Objective: This inpatient, randomised, three-way crossover study evaluated the steady-state pharmacokinetics and tolerability of generic clozapine (Creighton) versus Clozaril® (Novartis brand of clozapine) in patients with schizophrenia.
Setting: Patients were hospitalised throughout the study.
Patients: Thirty patients meeting DSM-III-R criteria for a diagnosis of schizophrenia participated in this study.
Design: Clozaril® was titrated over 5 days from 12.5 to 75mg twice daily, after which patients received all of the following 1-week regimens in random order: Clozaril® — one 100mg tablet twice daily; clozapine — four 25mg tablets twice daily; and clozapine — one 100mg tablet twice daily.
Main Outcome Measures and Results: Both the 25 and 100mg dose forms of clozapine were bioequivalent to Clozaril® 100mg, justifying their interchange-ability; mean area under the concentration-time curve (AUC0–12) values were 2683 ± 1613, 2781 ± 1775, and 2547 ± 1429 μg/L·h, respectively. The most common adverse events were dizziness and asthenia. Tolerability findings between groups were comparable, although a high incidence (20%) of symptomatic orthostatic hypotension during the initial titration of Clozaril® emphasised the need for careful monitoring, even in the target patient population.
Conclusions: The results of this study demonstrated that the 25 and 100mg dose forms of generic clozapine and Clozaril® 100mg are bioequivalent, which should ensure comparable efficacy and tolerability with the clinical use of either product.
Schizophrenia Adis International Limited Clozapine Schizophrenic Patient Bioequivalence Study
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