Clozapine Coffee

Raaska, K., Raitasuo, V., Laitila, J. Neuvonen, P. J. (2004). Effect of caffeine-containing versus decaffeinated coffee on serum clozapine concentrations in hospitalised patients. Pharmacol. Toxicol, 94, 13-18. 

Clozapine is principally metabolized to N -desmethylclozapine (norclozapine). It is also metabolized to and n-oxide, other hydroxyl metabolites, and a protein-reactive metabolite. The n-oxide can be converted back to clozapine. The enzyme responsible for the metabolism of clozapine to norclozapine is the cytochrome P450 1A2 enzyme (325). This is consistent with a study showing that caffeine, a marker for 1A2, is cleared in relationship to the conversion of clozapine to norclozapine ( 326). Discontinuation of coffee intake can decrease the clozapine plasma levels by more than 50%, and increasing caffeine intake can produce a reemergence of the side effects (e.g., drowsiness, excess salivation). Additionally, smoking, which induces 1A2, lowers clozapine plasma levels. Fluvoxamine, an inhibitor of 1A2, dramatically increases plasma levels, and on occasion, adverse effects are seen ( 327). This phenomenon can lead to clozapine intoxication in patients on high doses of fluvoxamine. 

The effects of caffeine-containing versus decaffeinated coffee on serum clozapine concentrations have been examined in 12 patients in a randomized, placebo-con-trolled, crossover study (248). Serum clozapine concentration increased, probably because of inhibition of CYP1A2. However, the effect was minor in most of the patients, although some individuals may be more sensitive to this interaction, owing for example to genetic factors. 

In a crossover study, 6 coffee-drinking patients taking clozapine were given decaffeinated or caffeine-containing instant coffee for 7 days. The plasma levels of clozapine were 26% higher while the patients were t ing caffeine. A study in 12 healthy subjects found that caffeine 400 mg to 1 g daily, raised the AUC and decreased the clearance of a single 12.5-mg dose of clozapine by 19% and 14%, respectively. A previous study in 7 patients had found that clozapine levels decreased by 47% when the subjects avoided caffeine for 5 days, and increased again when caffeine consumption was resumed. ... 

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