Drug Approvals
(British Approved Name, rINN)
International Nonproprietary Names (INNs) in main languages (French, Latin, and Spanish): Chloropropamid; Chlorpropamid; Chlorpropamidas; Chlorpropamidum; Clorpropamida; Klooripropamidi; Klorpropamid
Pharmacopoeias. In China, Europe, Japan, and US. European Pharmacopoeia, 6th ed. (Chlorpropamide). A white or almost white, crystalline powder. It exhibits polymorphism. Practically insoluble in water soluble in alcohol freely soluble in acetone and in dichlo-romethane dissolves in dilute solutions of alkali hydroxides. Protect from light.
The United States Pharmacopeia 31, 2008 (Chlorpropamide). A white crystalline powder having a slight odour. Practically insoluble in water soluble in alcohol sparingly soluble in chloroform.
Adverse Effects and Treatment
As for sulfonylureas in general. Chlorpropamide may be more likely than other sulfonylureas to induce a syndrome of inappropriate secretion of antidiuretic hormone characterised by water retention, hyponatraemia, and CNS effects. Patients receiving chlorpropamide may develop facial flushing after drinking alcohol.
Precautions
As for sulfonylureas in general. Chlorpropamide should be avoided in the elderly and in renal or hepatic impairment because its long half-life increases the risk of hypoglycaemia. The antidiuretic effect of chlorpropamide may cause problems in patients with conditions associated with fluid retention.
Fasting. For the view that although some sulfonylurea antidiabetics may be able to be used with caution in fasting Muslim patients during Ramadan, chlorpropamide is contra-indicated, see under Precautions of Insulin.
Porphyria. Chlorpropamide has been associated with acute attacks of porphyria and is considered unsafe in porphyric patients.
Thyroid disorders. Some manufacturers recommend that chlorpropamide should not be used in patients with impaired thyroid function, but see under Sulfonylureas.
Interactions
As for sulfonylureas in general. Chlorpropamide may produce profound facial flushing associated with alcohol ingestion.
Pharmacokinetics
Chlorpropamide is readily absorbed from the gastrointestinal tract and is extensively bound to plasma proteins. The half-life is about 35 hours. About 80% of a dose is metabolised in the liver metabolites and unchanged drug are excreted in the urine. Chlorpropamide crosses the placenta and has been detected in breast milk.
Uses and Administration
Chlorpropamide is a sulfonylurea antidiabetic. It has a duration of action of at least 24 hours, and is given orally in the treatment of type 2 diabetes mellitus in an initial daily dose of 250 mg as a single dose with breakfast. After 5 to 7 days the dose may be adjusted, in steps of 50 to 125 mg at intervals of 3 to 5 days, to achieve an optimum maintenance dose which is usually in the range 100 to 500 mg daily. Increasing the dose above 500 mg daily is unlikely to produce further benefit, and doses above 750 mg daily should be avoided. Although a reduced dose range has been proposed for the elderly, use of chlorpropamide is inadvisable in this group.
Chlorpropamide, though not the other sulfonylureas, is also sometimes used in cranial diabetes insipidus. It has been reported to act by sensitising the renal tubules to antidiuretic hormone. The dose has to be carefully adjusted to minimise the risk of hypogly-caemia. An initial dose of 100 mg daily, adjusted if necessary to a maximum of 350 mg daily has been recommended, although doses of up to 500 mg daily have been used.
Diabetes mellitus. Patients with type 2 diabetes whose blood glucose is adequately controlled at first by sulfonylureas often eventually have treatment failure and loss of diabetic control. Results from the UK Prospective Diabetes Study have suggested that the 6-year failure rate was higher in patients treated with glibenclamide (48%) than in those given chlorpropamide (40%). This difference was equivalent to delaying the requirement for additional therapy for a year in chlorpropamide-treated patients.
Preparations
British Pharmacopoeia 2008: Chlorpropamide Tablets
The United States Pharmacopeia 31, 2008: Chlorpropamide Tablets.
Proprietary Preparations:
Argentina: Diabinese Idle † Trane
Belgium: Diabinesef
Brazil: Clorpromini † Clorzin † Diabecontrol Diabinese Glicoben Glicorp Pramiclalin
Canada: Novo-Propamide
Chile: Diabinese
Greece: Diabinese
Hong Kong: Diabinese
India: Copamidef
Indonesia: Diabinese
Israel: Diabinese † Diabitex
Italy: Diabemide
Malaysia: Anti-D † Diabinese † Propamide
Mexico: Ap-oprod Diabiclor Diabinese Insogen
Philippines: Diabinese
South Africa: Diabinese Hypomide
Singapore: Anti-D Chlomide † Diabinese † Propamide
Spain: Diabinese
Thailand: Diabeedol Diabinese Dibecon Glycemin Propamide
Turkey: Diabinese
USA: Diabinese
Venezuela: Dabinese.
Multi-ingredient:
India: Chlorformin †
Italy: Bidiabe Pleiamide
Mexico: Insogen Plus Mellitron Obinese
Switzerland: Diabiformine
The symbol † denotes a preparation no longer actively marketed.