Rosiglitazone (maleate)

Indications & Dose:

Monotherapy:

Monotherapy as an adjunct to diet and exercise to improve glycaemic control in patients with type 2 diabetes mellitus.

Combination with metformin:Rosiglitazone is indicated for use in combination with metformin when diet, exercise, and Rosiglitazone alone or diet, exercise, and metformin alone do not result in adequate glycaemic control in patients with type 2 diabetes. For patients inadequately controlled with a maximum dose of metformin, Rosiglitazone should be added to, rather than substituted for, metformin.

Combination with sulfonylurea: Rosiglitazone is also indicated for use in combination with sulfonylurea when diet, exercise, and Rosiglitazone alone or diet, exercise, and sulfonylurea alone do not result in adequate glycaemic control in patients with type 2 diabetes. 

Combination with insulin: Rosiglitazone is also indicated for use in combination with insulin when diet, exercise, and Rosiglitazone alone or diet, exercise, and insulin alone do not result in adequate glycaemic control in patients with type 2 diabetes.

• BY MOUTH

Monotherapy: The usual starting dose of Rosiglitazone is 4 mg administered either as a single dose once daily or in divided doses twice daily. For patients who respond inadequately following 12 weeks of treatment as determined by reduction in FPG, the dose may be increased to 8 mg administered as a single dose once daily or in divided doses twice daily. Reductions in glycaemic parameters by dose and regimen are described under Pharmacodynamics and Clinical Effects. In clinical trials, the 4 mg twice daily regimen resulted in the greatest reduction in FPG and HbA1c.

Combination Therapy with Metformin: The usual starting dose of Rosiglitazone , in combination with metformin is 4 mg, administered as either a single dose once daily, or in divided doses twice daily. The dose of Rosiglitazone may be increased to 8 mg/ day following 12 weeks of therapy if there is insufficient reduction in FPG. Rosiglitazone may be administered as a single dose in the morning, or divided and administered in the morning and evening.

Combination Therapy with Sulfonylurea: The recommended starting dose of Rosiglitazone when used in combination with sulfonylurea is 4 mg administered as either a single dose once daily or in divided doses twice daily. Doses of Rosiglitazone greater than 4 mg daily in combination with sulfonylurea have not been studied. Because the incidence of hypoglycaemia using Rosiglitazone 4 mg daily in combination with sulfonylurea is low, patients who are inadequately controlled on 4 mg/ day of Rosiglitazone may benefit by cautious adjustment of the dose to 8 mg/day. The dose of Rosiglitazone may be increased 8 to 12 weeks after initiation of therapy if there is insufficient reduction in FPG. Rosiglitazone may be administered as a single daily dose in the morning, or divided and administered in the morning and evening. The dose of sulfonylurea may require lowering to optimise therapy.

Combination Therapy with Insulin: For patients stabilised on insulin, the insulin dose should be continued upon initiation of therapy with Rosiglitazone . Rosiglitazone should be dosed at 4 mg as the total daily dose, administered either once daily or in two divided doses. It is recommended that the insulin dose be decreased by 10% to 25% if the patient reports hypoglycaemia or if FPG concentrations decrease to less than 100 mg/dL. Further adjustments should be individualised based on glucose-lowering response.

Periodic fasting blood glucose measurements should be performed to monitor therapeutic response prior to up-titrating dose.

Note:

Rosiglitazone may be taken with or without food. No dosage adjustments are required for the elderly. No dosage adjustment is necessary when Rosiglitazone is used as monotherapy in patients with renal impairment. Since metformin is contraindicated in such patients, concomitant administration of metformin and Rosiglitazone is also contraindicated in patients with renal impairment. Therapy with Rosiglitazone should not be initiated if the patient exhibits clinical evidence of active liver disease or increased serum transaminase levels (ALT > 2.5 times the upper limit of normal at start of therapy.

There are no data on the use of Rosiglitazone in patients under 18 years of age; therefore, use of Rosiglitazone in paediatric patients is not recommended. 

Contraindications:

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

Side Effects:

Cautions:

Precautions:

Interaction:

Warnings:

Adverse Effects:

Lactations:

Pregnancy:

Pregnancy Category C: There was no effect on implantation or the embryo with rosiglitazone treatment during early pregnancy in rats, but treatment during mid-late gestation was associated with foetal death and growth retardation in both rats and rabbits. Teratogenicity was not observed at doses up to 3 mg/kg in rats and 100 mg/kg in rabbits (approximately 20 and 75 times human AUC at the maximum recommended human daily dose, respectively). Rosiglitazone caused placental pathology in rats (3 mg/kg/day). Treatment of rats during gestation through lactation reduced litter size, neonatal viability and postnatal growth, with growth retardation reversible after puberty. For effects on the placenta, embryo/foetus and offspring, the noeffect dose was 0.2 mg/kg/day in rats and 15 mg/ kg/day in rabbits. These no-effect levels are approximately 4 times human AUC at the maximum recommended human daily dose.

There are no adequate and well-controlled studies in pregnant women. Rosiglitazone should not be used during pregnancy unless the potential benefit outweighs the potential risk to the foetus.

Because current information strongly suggests that abnormal blood glucose levels during pregnancy are associated with a higher incidence of congenital anomalies as well as increased neonatal morbidity and mortality, most experts recommend that insulin be used during pregnancy to maintain blood glucose levels as close to normal as possible.

Labour and Delivery: The effect of rosiglitazone on labour and delivery in humans is not known.

Nursing Mothers: Drug related material was detected in milk from lactating rats. It is not known whether Rosiglitazone is excreted in human milk. Because many drugs are excreted in human milk, Rosiglitazone should not be administered to a nursing woman.

Special Precautions:

Counselling:

Side Effects Or Adverse Reactions:

Patients receiving rosiglitazone in combination with insulin or oral hypoglycaemic agents may be at risk for hypoglycaemic, and a reduction in the dose of the concomitant agent may be necessary There were a small number of patients treated with Rosiglitazone who had adverse experiences of anaemia, oedema (dose-related) and hypercholesterolaemia. Overall, these events were generally mild to moderate in severity and usually did not require discontinuation of treatment with Rosiglitazone.

In clinical trials, an increased incidence of heart failure has been observed when Rosiglitazone is used in combination with insulin compared to insulin alone. Patients who experienced heart failure were on average older, had a longer duration of diabetes, and were mostly on the higher 8 mg daily dose of Rosiglitazone .

Dose related weight gain was seen with Rosiglitazone alone and in combination with other hypoglycaemic agents. The mechanism of weight gain is unclear but probably involves a combination of fluid retention and fat accumulation.

Postmarketing reports of CHF and pulmonary oedema have been received rarely. It is known that the risk of developing heart failure is increased substantially in diabetic subjects compared to nondiabetic subjects.

Patient And Carer Advice: