Chlorpropamide

(BAN, rINN)
Chlorpropamide Chemical formula
Synonyms: Chloropropamid; Chlorpropamid; Chlorpropamidas; Chlorpropamidum; Clorpropamida; Klooripropamidi; Klórpropamid; Klorpropamid. 1-(4-Chlorobenzenesulphonyl)-3-propylurea.
Cyrillic synonym: Хлорпропамид.

💊 Chemical information

Chemical formula: C10H13ClN2O3S = 276.7.
CAS — 94-20-2.
ATC — A10BB02.
ATC Vet — QA10BB02.

Pharmacopoeias.

In Chin., Eur., Jpn, and US.

Ph. Eur. 6.2

(Chlorpropamide). A white or almost white, crystalline powder. It exhibits polymorphism. Practically insoluble in water; soluble in alcohol; freely soluble in acetone and in dichloromethane; dissolves in dilute solutions of alkali hydroxides. Protect from light.

USP 31

(Chlorpropamide). A white crystalline powder having a slight odour. Practically insoluble in water; soluble in alcohol; sparingly soluble in chloroform.

💊 Adverse Effects and Treatment

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

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

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 hypoglycaemia. 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 Study1 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.
1. Matthews DR, et al. UKPDS 26: sulphonylurea failure in noninsulin-dependent diabetic patients over six years. Diabet Med 1998; 15: 297–303.

💊 Preparations

BP 2008: Chlorpropamide Tablets; USP 31: Chlorpropamide Tablets.

Proprietary Preparations

Arg.: Diabinese; Idle†; Trane; Belg.: Diabinese†; Braz.: Clorpromini†; Clorzin†; Diabecontrol; Diabinese; Glicoben; Glicorp; Pramidalin; Canad.: Novo-Propamide; Chile: Diabinese; Gr.: Diabinese; Hong Kong: Diabinese; India: Copamide†; Indon.: Diabinese; Israel: Diabinese†; Diabitex; Ital.: Diabemide; Malaysia: Anti-D†; Diabinese†; Propamide; Mex.: Apoprod; Diabiclor; Diabinese; Insogen; Philipp.: Diabinese; S.Afr.: Diabinese; Hypomide; Singapore: Anti-D; Chlomide†; Diabinese†; Propamide; Spain: Diabinese; Thai.: Diabeedol; Diabinese; Dibecon; Glycemin; Propamide; Turk.: Diabinese; USA: Diabinese; Venez.: Dabinese. Multi-ingredient: India: Chlorformin†; Ital.: Bidiabe; Pleiamide; Mex.: Insogen Plus; Mellitron; Obinese; Switz.: Diabiformine.
Published October 17, 2018.