Pioglitazone Hydrochloride (9 brand names, 2 dosage forms, 1 route)
Available dosage forms: TABLET, TABLET, EXTENDED RELEASE.
Routes of administration: ORAL.
Brand Names
- ACTOPLUS MET
- ACTOPLUS MET XR
- ACTOS
- DUETACT
- OSENI
- PIOGLITAZONE
- PIOGLITAZONE HYDROCHLORIDE
- PIOGLITAZONE HYDROCHLORIDE AND GLIMEPIRIDE
- PIOGLITAZONE HYDROCHLORIDE AND METFORMIN HYDROCHLORIDE
Boxed Warning
Thiazolidinediones, including Pioglitazone Tablets, cause or exacerbate congestive heart failure in some patients [see Warnings and Precautions (5.1)]. After initiation of Pioglitazone Tablets, and after dose increases, monitor patients carefully for signs and symptoms of heart failure (e.g., excessive, rapid weight gain, dyspnea, and/or edema). If heart failure develops, it should be managed according to current standards of care and discontinuation or dose reduction of Pioglitazone Tabletsmust be considered. Pioglitazone Tablets is not recommended in patients with symptomatic heart failure. Initiation of pioglitazone in patients with established New York Heart Association (NYHA) Class III or IV heart failure is contraindicated [see Contraindications (4) and Warnings and Precautions (5.1)].
Indications and Usage
Monotherapy and Combination Therapy Pioglitazone Tablets is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus in multiple clinical settings [see Clinical Studies (14)]. Important Limitations of Use Pioglitazone Tablets exerts its antihyperglycemic effect only in the presence of endogenous insulin. Pioglitazone Tablets should not be used to treat type 1 diabetes or diabetic ketoacidosis, as it would not be effective in these settings. Use caution in patients with liver disease [see Warnings and Precautions (5.3)].
Contraindications
Initiation in patients with established NYHA Class III or IV heart failure [see Boxed Warning]. Use in patients with known hypersensitivity to pioglitazone or any other component of Pioglitazone Tablets.
Adverse Reactions
The following serious adverse reactions are discussed elsewhere in the labeling: Congestive heart failure [see Boxed Warning and Warnings and Precautions (5.1) ] Edema [see Warnings and Precautions (5.5) ] Fractures [see Warnings and Precautions (5.6) ]
Mechanism of Action
Pioglitazone is a thiazolidinedione that depends on the presence of insulin for its mechanism of action. Pioglitazone decreases insulin resistance in the periphery and in the liver resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output. Pioglitazone is not an insulin secretagogue. Pioglitazone is an agonist for peroxisome proliferator-activated receptor-gamma (PPARγ). PPAR receptors are found in tissues, important for insulin action such as adipose tissue, skeletal muscle, and liver. Activation of PPARγ nuclear receptors modulates the transcription of a number of insulin responsive genes involved in the control of glucose and lipid metabolism. In animal models of diabetes, pioglitazone reduces the hyperglycemia, hyperinsulinemia, and hypertriglyceridemia characteristic of insulin-resistant states such as type 2 diabetes. The metabolic changes produced by pioglitazone result in increased responsiveness of insulin- dependent tissues and are observed in numerous animal models of insulin resistance. Because pioglitazone enhances the effects of circulating insulin (by decreasing insulin resistance), it does not lower blood glucose in animal models that lack endogenous insulin.
Overdosage
During controlled clinical trials, one case of overdose with pioglitazone was reported. A male patient took 120 mg per day for four days, then 180 mg per day for seven days. The patient denied any clinical symptoms during this period. In the event of overdosage, appropriate supportive treatment should be initiated according to the patient’s clinical signs and symptoms.