Generic Clozapine

As a consequence of its prevalence, early onset and chronicity, schizophrenia imposes clinical and economic impediments to healthcare practitioners and society alike. Among the many antipsychotics available to treat the symptoms of this devastating illness, clozapine has emerged and differentiated itself from the others as the agent most efficacious for the treatment of refractory patients. Since the patent for Clozaril® 1 (Novartis) expired in 1998, three manufacturers of generic clozapine have submitted abbreviated new drug applications to the US FDA for review and approval to market a generic clozapine product. In each case, the US FDA deemed the generic formulations to be bioequivalent to the brand name Clozaril®. Apart from case reports, industry-sponsored studies have been conducted comparing Clozaril® with two generic formulations. In one case, a generic formulation of clozapine manufactured by Creighton Products Corporation (formerly a subsidiary [generic house] of Sandoz Pharmaceuticals) was found to be bioequivalent to Clozaril®. On the other hand, studies (sponsored by Novartis) have challenged the bioequivalence, therapeutic equivalence and interchangeability between Clozaril® and a generic formulation manufactured by Zenith Goldline Pharmaceuticals (now IVAX Corporation). The IVAX Corporation-sponsored studies refuted these claims citing data from two patient registry database studies and one small clinical trial. Apart from a single in-house bioequivalence study, no further investigations have been conducted with a third generic formulation manufactured by Mylan Pharmaceutical. Although the clinical significance of the above discrepancy is obvious, what is less than obvious is the pharmacoeconomic implications that arises from this debate. Clearly, if the brand name and generic formulations are ‘truly’ bioequivalent, then the cost savings realised would be the difference in acquisition cost. On the other hand, if the various formulations are not bioequivalent, then the economic benefits of a lower-priced generic formulation may be compromised. In the worst-case scenario, if a patient decompensates as a result of switching from Clozaril® to a generic formulation, the added direct costs (i.e. hospitalisation) and indirect cost (i.e. lost productivity) will most certainly offset any cost savings resulting from the use of a generic formulation. p ]Until further studies have been conducted, we suggest that patients who are treatment refractory and stabilised on Clozaril® are not switched to a generic formulation. On the other hand, if a patient is stabilised on Clozaril® and not treatment refractory, then cautious switching to a generic formulation may be reasonable. Finally, initiating a generic formulation in a ‘clozapine-naïve’ individual would be appropriate. The cost implications related to these recommendations will depend on the success or failure of treatment. Copyright Adis International Limited 2003