metformin/pioglitazone (Rx)

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

Contraindicated (0)

Serious - Use Alternative (10)

• 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.

Monitor Closely (246)

• acetazolamide

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

• albiglutide

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

  hydroxyprogesterone caproate 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.

• 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.

• opuntia ficus indica

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

• ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

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

• ondansetron

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

• opuntia ficus indica

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

• 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

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

• paroxetine

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

• pitavastatin

  pioglitazone increases toxicity of pitavastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

• pasireotide

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

• patiromer

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

• pentamidine

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

• perindopril

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

• perphenazine

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

• phendimetrazine

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

• phenelzine

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

• phentermine

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

• phenytoin

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

• 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 (148)

• 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.

• 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.

• acetazolamide

  Monitor Closely (1)acetazolamide increases toxicity of metformin by Other (see comment). Use Caution/Monitor. Comment: Decreases serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis.

• agrimony

  Minor (2)agrimony increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
  
  agrimony increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

• albiglutide

  Monitor Closely (2)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.

• American ginseng

  Minor (2)American ginseng increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.
  
  American ginseng increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• amiodarone

  Monitor Closely (1)amiodarone will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

• amitriptyline

  Minor (2)amitriptyline increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
  
  amitriptyline increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

• amlodipine

  Monitor Closely (1)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.

• amobarbital

  Minor (1)amobarbital will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• amoxapine

  Minor (2)amoxapine increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.
  
  amoxapine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• anamu

  Minor (2)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

  Minor (1)aprepitant will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• aripiprazole

  Monitor Closely (2)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.
  
  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.

• armodafinil

  Minor (1)armodafinil will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• artemether/lumefantrine

  Minor (1)artemether/lumefantrine will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• asenapine

  Monitor Closely (2)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

  Monitor Closely (1)atazanavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .Minor (1)atazanavir will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• atogepant

  Monitor Closely (1)pioglitazone will decrease the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• atorvastatin

  Monitor Closely (1)pioglitazone increases toxicity of atorvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

• axitinib

  Monitor Closely (1)pioglitazone decreases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• baricitinib

  Serious - Use Alternative (1)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.

• benazepril

  Monitor Closely (1)benazepril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• bendroflumethiazide

  Minor (2)bendroflumethiazide decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  bendroflumethiazide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• benzphetamine

  Monitor Closely (1)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

  Monitor Closely (1)betamethasone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• bexarotene

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (2)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.

• bosentan

  Minor (1)bosentan will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• brexpiprazole

  Monitor Closely (1)brexpiprazole decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• budesonide

  Minor (3)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.

• bumetanide

  Monitor Closely (1)bumetanide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• bupropion

  Monitor Closely (1)bupropion increases levels of metformin by Other (see comment). Use Caution/Monitor. Comment: Bupropion may inhibit OCT2 mediated renal excretion of metformin.

• butabarbital

  Minor (1)butabarbital will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• butalbital

  Minor (1)butalbital will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• cannabidiol

  Monitor Closely (1)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.

• captopril

  Monitor Closely (1)captopril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• carbamazepine

  Monitor Closely (1)carbamazepine will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cariprazine

  Monitor Closely (1)cariprazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• cephalexin

  Monitor Closely (1)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

  Monitor Closely (1)ceritinib decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• chlorothiazide

  Minor (2)chlorothiazide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  chlorothiazide decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• chlorpromazine

  Monitor Closely (1)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.

• chlorthalidone

  Minor (2)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.

• cholic acid

  Monitor Closely (1)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.

• chromium

  Minor (2)chromium increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.
  
  chromium increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• cimetidine

  Monitor Closely (2)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

  Monitor Closely (2)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

  Monitor Closely (2)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

  Monitor Closely (1)citalopram increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• clarithromycin

  Monitor Closely (1)clarithromycin will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• clevidipine

  Monitor Closely (1)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.

• clomipramine

  Minor (2)clomipramine increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.
  
  clomipramine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• clonidine

  Minor (4)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.

• clozapine

  Monitor Closely (2)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

  Monitor Closely (1)colesevelam increases levels of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• conivaptan

  Minor (1)conivaptan will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• conjugated estrogens

  Monitor Closely (1)conjugated estrogens decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• contrast media (iodinated)

  Serious - Use Alternative (1)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.

• cornsilk

  Minor (2)cornsilk increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).
  
  cornsilk increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).

• corticotropin

  Monitor Closely (1)corticotropin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• cortisone

  Minor (3)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

  Minor (1)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

  Minor (2)cyclopenthiazide decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  cyclopenthiazide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• dabrafenib

  Monitor Closely (1)dabrafenib decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• dalfampridine

  Monitor Closely (1)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.

• damiana

  Minor (2)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

  Minor (2)danazol increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
  
  danazol increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

• darifenacin

  Minor (1)darifenacin will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• darunavir

  Monitor Closely (1)darunavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .Minor (1)darunavir will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• dasatinib

  Minor (1)dasatinib will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• deferasirox

  Minor (1)deferasirox will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• deflazacort

  Minor (2)deflazacort decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown.
  
  deflazacort decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.

• desipramine

  Minor (2)desipramine increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.
  
  desipramine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• desogestrel

  Monitor Closely (1)desogestrel decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• devil's claw

  Minor (2)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

  Minor (3)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

  Minor (1)DHEA, herbal will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• diatrizoate

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)diazoxide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• dichlorphenamide

  Monitor Closely (1)dichlorphenamide, metformin. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Both drugs can cause metabolic acidosis.

• dienogest/estradiol valerate

  Monitor Closely (2)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.
  
  dienogest/estradiol valerate decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• diethylpropion

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (2)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.Minor (1)diltiazem will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• dofetilide

  Monitor Closely (1)dofetilide will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

• dolutegravir

  Monitor Closely (1)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

• doxepin

  Minor (2)doxepin increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
  
  doxepin increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

• dronedarone

  Minor (1)dronedarone will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• drospirenone

  Monitor Closely (1)drospirenone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• dulaglutide

  Monitor Closely (2)dulaglutide, metformin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
  
  dulaglutide, 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.

• efavirenz

  Minor (1)efavirenz will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• elderberry

  Minor (2)elderberry increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (in vitro research).
  
  elderberry increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (in vitro research).

• eluxadoline

  Serious - Use Alternative (1)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. .

• enalapril

  Monitor Closely (1)enalapril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• entecavir

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)erythromycin base will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• erythromycin ethylsuccinate

  Monitor Closely (1)erythromycin ethylsuccinate will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• erythromycin lactobionate

  Monitor Closely (1)erythromycin lactobionate will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• erythromycin stearate

  Monitor Closely (1)erythromycin stearate will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• escitalopram

  Monitor Closely (1)escitalopram increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• eslicarbazepine acetate

  Minor (1)eslicarbazepine acetate will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• estradiol

  Monitor Closely (1)estradiol decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• estrogens conjugated synthetic

  Monitor Closely (1)estrogens conjugated synthetic decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• estropipate

  Monitor Closely (1)estropipate decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• ethacrynic acid

  Monitor Closely (1)ethacrynic acid decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• ethanol

  Serious - Use Alternative (2)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.

• ethinylestradiol

  Monitor Closely (2)pioglitazone decreases levels of ethinylestradiol by unknown mechanism. Use Caution/Monitor.
  
  ethinylestradiol decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• ethiodized oil

  Monitor Closely (1)ethiodized oil increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• etonogestrel

  Monitor Closely (1)etonogestrel decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• etravirine

  Minor (1)etravirine will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• eucalyptus

  Minor (2)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.

• everolimus

  Monitor Closely (1)everolimus decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• exenatide injectable solution

  Monitor Closely (2)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.
  
  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

  Monitor Closely (2)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.

• famotidine

  Minor (1)famotidine increases levels of metformin by decreasing renal clearance. Minor/Significance Unknown.

• felodipine

  Monitor Closely (1)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

  Monitor Closely (2)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.
  
  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.

• fluconazole

  Minor (1)fluconazole will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• fludrocortisone

  Minor (3)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.

• fluoxetine

  Monitor Closely (1)fluoxetine increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• fluoxymesterone

  Minor (2)fluoxymesterone increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.
  
  fluoxymesterone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• fluphenazine

  Monitor Closely (1)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

  Monitor Closely (1)pioglitazone increases toxicity of fluvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

• fluvoxamine

  Monitor Closely (1)fluvoxamine increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• fo-ti

  Minor (2)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

  Minor (1)metformin decreases levels of folic acid by unspecified interaction mechanism. Minor/Significance Unknown.

• forskolin

  Minor (2)forskolin increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Colenol, a compound found in Coleus root, may stimulate insulin release.
  
  forskolin increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown. Colenol, a compound found in Coleus root, may stimulate insulin release.

• fosamprenavir

  Monitor Closely (1)fosamprenavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .Minor (1)fosamprenavir will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• fosinopril

  Monitor Closely (1)fosinopril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• fosphenytoin

  Monitor Closely (1)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.Minor (1)fosphenytoin will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• furosemide

  Minor (2)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.

• gemfibrozil

  Serious - Use Alternative (1)gemfibrozil will increase the level or effect of pioglitazone by decreasing metabolism. Avoid or Use Alternate Drug.

• gemifloxacin

  Monitor Closely (2)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

  Monitor Closely (1)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

  Monitor Closely (1)glucagon intranasal decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• glycopyrrolate

  Monitor Closely (1)glycopyrrolate increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. May require a dose reduction.

• goserelin

  Monitor Closely (1)goserelin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• gotu kola

  Minor (2)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

  Minor (1)grapefruit will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• griseofulvin

  Minor (1)griseofulvin will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• guanfacine

  Minor (4)guanfacine decreases effects of pioglitazone 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.
  
  guanfacine decreases effects of metformin 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

  Minor (2)gymnema increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
  
  gymnema increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

• histrelin

  Monitor Closely (1)histrelin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• horse chestnut seed

  Minor (2)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

  Minor (3)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

  Minor (3)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.

• hydroxyprogesterone caproate

  Monitor Closely (1)hydroxyprogesterone caproate decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• ibuprofen/famotidine

  Minor (1)ibuprofen/famotidine increases levels of metformin by decreasing renal clearance. Minor/Significance Unknown.

• ifosfamide

  Monitor Closely (1)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

  Monitor Closely (2)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

  Monitor Closely (1)imidapril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• imipramine

  Minor (2)imipramine increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.
  
  imipramine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• indapamide

  Minor (2)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

  Monitor Closely (1)indinavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .Minor (1)indinavir will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• insulin aspart

  Monitor Closely (3)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.
  
  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

  Monitor Closely (2)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

  Monitor Closely (2)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

  Monitor Closely (2)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

  Monitor Closely (3)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

  Monitor Closely (3)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

  Monitor Closely (3)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

  Monitor Closely (2)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

  Monitor Closely (2)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

  Monitor Closely (3)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

  Monitor Closely (2)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

  Monitor Closely (3)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

  Monitor Closely (3)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

  Monitor Closely (1)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. .

• ioflupane I 123

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)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. .Serious - Use Alternative (1)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.

• ioxilan

  Monitor Closely (1)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. .

• isavuconazonium sulfate

  Monitor Closely (1)pioglitazone will decrease the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• isocarboxazid

  Monitor Closely (1)isocarboxazid will increase the level or effect of metformin by unspecified interaction mechanism. Use Caution/Monitor.

• isoniazid

  Monitor Closely (1)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.Minor (2)isoniazid decreases effects of pioglitazone by unspecified interaction mechanism. Minor/Significance Unknown.
  
  isoniazid will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• isradipine

  Monitor Closely (1)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.

• juniper

  Minor (2)juniper increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).
  
  juniper increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).

• ketoconazole

  Monitor Closely (1)ketoconazole will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ketotifen, ophthalmic

  Monitor Closely (2)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.

• L-methylfolate

  Minor (1)metformin decreases levels of L-methylfolate by unspecified interaction mechanism. Minor/Significance Unknown.

• lanreotide

  Monitor Closely (1)lanreotide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• letermovir

  Monitor Closely (1)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

  Monitor Closely (1)leuprolide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• levofloxacin

  Monitor Closely (2)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

  Monitor Closely (1)levoketoconazole will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• levonorgestrel intrauterine

  Monitor Closely (1)levonorgestrel intrauterine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• levonorgestrel oral

  Monitor Closely (1)levonorgestrel oral decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• levothyroxine

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)linezolid will increase the level or effect of metformin by unspecified interaction mechanism. Use Caution/Monitor.

• liothyronine

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (2)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

  Monitor Closely (1)lisinopril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• lofepramine

  Minor (2)lofepramine increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.
  
  lofepramine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• lonapegsomatropin

  Monitor Closely (2)lonapegsomatropin decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Closely monitor blood glucose when treated with antidiabetic agents. Lonapegsomatropin may decrease insulin sensitivity, particularly at higher doses. Patients with diabetes mellitus may require adjustment of their doses of insulin and/or other antihyperglycemic agents.
  
  lonapegsomatropin decreases effects of 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.

• lopinavir

  Monitor Closely (1)lopinavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• lumefantrine

  Minor (1)lumefantrine will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• lurasidone

  Monitor Closely (2)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.

• lycopus

  Minor (2)lycopus increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).
  
  lycopus increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).

• maitake

  Minor (2)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

  Minor (2)maprotiline increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
  
  maprotiline increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

• marijuana

  Monitor Closely (2)marijuana decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
  
  marijuana decreases effects of pioglitazone by pharmacodynamic antagonism. Use Caution/Monitor.Minor (1)marijuana will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• mavacamten

  Monitor Closely (1)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

  Monitor Closely (2)mecasermin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Additive hypoglycemic effects.
  
  mecasermin increases effects of pioglitazone by pharmacodynamic synergism. Use Caution/Monitor. Additive hypoglycemic effects.

• medroxyprogesterone

  Monitor Closely (1)medroxyprogesterone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• memantine

  Minor (1)memantine will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• mesterolone

  Minor (2)mesterolone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
  
  mesterolone increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

• mestranol

  Minor (1)pioglitazone decreases levels of mestranol by unknown mechanism. Minor/Significance Unknown.

• methamphetamine

  Monitor Closely (1)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

  Monitor Closely (1)methazolamide increases toxicity of metformin by Other (see comment). Use Caution/Monitor. Comment: Decreases serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis.

• methyclothiazide

  Minor (3)methyclothiazide decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  methyclothiazide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  methyclothiazide will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• methylene blue

  Serious - Use Alternative (1)methylene blue will increase the level or effect of metformin by unspecified interaction mechanism. Avoid or Use Alternate Drug.

• methylprednisolone

  Minor (3)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

  Minor (2)methyltestosterone increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.
  
  methyltestosterone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• metolazone

  Minor (2)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

  Minor (1)metronidazole will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• miconazole vaginal

  Minor (1)miconazole vaginal will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• midodrine

  Minor (1)metformin will increase the level or effect of midodrine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• mifepristone

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)moexipril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• moxifloxacin

  Monitor Closely (2)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

  Monitor Closely (1)nefazodone will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nelfinavir

  Monitor Closely (1)nelfinavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .Minor (1)nelfinavir will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nettle

  Minor (2)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

  Minor (1)nevirapine will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• niacin

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)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.Minor (2)nifedipine increases levels of metformin by enhancing GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
  
  nifedipine will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nilotinib

  Monitor Closely (1)nilotinib decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.Minor (1)nilotinib will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nimodipine

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)nizatidine will increase the level or effect of metformin by decreasing renal clearance. Modify Therapy/Monitor Closely.

• norelgestromin

  Monitor Closely (1)norelgestromin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• norethindrone

  Monitor Closely (1)norethindrone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• norgestimate

  Monitor Closely (1)norgestimate decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• nortriptyline

  Minor (2)nortriptyline increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.
  
  nortriptyline increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• octreotide

  Monitor Closely (1)octreotide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• ofloxacin

  Monitor Closely (2)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.Minor (3)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.

• olanzapine

  Monitor Closely (2)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

  Monitor Closely (1)omacetaxine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (2)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.

• oxandrolone

  Minor (2)oxandrolone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
  
  oxandrolone increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

• oxcarbazepine

  Minor (1)oxcarbazepine will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• oxymetholone

  Minor (2)oxymetholone increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.
  
  oxymetholone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• paclitaxel

  Monitor Closely (1)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

• paclitaxel protein bound

  Monitor Closely (1)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

• pacritinib

  Serious - Use Alternative (2)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.

• paliperidone

  Monitor Closely (2)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.
  
  paliperidone, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• paroxetine

  Monitor Closely (1)paroxetine increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• pasireotide

  Monitor Closely (1)pasireotide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• patiromer

  Monitor Closely (1)patiromer will decrease the level or effect of metformin by drug binding in GI tract. Use Caution/Monitor. May administer 3 hours apart

• pegvisomant

  Minor (2)pegvisomant increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.
  
  pegvisomant increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• pentamidine

  Monitor Closely (1)pentamidine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• pentobarbital

  Minor (1)pentobarbital will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• perindopril

  Monitor Closely (1)perindopril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• perphenazine

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)phenelzine will increase the level or effect of metformin by unspecified interaction mechanism. Use Caution/Monitor.

• phenobarbital

  Minor (1)phenobarbital will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• phentermine

  Monitor Closely (1)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

  Monitor Closely (1)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.Minor (1)phenytoin will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• pitavastatin

  Monitor Closely (1)pioglitazone increases toxicity of pitavastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

• ponatinib

  Monitor Closely (1)pioglitazone increases toxicity of ponatinib by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

• posaconazole

  Minor (1)posaconazole will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• potassium acid phosphate

  Minor (2)potassium acid phosphate increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia.
  
  potassium acid phosphate increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia.

• potassium chloride

  Minor (2)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

  Minor (2)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.

• pravastatin

  Monitor Closely (1)pioglitazone increases toxicity of pravastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

• prednisolone

  Minor (2)prednisolone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.
  
  prednisolone decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown.

• prednisone

  Minor (3)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

  Minor (1)primidone will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• procainamide

  Monitor Closely (1)metformin will increase the level or effect of procainamide by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

• procarbazine

  Monitor Closely (1)procarbazine will increase the level or effect of metformin by unspecified interaction mechanism. Use Caution/Monitor.

• prochlorperazine

  Monitor Closely (1)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

  Monitor Closely (1)progesterone intravaginal gel decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• progesterone micronized

  Monitor Closely (1)progesterone micronized decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• progesterone, natural

  Monitor Closely (1)progesterone, natural decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• promethazine

  Monitor Closely (1)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.

• protriptyline

  Minor (2)protriptyline increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.
  
  protriptyline increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• quetiapine

  Monitor Closely (2)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

  Monitor Closely (1)quinapril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• quinidine

  Monitor Closely (1)quinidine will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

• quinine

  Minor (1)metformin will increase the level or effect of quinine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• quinupristin/dalfopristin

  Minor (1)quinupristin/dalfopristin will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ramipril

  Monitor Closely (1)ramipril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• ranolazine

  Serious - Use Alternative (1)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

• rasagiline

  Monitor Closely (1)rasagiline will increase the level or effect of metformin by unspecified interaction mechanism. Use Caution/Monitor.

• rifabutin

  Monitor Closely (1)rifabutin will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rifampin

  Monitor Closely (1)rifampin will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rifapentine

  Minor (1)rifapentine will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• risdiplam

  Serious - Use Alternative (1)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.

• risperidone

  Monitor Closely (2)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

  Monitor Closely (1)ritonavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .Minor (1)ritonavir will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• rosuvastatin

  Monitor Closely (1)pioglitazone increases toxicity of rosuvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

• rufinamide

  Minor (1)rufinamide will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• sacubitril/valsartan

  Monitor Closely (1)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

• sage

  Minor (2)sage increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.
  
  sage increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• saquinavir

  Monitor Closely (1)saquinavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• secobarbital

  Minor (1)secobarbital will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• selegiline

  Serious - Use Alternative (1)selegiline will increase the level or effect of metformin by unspecified interaction mechanism. Avoid or Use Alternate Drug.

• selegiline transdermal

  Serious - Use Alternative (1)selegiline transdermal will increase the level or effect of metformin by unspecified interaction mechanism. Avoid or Use Alternate Drug.

• selexipag

  Monitor Closely (1)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

  Monitor Closely (1)sertraline increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• shark cartilage

  Monitor Closely (2)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

  Monitor Closely (1)pioglitazone increases toxicity of simvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

• sirolimus

  Monitor Closely (1)sirolimus decreases levels of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• somapacitan

  Monitor Closely (2)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. .

• somatropin

  Monitor Closely (1)somatropin decreases levels of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• St John's Wort

  Monitor Closely (1)St John's Wort will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• stevia

  Minor (2)stevia increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
  
  stevia increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

• stiripentol

  Monitor Closely (1)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.

• sulfamethoxazole

  Minor (1)sulfamethoxazole will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• sulfamethoxypyridazine

  Monitor Closely (2)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

  Monitor Closely (1)tacrolimus decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• tafenoquine

  Serious - Use Alternative (1)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.

• tazemetostat

  Monitor Closely (1)pioglitazone will decrease the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tecovirimat

  Monitor Closely (1)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.

• tedizolid

  Serious - Use Alternative (1)tedizolid will increase the level or effect of metformin by unspecified interaction mechanism. Avoid or Use Alternate Drug.

• temsirolimus

  Monitor Closely (1)temsirolimus decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• tenofovir DF

  Monitor Closely (1)tenofovir DF increases levels of metformin by decreasing renal clearance. Use Caution/Monitor. Increased risk of lactic acidosis.

• teriflunomide

  Monitor Closely (1)teriflunomide increases levels of pioglitazone by Other (see comment). Use Caution/Monitor. Comment: Teriflunomide inhibits CYP2C8; caution when coadministered with CYP2C8 substrates.

• testosterone

  Minor (2)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

  Minor (2)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

  Minor (2)testosterone topical increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.
  
  testosterone topical increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• thioridazine

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)tibolone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• tipranavir

  Monitor Closely (2)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.

• tongkat ali

  Minor (2)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

  Monitor Closely (1)topiramate increases toxicity of metformin by Other (see comment). Use Caution/Monitor. Comment: Decreases serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis.Minor (1)topiramate will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• torsemide

  Monitor Closely (1)torsemide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• trandolapril

  Monitor Closely (1)trandolapril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• tranylcypromine

  Serious - Use Alternative (1)tranylcypromine will increase the level or effect of metformin by unspecified interaction mechanism. Avoid or Use Alternate Drug.

• trazodone

  Minor (2)trazodone increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.
  
  trazodone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• triamcinolone acetonide injectable suspension

  Monitor Closely (2)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.
  
  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.

• triamterene

  Minor (1)metformin will increase the level or effect of triamterene by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• trifluoperazine

  Monitor Closely (1)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.

• trilaciclib

  Serious - Use Alternative (1)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.

• trimethoprim

  Monitor Closely (1)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.Minor (1)metformin will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• trimipramine

  Minor (2)trimipramine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
  
  trimipramine increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

• triptorelin

  Monitor Closely (1)triptorelin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• trospium chloride

  Monitor Closely (1)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

• tucatinib

  Serious - Use Alternative (1)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.

• ubrogepant

  Monitor Closely (1)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

  Monitor Closely (1)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

• vanadium

  Minor (2)vanadium increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
  
  vanadium increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

• vandetanib

  Monitor Closely (1)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

  Monitor Closely (1)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.Minor (2)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.

• vilazodone

  Monitor Closely (1)vilazodone increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• voriconazole

  Minor (1)voriconazole will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• vorinostat

  Monitor Closely (1)vorinostat decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• vortioxetine

  Monitor Closely (1)vortioxetine increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• xipamide

  Monitor Closely (2)xipamide decreases levels of pioglitazone by increasing renal clearance. Use Caution/Monitor.
  
  xipamide decreases levels of metformin by increasing renal clearance. Use Caution/Monitor.

• zafirlukast

  Minor (1)zafirlukast will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ziprasidone

  Monitor Closely (2)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

  Monitor Closely (1)zonisamide increases toxicity of metformin by Other (see comment). Use Caution/Monitor. Comment: Decreases serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis.