Rosiglitazone may result in resumption of ovulation in pre-menopausal, anovulatory women with insulin resitence. Therefore adequate contraceptives measures are to be considered. If unexpected menstrual dysfunction occurs, then the benefits of continuing therapy must be reconsidered.

Decreases in haemoglobulin and hemocrit were observed in both monotherapy and in combination with metaformin.

Metformin -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 hyploglycemic action of metformin. Monitor glycemic control.

Alcohol increases the hyploglycemic and hyperlactatemic efect of metformin. Metformin may increase elimination of phenprocoumon due to increase in liver blood flow.

Non -insulin dependent type II diabetes

Rossiglitazone- Upper respiratory tract infection, back pain, hypoglycemia, headache, sinusitis, diarrhea, edema, lower pre-treatment hemogloin/haemotocrit value.

Metformin- Lactic acidosis, malabsorption of Vitamin B12 and folate, anorexia, vomiting, nausea, diarrhea, occasionally metallic taste.

Rosiglitazone -Hypersensitivity Metformin Impaired renal function, acute complications(severe infections, major operations, trauma) liver damage, alcoholism, ketosis-prone diabetes,deficiency of Viamin B12, folic acid, and iron, diabetes with significant late complications, general ill health, severe cardiovascular or respiratory disease, pregnancy and and lactation.

Special precautions

Rosiglitazone- Rosiglitazone may result in resumption of ovulation in premenopausal, anovulatory women with Insulin resistence.

These patients may be at risk for pregnancy if adequate contraception is not used. Should be used with caution in patients with edema Not indicated in patients with Class 3 and Class 4 cardiac status unless expected benefits outweighs the potential risk.

Caution in patients suffered with jaundice. If jaundice is observed during therapy, the drug should be discontinued.

Metformin- Caution to be excercised in elderly patients.

Non -insulin dependent type II diabetes

Dosage-

One tablet twice daily as indicated by the physician

Rosiglitazone -May result in resumption of of ovulation in premenopausal anovulatory wome.

May be at risk of pregnancy if adequate contrception is not used. To be used with caution in patients with edema.

Caution to be taken with patients suffered from jaundice.

Pharmacology

Rosiglitazone is a thiazolidinedione antidiabetic agent, improves insulin resistence, a key underlying metabolic abnormality in most patients with type 2 diabetes mellitus.It activates the nuclear receptor peroxisome proliferator activated receptor gamma(PPAR-gamma)

Metformin- Meformin binds to apolar biguanide hyrocarbon side chain to membrane phospholipids, evoking a change in the electrostatic surface potrential. It potentiates insulin action mainly by post receptor mechanism.. In this way, metformin ameliorates insulin resistence.

A study conducted to assess the efficacy of the combination of Rosiglitazone and Metformin. Rosiglitazone was administered in either once daily or twice daily to the patients who were inadequately controlled on a maximum dose of Metformin. The result of the study showed a statiscally improvement in fasting plasma glucose and HbA.

The combination also appears to be safe and well tolerated.

Pharmacokinetics:

Comparitive Pharmacokinetics parameters: Rosiglitazone Metformin Cmax 3.12ng/ml 5 mcg/m Tmax 1.75 hours l -3 hours t 1/2 3.15hours 1.5 - 1.6 hours Bioavailibility 99% 50 - 60%

Rosiglitazone may result in resumption of ovulation in premenopausal, anovulatory women with Insulin resistence.

These patients may be at risk for pregnancy if adequate contraception is not used.