metformin/repaglinide (Rx)

Brand and Other Names:PrandiMet
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

metformin/repaglinide

tablet

  • 500mg/1mg
  • 500mg/2mg

Type 2 Diabetes Mellitus

Indicated as adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus who are already treated with a meglitinide and metformin, or who have inadequate glycemic control on a meglitinide alone or metformin alone

Currently using comcomitant repaglinide and metformin

  • Start initial PrandiMet dose similar to patient's current repaglinide/metformin dosage, but do not exceed; titrate as necessary to acheive targeted glycemic control

Inadequately controlled with either metformin or a meglitinide monotherapy

  • 500 mg/1 mg PO q12hr ac initially
  • May gradually increase dose based on glycemic response

Dosage Modifications

Hepatic impairment: Do not administer

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 the drug

Safety and efficacy not established; not recommended for use in children

Currently using comcomitant repaglinide and metformin

Start initial PrandiMet dose similar to patient's current repaglinide/metformin dosage, but do not exceed; titrate as necessary to acheive targeted glycemic control

Do not administer to patients >80 years before assessing renal function and determined to be normal

Inadequately controlled with either metformin or meglitinide monotherapy

500 mg/1 mg PO q12hr ac initially

May gradually and conservatively increase dose based on glycemic response

Do not administer to patients >80 years before assessing renal function and determined to be normal

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Interactions

Interaction Checker

and metformin/repaglinide

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            Contraindicated (1)

            • gemfibrozil

              gemfibrozil will increase the level or effect of repaglinide by Other (see comment). Contraindicated. Repaglinide is a CYP2C8 substrate. Gemfibrozil inhibits CYP2C8 and substantially increases repaglinide levels.

            Serious - Use Alternative (34)

            • abametapir

              abametapir will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

            • apalutamide

              apalutamide will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

            • carbamazepine

              carbamazepine will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • cimetidine

              cimetidine will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • clarithromycin

              clarithromycin will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • clopidogrel

              clopidogrel will increase the level or effect of repaglinide by Other (see comment). Avoid or Use Alternate Drug. Clopidogrel inhibits CYP2C8. Coadministration significantly increases repaglinide serum levels. If unable to avoid coadministration, decrease initial repaglinide dose to 0.5 mg/meal and do not exceed 4 mg/day.

            • 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.

            • eluxadoline

              repaglinide increases levels of eluxadoline by decreasing metabolism. Avoid or Use Alternate Drug. Decrease eluxadoline dose to 75 mg PO BID if coadministered with OATP1B1 inhibitors. .

            • erythromycin base

              erythromycin base will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erythromycin lactobionate

              erythromycin lactobionate will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erythromycin stearate

              erythromycin stearate will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ethanol

              ethanol, repaglinide. Other (see comment). Contraindicated. Comment: Excessive EtOH consumption may alter glycemic control. Some sulfonylureas may produce a disulfiram like rxn.

              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.

            • fexinidazole

              fexinidazole will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

            • 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.

            • idelalisib

              idelalisib will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

            • ivosidenib

              ivosidenib will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

            • ketoconazole

              ketoconazole will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • letermovir

              letermovir, repaglinide. Either increases levels of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations. When letermovir is coadministered with cyclosporine, avoid use with repaglinide.

            • lumacaftor/ivacaftor

              lumacaftor/ivacaftor will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repaglinide is metabolized by CYP3A and CYP2C8. Lumacaftor /ivacaftor is a strong CYP3A4 inducer and may also induce CYP2C8.

            • methylene blue

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

            • nefazodone

              nefazodone will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • 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

            • rifabutin

              rifabutin will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • rifampin

              rifampin will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • St John's Wort

              St John's Wort will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • 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.

            • tucatinib

              tucatinib will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

            Monitor Closely (298)

            • 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.

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

            • alogliptin

              alogliptin, repaglinide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of alogliptin with insulin and/or insulin secretagogues (eg, sulfonylureas, meglitinide derivatives) may increase risk for hypoglycemia; may require lower dose of insulin or insulin secretagogue .

            • 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.

            • amobarbital

              amobarbital will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • apalutamide

              apalutamide will decrease the level or effect of repaglinide by increasing elimination. Use Caution/Monitor. Apalutamide weakly induces OATP1B1 and may decrease systemic exposure of drugs that are OATP1B1 substrates.

            • aprepitant

              aprepitant will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • aripiprazole

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

              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.

            • armodafinil

              armodafinil will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • 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.

            • artemether/lumefantrine

              artemether/lumefantrine will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • asenapine

              asenapine, repaglinide. 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 will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

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

            • atorvastatin

              repaglinide increases toxicity of atorvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • 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.

            • bexarotene

              bexarotene increases effects of repaglinide by pharmacodynamic synergism. Use Caution/Monitor. Based on the mechanism of action, bexarotene capsules may increase the action of insulin enhancing agents, resulting in hypoglycemia. Hypoglycemia has not been associated with bexarotene monotherapy.

            • 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 repaglinide by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypoglycemia.

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

            • bosentan

              bosentan will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • brexpiprazole

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

            • budesonide

              budesonide will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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.

            • butabarbital

              butabarbital will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • butalbital

              butalbital will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • canagliflozin

              repaglinide, canagliflozin. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with canagliflozin.

            • cannabidiol

              cannabidiol will increase the level or effect of repaglinide by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C8 activity. Consider reducing the dose when concomitantly using CYP2C8 substrates.

            • 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.

            • cenobamate

              cenobamate will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

            • 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.

            • chloramphenicol

              chloramphenicol will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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.

            • cholic acid

              repaglinide increases toxicity of cholic acid by decreasing elimination. Modify Therapy/Monitor Closely. Avoid concomitant use of inhibitors of the bile salt efflux pump (BSEP). May exacerbate accumulation of conjugated bile salts in the liver and result in clinical symptoms. If concomitant use is necessary, monitor serum transaminases and bilirubin.

            • 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 repaglinide by pharmacodynamic synergism. Use Caution/Monitor. Potential for hypoglycemia.

              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.

              ciprofloxacin increases effects of repaglinide 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.

            • clozapine

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

            • 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.

            • cobicistat

              cobicistat will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • colesevelam

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

            • conivaptan

              conivaptan will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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.

            • cortisone

              cortisone will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • crizotinib

              crizotinib increases levels of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • crofelemer

              crofelemer increases levels of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

            • cyclosporine

              cyclosporine will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Cyclosporine increases low dose repaglinide exposures by 2.5 fold. Do not exceed 6 mg/day of repaglinide. Consider increasing frequency of glucose monitoring if coadministered.

            • dabrafenib

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

              dabrafenib will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • 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.

            • dapagliflozin

              repaglinide, dapagliflozin. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with dapagliflozin.

            • darifenacin

              darifenacin will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • darunavir

              darunavir will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

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

            • dasatinib

              dasatinib will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • desogestrel

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

            • deferasirox

              deferasirox will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Consider repaglinide dose reduction and carefully monitor blood glucose levels when repaglinide is used concomitantly with deferasirox.

            • dexamethasone

              dexamethasone will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • DHEA, herbal

              DHEA, herbal will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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.

              diltiazem will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor glucose and hypoglycemic symptoms (eg, headache, dizziness, drowsiness, nervousness, confusion, tremor, hunger, weakness, perspiration, palpitations).

            • dofetilide

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

            • dronedarone

              dronedarone will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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.

              dulaglutide, repaglinide. 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.

            • efavirenz

              efavirenz will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • enalapril

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

            • elagolix

              elagolix decreases levels of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

            • eltrombopag

              eltrombopag increases levels of repaglinide by decreasing metabolism. Use Caution/Monitor. OATP transporter protein inhibition.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP3A4 inhibitor; contraindicated with CYP3A4 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

            • empagliflozin

              empagliflozin, repaglinide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with SGLT2 inhibitors.

            • encorafenib

              encorafenib, repaglinide. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

            • 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.

            • enzalutamide

              enzalutamide will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • 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.

            • ertugliflozin

              ertugliflozin, repaglinide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.

            • escitalopram

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

            • eslicarbazepine acetate

              eslicarbazepine acetate will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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.

            • etravirine

              etravirine will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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 solution, repaglinide. 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.

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

            • fedratinib

              fedratinib will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • 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 repaglinide 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.

              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.

            • fluconazole

              fluconazole will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fluoxetine

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

            • fludrocortisone

              fludrocortisone will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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.

            • fluvastatin

              repaglinide increases toxicity of fluvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • fluvoxamine

              fluvoxamine will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

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

            • fosamprenavir

              fosamprenavir will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              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 will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • 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.

            • fostemsavir

              fostemsavir will increase the level or effect of repaglinide by Other (see comment). Modify Therapy/Monitor Closely. Fostemsavir inhibits OATP1B1/3 transporter. If possible, avoid coadministration or modify dose of OATP1B1/3 substrates coadministered with fostemsavir.

            • gemifloxacin

              gemifloxacin increases effects of repaglinide 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.

              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.

            • glecaprevir/pibrentasvir

              repaglinide will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Use Caution/Monitor. Caution when coadministering glecaprevir/pibrentasvir with OATP1B1/OATP1B3 inhibitors

              glecaprevir/pibrentasvir will increase the level or effect of repaglinide by Other (see comment). Use Caution/Monitor. Coadministration with glecaprevir/pibrentasvir may increase plasma concentration of drugs that are substrates of OATP1B1 or OATP1B3

            • 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.

            • grapefruit

              grapefruit will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • griseofulvin

              griseofulvin will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • histrelin

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

            • hydrocortisone

              hydrocortisone will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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.

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

              iloperidone increases levels of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.

            • imidapril

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

            • indinavir

              indinavir will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • 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.

              isoniazid will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • 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.

            • istradefylline

              istradefylline will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

            • itraconazole

              itraconazole will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ketotifen, ophthalmic

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

              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.

            • lapatinib

              lapatinib will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • leuprolide

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

            • levofloxacin

              levofloxacin increases effects of repaglinide 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.

              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.

            • liraglutide

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

            • 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.

            • lopinavir

              lopinavir will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

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

            • lorlatinib

              lorlatinib will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • 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.

            • lumefantrine

              lumefantrine will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lurasidone

              lurasidone, repaglinide. 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.

              marijuana will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

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

            • mecasermin

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

              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.

            • methylprednisolone

              methylprednisolone will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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.

            • metreleptin

              repaglinide, metreleptin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of metreleptin with insulin and/or insulin secretagogues (eg, sulfonylureas, meglitinide derivatives) may increase risk for hypoglycemia; may require lower dose of insulin or insulin secretagogue.

            • metronidazole

              metronidazole will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • miconazole vaginal

              miconazole vaginal will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • mifepristone

              mifepristone will increase the level or effect of repaglinide by Other (see comment). Use Caution/Monitor. Inhibits CYP2C8/2C9; use smallest recommended doses for substrates and monitor

              mifepristone will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • mitotane

              mitotane decreases levels of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.

            • modafinil

              modafinil will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • 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.

              moxifloxacin increases effects of repaglinide 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.

            • nafcillin

              nafcillin will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nelfinavir

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

            • nelfinavir

              nelfinavir will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nevirapine

              nevirapine will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • 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.

              nifedipine will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nilotinib

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

              nilotinib will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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.

            • ofloxacin

              ofloxacin increases effects of repaglinide 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.

            • 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.

              olanzapine, repaglinide. 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.

            • opuntia ficus indica

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

            • ombitasvir/paritaprevir/ritonavir & dasabuvir

              ombitasvir/paritaprevir/ritonavir & dasabuvir 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.

            • oxcarbazepine

              oxcarbazepine will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • paliperidone

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

              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.

            • pentobarbital

              pentobarbital will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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. Use Caution/Monitor. May administer 3 hours apart

            • 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.

            • phenobarbital

              phenobarbital will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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 will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              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.

            • posaconazole

              posaconazole will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • procainamide

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

            • pravastatin

              repaglinide increases toxicity of pravastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • prednisone

              prednisone will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • primidone

              primidone will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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, repaglinide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

              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.

            • quinupristin/dalfopristin

              quinupristin/dalfopristin will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • 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.

            • ranolazine

              ranolazine increases toxicity of repaglinide by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • rasagiline

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

            • ribociclib

              ribociclib will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rifapentine

              rifapentine will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • risperidone

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

              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. .

              ritonavir will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rosuvastatin

              repaglinide increases toxicity of rosuvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • saquinavir

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

            • rucaparib

              rucaparib will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

            • rufinamide

              rufinamide will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • sacubitril/valsartan

              repaglinide will increase the level or effect of sacubitril/valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • saquinavir

              saquinavir will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • secobarbital

              secobarbital will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • semaglutide

              semaglutide, repaglinide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin secretagogues with GLP-1 agonists may increase hypoglycemia risk. Lowering the insulin secretagogue dose may reduce hypoglycemia risk. .

            • sertraline

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

            • shark cartilage

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

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

            • simvastatin

              repaglinide increases toxicity of simvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • sirolimus

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

            • sofosbuvir/velpatasvir

              sofosbuvir/velpatasvir increases levels of repaglinide by Other (see comment). Use Caution/Monitor. Comment: Velpatasvir inhibits OATP1B1, OATP1B3, and OATP2B1 transporters. .

            • 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.

            • spironolactone

              spironolactone will increase the level or effect of repaglinide by Other (see comment). Use Caution/Monitor. Spironolactone inhibits CYP2C8; repaglinice dose may need to be adjusted as it is metabolized by CYP2C8

            • stiripentol

              stiripentol, repaglinide. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.

              stiripentol will increase the level or effect of repaglinide by Other (see comment). Modify Therapy/Monitor Closely. Stiripentol is a CYP2C8 inhibitor. Consider dosage reduction for CYP2C8 substrates if adverse effects are experienced when coadministered.

            • sulfadiazine

              sulfadiazine increases levels of repaglinide by plasma protein binding competition. Use Caution/Monitor.

            • sulfamethoxazole

              sulfamethoxazole increases levels of repaglinide by plasma protein binding competition. Use Caution/Monitor.

            • sulfamethoxypyridazine

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

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

            • sulfisoxazole

              sulfisoxazole increases levels of repaglinide by plasma protein binding competition. Use Caution/Monitor.

            • tacrolimus

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

            • tazemetostat

              tazemetostat will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tecovirimat

              tecovirimat will increase the level or effect of repaglinide by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Tecovirimat is a weak inhibitor of CYP2C8 and CYP2C19. Monitor for adverse effects if coadministered with substrates of these enzymes. Monitor blood glucose and monitor for hypoglycemic symptoms.

              tecovirimat will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

            • 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.

            • teriflunomide

              teriflunomide increases levels of repaglinide by Other (see comment). Use Caution/Monitor. Comment: Teriflunomide inhibits CYP2C8; caution when coadministered with CYP2C8 substrates.

            • 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. .

              tipranavir will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              tipranavir, repaglinide. Other (see comment). Use Caution/Monitor. Comment: Tipranavir's effect on oral hypoglycemics via hepatic CYP2C9 unknown; carefully monitor blood glucose.

            • topiramate

              topiramate will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              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.

            • triamcinolone acetonide injectable suspension

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

            • 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 repaglinide by decreasing metabolism. Use Caution/Monitor. Hepatic cytochrome P450 2C8.

              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.

            • valsartan

              repaglinide will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • 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.

              verapamil will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • vilazodone

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

            • voriconazole

              voriconazole will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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 repaglinide by increasing renal clearance. Use Caution/Monitor.

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

            • zafirlukast

              zafirlukast will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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.

            • ziprasidone

              ziprasidone, repaglinide. 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 (95)

            • agrimony

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

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

            • American ginseng

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

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

            • amitriptyline

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

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

            • amoxapine

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

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

            • anamu

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

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

            • bendroflumethiazide

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

              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.

              budesonide decreases effects of repaglinide 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.

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

            • chlorthalidone

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

              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 repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

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

            • clomipramine

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

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

            • clonidine

              clonidine decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

              clonidine, repaglinide. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

              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 repaglinide by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).

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

            • cortisone

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

              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 repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • 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 repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Theoretical interaction.

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

            • danazol

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

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

            • deflazacort

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

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

            • desipramine

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

              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.

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

            • dexamethasone

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

              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 repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

            • doxepin

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

            • elderberry

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

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

            • eucalyptus

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

              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 repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown.

            • fludrocortisone

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

            • fluoxymesterone

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

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

            • fo-ti

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

              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 repaglinide by pharmacodynamic synergism. Minor/Significance Unknown. Colenol, a compound found in Coleus root, may stimulate insulin release.

            • 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 repaglinide by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction).

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

            • guanfacine

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

              guanfacine decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

              guanfacine decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

              guanfacine, repaglinide. 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.

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

            • horse chestnut seed

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

              horse chestnut seed increases effects of repaglinide 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 repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

              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 repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown.

              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 repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

            • imipramine

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

            • indapamide

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

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

            • isoniazid

              isoniazid decreases effects of repaglinide by unspecified interaction mechanism. Minor/Significance Unknown.

            • L-methylfolate

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

            • juniper

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

            • juniper

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

            • lofepramine

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

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

            • lycopus

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

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

            • maitake

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

              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.

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

            • mesterolone

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

            • methyclothiazide

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

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

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

            • methylprednisolone

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

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

            • methyltestosterone

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

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

            • metolazone

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

              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 repaglinide by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction).

            • 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 repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

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

            • ofloxacin

              ofloxacin, repaglinide. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Potential dysglycemia.

              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 repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

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

            • oxymetholone

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

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

            • pegvisomant

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

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

            • potassium chloride

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

              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 repaglinide by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia.

              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.

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

            • prednisone

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

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

            • protriptyline

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

              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 repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

            • sage

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

            • stevia

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

              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 repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

            • testosterone

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

            • testosterone buccal system

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

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

            • testosterone topical

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

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

            • tongkat ali

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

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

            • trazodone

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

              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.

            • trimipramine

              trimipramine increases effects of repaglinide by pharmacodynamic synergism. 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.

              vanadium increases effects of repaglinide 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.

            • voclosporin

              voclosporin will increase the level or effect of repaglinide by Other (see comment). Minor/Significance Unknown. Information suggests voclosporin (an OATP1B1 inhibitor) may increase in the concentration of OATP1B1 substrates is possible. Monitor for adverse reactions of OATP1B1 substrates when coadministered with voclosporin.

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            Adverse Effects

            Frequency Not Defined

            Diarrhea

            Nausea/vomiting

            Symptomatic hypoglycemia

            Headache

            Upper respiratory infection

            Hypoglycemia

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            Warnings

            Black Box Warnings

            Lactic acidosis is a rare but potentially severe consequence of therapy with metformin; characterized by elevated blood lactate levels (>5 mmol/L), decreased blood pH, electrolyte disturbances with an increased anion gap, and an increased lactate/pyruvate ratio. When metformin is implicated as the cause of lactic acidosis, metformin plasma concentrations >5 mcg/mL are generally found

            Patients with CHF requiring pharmacologic management, in particular those with unstable or acute CHF who are at risk of hypoperfusion and hypoxemia, are at an increased risk of lactic acidosis. The risk of lactic acidosis increases with the degree of renal dysfunction and the patient’s age

            Do not start in patients aged 80 years or older unless CrCl demonstrates that renal function is not reduced because these patients are more susceptible to developing lactic acidosis. Metformin should be promptly withheld in the presence of any condition associated with hypoxemia, dehydration, or sepsis

            Should generally be avoided in patients with clinical or laboratory evidence of hepatic disease; caution patients against excessive alcohol intake, either acute or chronic, during metformin therapy because alcohol potentiates the effects of metformin on lactate metabolism

            The onset of lactic acidosis often is subtle and accompanied by nonspecific symptoms (eg, malaise, myalgias, respiratory distress, increasing somnolence, nonspecific abdominal distress); with marked acidosis, hypothermia, hypotension, and resistant bradyarrhythmias may occur; instruct patients to recognize symptoms and notify their physician immediately if they occur; withdraw metformin until the situation is clarified

            Serum electrolytes, ketones, blood glucose, and if indicated, blood pH, lactate levels, and even blood metformin levels may be useful

            Once a patient is stabilized on any dose level of metformin, GI symptoms, which are common during initiation of therapy, are unlikely to be drug related; later occurrences of GI symptoms could be due to lactic acidosis or other serious disease

            Lactic acidosis is a medical emergency necessitating hospitalization and should be suspected in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonemia); discontinue metformin immediately if lactic acidosis suspected

            Metformin is highly dialyzable (clearance up to 170 mL/min under good hemodynamic conditions); prompt hemodialysis is recommended to correct the acidosis and to remove the accumulation

            Contraindications

            Severe renal disease: eGFR <30 ml/min/1.73 m²

            Acute or chronic metabolic acidosis, including diabetic ketoacidosis

            Concomitant gemfibrozil and itraconazole

            Hypersensitivity to repaglinide or metformin

            Cautions

            Risk of lactic acidosis due to accumulation of metformin; if metformin-associated lactic acidosis suspected, general supportive measures should be instituted promptly in a hospital setting, along with immediate discontinuation of therapy; in patients with a diagnosis or strong suspicion of lactic acidosis, prompt hemodialysis is recommended to correct acidosis and remove accumulated metformin (metformin hydrochloride is dialyzable, with a clearance of up to170 mL/minute under good hemodynamic conditions); hemodialysis has often resulted in reversal of symptoms and recovery

            Use caution in hepatic impairment

            Several of the postmarketing cases of metformin-associated lactic acidosis occurred in setting of acute congestive heart failure (particularly when accompanied by hypoperfusion and hypoxemia); cardiovascular collapse (shock) acute myocardial infarction, sepsis, and other conditions associated with hypoxemia have been associated with lactic acidosis and may also cause prerenal azotemia; discontinue therapy when such events occur

            Avoid excessive alcohol

            Can cause severe hypoglycemia, which can cause seizures, may be life-threatening, or cause death; hypoglycemia can impair concentration ability and reaction time; this may place an individual and others at risk in situations where these abilities are important (e.g., driving or operating other machinery); the elderly at at risk of hypoglycemia; symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic nerve disease, in patients using medications that block the sympathetic nervous system (e.g., beta-blockers), or in patients who experience recurrent hypoglycemia; patients should administer therapy before meals and be instructed to skip dose if a meal is skipped; in patients who experience hypoglycemia, the dose should be reduced; patients and caregivers must be educated to recognize and manage hypoglycemia; self-monitoring of blood glucose plays an essential role in prevention and management of hypoglycemia; in patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia, increased frequency of blood glucose monitoring recommended

            May decrease levels of Vit B12

            Withholding of food and fluids during surgical or other procedures may increase risk for volume depletion, hypotension, and renal impairment; therapy should be temporarily discontinued while patients have restricted food and fluid intake; suspend temporarily for any surgical procedure until patient is no longer NPO and normal renal function has resumed

            During loss of blood sugar control: suspend PrandiMet temporarily and administer insulin

            Before initiating therapy, obtain an estimated glomerular filtration rate

            Discontinue during hypoxic states: acute CHF, MI or other event

            Clinical recommendations based upon the patient’s renal function

            • Before initiating therapy, obtain an eGFR
            • Initiation of therapy is not recommended in patients with eGFR between 30 –45 mL/minute/1.73 m²
            • Obtain an eGFR at least annually in all patients receiving therapy
            • In patients at increased risk for development of renal impairment (e.g., the elderly), renal function should be assessed more frequently
            • If eGFR later falls below 45 mL/minute/1.73 m², assess benefit and risk of continuing therapy

            Iodinated contrast imaging procedures

            • Discontinue metformin at the time of or before an iodinated contrast imaging procedure in patients with an eGFR between 30-60 mL/minute/1.73 m²; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinate contrast
            • Reevaluate eGFR 48 hr after the imaging procedure; restart metformin if renal function is stable
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            Pregnancy & Lactation

            Pregnancy

            Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications

            Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity

            Metformin

            • Metformin crosses the placenta; concentrations may be comparable to those found in the maternal plasma
            • An increased risk of birth defects or adverse fetal/neonatal outcomes has not been observed following maternal use of metformin for gestational diabetes mellitus or type 2 diabetes mellitus when glycemic control is maintained
            • ADA guidelines recommend agents other than metformin to treat diabetes in pregnant women; metformin may be an alternative agent in some patients requiring therapy for gestational diabetes mellitus or type 2 diabetes mellitus

            Repaglinide

            • Limited available data from case reports and case series have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal, or fetal outcomes in women taking repaglinide while pregnant
            • Animal studies
              • Teratogenicity was not observed in rats and rabbits administered repaglinide during organogenesis at approximately 60 and 1 times the maximum daily clinical dose
              • Offspring of rat dams exposed to repaglinide at ≥22 times clinical exposure on a mg/m² basis during days 17 to 22 of gestation and during lactation were less viable and developed skeletal deformations consisting of shortening, thickening, and bending of the humerus during the postnatal period; this was not seen at doses up to 4 times clinical exposure

            Lactation

            No data on the presence of repaglinide in human milk, the effects on the breastfeeding infant, or the effects on milk production

            Metformin is present in breast milk

            Because of the potential for hypoglycemia in breastfed infants, repaglinide is not recommended for use when breastfeeding

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Administration

            Oral Administration

            May be administered PO q8-12hr

            Generally given within 15 minutes prior to meals, but timing can vary from immediately preceding the meal up to 30 minutes before the meal

            Not to exceed 1000 mg/4 mg per meal

            Not to exceed cumulative daily dose of 2500 mg/10 mg

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            Images

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            Patient Handout

            A Patient Handout is not currently available for this monograph.
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            Formulary

            FormularyPatient Discounts

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.