The effect of variable cigarette consumption on the interaction with clozapine and olanzapine

Abstract

A daily consumption of 7-12 cigarettes is probably sufficient for maximum induction of clozapine and olanzapine metabolism. A 50% lower starting dose of both drugs in non-smokers seems rational to avoid side effects.

Smoking and drug interactions

“…36 Methadone doses have been found to be higher in heavy smokers 37 and methadone has been shown to increase both smoking rates and smoking satisfaction. 38 Patients report less methadone-induced clozapine and olanzapine, 22 resulting in lower plasma concentrations. 7,16,21 The daily consumption of 7-12 cigarettes is probably sufficient to cause the maximum induction of clozapine and olanzapine metabolism.…”

“…7,16,21 The daily consumption of 7-12 cigarettes is probably sufficient to cause the maximum induction of clozapine and olanzapine metabolism. 22 A 50% difference in the mean daily dose of clozapine needed by smokers and nonsmokers to reach a given blood concentration has been reported. 23 Irrespective of smoking status, the mean oral bioavailability of clozapine is 27-47% and clozapine plasma concentrations have more than a 45-fold variability amongst individuals during chronic treatment.…”

“…25 Non-smokers are at higher risk of adverse effects if treated with standard doses, suggesting that there is an interaction between smoking, olanzapine and clozapine. 20,22 In one case report, a patient receiving olanzapine experienced extrapyramidal symptoms (including akathisia, akinesia and bradyphrenia) within days of significantly reducing tobacco consumption. 21 Case reports on smoking discontinuation by patients taking clozapine outline effects including confusion, 21 tonic-clonic seizures, stupor, coma 26 or aspiration pneumonia.…”

Tobakksrøyking og interaksjoner med legemidler

“…I en studie med CYP1A2-substratet koffein var det økende induksjonsgrad fra én til ti sigaretter per dag, men ingen vesentlig økning ved større forbruk enn dette (5). Tilsvarende ble det i en annen studie med CYP1A2-substratene klozapin og olanzapin ikke observert forskjeller i plasmakonsentrasjonen hos schizofrene som røykte henholdsvis 7-12 og mer enn 12 sigaretter per dag (6). I denne studien var det ikke noen som røykte under sju sigaretter per dag.…”

“…Et interessant fenomen er at mer enn 80 % av pasientene med schizofreni røyker (6). Det betyr at standard anbefalt dosering av klozapin og olanzapin primaert er tilpasset røykernes behov.…”