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Author: Admin | 2025-04-28
Be related to plasma volume expansion. Rarely associated with clinically important hematologic manifestations. Isolated elevations in serum CK >10 times ULN noted rarely during clinical trials. Resolved in most patients without apparent sequelae despite continued therapy with the drug; any relationship to pioglitazone therapy unknown.Use of Fixed CombinationsWhen used in fixed combination with metformin hydrochloride or glimepiride, consider the cautions, precautions, and contraindications associated with the concomitant agent. Specific PopulationsPregnancyData are lacking on use of pioglitazone in pregnant women. No adverse developmental effects observed in animal reproduction studies; however, delayed postnatal development (attributed to decreased body weight), delayed parturition, and reduced embryofetal viability were observed. Blood glucose abnormalities during pregnancy are associated with increased incidence of congenital anomalies and neonatal morbidity and mortality. LactationDistributed into milk in rats; not known whether distributed into human milk. Weigh the benefits of breast-feeding against the potential risk of adverse effects on the breast-fed infant from pioglitazone. Pediatric UseSafety and efficacy not established in pediatric patients Geriatric UseNo substantial differences in safety and efficacy relative to younger adults. Hepatic ImpairmentInitiate with caution in patients with abnormal liver function test results. Interrupt pioglitazone therapy if ALT >3 times the ULN and investigate the cause of liver test abnormalities. (See Hepatic Effects under Cautions.)Common Adverse EffectsUpper respiratory tract infection, headache, sinusitis, myalgia, pharyngitis, edema.Drug InteractionsMetabolized principally by CYP2C8 and, to a lesser extent, by CYP3A4 and other isoenzymes (e.g., CYP1A1). Weak inducer of CYP3A4.Drugs Affecting Hepatic Microsomal EnzymesPotent CYP2C8 inhibitors: Increased pioglitazone AUC and half-life; do not exceed maximum pioglitazone dosage of 15 mg once daily.Dosage of Pioglitazone as Monotherapy or in Fixed Combination in Patients Receiving Potent CYP2C8 InhibitorsDrug or CombinationDosage in Combination with a Potent CYP2C8 InhibitorPioglitazoneMaximum dosage: pioglitazone 15 mg once dailyPioglitazone/glimepiride fixed combinationSwitch to therapy with the individual drug components administered separately because the minimum pioglitazone dose in the fixed-combination preparation exceeds 15 mgPioglitazone/immediate-release metformin hydrochloride fixed combinationMaximum dosage: pioglitazone 15 mg/metformin hydrochloride 850 mg once dailyCYP2C8 inducers: Decreased pioglitazone AUC. Initiation or discontinuance of a CYP2C8 inducer during pioglitazone therapy may necessitate changes in antidiabetic therapy; however, do not exceed maximum recommended pioglitazone dosage of 45 mg daily.Specific DrugsDrugInteractionCommentsAntidiabetic agentsAdditive effects; possible hypoglycemia May need to reduce dosage of other antidiabetic agents AtorvastatinDecreased plasma concentrations and AUC for atorvastatin and pioglitazone DigoxinPharmacokinetic interaction unlikely FexofenadinePharmacokinetic interaction unlikely GemfibrozilIncreased pioglitazone AUC and half-life Do not exceed maximum pioglitazone dosage of 15 mg once daily KetoconazoleIncreased serum concentrations and AUC for pioglitazone MidazolamDecreased midazolam AUC and peak plasma concentrations Nifedipine, extended-releaseDecreased peak plasma nifedipine concentrations and AUC Clinical importance unknownOral contraceptives, hormonal (ethinyl estradiol/norethindrone)Small decreases in peak plasma ethinyl estradiol concentrations and AUC Clinical importance unknownRanitidinePharmacokinetic interaction unlikely RifampinDecreased pioglitazone AUC May require change in antidiabetic therapy if rifampin initiated or discontinued during pioglitazone therapy, but do not exceed maximum pioglitazone dosage of 45 mg daily TheophyllinePharmacokinetic interaction unlikelyTopiramateReductions in exposure (AUC) of pioglitazone and active metabolites (see Metabolism under Pharmacokinetics) with concomitant administration Clinical relevance unknown; however, manufacturer recommends monitoring for adequate
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