PIOGLITE Tablet

- As an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes (non-insulin-dependent diabetes mellitus, NIDDM).

- PIOGLITE can also be taken alone as a monotherapy, or it can be used in combination with a sulphonylurea, metformin, or insulin when diet and exercise plus the single agent does not result in adequate glycemic control.

DOSAGE AND ADMINISTRATION

PIOGLITE tablets are taken once daily with or without meals and should be taken about the same time every day. However, skipping meals while taking this medicine is not advised. This can cause hypoglycemia.

- Monotherapy: PIOGLITE may be initiated at 15mg or 30mg once daily, increasing after 4 weeks to 45mg once daily, if greater therapeutic effect is needed.

- Combination therapy: PIOGLITE in combination with sulphonylureas, insulin or metformin. If there is a particular risk of hypoglycemia, pioglitazone can be introduced at a dose of 15mg once daily.

- Maximum recommended dose: The dose of PIOGLITE should not exceed 45mg once daily, since doses higher than 45mg once daily have not been studied.

- Hepatic impaired patients: The intrinsic clearance of pioglitazone may be reduced in patients with hepatic disease. Dosage should start at 15mg once daily and be increased cautiously.

Dosage may be adjusted according to age and symptoms.

- Patients with known hypersensitivity to thiazolidinediones or any component of this product.

- Upper respiratory tract infections, headache, sinusitis, myalgia, tooth disorder, diabetes mellitus aggravated, pharyngitis.

- There was also a tendency to modest weight gain. Some people may also experience anaemia and fluid retention. These side effects do not happen in all people.

- There was an increase in the occurrence of edema in the patients treated with pioglitazone and insulin compared to insulin alone.

- Pioglitazone plus insulin developed dyspnea at some point during therapy.

1) Ketoconazole: Ketoconazole inhibited up to 85% of hepatic pioglitazone metabolism in vitro at a concentration equal molar to pioglitazone. Pending on the availability of additional data, patients receiving ketoconazole concomitantly with pioglitazone should be evaluated more frequently with respect to glycemic control.

2) Oral contraceptives: 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. Therefore, additional caution regarding contraception should be exercised in patients receiving pioglitazone and an oral contraceptive.

- Pioglitazone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

- 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 woman.

Congestive Heart Failure:

- Thiazolidinediones cause or exacerbate congestive heart failure in some patients. After initiation of pioglitazone and after dose increases, the patient should be observed carefully for signs and symptoms of heart failure (including excessive, rapid weight gain, dyspnea and/or edema). If these signs and symptoms develop, the heart failure should be managed according to the current standard of care. Furthermore, discontinuation or dose reduction of drug must be considered.

- Pioglitazone is not recommended in patients with symptomatic heart failure. Initiation of this drug in patients with established NYHA classⅢorⅣheart failure is contraindicated.

- General: Pioglitazone exerts its antihyperglycemic effect only in the presence of insulin. Therefore, pioglitazone should not be used in patients with typeⅠdiabetes or for the treatment of diabetic ketoacidosis.

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

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

- Hematologic: Pioglitazone may cause decreases in hemoglobin and hematocrit causing anemia. Hemoglobin monitoring is recommended if patients exhibit any signs and symptoms of anemia.

- Ovulation: Therapy with pioglitazone, like other thiazolidinediones, may result in ovulation in some pre-menopausal women. As a result, these patients may be at an increased risk for pregnancy while taking pioglitazone. Thus, adequate contraception in pre-menopausal women should be recommended.

- Hepatic effects: Therapy with pioglitazone should not be initiated if the patient exhibits clinical evidence of active liver disease or increased serum transaminase levels (ALT greater than 2.5 times the upper limit of normal) at start of therapy. Liver enzyme monitoring is recommended in all patients prior to initiation of therapy with pioglitazone and periodically thereafter.

- Pediatrics: Since data is unavailable for pediatric patients, use of pioglitazone is not recommended.

- 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.

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. Unlike sulfonylureas, pioglitazone is not an insulin secretagogue. Pioglitazone is a potent and highly selective agonist for peroxisome proliferator-activated receptor-gamma (PPARɤ). PPAR receptors are found in tissues important for insulin action such as adipose tissue, skeletal muscle, and liver. Activation of PPARɤ nuclear receptors modulated the transcription of a number of insulin responsive genes involved in the control of glucose and lipid metabolism.