Chlorpropamide

Indications

Chlorpropamide is used for: Type 2 diabetes mellitus

Adult Dose

Oral Type 2 diabetes mellitus Adult: Initially, 250 mg daily as a single dose in the morning. 5-7 days after treatment initiation, subsequent doses may be increased or decreased by 50-125 mg daily at intervals of 3-5 days until optimum therapeutic control is achieved. Maintenance: 100-500 mg daily. Elderly: Initial: 100-125 mg daily. 5-7 days after treatment initiation, subsequent doses may be increased or decreased by 50-125 mg daily at intervals of 3-5 days until optimum therapeutic control is achieved. Hepatic impairment: Severe: Contraindicated.

Child Dose

Safety and efficacy not established

Renal Dose

Renal Impairment CrCl <50 mL/minute: Avoid use CrCl >50 mL/minute: Monitor therapy closely; initial and maintenance dosing should be conservative to avoid hypoglycemia

Administration

Should be taken with food.

Contra Indications

Type 1 DM, diabetic ketoacidosis (w/ or w/o coma) or other acute complications (e.g. major surgery, severe infection or severe trauma), thyroid impairment. Severe hepatic and renal impairment.

Precautions

Hypersensitivity to sulfonamides. Patient w/ condition associated w/ fluid retention, G6PD deficiency. Mild to moderate hepatic and renal impairment. Elderly, debilitated and malnourished patients. Pregnancy and lactation. Patient Counselling Adhere strictly to the prescribed diabetic diet. Monitoring Parameters Monitor blood glucose, glycosylated Hb level, signs and symptoms of hypoglycaemia. Lactation: Excretion in milk unknown/not recommended

Pregnancy-Lactation

Pregnancy Category: C Lactation: Excretion in milk unknown/not recommended

Interactions

Diminished therapeutic effect w/ thiazide diuretics. Protein-bound drugs (e.g. oral anticoagulants, hydantoins, salicylates, other NSAIDs, sulfonamides) may potentiate hypoglycaemic action of chlorpropamide. Increased plasma concentrations w/ certain antifungals (e.g. miconazole, fluconazole).

Adverse Effects

Side effects of Chlorpropamide : GI disturbances (e.g. anorexia, nausea, vomiting, epigastric discomfort, abdominal cramps, constipation, diarrhoea), vague neurologic symptoms (e.g. headache, weakness, paraesthesia), syndrome of inappropriate secretion of antidiuretic hormone, jaundice, skin eruptions, blood dyscrasias, pruritus, urticaria, maculopapular eruptions and photosensitivity reactions, porphyria cutanea tarda, leucopenia, thrombocytopenia, haemolytic anaemia, wt gain. Associated with greater number of side effects in the geriatric and renally impaired; should not be used as first line agent in these populations Cholestatic jaundice and hepatitis may occur rarely which may progress to liver failure Potentially Fatal: Severe hypoglycaemia.

Mechanism of Action

Chlorpropamide stimulates the secretion of endogenous insulin from β-cells of the pancreas. It also exhibits antidiuretic activity by enhancing vasopressin in the renal tubules.