Dosing & Uses
Dosage Forms & Strengths
metformin/pioglitazone
tablet
- 500mg/15mg
- 850mg/15mg
tablet, extended-release
- 1,000mg/15mg
- 1,000mg/30mg
Type 2 Diabetes Mellitus
Patients on metformin monotherapy: 15-30 mg/day pioglitazone plus dose of metformin at time of initiating therapy
Patients on pioglitazone monotherapy: 1000-1700 mg metformin/day plus dose of pioglitazone at time of initiating therapy
Not to exceed 45 mg pioglitazone/2550 mg metformin/day
Dosage Modifications
Renal impairment: Do not use
Hepatic impairment
- Baseline ALT <2.5 xULN: Use caution
- Baseline ALT ≥2.5 xULN: Do not administer
- ALT >3 xULN or jaundice after initiating therapy: Discontinue
Renal impairment
- Obtain eGFR before starting metformin
- eGFR <30 mL/min/1.73 m²: Contraindicated
- eGFR 30-45 mL/min/1.73 m²: Not recommended to initiate treatment
- Monitor eGFR at least annually or more often for those at risk for renal impairment (eg, elderly)
- If eGFR falls below 45mL/min/1.73 m² while taking metformin, risks and benefits of continuing therapy should be evaluated
- If eGFR falls below 30 mL/min/1.73 m²: while taking metformin, discontinue the drug
Safety and efficacy not established
Type 2 Diabetes Mellitus
Same as adult dosing
Do not administer to patients >80 years before assessing renal function and determined to be normal
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Contraindicated (0)
Serious - Use Alternative (18)
- baricitinib
pioglitazone will increase the level or effect of baricitinib by decreasing elimination. Avoid or Use Alternate Drug. Coadministration of baricitinib with strong organic anion transporter 3 (OAT3) inhibitors is not recommended.
- 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.
- eluxadoline
pioglitazone increases levels of eluxadoline by decreasing metabolism. Avoid or Use Alternate Drug. Decrease eluxadoline dose to 75 mg PO BID if coadministered with OATP1B1 inhibitors. .
- ethanol
ethanol, pioglitazone. 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. - gemfibrozil
gemfibrozil will increase the level or effect of pioglitazone by decreasing metabolism. Avoid or Use Alternate Drug.
- ioversol
ioversol increases levels of metformin by decreasing renal clearance. Contraindicated. Acute renal failure or lactic acidosis may result. D/c metformin 48 hr before and after imaging study.
- methylene blue
methylene blue will increase the level or effect of metformin by unspecified interaction mechanism. Avoid or Use Alternate Drug.
- pacritinib
pacritinib will increase the level or effect of metformin by Other (see comment). Avoid or Use Alternate Drug. Concomitant administration of pacritinib (OCT1 inhibitor) with OCT1 substrates may increase the plasma concentrations of these substrates.
pioglitazone will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. - ranolazine
ranolazine will increase the level or effect of metformin by decreasing elimination. Avoid or Use Alternate Drug. Limit metformin dose to 1700 mg/day when used together with ranolazine 1000 mg twice daily; monitor closelly for signs or symptoms of metformin toxicity
- tucatinib
pioglitazone will increase the level or effect of tucatinib by Other (see comment). Avoid or Use Alternate Drug. Coadministration of tucatinib (a CYP2C8 substrate) with a strong or moderate CYP2C8 inhibitors increases tucatinib plasma concentrations and risk of toxicities.
- risdiplam
risdiplam will increase the level or effect of metformin by decreasing elimination. Avoid or Use Alternate Drug. Risdiplam inhibits MATE1 and MATE2-K. If unable to avoid coadministration with MATE substrates, consider dosage reduction of MATE substrate.
- selegiline
selegiline will increase the level or effect of metformin by unspecified interaction mechanism. Avoid or Use Alternate Drug.
- selegiline transdermal
selegiline transdermal will increase the level or effect of metformin by unspecified interaction mechanism. Avoid or Use Alternate Drug.
- tafenoquine
tafenoquine will increase the level or effect of metformin by Other (see comment). Avoid or Use Alternate Drug. Tafenoquine inhibits organic cation transporter-2 (OCT2) and multidrug and toxin extrusion (MATE) transporters in vitro. Avoid coadministration with OCT2 or MATE substrates. If coadministration cannot be avoided, monitor for substrate-related toxicities and consider dosage reduction if needed based on product labeling of the coadministered drug.
- tedizolid
tedizolid will increase the level or effect of metformin by unspecified interaction mechanism. Avoid or Use Alternate Drug.
- tranylcypromine
tranylcypromine will increase the level or effect of metformin by unspecified interaction mechanism. Avoid or Use Alternate Drug.
- trilaciclib
trilaciclib will decrease the level or effect of metformin by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of trilaciclib (OCT2, MATE1, and MATE-2K inhibitor) with substrates where minimal increased concentration in kidney or blood may lead to serious or life-threatening toxicities.
- zavegepant intranasal
pioglitazone will increase the level or effect of zavegepant intranasal by Other (see comment). Avoid or Use Alternate Drug. NTCP inhibitors may result in a significant increase in systemic exposure of zavegepant (a NTCP substrate).
Monitor Closely (248)
- acetazolamide
acetazolamide increases toxicity of metformin by Other (see comment). Use Caution/Monitor. Comment: Decreases serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis.
- albiglutide
albiglutide, metformin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.
albiglutide, pioglitazone. 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, pioglitazone. 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, pioglitazone. 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, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely. - atazanavir
atazanavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
- atogepant
pioglitazone will decrease the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- atorvastatin
pioglitazone increases toxicity of atorvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.
- axitinib
pioglitazone decreases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- benazepril
benazepril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.
- benzphetamine
benzphetamine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- betamethasone
betamethasone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- bexarotene
bexarotene increases effects of pioglitazone 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 pioglitazone by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypoglycemia.
bitter melon increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypoglycemia. - brexpiprazole
brexpiprazole decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- cannabidiol
cannabidiol will increase the level or effect of pioglitazone by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C8 activity. Consider reducing the dose when concomitantly using CYP2C8 substrates.
- bumetanide
bumetanide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- bupropion
bupropion increases levels of metformin by Other (see comment). Use Caution/Monitor. Comment: Bupropion may inhibit OCT2 mediated renal excretion of metformin.
- captopril
captopril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.
- carbamazepine
carbamazepine will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- cariprazine
cariprazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- cephalexin
cephalexin increases toxicity of metformin by decreasing renal clearance. Use Caution/Monitor. particularly in patients who may have other risk factors for metformin toxicity. .
- ceritinib
ceritinib decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- chlorpromazine
chlorpromazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- cholic acid
pioglitazone increases toxicity of cholic acid by decreasing elimination. Modify Therapy/Monitor Closely. Avoid concomitant use of inhibitors of the bile salt efflux pump (BSEP). May exacerbate accumulation of conjugated bile salts in the liver and result in clinical symptoms. If concomitant use is necessary, monitor serum transaminases and bilirubin.
- 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 pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - cinnamon
cinnamon increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Potential for hypoglycemia.
cinnamon increases effects of pioglitazone 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 pioglitazone 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 pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- clevidipine
clevidipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- clozapine
clozapine, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
clozapine, pioglitazone. 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.
- dienogest/estradiol valerate
pioglitazone will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Advise women to use alternative method of contraception or back-up method when moderate or weak enzyme inducer is used with combination contraceptives. Back-up contraception should be continued for 28 days after discontinuing medication to ensure contraceptive reliability.
- conjugated estrogens
conjugated estrogens decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- corticotropin
corticotropin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- dabrafenib
dabrafenib decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- dalfampridine
metformin, dalfampridine. Either increases levels of the other by Other (see comment). Use Caution/Monitor. Comment: Metformin and dalfampridine are organic cation transporter 2 (OCT2) substrates; both drugs may compete for renal tubular uptake and could potentially increase systemic exposure of either drug when administered concomitantly.
- darunavir
darunavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
- desogestrel
desogestrel decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- diatrizoate
diatrizoate increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .
- diatrizoate meglumine/diatrizoate sodium
diatrizoate meglumine/diatrizoate sodium increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .
- diazoxide
diazoxide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- dichlorphenamide
dichlorphenamide, metformin. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Both drugs can cause metabolic acidosis.
- dienogest/estradiol valerate
dienogest/estradiol valerate decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- diethylpropion
diethylpropion decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- digoxin
digoxin, metformin. Either increases levels of the other by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor. Measure serum digoxin concentrations before initiating metformin. Monitor patients who take both metformin and digoxin for possible digoxin toxicity and lactic acidosis. Reduce the digoxin and/or metformin dose as necessary.
- diltiazem
diltiazem decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
diltiazem will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - dofetilide
dofetilide will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.
- dulaglutide
dulaglutide, pioglitazone. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
- dolutegravir
dolutegravir will increase the level or effect of metformin by decreasing renal clearance. Modify Therapy/Monitor Closely. Dolutegravir inhibits the renal organic cation transporter, OCT2; when used with metformin, limit total daily dose of metformin to 1,000 mg either when starting metformin or dolutegravir; when stopping dolutegravir, adjustment of metformin dose may be necessary; monitor blood glucose when initiating concomitant use and after withdrawal of dolutegravir
- drospirenone
drospirenone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- dulaglutide
dulaglutide, metformin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
- enalapril
enalapril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.
- entecavir
entecavir, metformin. Either increases levels of the other by Other (see comment). Use Caution/Monitor. Comment: Coadministration of entecavir with metformin may increase the risk of lactic acidosis.
- erdafitinib
metformin increases levels of erdafitinib by decreasing renal clearance. Modify Therapy/Monitor Closely. Consider alternatives that are not OCT2 substrates or consider reducing the dose of OCT2 substrates based on tolerability.
- erythromycin base
erythromycin base will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- erythromycin ethylsuccinate
erythromycin ethylsuccinate will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- erythromycin lactobionate
erythromycin lactobionate will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- erythromycin stearate
erythromycin stearate will increase the level or effect of pioglitazone 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
pioglitazone decreases levels of ethinylestradiol by unknown mechanism. Use Caution/Monitor.
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. .
- exenatide injectable solution
exenatide injectable solution, pioglitazone. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.
- etonogestrel
etonogestrel decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- everolimus
everolimus decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- exenatide injectable solution
exenatide injectable solution, metformin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.
- exenatide injectable suspension
exenatide injectable suspension, metformin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.
exenatide injectable suspension, pioglitazone. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels. - felodipine
felodipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- fleroxacin
fleroxacin increases effects of pioglitazone 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
fleroxacin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.
- fluoxetine
fluoxetine increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.
- fluphenazine
fluphenazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- fluvastatin
pioglitazone increases toxicity of fluvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.
- fluvoxamine
fluvoxamine increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.
- fosamprenavir
fosamprenavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
- fosinopril
fosinopril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.
- fosphenytoin
fosphenytoin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- gemifloxacin
gemifloxacin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.
gemifloxacin increases effects of pioglitazone 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
pioglitazone will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Use Caution/Monitor. Caution when coadministering glecaprevir/pibrentasvir with OATP1B1/OATP1B3 inhibitors
- glucagon intranasal
glucagon intranasal decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- glycopyrrolate
glycopyrrolate increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. May require a dose reduction.
- goserelin
goserelin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- histrelin
histrelin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- hydroxyprogesterone caproate (DSC)
hydroxyprogesterone caproate (DSC) decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- ifosfamide
pioglitazone increases toxicity of ifosfamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inducers may increase the metabolism of ifosfamide to its active alkylating metabolites. CYP3A4 inducers may increase the formation of the neurotoxic/nephrotoxic ifosfamide metabolite, chloroacetaldehyde. Closely monitor patients taking ifosfamide with CYP3A4 inducers for toxicities and consider dose adjustment.
- 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, pioglitazone. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely. - imidapril
imidapril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.
- insulin aspart
insulin aspart increases toxicity of pioglitazone by unknown mechanism. Use Caution/Monitor. Insulin may increase the fluid retention associated with thiazolidinediones (peroxisome proliferator-activated receptor [PPAR]-gamma agonists).
pioglitazone, 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. - indinavir
indinavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
- insulin aspart
metformin, insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
- insulin aspart 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.
pioglitazone, 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
pioglitazone, 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
pioglitazone, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
metformin, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents. - insulin detemir
pioglitazone, 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.
metformin, insulin detemir. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
insulin detemir increases toxicity of pioglitazone by unknown mechanism. Use Caution/Monitor. Insulin may increase the fluid retention associated with thiazolidinediones (peroxisome proliferator-activated receptor [PPAR]-gamma agonists). - 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.
pioglitazone, 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 increases toxicity of pioglitazone by unknown mechanism. Use Caution/Monitor. Insulin may increase the fluid retention associated with thiazolidinediones (peroxisome proliferator-activated receptor [PPAR]-gamma agonists). - insulin glulisine
pioglitazone, 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.
metformin, insulin glulisine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
insulin glulisine increases toxicity of pioglitazone by unknown mechanism. Use Caution/Monitor. Insulin may increase the fluid retention associated with thiazolidinediones (peroxisome proliferator-activated receptor [PPAR]-gamma agonists). - insulin inhaled
pioglitazone, 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
pioglitazone, insulin isophane human/insulin regular human. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
metformin, insulin isophane human/insulin regular human. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents. - insulin lispro
insulin lispro increases toxicity of pioglitazone by unknown mechanism. Use Caution/Monitor. Insulin may increase the fluid retention associated with thiazolidinediones (peroxisome proliferator-activated receptor [PPAR]-gamma agonists).
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.
pioglitazone, 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
pioglitazone, insulin lispro protamine/insulin lispro. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
metformin, insulin lispro protamine/insulin lispro. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents. - insulin NPH
insulin NPH increases toxicity of pioglitazone by unknown mechanism. Use Caution/Monitor. Insulin may increase the fluid retention associated with thiazolidinediones (peroxisome proliferator-activated receptor [PPAR]-gamma agonists).
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.
pioglitazone, 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
pioglitazone, insulin regular human. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
metformin, insulin regular human. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
insulin regular human increases toxicity of pioglitazone by unknown mechanism. Use Caution/Monitor. Insulin may increase the fluid retention associated with thiazolidinediones (peroxisome proliferator-activated receptor [PPAR]-gamma agonists). - 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. .
- isavuconazonium sulfate
pioglitazone will decrease the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- 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.
- ketoconazole
ketoconazole will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- ketotifen, ophthalmic
ketotifen, ophthalmic, pioglitazone. Other (see comment). Use Caution/Monitor. Comment: Combination may result in thrombocytopenia (rare). Monitor CBC.
ketotifen, ophthalmic, metformin. Other (see comment). Use Caution/Monitor. Comment: Combination may result in thrombocytopenia (rare). Monitor CBC. - lanreotide
lanreotide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- letermovir
letermovir, pioglitazone. Either increases levels of the other by Other (see comment). Use Caution/Monitor. Comment: Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations. Monitor glucose levels.
- leuprolide
leuprolide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- levofloxacin
levofloxacin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.
levofloxacin increases effects of pioglitazone 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 pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- 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.
- linagliptin
pioglitazone will increase the level or effect of linagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Use of alternative treatments is strongly recommended when linagliptin is to be administered with a CYP3A4 inducer
- linezolid
linezolid will increase the level or effect of metformin by unspecified interaction mechanism. Use Caution/Monitor.
- liothyronine
liothyronine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- liotrix
liotrix decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- liraglutide
liraglutide, metformin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.
liraglutide, pioglitazone. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels. - lisinopril
lisinopril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.
- lonapegsomatropin
lonapegsomatropin decreases effects of pioglitazone 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.
- 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.
- lonapegsomatropin
lonapegsomatropin decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Closely monitor blood glucose when treated with antidiabetic agents. Lonapegsomatropin may decrease insulin sensitivity, particularly at higher doses. Patients with diabetes mellitus may require adjustment of their doses of insulin and/or other antihyperglycemic agents.
- lopinavir
lopinavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
- lurasidone
lurasidone, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
lurasidone, pioglitazone. 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 pioglitazone by pharmacodynamic antagonism. Use Caution/Monitor. - mavacamten
pioglitazone will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.
- mecasermin
mecasermin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Additive hypoglycemic effects.
- mecasermin
mecasermin increases effects of pioglitazone by pharmacodynamic synergism. Use Caution/Monitor. Additive hypoglycemic effects.
- medroxyprogesterone
medroxyprogesterone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- methamphetamine
methamphetamine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- methazolamide
methazolamide increases toxicity of metformin by Other (see comment). Use Caution/Monitor. Comment: Decreases serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis.
- mifepristone
mifepristone will increase the level or effect of pioglitazone by Other (see comment). Use Caution/Monitor. Inhibits CYP2C8/2C9; use smallest recommended doses for substrates and monitor
- mipomersen
mipomersen, pioglitazone. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.
- 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 pioglitazone 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 pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- nelfinavir
nelfinavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
- niacin
niacin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- nicardipine
nicardipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- nifedipine
nifedipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- nilotinib
nilotinib decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- nimodipine
nimodipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- nisoldipine
nisoldipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- nizatidine
nizatidine will increase the level or effect of metformin by decreasing renal clearance. Modify Therapy/Monitor Closely.
- norelgestromin
norelgestromin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- norethindrone
norethindrone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- norgestimate
norgestimate decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- octreotide
octreotide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- ofloxacin
ofloxacin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.
ofloxacin increases effects of pioglitazone 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, pioglitazone. 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.
- omaveloxolone
omaveloxolone will decrease the level or effect of pioglitazone by Other (see comment). Use Caution/Monitor. Omaveloxolone may reduce systemic exposure of sensitive CYP2C8 substrates. Check prescribing information of substrate if dosage modification is needed.
- 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.
opuntia ficus indica increases effects of pioglitazone by pharmacodynamic synergism. Use Caution/Monitor. - paclitaxel
pioglitazone will increase the level or effect of paclitaxel by Other (see comment). Use Caution/Monitor. Paclitaxel levels/toxicity may increase when coadministered with CYP2C8 inhibitors
- paliperidone
paliperidone, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- paclitaxel protein bound
pioglitazone will increase the level or effect of paclitaxel protein bound by Other (see comment). Use Caution/Monitor. Paclitaxel levels/toxicity may increase when coadministered with CYP2C8 inhibitors
- paliperidone
paliperidone, pioglitazone. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- paroxetine
paroxetine increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.
- pasireotide
pasireotide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- patiromer
patiromer will decrease the level or effect of metformin by drug binding in GI tract. 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.
- pitavastatin
pioglitazone increases toxicity of pitavastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.
- ponatinib
pioglitazone increases toxicity of ponatinib by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.
- pravastatin
pioglitazone increases toxicity of pravastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.
- 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.
quetiapine, pioglitazone. 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.
- rifabutin
rifabutin will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- quinidine
quinidine will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.
- ramipril
ramipril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.
- rasagiline
rasagiline will increase the level or effect of metformin by unspecified interaction mechanism. Use Caution/Monitor.
- rifampin
rifampin will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- risperidone
risperidone, pioglitazone. 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, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely. - ritonavir
ritonavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
- rosuvastatin
pioglitazone increases toxicity of rosuvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.
- sacubitril/valsartan
pioglitazone will increase the level or effect of sacubitril/valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure
- saquinavir
saquinavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
- selexipag
pioglitazone will increase the level or effect of selexipag by decreasing metabolism. Modify Therapy/Monitor Closely. Reduce selexipag dose to once daily if coadministered with moderate CYP2C8 inhibitors.
- sertraline
sertraline increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.
- shark cartilage
shark cartilage increases effects of pioglitazone by pharmacodynamic synergism. Use Caution/Monitor. Theoretical interaction.
shark cartilage increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Theoretical interaction. - simvastatin
pioglitazone increases toxicity of simvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.
- sirolimus
sirolimus decreases levels of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- somapacitan
somapacitan decreases effects of pioglitazone by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone products may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating somapacitan. .
somapacitan decreases effects of metformin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone products may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating somapacitan. . - St John's Wort
St John's Wort will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- somatropin
somatropin decreases levels of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- stiripentol
stiripentol will increase the level or effect of pioglitazone by Other (see comment). Modify Therapy/Monitor Closely. Stiripentol is a CYP2C8 inhibitor. Consider dosage reduction for CYP2C8 substrates if adverse effects are experienced when coadministered.
- sulfamethoxypyridazine
sulfamethoxypyridazine increases effects of metformin by unspecified interaction mechanism. Use Caution/Monitor. Risk of hypoglycemia.
sulfamethoxypyridazine increases effects of pioglitazone by unspecified interaction mechanism. Use Caution/Monitor. Risk of hypoglycemia. - tacrolimus
tacrolimus decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- tazemetostat
pioglitazone will decrease the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tecovirimat
tecovirimat will increase the level or effect of pioglitazone by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Tecovirimat is a weak inhibitor of CYP2C8 and CYP2C19. Monitor for adverse effects if coadministered with substrates of these enzymes. Monitor blood glucose and monitor for hypoglycemic symptoms.
- 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.
- teriflunomide
teriflunomide increases levels of pioglitazone by Other (see comment). Use Caution/Monitor. Comment: Teriflunomide inhibits CYP2C8; caution when coadministered with CYP2C8 substrates.
- 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, pioglitazone. Other (see comment). Use Caution/Monitor. Comment: Tipranavir's effect on oral hypoglycemics via hepatic CYP2C9 unknown; carefully monitor blood glucose. - 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.
- triamcinolone acetonide injectable suspension
triamcinolone acetonide injectable suspension decreases effects of pioglitazone by pharmacodynamic antagonism. Use Caution/Monitor. Corticosteroids may diminish hypoglycemic effect of antidiabetic agents. Monitor blood glucose levels carefully.
- torsemide
torsemide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- trandolapril
trandolapril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.
- triamcinolone acetonide injectable suspension
triamcinolone acetonide injectable suspension decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Corticosteroids may diminish hypoglycemic effect of antidiabetic agents. Monitor blood glucose levels carefully.
- trifluoperazine
trifluoperazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- trimethoprim
trimethoprim increases levels of metformin by Other (see comment). Use Caution/Monitor. Comment: Trimethoprim may inhibit active renal tubular secretion of metformin (eg, via OCT2, MATE1); dose adjustments may be necessary.
- triptorelin
triptorelin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- trospium chloride
metformin will decrease the level or effect of trospium chloride by increasing renal clearance. Use Caution/Monitor. Coadministration reduced steady state trospium systemic exposure (decreased AUC and Cmax) by competing for renal tubular secretion
- ubrogepant
pioglitazone will decrease the level or effect of ubrogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Dose adjustment is recommended with concomitant use of ubrogepant and moderate and weak CYP3A4 inducers. (see Dosage Modifications)
- valsartan
pioglitazone will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure
- vandetanib
vandetanib increases levels of metformin by Other (see comment). Modify Therapy/Monitor Closely. Comment: Vandetanib inhibits the uptake of substrates of organic cation transporter type 2 (OCT2).
- verapamil
verapamil decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Verapamil may inhibit hepatic uptake of metformin by OCT1 and/or other transporters.
- vilazodone
vilazodone increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.
- vorinostat
vorinostat decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
- vortioxetine
vortioxetine increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.
- xipamide
xipamide decreases levels of pioglitazone by increasing renal clearance. Use Caution/Monitor.
xipamide decreases levels of metformin by increasing renal clearance. Use Caution/Monitor. - ziprasidone
ziprasidone, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
ziprasidone, pioglitazone. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely. - zonisamide
zonisamide increases toxicity of metformin by Other (see comment). Use Caution/Monitor. Comment: Decreases serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis.
Minor (149)
- agrimony
agrimony increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
agrimony increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown. - American ginseng
American ginseng increases effects of pioglitazone 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 pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown. - amobarbital
amobarbital will decrease the level or effect of pioglitazone 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 pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.
- anamu
anamu increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown. Theoretical interaction.
anamu increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Theoretical interaction. - aprepitant
aprepitant will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- bendroflumethiazide
bendroflumethiazide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
- armodafinil
armodafinil will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- artemether/lumefantrine
artemether/lumefantrine will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- atazanavir
atazanavir will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- bendroflumethiazide
bendroflumethiazide decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
- bosentan
bosentan will decrease the level or effect of pioglitazone 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 pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
budesonide decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. - butabarbital
butabarbital will decrease the level or effect of pioglitazone 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 pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- chlorothiazide
chlorothiazide decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
- chlorthalidone
chlorthalidone decreases effects of pioglitazone 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 pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.
chromium increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. - clomipramine
clomipramine increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.
clomipramine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. - clonidine
clonidine, pioglitazone. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
clonidine decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
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. - conivaptan
conivaptan will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- cornsilk
cornsilk increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).
- cornsilk
cornsilk increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).
- cortisone
cortisone decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown.
cortisone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.
cortisone will decrease the level or effect of pioglitazone 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 pioglitazone 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.
- damiana
damiana decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Theoretical interaction.
damiana decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Theoretical interaction. - danazol
danazol increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
danazol increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown. - darifenacin
darifenacin will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- deflazacort
deflazacort decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.
- darunavir
darunavir will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- dasatinib
dasatinib will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- deferasirox
deferasirox will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- deflazacort
deflazacort decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown.
- desipramine
desipramine increases effects of pioglitazone 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 pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown. - dexamethasone
dexamethasone decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown.
dexamethasone will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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 pioglitazone 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 pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown. - dronedarone
dronedarone will increase the level or effect of pioglitazone 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 pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- elderberry
elderberry increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (in vitro research).
- eslicarbazepine acetate
eslicarbazepine acetate will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- etravirine
etravirine will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- eucalyptus
eucalyptus increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown. Theoretical interaction.
eucalyptus increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Theoretical interaction. - famotidine
famotidine increases levels of metformin by decreasing renal clearance. Minor/Significance Unknown.
- fluconazole
fluconazole will increase the level or effect of pioglitazone 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 pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
fludrocortisone decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. - fluoxymesterone
fluoxymesterone increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.
fluoxymesterone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. - fo-ti
fo-ti increases effects of pioglitazone 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 pioglitazone 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.
- fosamprenavir
fosamprenavir will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- fosaprepitant
fosaprepitant will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- fosphenytoin
fosphenytoin will decrease the level or effect of pioglitazone 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 pioglitazone 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 pioglitazone 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 pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- guanfacine
guanfacine decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
guanfacine, pioglitazone. 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 pioglitazone 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 pioglitazone 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 pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
hydrochlorothiazide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose. - hydrocortisone
hydrocortisone will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
hydrocortisone decreases effects of pioglitazone by pharmacodynamic antagonism. 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 pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.
- imipramine
imipramine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
- indapamide
indapamide decreases effects of pioglitazone 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. - indinavir
indinavir will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- L-methylfolate
metformin decreases levels of L-methylfolate by unspecified interaction mechanism. Minor/Significance Unknown.
- juniper
juniper increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).
- isoniazid
isoniazid will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
isoniazid decreases effects of pioglitazone by unspecified interaction mechanism. Minor/Significance Unknown. - juniper
juniper increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).
- lofepramine
lofepramine increases effects of pioglitazone 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 pioglitazone 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 pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).
- maitake
maitake increases effects of pioglitazone 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 pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown. - marijuana
marijuana will increase the level or effect of pioglitazone 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 pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown. - mestranol
pioglitazone decreases levels of mestranol by unknown mechanism. Minor/Significance Unknown.
- methyclothiazide
methyclothiazide will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
methyclothiazide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose. - methyclothiazide
methyclothiazide decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
- methylprednisolone
methylprednisolone decreases effects of pioglitazone 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 pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. - methyltestosterone
methyltestosterone increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.
methyltestosterone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. - metolazone
metolazone decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
metolazone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose. - metronidazole
metronidazole will increase the level or effect of pioglitazone 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 pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- nelfinavir
nelfinavir will increase the level or effect of pioglitazone 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 pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction). - nevirapine
nevirapine will decrease the level or effect of pioglitazone 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 pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- nilotinib
nilotinib will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- nortriptyline
nortriptyline increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.
nortriptyline increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. - ofloxacin
metformin will increase the level or effect of ofloxacin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
ofloxacin, metformin. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Potential dysglycemia.
ofloxacin, pioglitazone. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Potential dysglycemia. - oxandrolone
oxandrolone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
oxandrolone increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown. - oxcarbazepine
oxcarbazepine will decrease the level or effect of pioglitazone 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 pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.
- pegvisomant
pegvisomant increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.
pegvisomant increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. - pentobarbital
pentobarbital will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- potassium acid phosphate
potassium acid phosphate increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia.
- phenobarbital
phenobarbital will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- phenytoin
phenytoin will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- posaconazole
posaconazole will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- potassium acid phosphate
potassium acid phosphate increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia.
- potassium chloride
potassium chloride increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia.
potassium chloride increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia. - potassium citrate
potassium citrate increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia.
potassium citrate increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia. - prednisolone
prednisolone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.
prednisolone decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. - prednisone
prednisone decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown.
prednisone will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
prednisone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. - primidone
primidone will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- protriptyline
protriptyline increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
- protriptyline
protriptyline increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.
- quinine
metformin will increase the level or effect of quinine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
- quinupristin/dalfopristin
quinupristin/dalfopristin will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- rifapentine
rifapentine will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- ritonavir
ritonavir will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- rufinamide
rufinamide will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- sage
sage increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.
sage increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. - secobarbital
secobarbital will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- stevia
stevia increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
- stevia
stevia increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.
- sulfamethoxazole
sulfamethoxazole will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
- testosterone
testosterone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
testosterone increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown. - testosterone buccal system
testosterone buccal system increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.
testosterone buccal system increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. - testosterone topical
testosterone topical increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.
testosterone topical increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. - tongkat ali
tongkat ali increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypoglycemia.
tongkat ali increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypoglycemia. - topiramate
topiramate will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- trazodone
trazodone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
- trazodone
trazodone increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.
- triamterene
metformin will increase the level or effect of triamterene by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
- trimethoprim
metformin will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
- trimipramine
trimipramine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
trimipramine increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown. - vanadium
vanadium increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
vanadium increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown. - verapamil
metformin will increase the level or effect of verapamil by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
verapamil will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. - voriconazole
voriconazole will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- zafirlukast
zafirlukast will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
Adverse Effects
>10%
Lower limb edema (2.9-11.3%)
Upper respiratory infection (12-16)
1-10%
Weight gain (2.9-6.7%)
Diarrhea (4.8-5.8%)
Nausea (3.6-5.8%)
Urinary tract infection (5.3-5.8%)
Dizziness (4.8-5.4%)
Headache (4.6-5.3%)
Sinusitis (4.4-5%)
Edema (3%)
Postmarketing Reports
Hepatitis and hepatic enzyme elevations to >3 XUL, including very rare incidences of hepatic failure with and without fatal outcome
Cholestatic, hepatocellular, and mixed hepatocellular liver injury
Warnings
Black Box Warnings
Discontinue metformin at the time of or before an iodinated contrast imaging procedure in patients with an eGFR between 30-60 mL/minute/1.73 m²; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinate contrast
Congestive heart failure
- Thiazolidinediones, including pioglitazone and rosiglitazone, cause or exacerbate congestive heart failure in some patients
- Monitor carefully after initiation or dose increases for signs and symptoms of heart failure (including excessive, rapid weight gain; dyspnea; and/or edema); if these signs or symptoms develop, manage heart failure according current standards of care; consider discontinuing or reducing dose
- Not recommended in patients with symptomatic heart failure; initiation of these drugs in patients with established NYHA class III or IV heart failure is contraindicated
Lactic acidosis
- Characterized by elevated blood lactate levels (>5 mmol/L)
- Rare but serious complication that can occur because of metformin accumulation; increased risk with sepsis, dehydration, excess alcohol intake, hepatic insufficiency, renal impairment, and acute congestive heart failure
- Subtle onset with nonspecific symptoms (eg, malaise, myalgias, respiratory distress, somnolence, nonspecific abdominal distress)
- Monitor lab for decreased serum pH, increased anion gap, and elevated blood lactate If suspected, discontinue drug and hospitalize patient immediately
- Metformin is highly dialyzable (clearance up to 170 mL/min under good hemodynamic conditions); prompt hemodialysis is recommended to correct the acidosis and to remove accumulated metformin
Contraindications
Hypersensitivity
Severe renal disease: eGFR <30 ml/min/1.73 m²
Acute or chronic metabolic acidosis, including DKA with or without coma
NYHA Class III or IV heart failure
Cautions
Temporarily discontinue in patients undergoing radiologic exams using iodinated contrast agents
Do not initiate in patients aged ≥80 years CrCl demonstrates that renal function is not reduced because these patients are more susceptible to developing lactic acidosis
Withhold metformin in presence of any condition associated with hypoxemia, dehydration, or sepsis
Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonemia); lactic acidosis is a medical emergency that must be treated in a hospital setting
Pioglitazone may cause fluid retention and cause or exacerbate existing heart failure
Edema; thiazolidinediones, which are peroxisome proliferator-activated receptor (PPAR) gamma agonists, can cause dose-related fluid retention, particularly when used in combination with insulin
Pioglitazone exerts its antihyperglycemic effect only in presence of insulin; therefore, do not use in type 1 diabetes mellitus or for treatment of diabetic ketoacidosis
May cause hypoglycemia; patients receiving therapy in combination with insulin or other antidiabetic medications (particularly insulin secretagogues such as sulfonylureas) may be at risk for hypoglycemia; a reduction in dose of the concomitant antidiabetic medication may be necessary to reduce the risk of hypoglycemia; hypoglycemia can also occur when caloric intake is deficient or when strenuous be necessary to reduce the risk of hypoglycemia exercise is not compensated by caloric supplement; hypoglycemia may be difficult to recognize in the elderly, and in people who are taking beta-adrenergic blocking drugs
Rare reports of hepatitis and hepatic enzyme elevations to >3 xULN, including very rare incidences of hepatic failure with and without fatal outcome
In controlled clinical trials of metformin, a decrease to subnormal levels of previously normal serum vitamin B12 levels, without clinical manifestations, reported; certain individuals (those with inadequate vitamin B12 or calcium intake or absorption) appear to be predisposed to developing subnormal vitamin B12 levels; in these patients, routine serum vitamin B12 measurements at two- to three-year intervals may be useful
Metformin is substantially excreted by kidney, and risk of metformin accumulation and lactic acidosis increases with degree of renal impairment
Use of metformin in patients with hepatic impairment has been associated with some cases of lactic acidosis; therapy is not recommended in patients with hepatic impairment
Discuss potential for unintended pregnancy with premenopausal women as therapy with metformin/pioglitazone, may result in ovulation in some anovulatory women
Drug interactions review
- Topiramate or other carbonic anhydrase inhibitors (e.g., zonisamide, acetazolamide or dichlorphenamide) frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis; concomitant use of these drugs with metformin/pioglitazone combination may increase risk for lactic acidosis; consider more frequent monitoring of these patients
- Drugs that are eliminated by renal tubular secretion (e.g., cationic drugs such as cimetidine) have potential for interaction with metformin by competing for common renal tubular transport systems, and may increase accumulation of metformin and risk for lactic acidosis; consider more frequent monitoring of these patients
- Alcohol is known to potentiate the effect of metformin on lactate metabolism; warn patients against excessive alcohol intake while receiving therapy
- If hypoglycemia occurs in a patient coadministered pioglitazone/metformin and an insulin secretagogue (e.g., sulfonylurea), the dose of insulin secretagogue should be reduced; if hypoglycemia occurs in a patient coadministered and insulin, the dose of insulin should be decreased by 10% to 25%; further adjustments to insulin dose should be individualized based on glycemic response
Iodinated contrast imaging procedures
- Discontinue metformin at the time of or before an iodinated contrast imaging procedure in patients with an eGFR between 30-60 mL/minute/1.73 m²; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinate contrast
- Reevaluate eGFR 48 hr after the imaging procedure; restart metformin if renal function is stable
Cancer risk
Bladder cancer
- Pioglitazone may be linked to an increased risk of bladder cancer
- Do not prescribe for patients with active bladder cancer
- Consider benefit:risk ratio before prescribing in patients with a history of bladder cancer
- Instruct patients to contact their physician if signs of bladder cancer observed after initiating therapy (eg, blood or red colored urine, new or worsening urinary urgency, pain on urination)
Prostate cancer
- 7/22/2015: Compared with nonuse, pioglitazone use was associated with increased risk for prostate cancer (453.3 vs. 449.3 per 100,000 person-years) [JAMA 2015 July 21;314(3):265-277]
Pancreatic cancer
- 7/22/2015: Compared with nonuse, pioglitazone use was associated with increased risk for pancreatic cancer (81.1 vs. 48.4 per 100,000 person-years) [JAMA 2015 July 21;314(3):265-277]
Pregnancy & Lactation
Pregnancy: Limited data with metformin/pioglitazone or pioglitazone in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage; poorly controlled diabetes in pregnancy increases maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, still birth and delivery complications; poorly controlled diabetes increases fetal risk for major birth defects, still birth, and macrosomia related morbidity
Lactation: There is no information regarding the presence of metformin/pioglitazone or pioglitazone in human milk; effects on breastfed infant, or effects on milk production; there is insufficient information on effects of metformin on breastfed infant and no available information on effects of metformin on milk production; developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on the breastfed infant from metformin/pioglitazone or from underlying maternal condition
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Metformin: Biguanide; acts by decreasing endogenous hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization; improves glucose tolerance and lowers both basal and postprandial plasma glucose
Pioglitazone: Thiazolidinedione; insulin-sensitizing agent that acts by enhancing peripheral glucose utilization; decreased insulin resistance in the periphery and in the liver, resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output
Pharmacokinetics
Peak plasma time (ACTOplus Met)
- pioglitazone: 1.7-2 hr
- metformin: 2.3-2.5 hr
Peak plasma time (ACTOplus Met XR)
- pioglitazone: 3-3.5 hr
- metformin: 6.9-8 hr
Peak plasma concentration (ACTOplus Met)
- pioglitazone: 659-608 ng/mL
- metformin: 1,203-1,827 ng/mL
Peak plasma concentration (ACTOplus Met XR)
- pioglitazone: 487-866 ng/mL
- metformin: 1,322-1,590 ng/mL
AUC (ACTOplus Met)
- pioglitazone: 5,671-5,984 ng•hr/mL
- metformin: 7,599-11,927 ng•hr/mL
AUC (ACTOplus Met XR)
- pioglitazone: 5,113-9,177 ng•hr/mL
- metformin: 12,705-14,787 ng•hr/mL
Half-Life (ACTOplus Met)
- pioglitazone: 7.2-8.7 hr
- metformin: 6.7-17.6 hr
Half-Life (ACTOplus Met XR)
- pioglitazone: 5.8-7.6 hr
- metformin: 11-11.7 hr
Images
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