Dosing & Uses
Dosage Forms & Strengths
dapagliflozin/saxagliptin/metformin HCl extended-release
tablet
- 2.5mg/2.5mg/1000mg
- 5mg/2.5mg/1000mg
- 5mg/5mg/1000mg
- 10mg/5mg/1000mg
Type 2 Diabetes Mellitus
Sodium-glucose cotransporter 2 (SGLT2) inhibitor, a dipeptidyl peptidase-4 (DPP-4) inhibitor, and a biguanide combination product indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (DM)
Individualize starting total daily dose based on the patient’s current regimen, effectiveness, and tolerability
For patients not currently taking dapagliflozin, recommended starting dose is dapagliflozin 5 mg/saxagliptin 5 mg/metformin HCl extended-release 1000 mg or 2000 mg PO qDay
Maximum recommended daily dose is dapagliflozin 10 mg/saxagliptin 5 mg/metformin HCl extended-release 2000 mg
Dosage Modifications
Renal impairment
- Mild (eGFR ≥45 mL/min/1.73 m²): No dosage adjustment necessary
- Moderate-to-severe (eGFR <45 mL/min/1.73 m²): Contraindicated
- End-stage renal disease (ESRD) or patients on dialysis: Contraindicated
Hepatic impairment
- Not recommended; use of metformin in patients with hepatic impairment has been associated with some cases of lactic acidosis
Dosing Considerations
Discontinuation for iodinated contrast imaging procedures
- Discontinue 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
- Reevaluate eGFR 48 hr after imaging procedure; restart Qternmet XR if renal function is stable
Limitations of use
- Not indicated for treatment of type 1 diabetes mellitus or diabetic ketoacidosis
- Therapy initiation is intended only for patients currently taking metformin
- Vitamin B12: Monitor hematologic parameters on an annual basis is advised in patients receiving therapy and appropriately investigate and manage any apparent abnormalities
<18 years: Safety and efficacy not established
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Contraindicated (0)
Serious - Use Alternative (26)
- apalutamide
apalutamide will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.
- ceritinib
ceritinib will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- chloramphenicol
chloramphenicol will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- cobicistat
cobicistat will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- contrast media (iodinated)
contrast media (iodinated) increases levels of metformin by decreasing renal clearance. Contraindicated. Acute renal failure or lactic acidosis may result. D/c metformin 48 hr before and after imaging study.
- erdafitinib
erdafitinib will increase the level or effect of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If coadministration unavoidable, separate administration by at least 6 hr before or after administration of P-gp substrates with narrow therapeutic index.
- ethanol
ethanol, saxagliptin. Other (see comment). Contraindicated. Comment: Excessive EtOH consumption may alter glycemic control. Some sulfonylureas may produce a disulfiram like rxn.
ethanol increases toxicity of metformin by Other (see comment). Contraindicated. Comment: Excessive EtOH consumption may alter glycemic control. Some sulfonylureas may produce a disulfiram like rxn; alcohol may potentiate the risk of lactic acidosis. - fexinidazole
fexinidazole will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.
- ioversol
ioversol increases levels of metformin by decreasing renal clearance. Contraindicated. Acute renal failure or lactic acidosis may result. D/c metformin 48 hr before and after imaging study.
- idelalisib
idelalisib will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates
- ivosidenib
ivosidenib will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.
- lasmiditan
lasmiditan increases levels of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- lonafarnib
lonafarnib will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.
- methylene blue
methylene blue will increase the level or effect of metformin by unspecified interaction mechanism. Avoid or Use Alternate Drug.
- 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.
- sotorasib
sotorasib will decrease the level or effect of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications.
- tafenoquine
tafenoquine will increase the level or effect of metformin by Other (see comment). Avoid or Use Alternate Drug. Tafenoquine inhibits organic cation transporter-2 (OCT2) and multidrug and toxin extrusion (MATE) transporters in vitro. Avoid coadministration with OCT2 or MATE substrates. If coadministration cannot be avoided, monitor for substrate-related toxicities and consider dosage reduction if needed based on product labeling of the coadministered drug.
- tedizolid
tedizolid will increase the level or effect of metformin by unspecified interaction mechanism. Avoid or Use Alternate Drug.
- tepotinib
tepotinib will increase the level or effect of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If concomitant use unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.
- tranylcypromine
tranylcypromine will increase the level or effect of metformin by unspecified interaction mechanism. Avoid or Use Alternate Drug.
- trilaciclib
trilaciclib will decrease the level or effect of metformin by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of trilaciclib (OCT2, MATE1, and MATE-2K inhibitor) with substrates where minimal increased concentration in kidney or blood may lead to serious or life-threatening toxicities.
- tucatinib
tucatinib will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.
Monitor Closely (246)
- acetazolamide
acetazolamide increases toxicity of metformin by Other (see comment). Use Caution/Monitor. Comment: Decreases serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis.
- albiglutide
albiglutide, metformin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.
albiglutide, saxagliptin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels. - amiodarone
amiodarone will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.
- aripiprazole
aripiprazole, saxagliptin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- amlodipine
amlodipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- aripiprazole
aripiprazole, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- asenapine
asenapine, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
asenapine, saxagliptin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely. - atazanavir
atazanavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
atazanavir will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors - benazepril
saxagliptin increases toxicity of benazepril by Mechanism: unspecified interaction mechanism. Use Caution/Monitor. Increased risk of adverse/toxic effects, specifically increased risk of angioedema.
benazepril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis. - benzphetamine
benzphetamine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- berotralstat
berotralstat will increase the level or effect of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.
- betamethasone
betamethasone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- bexarotene
bexarotene increases effects of saxagliptin by pharmacodynamic synergism. Use Caution/Monitor. Based on the mechanism of action, bexarotene capsules may increase the action of insulin enhancing agents, resulting in hypoglycemia. Hypoglycemia has not been associated with bexarotene monotherapy.
- bictegravir
bictegravir will increase the level or effect of metformin by decreasing renal clearance. Modify Therapy/Monitor Closely. Bictegravir inhibits organic cation transporter 2 (OCT2) and multidrug and toxin extrusion transporter 1 (MATE1) in vitro. Coadministration with OCT2 and MATE1 substrates may increase their plasma concentrations. Metformin dose reduction may be required.
- bitter melon
bitter melon increases effects of saxagliptin by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypoglycemia.
bitter melon increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypoglycemia. - bosutinib
bosutinib increases levels of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- brexpiprazole
brexpiprazole decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- bumetanide
bumetanide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- bupropion
bupropion increases levels of metformin by Other (see comment). Use Caution/Monitor. Comment: Bupropion may inhibit OCT2 mediated renal excretion of metformin.
- captopril
saxagliptin increases toxicity of captopril by Mechanism: unspecified interaction mechanism. Use Caution/Monitor. Increased risk of adverse/toxic effects, specifically increased risk of angioedema.
captopril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis. - carbamazepine
carbamazepine will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- cariprazine
cariprazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- cenobamate
cenobamate will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.
- cephalexin
cephalexin increases toxicity of metformin by decreasing renal clearance. Use Caution/Monitor. particularly in patients who may have other risk factors for metformin toxicity. .
- ceritinib
ceritinib decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- chlorpromazine
chlorpromazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- 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.
cimetidine will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - cinnamon
cinnamon increases effects of saxagliptin by pharmacodynamic synergism. Use Caution/Monitor. Potential for hypoglycemia.
cinnamon increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Potential for hypoglycemia. - ciprofloxacin
ciprofloxacin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Hyper and hypoglycemia have been reported in patients treated concomitantly with quinolones and antidiabetic agents. Careful monitoring of blood glucose is recommended.
ciprofloxacin increases effects of saxagliptin by pharmacodynamic synergism. Use Caution/Monitor. Hyper and hypoglycemia have been reported in patients treated concomitantly with quinolones and antidiabetic agents. Careful monitoring of blood glucose is recommended. - citalopram
citalopram increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.
- clarithromycin
clarithromycin will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors
- clevidipine
clevidipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- clozapine
clozapine, saxagliptin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
clozapine, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely. - colesevelam
colesevelam increases levels of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- conivaptan
conivaptan will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors
- conjugated estrogens
conjugated estrogens decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- corticotropin
corticotropin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- crizotinib
crizotinib increases levels of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- crofelemer
crofelemer increases levels of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.
- dabrafenib
dabrafenib will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
dabrafenib decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. - dalfampridine
metformin, dalfampridine. Either increases levels of the other by Other (see comment). Use Caution/Monitor. Comment: Metformin and dalfampridine are organic cation transporter 2 (OCT2) substrates; both drugs may compete for renal tubular uptake and could potentially increase systemic exposure of either drug when administered concomitantly.
- darunavir
darunavir will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors
- darunavir
darunavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
- desogestrel
desogestrel decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- diatrizoate
diatrizoate increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .
- diatrizoate meglumine/diatrizoate sodium
diatrizoate meglumine/diatrizoate sodium increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .
- diazoxide
diazoxide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- dichlorphenamide
dichlorphenamide, metformin. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Both drugs can cause metabolic acidosis.
- dienogest/estradiol valerate
dienogest/estradiol valerate decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- diethylpropion
diethylpropion decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- digoxin
digoxin, metformin. Either increases levels of the other by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor. Measure serum digoxin concentrations before initiating metformin. Monitor patients who take both metformin and digoxin for possible digoxin toxicity and lactic acidosis. Reduce the digoxin and/or metformin dose as necessary.
- diltiazem
diltiazem decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
diltiazem will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Closely monitor glucose when saxagliptin is concomitantly used with moderate CYP3A4 inhibitors. - dofetilide
dofetilide will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.
- dulaglutide
dulaglutide, saxagliptin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
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. - 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
- 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.
- drospirenone
drospirenone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- dulaglutide
dulaglutide, metformin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
- duvelisib
duvelisib will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with duvelisib increases AUC of a sensitive CYP3A4 substrate which may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A substrate.
- elagolix
elagolix will increase the level or effect of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
elagolix decreases levels of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed. - eliglustat
eliglustat increases levels of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the P-gp substrate and titrate to clinical effect.
- elvitegravir/cobicistat/emtricitabine/tenofovir DF
elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors
- enalapril
enalapril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.
- encorafenib
encorafenib, saxagliptin. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.
- entecavir
entecavir, metformin. Either increases levels of the other by Other (see comment). Use Caution/Monitor. Comment: Coadministration of entecavir with metformin may increase the risk of lactic acidosis.
- enzalutamide
enzalutamide will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- erdafitinib
metformin increases levels of erdafitinib by decreasing renal clearance. Modify Therapy/Monitor Closely. Consider alternatives that are not OCT2 substrates or consider reducing the dose of OCT2 substrates based on tolerability.
- erythromycin base
erythromycin base will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- erythromycin ethylsuccinate
erythromycin ethylsuccinate will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- erythromycin lactobionate
erythromycin lactobionate will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- erythromycin stearate
erythromycin stearate will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- escitalopram
escitalopram increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.
- estradiol
estradiol decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- estrogens conjugated synthetic
estrogens conjugated synthetic decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- estropipate
estropipate decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- ethacrynic acid
ethacrynic acid decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- ethinylestradiol
ethinylestradiol decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- ethiodized oil
ethiodized oil increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .
- etonogestrel
etonogestrel decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- everolimus
everolimus decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- exenatide injectable solution
exenatide injectable solution, saxagliptin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.
exenatide injectable solution, metformin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels. - exenatide injectable suspension
exenatide injectable suspension, metformin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.
exenatide injectable suspension, saxagliptin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels. - fedratinib
fedratinib will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.
- felodipine
felodipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- fleroxacin
fleroxacin increases effects of saxagliptin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.
fleroxacin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely. - fluoxetine
fluoxetine increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.
- fosamprenavir
fosamprenavir will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors
- fluphenazine
fluphenazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- fluvoxamine
fluvoxamine increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.
- fosamprenavir
fosamprenavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
- fosinopril
fosinopril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.
- fosphenytoin
fosphenytoin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- gemifloxacin
gemifloxacin increases effects of saxagliptin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.
gemifloxacin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely. - glecaprevir/pibrentasvir
glecaprevir/pibrentasvir will increase the level or effect of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- 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 (DSC)
hydroxyprogesterone caproate (DSC) decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- iloperidone
iloperidone, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
iloperidone increases levels of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.
iloperidone, saxagliptin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely. - imatinib
imatinib will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors
- imidapril
imidapril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.
- indinavir
indinavir will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors
indinavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. . - insulin aspart
metformin, insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
saxagliptin, insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
insulin aspart, 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.
saxagliptin, insulin aspart protamine/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
dapagliflozin, insulin aspart protamine/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents. - insulin degludec
dapagliflozin, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
saxagliptin, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
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.
saxagliptin, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents. - insulin detemir
metformin, insulin detemir. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
saxagliptin, insulin detemir. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
insulin 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.
saxagliptin, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
insulin glargine, dapagliflozin. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with dapagliflozin.
dapagliflozin, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents. - insulin glulisine
metformin, insulin glulisine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
saxagliptin, insulin glulisine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
insulin glulisine, dapagliflozin. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with dapagliflozin.
dapagliflozin, insulin glulisine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents. - insulin inhaled
saxagliptin, insulin inhaled. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
dapagliflozin, insulin inhaled. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
metformin, insulin inhaled. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents. - insulin isophane human/insulin regular human
saxagliptin, insulin isophane human/insulin regular human. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
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
saxagliptin, insulin lispro. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
insulin lispro, dapagliflozin. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with dapagliflozin.
dapagliflozin, insulin lispro. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
metformin, insulin lispro. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents. - insulin lispro protamine/insulin lispro
saxagliptin, insulin lispro protamine/insulin lispro. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
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
saxagliptin, insulin NPH. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
insulin NPH, dapagliflozin. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with dapagliflozin.
dapagliflozin, insulin NPH. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
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.
saxagliptin, insulin regular human. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents. - iodixanol
iodixanol increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .
- letermovir
letermovir will increase the level or effect of dapagliflozin by unspecified interaction mechanism. Use Caution/Monitor. Monitor glucose concentrations.
- isoniazid
isoniazid will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors
- ioflupane I 123
ioflupane I 123 increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .
- iohexol
iohexol increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .
- iopamidol
iopamidol increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .
- iopromide
iopromide increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .
- ioversol
ioversol increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .
- ioxilan
ioxilan increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .
- isocarboxazid
isocarboxazid will increase the level or effect of metformin by unspecified interaction mechanism. Use Caution/Monitor.
- isoniazid
isoniazid decreases effects of metformin by unspecified interaction mechanism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- isradipine
isradipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- istradefylline
istradefylline will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.
istradefylline will increase the level or effect of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates. - itraconazole
itraconazole will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors
- ivacaftor
ivacaftor increases levels of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.
- ketoconazole
ketoconazole will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors
- ketotifen, ophthalmic
ketotifen, ophthalmic, saxagliptin. Other (see comment). Use Caution/Monitor. Comment: Combination may result in thrombocytopenia (rare). Monitor CBC.
ketotifen, ophthalmic, metformin. Other (see comment). Use Caution/Monitor. Comment: Combination may result in thrombocytopenia (rare). Monitor CBC. - lanreotide
lanreotide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- lenacapavir
lenacapavir will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.
- letermovir
letermovir increases levels of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- leuprolide
leuprolide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- levofloxacin
levofloxacin increases effects of saxagliptin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.
levofloxacin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely. - levoketoconazole
levoketoconazole will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors
- 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, saxagliptin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.
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.
- lithium
dapagliflozin decreases levels of lithium by Other (see comment). Use Caution/Monitor. Comment: Concomitant use of an SGLT2 inhibitor with lithium may decrease serum lithium concentrations; monitor serum lithium concentration more frequently during therapy initiation and dosage changes.
- lomitapide
lomitapide increases levels of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing dose when used concomitantly with lomitapide.
- lithium
metformin decreases levels of lithium by Other (see comment). Use Caution/Monitor. Comment: SGLT2 inhibitors with lithium may decrease serum lithium concentrations; monitor serum lithium concentration more frequently during therapy initiation and dosage changes.
- lonafarnib
lonafarnib will increase the level or effect of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Lonafarnib is a weak P-gp inhibitor. Monitor for adverse reactions if coadministered with P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities. Reduce P-gp substrate dose if needed.
- lonapegsomatropin
lonapegsomatropin decreases effects of saxagliptin by Other (see comment). Use Caution/Monitor. Comment: Closely monitor blood glucose when treated with antidiabetic agents. Lonapegsomatropin may decrease insulin sensitivity, particularly at higher doses. Patients with diabetes mellitus may require adjustment of their doses of insulin and/or other antihyperglycemic agents.
lonapegsomatropin decreases effects of 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.
lonapegsomatropin decreases effects of metformin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone.
lonapegsomatropin decreases effects of dapagliflozin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone.
lonapegsomatropin decreases effects of saxagliptin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone. - lopinavir
lopinavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
lopinavir will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors - nateglinide
nateglinide, dapagliflozin. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with dapagliflozin.
- lurasidone
lurasidone, saxagliptin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
lurasidone, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely. - marijuana
marijuana decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
marijuana decreases effects of saxagliptin by pharmacodynamic antagonism. Use Caution/Monitor. - mecasermin
mecasermin increases effects of saxagliptin by pharmacodynamic synergism. Use Caution/Monitor. Additive hypoglycemic effects.
mecasermin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Additive hypoglycemic effects. - medroxyprogesterone
medroxyprogesterone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- mifepristone
mifepristone will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. When coadministered, the initial dose of saxagliptin should be limited to 2.5 mg/day
- methamphetamine
methamphetamine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- methazolamide
methazolamide increases toxicity of metformin by Other (see comment). Use Caution/Monitor. Comment: Decreases serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis.
- mitotane
mitotane decreases levels of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.
- moexipril
moexipril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.
- moxifloxacin
moxifloxacin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.
moxifloxacin increases effects of saxagliptin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely. - nefazodone
nefazodone will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors
- nelfinavir
nelfinavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
- nelfinavir
nelfinavir will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors
- niacin
niacin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- nicardipine
nicardipine will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors
nicardipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia. - nifedipine
nifedipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- ofloxacin
ofloxacin increases effects of saxagliptin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.
- nilotinib
nilotinib decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- nimodipine
nimodipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- nisoldipine
nisoldipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- nizatidine
nizatidine will increase the level or effect of metformin by decreasing renal clearance. Modify Therapy/Monitor Closely.
- norelgestromin
norelgestromin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- norethindrone
norethindrone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- norgestimate
norgestimate decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- octreotide
octreotide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- ofloxacin
ofloxacin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.
- olanzapine
olanzapine, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
olanzapine, saxagliptin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely. - omacetaxine
omacetaxine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- opuntia ficus indica
opuntia ficus indica increases effects of saxagliptin by pharmacodynamic synergism. Use Caution/Monitor.
- ombitasvir/paritaprevir/ritonavir & dasabuvir (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, saxagliptin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
paliperidone, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely. - paroxetine
paroxetine increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.
- ponatinib
ponatinib increases levels of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- pasireotide
pasireotide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- patiromer
patiromer will decrease the level or effect of metformin by drug binding in GI tract. Modify Therapy/Monitor Closely. Separate administration by at least 3 hr from patiromer
- pentamidine
pentamidine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- perindopril
perindopril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.
- perphenazine
perphenazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- phendimetrazine
phendimetrazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- phenelzine
phenelzine will increase the level or effect of metformin by unspecified interaction mechanism. Use Caution/Monitor.
- phentermine
phentermine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- phenytoin
phenytoin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- posaconazole
posaconazole will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors
- procainamide
metformin will increase the level or effect of procainamide by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.
- procarbazine
procarbazine will increase the level or effect of metformin by unspecified interaction mechanism. Use Caution/Monitor.
- prochlorperazine
prochlorperazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- progesterone intravaginal gel
progesterone intravaginal gel decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- progesterone micronized
progesterone micronized decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- progesterone, natural
progesterone, natural decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- promethazine
promethazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- quetiapine
quetiapine, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- quinapril
quinapril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.
- quinidine
quinidine will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.
quinidine will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors - ramipril
ramipril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.
- repaglinide
repaglinide, dapagliflozin. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with dapagliflozin.
- ribociclib
ribociclib will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- rasagiline
rasagiline will increase the level or effect of metformin by unspecified interaction mechanism. Use Caution/Monitor.
- rifabutin
rifabutin will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- rifampin
rifampin will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- risperidone
risperidone, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
risperidone, saxagliptin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely. - ritonavir
ritonavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
ritonavir will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors - saquinavir
saquinavir will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors
saquinavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. . - sarecycline
sarecycline will increase the level or effect of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for toxicities of P-gp substrates that may require dosage reduction when coadministered with P-gp inhibitors.
- sertraline
sertraline increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.
- shark cartilage
shark cartilage increases effects of saxagliptin by pharmacodynamic synergism. Use Caution/Monitor. Theoretical interaction.
shark cartilage increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Theoretical interaction. - sirolimus
sirolimus decreases levels of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- somapacitan
somapacitan decreases effects of dapagliflozin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone.
somapacitan decreases effects of saxagliptin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone. - somapacitan
somapacitan decreases effects of metformin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone.
- somatrogon
somatrogon decreases effects of dapagliflozin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone.
- somatrogon
somatrogon decreases effects of saxagliptin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone.
somatrogon decreases effects of metformin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone. - somatropin
somatropin decreases effects of saxagliptin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone.
somatropin decreases effects of dapagliflozin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone.
somatropin decreases effects of metformin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone. - St John's Wort
St John's Wort will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tolazamide
tolazamide, dapagliflozin. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with dapagliflozin.
- sulfamethoxypyridazine
sulfamethoxypyridazine increases effects of metformin by unspecified interaction mechanism. Use Caution/Monitor. Risk of hypoglycemia.
- stiripentol
stiripentol, saxagliptin. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.
stiripentol will increase the level or effect of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing the dose of P-glycoprotein (P-gp) substrates, if adverse reactions are experienced when administered concomitantly with stiripentol. - sulfamethoxypyridazine
sulfamethoxypyridazine increases effects of saxagliptin by unspecified interaction mechanism. Use Caution/Monitor. Risk of hypoglycemia.
- tacrolimus
tacrolimus decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- tazemetostat
tazemetostat will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tecovirimat
tecovirimat will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.
- temsirolimus
temsirolimus decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- tenofovir DF
tenofovir DF increases levels of metformin by decreasing renal clearance. Use Caution/Monitor. Increased risk of lactic acidosis.
- thioridazine
thioridazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- thyroid desiccated
thyroid desiccated decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- tibolone
tibolone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- tipranavir
tipranavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
tipranavir will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 inhibitors - 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 (109)
- acetazolamide
acetazolamide will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- agrimony
agrimony increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
agrimony increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown. - American ginseng
American ginseng increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
American ginseng increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. - amitriptyline
amitriptyline increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
amitriptyline increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown. - amobarbital
amobarbital will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- amoxapine
amoxapine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
- amoxapine
amoxapine increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
- anamu
anamu increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown. Theoretical interaction.
anamu increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Theoretical interaction. - anastrozole
anastrozole will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- bendroflumethiazide
bendroflumethiazide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
- aprepitant
aprepitant will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- armodafinil
armodafinil will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- artemether/lumefantrine
artemether/lumefantrine will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- bendroflumethiazide
bendroflumethiazide decreases effects of saxagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
- bosentan
bosentan will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- budesonide
budesonide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.
budesonide will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
budesonide decreases effects of saxagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. - butabarbital
butabarbital will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- chlorothiazide
chlorothiazide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
- butalbital
butalbital will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- chlorothiazide
chlorothiazide decreases effects of saxagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
- chlorthalidone
chlorthalidone decreases effects of saxagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
chlorthalidone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose. - chromium
chromium increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
chromium increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. - clomipramine
clomipramine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
clomipramine increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown. - clonidine
clonidine decreases effects of saxagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
clonidine, saxagliptin. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
clonidine decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
clonidine, metformin. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production. - cornsilk
cornsilk increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).
cornsilk increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction). - cortisone
cortisone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.
cortisone decreases effects of saxagliptin by pharmacodynamic antagonism. Minor/Significance Unknown.
cortisone will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. - cyanocobalamin
metformin decreases levels of cyanocobalamin by unspecified interaction mechanism. Minor/Significance Unknown. It may take several years of metformin therapy to develop vitamin B12 deficiency.
- cyclopenthiazide
cyclopenthiazide decreases effects of saxagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
- cyclopenthiazide
cyclopenthiazide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
- cyclophosphamide
cyclophosphamide will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- cyclosporine
cyclosporine will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- damiana
damiana decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Theoretical interaction.
damiana decreases effects of saxagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Theoretical interaction. - danazol
danazol increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
danazol increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. - darifenacin
darifenacin will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- deflazacort
deflazacort decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.
- dasatinib
dasatinib will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- deferasirox
deferasirox will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- deflazacort
deflazacort decreases effects of saxagliptin by pharmacodynamic antagonism. Minor/Significance Unknown.
- desipramine
desipramine increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
desipramine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. - devil's claw
devil's claw increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
devil's claw increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown. - dexamethasone
dexamethasone will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
dexamethasone decreases effects of saxagliptin by pharmacodynamic antagonism. Minor/Significance Unknown.
dexamethasone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. - DHEA, herbal
DHEA, herbal will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- diltiazem
diltiazem will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
- doxepin
doxepin increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
doxepin increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown. - dronedarone
dronedarone will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- elderberry
elderberry increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (in vitro research).
- efavirenz
efavirenz will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- elderberry
elderberry increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (in vitro research).
- eslicarbazepine acetate
eslicarbazepine acetate will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- etravirine
etravirine will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- eucalyptus
eucalyptus increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Theoretical interaction.
eucalyptus increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown. Theoretical interaction. - famotidine
famotidine increases levels of metformin by decreasing renal clearance. Minor/Significance Unknown.
- fluconazole
fluconazole will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- fludrocortisone
fludrocortisone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.
fludrocortisone will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
fludrocortisone decreases effects of saxagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. - fluoxymesterone
fluoxymesterone increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
fluoxymesterone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. - fo-ti
fo-ti increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
fo-ti increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. - folic acid
metformin decreases levels of folic acid by unspecified interaction mechanism. Minor/Significance Unknown.
- forskolin
forskolin increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown. Colenol, a compound found in Coleus root, may stimulate insulin release.
- forskolin
forskolin increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Colenol, a compound found in Coleus root, may stimulate insulin release.
- fosaprepitant
fosaprepitant will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- fosphenytoin
fosphenytoin will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- furosemide
metformin decreases levels of furosemide by unspecified interaction mechanism. Minor/Significance Unknown.
furosemide increases levels of metformin by unspecified interaction mechanism. Minor/Significance Unknown. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia. - gotu kola
gotu kola increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction).
gotu kola increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction). - grapefruit
grapefruit will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- guanfacine
guanfacine decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
guanfacine, metformin. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production. - griseofulvin
griseofulvin will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- guanfacine
guanfacine decreases effects of saxagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
guanfacine, saxagliptin. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production. - gymnema
gymnema increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
gymnema increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown. - horse chestnut seed
horse chestnut seed increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
horse chestnut seed increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown. - hydrochlorothiazide
hydrochlorothiazide will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
hydrochlorothiazide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
hydrochlorothiazide decreases effects of saxagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose. - hydrocortisone
hydrocortisone decreases effects of saxagliptin by pharmacodynamic antagonism. Minor/Significance Unknown.
hydrocortisone will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
hydrocortisone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. - ibuprofen/famotidine
ibuprofen/famotidine increases levels of metformin by decreasing renal clearance. Minor/Significance Unknown.
- imipramine
imipramine increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
- imipramine
imipramine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
- indapamide
indapamide decreases effects of saxagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
indapamide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose. - juniper
juniper increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).
juniper increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction). - L-methylfolate
metformin decreases levels of L-methylfolate by unspecified interaction mechanism. Minor/Significance Unknown.
- lapatinib
lapatinib will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- larotrectinib
larotrectinib will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- lofepramine
lofepramine increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
lofepramine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. - lumefantrine
lumefantrine will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- lycopus
lycopus increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).
- lycopus
lycopus increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).
- maitake
maitake increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (animal research).
maitake increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (animal research). - maprotiline
maprotiline increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
maprotiline increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown. - marijuana
marijuana will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- memantine
memantine will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
- mesterolone
mesterolone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
mesterolone increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown. - methyclothiazide
methyclothiazide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
methyclothiazide will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
methyclothiazide decreases effects of saxagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose. - methylprednisolone
methylprednisolone decreases effects of saxagliptin by pharmacodynamic antagonism. Minor/Significance Unknown.
methylprednisolone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.
methylprednisolone will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. - methyltestosterone
methyltestosterone increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
methyltestosterone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. - metolazone
metolazone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
metolazone decreases effects of saxagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose. - metronidazole
metronidazole will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- midodrine
metformin will increase the level or effect of midodrine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
- miconazole vaginal
miconazole vaginal will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- nafcillin
nafcillin will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- nettle
nettle increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction).
nettle increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction). - nevirapine
nevirapine will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- nifedipine
nifedipine increases levels of metformin by enhancing GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
- nifedipine
nifedipine will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- nilotinib
nilotinib will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- nortriptyline
nortriptyline increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
nortriptyline increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown. - ofloxacin
metformin will increase the level or effect of ofloxacin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
ofloxacin, saxagliptin. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Potential dysglycemia.
ofloxacin, metformin. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Potential dysglycemia. - oxandrolone
oxandrolone increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
oxandrolone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. - oxcarbazepine
oxcarbazepine will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- oxymetholone
oxymetholone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
- oxymetholone
oxymetholone increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
- patiromer
patiromer, dapagliflozin. cation binding in GI tract. Minor/Significance Unknown. No observed clinically important interaction. No separation of dosing required.
- pegvisomant
pegvisomant increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
pegvisomant increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown.
Adverse Effects
1-10%
Urinary tract infection (5.7%)
Dyslipidemia (5.1%)
Headache (4.3%)
Diarrhea (3.7%)
Back pain (3.3%)
Genital infection (3%)
Arthralgia (2.4%)
Postmarketing Reports
Dapagliflozin
- Ketoacidosis
- Acute kidney injury
- Renal impairment
- Urosepsis
- Pyelonephritis
- Necrotizing fasciitis of the perineum (Fournier gangrene)
- Rash
Saxagliptin
- Hypersensitivity reactions including anaphylaxis, angioedema, and exfoliative skin conditions
- Pancreatitis
- Severe and disabling arthralgia
- Bullous pemphigoid
- Rhabdomyolysis
Metformin
- Cholestatic, hepatocellular, and mixed hepatocellular liver injury
Warnings
Black Box Warnings
Lactic acidosis
- Postmarketing cases of metformin-associated lactic acidosis resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias
- Onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms (eg, malaise, myalgias, respiratory distress, somnolence, abdominal pain)
- Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (>5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio, and metformin plasma levels generally >5 mcg/mL
- Risk factors for metformin-associated lactic acidosis may include renal impairment, concomitant use of certain drugs (eg, carbonic anhydrase inhibitors), patient age ≥65 years, having a radiological study with contrast, surgery and other procedures, hypoxic states (eg, acute congestive heart failure), excessive alcohol intake, and hepatic impairment
- Steps to reduce the risk of and to manage metformin-associated lactic acidosis in these high-risk groups are provided in the full prescribing information
- If metformin-associated lactic acidosis is suspected, immediately discontinue treatment and institute general supportive measures in a hospital setting
- Prompt hemodialysis is recommended
Contraindications
Hypersensitivity to dapagliflozin, saxagliptin, or metformin
Moderate-to-severe renal impairment (eGFR <45 mL/min/1.73 m²), ESRD, or patients on dialysis
Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma
Cautions
Postmarketing cases of metformin-associated lactic acidosis, including fatal cases, were reported (see Black Box Warnings)
Postmarketing cases of serious urinary tract infections including urosepsis were reported; evaluate for signs and symptoms and treat appropriately
In cardiovascular outcomes trial, cases of definite acute pancreatitis were confirmed with patients treated with saxagliptin; if pancreatitis suspected, promptly discontinue treatment and initiate appropriate management; unknown if patients with history of pancreatitis are at increased risk for the development of pancreatitis while using Qternmet XR
Increased risk of hospitalization for heart failure in patients treated with saxagliptin reported; those with previous history of heart failure or renally impaired were at high risk
Dapagliflozin causes intravascular volume contraction; symptomatic hypotension may occur after starting therapy; assess volume status and correct
Necrotizing fasciitis of the perineum (Fournier gangrene) reported in postmarketing surveillance with SGLT2 inhibitors; it is a rare life-threatening necrotizing infection requiring urgent surgical intervention
Hypersensitivity reactions reported with saxagliptin; onset of reactions occurred within the first 3 months after initiating saxagliptin; exercise caution with history of angioedema to another DPP-4 inhibitor
In controlled clinical trials of metformin, a decrease to subnormal levels of serum vitamin B12 levels, without clinical manifestations, was observed
Dapagliflozin increases the risks of genital mycotic infections; patients with a history of genital mycotic infections were more likely to develop genital mycotic infections; monitor and treat appropriately
Increased LDL–C may occur with dapagliflozin; monitor LDL-C and treat per standard of care
In clinical studies for dapagliflozin, newly diagnosed cases of bladder cancer were reported; there were too few cases to determine whether the emergence of these events is related to dapagliflozin
Severe and disabling arthralgia in patients taking DPP-4 inhibitors have been reported; consider discontinuing drug if DPP-4 inhibitor is a cause for severe joint pain
Postmarketing cases of bullous pemphigoid requiring hospitalization have been reported with DPP-4 inhibitor use
No clinical studies establishing conclusive evidence of macrovascular risk reduction with treatment SGLT2 inhibitors increase urinary glucose excretion and will lead to positive urine glucose tests
Measurements of 1,5-AG are unreliable in assessing glycemic control in patients taking SGLT2 inhibitors
Ketoacidosis
- Reports of ketoacidosis, a serious life-threatening condition requiring urgent hospitalization, were identified in postmarketing surveillance in patients with type 1 and type 2 DM receiving SGLT2 inhibitors, including dapagliflozin; fatal cases of ketoacidosis have been reported in patients taking dapagliflozin
- Signs and symptoms at presentation were consistent with dehydration and severe metabolic acidosis and included nausea, vomiting, abdominal pain, generalized malaise, and shortness of breath
- 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; for patients who undergo elective surgery, consider temporarily discontinuing drug for at least 3 days prior to surgery
- Consider monitoring for ketoacidosis and temporarily discontinuing therapy in other clinical situations known to predispose to ketoacidosis (e.g., prolonged fasting due to acute illness or post-surgery); ensure risk factors for ketoacidosis are resolved prior to restarting drug
- Educate patients on signs and symptoms of ketoacidosis and instruct patients to discontinue therapy and seek medical attention immediately if signs and symptoms occur
Renal impairment
- Treatment causes intravascular volume contraction causing acute kidney injury; there have been postmarketing reports of acute kidney injury, some requiring hospitalization and dialysis, in patients receiving drug
- Consider temporarily discontinuing drug in the setting of reduced oral intake (such as acute illness or fasting) or fluid losses (such as gastrointestinal illness or excessive heat exposure); monitor patients for signs and symptoms of acute kidney injury; if acute kidney injury occurs, discontinue drug promptly and institute treatment
- Renal function should be evaluated prior to initiation of treatment and monitored periodically thereafter
- Obtain an eGFR at least annually in all patients receiving therapy; in patients at increased risk for the development of renal impairment (eg, the elderly), renal function should be assessed more frequentl
- Increases in serum creatinine and decreases in estimated GFR may also be observed with initiation of dapagliflozin; elderly patients and patients with impaired renal function may be more susceptible to these changes
- Before initiating therapy, consider factors that may predispose patients to acute kidney injury including hypovolemia, chronic renal insufficiency, congestive heart failure and concomitant medications (diuretics, ACE inhibitors, ARBs and NSAIDs)
Drug interactions overview
- Insulin and insulin secretagogues, such as sulfonylureas, are known to cause hypoglycemia; may require a lower dose of insulin or insulin secretagogue to reduce the risk of hypoglycemia when these agents are used in combination with Qternmet XR Ketoconazole, a strong CYP3A4/5 inhibitor, significantly increased saxagliptin exposure; avoid coadministration with strong CYP3A4/5 inhibitors
- Topiramate or other carbonic anhydrase inhibitors (eg, zonisamide, acetazolamide, dichlorphenamide) frequently causes a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis
- Concomitant use of drugs that interfere with common renal tubular transport systems involved in the renal elimination of metformin (eg, organic cationic transporter-2 [OCT2]/multidrug and toxin extrusion [MATE] inhibitors such as ranolazine, vandetanib, dolutegravir, and cimetidine) could increase systemic exposure to metformin and may increase the risk for lactic acidosis
- Alcohol potentiates the effects of metformin on lactate metabolism
Pregnancy & Lactation
Pregnancy
Not recommended during the second and third trimesters
Limited available data with dapagliflozin and saxagliptin in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage
Published studies with metformin use during pregnancy have not reported a clear association with metformin and major birth defect or miscarriage risk; there are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy
Adverse renal effects shown in animal studies Discuss potential for unintended pregnancy with premenopausal women as therapy with metformin may result in ovulation in some anovulatory women
Animal studies
- Adverse renal pelvic and tubular dilatations, that were not fully reversible, were observed in juvenile rats when dapagliflozin was administered at an exposure 15-times the exposure at the 10-mg clinical dose during a period of renal development corresponding to the late second and third trimesters of human pregnancy
- Saxagliptin did not show adverse effects during organogenesis, corresponding to the first trimester of human pregnancy
Clinical considerations
- Disease-associated maternal and/or embryo-fetal risk
- Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery and delivery complications
- Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity
Lactation
Published clinical lactation studies report that metformin is present in human milk
Saxagliptin and dapagliflozin are present in the milk of lactating rats; since human kidney maturation occurs in utero and during the first 2 years of life when lactational exposure may occur, there may be risk to the developing human kidney
Because of the potential for serious adverse reactions in a breastfed infant, advise women that use of dapagliflozin/saxagliptin is not recommended while breastfeeding
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Dapagliflozin: SGLT-2, expressed in the proximal renal tubules, is responsible for the majority of the reabsorption of filtered glucose from the tubular lumen; SGLT2 inhibitors reduce glucose reabsorption and lower the renal threshold for glucose, thereby increasing urinary glucose excretion
Saxagliptin: Dipeptidyl peptidase IV (DPP-4) inhibition that results in increased incretin hormones and enhanced glycemic control
Metformin: Biguanide; acts by decreasing endogenous hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and use; improves glucose tolerance and lowers both basal and postprandial plasma glucose
Absorption
Saxagliptin
- Peak plasma concentration: 24-47 ng/mL
- Peak plasma time: 2 hr (saxagliptin); 1.5 hr (active metabolite)
- AUC: 78-214 ng·hr/mL
Metformin
- Both high- and low-fat meals had the same effect on the pharmacokinetics of metformin extended-release
Dapagliflozin
- Oral bioavailability: 78%
- Peak plasma time: 2 hr
Distribution
Saxagliptin
- Changes in blood protein levels in various disease states (eg, renal or hepatic impairment) are not expected to alter the disposition of saxagliptin
Metformin
- Vd: 654 L
Dapagliflozin
- Protein bound: ~91%; not altered by hepatic impairment
Metabolism
Saxagliptin
- Primarily mediated by UGT1A9
- CYP-mediated metabolism is a minor clearance pathway in humans Extensively metabolized, primarily to dapagliflozin 3-O-glucuronide (inactive)
Metformin
- Excreted unchanged in the urine and does not undergo hepatic metabolism
Dapagliflozin
- Primarily mediated by CYP3A4/5
- The major metabolite of saxagliptin is also a DPP-4 inhibitor, which is 50% as potent as saxagliptin
- Strong CYP3A4/5 inhibitors and inducers alter the pharmacokinetics of saxagliptin and its active metabolite
Elimination
Saxagliptin
- Excretion: Urine (24% [36% active metabolite]; feces (22%)
- Half-life: 2.5 hr
Metformin
- Half-Life: 4-9 hr
- Dialyzable: Yes (hemodialysis)
- Renal clearance: 450-540 mL/min (regular-release)
- Excretion: Urine (90%, by tubular secretion)
Dapagliflozin
- Excretion: Urine (75% [<2% as parent drug]; feces (21% [15% as parent drug])
- Half-life: 12.9 hr
Administration
Oral Administration
Swallow whole; do not crush, cut, or chew tablet
Occasionally, inactive ingredients will be eliminated in the feces as a soft, hydrated mass that may resemble the original tablet
Missed dose
- If a dose is missed and ≥12 hr until the next dose, take the dose
- If missed dose is less than 12 hr until the next dose, skip missed dose and take the next dose at the usual time
Storage
Store at controlled room temperature; 20-25°C (68-77°F); excursion permitted to 15-30°C (59-86°F)
Images
Formulary
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