Converting from brand-name to generic clozapine: A review of effectiveness and tolerability data

Abstract

Available literature supports the effectiveness and safety of generic clozapine formulations in patients who previously were stable during treatment with brand-name clozapine. The risk of poor outcome after conversion to a generic clozapine formulation appears to be low but difficult to predict. Patients should be closely monitored during the first one to three months after conversion from one formulation to another.

Bioequivalence and therapeutic equivalence of psychotropic drugs

“…Also none of the patients discontinued their treatment in the six months of observation, after switching to a generic drug, and no differences in compliance were noted between the reference and generic drug treatment. Similar data were obtained in the review summarizing 966 cases of reference clozapine replacement with one of the 4 generic drugs available in the American market [14]. In most of the studies no clinical deterioration, changes in the serum concentration of clozapine or decreased tolerance for the treatment was observed [15]However, some changes have been reported in the concentrations of the metabolite of clozapine, norclozapine, in patients who have been switched from the reference to generic drug [16].…”

“…U żadnego z pacjentów nie przerwano leczenia w ciągu 6 miesięcy obserwacji po zamianie leku referencyjnego na generyczny, nie odnotowano też różnic w przestrzeganiu leczenia (compliance) w trakcie leczenia produktem referencyjnym i generycznym. Zbliżone dane otrzymano w pracy przeglądowej, podsumowującej 966 przypadków zastąpienia produktu referencyjnego klozapiny jednym z 4 produktów generycznych, dostępnych na rynku amerykańskim [14]. W większości analizowanych badań nie stwierdzono objawów pogorszenia stanu klinicznego, zmian stężenia klozapiny w surowicy lub zmniejszenia tolerancji leczenia.…”

Switching from Brand‐Name to Generic Psychotropic Medications: A Literature Review

“…A recent review [80] pointed out that the IVAX and Zenith Goldline generics are now both marketed by Teva and that several of the above studies had methodological limitations. These authors recommend that generic substitution be done with caution, with the patient and caregiver's knowledge and with documentation of pre‐ and postsubstitution clinical status and clozapine levels.…”

Regulatory and clinical aspects of psychotropic medicinal products bioequivalence

“…It should however be emphasized that the above-mentioned US reports of clinical state deterioration refer only to the first clozapine generic that was registered by the FDA in 1999 (Ereshefsky and Glazer, 2001). In a study summing up all primary research published between 1995 and 2008, including cases of 966 patients who switched from reference clozapine to one of its 4 generics available on the American market, no symptoms of clinical status worsening, changes in clozapine serum concentration nor incidences of reduced treatment tolerability have been observed after switching from reference to generic treatment in the majority of the analyzed studies (Bobo et al, 2010).…”