Clinical Drug Investigation

, Volume 28, Issue 4, pp 231–239 | Cite as

Bioequivalence of Clozapine Orally Disintegrating 100-mg Tablets Compared with Clozapine Solid Oral 100-mg Tablets after Multiple Doses in Patients with Schizophrenia

Original Research Article


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.


  1. 1.
    American Psychiatric Association. Practice guidelines for the treatment of patients with schizophrenia. 2nd ed. Washington, DC: American Psychiatric Publishing, 2004Google Scholar
  2. 2.
    Meltzer HY, Alphs L, Green AI, et al. Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT). Arch Gen Psychiatry 2003 Jan; 60(1): 82–91PubMedCrossRefGoogle Scholar
  3. 3.
    Ebrahim GM, Gibier B, Gacono CB, et al. Patient response to clozapine in a forensic psychiatric hospital. Hosp Community Psychiatry 1994 Mar; 45(3): 271–3PubMedGoogle Scholar
  4. 4.
    Meltzer HY, Fatemi H. Suicide in schizophrenia: the effect of clozapine. Clin Neuropharmacol 1995; 18Suppl. 3: S18–24CrossRefGoogle Scholar
  5. 5.
    Krakowski MI, Czobor P, Citrome L, et al. Atypical anti-psychotic agents in the treatment of violent patients with schizophrenia and schizoaffective disorder. Arch Gen Psychiatry 2006 Jun; 63(6): 622–9PubMedCrossRefGoogle Scholar
  6. 6.
    McEvoy JP, Lieberman JA, Stroup TS, et al. Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment. Am J Psychiatry 2006 Apr; 163(4): 600–10PubMedCrossRefGoogle Scholar
  7. 7.
    US FDA. Approved drug products with therapeutic equivalence evaluations. 26th ed. Rockville, MD 2006Google Scholar
  8. 8.
    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 23-4PubMedGoogle Scholar
  9. 9.
    US FDA. Clozapine tablets: in vivo bioequivalence and in vitro dissolution testing [online]. Available from URL: http://www. [Accessed 2007 Oct 17]Google Scholar
  10. 10.
    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): 47–53PubMedGoogle Scholar
  11. 11.
    Freeman DJ, Oyewumi LK. Will routine therapeutic drug monitoring have a place in clozapine therapy? Clin Pharmacokinet 1997 Feb; 32(2): 93–100PubMedCrossRefGoogle Scholar
  12. 12.
    Khan AY, Preskorn SH. Examining concentration-dependent toxicity of clozapine: role of therapeutic drug monitoring. J Psychiatr Pract 2005 Sep; 11(5): 289–301PubMedCrossRefGoogle Scholar
  13. 13.
    Ereshefsky L, GlazerWM. Comparison of the bioequivalence of generic versus branded clozapine. J Clin Psychiatry 2001; 62Suppl. 5: 25–7PubMedGoogle Scholar
  14. 14.
    Mofsen R, Balter J. Case reports of the reemergence of psychotic symptoms after conversion from brand-name clozapine to a generic formulation. Clin Ther 2001 Oct; 23(10): 1720–31PubMedCrossRefGoogle Scholar
  15. 15.
    Leucht S, Heres S. Epidemiology, clinical consequences, and psychosocial treatment of nonadherence in schizophrenia. J Clin Psychiatry 2006; 67 Suppl. 5: 3–8PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  1. 1.Medical Affairs, Azur Pharma, Inc.PhiladelphiaUSA
  2. 2.Azur Pharma, Inc.PhiladelphiaUSA

Personalised recommendations