saxagliptin/metformin (Rx)

Brand and Other Names:Kombiglyze XR
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Dosing & Uses

AdultPediatricGeriatric

Dosing Forms & Strengths

saxagliptin/metformin

tablet, extended-release

  • 5mg/500mg
  • 2.5mg/1000mg
  • 5mg/1000mg

Diabetes Mellitus Type 2

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

Individualize starting dose based on patient’s current regimen

Adjust dose according to effectiveness and tolerability; not to exceed daily dose of 5 mg/2000 mg

Administer qDay with evening meal

Inadequately controlled on metformin alone

  • 2.5-5 mg/day saxagliptin PO plus current dose of metformin

Inadequately controlled on saxagliptin alone

  • 500 mg/day metformin PO plus 5 mg/day PO saxagliptin

Dosage Modifications

Coadministration with strong CYP3A4/5 inhibitors: Not to exceed 2.5 mg/day saxagliptin or 1000 mg/day metformin

Hepatic impairment: Do not administer

Renal impairment

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

Safety and efficacy not established

Initial and maintenance dosing should be conservative due to possibility of decreased renal function. Adjust dose gradually and conservatively considering effectiveness and tolerability

Inadequately controlled on metformin alone

2.5-5 mg/day saxagliptin PO plus current dose of metformin

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

Inadequately controlled on saxagliptin alone

500 mg/day metformin PO plus 5 mg/day PO saxagliptin

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

Concomitant administration with strong CYP3A4/5 inhibitors

Not to exceed 2.5 mg/day saxagliptin or 1000 mg/day metformin

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

Metformin

Contraindicated in patients with renal impairment, carefully monitor renal function in the elderly and use with caution as age increases

Initial and maintenance dosing of metformin should be conservative in patients with advanced age due to the potential for decreased renal function in this population

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

Saxagliptin

Saxagliptin: In the 6, double-blind, controlled clinical safety and efficacy trials of saxagliptin, 634 (15.3%) of the 4148 randomized patients were 65 years or older, and 59 (1.4%) patients were 75 years or older

No overall differences in safety or effectiveness were observed between patients 65 years or older and younger patients

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Interactions

Interaction Checker

and saxagliptin/metformin

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              Serious - Use Alternative (25)

              • abametapir

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

              • apalutamide

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

              • chloramphenicol

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

              • cobicistat

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

              • 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.

              • erdafitinib

                erdafitinib will increase the level or effect of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If coadministration unavoidable, separate administration by at least 6 hr before or after administration of P-gp substrates with narrow therapeutic index.

              • ethanol

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

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

              • fexinidazole

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

              • ioversol

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

              • idelalisib

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

              • ivosidenib

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

              • lasmiditan

                lasmiditan increases levels of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

              • lonafarnib

                lonafarnib will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.

              • 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.

              • sotorasib

                sotorasib will decrease the level or effect of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications.

              • 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.

              • tepotinib

                tepotinib will increase the level or effect of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If concomitant use unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.

              • tranylcypromine

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

              • trilaciclib

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

              • tucatinib

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

              Monitor Closely (248)

              • 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, saxagliptin. 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.

              • aripiprazole

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

              • 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.

                asenapine, saxagliptin. 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. .

                atazanavir will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors

              • benazepril

                saxagliptin increases toxicity of benazepril by Mechanism: unspecified interaction mechanism. Use Caution/Monitor. Increased risk of adverse/toxic effects, specifically increased 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.

              • berotralstat

                berotralstat will increase the level or effect of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

              • betamethasone

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

              • bexarotene

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

              • bictegravir

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

              • bitter melon

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

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

              • bosutinib

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

              • 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

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

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

              • carbamazepine

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

              • cariprazine

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

              • cenobamate

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

              • cephalexin

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

              • ceritinib

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

              • chlorpromazine

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

              • cimetidine

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

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

              • cinnamon

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

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

              • ciprofloxacin

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

                ciprofloxacin increases effects of saxagliptin 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 will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors

              • 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, saxagliptin. 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, 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.

              • conivaptan

                conivaptan will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors

              • 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.

              • crizotinib

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

              • crofelemer

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

              • dabrafenib

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

                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 will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors

              • 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.

                diltiazem will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Closely monitor glucose when saxagliptin is concomitantly used with moderate CYP3A4 inhibitors.

              • dofetilide

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

              • dulaglutide

                dulaglutide, saxagliptin. 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.

              • 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.

              • duvelisib

                duvelisib will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with duvelisib increases AUC of a sensitive CYP3A4 substrate which may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A substrate.

              • elagolix

                elagolix will increase the level or effect of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

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

              • eliglustat

                eliglustat increases levels of saxagliptin 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.

              • elvitegravir/cobicistat/emtricitabine/tenofovir DF

                elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors

              • enalapril

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

              • encorafenib

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

              • entecavir

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

              • enzalutamide

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

              • erdafitinib

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

              • erythromycin base

                erythromycin base will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • erythromycin ethylsuccinate

                erythromycin ethylsuccinate will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • erythromycin lactobionate

                erythromycin lactobionate will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • erythromycin stearate

                erythromycin stearate will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • 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, saxagliptin. 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, 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.

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

              • fedratinib

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

              • felodipine

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

              • fleroxacin

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

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

              • fluoxetine

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

              • fosamprenavir

                fosamprenavir will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors

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

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

              • glecaprevir/pibrentasvir

                glecaprevir/pibrentasvir will increase the level or effect of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              • glucagon intranasal

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

              • glycopyrrolate

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

              • goserelin

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

              • histrelin

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

              • hydroxyprogesterone caproate

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

              • iloperidone

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

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

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

              • imatinib

                imatinib will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors

              • imidapril

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

              • indinavir

                indinavir will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors

                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.

                saxagliptin, 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.

                saxagliptin, 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

                saxagliptin, 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.

                saxagliptin, 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.

                saxagliptin, 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.

                saxagliptin, 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.

                saxagliptin, 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

                saxagliptin, 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

                saxagliptin, 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

                saxagliptin, 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

                saxagliptin, 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

                saxagliptin, 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

                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.

                saxagliptin, 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. .

              • isoniazid

                isoniazid will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors

              • 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.

              • istradefylline

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

                istradefylline will increase the level or effect of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates.

              • itraconazole

                itraconazole will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors

              • ivacaftor

                ivacaftor increases levels of saxagliptin 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.

              • ketoconazole

                ketoconazole will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors

              • ketotifen, ophthalmic

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

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

              • lanreotide

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

              • letermovir

                letermovir increases levels of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • leuprolide

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

              • levofloxacin

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

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

              • levonorgestrel intrauterine

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

              • liraglutide

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

              • levonorgestrel oral

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

              • levothyroxine

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

              • linezolid

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

              • liothyronine

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

              • liotrix

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

              • liraglutide

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

              • lisinopril

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

              • lomitapide

                lomitapide increases levels of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing dose when used concomitantly with lomitapide.

              • lonafarnib

                lonafarnib will increase the level or effect of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Lonafarnib is a weak P-gp inhibitor. Monitor for adverse reactions if coadministered with P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities. Reduce P-gp substrate dose if needed.

              • lopinavir

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

                lopinavir will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors

              • lurasidone

                lurasidone, saxagliptin. 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, 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.

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

              • mecasermin

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

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

              • medroxyprogesterone

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

              • mifepristone

                mifepristone will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. When coadministered, the initial dose of saxagliptin should be limited to 2.5 mg/day

              • 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.

              • mitotane

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

              • moexipril

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

              • moxifloxacin

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

                moxifloxacin increases effects of saxagliptin 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.

              • nefazodone

                nefazodone will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors

              • nelfinavir

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

              • nelfinavir

                nelfinavir will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 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 will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors

                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.

              • ofloxacin

                ofloxacin increases effects of saxagliptin 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.

              • 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.

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

              • omacetaxine

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

              • opuntia ficus indica

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

              • ombitasvir/paritaprevir/ritonavir & dasabuvir

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

              • ondansetron

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

              • opuntia ficus indica

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

              • paliperidone

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

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

              • paroxetine

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

              • ponatinib

                ponatinib increases levels of saxagliptin by P-glycoprotein (MDR1) efflux transporter. 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.

              • posaconazole

                posaconazole will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors

              • 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.

                quinidine will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors

              • ramipril

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

              • ribociclib

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

              • rasagiline

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

              • rifabutin

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

              • rifampin

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

              • risperidone

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

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

              • ritonavir

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

                ritonavir will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors

              • saquinavir

                saquinavir will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors

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

              • sarecycline

                sarecycline will increase the level or effect of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for toxicities of P-gp substrates that may require dosage reduction when coadministered with P-gp inhibitors.

              • sertraline

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

              • shark cartilage

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

                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.

              • St John's Wort

                St John's Wort will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • somapacitan

                somapacitan decreases effects of saxagliptin 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

                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.

              • stiripentol

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

                stiripentol will increase the level or effect of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing the dose of P-glycoprotein (P-gp) substrates, if adverse reactions are experienced when administered concomitantly with stiripentol.

              • sulfamethoxypyridazine

                sulfamethoxypyridazine increases effects of saxagliptin 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.

              • tacrolimus

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

              • tazemetostat

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

              • tecovirimat

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

              • temsirolimus

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

              • tenofovir DF

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

              • thioridazine

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

              • thyroid desiccated

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

              • tibolone

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

              • tipranavir

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

                tipranavir will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors

              • topiramate

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

              • tucatinib

                tucatinib will increase the level or effect of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.

              • torsemide

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

              • trandolapril

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

              • triamcinolone acetonide injectable suspension

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

              • trifluoperazine

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

              • trimethoprim

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

              • triptorelin

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

              • trospium chloride

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

              • vandetanib

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

              • vemurafenib

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

              • 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 will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors

              • 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 saxagliptin 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, saxagliptin. 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 (139)

              • agrimony

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

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

              • American ginseng

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

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

              • amitriptyline

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

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

              • amobarbital

                amobarbital will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • amoxapine

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

              • amoxapine

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

              • anamu

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

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

              • aprepitant

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

              • bendroflumethiazide

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

              • armodafinil

                armodafinil will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • artemether/lumefantrine

                artemether/lumefantrine will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • bendroflumethiazide

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

              • bosentan

                bosentan will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • budesonide

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

                budesonide will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

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

              • butabarbital

                butabarbital will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 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.

              • butalbital

                butalbital will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • chlorothiazide

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

              • chlorthalidone

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

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

              • chromium

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

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

              • clomipramine

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

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

              • clonidine

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

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

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

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

              • cornsilk

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

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

              • cortisone

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

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

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

              • cyclosporine

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

              • damiana

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

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

              • danazol

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

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

              • darifenacin

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

              • deflazacort

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

              • dasatinib

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

              • deferasirox

                deferasirox will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • deflazacort

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

              • desipramine

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

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

              • devil's claw

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

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

              • dexamethasone

                dexamethasone will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

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

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

              • DHEA, herbal

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

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

              • dronedarone

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

              • elderberry

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

              • efavirenz

                efavirenz will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • elderberry

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

              • eslicarbazepine acetate

                eslicarbazepine acetate will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • etravirine

                etravirine will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • eucalyptus

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

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

              • famotidine

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

              • fluconazole

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

              • fludrocortisone

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

                fludrocortisone will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

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

              • fluoxymesterone

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

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

              • fo-ti

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

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

              • folic acid

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

              • forskolin

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

              • forskolin

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

              • fosphenytoin

                fosphenytoin will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

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

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

              • grapefruit

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

              • 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.

              • griseofulvin

                griseofulvin will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • guanfacine

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

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

              • gymnema

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

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

              • horse chestnut seed

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

                horse chestnut seed increases effects of saxagliptin 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.

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

              • hydrocortisone

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

                hydrocortisone will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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 saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown.

              • imipramine

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

              • indapamide

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

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

              • juniper

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

                juniper increases effects of saxagliptin 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.

              • lapatinib

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

              • lofepramine

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

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

              • lumefantrine

                lumefantrine will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • lycopus

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

              • lycopus

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

              • maitake

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

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

              • maprotiline

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

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

              • marijuana

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

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

              • methyclothiazide

                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.

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

              • methylprednisolone

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

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

                methylprednisolone will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • methyltestosterone

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

                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.

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

              • metronidazole

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

              • midodrine

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

              • miconazole vaginal

                miconazole vaginal will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • modafinil

                modafinil will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • nafcillin

                nafcillin will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • nettle

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

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

              • nevirapine

                nevirapine will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • nifedipine

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

              • nifedipine

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

              • nilotinib

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

              • nortriptyline

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

                nortriptyline increases effects of saxagliptin 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, saxagliptin. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Potential dysglycemia.

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

              • oxandrolone

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

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

              • oxcarbazepine

                oxcarbazepine will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • oxymetholone

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

              • oxymetholone

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

              • pegvisomant

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

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

              • pentobarbital

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

              • phenobarbital

                phenobarbital will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • phenytoin

                phenytoin will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • potassium acid phosphate

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

              • potassium chloride

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

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

              • potassium citrate

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

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

              • prednisolone

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

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

              • prednisone

                prednisone will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

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

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

              • primidone

                primidone will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • protriptyline

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

              • protriptyline

                protriptyline increases effects of saxagliptin 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.

              • quinupristin/dalfopristin

                quinupristin/dalfopristin will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • rifapentine

                rifapentine will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • rufinamide

                rufinamide will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • sage

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

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

              • secobarbital

                secobarbital will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • stevia

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

              • stevia

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

              • testosterone buccal system

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

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

              • testosterone topical

                testosterone topical increases effects of saxagliptin 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 saxagliptin 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 saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • trazodone

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

              • trazodone

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

              • triamcinolone acetonide injectable suspension

                triamcinolone acetonide injectable suspension decreases effects of saxagliptin by pharmacodynamic antagonism. 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 saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown.

              • vanadium

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

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

              • verapamil

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

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

              • zafirlukast

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

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              Adverse Effects

              1-10%

              Diarrhea (9.6%)

              Nausea/vomiting (6.5%)

              Headache (6.5%)

              Hypoglycemia, saxagliptin (1.6%)

              <1%

              Rash

              Lymphopenia

              Postmarketing reports

              Saxagliptin

              • Hypersensitivity reactions including anaphylaxis, angioedema, and exfoliative skin conditions
              • Pancreatitis
              • Severe and disabling arthralgia
              • Bullous pemphigoid
              • Rhabdomyolysis

              Metformin

              • Cholestatic, hepatocellular, and mixed hepatocellular liver injury
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              Warnings

              Black Box Warnings

              Lactic acidosis caused by metformin accumulation (plasma concentration >5 mcg/mL) is a rare but potentially severe consequence; if it occurs, mortality is ~50%

              Incidence is rare (~0.03 cases/1000 patient-years with 0.015 fatal cases/100 patient-years)

              Patients with CHF requiring pharmacologic management, in particular those with unstable or acute CHF who are at risk of hypoperfusion and hypoxemia, are at an increased risk of lactic acidosis

              Risk of lactic acidosis increases with the degree of renal dysfunction and age

              Do not start in patients aged 80 years or older unless CrCl demonstrates that renal function is not reduced because these patients are more susceptible to developing lactic acidosis

              Promptly withhold metformin with hypoxemia, dehydration, or sepsis

              Avoided with clinical or laboratory evidence of hepatic disease

              Caution against excessive alcohol intake, either acute or chronic, during metformin therapy because alcohol potentiates the effects of metformin on lactate metabolism

              Should be temporarily discontinued prior to any intravascular radiocontrast study and for any surgical procedure

              The onset of lactic acidosis often is subtle and accompanied by nonspecific symptoms (eg, malaise, myalgias, respiratory distress, increasing somnolence, nonspecific abdominal distress)

              DPP-4 inhibitors may cause joint pain that can be severe and disabling; resolves within a month upon discontinuing the drug

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

              Contraindications

              History of serious hypersensitivity (eg, anaphylaxis, angioedema, exfoliative skin conditions)

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

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

              Cautions

              Gradual increase of metformin dose may reduce GI side effects

              Metformin may decrease serum vitamin B12 concentration

              Do not exceed saxagliptin 2.5 mg/day when coadministered with strong cytochrome P450 3A4/5 (CYP3A4/5) inhibitors (eg, ketoconazole, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin)

              Coadministration of saxagliptin with thiazolidinediones (eg, rosiglitazone, pioglitazone) increases risk for peripheral edema

              Inactive tablet ingredients (ie, ghost tablet) may be eliminated in the feces as a soft, hydrated mass

              Pancreatitis reported with saxagliptin; monitor for signs and symptoms and discontinue if pancreatitis suspected

              Serious hypersensitivity reactions with saxagliptin reported (typically within the first 3 months of therapy)

              Caution with history of angioedema

              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

              Hypoglycemia

              • Hypoglycemia does not occur in patients receiving metformin alone under usual circumstances of use, but could occur when caloric intake is deficient, when strenuous exercise is not compensated by caloric supplementation, or during concomitant use with other glucose-lowering agents (such as sulfonylureas and insulin) or ethanol
              • Elderly, debilitated, or malnourished patients and those with adrenal or pituitary insufficiency or alcohol intoxication are particularly susceptible to hypoglycemic effects
              • Insulin secretagogues, such as sulfonylureas, cause hypoglycemia; therefore, when used in combination with saxagliptin, a lower dose of the insulin secretagogue may be required to reduce the risk of hypoglycemia

              Congestive heart failure (CHF) risks

              • In the SAVOR-TIMI 53 trial (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus) 16,492 patients with type 2 diabetes mellitus and a history of, or at risk of, cardiovascular events were randomized to saxagliptin or placebo
              • A higher incidence of hospitalization for CHF was observed in patients treated with saxagliptin compared with those treated with placebo (3.5% vs 2.8%; P=0.007); this increased risk was highest among patients with elevated levels of natriuretic peptides, previous heart failure, or chronic kidney disease
              • Circulation. 2014 Oct 28;130(18):1579-88
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              Pregnancy & Lactation

              Pregnancy

              Limited available data in pregnant women are not sufficient to determine 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

              No adverse developmental effects independent of maternal toxicity observed when saxagliptin and metformin were administered separately or in combination to pregnant rats and rabbits during period of organogenesis

              Poorly controlled diabetes in pregnancy increases maternal risk for diabetic ketoacidosis, pre- eclampsia, spontaneous abortions, preterm delivery, stillbirth 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

              Saxagliptin: Dipeptidyl peptidase IV (DPP-4) inhibition that results in increased incretin hormones and enhanced glycemic control

              Metformin: Biguanide; acts by decreasing endogenous hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization; improves glucose tolerance and lowers both basal and postprandial plasma glucose

              Pharmacokinetics

              Half-Life: saxagliptin 2.5-3.1 hr; metformin 6.2 hr (plasma) and 17.6 hr (blood)

              Peak Plasma Time: metformin extended-release 4-8 hr

              Peak Plasma Concentration: saxagliptin and active metabolite (24 ng/mL, 47 ng/mL)

              Protein Bound: negligible for both saxagliptin and metformin

              Metabolism: saxagliptin by CYP3A4/5; major active metabolite is also a DPP4 inhibitor (50% as potent); metformin is excreted unchanged in urine and does not undergo hepatic metabolism

              Excretion: feces (saxagliptin 22%), urine (saxagliptin 75%; metformin 90%)

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              Administration

              Oral Administration

              Administer qDay with evening meal

              Swallow whole, do not chew, cut, or crush

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              Images

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              Patient Handout

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

              FormularyPatient Discounts

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              Tier Description
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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.