glimepiride/pioglitazone (Rx)

Type 2 Diabetes Mellitus

Indicated for management of type 2 diabetes mellitus as adjunct to diet and exercise

Indicated for type 2 diabetes mellitus in patients treated with combination of pioglitazone and a sulfonylurea, or patients not adequately controlled on a sulfonylurea alone, or who have initially responded to pioglitazone and require additional glycemic control Management of diabetes mellitus as adjunct to diet and exercise

30 mg/2 mg, OR 30 mg/4 mg PO qDay; not to exceed 45 mg/8 mg

Dosage Modifications

Renal Impairment

• CrCl <22 mL/min: 1 mg/day glimepiride PO prior to initiating glimepiride/pioglitazone; titrate conservatively to avoid hypoglycemia
• Base dose titration on fasting glucose levels
• CrCl ≥22 mL/min: 30 mg/2 mg or 30 mg/4 mg PO qDay initially

Hepatic Impairment

• 1 mg/day glimpiride PO prior to initiating glimepiride/pioglitazone; titrate conservatively to avoid hypoglycemia
• Baseline ALT <2.5 xULN: Use caution
• Baseline ALT ≥2.5 xULN: Do not initiate
• ALT >3 xULN or jaundice after initiating therapy: Discontinue

Dosing Considerations

Systolic dysfunction (NYHA I/II): Initiate after patient has been safely titrated to 30 mg of pioglitazone monotherapy

For use in type 2 DM patients treated with combination of pioglitazone and a sulfonylurea, or patients not adequately controlled on a sulfonylurea alone, or patients who have initially responded to pioglitazone and require additional glycemic control

Safety and efficacy not established

1 mg/day glimpiride (as monotherapy) PO prior to initiating glimepiride/pioglitazone; titrate conservatively to avoid hypoglycemia

Contraindicated (0)

Serious - Use Alternative (11)

• aminolevulinic acid oral

  aminolevulinic acid oral, glimepiride. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid administering other phototoxic drugs with aminolevulinic acid oral for 24 hr during perioperative period.

• aminolevulinic acid topical

  glimepiride increases toxicity of aminolevulinic acid topical by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration of photosensitizing drugs may enhance the phototoxic reaction to photodynamic therapy with aminolevulinic acid.

• 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.

• 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, glimepiride. Other (see comment). Contraindicated. Comment: Excessive EtOH consumption may alter glycemic control. Some sulfonylureas may produce a disulfiram like rxn.

• etrasimod

  pioglitazone will increase the level or effect of etrasimod by Other (see comment). Avoid or Use Alternate Drug. Increased exposure of etrasimod expected in patients who are CYP2C9 poor metabolizers if coadministered with moderate to strong CYP2C8 inhibitors.

• ivosidenib

  ivosidenib will decrease the level or effect of glimepiride by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2C9 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

• gemfibrozil

  gemfibrozil will increase the level or effect of pioglitazone by decreasing metabolism. Avoid or Use Alternate Drug.

• lumacaftor/ivacaftor

  lumacaftor/ivacaftor will decrease the level or effect of glimepiride by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Sulfonylureas are CYP2C9 substrates. Lumacaftor/ivacaftor has the potential to induce CYP2C9.

• methyl aminolevulinate

  glimepiride, methyl aminolevulinate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Each drug may increase the photosensitizing effect of the other.

• pacritinib

  pioglitazone will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

Monitor Closely (213)

• aceclofenac

  aceclofenac increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• acemetacin

  acemetacin increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• albiglutide

  albiglutide, glimepiride. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Serious hypoglycemia may occur when insulin secretagogues and GLP-1 agonists are concurrently administered. Consider lowering the dose of insulin secretagogue to reduce the risk of hypoglycemia. .
  
  albiglutide, pioglitazone. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.

• alogliptin

  alogliptin, glimepiride. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of alogliptin with insulin and/or insulin secretagogues (eg, sulfonylureas, meglitinide derivatives) may increase risk for hypoglycemia; may require lower dose of insulin or insulin secretagogue .

• 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.

• alpelisib

  alpelisib will decrease the level or effect of glimepiride by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.

• apalutamide

  apalutamide will decrease the level or effect of glimepiride by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Coadministration of apalutamide, a weak CYP2C9 inducer, with drugs that are CYP2C9 substrates can result in lower exposure to these medications. Evaluate for loss of therapeutic effect if medication must be coadministered.

• aripiprazole

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

• aspirin

  aspirin increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• atogepant

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

• aspirin rectal

  aspirin rectal increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• aspirin/citric acid/sodium bicarbonate

  aspirin/citric acid/sodium bicarbonate increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• atazanavir

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

• 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 effects of glimepiride by pharmacodynamic synergism. Use Caution/Monitor. Additive hypoglycemic effects.

• bexagliflozin

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

• 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.
  
  bexarotene increases effects of glimepiride by pharmacodynamic synergism. Use Caution/Monitor. Based on the mechanism of action, bexarotene capsules may increase the action of insulin enhancing agents, resulting in hypoglycemia. Hypoglycemia has not been associated with bexarotene monotherapy.

• bitter melon

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

• canagliflozin

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

• 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.

• cannabidiol

  cannabidiol will increase the level or effect of glimepiride by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

• captopril

  captopril increases effects of glimepiride by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood glucose. Monitor blood glucose.

• carbamazepine

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

• celecoxib

  celecoxib increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• cholic acid

  glimepiride 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.
  
  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.

• choline magnesium trisalicylate

  choline magnesium trisalicylate increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• cimetidine

  cimetidine will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cinnamon

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

• ciprofibrate

  ciprofibrate increases effects of glimepiride by plasma protein binding competition. Use Caution/Monitor. Hypoglycemia; increased risk in hypoalbuminemia.

• ciprofloxacin

  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.

• ciprofloxacin

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

• clarithromycin

  clarithromycin will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  clarithromycin increases levels of glimepiride by plasma protein binding competition. Use Caution/Monitor. Risk of hypoglycemia.

• clotrimazole

  clotrimazole increases levels of glimepiride by decreasing metabolism. Use Caution/Monitor.

• clozapine

  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.

• clozapine

  clozapine, glimepiride. 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 decreases levels of glimepiride by drug binding in GI tract. Use Caution/Monitor. Concomitant administration decreases glimepiride absorption; however, absorption is not reduced when glimepiride is administered 4 hr before colesevelam.

• cyclosporine

  glimepiride, cyclosporine. unknown mechanism. Use Caution/Monitor. Cyclosporine may decrease the effects of sulfonylureas. Sulfonylureas may increase the effects of cyclosporine.

• dapagliflozin

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

• daprodustat

  pioglitazone will increase the level or effect of daprodustat by Other (see comment). Modify Therapy/Monitor Closely. Moderate CYP2C8 inhibitors increase daprodustat exposure. If coadministered with moderate CYP2C8 inhibitors, reduce daprodustat starting dose by half (except if starting dose is already 1 mg). Monitor hemoglobin and adjust daprodustat dose when initiating or stopping therapy with moderate CYP2C8 inhibitors during treatment

• darunavir

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

• diclofenac

  diclofenac increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• 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.

• diflunisal

  diflunisal increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• diltiazem

  diltiazem will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• disopyramide

  disopyramide increases effects of glimepiride by unspecified interaction mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• 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.
  
  dulaglutide, glimepiride. 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.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  elvitegravir/cobicistat/emtricitabine/tenofovir DF decreases levels of glimepiride by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely. Elvitegravir is a moderate CYP2C9 inducer.

• erythromycin base

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

• empagliflozin

  empagliflozin, glimepiride. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with SGLT2 inhibitors.

• enalapril

  enalapril increases effects of glimepiride by pharmacodynamic synergism. Use Caution/Monitor.

• ertugliflozin

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

• 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.

• ethinylestradiol

  pioglitazone decreases levels of ethinylestradiol by unknown mechanism. Use Caution/Monitor.

• etodolac

  etodolac increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• 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.
  
  exenatide injectable solution, glimepiride. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypoglycemia when exenatide is used in combination with agents that induce hypoglycemia. Consider lowering dose of sulfonylureas to reduce risk of hypoglycemia. .

• exenatide injectable suspension

  exenatide injectable suspension, glimepiride. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypoglycemia when exenatide is used in combination with agents that induce hypoglycemia. Consider lowering dose of sulfonylureas to reduce risk of hypoglycemia.
  
  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.

• fenofibrate

  fenofibrate increases effects of glimepiride by plasma protein binding competition. Use Caution/Monitor. Hypoglycemia; increased risk in hypoalbuminemia.

• 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.

• fenofibrate micronized

  fenofibrate micronized increases effects of glimepiride by plasma protein binding competition. Use Caution/Monitor. Hypoglycemia; increased risk in hypoalbuminemia.

• fenofibric acid

  fenofibric acid increases effects of glimepiride by plasma protein binding competition. Use Caution/Monitor. Hypoglycemia; increased risk in hypoalbuminemia.

• fenoprofen

  fenoprofen increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• fleroxacin

  fleroxacin increases effects of glimepiride 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

  fluconazole increases levels of glimepiride by decreasing metabolism. Use Caution/Monitor.

• fluoxetine

  fluoxetine increases effects of glimepiride by unspecified interaction mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• flurbiprofen

  flurbiprofen increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• fluvastatin

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

• fosamprenavir

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

• fosinopril

  fosinopril increases effects of glimepiride by pharmacodynamic synergism. Use Caution/Monitor.

• gemfibrozil

  gemfibrozil increases effects of glimepiride by plasma protein binding competition. Use Caution/Monitor. Hypoglycemia; increased risk in hypoalbuminemia.

• gemifloxacin

  gemifloxacin increases effects of glimepiride 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

• ibuprofen

  ibuprofen increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• ibuprofen IV

  ibuprofen IV increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• 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, 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.
  
  iloperidone, glimepiride. 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 effects of glimepiride by pharmacodynamic synergism. Use Caution/Monitor.

• 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 glimepiride by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• indomethacin

  indomethacin increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• insulin aspart

  glimepiride, 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

  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.
  
  glimepiride, 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.
  
  glimepiride, 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

  glimepiride, 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.
  
  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.

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

• insulin glargine

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

• insulin glulisine

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

• insulin inhaled

  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.
  
  glimepiride, 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

  glimepiride, 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.
  
  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.

• 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).
  
  glimepiride, 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

  glimepiride, 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.
  
  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.

• insulin NPH

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

  glimepiride, 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.
  
  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.
  
  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).

• isavuconazonium sulfate

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

• isocarboxazid

  isocarboxazid increases effects of glimepiride by unknown mechanism. Use Caution/Monitor.

• ketoconazole

  ketoconazole increases levels of glimepiride by decreasing metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ketoprofen

  ketoprofen increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• ketotifen, ophthalmic

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

• ketorolac

  ketorolac increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• ketorolac intranasal

  ketorolac intranasal increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• ketotifen, ophthalmic

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

• 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.

• levofloxacin

  levofloxacin increases effects of glimepiride 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 increases levels of glimepiride by decreasing metabolism. Use Caution/Monitor.
  
  levoketoconazole will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• linagliptin

  glimepiride, linagliptin. Other (see comment). Use Caution/Monitor. Comment: When linagliptin is used in combination with sulfonylureas, a lower dose of the sulfonylurea may be required to reduce risk of hypoglycemia.
  
  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 increases effects of glimepiride by unknown mechanism. Use Caution/Monitor.

• liraglutide

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

• liraglutide

  liraglutide, glimepiride. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Serious hypoglycemia may occur when insulin secretagogues and GLP-1 agonists are concurrently administered. Consider lowering the dose of insulin secretagogue to reduce the risk of hypoglycemia. .

• lisinopril

  lisinopril increases effects of glimepiride by pharmacodynamic synergism. Use Caution/Monitor.

• lixisenatide (DSC)

  lixisenatide (DSC), glimepiride. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Risk of hypoglycemia increased when coadministered with sulfonylureas. Sulfonylurea dosage reduction may be required.

• lonapegsomatropin

  lonapegsomatropin decreases effects of pioglitazone by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone.
  
  lonapegsomatropin decreases effects of glimepiride 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 glimepiride by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone.
  
  lonapegsomatropin decreases effects of 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

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

• lurasidone

  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.

• lornoxicam

  lornoxicam increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• lurasidone

  lurasidone, glimepiride. 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 glimepiride 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 glimepiride by pharmacodynamic synergism. Use Caution/Monitor. Additive hypoglycemic effects.

• mecasermin

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

• meclofenamate

  meclofenamate increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• mefenamic acid

  mefenamic acid increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• meloxicam

  meloxicam increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• metreleptin

  glimepiride, metreleptin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of metreleptin with insulin and/or insulin secretagogues (eg, sulfonylureas, meglitinide derivatives) may increase risk for hypoglycemia; may require lower dose of insulin or insulin secretagogue.

• miconazole vaginal

  miconazole vaginal increases levels of glimepiride by decreasing metabolism. Use Caution/Monitor.

• 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, glimepiride. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.
  
  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 effects of glimepiride by pharmacodynamic synergism. Use Caution/Monitor.

• moxifloxacin

  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.

• moxifloxacin

  moxifloxacin increases effects of glimepiride 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.

• nabumetone

  nabumetone increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• nadolol

  nadolol decreases effects of glimepiride by pharmacodynamic antagonism. Use Caution/Monitor. Non selective beta blockers may also mask the symptoms of hypoglycemia.

• naproxen

  naproxen increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• 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 glimepiride by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• nitisinone

  nitisinone will increase the level or effect of glimepiride by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

• ofloxacin

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

• omaveloxolone

  omaveloxolone will decrease the level or effect of pioglitazone by Other (see comment). Use Caution/Monitor. Omaveloxolone may reduce systemic exposure of sensitive CYP2C8 substrates. Check prescribing information of substrate if dosage modification is needed.

• opuntia ficus indica

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

• opuntia ficus indica

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

• oxaprozin

  oxaprozin increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

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

• parecoxib

  parecoxib increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• pitavastatin

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

• peginterferon alfa 2b

  peginterferon alfa 2b decreases levels of glimepiride by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. When patients are administered peginterferon alpha-2b with CYP2C9 substrates, the therapeutic effect of these drugs may be altered. .

• perindopril

  perindopril increases effects of glimepiride by pharmacodynamic synergism. Use Caution/Monitor.

• phenelzine

  phenelzine increases effects of glimepiride by unknown mechanism. Use Caution/Monitor.

• pindolol

  pindolol decreases effects of glimepiride by pharmacodynamic antagonism. Use Caution/Monitor. Non selective beta blockers may also mask the symptoms of hypoglycemia.

• piroxicam

  piroxicam increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• ponatinib

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

• posaconazole

  posaconazole increases levels of glimepiride by decreasing metabolism. Use Caution/Monitor.

• pravastatin

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

• probenecid

  probenecid increases levels of glimepiride by unspecified interaction mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• propranolol

  propranolol decreases effects of glimepiride by pharmacodynamic antagonism. Use Caution/Monitor. Non selective beta blockers may also mask the symptoms of hypoglycemia.

• quetiapine

  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.
  
  quetiapine, glimepiride. 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 effects of glimepiride by pharmacodynamic synergism. Use Caution/Monitor.

• rifabutin

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

• ramipril

  ramipril increases effects of glimepiride by pharmacodynamic synergism. Use Caution/Monitor.

• rifabutin

  rifabutin decreases levels of glimepiride by increasing metabolism. Use Caution/Monitor.

• rifampin

  rifampin will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  rifampin decreases levels of glimepiride by increasing metabolism. Use Caution/Monitor.

• rifapentine

  rifapentine decreases levels of glimepiride by increasing 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

  risperidone, glimepiride. 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, glimepiride. Other (see comment). Use Caution/Monitor. Comment: Ritonavir may increase or decrease levels of glimepiride. Use alternatives if available. 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.

• rucaparib

  rucaparib will increase the level or effect of glimepiride by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP2C9 substrates, if clinically indicated.

• 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

• salicylates (non-asa)

  salicylates (non-asa) increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• salsalate

  salsalate increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• saquinavir

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

• selegiline

  selegiline increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Serum glucose should be monitored closely when MAOIs are added to any regimen containing antidiabetic medications. Hypoglycemic effects may be increased.

• selegiline transdermal

  selegiline transdermal increases effects of glimepiride by unknown mechanism. Use Caution/Monitor.

• 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.

• semaglutide

  semaglutide, glimepiride. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin secretagogues with GLP-1 agonists may increase hypoglycemia risk. Lowering the insulin secretagogue dose may reduce hypoglycemia risk. .

• shark cartilage

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

• somapacitan

  somapacitan decreases effects of glimepiride by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone.

• somapacitan

  somapacitan decreases effects of pioglitazone by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone.

• somatrogon

  somatrogon decreases effects of pioglitazone by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone.
  
  somatrogon decreases effects of glimepiride by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone.

• somatropin

  somatropin decreases effects of glimepiride by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone.
  
  somatropin decreases effects of pioglitazone by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone.

• St John's Wort

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

• sotagliflozin

  sotagliflozin increases effects of glimepiride by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Hypoglycemia risk increased. Lower dose of sulfonylurea may be required.

• sparsentan

  sparsentan will decrease the level or effect of glimepiride by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C9 inducer) decreases exposure of CYP2C9 substrates and reduces efficacy related to these substrates.

• 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.

• sulfadiazine

  sulfadiazine increases levels of glimepiride by plasma protein binding competition. Use Caution/Monitor.

• sulfamethoxazole

  sulfamethoxazole increases levels of glimepiride by plasma protein binding competition. Use Caution/Monitor.

• sulfamethoxypyridazine

  sulfamethoxypyridazine increases effects of glimepiride 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.

• sulfasalazine

  sulfasalazine increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• tazemetostat

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

• sulfisoxazole

  sulfisoxazole increases levels of glimepiride by plasma protein binding competition. Use Caution/Monitor.

• sulindac

  sulindac increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• 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.

• teriflunomide

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

• timolol

  timolol decreases effects of glimepiride by pharmacodynamic antagonism. Use Caution/Monitor. Non selective beta blockers may also mask the symptoms of hypoglycemia.

• tipranavir

  tipranavir, pioglitazone. Other (see comment). Use Caution/Monitor. Comment: Tipranavir's effect on oral hypoglycemics via hepatic CYP2C9 unknown; carefully monitor blood glucose.
  
  tipranavir decreases effects of glimepiride by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• tolfenamic acid

  tolfenamic acid increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• 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.

• tolmetin

  tolmetin increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• trandolapril

  trandolapril increases effects of glimepiride by pharmacodynamic synergism. Use Caution/Monitor.

• tranylcypromine

  tranylcypromine increases effects of glimepiride by unknown mechanism. Use Caution/Monitor.

• triamcinolone acetonide injectable suspension

  triamcinolone acetonide injectable suspension decreases effects of glimepiride by pharmacodynamic antagonism. Use Caution/Monitor. Corticosteroids may diminish hypoglycemic effect of antidiabetic agents. Monitor blood glucose levels carefully.

• trimagnesium citrate anhydrous

  trimagnesium citrate anhydrous increases levels of glimepiride by enhancing GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• 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

• voriconazole

  voriconazole increases levels of glimepiride by decreasing metabolism. Use Caution/Monitor.

• warfarin

  glimepiride, warfarin. Either increases effects of the other by receptor binding competition. Use Caution/Monitor. Monitor for decreased vitamin K antagonist effects (eg, decreased INR, thrombosis) when combined with metformin. Additionally, consider increased monitoring for hypoglycemia with this combination. Competitive inhibition of CYP2C9-mediated metabolism may also contribute to mechanism.

• xipamide

  xipamide decreases levels of glimepiride by increasing renal clearance. Use Caution/Monitor.
  
  xipamide decreases levels of pioglitazone by increasing renal clearance. Use Caution/Monitor.

• ziprasidone

  ziprasidone, glimepiride. 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.

Minor (147)

• agrimony

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

• American ginseng

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

• amitriptyline

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

• amoxapine

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

• anamu

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

• aspirin

  aspirin increases effects of glimepiride by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• 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.

• aspirin rectal

  aspirin rectal increases effects of glimepiride by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• aspirin/citric acid/sodium bicarbonate

  aspirin/citric acid/sodium bicarbonate increases effects of glimepiride by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• atazanavir

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

• balsalazide

  balsalazide increases effects of glimepiride by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• bendroflumethiazide

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

• budesonide

  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.

• butalbital

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

• chloramphenicol

  chloramphenicol increases levels of glimepiride by decreasing 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.
  
  chlorothiazide decreases effects of glimepiride by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• chlorthalidone

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

• choline magnesium trisalicylate

  choline magnesium trisalicylate increases effects of glimepiride by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• chromium

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

• chromium

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

• clomipramine

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

• clonidine

  clonidine decreases effects of glimepiride by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  clonidine, glimepiride. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
  
  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.

• 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 glimepiride 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 glimepiride 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.

• cyclopenthiazide

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

• danazol

  danazol increases effects of glimepiride 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 glimepiride 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 glimepiride by pharmacodynamic synergism. Minor/Significance Unknown.
  
  desipramine increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

• devil's claw

  devil's claw increases effects of glimepiride 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 glimepiride 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.

• diflunisal

  diflunisal increases effects of glimepiride by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• doxepin

  doxepin increases effects of glimepiride 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 glimepiride 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 glimepiride by pharmacodynamic synergism. Minor/Significance Unknown. Theoretical interaction.

• 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 glimepiride by pharmacodynamic antagonism. Minor/Significance Unknown.

• fludrocortisone

  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 glimepiride by pharmacodynamic synergism. Minor/Significance Unknown.

• fo-ti

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

• forskolin

  forskolin increases effects of glimepiride 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

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

• gotu kola

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

• fosaprepitant

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

• fosphenytoin

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

• gotu kola

  gotu kola increases effects of pioglitazone 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.

• 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, glimepiride. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
  
  guanfacine decreases effects of glimepiride 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 glimepiride 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 glimepiride by pharmacodynamic synergism. Minor/Significance Unknown.
  
  horse chestnut seed increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

• hydrochlorothiazide

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

• hydrocortisone

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

• imipramine

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

• isoniazid

  isoniazid decreases effects of glimepiride by unspecified interaction mechanism. Minor/Significance Unknown.

• 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).
  
  juniper increases effects of glimepiride 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 glimepiride 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 glimepiride 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 glimepiride by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (animal research).

• maprotiline

  maprotiline increases effects of glimepiride 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.

• mesalamine

  mesalamine increases effects of glimepiride by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• mesterolone

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

• mestranol

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

• methyclothiazide

  methyclothiazide decreases effects of glimepiride 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 will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  methylprednisolone decreases effects of glimepiride by pharmacodynamic antagonism. Minor/Significance Unknown.

• methyltestosterone

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

• nettle

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

• 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 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 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 glimepiride by pharmacodynamic synergism. Minor/Significance Unknown.

• ofloxacin

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

• orlistat

  orlistat increases effects of glimepiride by pharmacodynamic synergism. Minor/Significance Unknown.

• oxandrolone

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

• oxandrolone

  oxandrolone increases effects of glimepiride 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 pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.
  
  oxymetholone increases effects of glimepiride by pharmacodynamic synergism. Minor/Significance Unknown.

• pegvisomant

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

• prednisolone

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

• prednisone

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

• 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 glimepiride by pharmacodynamic synergism. Minor/Significance Unknown.

• protriptyline

  protriptyline increases effects of pioglitazone by pharmacodynamic synergism. 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 glimepiride by pharmacodynamic synergism. Minor/Significance Unknown.
  
  sage increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

• salicylates (non-asa)

  salicylates (non-asa) increases effects of glimepiride by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• secobarbital

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

• salsalate

  salsalate increases effects of glimepiride by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• sitagliptin

  sitagliptin, glimepiride. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypoglycemia with combination is unknown.

• stevia

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

• sulfasalazine

  sulfasalazine increases effects of glimepiride by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• testosterone

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

• tacrolimus

  glimepiride increases levels of tacrolimus by unknown mechanism. Minor/Significance Unknown.

• testosterone

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

• testosterone topical

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

• tongkat ali

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

• trazodone

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

• trimipramine

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

• vanadium

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

• verapamil

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

• willow bark

  willow bark increases effects of glimepiride by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• aceclofenac

  Monitor Closely (1)aceclofenac increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• acemetacin

  Monitor Closely (1)acemetacin increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• agrimony

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

• albiglutide

  Monitor Closely (2)albiglutide, glimepiride. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Serious hypoglycemia may occur when insulin secretagogues and GLP-1 agonists are concurrently administered. Consider lowering the dose of insulin secretagogue to reduce the risk of hypoglycemia. .
  
  albiglutide, pioglitazone. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.

• alogliptin

  Monitor Closely (1)alogliptin, glimepiride. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of alogliptin with insulin and/or insulin secretagogues (eg, sulfonylureas, meglitinide derivatives) may increase risk for hypoglycemia; may require lower dose of insulin or insulin secretagogue .

• alpelisib

  Monitor Closely (1)alpelisib will decrease the level or effect of glimepiride by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.

• American ginseng

  Minor (1)American ginseng increases effects of glimepiride by pharmacodynamic synergism. Minor/Significance Unknown.

• aminolevulinic acid oral

  Serious - Use Alternative (1)aminolevulinic acid oral, glimepiride. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid administering other phototoxic drugs with aminolevulinic acid oral for 24 hr during perioperative period.

• aminolevulinic acid topical

  Serious - Use Alternative (1)glimepiride increases toxicity of aminolevulinic acid topical by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration of photosensitizing drugs may enhance the phototoxic reaction to photodynamic therapy with aminolevulinic acid.

• amitriptyline

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

• 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 glimepiride by pharmacodynamic synergism. Minor/Significance Unknown.
  
  amoxapine increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

• anamu

  Minor (2)anamu increases effects of glimepiride by pharmacodynamic synergism. Minor/Significance Unknown. Theoretical interaction.
  
  anamu increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown. Theoretical interaction.

• apalutamide

  Monitor Closely (1)apalutamide will decrease the level or effect of glimepiride by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Coadministration of apalutamide, a weak CYP2C9 inducer, with drugs that are CYP2C9 substrates can result in lower exposure to these medications. Evaluate for loss of therapeutic effect if medication must be coadministered.

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

• aspirin

  Monitor Closely (1)aspirin increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.Minor (1)aspirin increases effects of glimepiride by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• aspirin rectal

  Monitor Closely (1)aspirin rectal increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.Minor (1)aspirin rectal increases effects of glimepiride by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• aspirin/citric acid/sodium bicarbonate

  Monitor Closely (1)aspirin/citric acid/sodium bicarbonate increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.Minor (1)aspirin/citric acid/sodium bicarbonate increases effects of glimepiride by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• atazanavir

  Monitor Closely (1)atazanavir decreases effects of glimepiride 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.

• balsalazide

  Minor (1)balsalazide increases effects of glimepiride by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• 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 effects of glimepiride by pharmacodynamic synergism. Use Caution/Monitor. Additive hypoglycemic effects.

• bendroflumethiazide

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

• bexagliflozin

  Monitor Closely (1)bexagliflozin, glimepiride. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin secretagogue to avoid hypoglycemia when coadministered with bexagliflozin.

• bexarotene

  Monitor Closely (2)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.
  
  bexarotene increases effects of glimepiride by pharmacodynamic synergism. Use Caution/Monitor. Based on the mechanism of action, bexarotene capsules may increase the action of insulin enhancing agents, resulting in hypoglycemia. Hypoglycemia has not been associated with bexarotene monotherapy.

• bitter melon

  Monitor Closely (2)bitter melon increases effects of glimepiride by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypoglycemia.
  
  bitter melon increases effects of pioglitazone 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.

• budesonide

  Minor (3)budesonide decreases effects of glimepiride 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

  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.

• canagliflozin

  Monitor Closely (1)glimepiride, canagliflozin. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with canagliflozin.

• cannabidiol

  Monitor Closely (2)cannabidiol will increase the level or effect of glimepiride by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.
  
  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 effects of glimepiride by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood glucose. Monitor blood glucose.

• carbamazepine

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

• celecoxib

  Monitor Closely (1)celecoxib increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• chloramphenicol

  Minor (1)chloramphenicol increases levels of glimepiride by decreasing metabolism. Minor/Significance Unknown.

• chlorothiazide

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

• chlorthalidone

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

• cholic acid

  Monitor Closely (2)glimepiride 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.
  
  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.

• choline magnesium trisalicylate

  Monitor Closely (1)choline magnesium trisalicylate increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.Minor (1)choline magnesium trisalicylate increases effects of glimepiride by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• chromium

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

• cimetidine

  Monitor Closely (1)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 glimepiride by pharmacodynamic synergism. Use Caution/Monitor. Potential for hypoglycemia.
  
  cinnamon increases effects of pioglitazone by pharmacodynamic synergism. Use Caution/Monitor. Potential for hypoglycemia.

• ciprofibrate

  Monitor Closely (1)ciprofibrate increases effects of glimepiride by plasma protein binding competition. Use Caution/Monitor. Hypoglycemia; increased risk in hypoalbuminemia.

• ciprofloxacin

  Monitor Closely (2)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.
  
  ciprofloxacin increases effects of glimepiride by pharmacodynamic synergism. Use Caution/Monitor. Hyper and hypoglycemia have been reported in patients treated concomitantly with quinolones and antidiabetic agents. Careful monitoring of blood glucose is recommended.

• clarithromycin

  Monitor Closely (2)clarithromycin will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  clarithromycin increases levels of glimepiride by plasma protein binding competition. Use Caution/Monitor. Risk of hypoglycemia.

• clomipramine

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

• clonidine

  Minor (4)clonidine decreases effects of glimepiride by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  clonidine, glimepiride. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
  
  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.

• clotrimazole

  Monitor Closely (1)clotrimazole increases levels of glimepiride by decreasing metabolism. Use Caution/Monitor.

• clozapine

  Monitor Closely (2)clozapine, glimepiride. 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 decreases levels of glimepiride by drug binding in GI tract. Use Caution/Monitor. Concomitant administration decreases glimepiride absorption; however, absorption is not reduced when glimepiride is administered 4 hr before colesevelam.

• conivaptan

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

• cornsilk

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

• cortisone

  Minor (3)cortisone decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown.
  
  cortisone decreases effects of glimepiride 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.

• 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 glimepiride by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• cyclosporine

  Monitor Closely (1)glimepiride, cyclosporine. unknown mechanism. Use Caution/Monitor. Cyclosporine may decrease the effects of sulfonylureas. Sulfonylureas may increase the effects of cyclosporine.

• damiana

  Minor (2)damiana decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Theoretical interaction.
  
  damiana decreases effects of glimepiride by pharmacodynamic antagonism. Minor/Significance Unknown. Theoretical interaction.

• danazol

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

• dapagliflozin

  Monitor Closely (1)glimepiride, dapagliflozin. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with dapagliflozin.

• daprodustat

  Monitor Closely (1)pioglitazone will increase the level or effect of daprodustat by Other (see comment). Modify Therapy/Monitor Closely. Moderate CYP2C8 inhibitors increase daprodustat exposure. If coadministered with moderate CYP2C8 inhibitors, reduce daprodustat starting dose by half (except if starting dose is already 1 mg). Monitor hemoglobin and adjust daprodustat dose when initiating or stopping therapy with moderate CYP2C8 inhibitors during treatment

• 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 glimepiride 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 glimepiride by pharmacodynamic antagonism. Minor/Significance Unknown.
  
  deflazacort decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown.

• desipramine

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

• devil's claw

  Minor (2)devil's claw increases effects of glimepiride 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 glimepiride 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.

• diclofenac

  Monitor Closely (1)diclofenac increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• dienogest/estradiol valerate

  Monitor Closely (1)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.

• diflunisal

  Monitor Closely (1)diflunisal increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.Minor (1)diflunisal increases effects of glimepiride by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• diltiazem

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

• disopyramide

  Monitor Closely (1)disopyramide increases effects of glimepiride by unspecified interaction mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• doxepin

  Minor (2)doxepin increases effects of glimepiride 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.

• dulaglutide

  Monitor Closely (2)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.
  
  dulaglutide, glimepiride. 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 glimepiride 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. .

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  Monitor Closely (1)elvitegravir/cobicistat/emtricitabine/tenofovir DF decreases levels of glimepiride by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely. Elvitegravir is a moderate CYP2C9 inducer.

• empagliflozin

  Monitor Closely (1)empagliflozin, glimepiride. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with SGLT2 inhibitors.

• enalapril

  Monitor Closely (1)enalapril increases effects of glimepiride by pharmacodynamic synergism. Use Caution/Monitor.

• ertugliflozin

  Monitor Closely (1)ertugliflozin, glimepiride. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.

• 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.

• eslicarbazepine acetate

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

• 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, glimepiride. Other (see comment). Contraindicated. Comment: Excessive EtOH consumption may alter glycemic control. Some sulfonylureas may produce a disulfiram like rxn.

• ethinylestradiol

  Monitor Closely (1)pioglitazone decreases levels of ethinylestradiol by unknown mechanism. Use Caution/Monitor.

• etodolac

  Monitor Closely (1)etodolac increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• etrasimod

  Serious - Use Alternative (1)pioglitazone will increase the level or effect of etrasimod by Other (see comment). Avoid or Use Alternate Drug. Increased exposure of etrasimod expected in patients who are CYP2C9 poor metabolizers if coadministered with moderate to strong CYP2C8 inhibitors.

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

• 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, glimepiride. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypoglycemia when exenatide is used in combination with agents that induce hypoglycemia. Consider lowering dose of sulfonylureas to reduce risk of hypoglycemia. .

• exenatide injectable suspension

  Monitor Closely (2)exenatide injectable suspension, glimepiride. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypoglycemia when exenatide is used in combination with agents that induce hypoglycemia. Consider lowering dose of sulfonylureas to reduce risk of hypoglycemia.
  
  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.

• fenofibrate

  Monitor Closely (1)fenofibrate increases effects of glimepiride by plasma protein binding competition. Use Caution/Monitor. Hypoglycemia; increased risk in hypoalbuminemia.

• fenofibrate micronized

  Monitor Closely (1)fenofibrate micronized increases effects of glimepiride by plasma protein binding competition. Use Caution/Monitor. Hypoglycemia; increased risk in hypoalbuminemia.

• fenofibric acid

  Monitor Closely (1)fenofibric acid increases effects of glimepiride by plasma protein binding competition. Use Caution/Monitor. Hypoglycemia; increased risk in hypoalbuminemia.

• fenoprofen

  Monitor Closely (1)fenoprofen increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• fleroxacin

  Monitor Closely (2)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 increases effects of glimepiride 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

  Monitor Closely (1)fluconazole increases levels of glimepiride by decreasing metabolism. Use Caution/Monitor.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 will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  fludrocortisone decreases effects of glimepiride by pharmacodynamic antagonism. Minor/Significance Unknown.
  
  fludrocortisone decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown.

• fluoxetine

  Monitor Closely (1)fluoxetine increases effects of glimepiride by unspecified interaction mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• fluoxymesterone

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

• flurbiprofen

  Monitor Closely (1)flurbiprofen increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of 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.

• fo-ti

  Minor (2)fo-ti increases effects of glimepiride by pharmacodynamic synergism. Minor/Significance Unknown.
  
  fo-ti increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

• forskolin

  Minor (2)forskolin increases effects of glimepiride 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 glimepiride 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.

• fosaprepitant

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

• fosinopril

  Monitor Closely (1)fosinopril increases effects of glimepiride by pharmacodynamic synergism. Use Caution/Monitor.

• fosphenytoin

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

• gemfibrozil

  Monitor Closely (1)gemfibrozil increases effects of glimepiride by plasma protein binding competition. Use Caution/Monitor. Hypoglycemia; increased risk in hypoalbuminemia.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 glimepiride 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

• gotu kola

  Minor (2)gotu kola increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction).
  
  gotu kola increases effects of glimepiride 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, glimepiride. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
  
  guanfacine decreases effects of glimepiride 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 glimepiride by pharmacodynamic synergism. Minor/Significance Unknown.
  
  gymnema increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

• horse chestnut seed

  Minor (2)horse chestnut seed increases effects of glimepiride by pharmacodynamic synergism. Minor/Significance Unknown.
  
  horse chestnut seed increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

• hydrochlorothiazide

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

• hydrocortisone

  Minor (3)hydrocortisone decreases effects of glimepiride by pharmacodynamic antagonism. Minor/Significance Unknown.
  
  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.

• ibuprofen

  Monitor Closely (1)ibuprofen increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• ibuprofen IV

  Monitor Closely (1)ibuprofen IV increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• 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, 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.
  
  iloperidone, glimepiride. 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 effects of glimepiride by pharmacodynamic synergism. Use Caution/Monitor.

• imipramine

  Minor (2)imipramine increases effects of glimepiride by pharmacodynamic synergism. Minor/Significance Unknown.
  
  imipramine increases effects of pioglitazone 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 glimepiride by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• indinavir

  Monitor Closely (1)indinavir decreases effects of glimepiride 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.

• indomethacin

  Monitor Closely (1)indomethacin increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• 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.
  
  glimepiride, 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)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.
  
  glimepiride, 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.
  
  glimepiride, 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)glimepiride, 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.
  
  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.

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

• insulin glargine

  Monitor Closely (3)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).
  
  glimepiride, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin glulisine

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

• insulin inhaled

  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.
  
  glimepiride, 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)glimepiride, 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.
  
  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.

• 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).
  
  glimepiride, 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)glimepiride, 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.
  
  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.

• insulin NPH

  Monitor Closely (3)glimepiride, insulin NPH. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
  
  insulin NPH 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 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)glimepiride, 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.
  
  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.
  
  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).

• 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 increases effects of glimepiride by unknown mechanism. Use Caution/Monitor.

• isoniazid

  Minor (3)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.
  
  isoniazid decreases effects of glimepiride by unspecified interaction mechanism. Minor/Significance Unknown.

• ivosidenib

  Serious - Use Alternative (1)ivosidenib will decrease the level or effect of glimepiride by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2C9 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

• juniper

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

• ketoconazole

  Monitor Closely (2)ketoconazole increases levels of glimepiride by decreasing metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ketoprofen

  Monitor Closely (1)ketoprofen increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• ketorolac

  Monitor Closely (1)ketorolac increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• ketorolac intranasal

  Monitor Closely (1)ketorolac intranasal increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• ketotifen, ophthalmic

  Monitor Closely (2)ketotifen, ophthalmic, glimepiride. Other (see comment). Use Caution/Monitor. Comment: Combination may result in thrombocytopenia (rare). Monitor CBC.
  
  ketotifen, ophthalmic, pioglitazone. Other (see comment). Use Caution/Monitor. Comment: Combination may result in thrombocytopenia (rare). Monitor CBC.

• 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.

• levofloxacin

  Monitor Closely (2)levofloxacin increases effects of glimepiride 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 (2)levoketoconazole increases levels of glimepiride by decreasing metabolism. Use Caution/Monitor.
  
  levoketoconazole will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• linagliptin

  Monitor Closely (2)glimepiride, linagliptin. Other (see comment). Use Caution/Monitor. Comment: When linagliptin is used in combination with sulfonylureas, a lower dose of the sulfonylurea may be required to reduce risk of hypoglycemia.
  
  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 increases effects of glimepiride by unknown mechanism. Use Caution/Monitor.

• liraglutide

  Monitor Closely (2)liraglutide, pioglitazone. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.
  
  liraglutide, glimepiride. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Serious hypoglycemia may occur when insulin secretagogues and GLP-1 agonists are concurrently administered. Consider lowering the dose of insulin secretagogue to reduce the risk of hypoglycemia. .

• lisinopril

  Monitor Closely (1)lisinopril increases effects of glimepiride by pharmacodynamic synergism. Use Caution/Monitor.

• lixisenatide (DSC)

  Monitor Closely (1)lixisenatide (DSC), glimepiride. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Risk of hypoglycemia increased when coadministered with sulfonylureas. Sulfonylurea dosage reduction may be required.

• lofepramine

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

• lonapegsomatropin

  Monitor Closely (4)lonapegsomatropin decreases effects of pioglitazone by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone.
  
  lonapegsomatropin decreases effects of glimepiride 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 glimepiride by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone.
  
  lonapegsomatropin decreases effects of 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 glimepiride by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• lornoxicam

  Monitor Closely (1)lornoxicam increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• lumacaftor/ivacaftor

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of glimepiride by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Sulfonylureas are CYP2C9 substrates. Lumacaftor/ivacaftor has the potential to induce CYP2C9.

• 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, 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.
  
  lurasidone, glimepiride. 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 pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).
  
  lycopus increases effects of glimepiride 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 glimepiride by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (animal research).

• maprotiline

  Minor (2)maprotiline increases effects of glimepiride 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 glimepiride 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 glimepiride by pharmacodynamic synergism. Use Caution/Monitor. Additive hypoglycemic effects.
  
  mecasermin increases effects of pioglitazone by pharmacodynamic synergism. Use Caution/Monitor. Additive hypoglycemic effects.

• meclofenamate

  Monitor Closely (1)meclofenamate increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• mefenamic acid

  Monitor Closely (1)mefenamic acid increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• meloxicam

  Monitor Closely (1)meloxicam increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• mesalamine

  Minor (1)mesalamine increases effects of glimepiride by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• mesterolone

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

• mestranol

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

• methyclothiazide

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

• methyl aminolevulinate

  Serious - Use Alternative (1)glimepiride, methyl aminolevulinate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Each drug may increase the photosensitizing effect of the other.

• methylprednisolone

  Minor (3)methylprednisolone decreases effects of pioglitazone 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.
  
  methylprednisolone decreases effects of glimepiride by pharmacodynamic antagonism. Minor/Significance Unknown.

• methyltestosterone

  Minor (2)methyltestosterone increases effects of glimepiride by pharmacodynamic synergism. Minor/Significance Unknown.
  
  methyltestosterone increases effects of pioglitazone 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 glimepiride by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• metreleptin

  Monitor Closely (1)glimepiride, metreleptin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of metreleptin with insulin and/or insulin secretagogues (eg, sulfonylureas, meglitinide derivatives) may increase risk for hypoglycemia; may require lower dose of insulin or insulin secretagogue.

• metronidazole

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

• miconazole vaginal

  Monitor Closely (1)miconazole vaginal increases levels of glimepiride by decreasing metabolism. Use Caution/Monitor.Minor (1)miconazole vaginal will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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 (2)mipomersen, glimepiride. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.
  
  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 effects of glimepiride by pharmacodynamic synergism. Use Caution/Monitor.

• moxifloxacin

  Monitor Closely (2)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.
  
  moxifloxacin increases effects of glimepiride 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.

• nabumetone

  Monitor Closely (1)nabumetone increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• nadolol

  Monitor Closely (1)nadolol decreases effects of glimepiride by pharmacodynamic antagonism. Use Caution/Monitor. Non selective beta blockers may also mask the symptoms of hypoglycemia.

• naproxen

  Monitor Closely (1)naproxen increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• 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 glimepiride 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 glimepiride 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.

• nifedipine

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

• nilotinib

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

• nitisinone

  Monitor Closely (1)nitisinone will increase the level or effect of glimepiride by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

• nortriptyline

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

• ofloxacin

  Monitor Closely (2)ofloxacin increases effects of glimepiride 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 (2)ofloxacin, pioglitazone. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Potential dysglycemia.
  
  ofloxacin, glimepiride. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Potential dysglycemia.

• olanzapine

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

• omaveloxolone

  Monitor Closely (1)omaveloxolone will decrease the level or effect of pioglitazone by Other (see comment). Use Caution/Monitor. Omaveloxolone may reduce systemic exposure of sensitive CYP2C8 substrates. Check prescribing information of substrate if dosage modification is needed.

• opuntia ficus indica

  Monitor Closely (2)opuntia ficus indica increases effects of glimepiride by pharmacodynamic synergism. Use Caution/Monitor.
  
  opuntia ficus indica increases effects of pioglitazone by pharmacodynamic synergism. Use Caution/Monitor.

• orlistat

  Minor (1)orlistat increases effects of glimepiride by pharmacodynamic synergism. Minor/Significance Unknown.

• oxandrolone

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

• oxaprozin

  Monitor Closely (1)oxaprozin increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• 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 glimepiride 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 (1)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, glimepiride. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• parecoxib

  Monitor Closely (1)parecoxib increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• peginterferon alfa 2b

  Monitor Closely (1)peginterferon alfa 2b decreases levels of glimepiride by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. When patients are administered peginterferon alpha-2b with CYP2C9 substrates, the therapeutic effect of these drugs may be altered. .

• pegvisomant

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

• 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 effects of glimepiride by pharmacodynamic synergism. Use Caution/Monitor.

• phenelzine

  Monitor Closely (1)phenelzine increases effects of glimepiride by unknown 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.

• phenytoin

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

• pindolol

  Monitor Closely (1)pindolol decreases effects of glimepiride by pharmacodynamic antagonism. Use Caution/Monitor. Non selective beta blockers may also mask the symptoms of hypoglycemia.

• piroxicam

  Monitor Closely (1)piroxicam increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• 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

  Monitor Closely (1)posaconazole increases levels of glimepiride by decreasing metabolism. Use Caution/Monitor.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 glimepiride 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 glimepiride by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia.
  
  potassium chloride increases effects of pioglitazone 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 glimepiride 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 glimepiride by pharmacodynamic antagonism. Minor/Significance Unknown.
  
  prednisolone decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown.

• prednisone

  Minor (3)prednisone decreases effects of glimepiride by pharmacodynamic antagonism. Minor/Significance Unknown.
  
  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.

• primidone

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

• probenecid

  Monitor Closely (1)probenecid increases levels of glimepiride by unspecified interaction mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• propranolol

  Monitor Closely (1)propranolol decreases effects of glimepiride by pharmacodynamic antagonism. Use Caution/Monitor. Non selective beta blockers may also mask the symptoms of hypoglycemia.

• protriptyline

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

• quetiapine

  Monitor Closely (2)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.
  
  quetiapine, glimepiride. 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 effects of glimepiride by pharmacodynamic synergism. Use Caution/Monitor.

• 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 effects of glimepiride by pharmacodynamic synergism. Use Caution/Monitor.

• rifabutin

  Monitor Closely (2)rifabutin decreases levels of glimepiride by increasing metabolism. Use Caution/Monitor.
  
  rifabutin will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rifampin

  Monitor Closely (2)rifampin will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  rifampin decreases levels of glimepiride by increasing metabolism. Use Caution/Monitor.

• rifapentine

  Monitor Closely (1)rifapentine decreases levels of glimepiride by increasing metabolism. Use Caution/Monitor.Minor (1)rifapentine will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• 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, glimepiride. 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, glimepiride. Other (see comment). Use Caution/Monitor. Comment: Ritonavir may increase or decrease levels of glimepiride. Use alternatives if available. 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.

• rucaparib

  Monitor Closely (1)rucaparib will increase the level or effect of glimepiride by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP2C9 substrates, if clinically indicated.

• 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 glimepiride by pharmacodynamic synergism. Minor/Significance Unknown.
  
  sage increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

• salicylates (non-asa)

  Monitor Closely (1)salicylates (non-asa) increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.Minor (1)salicylates (non-asa) increases effects of glimepiride by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• salsalate

  Monitor Closely (1)salsalate increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.Minor (1)salsalate increases effects of glimepiride by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• saquinavir

  Monitor Closely (1)saquinavir decreases effects of glimepiride 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

  Monitor Closely (1)selegiline increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Serum glucose should be monitored closely when MAOIs are added to any regimen containing antidiabetic medications. Hypoglycemic effects may be increased.

• selegiline transdermal

  Monitor Closely (1)selegiline transdermal increases effects of glimepiride by unknown mechanism. Use Caution/Monitor.

• 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.

• semaglutide

  Monitor Closely (1)semaglutide, glimepiride. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin secretagogues with GLP-1 agonists may increase hypoglycemia risk. Lowering the insulin secretagogue dose may reduce hypoglycemia risk. .

• shark cartilage

  Monitor Closely (2)shark cartilage increases effects of pioglitazone by pharmacodynamic synergism. Use Caution/Monitor. Theoretical interaction.
  
  shark cartilage increases effects of glimepiride 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.

• sitagliptin

  Minor (1)sitagliptin, glimepiride. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypoglycemia with combination is unknown.

• somapacitan

  Monitor Closely (2)somapacitan decreases effects of glimepiride by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone.
  
  somapacitan decreases effects of pioglitazone by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone.

• somatrogon

  Monitor Closely (2)somatrogon decreases effects of pioglitazone by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone.
  
  somatrogon decreases effects of glimepiride by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone.

• somatropin

  Monitor Closely (2)somatropin decreases effects of glimepiride by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone.
  
  somatropin decreases effects of pioglitazone by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone.

• sotagliflozin

  Monitor Closely (1)sotagliflozin increases effects of glimepiride by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Hypoglycemia risk increased. Lower dose of sulfonylurea may be required.

• sparsentan

  Monitor Closely (1)sparsentan will decrease the level or effect of glimepiride by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C9 inducer) decreases exposure of CYP2C9 substrates and reduces efficacy related to these substrates.

• 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 glimepiride 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.

• sulfadiazine

  Monitor Closely (1)sulfadiazine increases levels of glimepiride by plasma protein binding competition. Use Caution/Monitor.

• sulfamethoxazole

  Monitor Closely (1)sulfamethoxazole increases levels of glimepiride by plasma protein binding competition. Use Caution/Monitor.

• sulfamethoxypyridazine

  Monitor Closely (2)sulfamethoxypyridazine increases effects of glimepiride 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.

• sulfasalazine

  Monitor Closely (1)sulfasalazine increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.Minor (1)sulfasalazine increases effects of glimepiride by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• sulfisoxazole

  Monitor Closely (1)sulfisoxazole increases levels of glimepiride by plasma protein binding competition. Use Caution/Monitor.

• sulindac

  Monitor Closely (1)sulindac increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• tacrolimus

  Minor (1)glimepiride increases levels of tacrolimus by unknown mechanism. Minor/Significance Unknown.

• 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.

• 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 pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.
  
  testosterone increases effects of glimepiride 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 glimepiride by pharmacodynamic synergism. Minor/Significance Unknown.

• testosterone topical

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

• timolol

  Monitor Closely (1)timolol decreases effects of glimepiride by pharmacodynamic antagonism. Use Caution/Monitor. Non selective beta blockers may also mask the symptoms of hypoglycemia.

• tipranavir

  Monitor Closely (2)tipranavir, pioglitazone. Other (see comment). Use Caution/Monitor. Comment: Tipranavir's effect on oral hypoglycemics via hepatic CYP2C9 unknown; carefully monitor blood glucose.
  
  tipranavir decreases effects of glimepiride by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• tolfenamic acid

  Monitor Closely (1)tolfenamic acid increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• tolmetin

  Monitor Closely (1)tolmetin increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• tongkat ali

  Minor (2)tongkat ali increases effects of glimepiride by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypoglycemia.
  
  tongkat ali increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypoglycemia.

• topiramate

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

• trandolapril

  Monitor Closely (1)trandolapril increases effects of glimepiride by pharmacodynamic synergism. Use Caution/Monitor.

• tranylcypromine

  Monitor Closely (1)tranylcypromine increases effects of glimepiride by unknown mechanism. Use Caution/Monitor.

• trazodone

  Minor (2)trazodone increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.
  
  trazodone increases effects of glimepiride 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 glimepiride by pharmacodynamic antagonism. Use Caution/Monitor. Corticosteroids may diminish hypoglycemic effect of antidiabetic agents. Monitor blood glucose levels carefully.

• trimagnesium citrate anhydrous

  Monitor Closely (1)trimagnesium citrate anhydrous increases levels of glimepiride by enhancing GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• trimipramine

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

• 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 glimepiride by pharmacodynamic synergism. Minor/Significance Unknown.
  
  vanadium increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

• verapamil

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

• voriconazole

  Monitor Closely (1)voriconazole increases levels of glimepiride by decreasing metabolism. Use Caution/Monitor.Minor (1)voriconazole will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• warfarin

  Monitor Closely (1)glimepiride, warfarin. Either increases effects of the other by receptor binding competition. Use Caution/Monitor. Monitor for decreased vitamin K antagonist effects (eg, decreased INR, thrombosis) when combined with metformin. Additionally, consider increased monitoring for hypoglycemia with this combination. Competitive inhibition of CYP2C9-mediated metabolism may also contribute to mechanism.

• willow bark

  Minor (1)willow bark increases effects of glimepiride by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• xipamide

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

• zavegepant intranasal

  Serious - Use Alternative (1)pioglitazone will increase the level or effect of zavegepant intranasal by Other (see comment). Avoid or Use Alternate Drug. NTCP inhibitors may result in a significant increase in systemic exposure of zavegepant (a NTCP substrate).

• ziprasidone

  Monitor Closely (2)ziprasidone, glimepiride. 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.