Memin

COMPOSITION

Each film coated tablet contains

Metformin            500/850 mg

DESCRIPTION

-          Metformin belongs to the biguanide class of oral hypoglycemic agent.

-          It is used for the treatment of type II DM

-          It causes little or no hypoglycemia in nondiabetic subjects and do not stimulate pancreatic β cells.

-          It has been reported to improve lipid profile as well as type II diabetes.

MECHANISM OF ACTION

 It reduces elevated blood glucose concentration and improves glucose tolerance in type II diabetic patient irrespective of insulin release. Thus it is less likely to cause hypoglycemia.

-It suppresses hepatic gluconeogenesis and glucose out put from liver.

- Inhibiting glucose, other hexoses, amino acids and Vit. B12 from the intestine.

- Interfere with mitochondrial respiratory chain promote peripheral glucose utilization by enhancing anaerobic glycolysis.

-  Reducing plaque formation on endothelium of blood vessels.

-  They enhance GLUT₁ transport from intracellular site to plasma membrane.

Metformin has been beneficial act on glucose, insulin & lipids as well as offers cardiovascular protective effect.

-          Effective control of blood glucose, without causing release of insulin.

-          Reduces cardiovascular complications like Angina pectoris and myocardial infraction.

-          Improve insulin sensitivity, resulting in improved hemodynamic effects.

-          Reduces harmful lipids like very low density lipoprotein (VLDL).

-          Increases the beneficial lipids like high density lipoprotein (HDL).

-          Reduces the fibrinogen levels in the blood which minimizes intravascular coagulation coronary arteries.

-          Reduce uptake of cholesterol by blood vessels.

-          Reduces platelet aggregation which minimizes the possibility of ischemic heart disease such as coronary thrombosis.

PHARMACOKINETICS

·         It is completely absorbed after an oral dose.

·         Peak plasma concentration is reached after 2 hours.

·         Oral bioavailability is 50-60%.

·         It is rapidly distributed.

·         It doesnot under go metabolism and is unchanged through the urine.

·         Mean half life range from 1.5 -4.5 hr, it is prolonged in patients with renal impairment, elderly due to deteriorating renal function.

INDICATIONS

NIDDM, specially obese, primary and secondary sulphonylurea failure.

Type II DM not responding to diet & exercise alone.

DOSAGE & ADMINISTRATION

Metformin 500mg: 500mg TID with meal may be increased to 3g/day.

Metformin 850mg: 850mg BID with meal

When good control has been achieved the dose may be reduced gradually, in order to minimize G.I. side effects. It can be used with other sulphonylurea.

ADVERSE EFFECT

1.        Lactic acidosis: Excess production of lactic acid may occur in body in reduced oxygen concentration, causes impairment of cellular respiration which may cause instant death. It is more common with phenformin but even metformin may also lead to lactic acidosis especially in impaired hepatic function, renal failure, lung disease, septicemia, dehydration.

CLINICAL FEATURE

·         Myalgia (pain in muscles)

·         Non-specific (Abdominal) distress.

·         Associated hypothermia

·         Hypotension

·         Bradycardaia

·         Nausea and vomiting

·         Restlessness & altered respiration.

·         Coma (rarely)

·         Decrease PH of blood

·         Electrolyte disturbances

Treatment of this condition is essential since it may be life threatening. This condition require intensive care with

·         IV carbonate to raise the blood PH

·         Administration of insulin & glucose

Lactic acidosis is more commonly observed with Phenformin & this being the reason for withdrawal from the market. Metformin  has been very rarely implicated as a culprit in the condition of lactic acidosis.

2.        Vit.B12 deficiency: Due to interfere with its absorption, Vit.B12 deficiency can occur specially with high dose of Metformin.

OTHER ADVERSE EFFECT

Diarrhea, nausea, vomiting, flatulence, anorexia are the most common reaction. Around 9% of the patient experience unpleasant or metallic taste which generally resolves spontaneously during Metformin therapy.

USE IN PREGNANCY & LACTATION

Safety and use of Metformin has not been established

CONTRAINDICATION

-          Diabetic coma

-          Severe Ketoacidosis

-          Severe hepatic or renal in sufficiency

-          Cardiac failure

-          IDDM

-          Dehydration

-          Acute and chronic alcoholism

-          Severe infection, stress, trauma

DRUG INTERACTION

 Cimetidin may increase plasma Metformin level.