PPAR

PPAR

pioglitazone

Manufacturer:

Medley Pharma

Distributor:

Bell-Kenz Pharma

Marketer:

Ambica
Full Prescribing Info
Contents
Pioglitazone hydrochloride.
Description
Each uncoated tablet contains: Pioglitazone Hydrochloride Equivalent to Pioglitazone 30 mg.
Action
Pharmacology: Pharmacodynamics: Pioglitazone is a thiazolidinedione antidiabetic agent 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 a potent and highly selective 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.
Pharmacokinetics: Following oral administration, in the fasting state, Pioglitazone is first measurable in serum within 30 minutes, with peak concentrations observed within 2 hours. Food slightly delays the time to peak serum concentration to 3 to 4 hours, but does not alter the extent of absorption. Pioglitazone is extensively protein bound (>99%) in human serum, principally to serum albumin. Pioglitazone is extensively metabolized by hydroxylation and oxidation; the metabolites also partly convert to glucuronide or sulfate conjugates. 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 faeces.
Indications/Uses
Pioglitazone is indicated in the treatment of type 2 diabetes mellitus: As monotherapy: In patients (particularly overweight patients) inadequately controlled by diet and exercise for whom metformin is inappropriate because of contraindications or intolerance.
As dual oral therapy in combination with: Metformin, in patients (particularly overweight patients) with insufficient glycemic control despite maximal tolerated dose of monotherapy with metformin.
A sulphonylurea, only in patients who show intolerance to metformin or for whom metformin is contraindicated, with insufficient glycemic control despite maximal tolerated dose of monotherapy with a sulphonylurea.
As triple oral therapy in combination with: Metformin and a sulphonylurea, in patients (particularly overweight patients) with insufficient glycemic control despite dual oral therapy.
Dosage/Direction for Use
Pioglitazone tablets are taken orally once daily with or without food. Initially 15-30 mg once daily increased to 45 mg once daily according to response. The dose may be increased in increments up to 45 mg once daily or as prescribed by the physician.
Overdosage
In clinical studies, patients have taken Pioglitazone at higher than the recommended highest dose of 45 mg daily. The maximum reported dose of 120 mg/day for four days, then 180 mg/day for seven days was not associated with any symptoms.
Hypoglycaemia may occur in combination with sulphonylureas or insulin. Symptomatic and general supportive measures should be taken in case of overdose.
Contraindications
Pioglitazone (PPAR) is contraindicated in patients with: Hypersensitivity to the active substance or to any of the excipients; Hepatic impairment; Cardiac failure or history of cardiac failure (NYHA stages I to IV); Pregnancy; Breastfeeding.
Warnings
Cardiac failure and other cardiac effects: Pioglitazone, like other thiazolidinediones, can cause fluid retention when used alone or in combination with other antidiabetic agents, including insulin. Fluid retention may lead to or exacerbate heart failure. Patients should be observed for signs and symptoms of heart failure. Pioglitazone should be discontinued if any deterioration in cardiac status occurs.
MHRA (Medicines and Healthcare products Regulatory Agency)/CHM (Commission on Human Medicines) advice: Rosiglitazone and Pioglitazone cardiovascular safety (December 2007 and February 2008): Rosiglitazone and Pioglitazone should not be used in patients with heart failure or history of heart failure; incidence of heart failure is increased when rosiglitazone or Pioglitazone is combined with insulin.
Do not use Pioglitazone in patients with active bladder cancer.
Use Pioglitazone with caution in patients with a prior history of bladder cancer. The benefits of the blood sugar control with Pioglitazone should be weighed against the unknown risks for cancer recurrence.
Special Precautions
Hypoglycemia: Patients receiving Pioglitazone in combination with other oral hypoglycemic agents may be at risk for hypoglycemia, and a reduction in the dose of the concomitant agent may be necessary.
Cardiovascular: A small number of patients with a history of previously existing cardiac disease developed congestive heart failure when treated with Pioglitazone in combination with insulin. Pioglitazone is not indicated in patients with NYHA class III or IV cardiac status.
Edema: Pioglitazone should be used with caution in patients with edema.
Weight gain: Dose-related weight gain was seen with Pioglitazone and in combination with other hypoglycemic agents.
Ovulation: In premenopausal anovulatory patients with insulin resistance, treatment with thiazolidinediones, including Pioglitazone may result in resumption of ovulation. As a consequence of their improved insulin sensitivity, these patients may be at risk for pregnancy if adequate contraception is not used.
Hematologic: Patients treated with Pioglitazone may cause dose-dependent decreased in (2-4%) hemoglobin and hematocrit.
Hepatic effects: Rare reports of liver dysfunction. Monitor liver functions before treatment, and periodically thereafter; advice patient to seek immediate medical help if symptoms such as nausea, vomiting, abdominal pain, fatigue and dark urine develop; discontinue if jaundice occurs.
Use In Pregnancy & Lactation
Pregnancy: Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. Pioglitazone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nursing Mothers: Pioglitazone is secreted in the milk of lactating rats. It is not known whether Pioglitazone is secreted in human milk. Because many drugs are excreted in human milk, Pioglitazone should not be administered to a breastfeeding woman.
Adverse Reactions
Pioglitazone is well tolerated. The most common adverse reaction with Pioglitazone includes gastrointestinal disturbances, weight gain, edema, anemia, headache, visual disturbances, dizziness, arthralgia, hypoesthesia, haematuria, upper respiratory tract infection, and sinusitis.
Less commonly: Hypoglycemia, fatigue, insomnia, vertigo, sweating, altered blood lipids, and proteinuria.
Drug Interactions
In vivo drug-drug interaction studies have suggested that Pioglitazone may be a weak inducer of CYP 450 isoform 3A4 substrate. An enzyme inhibitor of CYP2C8 (such as Gemfibrozil) may be significantly increase the AUC of Pioglitazone and an enzyme inducer of CYP2C8 (such as Rifampin) may significantly decrease the AUC of Pioglitazone. Therefore, if an inhibitor or inducer of CYP2C8 is started or stopped during treatment with Pioglitazone, changes in diabetes treatment may be needed based on clinical response.
In vitro, Ketoconazole appears to significantly inhibit the metabolism of Pioglitazone. Patients receiving Ketoconazole concomitantly with Pioglitazone should be evaluated more frequently with respect to glycemic control.
Storage
Store at temperatures not exceeding 30°C.
MIMS Class
ATC Classification
A10BG03 - pioglitazone ; Belongs to the class of thiazolidinediones. Used in the treatment of diabetes.
Presentation/Packing
Tab (white, circular, flat, beveled edge, uncoated, with "medley" emblem debossed on one side and breakline on the other side) 30 mg x 30's.
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