Is there any known adverse interaction between Antabus (disulfiram) and Parsitan (ethopropazine = p

Fråga: Is there any known adverse interaction between Antabus (disulfiram) and Parsitan (ethopropazine = profenamine rINN)?

Background: A 49-year-old patient had been treated for Parkinson´s disease with Parsitan on licence, which was discontinued three weeks ago. Now Antabus 400 mg x1 is planned. The patient may be treated with Parsitan again. The patient also takes Propavan (propiomazine 25 mg x1) and Atarax (hydroxizine 25 mg x3).

Sammanfattning: Adverse interactions between ethopropazine and disulfiram have not been documented in the literature. Metabolic interaction between disulfiram and perphenazine, another phenothiazine derivative, has been suspected in a case report. An antihistaminic effect of some neuroleptics has been suggested to decrease the effect of disulfiram.

Svar: No documentation has been found in the literature concerning adverse interactions between ethopropazine and disulfiram. The manufacturer of Parsitan does not have any more information concerning this interaction (1).

Ethopropazine is a phenothiazine derivative with antimuscarinic, adrenergic-blocking, slight antihistaminic, local anaesthetic and ganglion-blocking properties (2). The pharmacokinetic data on ethopropazine are not well documented (3). It is known that most of the other phenothiazine derivatives are metabolised by a hepatic enzyme called cytochrome P450-2D6, which is not readily inhibited by disulfiram (4). However, one documentation in Drugline (5) has described a possible interaction between disulfiram and perphenazine, a phenothiazine derivative. Decreased plasma concentration of oral perphenazine and worsened psychosis have been observed after co-administration of disulfiram (6). The authors suggested that disulfiram might have induced the enzyme activity for perphenazine biotransformation and increased the "first-pass" effect in the liver since the enzyme induction effect disappeared when perphenazine was given intramuscularly (6). A marked disulfiram inhibition of the metabolism of chlorzoxazone, a commonly used muscle-relaxing agent in Sweden (Paraflex, Paraflex comp), was recently reported (7).

An antihistaminic effect of neuroleptics has been suggested to decrease the effect of disulfiram in a case report including two patients. The patients reacted strongly to alcohol during disulfiram treatment. When levomepromazine or antidepressant doxepin (not registered in Sweden) were co-administered, the patients could tolerate larger amounts of alcohol (cf 5). It should be mentioned that the present patient is now receiving hydroxizine treatment which also has antihistaminic effect.

Interaction between antihistaminic drugs and calcium carbamide (Dipsan), another alcohol-sensitizing drug, has also been documented in Drugline (8). Similar to the case of disulfiram, the effect of calcium carbamide was decreased by diphenhydramine, a H1-receptor blocker (8). 1 Personal communication, Björn Rubin, Rhone-Poulenc Rorer, the manufacturer of Parsitan

2 Martindale, Extra pharmacopoeia, 1993; 30th ed: 424
3 Drugline nr 06786 (year 1989)
4 Personal communication with Leif Bertilsson, Department of Clinical Pharmacology, Huddinge Hospital
5 Drugline nr 06599 (year 1989) (enclosed)
6 Hansen LB, Larsen N-E: Metabolic interaction between perphenazine and disulfiram. Lancet 1982; II: 1472

7 Kharasch, ED, Thummel KE, Mhyre J, Lillibridge JH: Single-dose disulfiram inhibition of chlorzoxazone metabolism: A clinical probe for P450 2E1. Clin Pharmacol Ther 1993; 53: 653-650 8 Drugline nr 05179 (year 1986)