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Pioglitazone Hydrochloride


Pronunciation: PYE-oh-GLI-ta-zone HYE-droe-KLOR-ide
Class: Thiazolidinedione

Trade Names

- Tablet, oral 15 mg
- Tablet, oral 30 mg
- Tablet, oral 45 mg


Increases insulin sensitivity in muscle and adipose tissue, and inhibits hepatic gluconeogenesis.

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Rapid. T max is 2 h. Food slightly delays T max 3 to 4 h. Steady state is reached in 7 days.


Vd is 0.63 L/kg (single dose). Protein binding is extensive (more than 99%), mainly to albumin.


Extensively metabolized in the liver by hydroxylation and oxidation. Metabolites M-III (keto derivative) and M-IV (hydroxy derivative) are the major circulatory active metabolites in humans. The major isoforms involved include CYP2C8, CYP3A4, and CYP1A1.


15% to 30% excreted primarily as metabolites in urine. Excreted into bile (unchanged as metabolites) and then eliminated in the feces. Serum half-life is 3 to 7 h (pioglitazone) and 16 to 24 h (metabolites M-III and M-IV). Apparent Cl is 5 to 7 L/h.

Special Populations

Renal Function Impairment

The serum elimination half-life of pioglitazone, M-III, and M-IV remains unchanged in patients with moderate and severe renal impairment.

Hepatic Function Impairment

There is a 45% reduction in mean C max , but no change in AUC values.


AUC value is slightly higher (approximately 21%); terminal half-life is slightly longer (approximately 10 h).


Data are not available.


The mean C max and AUC are increased 20% to 60% in women.


Data are not available.

Indications and Usage

As an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes in multiple clinical settings.

Unlabeled Uses

Polycystic ovary syndrome; prevention of in-stent restenosis.


Established New York Heart Association (NYHA) class III or IV heart failure; hypersensitivity to any component of the product.

Dosage and Administration


PO Initially, 15 or 30 mg/day (start with 15 mg in patients with CHF [NYHA class I or II]); may titrate in increments of 15 mg daily (max, 45 mg daily).

Combination Therapy
Insulin secretagogues Adults

PO In combination with insulin secretagogues (eg, sulfonylurea); decrease insulin secretagogue dose if the patient reports hypoglycemia.

Insulin Adults

PO Decrease the insulin dose by 10% to 25% if the patient reports hypoglycemia. Individualize further adjustment based on glucose-lowering response.

Strong CYP2C8 inhibitors

PO Max recommended dose of pioglitazone is 15 mg when used with gemfibrozil or other strong CYP2C8 inhibitors.

General Advice

  • Should be taken once daily without regard to meals.


Store at 59° to 86°F. Protect from moisture and humidity.

Drug Interactions


Pioglitazone and atorvastatin serum concentrations may be decreased.

Contraceptives, hormonal

Oral contraceptives may decrease both hormone components about 30%, potentially reducing contraceptive effectiveness.

CYP2C8 enzyme inhibitors (eg, azole antifungal agents [eg, ketoconazole], fluvoxamine, gemfibrozil, trimethoprim)

Pioglitazone plasma levels may be elevated, increasing the pharmacologic effects and adverse reactions. A maximum dose of pioglitazone 15 mg daily is recommended when administered with gemfibrozil or other strong CYP2C8 inhibitors.

CYP2C8 inducers (eg, rifampin)

Pioglitazone plasma concentrations may be reduced, decreasing the efficacy. If a CYP2C8 inducer is started or stopped, changes in the pioglitazone dose may be needed. The maximum recommended daily dose of pioglitazone 45 mg should not be exceeded.


The digoxin AUC and C max may be increased. Because digoxin has a narrow therapeutic index, use with caution. Monitoring for clinical and laboratory evidence of digoxin toxicity is warranted.


Coadministration may increase the fexofenadine AUC and C max . The clinical importance is unknown.


Food slightly delays the T max but does not alter the extent of absorption. Pioglitazone may be taken without regard to meals.


Severe and persistent hypoglycemia may occur. If coadministration cannot be avoided, closely monitor blood glucose.

Insulin, sulfonylureas (eg, tolbutamide)

The risk of hypoglycemia may be increased. If hypoglycemia occurs, reduce the dose of insulin or sulfonylurea.


Plasma concentrations may be reduced by pioglitazone, decreasing the efficacy.


Concurrent use of pioglitazone and nifedipine ER may decrease nifedipine concentrations. The clinical importance is unknown.


The anticoagulant effect of warfarin may be increased or decreased. Monitor anticoagulant activity.

Adverse Reactions




Headache (9%).


Pharyngitis (5%); macular edema (postmarketing).


Hepatic failure (postmarketing).

Lab Tests

Decreased Hgb and Hct, elevated CPK levels.


Hypoglycemia, weight gain.


Bone fractures, myalgia (5%).


Upper respiratory tract infection (13%); sinusitis (6%).


Edema (27%); urinary bladder tumors.



Pioglitazone can cause or exacerbate CHF in some patients. Consider discontinuing or reducing the dose if symptoms of heart failure (including excessive, rapid weight gain, dyspnea, and/or edema) occur. Treatment of patients with symptomatic heart failure is not recommended. Initiation of pioglitazone in patients with established NYHA class III or IV heart failure is contraindicated.


After starting treatment or increasing the dose, carefully observe patients for signs and symptoms of heart failure (including excessive, rapid weight gain, dyspnea, and/or edema). Monitor liver enzymes (serum ALT, AST, alkaline phosphatase, total bilirubin) prior to the start of therapy.

Perform fasting blood glucose and hemoglobin A 1c (HbA 1c ) measurements periodically; regular eye exams by an ophthalmologist are recommended.


Category C . Most experts recommend that insulin be used during pregnancy to maintain blood glucose levels as close to normal as possible.




Safety and efficacy not established; use is not recommended.

Hepatic Function

Use with caution.

Bone fractures

Increased incidence of bone fractures noted in women but not men.


Use caution; can cause fluid retention.

Hepatic effects

Fatal and nonfatal hepatic failure has been reported.


May increase the risk of hypoglycemia when used in combination with insulin or oral hypoglycemic agents (particularly insulin secretagogues such as sulfonylureas); may need dose reduction of concomitant agents.

Macular edema

Has been reported.


May result in ovulation in premenopausal anovulatory women.

Urinary bladder tumors

Do not use in patients with active bladder cancer.



No symptoms were reported after ingestion of 120 to 180 mg daily for 11 days.

Patient Information

  • Advise patients to read the Medication Guide before starting therapy and with each refill.
  • Advise patients to take every day without regard to meals.
  • Educate patient, family, or caregiver regarding type 2 diabetes and its management.
  • Instruct patients that this drug is not a substitute for diet and exercise and to follow prescribed regimens.
  • Advise the patient that if a dose is missed on 1 day, the dose should not be doubled the next day.
  • Emphasize the importance of regular daily blood glucose monitoring and periodic HbA 1c tests.
  • Advise diabetic patients to carry medical identification (eg, card, bracelet).
  • Advise patients to report any of the following to health care provider immediately: abdominal pain, anorexia, dark urine, edema, fatigue, increase in weight, nausea, shortness of breath, vomiting, yellowing of the skin or eyes, other symptoms of CHF.
  • Review symptoms of hypoglycemia and hyperglycemia and action plans to undertake in the event either occurs. Instruct patients to report hypoglycemic or hyperglycemic episodes to health care provider.
  • Caution women that drug can cause resumption of ovulation in premenopausal anovulatory women with insulin resistance. Address adequate contraceptive measures for these women.
  • Advise patients to promptly report any sign of macroscopic hematuria or other symptoms, such as dysuria or urinary urgency, that develop or increase during treatment, because these may be due to bladder cancer.

Copyright © 2009 Wolters Kluwer Health.