Pioglitazone is an oral antidiabetic agent belonging to the class of thiazolidinediones. Pioglitazone is used in the management of type 2 diabetes mellitus.

Pioglitazone decreases insulin resistance in the periphery and in the liver resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output.

Pioglitazone enhances cellular responsiveness to insulin, increases insulin-dependent glucose disposal, improves hepatic sensitivity to insulin and improves dysfunctional glucose homeostasis. In patients with type 2 diabetes, the decreased insulin resistance produced by Pioglitazone results in lower blood glucose concentrations, lower plasma insulin levels and lower HbA1c values.

 

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. Metabolites hydroxy derivative of Pioglitazone and keto derivative of Pioglitazone are pharmacologically active.

It is presumed that most of the oral dose is excreted into the bile either unchanged or as metabolites and eliminated in the feces. The mean serum half-life of Pioglitazone and total Pioglitazone ranges from 3 to 7 hours and 16 to 24 hours, respectively.

 

- PLIZONE is indicated for monotherapy to improve glycemic control in patients with non-insulin dependent diabetes mellitus (type 2 diabetes)

- PLIZONE is indicated as an adjunct to diet and exercise to improve glycemic control in patients with non-insulin dependent diabetes mellitus (type 2 diabetes).

- PLIZONE is also indicated for use in combination with a sulfonylurea, metformin or insulin when diet and exercise plus the single agent does not result in adequate glycemic control in patients with non-insulin dependent diabetes mellitus (type 2 diabetes).

Management of non-insulin dependent diabetes mellitus (type 2 diabetes ) should also include nutritional counseling, weight reduction as needed, and exercise to maintain the efficacy of drug therapy.

 

Pioglitazone is contraindicated in patients with known hypersensitivity to this product or any of its components.

 

-Pioglitazone exerts its antihyperglycemic effect only in the presence of insulin. Therefore, Pioglitazone should not be used in patients with type 1 diabetes for the treatment of diabetic ketoacidosis.

-Patients receiving Pioglitazone in combination with insulin or oral hypoglycemia agents may be at risk for hypoglycemia, and reduction in the dose of the concomitant agent may be necessary.

-Pioglitazone may cause decreases in haemoglobin and haematocrit.

-Pioglitazone should be used with caution in patients with edema.

-It is recommended that patients treated with Pioglitazone undergo periodic monitoring of liver enzymes.

-Safety and effectiveness of  Pioglitazone in pediatric patients have not been established.

 

Pioglitazone should be used during pregnancy only if clearly needed.

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 breast-feeding women.

 

Administration of another thiazolidinedione with an oral contraceptive containing ethinyl estradiol and norethindrone reduced the plasma concentrations of both hormones by approximately 30%, which could result in loss of contraception. Additional caution regarding contraception should be exercised in patients receiving Pioglitazone and an oral contraceptive.

Coadministration of Pioglitazone does not alter pharmacokinetics of glipizide, digoxin, metformin or warfarin.

Until addition data are available, Patients receiving ketoconazole concomitantly with Pioglitazone should be evaluated more frequently with respect to glycemic control.

 

Headache, upper respiratory tract infection, myalgia, sinusitis and pharyngitis. Similar types of adverse events have been reported when Pioglitazone was used in combination with sulfonylureas, metformin or insulin (mild to moderate hypoglycemia) with the exception of an increase in the occurrence of edema.

Cases of anemia have been reported, although infrequently, in patients receiving Pioglitazone.

 

PLIZONE monotherapy in patients not adequately controlled with diet and exercise may be initiated at 15 mg or 30 mg once daily. For patients who respond inadequately to the initial dose of PLIZONE, the dose can be increased in increments up to 45 mg once daily. For patients not responding adequately to monotherapy, combination therapy should be considered.

Sulfonylureas: PLIZONE in combination with a  sulfonylurea may be initiated at 15 mg or 30 mg once daily. The current sulfonylurea dose can be continued upon initiated of PLIZONE therapy. If patients report hypoglycemia, the dose of the sulfonylurea should be decreased.

Metformin: PLIZONE in combination with metformin may be initiated at 15 mg or 30 mg once daily. The current metformin dose can be continued upon initiation of PLIZONE therapy. It is unlikely that the dose of metformin will require adjustment due to hypoglycemia during combination therapy with PLIZONE.

Insulin: PLIZONE in combination with insulin may be initiated at 15 mg or 30 mg once daily. The current insulin dose can be continued upon initiation of PLIZONE therapy. In patients receiving PLIZONE and insulin, the insulin dose can be decreased by 10% to 25% if the patient reports hypoglycemia or if plasma glucose concentrations decrease to less than 100 mg/dL. Further adjustments should be individualized based on glucose-lowering response.

Maximum Recommended Dose: The dose of Pioglitazone should not exceed 45 mg once daily since .

Dosage in renal insufficiency: Dose adjustment in patients with renal insufficiency is not recommended.

Dosage in hepatic insufficiency: Therapy with PLIZONE should not be initiated if the patient exhibits clinical evidence of active liver disease or increased serum transaminase levels at start of therapy. Liver enzyme monitoring is recommended in all patients prior to initiation of therapy with PLIZONE and periodically thereafter.

 

-PLIZONE 15 – Tablets: A pack of 30 tablets. Each tablet contains Pioglitazone (Hydrochloride) 15 mg.

-PLIZONE 30 – Tablets: A pack of 30 tablets. Each tablet contains Pioglitazone (Hydrochloride) 30 mg.

 

Store PLIZONE – Tablets at temperature between (15-30)°C. Protect from moisture.