alogliptin/metformin (Rx)

Brand and Other Names:Kazano
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Dosing & Uses

AdultPediatric

Dosing Forms & Strengths

alogliptin/metformin

tablet

  • 12.5mg/500mg
  • 12.5mg/1000mg

Diabetes Mellitus Type 2

Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus

Starting dose based on patient’s current regimen

Take PO BID with food; gradually escalation dose to reduce GI side effects caused by metformin

Not to exceed 25 mg/2000 mg per day

Dosage Modifications

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

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Interactions

Interaction Checker

and alogliptin/metformin

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              Serious - Use Alternative (12)

              • contrast media (iodinated)

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

              • ethanol

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

              • ioversol

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

              • methylene blue

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

              • ranolazine

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

              • risdiplam

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

              • selegiline

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

              • selegiline transdermal

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

              • tafenoquine

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

              • tedizolid

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

              • tranylcypromine

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

              • trilaciclib

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

              Monitor Closely (187)

              • acetazolamide

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

              • albiglutide

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

              • amiodarone

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

              • amlodipine

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

              • aripiprazole

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

              • asenapine

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

              • atazanavir

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

              • benazepril

                alogliptin increases toxicity of benazepril by unspecified interaction mechanism. Use Caution/Monitor. May increase risk of angioedema.

                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.

              • captopril

                alogliptin increases toxicity of captopril by Mechanism: unspecified interaction mechanism. Use Caution/Monitor. Increased risk of advers/toxic effects, specifically increased risk of angioedema.

              • betamethasone

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

              • bictegravir

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

              • bitter melon

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

              • brexpiprazole

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

              • bumetanide

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

              • bupropion

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

              • captopril

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

              • cariprazine

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

              • cephalexin

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

              • ceritinib

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

              • chlorpromazine

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

              • chlorpropamide

                alogliptin, chlorpropamide. 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 .

              • cimetidine

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

              • cinnamon

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

              • ciprofloxacin

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

              • citalopram

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

              • clevidipine

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

              • clozapine

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

              • colesevelam

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

              • conjugated estrogens

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

              • corticotropin

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

              • dabrafenib

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

              • dalfampridine

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

              • darunavir

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

              • desogestrel

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

              • diatrizoate

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

              • diatrizoate meglumine/diatrizoate sodium

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

              • diazoxide

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

              • dichlorphenamide

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

              • dienogest/estradiol valerate

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

              • diethylpropion

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

              • digoxin

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

              • diltiazem

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

              • dofetilide

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

              • dolutegravir

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

              • drospirenone

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

              • dulaglutide

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

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

              • enalapril

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

              • glimepiride

                alogliptin, glimepiride. 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 .

              • entecavir

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

              • erdafitinib

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

              • escitalopram

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

              • estradiol

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

              • estrogens conjugated synthetic

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

              • estropipate

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

              • ethacrynic acid

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

              • ethinylestradiol

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

              • ethiodized oil

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

              • etonogestrel

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

              • everolimus

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

              • exenatide injectable solution

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

              • exenatide injectable suspension

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

              • felodipine

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

              • fleroxacin

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

              • fluoxetine

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

              • fluphenazine

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

              • fluvoxamine

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

              • fosamprenavir

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

              • fosinopril

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

              • fosphenytoin

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

              • gemifloxacin

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

              • glipizide

                alogliptin, glipizide. 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 .

              • glucagon intranasal

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

              • glyburide

                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 .

              • glycopyrrolate

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

              • goserelin

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

              • histrelin

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

              • hydroxyprogesterone caproate

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

              • iloperidone

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

              • imidapril

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

              • indinavir

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

              • insulin aspart

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

                alogliptin, 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.

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

              • insulin degludec

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

                alogliptin, 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

                alogliptin, 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.

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

              • insulin detemir

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

                alogliptin, 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.

                alogliptin, 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.

                alogliptin, 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

                alogliptin, 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

                alogliptin, 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

                alogliptin, 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.

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

              • insulin lispro protamine/insulin lispro

                alogliptin, 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.

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

              • insulin NPH

                alogliptin, 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.

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

              • insulin regular human

                alogliptin, 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 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. .

              • nateglinide

                alogliptin, nateglinide. 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 .

              • ioflupane I 123

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

              • iohexol

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

              • iopamidol

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

              • iopromide

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

              • ioversol

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

              • ioxilan

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

              • isocarboxazid

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

              • isoniazid

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

              • isradipine

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

              • ketotifen, ophthalmic

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

              • lanreotide

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

              • leuprolide

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

              • levofloxacin

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

              • levonorgestrel intrauterine

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

              • levonorgestrel oral

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

              • levothyroxine

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

              • linezolid

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

              • liothyronine

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

              • liotrix

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

              • liraglutide

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

              • lisinopril

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

              • lopinavir

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

              • lurasidone

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

              • marijuana

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

              • mecasermin

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

              • medroxyprogesterone

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

              • methamphetamine

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

              • methazolamide

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

              • moexipril

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

              • moxifloxacin

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

              • nelfinavir

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

              • niacin

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

              • nicardipine

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

              • nifedipine

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

              • nilotinib

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

              • nimodipine

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

              • nisoldipine

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

              • nizatidine

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

              • norelgestromin

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

              • norethindrone

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

              • norgestimate

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

              • octreotide

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

              • ofloxacin

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

              • olanzapine

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

              • omacetaxine

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

              • ombitasvir/paritaprevir/ritonavir & dasabuvir

                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.

              • paliperidone

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

              • paroxetine

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

              • pasireotide

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

              • patiromer

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

              • pentamidine

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

              • perindopril

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

              • perphenazine

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

              • phendimetrazine

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

              • phenelzine

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

              • phentermine

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

              • phenytoin

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

              • procainamide

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

              • procarbazine

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

              • prochlorperazine

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

              • progesterone intravaginal gel

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

              • progesterone micronized

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

              • progesterone, natural

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

              • promethazine

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

              • quetiapine

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

              • quinapril

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

              • quinidine

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

              • ramipril

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

              • rasagiline

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

              • repaglinide

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

              • risperidone

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

              • ritonavir

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

              • saquinavir

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

              • sertraline

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

              • shark cartilage

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

              • sirolimus

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

              • somapacitan

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

              • somatropin

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

              • tolazamide

                alogliptin, tolazamide. 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 .

              • sulfamethoxypyridazine

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

              • tacrolimus

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

              • temsirolimus

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

              • tenofovir DF

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

              • thioridazine

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

              • thyroid desiccated

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

              • tibolone

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

              • tipranavir

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

              • tolbutamide

                alogliptin, tolbutamide. 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 .

              • 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.

              Minor (82)

              • agrimony

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

              • American ginseng

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

              • amitriptyline

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

              • amoxapine

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

              • anamu

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

              • bendroflumethiazide

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

              • budesonide

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

              • chlorothiazide

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

              • chlorthalidone

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

              • chromium

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

              • clomipramine

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

              • clonidine

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

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

              • cornsilk

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

              • cortisone

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

              • cyanocobalamin

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

              • cyclopenthiazide

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

              • damiana

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

              • danazol

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

              • deflazacort

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

              • desipramine

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

              • devil's claw

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

              • dexamethasone

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

              • diltiazem

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

              • doxepin

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

              • elderberry

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

              • eucalyptus

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

              • famotidine

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

              • fludrocortisone

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

              • fluoxymesterone

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

              • fo-ti

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

              • folic acid

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

              • forskolin

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

              • furosemide

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

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

              • gotu kola

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

              • guanfacine

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

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

              • gymnema

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

              • horse chestnut seed

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

              • hydrochlorothiazide

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

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

              • hydrocortisone

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

              • ibuprofen/famotidine

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

              • imipramine

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

              • indapamide

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

              • juniper

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

              • L-methylfolate

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

              • lofepramine

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

              • lycopus

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

              • maitake

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

              • maprotiline

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

              • memantine

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

              • mesterolone

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

              • methyclothiazide

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

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

              • methylprednisolone

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

              • methyltestosterone

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

              • metolazone

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

              • midodrine

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

              • nettle

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

              • nifedipine

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

              • nortriptyline

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

              • ofloxacin

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

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

              • oxandrolone

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

              • oxymetholone

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

              • pegvisomant

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

              • potassium acid phosphate

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

              • potassium chloride

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

              • potassium citrate

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

              • prednisolone

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

              • prednisone

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

              • protriptyline

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

              • quinine

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

              • sage

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

              • stevia

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

              • sulfamethoxazole

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

              • testosterone

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

              • testosterone buccal system

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

              • testosterone topical

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

              • tongkat ali

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

              • trazodone

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

              • triamterene

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

              • trimethoprim

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

              • trimipramine

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

              • vanadium

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

              • verapamil

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

              Previous
              Next:

              Adverse Effects

              1-10%

              Upper respiratory tract infection (8%)

              Nasopharyngitis (6.8%)

              Hypoglycemia (1.8-6.3%)

              Diarrhea (5.5%)

              Hypertension (5.5%)

              Headache (5.3%)

              Back pain (4.3%)

              Urinary tract infection (4.2%)

              <1%

              Hypersensitivity (0.6%)

              Pancreatitis (0.2%)

              Postmarketing reports

              Severe and disabling arthralgia

              Anaphylaxis, angioedema, rash, urticaria

              Severe cutaneous adverse reactions, including Stevens-Johnson syndrome

              Hepatic enzyme elevations

              Fulminant hepatic failure

              Bullous pemphigoid

              Rhabdomyolysis

              Constipation

              Nausea

              Ileus

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              Next:

              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

              • Lactic acidosis is a rare, but serious complication that can occur due to metformin accumulation
              • Characterized by blood lactate levels >5 mmol/L, decreased blood pH, electrolyte disturbances with an increased anion gap, and increased lactate/pyruvate ratio
              • Risk increases with conditions such as sepsis, dehydration, excess alcohol intake, hepatic impairment, renal impairment, and acute CHF
              • Onset is often subtle, accompanied only by nonspecific symptoms (eg, malaise, myalgias, respiratory distress, increasing somnolence, nonspecific abdominal distress)
              • Laboratory abnormalities include low pH, increased anion gap, and elevated blood lactate
              • If acidosis is suspected, discontinue alogliptin/metformin and hospitalize the patient immediately

              Contraindications

              Renal impairment (ie, eGFR <30 ml/min/1.73 m²); renal impairment may also result from medical conditions (eg, shock, acute MI, septicemia)

              Acute or chronic metabolic acidosis, including diabetic ketoacidosis; diabetic ketoacidosis should be treated with insulin

              Hypersensitivity to alogliptin or metformin, including anaphylaxis, angioedema, or severe cutaneous adverse reactions including Stevens-Johnson syndrome

              Cautions

              Lactic acidosis (see Black Box Warnings)

              Pancreatitis reported

              Caution with sensitivity to another DPP-4 inhibitor or metformin; discontinue if serious hypersensitivity reaction suspected (see Contraindications)

              Fatal and nonfatal hepatic failure reported; type 2 DM is also known to cause fatty liver disease and liver enzyme elevation; monitor carefully and interrupt alogliptin treatment if LFTs elevated, do not restart alogliptin without another explanation for the liver test abnormalities

              Insulin and insulin secretagogues (eg, sulfonylureas) are known to cause hypoglycemia; therefore, a lower dose of insulin of insulin secretagogue may be needed to minimize hypoglycemia risk

              Coadministration with drugs that may affect renal function or metformin elimination

              Temporarily withhold metformin for any surgical procedures that restrict fluid/food intake

              Hypoxic conditions (eg, shock, acute CHF, acute MI) associated with lactic acidosis (see Black Box Warnings)

              Alcohol potentiates metformin’s effect on lactate metabolism; avoid excessive alcohol intake

              Metformin may decrease vitamin B12 levels

              Hypoglycemia may occur with metformin if calorie intake is deficient

              Severe and disabling arthralgia reported in patients taking DPP-4 inhibitors; consider as a possible cause for severe joint pain and discontinue drug if appropriate

              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

              Congestive heart failure (CHF) risk

              • The EXAMINE (Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care) trial enrolled 5,380 patients with type 2 diabetes and recent acute coronary syndrome
              • Hospitalization for CHF was observed in 106 (3.9%) patients treated with alogliptin and 89 (3.3%) patients treated with placebo; although the difference was not statistically significant (hazard ratio, 1.19), heart failure was not an end point of the study
              • Health care professionals should consider discontinuing medications containing alogliptin in patients who develop heart failure and monitor their diabetes control
              • Lancet. 2015 May 23;385(9982):2067-76
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              Pregnancy & Lactation

              Pregnancy

              Limited available data in pregnant women are not sufficient to inform a drug-associated risk for major birth defects and 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 the mother and fetus associated with poorly controlled diabetes in pregnancy

              Poorly controlled diabetes in pregnancy increases maternal risk for diabetic ketoacidosis, pre- eclampsia, spontaneous abortions, preterm delivery, still birth and delivery complications. Poorly controlled diabetes increases fetal risk for major malformations, still birth, and macrosomia related morbidity

              Lactation

              There is no information regarding presence of metformin or alogliptin in human milk, effects on breastfed infant, or effects 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; the developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from therapy or from underlying maternal condition

              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

              Alogliptin: Selective dipeptidyl peptidase-4 (DPP-4) inhibitor; slows inactivation of incretin hormones (eg, GLP-1, GIP), thereby reducing fasting and postprandial glucose concentrations in a glucose-dependent manner

              Metformin: Biguanide; decreases hepatic glucose production, decreases GI glucose absorption, and increases target cell insulin sensitivity

              Absorption

              Bioavailability: ~100% (alogliptin); 50-60% (metformin [fasted])

              Peak plasma time: 1-2 hr (alogliptin)

              Distribution

              Protein bound: 20% (alogliptin); negligible (metformin)

              Vd: 417 L (alogliptin)

              Metabolism

              alogliptin

              • Does not undergo extensive metabolism and 60-71% of the dose is excreted unchanged in the urine
              • Active metabolite: N-demethylated (<1% of parent compound)
              • Inactive metabolite: N-acetylated alogliptin (<6% of parent compound)
              • Minor substrate of CYP3A4 and CYP2D6

              metformin

              • Excreted unchanged in the urine and does not undergo hepatic metabolism (no metabolites have been identified in humans) nor biliary excretion

              Elimination

              alogliptin

              • Half-life: 21 hr
              • Renal clearance: 9.6 L/hr
              • Total body clearance: 14 L/hr
              • Excretion: 76% urine; 13% feces

              metformin

              • Half-life: 6.2 hr (plasma), 17.6 hr (blood); suggests erythrocyte mass a compartment of distribution
              • Excretion: 90% urine
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              Administration

              Instructions

              Metformin must be taken with food

              Swallow whole, do not chew, split, or crush

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              Images

              No images available for this drug.
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              Patient Handout

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

              FormularyPatient Discounts

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              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
              2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
              3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
              4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
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              NC NOT COVERED – Drugs that are not covered by the plan.
              Code Definition
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              Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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              Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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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.