【藥品性質提示】 根據 2019 AGS Beers Criteria，本藥品為【潛在不適當用藥 (PIM)】，不建議用於心衰竭之老年人。

Diabetes mellitus, type 2

Thiazolidinedione antidiabetic agent that lowers blood glucose by improving target cell response to insulin, without increasing pancreatic insulin secretion. It has a mechanism of action that is dependent on the presence of insulin for activity. Pioglitazone is a potent and selective agonist for peroxisome proliferator-activated receptor-gamma (PPARgamma). Activation of nuclear PPARgamma receptors influences the production of a number of gene products involved in glucose and lipid metabolism. PPARgamma is abundant in the cells within the renal collecting tubules; fluid retention results from stimulation by thiazolidinediones which increases sodium reabsorption.

Onset of action: Delayed
Peak effect: Glucose control: Several weeks
Distribution: Vd (apparent): 0.63 ± 0.41 L/kg
Protein binding: Pioglitazone >99% and active metabolites >98%; primarily to albumin
Metabolism: Hepatic (99%) via CYP2C8 and 3A4 to active and inactive metabolites; M-III and M-IV are major circulating active metabolites
Half-life elimination: Parent drug: 3 to 7 hours; M-III and M-IV metabolites: 16 to 24 hours
Time to peak: ~2 hours; delayed with food
Excretion: Urine (15% to 30%) and feces as metabolites

Hypersensitivity to pioglitazone or any component of the formulation; NYHA Class III/IV heart failure (initiation of therapy)

Information related to the use of pioglitazone in pregnant women is limited. Thiazolidinediones may cause ovulation in anovulatory premenopausal women, increasing the risk of unintended pregnancy.
In women with diabetes, maternal hyperglycemia can be associated with congenital malformations as well as adverse effects in the fetus, neonate, and the mother (ACOG 2005; ADA 2018c; Metzger 2007). To prevent adverse outcomes, prior to conception and throughout pregnancy maternal blood glucose and HbA1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ADA 2018c; Blumer 2013).
Agents other than pioglitazone are currently recommended to treat diabetes in pregnant women (ADA 2018c).

It is not known if pioglitazone is present in breast milk. Although breastfeeding is encouraged for all women, including those with diabetes, the safety of pioglitazone during breastfeeding has not yet been established (Metzger 2007). According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Cardiovascular: Edema (combination trials: ?27%)
Endocrine and metabolic: Hypoglycemia (combination trials: ?27%)
Respiratory: Upper respiratory tract infection (13%)

Initial: 15 to 30 mg once daily; patients with heart failure (NYHA Class I or II) should initiate therapy with 15 mg once daily. Note: Not recommended in patients with symptomatic heart failure
Dosage titration: Based on HbA1c, the dosage may be increased in 15 mg increments up to a maximum of 45 mg once daily; monitor closely during titration for adverse effects (eg, weight gain, edema, signs/symptoms of heart failure)
Dosage adjustment for hypoglycemia with combination therapy:
With an insulin secretagogue (eg, sulfonylurea): Decrease the insulin secretagogue dose.
With insulin: Decrease insulin dose by 10% to 25%; individualize further adjustments per glycemic response
Dosage adjustment with strong CYP2C8 inhibitors (eg, gemfibrozil): Maximum recommended dose: 15 mg once daily

No dosage adjustment necessary.

Hepatic impairment prior to initiation: No dosage adjustment necessary; use with caution if baseline liver tests are abnormal
Hepatic impairment during therapy: If liver injury is suspected (eg, fatigue, jaundice, dark urine): Interrupt therapy, measure serum liver tests, and investigate possible etiologies:
If an alternative etiology is not identified and ALT >3 x ULN: Do not reinitiate therapy.
If an alternative etiology is identified and ALT elevated (but <3 x ULN) or total bilirubin elevated (but <2 x ULN): May reinitiate with caution.