Drug information of Pioglitazone
Pioglitazone is a thiazolidinedione antidiabetic. It works by lowering blood sugar by making the cells of the body more sensitive to the action of insulin .
Mechanism of effect
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..
Clinical studies demonstrate that pioglitazone improves insulin sensitivity in insulin-resistant patients. Pioglitazone enhances cellular responsiveness to insulin, increases insulin-dependent glucose disposal and improves hepatic sensitivity to insulin.
In patients with type 2 diabetes, the decreased insulin resistance produced by pioglitazone results in lower plasma glucose concentrations, lower plasma insulin concentrations and lower HbA1c values .
Absorption : Following oral administration of pioglitazone, Tmax of pioglitazone was within 2 hours. Food delays the Tmax to 3 to 4 hours, but does not alter the extent of absorption (AUC) .
Distribution : The mean apparent volume of distribution (Vd/F) of pioglitazone following single-dose administration is 0.63 ± 0.41 (mean ± SD) L/kg of body weight. Pioglitazone is extensively protein bound (> 99%) in human serum, principally to serum albumin. Pioglitazone also binds to other serum proteins, but with lower affinity. M-III and M-IV are also extensively bound (> 98%) to serum albumin .
Metabolism : Pioglitazone is extensively metabolized by hydroxylation and oxidation; the metabolites also partly convert to glucuronide or sulfate conjugates. Metabolites M-III and M-IV are the major circulating active metabolites in humans .
Excretion and Elimination : Following oral administration, approximately 15% to 30% of the pioglitazone dose is recovered in the urine. Renal elimination of pioglitazone is negligible, and the drug is excreted primarily as metabolites and their conjugates. It is presumed that most of the oral dose is excreted into the bile either unchanged or as metabolites and eliminated in the feces .
Usual Adult Dose for Diabetes Type 2
- Patients without congestive heart failure : Initial dose : 15 mg or 30 mg orally once a day
- Patients with congestive heart failure (New York Heart Association [NYHA] Class I or II) :
- Initial dose : 15 mg orally once a day
- Maintenance dose: 15 mg to 45 mg orally once a day based on glycemic response as determined by HbA1c
- Maximum dose : 45 mg orally once a day.
Drug contraindicationsActive liver disease , Type 1 diabetes , severe hypersensitivity reactions
InteractionsThyrotropin alfa , Ketoconazole , Clopidogrel , teriflunomide , Rosiglitazone , Mitiglinide , Baricitinib , Vorinostat , Omacetaxine , Methyclothiazide , Remdesivir , Cannabidiol , Alclometasone , flurandrenolide
Pioglitazone , like other thiazolidinediones, can cause dose related fluid retention when used alone or in combination with other antidiabetic medications and is most common when pioglitazone is used in combination with insulin . Fluid retention may lead to or exacerbate congestive heart failure.Patients receiving pioglitazone in combination with insulin or other antidiabetic medications (particularly insulin secretagogues such as sulfonylureas) may be at risk for hypoglycemia .
Measure liver tests promptly in patients who report symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice.edema was reported more frequently in patients treated with pioglitazone than in placebo-treated patients and is dose related .
Points of recommendation
Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you :
• if you are pregnant, planning to become pregnant, or are breast-feeding
• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement
• if you have allergies to medicines, foods, or other substances
• if you have a history of liver problems, abnormal liver function tests, heart problems (eg, congestive heart failure [CHF]), bladder cancer, or eye or vision problems (eg, macular edema)
• if you have swelling problems (edema)
Ask a Pharmacist