A Program to Convert Patients from Trade‐Name to Generic Clozapine

Abstract

In spring 2000, the Missouri Department of Mental Health mandated that its psychiatric inpatient facilities convert patients from trade-name to generic clozapine. The pharmacy department at our facility was encouraged to develop a conversion program to oversee and assess the efficacy and tolerability of the change. A protocol to monitor the conversion of patients to generic clozapine hospitalwide was developed. The primary objective was to determine whether therapeutic response and level of tolerability were the same with generic versus trade-name clozapine. The secondary objective was to determine whether changes in monitoring white blood cell and absolute neutrophil counts were necessary after conversion. Our results showed that most patients did not experience changes greater than a mean of 5 points in their scores on the Brief Psychiatric Rating Scale (BPRS). However, a statistically significant difference was seen in 22 patients who had a mean reduction or an increase of less than 5 points (p=0.0139) in BPRS scores compared with two patients who had a mean increase greater than 5 points. Assessment of percentage change in BPRS scores indicated that 14 (58%) converted patients had a 1-50% decrease in mean BPRS scores, and 10 (42%) had a 1-40% increase. However, of those with a mean BPRS increase, five (50%) had an increase of 10% or less. Our clozapine conversion program resulted in the successful conversion of all 24 patients.

Clinical Equivalence of Generic Clozapine

“…Therefore, it is extremely unlikely that our design merely failed to detect a small increase in utilization. The lack of an increase in utilization is consistent with previous reports by Makela et al (2003) and Stoner et al (2003) demonstrating that patients switched to generic clozapine did not show a deterioration in clinical status 2-4 months after the switch. Further, Sajbel, Carter, and Wiley (2001) showed a lack of leucopenia or a need to change clozapine dosages when patients were switched to Zenith Goldline Pharmaceuticals clozapine, which is also consistent with our data.…”

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

“…Stoner and colleagues 48 reported clinical results from an intensive monitoring program for the conversion of Clozaril-treated patients (mean ± S.D. dose of 508.3 ± 140.4 mg/day) to generic clozapine (Zenith Goldline) in a cohort of 24 patients (mean ± S.D.…”

“…64 Although there were no reports of patients discovering which type of clozapine they were taking, this does not exclude possible loss of blinding. Interestingly, studies with no sponsorship and those supported by a generic manufacturer 27,48 tended to demonstrate good tolerability of the generic formulation while the one study that was supported by the manufacturer of Clozaril reported clinical deterioration in several enrolled patients while receiving a generic formulation. 64 While our review supports the general effectiveness and safety of conversion from brand-name to generic clozapine, there are several clinical caveats to consider.…”

“…Most studies had very small sample sizes-only three studies involved 50 or more patients. 55,59,60 Preswitch observation periods were very short in several studies, 48,52,63,64 an important consideration given the wide intraindividual and interindividual variability in clinical symptom burden and clozapine concentrations that may be encountered in clinical practice. In addition, we might expect further symptomatic and functional improvement after a switch to generic clozapine if the medication was taken for less than six months, since this is generally accepted as the amount of time required for many treatment-resistant patients with schizophrenia to show substantial improvement.…”

Regulatory and clinical aspects of psychotropic medicinal products bioequivalence

“…In addition, there have been no observations of any significant clinical status worsening after introduction of a generic clozapine (Oluboka et al, 2010;Makela et al, 2003). Moreover, Stoner et al (2003) have reported a significant improvement in the clinical status as measured by the BPRS (Brief Psychiatric Rating Scale) in three months since switching from the reference to generic clozapine in 58% of patients.…”