Branded versus generic clozapine: bioavailability comparison and interchangeability issues.
Clozapine has been the treatment of choice for patients with refractory schizophrenia. Generic clozapine has recently become available, because of a waiver of the usual criteria for establishing bioequivalence. However, there are biopharmaceutical, bioavailability, and clinical concerns related to the generic formulation raised by both clinicians and academic researchers. We conducted a prospective, randomized, crossover study to evaluate steady-state pharmacokinetics, pharmacodynamics, and tolerability of generic clozapine (Zenith Goldline Pharmaceuticals) versus Clozaril (Novartis Pharmaceuticals) in schizophrenic patients. A preliminary report of the pertinent bioavailability results is presented here. Despite comparable mean plasma concentration-time curves, significant differences were found in the primary pharmacokinetic parameters of the 2 formulations in almost 40% of patients. Such intraindividual differences raise the issue of average bioequivalence versus individual bioequivalence and the implication for interchangeability of different clozapine formulations. The decision to switch a patient from branded to generic clozapine should be made on an individual basis with special emphasis on clinical outcome, and patients should be monitored closely during the transition.
Lam
Y W
YW
Department of Pharmacology, University of Texas Health Science Center at San Antonio, 78229-3900, USA. lamf@uthscsa.edu
Ereshefsky
L
L
Toney
G B
GB
Gonzales
C
C
D000328:Adult; D014150:Antipsychotic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D001682:Biological Availability; D003024:Clozapine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018592:Cross-Over Studies; D016568:Drugs, Generic / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D013810:Therapeutic Equivalency; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D016568:Drugs, Generic; D003024:Clozapine