Pioglitazone

Oral
Type 2 diabetes mellitus
Adult: As an adjunct to diet and exercise to improve glycaemic control: Monotherapy or in combination with other antidiabetic agents: 15-30 mg once daily. May increase dose in 15 mg daily increments every 4-12 weeks, as needed. Max: 45 mg daily. Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).
Hepatic impairment: Contraindicated.

Special Populations: Patient taking gemfibrozil and other strong CYP2C8 inhibitors: Max: 15 mg daily.

May be taken with or without food.

History or current heart failure (NYHA stages I-IV); diabetic ketoacidosis, active or history of bladder cancer; uninvestigated macroscopic haematuria, hepatic impairment.

Patient with oedema, risk factors for CHF (e.g. previous MI, symptomatic coronary artery disease). Elderly. Pregnancy and lactation. Monitoring Parameters Monitor HbA_1c (at least twice yearly in patients with stable glycaemic control; quarterly in patients not meeting therapy goals or with changes in treatment); serum glucose; liver function (e.g. ALT, AST, alkaline phosphatase, total bilirubin) at baseline (for all patients) and periodically during therapy for patients with active or suspected liver disease; weight. Monitor for signs and symptoms of liver injury, fluid retention, heart failure, and bladder cancer.

Significant: Decreased Hb or haematocrit, hypoglycaemia (if combined with other antidiabetic agents or insulin), macular oedema with decreased visual acuity, weight gain; increased risk of bladder carcinoma, bone fracture (higher risk in women), and cardiac failure; fluid retention;, resumption of ovulation. Blood and lymphatic system disorders: Anaemia. Eye disorders: Visual disturbance. Gastrointestinal disorders: Flatulence. General disorders and administration site conditions: Oedema. Musculoskeletal and connective tissue disorders: Arthralgia. Nervous system disorders: Hypo-aesthesia, headache. Renal and urinary disorders: Haematuria. Reproductive system and breast disorders: Erectile dysfunction. Respiratory, thoracic and mediastinal disorders: Upper respiratory tract infection; dyspnoea, bronchitis.
Potentially Fatal: Very rarely, hepatic failure.

Increased serum concentration with strong CYP2C8 inhibitors (e.g. gemfibrozil). Decreased serum concentration with CYP2C8 inducers (e.g. rifampicin), and topiramate.

Pioglitazone, a thiazolidinedione, is a potent and highly selective agonist for the peroxisome proliferator activated receptor-γ (PPAR-γ). Activation of these receptors promotes the production of gene products involved in lipid and glucose metabolism. It also improves insulin response to target cells without increasing the pancreatic secretion of insulin.
Onset: Delayed.
Absorption: Rapidly absorbed. Bioavailability: >80%. Time to peak plasma concentration: Approx 2 hours; delayed with food.
Distribution: Apparent volume of distribution: 0.63 ± 0.41 L/kg. Plasma protein binding: >99%, mainly to albumin.
Metabolism: Extensively metabolised in the liver via hydroxylation and oxidation by CYP2C8 and CYP3A4 isoenzymes to active (e.g. M-III and M-IV) and inactive metabolites.
Excretion: Via urine (15-30%) and faeces, as metabolites. Elimination half-life: Pioglitazone: 3-7 hours; M-III and M-IV metabolites: 16-24 hours.

Oral: Store between 20-25°C. Protect from light, moisture, and humidity.

Antidiabetic Agents

A10BG03 - pioglitazone ; Belongs to the class of thiazolidinediones. Used in the treatment of diabetes.