What can cause blood or serum levels of clozapine to change or vary on a given dosage?

Many factors can cause substantial variation in clozapine levels on a given dosage. First, drug-drug interactions are important. Clozapine levels are raised by inhibitors of CYP1A2, including ciprofloxacin, fluvoxamine and oral contraceptives. Caffeine can compete with clozapine for CYP1A2, which may increase clozapine levels. Large reductions in clozapine levels are seen with cigarette smoking (as few as 7 cigarettes per day) and omeprazole. Note that vaping does not typically include the compounds that cause levels to change with smoking, and therefore may not produce a change in clozapine levels. Second, even with the same lab, same patient, same dose, large variation in clozapine levels has been seen (plus or minus 30% in some studies). Third, serious viral or bacterial infections can substantially increase clozapine levels. Fourth, lab error has been reported to be substantially more common with clozapine than other levels. Fifth, the timing of the lab after the last dosage is important. Substantially higher levels are seen when the level is drawn less than 12 hours after the last dosage. Finally, changes in adherence can produce changes in clozapine levels. Because of observed variation in levels and the inconsistent association between levels and response with clozapine, routine serial clozapine levels are not recommended. Levels should be drawn when clinically indicated, to inform clinical decision-making, and interpreted within the context of the patient’s treatment. Clinicians primarily determine dosage of clozapine based on an individual patient’s side effects and symptom response, considering all other information.

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