dapagliflozin/saxagliptin (Rx)

Brand and Other Names:Qtern
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

dapagliflozin/saxagliptin

tablet

  • 10mg/5mg

Type 2 Diabetes Mellitus

Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (T2DM) who have inadequate control with dapagliflozin or who are already treated with dapagliflozin and saxagliptin

1 tablet (ie, 10mg/5mg) PO qDay in AM with or without food

Dosage Modifications

Renal impairment

  • eGFR <60 mL/min/1.73 m²: Do not initiate
  • Discontinue if eGFR persistently falls to <60 mL/min/1.73 m²
  • eGFR <45 mL/min/1.73 m²: Contraindicated

Hepatic impairment

  • May be administered with hepatic impairment
  • Severe hepatic impairment: Individually assess benefit-risk

Coadministration with strong CYP3A4/5 inhibitors

  • Do not coadminister with strong CYP3A4/5 inhibitors
  • Examples include ketoconazole, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin

Dosing Considerations

In patients with volume depletion, correct this condition prior to initiating drug

Assess renal function before initiating and periodically thereafter

Limitations of use

  • Not indicated for type 1 diabetes mellitus or diabetic ketoacidosis
  • Should only be used in patients who tolerate dapagliflozin 10 mg

Safety and efficacy not established

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Interactions

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              Serious - Use Alternative (15)

              • 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.

              • 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.

              • 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.

              • 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.

              • 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.

              • 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.

              • 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.

              • voxelotor

                voxelotor will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

              Monitor Closely (113)

              • albiglutide

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

              • 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.

              • asenapine

                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 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.

              • 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.

              • 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.

              • bitter melon

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

              • bosutinib

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

              • 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.

              • carbamazepine

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

              • chlorpropamide

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

              • cimetidine

                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.

              • ciprofloxacin

                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.

              • 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

              • 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.

              • 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

              • 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.

              • 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

              • diltiazem

                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.

              • 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.

                dulaglutide, dapagliflozin. 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.

              • glimepiride

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

              • 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

              • 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.

              • enzalutamide

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

              • 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.

              • 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 suspension

                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.

              • 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.

              • 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

              • 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.

              • glecaprevir/pibrentasvir

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

              • glipizide

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

              • glyburide

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

              • iloperidone

                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.

                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.

              • 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

              • 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

              • insulin aspart

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

                dapagliflozin, 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

                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.

                dapagliflozin, 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

                dapagliflozin, 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.

                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.

              • insulin degludec/insulin aspart

                dapagliflozin, 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

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

                dapagliflozin, 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

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

                dapagliflozin, 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

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

                dapagliflozin, 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.

                dapagliflozin, 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.

                dapagliflozin, 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.

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

                dapagliflozin, 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.

                dapagliflozin, 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.

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

                dapagliflozin, 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

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

                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.

              • 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

              • letermovir

                letermovir will increase the level or effect of dapagliflozin by unspecified interaction mechanism. Use Caution/Monitor. Monitor glucose concentrations.

              • 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.

              • letermovir

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

              • levoketoconazole

                levoketoconazole 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

              • 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.

              • lithium

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

              • 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.

              • lonapegsomatropin

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

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

              • lopinavir

                lopinavir 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

              • nateglinide

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

              • 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.

              • marijuana

                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.

              • 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

              • 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.

              • moxifloxacin

                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 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

                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

              • 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.

              • olanzapine

                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.

              • opuntia ficus indica

                opuntia ficus indica increases effects of saxagliptin 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.

              • ponatinib

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

              • 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

              • quinidine

                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

              • repaglinide

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

              • ribociclib

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

              • 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.

              • shark cartilage

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

              • somapacitan

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

                somapacitan decreases effects of 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. .

              • 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.

              • tolazamide

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

              • 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.

              • 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.

              • tipranavir

                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

              • tolbutamide

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

              • 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.

              Minor (109)

              • agrimony

                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.

              • amitriptyline

                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 saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown.

              • anamu

                anamu increases effects of saxagliptin 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.

              • 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 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.

              • 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.

              • chromium

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

              • clomipramine

                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.

              • cornsilk

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

              • cortisone

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

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

              • cyclopenthiazide

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

              • danazol

                danazol increases effects of saxagliptin 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.

              • 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.

              • devil's claw

                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.

              • DHEA, herbal

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

              • doxepin

                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.

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

              • fluconazole

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

              • fludrocortisone

                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.

              • fo-ti

                fo-ti increases effects of saxagliptin by pharmacodynamic synergism. 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.

              • fosphenytoin

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

              • gotu kola

                gotu kola increases effects of saxagliptin 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.

              • 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 saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown.

              • horse chestnut seed

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

              • hydrochlorothiazide

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

              • hydrocortisone

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

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

              • imipramine

                imipramine increases effects of saxagliptin 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.

              • juniper

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

              • 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.

              • 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 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).

              • maprotiline

                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.

              • mesterolone

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

              • methyclothiazide

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

              • methylprednisolone

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

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

              • methyltestosterone

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

              • metolazone

                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.

              • miconazole vaginal

                miconazole vaginal will increase 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 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 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 saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown.

              • ofloxacin

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

              • oxandrolone

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

              • pegvisomant

                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.

              • 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 citrate

                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 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.

              • 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 saxagliptin by pharmacodynamic synergism. 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.

              • 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 saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown.

              • testosterone

                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 topical

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

              • tongkat ali

                tongkat ali increases effects of saxagliptin 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 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.

              • trimipramine

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

              • vanadium

                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.

              • zafirlukast

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

              Previous
              Next:

              Adverse Effects

              >10%

              Upper respiratory tract infection (13.6%)

              1-10%

              Urinary tract infection (5.7%)

              Dyslipidemia (5.1%)

              Headache (4.3%)

              Diarrhea (3.7%)

              Back pain (3.3%)

              Genital infection (3%)

              Arthralgia (2.4%)

              Renal impairment (2%)

              Increased serum inorganic phosphorus (1.7%)

              Hypoglycemia (1.6%)

              Increased hematocrit (1.3%)

              Elevated creatine kinase (1%)

              <1%

              Volume depletion (hypotension, dehydration, hypovolemia)

              Acute pancreatitis

              Decreased lymphocyte count

              Newly diagnosed bladder cancer

              Postmarketing Reports

              Saxagliptin

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

              Dapagliflozin

              • Ketoacidosis
              • Acute kidney injury and impaired renal function
              • Urosepsis and pyelonephritis
              • Rash
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              Next:

              Warnings

              Contraindications

              History of hypersensitivity to dapagliflozin or saxagliptin, including anaphylaxis, angioedema, or exfoliative skin conditions

              Moderate-to-severe renal impairment (eGFR <45 mL/min/1.73 m²), end-stage renal disease, or patients on dialysis

              Cautions

              Acute pancreatitis reported; after initiating drug, monitor for signs and symptoms of pancreatitis; if suspected, promptly discontinue dapagliflozin/saxagliptin and initiate appropriate management

              Necrotizing fasciitis of the perineum (Fournier gangrene) reported with SGLT2 inhibitors; signs and symptoms include tenderness, redness, or swelling of the genitals or the area from the genitals back to the rectum, and have a fever above 100.4 F or a general feeling of being unwell; if suspected, discontinue SGLT2 inhibitor and start treatment immediately with broad-spectrum antibiotics and surgical debridement if necessary

              May increase risk for developing heart failure (HF) or exacerbation of existing HR; observe patients for signs and symptoms of HF

              Patients with diabetes and renal impairment using dapagliflozin for glycemic control may be more likely to experience hypotension and may be at higher risk for acute kidney injury secondary to volume depletion; evaluate renal function prior to initiation of therapy and monitor periodically thereafter; contraindicated in patients with an eGFR <45 mL/min/1.73 m²

              Hypoglycemia risk increased with insulin and insulin secretagogues; adjust dose

              Genital mycotic infections may occur; patients with history of genital mycotic infections and uncircumcised males are more susceptible

              Serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalization reported in patients receiving SGLT2 inhibitors, including dapagliflozin; treatment with SGLT2 inhibitors increases risk for urinary tract infections; evaluate patients for signs and symptoms of urinary tract infections and treat promptly, if indicated

              Dose-related increases in LDL-C reported with dapagliflozin

              Across 22 clinical studies, newly diagnosed cases of bladder cancer were reported in 10 (0.17%)/6045 patients treated with dapagliflozin and 1 (0.03%)/3512 patient treated with placebo/comparator; bladder cancer risk factors and hematuria (a potential indicator of preexisting tumors) were balanced between treatment arms at baseline and there were too few cases to determine whether the emergence of these events is related to dapagliflozin

              Do not administer to patients with active bladder cancer and should be administered with caution in patients with a prior history of bladder cancer

              No conclusive evidence of macrovascular risk reduction with dapagliflozin or any other antidiabetic agent

              GLT2 inhibitors increase urinary glucose excretion and will lead to positive urine glucose tests; use alternative methods to monitor glycemic control

              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

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

              Postmarketing cases of bullous pemphigoid requiring hospitalization have been reported with DPP-4 inhibitor use; patients typically recovered with topical or systemic immunosuppressive treatment and discontinuation of the DPP-4 inhibitor

              Volume depletion

              • Therapy causes volume depletion that manifest as symptomatic hypotension or acute transient changes in creatinine
              • There have been postmarketing reports of acute kidney injury, some requiring hospitalization and dialysis, in patients with type 2 diabetes mellitus receiving SGLT2 inhibitors, including dapagliflozin
              • Patients with impaired renal function (eGFR <60 mL/min/1.73 m2), elderly patients, or patients on loop diuretics may be at increased risk for volume depletion or hypotension
              • Before initiating patients with one or more of these characteristics, assess volume status and renal function; therapy is contraindicated in patients with an eGFR <45 mL/min/1.73 m2; monitor for signs and symptoms of hypotension, and renal function after initiating therapy

              Ketoacidosis

              • Reports of ketoacidosis, a serious life-threatening condition requiring urgent hospitalization, identified in patients with type 1 and type 2 diabetes mellitus receiving therapy; this medication is not indicated for treatment of patients with type 1 diabetes mellitus
              • Before initiating therapy, consider factors in patient history that may predispose to ketoacidosis, including pancreatic insulin deficiency from any cause, caloric restriction, and alcohol abuse
              • Consider temporarily discontinuing therapy for at least 3 days for patients who undergo scheduled surgery
              • Consider monitoring for ketoacidosis and temporarily discontinuing therapy in other clinical situations known to predispose to ketoacidosis (eg, prolonged fasting due to acute illness or post-surgery); ensure risk factors for ketoacidosis are resolved prior to restarting therapy
              • Educate patients on signs and symptoms of ketoacidosis and instruct patients to discontinue therapy and seek medical attention immediately if signs and symptoms occur
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              Pregnancy

              Pregnancy

              Not recommended during the second and third trimesters

              Adverse renal affects shown in animal studies

              Animal studies

              • Adverse renal pelvic and tubular dilatations, that were not fully reversible, were observed in juvenile rats when dapagliflozin was administered at an exposure 15-times the exposure at the 10-mg clinical dose during a period of renal development corresponding to the late second and third trimesters of human pregnancy
              • Saxagliptin did not show adverse effects during organogenesis, corresponding to the first trimester of human pregnancy

              Lactation

              Unknown if distributed in human breast milk

              Saxagliptin and dapagliflozin are present in the milk of lactating rats; since human kidney maturation occurs in utero and during the first 2 years of life when lactational exposure may occur, there may be risk to the developing human kidney

              Because of the potential for serious adverse reactions in a breastfed infant, advise women that use of dapagliflozin/saxagliptin is not recommended while breastfeeding

              Pregnancy Categories

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

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

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

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

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

              NA: Information not available.

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              Pharmacology

              Mechanism of Action

              Dapagliflozin: Selective sodium-glucose transporter-2 (SGLT2) inhibitor; SGLT-2, expressed in the proximal renal tubules, is responsible for the majority of the reabsorption of filtered glucose from the tubular lumen; SGLT2 inhibitors reduce glucose reabsorption and lower the renal threshold for glucose, thereby increasing urinary glucose excretion

              Saxagliptin: Dipeptidyl peptidase IV (DPP-4) inhibition that results in increased incretin hormones and enhanced glycemic control; incretin hormones cause insulin release from the pancreatic beta cells in a glucose-dependent manner, but are inactivated by the DDP-4 enzyme within minutes

              Absorption

              Bioavailability

              • Dapagliflozin: 78%; high-fat meal decreases absolute bioavailability by 50%

              Peak plasma time

              • Dapagliflozin: 2 hr (fasting); 3 hr (high-fat meal)
              • Saxagliptin: 2 hr; 4 hr (active metabolite)

              Peak plasma concentration

              • Saxagliptin: 24 ng/mL
              • Saxagliptin active metabolite: 47 ng/mL

              AUC

              • Saxagliptin: 78 ng·h/mL
              • Saxagliptin active metabolite: 214 ng·h/mL

              Distribution

              Protein bound

              • Dapagliflozin: 91%
              • Saxagliptin and active metabolite: Negligible

              Metabolism

              Dapagliflozin

              • Primarily mediated by UGT1A9
              • CYP-mediated metabolism is a minor clearance pathway in humans
              • Extensively metabolized, primarily to dapagliflozin 3-O-glucuronide (inactive)

              Saxagliptin

              • Primarily mediated by CYP3A4/5
              • The major metabolite of saxagliptin is also a DPP-4 inhibitor, which is 50% as potent as saxagliptin
              • Strong CYP3A4/5 inhibitors and inducers alter the pharmacokinetics of saxagliptin and its active metabolite

              Elimination

              Half-life

              • Dapagliflozin: 12.9 hr
              • Saxagliptin: 2.5 hr; 3.1 hr (active metabolite)

              Renal clearance

              • Saxagliptin: 230 mL/min

              Excretion

              • Dapagliflozin
                • Renal: 75% (<2% as parent drug)
                • Feces: 21% (15% as parent drug)
              • Saxagliptin
                • Renal: 24%; 36% (active metabolite); 75% (total radioactivity)
                • Feces: 22%
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              Administration

              Oral Administration

              Take once daily in the morning

              May take with or without food

              Do not split or cut tablets

              Storage

              Store at controlled room temperature; 20-25°C (68-77°F)

              Excursion permitted to 15-30°C (59-86°F)

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              Images

              No images available for this drug.
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              Patient Handout

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

              FormularyPatient Discounts

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              The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
              2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
              3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
              4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              NC NOT COVERED – Drugs that are not covered by the plan.
              Code Definition
              PA Prior Authorization
              Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
              QL Quantity Limits
              Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
              ST Step Therapy
              Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
              OR Other Restrictions
              Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.