Prescription Medicines -Glucophage ,

Glucophage SR 500mg / Glyciphage-SR 500 mg

METFORMIN

(Phenformin, Metformin). They are completely different from the hypoglycaemic sulfonamides both in its structure and its mode of actions. They cause little or no hypoglycaemia in non-diabetic. Possible mode of action suggested is that they interfere with mitochondrial respiratory chains-promote peripheral glucose utilization by enhancing anaerobic glycolysis or they enhance blinding of insulin to its receptors & potentiate its action. Other is that they suppress hepatic glucon- eogenesis & inhibit intestinal absorption of glucose.

Indications:

Monotherapy for adults (above 17 yrs.) with Type 2 Diabetes Mellitus, where balanced diet, weight control and exercise have failed to control blood sugar levels.
GLYCIPHAGE ® SR is especially useful if the patient is obese, as it helps to reduce weight. However, there is no contraindication to the use of the drug in patients who are not overweight, as it helps to normalize weight and blood sugar levels rather than reduce it below normal.
GLYCIPHAGE ® SR may be added as a co-prescription with sulfonylureas and /or insulin, where the latter when given alone failed to control hyperglycemia.
In IGT
In PCOS
In essential hypertension

Dosage:

For the treatment of Type 2 (non-insulin dependent, NIDDM) Diabetes Mellitus controlled by diet alone:

For monotherapy: Oral dosage- Adults: Initially, 500mg once daily with the evening meal. Increase in increments of 500 mg weekly, as needed, upto a maximum of 2000 mg once daily with the evening meal. If glycemic control is not achieved with 2000 mg once daily, a trial of GLYCIPHAGE ® SR tablet as 1000 mg twice daily should be considered. If doses of more than 2000 mg/day are required, change to the appropriate dosage of immediate release Metfromin tablets GLYCIPHAGE ® SR in divided doses.

Elderly or debilitated patients: Same as adult dosage. Avoid use if ≥ 80 years of age unless normal renal function is documented. In general, don not titrate to the maximum dose.

Adolescents & children: Safe and effective use has not been established.

Switching to Metformin from other antidiabetic therapy:

Adults and Elderly: When transferring from antidiabetic agents other than Chlorpropamide, no transition period is required. When transferring from Chlorpropamide, use caution during the first 2 weeks as there may be prolonged retention of Chlorpropamide in the body, which may increase the potential for hypoglycemia.

Addition of a sulfonylurea or an alpha-glycosidase inhibitor to Metformin:

Adults and Elderly: After 4 weeks of the maximum dose of Metfromin as described in monotherapy without adequate response, consider the gradual addition of an oral sulfonylurea, even if prior failure to a sulfonylurea has occurred. If after 1-3 months of concomitant therapy responses are unsatisfactory, consider insulin therapy and discontinuation of oral agents.

Addition of Metformin in combination with insulin therapy:

Adults: The current insulin dose should be continued; initiate Metformin dose at 500 mg at the evening meal. For patients not responding adequately, the dose of Metfromin may be increased by 500 mg after approximately 1 week and by 500 mg every week thereafter until adequate glycemic control is achieved. The dose should not exceed 2000 mg/day. The insulin dose should usually be decreased by 10-25 % when fasting plasma glucose decreases to less than 120 mg/dl. Individualize dosage of antidiabetic drugs as needed.

Elderly or debilitated patients: Avoid use if ≥ 80 years of age unless normal renal function is documented. In general, do not titrate to the maximum dose.

Adolescents and children: Safe and effective use has not been established.

Patients with renal impairment:

Generally, avoid Metformin use in hepatic impairment. Hepatic disease increase the risk of Metfromin associated lactic acidosis.

Patients with renal impairment:

CrCl ≤ 60 ml/min: Metfromin use is contraindicate

CONTRA-INDICATIONS

Renal disease/ dysfunction

(Serum Creatinine level ≥ 1.5 mg/dl) which may result from

- Cardiovascular shock

- Acute myocardial infarction

- Septicemia

Congestive heart failure requiring pharmacological treatment
Metabolic acidosis ( acute/chronic)

- diabetic ketoacidosis

- lactic acidosis

Do not use Metfromin in patients who have known Metformin hypersensitivity.

Use Metfromin with caution in the elderly. Metformin is substantially excreted by the kidney and the risk of adverse reactions is greater in patients with reduced renal function. Because aging is associated with decline in renal function, care should be taken with doe selection and titrations.

Metfromin is classified in FDA pregnancy risk category B, and is not recommended for use during pregnancy.

DRUG INTERACTIONS

Certain medications used concomitantly with Metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretions (e.g.: Amiloride, Cimetidine, Digoxin, Morphine, Procainamide, Quinidine, Ranitidine or Vanocomycin) may decrease Metfromin elimination by competing for common renal tubular transport systems. Hence, careful patient monitoring and dose adjustment of Metfromin and/or interfering cationic drug is recommended.
Metfromin may result in suboptimal oral Vitamin B12 absorption by competively blocking the calcium dependent binding of the intrinsic factor- Vitamin B 12 complex to its receptor. The reaction very rarely results in pernicious anemia that is reversible with discontinuation of Metfromin or with Vitamin B 12 supplementation.
Nifedipine enhances the absorption of Metformin, it increase plasma Metfromin (Maximum by 20% and increase the amount of Metformin excrete in the urine).

Concomitant administration of Captopril or Enalapril increases sensitivity to insulin and hence dosage of the oral antidiabetics agent may need to be reduced.
If salicylates are administered or discontinued in patients receiving oral antidiabetic agent, patients should e monitored for hypoglycemia or loss of blood glucose control.
Interactions between thiazide diuretics and oral antidiabetic agents decreases insulin sensitivity thereby leading to glucose intolerance and hyperglycemia, thus leading to a loss of diabetic control. Hence diabetic patients should be monitored closely.
Patient receiving estrogens, progestins or oral contraceptives, phenytoin, quinolones should be closely monitored for loss of diabetic control when therapy is instituted for discontinued.

PRECAUTIONS

The kidneys excrete Metformin, hence regular monitoring of renal function is advised in all diabetics.

GLYCIPHAGE ® SR should be stopped 2-3 days before surgery or invasive investigations and restarted only after normal renal function has been regained.

GLYCIPHAGE ® SR should be avoided in conditions that may cause dehydration or in patients suffering from serious infections or trauma.

Patients on long term Metfromin therapy should be checked yearly for sings of Vitamin B 12 deficiency and frequently in those who have a tendency of malabsorption, as Metfromin reduces intestinal absorption or Vitamin B 12 and Folic Acid, though cases are rare.

Special Precautions:

Pregnancy: Use of Metformin is not advisable during pregnancy.

Lactation: Adequate human safety data is not available.

Children: Not recommended for use in children.

ADVERSE REACTIONS

GLYCIPHAGE ® SR is usually well tolerated. The most common side-effect is minor gastrointestinal disturbance, which is often self-limiting or minimized by lowering the dose.

Lactatic acidosis has occurred but is very rare, and is usually due to a specific contraindicated state rather than the drug. In patients with metabolic acidosis, even if there is no evidence of ketoacidosis as yet, GLYCIPHAGE ® SR must be stopped and the condition treated as medical emergency.

GLYCIPHAGE ® SR does not lower blood sugar levels in non-diabetics when used as a monotherapy.

Weight loss often occurs during therapy and levels of serum cholesterol, triglycerides and pre-β- lipoproteins may be lowered.

PRESENTATION

GLYCIPHAGE ® SR tablet are available in a blister pack 10 tablets, 10 such blister packs in a carton.