Composition:

Aromet-1 Tablet: Each film-coated tablet contains Rosiglitazone Maleate INN equivalent to Rosiglitazone 1 mg and Metformin HCl BP 500 mg.

Aromet-2 Tablet: Each film-coated tablet contains Rosiglitazone Maleate INN equivalent to Rosiglitazone 2 mg and Metformin HCl BP 500 mg.

Pharmacology:

Aromet tablet is a combination of 2 antidiabetic agents, Rosiglitazone maleate & Metformin HCl with different mechanisms of action to improve glycemic control in patients with type 2 diabetes.

Rosiglitazone is a member of the thiazolidinedione class, which improves glycemic control by improving insulin sensitivity. Rosiglitazone is a highly selective and potent agonist of the peroxisome proliferator-activated receptor-gamma (PPAR ). PPAR nuclear receptors regulates the transcription of insulin-responsive genes involved in the control of glucose production, transport, and utilization. In addition, PPAR?-responsive genes also participate in the regulation of fatty acid metabolism.

Metformin HCl is a member of the biguanide class, which improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Metformin also decreases hepatic glucose production, decreases intestinal absorption of glucose, and increases peripheral glucose uptake and utilization.

Indications:

Aromet tablet is indicated as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes when treatment with dual Rosiglitazone and Metformin therapy is appropriate. Caloric restriction, weight loss, and exercise are essential for the proper treatment of the diabetic patient because they help improve insulin sensitivity. This is important not only in the primary treatment of type 2 diabetes but also in maintaining the efficacy of drug therapy.

Dosage and administration:

The dosage of Aromet tablet should be individualized on the basis of effectiveness and tolerability while not exceeding the maximum recommended daily dose of 8mg/2000 mg (Rosiglitazone/Metformin).

Aromet tablet in Drug-Naive Patients: The recommended starting dose of Aromet is 2 mg/500 mg once or twice daily. For patients with HbA1c >11% or FPG>270 mg/dL, a starting dose of 2 mg/500 mg twice daily may be considered. The dose of Aromet tablet may be increased by increment of 2 mg/500 mg per day to a maximum of 8 mg/2,000 mg per day in divided doses if patients are not adequately controlled after 4 weeks.

Aromet tablet in patients inadequately controlled with rosiglitazone or metformin monotherapy: The dose of Aromet in patients treated with Rosiglitazone and/or Metformin therapy should be based on the patient's current doses of Rosiglitazone and/or Metformin. After an increase in Metformin dosage, dose titration is recommended if patients are not adequately controlled after 1 to 2 weeks. After an increase in Rosiglitazone dosage, dose titration is recommended if patients are not adequately controlled after 8 to 12 weeks. For patients inadequately controlled on Metformin monotherapy, the usual starting dose of Aromet is 4 mg Rosiglitazone (daily dose) plus the dose of Metformin already being taken.

For patients inadequately controlled on Rosiglitazone monotherapy, the usual starting dose of Aromet is 1000 mg Metformin (daily dose) plus the dose of Rosiglitazone already being taken. When switching from combination therapy of Rosiglitazone plus Metformin as separate tablets, the usual starting dose of Aromet is the dose of Rosiglitazone and Metformin already being taken. If additional glycemic control is needed, the daily dose of Aromet may be increased by increment of 4 mg Rosiglitazone and/or 500 mg Metformin, up to the maximum recommended total daily dose of 8 mg/2000 mg.

Contraindications:

Aromet tablet is contraindicated in patients with renal disease or renal dysfunction (e.g., as suggested by serum creatinine levels .1.5 mg/dl (males), 1.4 mg/dl (females), or abnormal creatinine clearance), acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma & known hypersensitivity to rosiglitazone maleate or metformin HCl.

Side-effects:

Rosiglitazone: The commonly reported adverse events are upper respiratory tract infections, injury, headache, back pain, fatigue, sinusitis, diarrhoea and hypoglycemia. There were a small number of patients who had anemia and edema. All these events were generally mild to moderate in severity and usually do not require discontinuation of treatment with Rosiglitazone.

Metformin: Some patients may develop asymptomatic subnormal levels of serum vitamin B12.

Incidence of lactic acidosis is also very rare. Diarrhoea, nausea, vomiting, abdominal bloating, flatulence and anorexia are common reactions to Metformin.

Precautions:

Rosiglitazone: Aromet tablet should not be used in patients with type 1 diabetes. This should be used with caution in patients with edema. Dose-related weight gain was seen with rosiglitazone alone and rosiglitazone together with other hypoglycemic agents.

Metformin: Monitoring of renal function: Patients with serum creatinine levels above the upper limit of normal should not receive Aromet tablet. In patients with advanced age, Aromet tablet should be carefully titrated to establish the minimum dose for adequate glycemic effect, because aging is associated with reduced renal function.

High risk group:

Pregnancy: Aromet tablet is not recommended for use in pregnancy.

Renal impairment: Generally, elderly, debilitated, and malnourished patients should not be titrated to the maximum dose of Aromet tablet. Monitoring of renal function is necessary to aid in prevention of metformin-associated lactic acidosis, particularly in the elderly.

Hepatic impairment: Aromet tablet should not be initiated if the patient has active liver disease or increased serum transaminase levels (ALT>2.5X upper limit of normal at start of therapy). Liver enzyme monitoring is recommended in all patients prior to therapy with Aromet tablet and periodically thereafter.

Geriatric: The initial and maintenance dosing of Aromet tablet should be conservative in patients with advanced age.

Pediatric: Safety and effectiveness of Aromet tablet in pediatric patients have not been established.

Drug interactions:

Rosiglitazone has no clinically relevant effect on the pharmacokinetics of nifedipine and oral contraceptives (ethinylestradiol and norethindrone). Rosiglitazone does not alter the metabolism of glyburide, metformin, acarbose, warfarin and digoxin when administered concomitantly.

Metformin interacts with cimetidine which increases the availability of Metformin and reduces its renal clearance. Therefore the dose of Metformin should be reduced if cimetidine is co-prescribed. Drugs with hyperglycemic potential like thiazides, corticosteroids may partly offset the hypoglycemic action of Metformin. Alcohol increases the hypoglycemic and hyperlactaemic effect of Metformin.

Benefits:

Aromet is US FDA approved initial therapy for type 2 diabetes.

Aromet is highly effective as initial therapy in the treatment of type 2 diabetes.

Aromet is highly effective as initial therapy in improving lipid profiles of diabetic patients.

Aromet can be given with insulin therapy.

Packing:

Aromet-1 Tablet: Each box contains 5x10's tablets in blister pack.

Aromet-2 Tablet: Each box contains 3x 10's tablets in blister pack.