alogliptin/pioglitazone (Rx)

Brand and Other Names:Oseni
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Dosing & Uses

AdultPediatric

Dosing Forms & Strengths

alogliptin/pioglitazone

tablet

  • 12.5mg/15mg
  • 12.5mg/30mg
  • 12.5mg/45mg
  • 25mg/15mg
  • 25mg/30mg
  • 25mg/45mg

Diabetes Mellitus Type 2

Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus

Starting dose based on patient’s current regimen

Dosage Modifications

Limit initial dose of pioglitazone to 15 mg/day with NYHA Class 1 or II heart failure

Coadministration with strong CYP2C8 inhibitors (eg, gemfibrozil): Do not exceed 15 mg/day pioglitazone

Renal impairment

  • Moderate (CrCl >30 to <60 mL/min): Not to exceed 12.5 mg/day alogliptin
  • Severe (CrCl <30 mL/min or ESRD): Not recommended; coadministration of pioglitazone and alogliptin 6.25 mg qDay may be considered

Dosing Considerations

Assess renal function before initiating alogliptin and periodically thereafter

Safety and efficacy not established

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Interactions

Interaction Checker

and alogliptin/pioglitazone

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              Serious - Use Alternative (6)

              • 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.

              • gemfibrozil

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

              • pacritinib

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

              • 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 (100)

              • albiglutide

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

              • 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.

              • 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.

              • atogepant

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

              • atorvastatin

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

              • axitinib

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

              • benazepril

                alogliptin increases toxicity of benazepril by unspecified interaction mechanism. Use Caution/Monitor. May increase risk of angioedema.

              • 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.

              • bitter melon

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

              • 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.

              • captopril

                alogliptin increases toxicity of captopril by Mechanism: unspecified interaction mechanism. Use Caution/Monitor. Increased risk of advers/toxic effects, specifically increased risk of angioedema.

              • carbamazepine

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

              • chlorpropamide

                alogliptin, chlorpropamide. 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 .

              • cholic acid

                pioglitazone increases toxicity of cholic acid by decreasing elimination. Modify Therapy/Monitor Closely. Avoid concomitant use of inhibitors of the bile salt efflux pump (BSEP). May exacerbate accumulation of conjugated bile salts in the liver and result in clinical symptoms. If concomitant use is necessary, monitor serum transaminases and bilirubin.

              • cimetidine

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

              • cinnamon

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

              • 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.

              • clarithromycin

                clarithromycin will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 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.

              • 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.

              • diltiazem

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

              • dulaglutide

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

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

              • erythromycin base

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

              • glimepiride

                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 .

              • 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.

              • 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 suspension

                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.

              • 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.

              • fluvastatin

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

              • gemifloxacin

                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

              • glipizide

                alogliptin, glipizide. 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 .

              • glyburide

                alogliptin, glyburide. 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 .

              • 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.

              • 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.

                alogliptin, 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.

                alogliptin, 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.

                alogliptin, 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

                alogliptin, 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).

                alogliptin, 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).

                alogliptin, 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).

                alogliptin, 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.

                alogliptin, 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

                alogliptin, 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).

                alogliptin, 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

                alogliptin, 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

                alogliptin, 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

                alogliptin, 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.

              • lonapegsomatropin

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

              • ketoconazole

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

              • ketotifen, ophthalmic

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

              • 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 pioglitazone by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.

              • levoketoconazole

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

              • linagliptin

                pioglitazone will increase the level or effect of linagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Use of alternative treatments is strongly recommended when linagliptin is to be administered with a CYP3A4 inducer

              • 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.

              • lonapegsomatropin

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

              • 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.

              • marijuana

                marijuana decreases effects of pioglitazone by pharmacodynamic antagonism. Use Caution/Monitor.

              • mavacamten

                pioglitazone will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

              • mecasermin

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

              • mifepristone

                mifepristone will increase the level or effect of pioglitazone by Other (see comment). Use Caution/Monitor. Inhibits CYP2C8/2C9; use smallest recommended doses for substrates and monitor

              • mipomersen

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

              • 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.

              • nateglinide

                alogliptin, nateglinide. 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 .

              • nefazodone

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

              • ofloxacin

                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.

              • opuntia ficus indica

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

              • paclitaxel

                pioglitazone will increase the level or effect of paclitaxel by Other (see comment). Use Caution/Monitor. Paclitaxel levels/toxicity may increase when coadministered with CYP2C8 inhibitors

              • 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.

              • pitavastatin

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

              • ponatinib

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

              • pravastatin

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

              • 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.

              • repaglinide

                alogliptin, repaglinide. 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 .

              • rifabutin

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

              • rifampin

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

              • risperidone

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

              • rosuvastatin

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

              • sacubitril/valsartan

                pioglitazone will increase the level or effect of sacubitril/valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

              • 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.

              • shark cartilage

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

                somapacitan decreases effects of alogliptin 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.

              • tolazamide

                alogliptin, tolazamide. 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 .

              • stiripentol

                stiripentol will increase the level or effect of pioglitazone by Other (see comment). Modify Therapy/Monitor Closely. Stiripentol is a CYP2C8 inhibitor. Consider dosage reduction for CYP2C8 substrates if adverse effects are experienced when coadministered.

              • sulfamethoxypyridazine

                sulfamethoxypyridazine increases effects of pioglitazone by unspecified interaction 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.

              • 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.

              • tipranavir

                tipranavir, pioglitazone. Other (see comment). Use Caution/Monitor. Comment: Tipranavir's effect on oral hypoglycemics via hepatic CYP2C9 unknown; carefully monitor blood glucose.

              • tolbutamide

                alogliptin, tolbutamide. 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 .

              • 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.

              Minor (116)

              • agrimony

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

              • American ginseng

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

              • amitriptyline

                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 pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

              • anamu

                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.

              • armodafinil

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

              • artemether/lumefantrine

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

              • atazanavir

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

              • bendroflumethiazide

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

              • bosentan

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

              • budesonide

                budesonide 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.

              • chlorothiazide

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

              • chlorthalidone

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

              • chromium

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

              • clomipramine

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

              • clonidine

                clonidine decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

                clonidine, pioglitazone. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

              • conivaptan

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

              • cornsilk

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

              • cortisone

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

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

              • cyclopenthiazide

                cyclopenthiazide decreases effects of pioglitazone 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.

              • danazol

                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.

              • darunavir

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

              • dasatinib

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

              • deferasirox

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

              • deflazacort

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

              • desipramine

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

              • devil's claw

                devil's claw increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

              • dexamethasone

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

                dexamethasone decreases effects of pioglitazone 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.

              • doxepin

                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.

              • 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.

              • fluconazole

                fluconazole will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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.

              • fo-ti

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

              • forskolin

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

              • fosamprenavir

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

              • fosphenytoin

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

              • 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, pioglitazone. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

              • gymnema

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

              • horse chestnut seed

                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.

              • hydrocortisone

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

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

              • imipramine

                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.

              • indinavir

                indinavir will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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).

              • lofepramine

                lofepramine increases effects of pioglitazone 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 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).

              • maprotiline

                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.

              • mesterolone

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

              • mestranol

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

              • methyclothiazide

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

              • methylprednisolone

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

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

              • methyltestosterone

                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.

              • metronidazole

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

              • miconazole vaginal

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

              • nelfinavir

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

              • nettle

                nettle increases effects of 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.

              • ofloxacin

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

              • oxandrolone

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

              • oxcarbazepine

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

              • oxymetholone

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

              • pegvisomant

                pegvisomant increases effects of pioglitazone 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.

              • phenobarbital

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

              • phenytoin

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

              • posaconazole

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

              • potassium acid phosphate

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

              • potassium chloride

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

              • potassium citrate

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

              • prednisolone

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

              • prednisone

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

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

              • primidone

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

              • protriptyline

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

              • secobarbital

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

              • stevia

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

              • testosterone

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

              • testosterone buccal system

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

              • testosterone topical

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

              • tongkat ali

                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 pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

              • trimipramine

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

              • vanadium

                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.

              • voriconazole

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

              • zafirlukast

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

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              Adverse Effects

              >10% (pioglitazone)

              Worsening CHF (9.9-13.4%)

              Edema when used in combination with sulfonylurea or insulin

              1-10%

              Hypoglycemia (0.8-4.5%)

              Nasopharyngitis (4%)

              Back pain (4.2%)

              Upper respiratory tract infection (4.1%)

              <1% (alogliptin)

              Hypersensitivity (0.6%)

              Pancreatitis (0.2%)

              Postmarketing reports (alogliptin)

              Severe and disabling arthralgia

              Anaphylaxis, angioedema, rash, urticaria

              Severe cutaneous adverse reactions, including Stevens-Johnson syndrome

              Hepatic enzyme elevations

              Fulminant hepatic failure

              Bullous pemphigoid

              Rhabdomyolysis

              Constipation

              Diarrhea

              Nausea

              Ileus

              Tubulointerstitial nephritis

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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 to alogliptin or pioglitazone, including anaphylaxis, angioedema, or severe cutaneous adverse reactions including Stevens-Johnson syndrome

              Do not initiate pioglitazone in patients with NYHA Class III or IV heart failure (see Black Box Warnings)

              Cautions

              Pioglitazone can cause dose-related fluid retention that may lead to or exacerbate CHF (see Black Box Warnings)

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

              Pancreatitis reported

              Caution with sensitivity to another DPP-4 inhibitor; discontinue if serious hypersensitivity reaction suspected (see Contraindications)

              Fatal and nonfatal hepatic failure reported; type 2 DM is also known to cause fatty liver disease and liver enzyme elevation; monitor carefully and interrupt alogliptin/pioglitazone treatment if LFTs elevated, do not restart alogliptin/pioglitazone without another explanation for the liver test abnormalities

              Insulin secretagogues (eg, sulfonylureas) are known to cause hypoglycemia; therefore, a lower dose may be needed to minimize hypoglycemia risk

              Increased fracture risk in females

              Macular edema reported with thiazolidinediones (eg, pioglitazone)

              Discuss potential for unintended pregnancy with premenopausal women as therapy with pioglitazone, like other thiazolidinediones, may result in ovulation in some anovulatory women

              Severe and disabling arthralgia reported in patients taking DPP-4 inhibitors; consider as a possible cause for severe joint pain and discontinue drug if appropriate

              Congestive heart failure (CHF) risk

              • Also see Black Box Warnings regarding CHF risk of pioglitazone
              • The EXAMINE (Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care) trial enrolled 5,380 patients with type 2 diabetes and recent acute coronary syndrome
              • Hospitalization for CHF was observed in 106 (3.9%) patients treated with alogliptin and 89 (3.3%) patients treated with placebo; although the difference was not statistically significant (hazard ratio, 1.19), heart failure was not an end point of the study
              • Health care professionals should consider discontinuing medications containing alogliptin in patients who develop heart failure and monitor their diabetes control
              • Lancet. 2015 May 23;385(9982):2067-76

              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]
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              Pregnancy & Lactation

              Pregnancy

              Limited data in pregnant women are not sufficient to inform a drug-associated risk for major birth defects or miscarriage; 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

              Lactation

              There is no information regarding presence of pioglitazone or alogliptin in human milk, effects on breastfed infant, or effects on milk production; 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 treatment 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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              Pharmacology

              Mechanism of Action

              Alogliptin: Selective dipeptidyl peptidase-4 (DPP-4) inhibitor; slows inactivation of incretin hormones (eg, GLP-1, GIP), thereby reducing fasting and postprandial glucose concentrations in a glucose-dependent manner

              Pioglitazone: Thiazolidinedione; improves target cell response to insulin; decreases hepatic gluconeogenesis

              Absorption

              Bioavailability: ~100% (alogliptin)

              Duration: 24 hr (pioglitazone)

              Peak plasma time: 1-2 hr (alogliptin); 2-4 hr (pioglitazone)

              Distribution

              Protein bound: 20% (alogliptin); >99% (pioglitazone)

              Vd: 417 L (alogliptin); 0.63 L/kg (pioglitazone)

              Metabolism

              alogliptin

              • Does not undergo extensive metabolism and 60-71% of the dose is excreted unchanged in the urine
              • Active metabolite: N-demethylated (<1% of parent compound)
              • Inactive metabolite: N-acetylated alogliptin (<6% of parent compound)
              • Minor substrate of CYP3A4 and CYP2D6

              pioglitazone

              • Metabolized to active metabolites by hepatic CYP2C8 and CYP3A4
              • Metabolites: metabolite II (hydroxy derivative), metabolite III (keto derivative), metabolite IV (active hydroxy derivative) (active)

              Elimination

              alogliptin

              • Half-life: 21 hr
              • Renal clearance: 9.6 L/hr
              • Total body clearance: 14 L/hr
              • Excretion: 76% urine; 13% feces

              pioglitazone

              • Half-Life: 3-7 hr
              • Excretion: 15-30% urine
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              Administration

              Instructions

              May take with or without food

              Swallow whole, do not chew, split, or crush

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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.
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              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.