PHARMACOLOGY

Pharmacotherapeutic Group:  Oral hypoglycemic agent

Pharmacodynamic properties:Metformin hydrochloride is a biguanide with antihyperglycaemic effects, lowering both basal and postprandial plasma glucose. It does not stimulate insulin secretion and therefore does not produce hypoglycaemia. Metformin hydrochloride may act via 3 mechanisms: (1) reduction of hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis ; (2) in muscle, by increasing insulin sensitivity, improving peripheral glucose uptake and utilization; (3) and delay of intestinal glucose absorption.

Pharmacokinetic properties: Absorption: Slow and incomplete from the GI tract (oral); reduced if taken with food.; Distribution: Protein-binding: Negligible.; Excretion: Urine (as unchanged drug).

 INDICATIONS :  T2DM, Polycystic Ovarian Syndrome, Non Alcoholic Fatty Liver Disease, Premature Puberty

 DOSE :  1 Tab OD, titrate as required. 

Type 2 Diabetes Mellitus:  Initially 500 mg bid-tid or 850 mg 1-2 times daily, may increase doses in steps of 500 mg at intervals of at least 1 wk. Max: 2.25 g daily. Child: ≥10 yr: Initiate therapy slowly in order to minimise adverse gastric events. Initially 500 or 850 mg once daily, increase doses either wkly by 500 mg daily or every 2 wk by 850 mg daily to a maintenance dose of 1500 - 2000 mg daily in 2 or 3 divided doses. Max dose 2000 mg daily. Elderly: Doses may need to be reduced by around a third in elderly patients.
Polycystic ovarian syndrome: Initially 500 mg daily in the morning for 1 wk, then 500 mg bid for 1 wk, then 1.5-1.7 g daily in 2-3 divided doses.

CONTRAINDICATIONS :  Acute or chronic metabolic acidosis with or without coma (including diabetic ketoacidosis). Renal failure, severe renal or hepatic impairment, acute conditions which may affect renal function e.g. dehydration, severe infection or shock. Cardiac failure, CHF, IDDM, severe impairment of thyroid function; acute or chronic alcoholism. Acute or chronic diseases which may cause tissue hypoxia e.g. cardiac or respiratory failure, recent MI or shock. Pregnancy, lactation.

 SPECIAL PRECAUTIONS :

Caution when used in patients with CHF especially in those with unstable or acute heart failure. Risk of lactic acid accumulation increases with the degree of renal impairment. May need to discontinue treatment in patients with stress-related states e.g. fever, trauma, infection or surgery. Metformin should be temporarily discontinued for 48 hr in patients undergoing radiologic studies involving intravascular admin of iodinated contrast materials. Elderly. May impair ability to drive or operate machinery.

 ADVERSE DRUG REACTIONS : Anorexia, nausea, vomiting, diarrhoea, wt loss, flatulence, occasional metallic taste; weakness; hypoglycaemia; rash, malabsorption of vit B₁₂. Chest discomfort, flushing, palpitation, chills, headache, lightheadedness, indigestion, abdominal discomfort. Potentially Fatal: Lactic acidosis in presence of renal failure and alcoholism.

 DRUG INTERACTIONS : Additive effect with sulphonylureas. Glycaemic control may be affected by diuretics, corticosteroids, phenothiazines, thyroid products, oestrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, chlorpromazine and isoniazid. Metformin effects may be increased by ACE inhibitors, disopyramide, MAOIs. Cimetidine may increase the serum levels of metformin. Concurrent use with contrast agents may increase the risk of metformin-induced lactic acidosis. May decrease the anticoagulant effect of phenprocoumon, therefore routine anticoagulant monitoring is recommended. Potentially Fatal: Lactic acidosis with alcohol. Thrombocytopenia has been reported with ketotifen.