glyburide/metformin (Rx)

Brand and Other Names:Glucovance
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

glyburide/metformin

tablet

  • 1.25mg/250mg
  • 2.5mg/500mg
  • 5mg/500mg

Type 2 Diabetes Mellitus

1.25/250 mg glyburide/metformin PO qDay or q12hr

May titrate up at 2 week intervals; maximum 20/2000 mg/day

Dosage Modifications

Hepatic impairment: Avoid use; cases of lactic acidosis reported

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

1.25/250 mg glyburide/metformin PO qDay or q12hr

Adjust conservatively in patients with advanced age; do not use in patients >80 years unless renal function is assessed (do not titrate to maximum dose)

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Interactions

Interaction Checker

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            Contraindicated (1)

            • bosentan

              bosentan, glyburide. Either decreases levels of the other by increasing metabolism. Contraindicated.

              bosentan, glyburide. Either increases toxicity of the other by Other (see comment). Contraindicated. Comment: Coadministration increases risk of liver enzyme elevations; alternative hypoglycemic agents should be considered.

            Serious - Use Alternative (14)

            • aminolevulinic acid oral

              aminolevulinic acid oral, glyburide. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid administering other phototoxic drugs with aminolevulinic acid oral for 24 hr during perioperative period.

            • aminolevulinic acid topical

              glyburide increases toxicity of aminolevulinic acid topical by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration of photosensitizing drugs may enhance the phototoxic reaction to photodynamic therapy with aminolevulinic acid.

            • 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.

            • darolutamide

              darolutamide will increase the level or effect of glyburide by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).

            • eluxadoline

              glyburide 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. .

            • ethanol

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

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

            • fluvastatin

              fluvastatin increases levels of glyburide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • 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.

            • ivosidenib

              ivosidenib will decrease the level or effect of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2C9 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

            • lasmiditan

              lasmiditan increases levels of glyburide by Other (see comment). Avoid or Use Alternate Drug. Comment: Lasmiditan inhibits BCRP in vitro. Avoid coadministration of lasmiditan with BCRP substrates.

            • lonafarnib

              glyburide will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.

            • lumacaftor/ivacaftor

              lumacaftor/ivacaftor will decrease the level or effect of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Sulfonylureas are CYP2C9 substrates. Lumacaftor/ivacaftor has the potential to induce CYP2C9.

            • methyl aminolevulinate

              glyburide, methyl aminolevulinate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Each drug may increase the photosensitizing effect of the other.

            • methylene blue

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

            Monitor Closely (340)

            • acalabrutinib

              acalabrutinib increases levels of glyburide by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.

            • aceclofenac

              aceclofenac increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • acemetacin

              acemetacin increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • 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, glyburide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Serious hypoglycemia may occur when insulin secretagogues and GLP-1 agonists are concurrently administered. Consider lowering the dose of insulin secretagogue to reduce the risk of hypoglycemia. .

            • alogliptin

              alogliptin, glyburide. 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.

            • alpelisib

              alpelisib will decrease the level or effect of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.

            • aluminum hydroxide

              aluminum hydroxide will increase the level or effect of glyburide by increasing gastric pH. Applies only to oral form of both agents. 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.

            • apalutamide

              apalutamide will decrease the level or effect of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Coadministration of apalutamide, a weak CYP2C9 inducer, with drugs that are CYP2C9 substrates can result in lower exposure to these medications. Evaluate for loss of therapeutic effect if medication must be coadministered.

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

            • aripiprazole

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

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

            • asenapine

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

              asenapine, 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.

            • aspirin

              aspirin increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • atazanavir

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

            • aspirin rectal

              aspirin rectal increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • aspirin/citric acid/sodium bicarbonate

              aspirin/citric acid/sodium bicarbonate increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • atazanavir

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

            • atorvastatin

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

            • axitinib

              glyburide increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • benazepril

              benazepril increases effects of glyburide by pharmacodynamic synergism. Use Caution/Monitor. Additive hypoglycemic effects.

              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.

            • bexarotene

              bexarotene increases effects of glyburide 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.

            • betamethasone

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

            • bictegravir

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

            • bitter melon

              bitter melon increases effects of glyburide 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 decreases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inducers may increase glyburide metabolism.

            • brexpiprazole

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

            • bumetanide

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

            • bupropion

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

            • calcium carbonate

              calcium carbonate will increase the level or effect of glyburide by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

            • canagliflozin

              glyburide, 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 glyburide by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            • capecitabine

              capecitabine increases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inhibitors may decrease glyburide metabolism.

            • captopril

              captopril increases effects of glyburide by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood glucose. Monitor blood glucose.

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

            • carbamazepine

              carbamazepine decreases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inducers may increase glyburide metabolism.

            • cariprazine

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

            • celecoxib

              celecoxib increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • cephalexin

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

            • ceritinib

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

            • chlorpromazine

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

            • cholic acid

              glyburide 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.

            • choline magnesium trisalicylate

              choline magnesium trisalicylate increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • cimetidine

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

              cimetidine will increase the level or effect of glyburide by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

            • cinnamon

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

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

            • ciprofibrate

              ciprofibrate increases effects of glyburide by plasma protein binding competition. Use Caution/Monitor. Hypoglycemia; increased risk in hypoalbuminemia.

            • 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

              ciprofloxacin increases effects of glyburide 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.

            • clarithromycin

              clarithromycin increases levels of glyburide by plasma protein binding competition. Use Caution/Monitor. Risk of hypoglycemia.

            • 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.

            • clotrimazole

              clotrimazole increases levels of glyburide by decreasing metabolism. Use Caution/Monitor.

            • 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.

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

            • colesevelam

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

              colesevelam decreases levels of glyburide by drug binding in GI tract. Use Caution/Monitor. Concomitant administration decreases glyburide absorption; however, absorption is not reduced when glyburide is administered 4 hr before colesevelam.

            • conjugated estrogens

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

            • cyclosporine

              glyburide, cyclosporine. unknown mechanism. Use Caution/Monitor. Cyclosporine may decrease the effects of sulfonylureas. Sulfonylureas may increase the effects of cyclosporine.

            • corticotropin

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

            • dabrafenib

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

            • dalfampridine

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

            • dapagliflozin

              glyburide, 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.

            • darunavir

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

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

            • desogestrel

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

            • diclofenac

              diclofenac increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • 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.

            • diflunisal

              diflunisal increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of 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.

            • disopyramide

              disopyramide increases effects of glyburide by unspecified interaction mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • dofetilide

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

            • dolutegravir

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

            • drospirenone

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

            • dulaglutide

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

              dulaglutide, glyburide. 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.

            • eliglustat

              eliglustat increases levels of glyburide by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the P-gp substrate and titrate to clinical effect.

            • enalapril

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

            • eluxadoline

              eluxadoline increases levels of glyburide by decreasing metabolism. Use Caution/Monitor. Eluxadoline may increase the systemic exposure of coadministered BCRP substrates.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF decreases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Elvitegravir is a moderate CYP2C9 inducer.

            • empagliflozin

              empagliflozin, glyburide. 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.

            • enalapril

              enalapril increases effects of glyburide by pharmacodynamic synergism. Use Caution/Monitor.

            • entecavir

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

            • erdafitinib

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

            • ertugliflozin

              ertugliflozin, glyburide. 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.

            • esomeprazole

              esomeprazole will increase the level or effect of glyburide by increasing gastric pH. Applies only to oral form of both agents. 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. .

            • etodolac

              etodolac increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • etonogestrel

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

            • everolimus

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

            • exenatide injectable solution

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

              exenatide injectable solution, glyburide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypoglycemia when exenatide is used in combination with agents that induce hypoglycemia. Consider lowering dose of sulfonylureas to reduce risk of hypoglycemia. .

            • 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, glyburide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypoglycemia when exenatide is used in combination with agents that induce hypoglycemia. Consider lowering dose of sulfonylureas to reduce risk of hypoglycemia.

            • famotidine

              famotidine will increase the level or effect of glyburide by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

            • 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.

            • fenofibrate

              fenofibrate increases effects of glyburide by plasma protein binding competition. Use Caution/Monitor. Hypoglycemia; increased risk in hypoalbuminemia.

            • fenofibrate micronized

              fenofibrate micronized increases effects of glyburide by plasma protein binding competition. Use Caution/Monitor. Hypoglycemia; increased risk in hypoalbuminemia.

            • fenofibric acid

              fenofibric acid increases effects of glyburide by plasma protein binding competition. Use Caution/Monitor. Hypoglycemia; increased risk in hypoalbuminemia.

            • fenoprofen

              fenoprofen increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • finerenone

              glyburide will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or weak CYP3A4 inhibitors. Adjust finererone dosage as needed.

            • fleroxacin

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

              fleroxacin increases effects of glyburide 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.

            • flibanserin

              glyburide will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased flibanserin adverse effects may occur if coadministered with multiple weak CYP3A4 inhibitors.

            • fluoxetine

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

            • fluconazole

              fluconazole increases levels of glyburide by decreasing metabolism. Use Caution/Monitor.

              fluconazole increases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inhibitors may decrease glyburide metabolism.

            • fluorouracil

              fluorouracil increases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inhibitors may decrease glyburide metabolism.

            • fluoxetine

              fluoxetine increases effects of glyburide by unspecified interaction mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • 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.

            • flurbiprofen

              flurbiprofen increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              flurbiprofen increases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inhibitors may decrease glyburide metabolism.

            • fluvastatin

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

            • fluvoxamine

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

            • fosamprenavir

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

              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 effects of glyburide by pharmacodynamic synergism. Use Caution/Monitor.

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

            • fosphenytoin

              fosphenytoin decreases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inducers may increase glyburide metabolism.

              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 glyburide by Other (see comment). Modify Therapy/Monitor Closely. Fostemsavir inhibits OATP1B1/3 and BCRP transporters. If possible, avoid coadministration or modify dose of OATP1B1/3 or BCRP substrates coadministered with fostemsavir.

            • gemifloxacin

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

            • gemfibrozil

              gemfibrozil increases effects of glyburide by plasma protein binding competition. Use Caution/Monitor. Hypoglycemia; increased risk in hypoalbuminemia.

              gemfibrozil increases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inhibitors may decrease glyburide metabolism.

            • gemifloxacin

              gemifloxacin increases effects of glyburide 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

              glyburide 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 glyburide by Other (see comment). Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of P-gp and BCRP substrates.

            • glucagon intranasal

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

            • glycopyrrolate

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

            • goserelin

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

            • histrelin

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

            • hydroxyprogesterone caproate

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

            • ibuprofen

              ibuprofen increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              ibuprofen increases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inhibitors may decrease glyburide metabolism.

            • ibuprofen IV

              ibuprofen IV increases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inhibitors may decrease glyburide metabolism.

              ibuprofen IV increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • ibuprofen/famotidine

              ibuprofen/famotidine will increase the level or effect of glyburide by increasing gastric pH. Applies only to oral form of both agents. 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, glyburide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

            • imidapril

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

              imidapril increases effects of glyburide by pharmacodynamic synergism. Use Caution/Monitor.

            • indinavir

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

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

            • indomethacin

              indomethacin increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              indomethacin increases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inhibitors may decrease glyburide metabolism.

            • 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

              glyburide, 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.

              glyburide, 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

              glyburide, 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.

              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.

              glyburide, 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.

              glyburide, 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.

              glyburide, 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.

              glyburide, 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

              glyburide, 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.

              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

              glyburide, 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.

              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.

              glyburide, 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.

              glyburide, 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.

              glyburide, 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.

              glyburide, 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. .

            • isocarboxazid

              isocarboxazid increases effects of glyburide by unknown mechanism. Use Caution/Monitor.

            • 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. .

            • isavuconazonium sulfate

              isavuconazonium sulfate increases levels of metformin by Other (see comment). Use Caution/Monitor. Comment: Isavuconazonium inhibition of OCT1, OCT2, and/or MATE1 transporters my play a role in reducing metformin elimination .

            • isocarboxazid

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

            • isoniazid

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

            • isradipine

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

            • ivacaftor

              ivacaftor increases levels of glyburide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

              glyburide increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • ketoconazole

              ketoconazole increases levels of glyburide by decreasing metabolism. Use Caution/Monitor.

              ketoconazole increases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inhibitors may decrease glyburide metabolism.

            • ketoprofen

              ketoprofen increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • ketorolac

              ketorolac increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • ketorolac intranasal

              ketorolac intranasal increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • ketotifen, ophthalmic

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

              ketotifen, ophthalmic, glyburide. 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.

            • lemborexant

              glyburide will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.

            • letermovir

              letermovir, glyburide. Either increases levels of the other by Other (see comment). Use Caution/Monitor. Comment: Monitor glucose concentrations.

            • leuprolide

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

            • levofloxacin

              levofloxacin increases effects of glyburide 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.

            • linagliptin

              glyburide, linagliptin. Other (see comment). Use Caution/Monitor. Comment: When linagliptin is used in combination with sulfonylureas, a lower dose of the sulfonylurea may be required to reduce risk of hypoglycemia.

            • 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.

              linezolid increases effects of glyburide by unknown 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.

            • liraglutide

              liraglutide, glyburide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Serious hypoglycemia may occur when insulin secretagogues and GLP-1 agonists are concurrently administered. Consider lowering the dose of insulin secretagogue to reduce the risk of 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.

              lisinopril increases effects of glyburide by pharmacodynamic synergism. Use Caution/Monitor.

            • lixisenatide

              lixisenatide, glyburide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Risk of hypoglycemia increased when coadministered with sulfonylureas. Sulfonylurea dosage reduction may be required.

            • lopinavir

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

            • lomitapide

              glyburide increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.

            • lopinavir

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

            • lornoxicam

              lornoxicam increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • 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.

              lurasidone, glyburide. 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 decreases effects of glyburide by pharmacodynamic antagonism. Use Caution/Monitor.

            • mecasermin

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

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

            • meclofenamate

              meclofenamate increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • medroxyprogesterone

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

            • mefenamic acid

              mefenamic acid increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              mefenamic acid increases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inhibitors may decrease glyburide metabolism.

            • meloxicam

              meloxicam increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • 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

              glyburide, 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.

            • miconazole vaginal

              miconazole vaginal increases levels of glyburide by decreasing metabolism. Use Caution/Monitor.

            • midazolam intranasal

              glyburide will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of mild CYP3A4 inhibitors with midazolam intranasal may cause higher midazolam systemic exposure, which may prolong sedation.

            • mipomersen

              mipomersen, glyburide. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.

            • moexipril

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

              moexipril increases effects of glyburide by pharmacodynamic synergism. Use Caution/Monitor.

            • 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 glyburide 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.

            • nabumetone

              nabumetone increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • nelfinavir

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

            • nadolol

              nadolol decreases effects of glyburide by pharmacodynamic antagonism. Use Caution/Monitor. Non selective beta blockers may also mask the symptoms of hypoglycemia.

            • naproxen

              naproxen increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • nelfinavir

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

            • niacin

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

            • nicardipine

              nicardipine increases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inhibitors may decrease glyburide metabolism.

              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.

            • nitazoxanide

              nitazoxanide, glyburide. Either increases levels of the other by Mechanism: plasma protein binding competition. Use Caution/Monitor.

            • nilotinib

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

            • nimodipine

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

            • nisoldipine

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

            • nitisinone

              nitisinone will increase the level or effect of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

            • 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.

              ofloxacin increases effects of glyburide 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, glyburide. 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.

            • omeprazole

              omeprazole will increase the level or effect of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. 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.

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

            • osimertinib

              osimertinib will increase the level or effect of glyburide by Other (see comment). Modify Therapy/Monitor Closely. Osimertinib is an inhibitor of BCRP transport. Caution if coadministered with sensitive BCRP substrates.

            • paliperidone

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

            • ospemifene

              glyburide, ospemifene. Either increases levels of the other by plasma protein binding competition. Modify Therapy/Monitor Closely.

            • oxaprozin

              oxaprozin increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • paliperidone

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

            • parecoxib

              parecoxib increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • paroxetine

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

            • pasireotide

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

            • patiromer

              patiromer will decrease the level or effect of metformin by drug binding in GI tract. Use Caution/Monitor. May administer 3 hours apart

            • peginterferon alfa 2b

              peginterferon alfa 2b decreases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. When patients are administered peginterferon alpha-2b with CYP2C9 substrates, the therapeutic effect of these drugs may be altered. .

            • pentamidine

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

            • perindopril

              perindopril increases effects of glyburide by pharmacodynamic synergism. Use Caution/Monitor.

              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.

            • phenelzine

              phenelzine increases effects of glyburide by unknown mechanism. Use Caution/Monitor.

            • 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 decreases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inducers may increase glyburide metabolism.

            • phentermine

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

            • phenytoin

              phenytoin decreases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inducers may increase glyburide metabolism.

              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.

            • pindolol

              pindolol decreases effects of glyburide by pharmacodynamic antagonism. Use Caution/Monitor. Non selective beta blockers may also mask the symptoms of hypoglycemia.

            • procainamide

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

            • piroxicam

              piroxicam increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              piroxicam increases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inhibitors may decrease glyburide metabolism.

            • pitavastatin

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

            • ponatinib

              ponatinib increases levels of glyburide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              ponatinib increases levels of glyburide by Other (see comment). Use Caution/Monitor.

            • posaconazole

              posaconazole increases levels of glyburide by decreasing metabolism. Use Caution/Monitor.

            • pravastatin

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

            • primidone

              primidone decreases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inducers may increase glyburide metabolism.

            • probenecid

              probenecid increases levels of glyburide by unspecified interaction mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • 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.

            • propranolol

              propranolol decreases effects of glyburide by pharmacodynamic antagonism. Use Caution/Monitor. Non selective beta blockers may also mask the symptoms of hypoglycemia.

            • quetiapine

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

              quetiapine, glyburide. 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.

              quinapril increases effects of glyburide by pharmacodynamic synergism. 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 effects of glyburide by pharmacodynamic synergism. Use Caution/Monitor.

            • ramipril

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

            • rasagiline

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

            • regorafenib

              regorafenib will increase the level or effect of glyburide by Other (see comment). Modify Therapy/Monitor Closely. Regorafenib likely inhibits BCRP (ABCG2) transport. Coadministration with a BCRP substrate may increase systemic exposure to the substrate and related toxicity.

            • rifabutin

              rifabutin decreases levels of glyburide by increasing metabolism. Use Caution/Monitor.

            • rifampin

              rifampin decreases levels of glyburide by increasing metabolism. Use Caution/Monitor.

              rifampin decreases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inducers may increase glyburide metabolism.

            • rifapentine

              rifapentine decreases levels of glyburide by increasing metabolism. Use Caution/Monitor.

              rifapentine decreases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inducers may increase glyburide metabolism.

            • risperidone

              risperidone, glyburide. 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, glyburide. Other (see comment). Use Caution/Monitor. Comment: Ritonavir may increase or decrease levels of glyburide. Use alternatives if available. Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

            • rosuvastatin

              glyburide increases toxicity of rosuvastatin by Other (see comment). Use Caution/Monitor. Comment: Coadministration of rosuvastatin with OATP1B1 inhibitors may increase rosuvastatin levels and risk for 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 glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP2C9 substrates, if clinically indicated.

            • sacubitril/valsartan

              glyburide 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

            • safinamide

              safinamide will increase the level or effect of glyburide by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

            • salicylates (non-asa)

              salicylates (non-asa) increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • salsalate

              salsalate increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • saquinavir

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

            • secobarbital

              secobarbital decreases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inducers may increase glyburide metabolism.

            • selegiline

              selegiline increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Serum glucose should be monitored closely when MAOIs are added to any regimen containing antidiabetic medications. Hypoglycemic effects may be increased.

            • selegiline transdermal

              selegiline transdermal increases effects of glyburide by unknown mechanism. Use Caution/Monitor.

            • semaglutide

              semaglutide, glyburide. 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 metformin by pharmacodynamic synergism. Use Caution/Monitor. Theoretical interaction.

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

            • simvastatin

              glyburide 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.

            • sodium bicarbonate

              sodium bicarbonate will increase the level or effect of glyburide by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

            • sodium citrate/citric acid

              sodium citrate/citric acid will increase the level or effect of glyburide by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

            • sodium zirconium cyclosilicate

              sodium zirconium cyclosilicate will increase the level or effect of glyburide by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Check specific recommendations for drugs that exhibit pH-dependent solubility that may affect their systemic exposure and efficacy. In general, administer drugs at least 2 hr before or after sodium zirconium cyclosilicate.

            • sofosbuvir/velpatasvir

              sofosbuvir/velpatasvir will increase the level or effect of glyburide by Other (see comment). Use Caution/Monitor. Velpatasvir is an inhibitor of the drug transporter BCRP. Coadministration may increase systemic exposure of drugs that are BCRP substrates.

            • 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. .

              somapacitan decreases effects of glyburide 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.

            • stiripentol

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

            • sulfadiazine

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

              sulfadiazine increases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inhibitors may decrease glyburide metabolism.

            • sulfamethoxazole

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

              sulfamethoxazole increases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inhibitors may decrease glyburide metabolism.

            • sulfamethoxypyridazine

              sulfamethoxypyridazine increases effects of glyburide 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.

            • sulfasalazine

              sulfasalazine increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • tacrolimus

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

            • sulfisoxazole

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

            • sulindac

              sulindac increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • tafamidis

              tafamidis will increase the level or effect of glyburide by Other (see comment). Use Caution/Monitor. Tafamidis inhibits breast cancer resistant protein (BCRP) in vitro and may increase exposure of BCRP substrates following tafamidis or tafamidis meglumine administration. Dosage adjustment of these BCRP substrates may be necessary.

            • tafamidis meglumine

              tafamidis meglumine will increase the level or effect of glyburide by Other (see comment). Use Caution/Monitor. Tafamidis inhibits breast cancer resistant protein (BCRP) in vitro and may increase exposure of BCRP substrates following tafamidis or tafamidis meglumine administration. Dosage adjustment of these BCRP substrates may be necessary.

            • tazemetostat

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

            • temsirolimus

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

            • tenofovir DF

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

            • thioridazine

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

            • thyroid desiccated

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

            • tibolone

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

            • timolol

              timolol decreases effects of glyburide by pharmacodynamic antagonism. Use Caution/Monitor. Non selective beta blockers may also mask the symptoms of hypoglycemia.

            • tinidazole

              glyburide will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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 decreases effects of glyburide by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

            • tolbutamide

              tolbutamide increases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inhibitors may decrease glyburide metabolism.

            • topiramate

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

            • tolfenamic acid

              tolfenamic acid increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • tolmetin

              tolmetin increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • torsemide

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

            • trandolapril

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

              trandolapril increases effects of glyburide by pharmacodynamic synergism. Use Caution/Monitor.

            • tranylcypromine

              tranylcypromine increases effects of glyburide by unknown mechanism. Use Caution/Monitor.

            • 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.

            • triamcinolone acetonide injectable suspension

              triamcinolone acetonide injectable suspension decreases effects of glyburide 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.

            • trimagnesium citrate anhydrous

              trimagnesium citrate anhydrous increases levels of glyburide by enhancing GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

            • trimethoprim

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

            • triptorelin

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

            • trospium chloride

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

            • valsartan

              glyburide 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

            • vandetanib

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

            • verapamil

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

            • vilazodone

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

            • voriconazole

              voriconazole increases levels of glyburide by decreasing metabolism. Use Caution/Monitor.

              voriconazole increases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inhibitors may decrease glyburide metabolism.

            • 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 glyburide by increasing renal clearance. Use Caution/Monitor.

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

            • ziprasidone

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

              ziprasidone, glyburide. 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 (130)

            • agrimony

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

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

            • American ginseng

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

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

            • amitriptyline

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

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

            • amoxapine

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

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

            • anamu

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

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

            • antithrombin alfa

              glyburide increases effects of antithrombin alfa by unspecified interaction mechanism. Minor/Significance Unknown.

            • bendroflumethiazide

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

            • antithrombin III

              glyburide increases effects of antithrombin III by unspecified interaction mechanism. Minor/Significance Unknown.

            • argatroban

              glyburide increases effects of argatroban by unspecified interaction mechanism. Minor/Significance Unknown.

            • aspirin

              aspirin increases effects of glyburide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

            • aspirin rectal

              aspirin rectal increases effects of glyburide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

            • aspirin/citric acid/sodium bicarbonate

              aspirin/citric acid/sodium bicarbonate increases effects of glyburide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

            • balsalazide

              balsalazide increases effects of glyburide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

            • bemiparin

              glyburide increases effects of bemiparin by unspecified interaction mechanism. Minor/Significance Unknown.

            • bendroflumethiazide

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

            • bivalirudin

              glyburide increases effects of bivalirudin by unspecified interaction mechanism. Minor/Significance Unknown.

            • budesonide

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

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

            • chloramphenicol

              chloramphenicol increases levels of glyburide by decreasing metabolism. 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

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

            • chlorthalidone

              chlorthalidone decreases effects of glyburide 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.

            • choline magnesium trisalicylate

              choline magnesium trisalicylate increases effects of glyburide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

            • chromium

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

            • chromium

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

            • clomipramine

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

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

            • clonidine

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

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

              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.

            • coenzyme Q10

              glyburide decreases levels of coenzyme Q10 by unspecified interaction mechanism. Minor/Significance Unknown.

            • cornsilk

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

            • cornsilk

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

            • cortisone

              cortisone decreases effects of glyburide 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 glyburide 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.

            • dalteparin

              glyburide increases effects of dalteparin by unspecified interaction mechanism. Minor/Significance Unknown.

            • damiana

              damiana decreases effects of glyburide 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 glyburide by pharmacodynamic synergism. Minor/Significance Unknown.

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

            • deflazacort

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

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

            • desipramine

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

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

            • dexamethasone

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

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

            • diflunisal

              diflunisal increases effects of glyburide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

            • diltiazem

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

            • doxepin

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

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

            • elderberry

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

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

            • enoxaparin

              glyburide increases effects of enoxaparin by unspecified interaction mechanism. Minor/Significance Unknown.

            • eucalyptus

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

            • eucalyptus

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

            • famotidine

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

            • fludrocortisone

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

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

            • fluoxymesterone

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

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

            • fo-ti

              fo-ti increases effects of glyburide 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.

            • fondaparinux

              glyburide increases effects of fondaparinux by unspecified interaction mechanism. Minor/Significance Unknown.

            • forskolin

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

              forskolin increases effects of glyburide 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 glyburide by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction).

            • gotu kola

              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 glyburide by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

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

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

            • gymnema

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

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

            • heparin

              glyburide increases effects of heparin by unspecified interaction mechanism. Minor/Significance Unknown.

            • horse chestnut seed

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

            • horse chestnut seed

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

            • imipramine

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

            • indapamide

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

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

            • isoniazid

              isoniazid decreases effects of glyburide 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 glyburide by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).

            • lofepramine

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

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

            • lycopus

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

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

            • maitake

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

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

            • maprotiline

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

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

            • memantine

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

            • mesalamine

              mesalamine increases effects of glyburide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

            • mesterolone

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

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

            • methyclothiazide

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

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

            • methyltestosterone

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

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

            • metolazone

              metolazone decreases effects of glyburide 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.

            • miglitol

              miglitol decreases levels of glyburide by unspecified interaction mechanism. Minor/Significance Unknown.

            • nettle

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

              nettle increases effects of glyburide 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.

            • nizatidine

              nizatidine will increase the level or effect of glyburide by increasing gastric pH. Applies only to oral form of both agents. Minor/Significance Unknown.

            • nortriptyline

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

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

            • ofloxacin

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

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

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

            • orlistat

              orlistat increases effects of glyburide by pharmacodynamic synergism. Minor/Significance Unknown.

            • oxandrolone

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

            • oxandrolone

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

            • oxymetholone

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

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

            • pegvisomant

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

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

            • phenindione

              glyburide increases effects of phenindione by unspecified interaction mechanism. 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

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

            • potassium chloride

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

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

            • potassium citrate

              potassium citrate increases effects of glyburide 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 glyburide by pharmacodynamic antagonism. Minor/Significance Unknown.

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

            • prednisone

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

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

            • protamine

              glyburide increases effects of protamine by unspecified interaction mechanism. Minor/Significance Unknown.

            • protriptyline

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

            • protriptyline

              protriptyline increases effects of glyburide 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.

            • ruxolitinib

              glyburide will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • sage

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

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

            • salicylates (non-asa)

              salicylates (non-asa) increases effects of glyburide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

            • stevia

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

            • salsalate

              salsalate increases effects of glyburide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

            • sitagliptin

              sitagliptin, glyburide. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypoglycemia with combination is unknown.

            • stevia

              stevia increases effects of glyburide 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.

            • sulfasalazine

              sulfasalazine increases effects of glyburide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

            • tacrolimus

              glyburide increases levels of tacrolimus by unknown mechanism. Minor/Significance Unknown.

            • testosterone

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

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

            • testosterone buccal system

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

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

            • testosterone topical

              testosterone topical increases effects of glyburide 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 glyburide by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypoglycemia.

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

            • topiramate

              topiramate will decrease the level or effect of glyburide by unknown mechanism. Minor/Significance Unknown. Effect in glycemic control is likely small.

            • trazodone

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

            • trazodone

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

            • triamterene

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

            • trimethoprim

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

            • trimipramine

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

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

            • vanadium

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

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

            • verapamil

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

            • warfarin

              glyburide increases effects of warfarin by unspecified interaction mechanism. Minor/Significance Unknown.

            • willow bark

              willow bark increases effects of glyburide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

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            Adverse Effects

            Frequency Not Defined

            Dermatologic reactions

            Heartburn

            Hypoglycemia

            Nausea/vomiting

            Postmarketing Reports

            Gastrointestinal: Cholestatic jaundice and hepatitis may occur rarely which may progress to liver failure; discontinue drug

            Allergic: Angioedema, arthralgia, myalgia, and vasculitis

            Dermatologic: Porphyria cutanea tarda and photosensitivity

            Hematologic: Leukopenia, agranulocytosis, thrombocytopenia, which occasionally may present as purpura, hemolytic anemia, aplastic anemia, and pancytopenia

            Metabolic: Hepatic porphyria reactions reported with sulfonylureas but not with glyburide; disulfiram-like reactions reported very rarely with glyburide; cases of hyponatremia reported most often in patients who are on other medications or have medical conditions known to cause hyponatremia or increase release of antidiuretic hormone

            Liver function abnormalities, including isolated transaminase elevations (glyburide)

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            Warnings

            Black Box Warnings

            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

            Lactic acidosis

            • Characterized by elevated blood lactate levels (>5 mmol/L)
            • Rare but serious complication that can occur because of metformin accumulation; increased risk with sepsis, dehydration, excess alcohol intake, hepatic insufficiency, renal impairment, and acute congestive heart failure
            • Subtle onset with nonspecific symptoms (eg, malaise, myalgias, respiratory distress, somnolence, nonspecific abdominal distress)
            • Monitor lab for decreased serum pH, increased anion gap, and elevated blood lactate
            • If lactic acidosis suspected, discontinue drug and hospitalize patient immediately
            • 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 accumulated metformin

            Contraindications

            Hypersensitivity to glyburide or metformin

            Congestive heart failure, metabolic acidosis

            Diabetic ketoacidosis, with or without coma (treat with insulin)

            Coadministration with bosentan (increased risk of hepatotoxicity)

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

            Cautions

            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

            Allergic skin reactions, eg, pruritus, erythema, urticaria, and morbilliform or maculopapular eruptions, occur in 1.5% of glyburide-treated patients, which may be transient and may disappear despite continued use; if skin reactions persist, drug should be discontinued

            Use with caution in patients with risk of severe hypoglycemia: elderly, debilitated, or malnourished, adrenal or pituitary insufficiency

            Use with caution in patients with stress due to infection, fever, trauma, or surgery

            Before initiating therapy, obtain an estimated glomerular filtration rate

            Pregnancy/lactation

            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

            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

            Use with caution in patients with dehydration, heavy use of alcohol, hypoxic states, impaired hepatic or renal function

            Hemolytic anemia may occur with glucose 6-phosphate dehydrogenase (G6PD) deficiency when treated with sulfonylurea agents

            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

            Available data from a small number of published studies and postmarketing experience with glyburide use in pregnancy over decades have not identified any drug associated risks for major birth defects, miscarriage, or adverse maternal outcomes; however, sulfonylureas (including glyburide) cross placenta and have been associated with neonatal adverse reactions such as hypoglycemia; therapy should be discontinued at least two weeks before expected delivery

            Limited data with metformin in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage; published studies with metformin use during pregnancy have not reported a clear association with metformin and major birth defect or miscarriage risk; there are risks to mother and fetus associated with poorly controlled diabetes mellitus in pregnancy

            Poorly controlled diabetes mellitus in pregnancy increases maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications; poorly controlled diabetes mellitus increases fetal risk for major birth defects, stillbirth, and macrosomia related morbidity

            Neonates of women with gestational diabetes who are treated with sulfonylureas during pregnancy may be at increased risk for neonatal intensive care admission and may develop respiratory distress, hypoglycemia, birth injury, and be large for gestational age; prolonged severe hypoglycemia, lasting 4-10 days, has been reported in neonates born to mothers receiving a sulfonylurea at time of delivery and has been reported with use of agents with a prolonged half-life; observe newborns for symptoms of hypoglycemia and respiratory distress and manage accordingly

            Due to reports of prolonged severe hypoglycemia in neonates born to mothers receiving a sulfonylurea at time of delivery, therapy should be discontinued at least two weeks before expected delivery

            Animal data

            • No evidence of harm to fetus observed when doses up to 500 times the maximum recommended human dose of 20 mg of glyburide, based on body surface area, were administered to rats and rabbits in reproduction studies
            • No adverse developmental effects were observed when metformin was administered to pregnant Sprague Dawley rats and rabbits during period of organogenesis at doses up to 3- and 6- times, respectively, a 2000 mg clinical dose, based on body surface area

            Lactation

            Breastfed infants of lactating women on therapy should be monitored for symptoms of hypoglycemia; although glyburide was negligible in human milk in one small clinical lactation study; this result is not conclusive because of limitations of assay used in the study; there are no data on effects of glyburide on milk production; limited published studies report that metformin is present in human milk; however, there is insufficient information to determine effects of metformin on breastfed infant and no available information on effects of metformin on milk production; therefore, developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from drug or from the underlying maternal condition

            Monitor breastfed infants for signs of hypoglycemia (eg, jitters, cyanosis, apnea, hypothermia, excessive sleepiness, poor feeding, seizures)

            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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            Pharmacology

            Mechanism of Action

            Initial effect is to increase beta-cell insulin secretion

            May also decrease rate of hepatic glucose production, increase insulin receptor sensitivity, and increase number of insulin receptors

            Pharmacokinetics

            Onset: 2-3 hr

            Metabolites: 4-trans-hydroxyglyburide, 3-cis-hydroxyglyburide (active)

            Half-Life

            • Glyburide: Approx. 10 hr
            • Metformin: Approx. 6 hr

            Duration

            • Glyburide: 24 hr
            • Metformin: No data

            Protein Bound

            • Glyburide: 99%
            • Metformin: Minimal

            Vd

            • Glyburide: No studies
            • Metformin: 650 L

            Metabolism

            • Glyburide: Extensively, in liver to less active metabolites
            • Metformin: Not metabolized

            Excretion

            • Glyburide: Urine 50%, bile 50%
            • Metformin: Urine 90%

            Dialyzable

            • Glyburide: No data
            • Metformin: Hemodialysis
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            Patient Handout

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

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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.