General information about the antiarrhythmic agent cibenzoline (Cipralan) which is not registered i

Fråga: General information about the antiarrhythmic agent cibenzoline (Cipralan) which is not registered in Sweden, but registered in France and mentioned in Dictionnaire Vidal at least since 1985.

Sammanfattning: Cibenzoline is an antiarrhytmic agent with class IA and some class III and IV activity according to the Vaughan-Williams classification. The results from long term studies seem to vary and further evaluation is required to assess its place in therapy.

Svar: According to pharmacological handbooks (1-2) and an overview article (3), cibenzoline (also called cifenline) is structurally unrelated to other antiarrhythmics. Its effect on cardiac conduction is primarily of the Vaughan Williams class IA type, though it has some class III and class IV activity as well. Its electrocardiographic effects are similar to those of quinidine, procainamide and disopyramide (1).

Cibenzoline can be administered both orally and intravenously. The absorption is almost complete and the bioavailability is about 90 per cent. Approximately 60 per cent of the drug is protein bound. More than one half of an oral dose is excreted unchanged in the urine. A smaller part is metabolized to an inactive agent. The mean half-life is about 7-8 hours (range 4-13 hours). In patients with renal insufficiency accumulation can be expected and, therefore, the dosage should be reduced.

Most patients demonstrate (3) therapeutic effects at an oral dose of 3 to 4 mg/kg/day. The recommendations for dosage differ from twice daily (1) to 3-4 times daily (3).

Clinical studies (3) have shown cibenzoline to be reasonably effective in suppressing premature complexes and possibly in suppressing ventricular tachycardia. Its efficacy has been compared with disopyramide, mexiletin (3) and quinidine (4).

The results from long-term studies (10-24 months) seem to vary (5-6). Further evaluation is required to assess its place in therapy (3).

Oral cibenzoline seems to be well-tolerated. Gastrointestinal adverse effects are the most frequent (1-4 per cent), e.g. epigastric pain and diarrhoea. Less commonly headache, vertigo, tremors, blurred vision, urinary retention and hypotension/syncope have been reported. A proarrhythmic effect and possibly an increase in congestive heart failure have also been noted (1,3). There are some reports of hypoglycemia and monitoring of blood sugar is therefore routinely required in patients treated with cibenzoline (7). 1 Avery´s, Drug treatment. 1987; pp 638-639 2 Martindale, The extra pharmacopoeia. 1989; 29th ed: 75 3 Nestico PF, Morganroth J, Horowitz LN: New antiarrhythmic drugs. Drugs 1988; 35: 309-310 4 Mohiuddin SM, Woodruff MP, Esterbrooks DJ, Mooss AN, Hansen JM et al: Crossover comparison of cibenzoline and quinidine in ambulatory patients with chronic ventricular arrhythmias. J Cardiovasc Pharmacol 1989; 13: 525-529 (cited in Inpharma 1989; no 683) 5 Mohiuddin SM, Hilleman DE, Esterbrooks D, Mooss AN, Stengel LA: Short term control of PVCs is achieved with cibenzoline. J Clin Pharmacol 1987; 27: 400-406 (cited in Inpharma 1987; no 593) 6 Mohiuddin SM, Hilleman DE: Efficacy, side effects, and plasma concnetrations of cibenzoline in patients with ventricular arrhythmias. DICP 1984; 18: 499 7 Noury JF, Delvaux JC: Hypoglycemia caused by cibenzoline. Apropos of a new case. Ann Cardiol Angeiol (Paris) 1989; 38: 7-8