (1)lonapegsomatropin decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Closely monitor blood glucose when treated with antidiabetic agents. Lonapegsomatropin may decrease insulin sensitivity, particularly at higher doses. Patients with diabetes mellitus may require adjustment of their doses of insulin and/or other antihyperglycemic agents.

• lopinavir

  Monitor Closely (1)lopinavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• lurasidone

  Monitor Closely (1)lurasidone, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• lycopus

  Minor (1)lycopus increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).

• maitake

  Minor (1)maitake increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (animal research).

• maprotiline

  Minor (1)maprotiline increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• marijuana

  Monitor Closely (1)marijuana decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• mecasermin

  Monitor Closely (1)mecasermin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Additive hypoglycemic effects.

• medroxyprogesterone

  Monitor Closely (1)medroxyprogesterone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• memantine

  Minor (1)memantine will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• mesterolone

  Minor (1)mesterolone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• methamphetamine

  Monitor Closely (1)methamphetamine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• methazolamide

  Monitor Closely (1)methazolamide increases toxicity of metformin by Other (see comment). Use Caution/Monitor. Comment: Decreases serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis.

• methyclothiazide

  Minor (2)methyclothiazide will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  methyclothiazide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• methylene blue

  Serious - Use Alternative (1)methylene blue will increase the level or effect of metformin by unspecified interaction mechanism. Avoid or Use Alternate Drug.

• methylprednisolone

  Minor (1)methylprednisolone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.

• methyltestosterone

  Minor (1)methyltestosterone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• metolazone

  Minor (1)metolazone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• midodrine

  Minor (1)metformin will increase the level or effect of midodrine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• moexipril

  Monitor Closely (1)moexipril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• moxifloxacin

  Monitor Closely (1)moxifloxacin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.

• nelfinavir

  Monitor Closely (1)nelfinavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• nettle

  Minor (1)nettle increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction).

• niacin

  Monitor Closely (1)niacin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• nicardipine

  Monitor Closely (1)nicardipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• nifedipine

  Monitor Closely (1)nifedipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.Minor (1)nifedipine increases levels of metformin by enhancing GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• nilotinib

  Monitor Closely (1)nilotinib decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• nimodipine

  Monitor Closely (1)nimodipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• nisoldipine

  Monitor Closely (1)nisoldipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• nizatidine

  Monitor Closely (1)nizatidine will increase the level or effect of metformin by decreasing renal clearance. Modify Therapy/Monitor Closely.

• norelgestromin

  Monitor Closely (1)norelgestromin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• norethindrone

  Monitor Closely (1)norethindrone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• norgestimate

  Monitor Closely (1)norgestimate decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• nortriptyline

  Minor (1)nortriptyline increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• octreotide

  Monitor Closely (1)octreotide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• ofloxacin

  Monitor Closely (1)ofloxacin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.Minor (2)metformin will increase the level or effect of ofloxacin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  ofloxacin, metformin. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Potential dysglycemia.

• olanzapine

  Monitor Closely (1)olanzapine, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• omacetaxine

  Monitor Closely (1)omacetaxine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

  Monitor Closely (1)ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Monitor for signs of onset of lactic acidosis such as respiratory distress, somnolence, and non-specific abdominal distress or worsening renal function; concomitant metformin use in patients with renal insufficiency or hepatic impairment not recommended.

• ondansetron

  Monitor Closely (1)ondansetron increases levels of metformin by Other (see comment). Use Caution/Monitor. Comment: Ondansetron inhibition of transporters (MATE or OCTs), which are responsible for active renal secretion of metformin may play a role.

• opuntia ficus indica

  Monitor Closely (1)opuntia ficus indica increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• oxandrolone

  Minor (1)oxandrolone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• oxymetholone

  Minor (1)oxymetholone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• pacritinib

  Serious - Use Alternative (1)pacritinib will increase the level or effect of metformin by Other (see comment). Avoid or Use Alternate Drug. Concomitant administration of pacritinib (OCT1 inhibitor) with OCT1 substrates may increase the plasma concentrations of these substrates.

• paliperidone

  Monitor Closely (1)paliperidone, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• paroxetine

  Monitor Closely (1)paroxetine increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• pasireotide

  Monitor Closely (1)pasireotide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• patiromer

  Monitor Closely (1)patiromer will decrease the level or effect of metformin by drug binding in GI tract. Modify Therapy/Monitor Closely. Separate administration by at least 3 hr from patiromer

• pegvisomant

  Minor (1)pegvisomant increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• pentamidine

  Monitor Closely (1)pentamidine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• perindopril

  Monitor Closely (1)perindopril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• perphenazine

  Monitor Closely (1)perphenazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• phendimetrazine

  Monitor Closely (1)phendimetrazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• phenelzine

  Monitor Closely (1)phenelzine will increase the level or effect of metformin by unspecified interaction mechanism. Use Caution/Monitor.

• phentermine

  Monitor Closely (1)phentermine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• phenytoin

  Monitor Closely (1)phenytoin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• potassium acid phosphate

  Minor (1)potassium acid phosphate increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia.

• potassium chloride

  Minor (1)potassium chloride increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia.

• potassium citrate

  Minor (1)potassium citrate increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia.

• prednisolone

  Minor (1)prednisolone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.

• prednisone

  Minor (1)prednisone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.

• procainamide

  Monitor Closely (1)metformin will increase the level or effect of procainamide by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

• procarbazine

  Monitor Closely (1)procarbazine will increase the level or effect of metformin by unspecified interaction mechanism. Use Caution/Monitor.

• prochlorperazine

  Monitor Closely (1)prochlorperazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• progesterone intravaginal gel

  Monitor Closely (1)progesterone intravaginal gel decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• progesterone micronized

  Monitor Closely (1)progesterone micronized decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• progesterone, natural

  Monitor Closely (1)progesterone, natural decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• promethazine

  Monitor Closely (1)promethazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• protriptyline

  Minor (1)protriptyline increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• quetiapine

  Monitor Closely (1)quetiapine, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• quinapril

  Monitor Closely (1)quinapril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• quinidine

  Monitor Closely (1)quinidine will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

• quinine

  Minor (1)metformin will increase the level or effect of quinine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ramipril

  Monitor Closely (1)ramipril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• ranolazine

  Serious - Use Alternative (1)ranolazine will increase the level or effect of metformin by decreasing elimination. Avoid or Use Alternate Drug. Limit metformin dose to 1700 mg/day when used together with ranolazine 1000 mg twice daily; monitor closelly for signs or symptoms of metformin toxicity

• rasagiline

  Monitor Closely (1)rasagiline will increase the level or effect of metformin by unspecified interaction mechanism. Use Caution/Monitor.

• risdiplam

  Serious - Use Alternative (1)risdiplam will increase the level or effect of metformin by decreasing elimination. Avoid or Use Alternate Drug. Risdiplam inhibits MATE1 and MATE2-K. If unable to avoid coadministration with MATE substrates, consider dosage reduction of MATE substrate.

• risperidone

  Monitor Closely (1)risperidone, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• ritonavir

  Monitor Closely (1)ritonavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• sage

  Minor (1)sage increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• saquinavir

  Monitor Closely (1)saquinavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• selegiline

  Serious - Use Alternative (1)selegiline will increase the level or effect of metformin by unspecified interaction mechanism. Avoid or Use Alternate Drug.

• selegiline transdermal

  Serious - Use Alternative (1)selegiline transdermal will increase the level or effect of metformin by unspecified interaction mechanism. Avoid or Use Alternate Drug.

• sertraline

  Monitor Closely (1)sertraline increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• shark cartilage

  Monitor Closely (1)shark cartilage increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Theoretical interaction.

• sirolimus

  Monitor Closely (1)sirolimus decreases levels of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• somapacitan

  Monitor Closely (1)somapacitan decreases effects of metformin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone products may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating somapacitan. .

• somatropin

  Monitor Closely (1)somatropin decreases levels of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• stevia

  Minor (1)stevia increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• sulfamethoxazole

  Minor (1)sulfamethoxazole will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• sulfamethoxypyridazine

  Monitor Closely (1)sulfamethoxypyridazine increases effects of metformin by unspecified interaction mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• tacrolimus

  Monitor Closely (1)tacrolimus decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• tafenoquine

  Serious - Use Alternative (1)tafenoquine will increase the level or effect of metformin by Other (see comment). Avoid or Use Alternate Drug. Tafenoquine inhibits organic cation transporter-2 (OCT2) and multidrug and toxin extrusion (MATE) transporters in vitro. Avoid coadministration with OCT2 or MATE substrates. If coadministration cannot be avoided, monitor for substrate-related toxicities and consider dosage reduction if needed based on product labeling of the coadministered drug.

• tedizolid

  Serious - Use Alternative (1)tedizolid will increase the level or effect of metformin by unspecified interaction mechanism. Avoid or Use Alternate Drug.

• temsirolimus

  Monitor Closely (1)temsirolimus decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• tenofovir DF

  Monitor Closely (1)tenofovir DF increases levels of metformin by decreasing renal clearance. Use Caution/Monitor. Increased risk of lactic acidosis.

• testosterone

  Minor (1)testosterone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• testosterone buccal system

  Minor (1)testosterone buccal system increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• testosterone topical

  Minor (1)testosterone topical increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• thioridazine

  Monitor Closely (1)thioridazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• thyroid desiccated

  Monitor Closely (1)thyroid desiccated decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• tibolone

  Monitor Closely (1)tibolone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• tipranavir

  Monitor Closely (1)tipranavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• tongkat ali

  Minor (1)tongkat ali increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypoglycemia.

• topiramate

  Monitor Closely (1)topiramate increases toxicity of metformin by Other (see comment). Use Caution/Monitor. Comment: Decreases serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis.

• torsemide

  Monitor Closely (1)torsemide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• trandolapril

  Monitor Closely (1)trandolapril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• tranylcypromine

  Serious - Use Alternative (1)tranylcypromine will increase the level or effect of metformin by unspecified interaction mechanism. Avoid or Use Alternate Drug.

• trazodone

  Minor (1)trazodone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• triamcinolone acetonide injectable suspension

  Monitor Closely (1)triamcinolone acetonide injectable suspension decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Corticosteroids may diminish hypoglycemic effect of antidiabetic agents. Monitor blood glucose levels carefully.

• triamterene

  Minor (1)metformin will increase the level or effect of triamterene by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• trifluoperazine

  Monitor Closely (1)trifluoperazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• trilaciclib

  Serious - Use Alternative (1)trilaciclib will decrease the level or effect of metformin by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of trilaciclib (OCT2, MATE1, and MATE-2K inhibitor) with substrates where minimal increased concentration in kidney or blood may lead to serious or life-threatening toxicities.

• trimethoprim

  Monitor Closely (1)trimethoprim increases levels of metformin by Other (see comment). Use Caution/Monitor. Comment: Trimethoprim may inhibit active renal tubular secretion of metformin (eg, via OCT2, MATE1); dose adjustments may be necessary.Minor (1)metformin will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• trimipramine

  Minor (1)trimipramine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• triptorelin

  Monitor Closely (1)triptorelin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• trospium chloride

  Monitor Closely (1)metformin will decrease the level or effect of trospium chloride by increasing renal clearance. Use Caution/Monitor. Coadministration reduced steady state trospium systemic exposure (decreased AUC and Cmax) by competing for renal tubular secretion

• vanadium

  Minor (1)vanadium increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• vandetanib

  Monitor Closely (1)vandetanib increases levels of metformin by Other (see comment). Modify Therapy/Monitor Closely. Comment: Vandetanib inhibits the uptake of substrates of organic cation transporter type 2 (OCT2).

• verapamil

  Monitor Closely (1)verapamil decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Verapamil may inhibit hepatic uptake of metformin by OCT1 and/or other transporters.Minor (1)metformin will increase the level or effect of verapamil by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• vilazodone

  Monitor Closely (1)vilazodone increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• vorinostat

  Monitor Closely (1)vorinostat decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• vortioxetine

  Monitor Closely (1)vortioxetine increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• xipamide

  Monitor Closely (1)xipamide decreases levels of metformin by increasing renal clearance. Use Caution/Monitor.

• ziprasidone

  Monitor Closely (1)ziprasidone, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• zonisamide

  Monitor Closely (1)zonisamide increases toxicity of metformin by Other (see comment). Use Caution/Monitor. Comment: Decreases serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis.