Are there any possible interactions between clozapine and the following drugs: levodopa, benserazid

Fråga: Are there any possible interactions between clozapine and the following drugs: levodopa, benserazide, dextropropoxyphene, acetaminophen and citalopram?

A 67-year-old man with severe Parkinson´s disease is being treated with Madopark mite 12 tablets daily, Distalgesic 3 tablets daily and Cipramil 10 mg daily. Because of visual hallucinations, a low dose of Leponex (clozapine) was added. Hallucinations disappeared, but the patient became very tired.

Sammanfattning: Clozapine is not known to interact with levodopa, dextropropoxyphene or citalopram. The combination of clozapine, dextropropoxyphene and citalopram may cause tiredness, even in the absence of specific drug interactions.

Svar: Clozapine is considered a drug of choice in the treatment of drug-induced psychosis in Parkinson´s disease, with a therapeutic effect at doses lower than those required to treat schizophrenia (1, 2). Clozapine is not known to interact adversely with the levodopa-benserazide combination (1, 3). However, somnolence was somewhat more frequent among 32 patients who received active treatment (with a mean dose of 36 mg daily), compared with placebo, in a double-blind study of clozapine treated psychosis in Parkinson´s disease (4).

Clozapine is mainly metabolised by the liver enzyme CYP1A2. There is no reason to suspect a pharmacokinetic interaction with citalopram, dextropropoxyphene or acetaminophen, as these drugs are metabolised via other pathways. Clozapine levels were not affected by co-administration of citalopram in five patients (5).

Furthermore dextropropoxyphene can sometimes induce hallucinations (6). Dextropropoxyphene can inhibit the metabolism of citalopram via the liver enzyme CYP2D6. We have previously received a question concerning hallucinations in a 42-year-old woman treated with this combination, and one such case has also been reported to the Swedish Adverse Drug Reactions Advisory Committee (7).

Clozapine, dextropropoxyphene and citalopram can all induce tiredness. In the present case, tiredness may well be due to a combined effect of the three drugs, even in the absence of any interactions. 1 Drugline no 16291 (year 1999) 2 Meltzer HY, Kennedy J, Dai J, Parsa M, Riley D: Plasma clozapine levels and the treatment of L-Dopa-induced psychosis in Parkinson´s disease. A high potency effect of clozapine. Neuropsychopharmacol 1995; 12: 39-45 3 Aravelo GJ, Gershanik OS: Modulatory effect of clozapine on levodopa response in Parkinson´s disease: a preliminary study. Mov Disord 1993; 8: 349-354 4 The French Clozapine Parkinson Study Group: Clozapine in drug-induced psychosis in Parkinson´s disease. Lancet 1999; VOL: 2041-2042 5 Taylor D, Ellison Z, Ementon Shaw L, Wickham H, Murray R: Co-administration of citalopram and clozapine: effect on plasma clozapine levels. Int Clin Pshychopharmacol 1998; 13: 19-21 6 FASS 2000 (The Swedish catalogue of approved medical products) 7 Drugline no 11736 (year 1994)