dapagliflozin/metformin (Rx)

Brand and Other Names:Xigduo XR
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

dapagliflozin/metformin extended-release

tablet, extended-release

  • 2.5mg/1000mg
  • 5mg/500mg
  • 5mg/1000mg
  • 10mg/500mg
  • 10mg/1000mg

Type 2 Diabetes Mellitus

Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (T2DM) when treatment with both dapagliflozin and metformin is appropriate

Individualize starting dose based on current regimen

Not already taking dapagliflozin: Initiate dapagliflozin at 5 mg PO qDay

Adjust dose based on effectiveness and tolerability; not to exceed 10 mg dapagliflozin and 2,000 mg metformin

Heart Failure and/or Chronic Kidney Disease

Dapagliflozin indicated to reduce risk of

  • Hospitalization risk for heart failure (HF) in adults with T2DM and established cardiovascular disease (CVD) or multiple CV risk factors
  • CV death and hospitalization for HF in adults with T2DM who have HF (NYHA class II-IV) with reduced ejection fraction
  • Sustained eGFR rate decline, end-stage renal disease (ESRD), CV death, and hospitalization for HF in adults with chronic kidney disease at risk of progression

Dose

  • Individualize starting dose based on current regimen
  • For indications related to heart failure and/or chronic kidney disease, recommended dapagliflozin is 10 mg PO qDay
  • Adjust dose based on effectiveness and tolerability; not to exceed 10 mg dapagliflozin and 2,000 mg metformin

Dosage Modifications

Renal impairment

  • Obtain eGFR before starting metformin
  • eGFR ≥45 mL/min/1.73 m²: No dosage adjustment required
  • eGFR 30-45 mL/min/1.73 m²: Not recommended
  • eGFR <30 mL/min/1.73 m²: Contraindicated
  • Monitor eGFR at least annually or more often for those at risk for renal impairment (eg, elderly)

Discontinuation for iodinated contrast imaging procedures

  • Discontinue dapagliflozin/metformin at time of, or prior to, an iodinated contrast imaging procedure in patients with a history of liver disease, alcoholism or heart failure; or in patients who will be administered intra-arterial iodinated contrast
  • Re-evaluate eGFR 48 hr after imaging procedure; restart if renal function is stable

Dosing Considerations

Assess patient's current therapy

  • Individualize starting dose based on current therapy
  • If taking an evening dose of metformin XR, skip last dose before starting dapagliflozin/metformin
  • Adjust dose based on effectiveness and tolerability; not to exceed daily dose of dapagliflozin 10 mg and metformin 2000 mg

Before initiating

  • Assess renal function before initiating and periodically thereafter
  • Assess volume status and, if necessary, correct volume depletion before initiating

Limitations of use

  • Not for type 1 diabetes mellitus or diabetic ketoacidosis
  • Because of the metformin component, use limited to adults with type 2 diabetes mellitus for all indications

Safety and efficacy not established

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Interactions

Interaction Checker

and dapagliflozin/metformin

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              Serious - Use Alternative (13)

              • contrast media (iodinated)

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

              • ethanol

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

              • ioversol

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

              • methylene blue

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

              • pacritinib

                pacritinib will increase the level or effect of metformin by Other (see comment). Avoid or Use Alternate Drug. Concomitant administration of pacritinib (OCT1 inhibitor) with OCT1 substrates may increase the plasma concentrations of these substrates.

              • ranolazine

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

              • risdiplam

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

              • selegiline

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

              • selegiline transdermal

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

              • tafenoquine

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

              • tedizolid

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

              • tranylcypromine

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

              • trilaciclib

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

              Monitor Closely (188)

              • acetazolamide

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

              • albiglutide

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

              • amiodarone

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

              • amlodipine

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

              • aripiprazole

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

              • asenapine

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

              • atazanavir

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

              • benazepril

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

              • benzphetamine

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

              • betamethasone

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

              • bictegravir

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

              • bitter melon

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

              • brexpiprazole

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

              • bumetanide

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

              • bupropion

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

              • captopril

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

              • cariprazine

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

              • cephalexin

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

              • ceritinib

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

              • chlorpromazine

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

              • chlorpropamide

                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 metformin by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

              • cinnamon

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

              • ciprofloxacin

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

              • citalopram

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

              • clevidipine

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

              • clozapine

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

              • colesevelam

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

              • conjugated estrogens

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

              • corticotropin

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

              • dabrafenib

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

              • dalfampridine

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

              • darunavir

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

              • desogestrel

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

              • diatrizoate

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

              • diatrizoate meglumine/diatrizoate sodium

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

              • diazoxide

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

              • dichlorphenamide

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

              • dienogest/estradiol valerate

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

              • diethylpropion

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

              • digoxin

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

              • diltiazem

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

              • dofetilide

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

              • dolutegravir

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

              • drospirenone

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

              • dulaglutide

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

                dulaglutide, 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.

              • enalapril

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

              • 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.

              • entecavir

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

              • erdafitinib

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

              • escitalopram

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

              • estradiol

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

              • estrogens conjugated synthetic

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

              • estropipate

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

              • ethacrynic acid

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

              • ethinylestradiol

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

              • ethiodized oil

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

              • etonogestrel

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

              • everolimus

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

              • exenatide injectable solution

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

              • exenatide injectable suspension

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

              • felodipine

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

              • fleroxacin

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

              • fluoxetine

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

              • fluphenazine

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

              • fluvoxamine

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

              • fosamprenavir

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

              • fosinopril

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

              • fosphenytoin

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

              • gemifloxacin

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

              • glipizide

                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.

              • glucagon intranasal

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

              • 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.

              • glycopyrrolate

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

              • goserelin

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

              • histrelin

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

              • hydroxyprogesterone caproate

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

              • iloperidone

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

              • imidapril

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

              • indinavir

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

              • insulin aspart

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

                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

                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.

                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.

                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

                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.

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

              • insulin detemir

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

                insulin 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

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

                insulin 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

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

                insulin 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

                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.

                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

                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.

                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

                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.

                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

                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.

                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

                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.

                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

                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.

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

              • iodixanol

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

              • letermovir

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

              • ioflupane I 123

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

              • iohexol

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

              • iopamidol

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

              • iopromide

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

              • ioversol

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

              • ioxilan

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

              • isocarboxazid

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

              • isoniazid

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

              • isradipine

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

              • ketotifen, ophthalmic

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

              • lanreotide

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

              • leuprolide

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

              • levofloxacin

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

              • levonorgestrel intrauterine

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

              • levonorgestrel oral

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

              • levothyroxine

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

              • linezolid

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

              • liothyronine

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

              • liotrix

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

              • liraglutide

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

              • lisinopril

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

              • lonapegsomatropin

                lonapegsomatropin decreases effects of metformin 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 decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease 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, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

              • marijuana

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

              • mecasermin

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

              • medroxyprogesterone

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

              • methamphetamine

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

              • methazolamide

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

              • moexipril

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

              • moxifloxacin

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

              • nelfinavir

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

              • niacin

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

              • nicardipine

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

              • nifedipine

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

              • nilotinib

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

              • nimodipine

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

              • nisoldipine

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

              • nizatidine

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

              • norelgestromin

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

              • norethindrone

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

              • norgestimate

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

              • octreotide

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

              • ofloxacin

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

              • olanzapine

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

              • omacetaxine

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

              • ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

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

              • ondansetron

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

              • opuntia ficus indica

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

              • paliperidone

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

              • paroxetine

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

              • pasireotide

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

              • patiromer

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

              • pentamidine

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

              • perindopril

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

              • perphenazine

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

              • phendimetrazine

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

              • phenelzine

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

              • phentermine

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

              • phenytoin

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

              • procainamide

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

              • procarbazine

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

              • prochlorperazine

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

              • progesterone intravaginal gel

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

              • progesterone micronized

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

              • progesterone, natural

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

              • promethazine

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

              • quetiapine

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

              • quinapril

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

              • quinidine

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

              • ramipril

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

              • rasagiline

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

              • repaglinide

                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.

              • risperidone

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

              • ritonavir

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

              • saquinavir

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

              • sertraline

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

              • shark cartilage

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

              • sirolimus

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

              • somapacitan

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

              • somatropin

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

              • tolazamide

                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.

              • sulfamethoxypyridazine

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

              • tacrolimus

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

              • temsirolimus

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

              • tenofovir DF

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

              • thioridazine

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

              • thyroid desiccated

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

              • tibolone

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

              • tipranavir

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

              • tolbutamide

                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.

              • topiramate

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

              Minor (82)

              • agrimony

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

              • American ginseng

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

              • amitriptyline

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

              • amoxapine

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

              • anamu

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

              • bendroflumethiazide

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

              • budesonide

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

              • chlorothiazide

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

              • chlorthalidone

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

              • chromium

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

              • clomipramine

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

              • clonidine

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

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

              • cornsilk

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

              • cortisone

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

              • cyanocobalamin

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

              • cyclopenthiazide

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

              • damiana

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

              • danazol

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

              • deflazacort

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

              • desipramine

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

              • devil's claw

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

              • dexamethasone

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

              • diltiazem

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

              • doxepin

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

              • elderberry

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

              • eucalyptus

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

              • famotidine

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

              • fludrocortisone

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

              • fluoxymesterone

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

              • fo-ti

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

              • folic acid

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

              • forskolin

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

              • furosemide

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

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

              • gotu kola

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

              • guanfacine

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

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

              • gymnema

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

              • horse chestnut seed

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

              • hydrochlorothiazide

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

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

              • hydrocortisone

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

              • ibuprofen/famotidine

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

              • imipramine

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

              • indapamide

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

              • juniper

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

              • L-methylfolate

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

              • lofepramine

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

              • lycopus

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

              • maitake

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

              • maprotiline

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

              • memantine

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

              • mesterolone

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

              • methyclothiazide

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

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

              • methylprednisolone

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

              • methyltestosterone

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

              • metolazone

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

              • midodrine

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

              • nettle

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

              • nifedipine

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

              • nortriptyline

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

              • ofloxacin

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

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

              • oxandrolone

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

              • oxymetholone

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

              • pegvisomant

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

              • potassium acid phosphate

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

              • potassium chloride

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

              • potassium citrate

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

              • prednisolone

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

              • prednisone

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

              • protriptyline

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

              • quinine

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

              • sage

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

              • stevia

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

              • sulfamethoxazole

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

              • testosterone

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

              • testosterone buccal system

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

              • testosterone topical

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

              • tongkat ali

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

              • trazodone

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

              • triamterene

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

              • trimethoprim

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

              • trimipramine

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

              • vanadium

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

              • verapamil

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

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              Adverse Effects

              1-10%

              Female genital mycotic infections (9.3-9.4%)

              Nasopharyngitis (5.2-6.3%)

              Urinary tract infections (5.5-6.1%)

              Diarrhea (4.2-5.9%)

              Headache (3.3-5.4%)

              Male genital mycotic infections (3.6-4.3%)

              Influenza (2.6-4.1%)

              Nausea (2.6-3.9%)

              Back pain (2.5-3.4%)

              Dizziness (1.8-3.2%)

              Constipation (1.9-2.9%)

              Dyslipidemia (1.5-2.7%)

              Pharyngitis (1.5-2.7%)

              Increased urination (2.4-2.6%)

              Discomfort with urination (1.6-2.2%)

              Postmarketing Reports

              Lactic acidosis

              Acute kidney injury and impairment in renal function

              Dapagliflozin

              • Ketoacidosis
              • Acute kidney injury
              • Impairment in renal function
              • Urosepsis
              • Pyelonephritis rash

              Metformin hydrochloride

              • Cholestatic, hepatocellular, and mixed hepatocellular liver injury
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              Warnings

              Black Box Warnings

              Lactic acidosis

              • Lactic acidosis caused by metformin accumulation (plasma concentration >5 mcg/mL) is a rare but potentially severe consequence; if it occurs, mortality is ~50%
              • Risk increases with certain conditions (eg, renal impairment, sepsis, dehydration, excess alcohol intake, and hepatic impairment); concomitant use of certain drugs (eg, carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (eg, acute congestive heart failure)
              • Onset is subtle, accompanied only by nonspecific symptoms (eg, malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress)
              • Laboratory abnormalities include low pH, increased anion gap, and elevated blood lactate
              • If lactic acidosis is suspected, discontinue drug and immediately hospitalize the patient
              • 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 imaging procedure; restart therapy if renal function stable

              Contraindications

              Severe renal impairment (eg, eGFR <30 ml/min/1.73 m2), end stage renal disease or patients on dialysis, which may also result from conditions such as shock, acute MI, and septicemia

              Acute or chronic metabolic acidosis, including diabetic ketoacidosis

              Hypersensitivity

              Cautions

              Dapagliflozin increases risk of urinary tract infections (UTIs), including life-threatening urosepsis and pyelonephritis that started as UTIs; evaluate for signs and symptoms of urinary tract infections and treat promptly, if indicated

              Dapagliflozin increases risk for genital mycotic infections

              Metformin associated with a decrease to subnormal levels of previously normal serum vitamin B-12 levels, without clinical manifestations; measure hematological parameters annually and vitamin B12 at 2- to 3-year intervals and manage any abnormalities

              Lactic acidosis

              • Postmarketing cases of metformin-associated lactic acidosis, including fatal cases, reported
              • Lactic acidosis has a subtle onset and may be accompanied by nonspecific symptoms (eg, malaise, myalgias, abdominal pain, respiratory distress, increased somnolence); however, hypothermia, hypotension, and resistant bradyarrhythmias have occurred with severe acidosis
              • Metformin-associated lactic acidosis characterized by elevated blood lactate concentrations (>5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), and increased lactate: pyruvate ratio; metformin plasma levels generally >5 mcg/mL
              • Metformin decreases liver uptake of lactate increasing lactate blood levels, which may increase risk of lactic acidosis, especially in patients at risk
              • If lactic acidosis suspected, institute general supportive measures promptly in a hospital setting, along with immediate discontinuation metformin-containing product
              • Prompt hemodialysis recommended for diagnosis or strong suspicion of lactic acidosis to correct acidosis and remove accumulated metformin; hemodialysis often results in symptom reversal and recovery
              • Lactic acid risk factors and management
                • Renal impairment: Obtain eGFR before initiating, contraindicated if eGFR <30 mL/min/1.73 m2; obtain eGFR at least annually, and more often for patients at higher risk (eg, elderly)
                • Drug interactions: Coadministration with certain drugs may increase risk, such as those that impair renal function, result in significant hemodynamic change, interfere with acid-base balance, or increase metformin accumulation (eg, cationic drugs)
                • Aged ≥65 years greater likelihood of hepatic, renal, or cardiac impairment compared with younger patients; assess renal function more frequently
                • Radiological studies with iodinated contrast: May cause acute decrease in renal function and occurrence of lactic acidosis; discontinue metformin-containing products at time of, or prior to, iodinated contrast imaging procedure in patients with history of hepatic impairment, alcoholism, heart failure, or if administered intra-arterial iodinated contrast; reevaluate eGFR 48 hr after procedure, and restart metformin-containing drug if renal function stable
                • Surgery/procedures: Withholding food and fluids during surgical or other procedures may increase risk for volume depletion, hypotension, and renal impairment; temporarily discontinue metformin-containing product while food and fluid intake is restricted
                • Hypoxic states: Metformin-associated lactic acidosis reported with acute congestive heart failure (particularly when accompanied by hypoperfusion and hypoxemia); cardiovascular collapse, acute myocardial infarction, sepsis, and other conditions associated with hypoxemia have been associated with lactic acidosis and may also cause prerenal azotemia; if such events occur, discontinue metformin-containing product
                • Excessive alcohol intake: Alcohol potentiates effect of metformin on lactate metabolism and may increase risk of lactic acidosis
                • Hepatic impairment: Risk of lactic acidosis increased; this may be due to impaired lactate clearance resulting in higher lactate blood levels; avoid metformin-containing products with clinical or laboratory evidence of hepatic disease

              Volume depletion

              • Dapagliflozin can cause intravascular volume depletion which may sometimes manifest as symptomatic hypotension or acute transient changes in creatinine
              • Postmarketing reports of acute kidney injury, some requiring hospitalization and dialysis, in patients with T2DM receiving SGLT2 inhibitors
              • Patients with impaired renal function (eGFR <60 mL/min/1.73 m2), elderly patients, or coadministration with loop diuretics may be at increased risk for volume depletion or hypotension
              • Assess volume status and renal function before initiating
              • Monitor renal function and blood pressure after initiating

              Ketoacidosis

              • 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

              Necrotizing fasciitis of perineum (Fournier gangrene)

              • Rare but serious and life-threatening necrotizing infection requiring urgent surgical intervention, have been identified with SGLT2 inhibitors in both males and females
              • 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 >100.4°F or a general feeling of being unwell
              • If suspected, discontinue SGLT2 inhibitor, closely monitor blood glucose levels, and provide appropriate alternative therapy for glycemic control; start broad-spectrum antibiotics immediately and surgical debridement if necessary

              Hypoglycemia

              • Dapagliflozin can increase the risk of hypoglycemia when combined with insulin or an insulin secretagogue; a lower dose of insulin or insulin secretagogue may be required
              • 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 (eg, sulfonylureas, insulin) or ethanol
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              Pregnancy & Lactation

              Pregnancy

              Based on animal data showing adverse renal effects, not recommended during the second and third trimesters of pregnancy

              Limited data in pregnant women are not sufficient to determine drug-associated risk for major birth defects or miscarriage

              Published studies with metformin use during pregnancy have not reported a clear association with metformin and major birth defect or miscarriage risk

              There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy

              Discuss potential for unintended pregnancy with premenopausal women as therapy with metformin may result in ovulation in some anovulatory women

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

              Reproductive potential

              • Discuss potential for unintended pregnancy with premenopausal women as therapy with metformin may result in ovulation in some anovulatory women

              Animal data

              • In animal studies, adverse renal pelvic and tubule dilatations, that were not fully reversible, were observed in rats when dapagliflozin was administered during a period of renal development corresponding to the late second and third trimesters of human pregnancy, at all doses tested; the lowest of which provided an exposure 15-times the 10 mg clinical dose

              Lactation

              There is no information regarding the presence in human milk, the effects on the breastfed infant, or the effects on milk production

              Limited published studies report that metformin is present in human milk

              However, there is insufficient information on the effects of metformin on the breastfed infant and no available information on the effects of metformin on milk production

              Dapagliflozin is present in the milk of lactating rats

              Because of the potential for serious adverse reactions in breastfed infants, advise women that use 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; SGLT2 is expressed in the proximal renal tubules and 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

              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

              Absorption

              Bioavailability: 78% (dapagliflozin)

              Distribution

              Protein bound: 91% (dapagliflozin); negligible (metformin)

              Metabolism

              Metformin: Excreted unchanged in the urine and does not undergo hepatic metabolism

              Dapagliflozin

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

              Elimination

              Dapagliflozin

              • Half-life: 12.9 hr
              • Excretion: 75% urine (<2% as parent drug); 21% feces (~15% as parent drug)

              Metformin

              • Half-life: 6.2 hr (plasma); 17.6 hr (blood) – Suggests erythrocyte mass may be a compartment of distribution
              • Renal clearance: ~3.5 times greater than CrCl
              • Excretion: 90% urine
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              Administration

              Oral Administration

              Administer once daily in morning with food

              Swallow whole; do not crush, cut, or chew

              Occasionally, the inactive ingredients of the extended-release tablet will be eliminated in the feces as a soft, hydrated mass that may resemble the original tablet

              Storage

              Store at 20-25°C (68-77°F); excursions permitted between 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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              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
              2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
              3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
              4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
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              NC NOT COVERED – Drugs that are not covered by the plan.
              Code Definition
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              Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.