glimepiride/pioglitazone (Rx)

Brand and Other Names:Duetact
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

pioglitazone/glimepiride

tablet

  • 30mg/2mg
  • 30mg/4mg

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

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Interactions

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              • 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.

              • gemfibrozil

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

              • 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.

              • 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.

              • tucatinib

                pioglitazone will increase the level or effect of tucatinib by Other (see comment). Avoid or Use Alternate Drug. Coadministration of tucatinib (a CYP2C8 substrate) with a strong or moderate CYP2C8 inhibitors increases tucatinib plasma concentrations and risk of toxicities.

              Monitor Closely (198)

              • 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.

              • atorvastatin

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

              • 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. .

              • 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.

              • 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.

              • 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.

              • 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

                lixisenatide, 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.

              • lopinavir

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

              • lornoxicam

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

              • 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.

                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.

              • mecasermin

                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

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

              • 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

              • 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.

              • 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.

              • opuntia ficus indica

                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.

              • 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 products may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating somapacitan. .

              • somapacitan

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

              • 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.

              • 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.

              • 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).

              • 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.

              • modafinil

                modafinil will decrease 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.

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              Adverse Effects

              >10%

              Peripheral edema (6-12%)

              Upper respiratory tract infection (12-15%)

              Weight gain (9-13%)

              Hypoglycemia (13-16%)

              1-10%

              Anemia (<2%)

              Limb pain (4-5%)

              Urinary tract infection (6-7%)

              Headache (4-7%)

              Diarrhea (4-6%)

              Nausea (4-5%)

              Postmarketing Reports

              Thrombocytopenia and thrombocytopenic purpura

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              Warnings

              Black Box Warnings

              Thiazolidinediones (eg, pioglitazone) can cause or exacerbate congestive heart failure in some patients

              After initiation and dose increases, observe patients carefully for signs and symptoms of heart failure (including excessive, rapid weight gain; dyspnea; and/or edema)

              If these signs or symptoms develop, the heart failure should be managed according to the current standards of care

              Discontinuation or dose reduction of thiazolidinedione must be considered

              Thiazolidinediones not recommended with symptomatic heart failure; initiation in patients with established NYHA class III or IV heart failure is contraindicated

              Contraindications

              Hypersensitivity

              Diabetic ketoacidosis with of without coma

              Active liver disease, increased serum transaminase levels

              Not recommended in heart failure NYHA III-IV patients

              Cautions

              Increased risk of cardiovascular mortality

              Edema; thiazolidinediones, which are peroxisome proliferator-activated receptor (PPAR) gamma agonists, can cause dose-related fluid retention, particularly when used in combination with insulin

              Hemolytic anemia may occur with glucose 6-phosphate dehydrogenase (G6PD) deficiency when treated with sulfonylurea agents

              Fluid retention may occur and can exacerbate or lead to congestive heart failure; combination use with insulin and use in congestive heart failure NYHA Class I and II may increase risk; monitor patients for signs and symptoms

              Hypoglycemia may be severe. when insulin or an insulin secretagogue is used with pioglitazone, a lower insulin dose or insulin secretagogue dose may be needed to reduce risk of hypoglycemia

              Postmarketing reports for glimepiride include anaphylaxis, angioedema, and Stevens-Johnson syndrome; promptly discontinue glimepiride, assess for other causes, institute appropriate monitoring and treatment, and initiate alternative treatment for diabetes

              Postmarketing reports of hepatic failure, sometimes fatal; causality cannot be excluded; if liver injury detected, promptly interrupt therapy and assess patient for probable cause, then treat cause if possible, to resolution or stabilization; do not restart therapy if liver injury confirmed and no alternate etiology can be found

              Dose-related edema may occur

              Increased incidence of bone fracture reported

              Macular edema reported; recommend regular eye exams in all patients with diabetes according to current standards of care with prompt evaluation for acute visual changes

              No clinical studies establishing conclusive evidence of macrovascular risk reduction with glimepiride/pioglitazone or any other antidiabetic drug exist

              Increase in weight gain possibly related to pioglitazone effects on fluid retention and fat accumulation

              Cancer risk

              • Bladder cancer
                • Pioglitazone may be linked to an increased risk of bladder cancer
                • Do not prescribe for patients with active bladder cancer
                • Consider benefit:risk ratio before prescribing in patients with a history of bladder cancer
                • Instruct patients to contact their physician if signs of bladder cancer observed after initiating therapy (eg, blood or red colored urine, new or worsening urinary urgency, pain on urination)
              • Prostate cancer
                • 7/22/2015: Compared with nonuse, pioglitazone use was associated with increased risk for prostate cancer (453.3 vs. 449.3 per 100,000 person-years) [JAMA 2015 July 21;314(3):265-277]
              • Pancreatic cancer
                • 7/22/2015: Compared with nonuse, pioglitazone use was associated with increased risk for pancreatic cancer (81.1 vs. 48.4 per 100,000 person-years) [JAMA 2015 July 21;314(3):265-277]

              See also individual monographs

              • Pioglitazone
              • Glimepiride
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              Pregnancy & Lactation

              Pregnancy

              Limited data in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage; there are clinical considerations related to fetal and neonatal adverse reactions and drug discontinuation if glimepiride is used during pregnancy; there are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy

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

              Neonates of women with gestational diabetes, who are treated with sulfonylureas during pregnancy, may be at increased risk for neonatal intensive care unit admission, and may develop respiratory distress, hypoglycemia, birth injury, and be large for gestational age; prolonged severe hypoglycemia, lasting 4-10 days, reported in neonates born to mothers receiving a sulfonylurea at time of delivery and has been reported with use of agents with a prolonged half-life; observe newborns for symptoms of hypoglycemia and respiratory distress and manage accordingly

              Due to reports of prolonged severe hypoglycemia in neonates born to mothers receiving a sulfonylurea at time of delivery, therapy should be discontinued at least two weeks before expected delivery

              Lactation

              There is no information regarding presence of pioglitazone or glimepiride in human milk, effects on breastfed infant, or on milk production; pioglitazone and glimepiride are present in rat milk; however, due to species-specific differences in lactation physiology, animal data may not reliably predict drug levels in human milk

              The developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from therapy or from underlying maternal condition

              Pregnancy Categories

              A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

              B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

              C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

              D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

              X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

              NA: Information not available.

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              Images

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              Patient Handout

              A Patient Handout is not currently available for this monograph.
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              Formulary

              FormularyPatient Discounts

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              The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
              2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
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              5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              NC NOT COVERED – Drugs that are not covered by the plan.
              Code Definition
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              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.