Date: 24 Aug 2012
Bioequivalence of Clozapine Orally Disintegrating 100-mg Tablets Compared with Clozapine Solid Oral 100-mg Tablets after Multiple Doses in Patients with Schizophrenia
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
Background: This study compared the bioequivalence of FazaClo® (clozapine orally disintegrating tablets) 100 mg to Clozaril® (clozapine standard oral tablets) 100 mg after multiple doses in patients with schizophrenia.
Methods: This was a randomized, open-label, multiple-dose study in which patients with schizophrenia received FazaClo® or Clozaril® 100 mg twice daily for 5 days before crossing over to the alternate therapy. Blood samples were obtained at regular intervals during and after the completion of treatment, and standard pharmacokinetic parameters were calculated. Safety and patient satisfaction with FazaClo® were also assessed.
Results: Thirty-six patients were enrolled, of whom 33 completed the study and 30 were included in the steady-state analyses. All pharmacokinetic parameters for clozapine and desmethylclozapine (the major metabolite of clozapine) were similar between FazaClo® and Clozaril® in both the completer and steady-state populations. Geometric mean values for steady-state maximum and minimum concentrations and area under the plasma concentration-time curve for FazaClo® were all within 95–105% of those for Clozaril®, well within the range considered by the US FDA as acceptable for bioequivalence (80–125%). Patients also expressed a high level of satisfaction with the FazaClo® orally disintegrating tablet formulation.
Conclusions: FazaClo® produced pharmacokinetic profiles almost identical to those of Clozaril®. This should provide clinicians with reassurance that patients who receive FazaClo® will achieve plasma drug concentrations similar to those produced by the same daily dose of Clozaril®, and that no cross-titration is necessary when switching from one of these clozapine formulations to the other.
American Psychiatric Association. Practice guidelines for the treatment of patients with schizophrenia. 2nd ed. Washington, DC: American Psychiatric Publishing, 2004
Ebrahim GM, Gibier B, Gacono CB, et al. Patient response to clozapine in a forensic psychiatric hospital. Hosp Community Psychiatry 1994 Mar; 45(3): 271–3PubMed
Meltzer HY, Fatemi H. Suicide in schizophrenia: the effect of clozapine. Clin Neuropharmacol 1995; 18Suppl. 3: S18–24CrossRef
US FDA. Approved drug products with therapeutic equivalence evaluations. 26th ed. Rockville, MD 2006
Lam YW, Ereshefsky L, Toney GB, et al. Branded versus generic clozapine: bioavailability comparison and interchangeability issues. J Clin Psychiatry 2001; 62Suppl. 5: 18–22; discussion 23-4PubMed
US FDA. Clozapine tablets: in vivo bioequivalence and in vitro dissolution testing [online]. Available from URL: http://www. fda.gov/cder/Guidance/6077fnl.pdf [Accessed 2007 Oct 17]
Tassaneeyakul W, Kittiwattanagul K, Vannaprasaht S, et al. Steady-state bioequivalence study of clozapine tablet in schizophrenic patients. J Pharm Pharm Sci 2005; 8(1): 47–53PubMed
Ereshefsky L, GlazerWM. Comparison of the bioequivalence of generic versus branded clozapine. J Clin Psychiatry 2001; 62Suppl. 5: 25–7PubMed
Leucht S, Heres S. Epidemiology, clinical consequences, and psychosocial treatment of nonadherence in schizophrenia. J Clin Psychiatry 2006; 67 Suppl. 5: 3–8PubMed
- Bioequivalence of Clozapine Orally Disintegrating 100-mg Tablets Compared with Clozapine Solid Oral 100-mg Tablets after Multiple Doses in Patients with Schizophrenia
Clinical Drug Investigation
Volume 28, Issue 4 , pp 231-239
- Cover Date
- Print ISSN
- Online ISSN
- Springer International Publishing
- Additional Links
- Industry Sectors