clozapine (Clozaril)

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Introduction

Tradename: Clozaril.

Indications

Contraindications

Caution:

  • no NOT stop medication abrubtly
  • taper of 1-2 weeks if possible
  • use with caution in patients with seizure disorder
  • use with caution in patients with cardiovascular disease

pregnancy category = b

safety in lactation = -

Dosage

Tabs: 25 & 100 mg.

Pharmacokinetics

elimination via liver

elimination via kidney

1/2life = 8-12 hours initial

1/2life = 20 hours terminal

protein binding = 95 %

Monitor

(see Notes below)

  • WBC* weekly for 1st 6 months
  • WBC* every other week after 6 months
  • WBC* monthly after one year[9]
  • baseline EEG recommended prior to therapy

* WBC should include absolute neutrophil count[9]

Adverse effects

* benign, self-limited temperature elevations may occur in the 1st 3 weeks of therapy

# mandatory participation in Clozapine REMS Program (see notes)[15]

Drug interactions

Laboratory

Mechanism of action

Notes

More general terms

Additional terms

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 1146-47
  3. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  4. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  5. 5.0 5.1 Journal Watch 21(14):113-114, 2001 Coulter et al, BMJ 322:1207, 2001
  6. 6.0 6.1 6.2 6.3 Prescriber's Letter 9(3):13 2002
  7. 7.0 7.1 Prescriber's Letter 10(11):62 2003
  8. 8.0 8.1 8.2 Bronstein J, In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 29-Oct 2, 2004
  9. 9.0 9.1 9.2 http://www.fda.gov/medwatch/safety/2006/safety06.htm#Clozaril
  10. 10.0 10.1 Tiihonen J et al. 11-year follow-up of mortality in patients with schizophrenia: A population-based cohort study (FIN11 study). Lancet 2009 Jul 11 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/19595447 <Internet> http://dx.doi.org/10.1016/S0140-6736(09)60742-X
  11. Closaril registry http://www.clozarilregistry.com Contact: (800) 448-5938
  12. Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=260704&pb=PRL (subscription needed) http://www.prescribersletter.com
  13. 13.0 13.1 Deprecated Reference
  14. 14.0 14.1 14.2 Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013
  15. 15.0 15.1 15.2 15.3 FDA Safety Alert. Sept 15, 2015 Clozapine: Drug Safety Communication - FDA Modifies Monitoring for Neutropenia; Approves New Shared REMS Program. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm462229.htm
  16. 16.0 16.1 Medical Knowledge Self Assessment Program (MKSAP) 17, 18. American College of Physicians, Philadelphia 2015, 2018.
  17. FDA Drug Safety and Availability. Jan 16, 2019 The Clozapine Risk Evaluation and Mitigation Strategy (REMS) Program Modification will go live on February 28, 2019. https://www.fda.gov/drugs/drugsafety/ucm467560.htm
    Information on Clozapine. https://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm497790.htm
    Cloxapine REMS program https://www.clozapinerems.com/CpmgClozapineUI/home.u
  18. 18.0 18.1 fDA MedWatch. Safety Alert. Jan 28, 2020 Clozaril, Fazaclo ODT, Versacloz (clozapine): Drug Safety Communication - FDA Strengthens Warning That Untreated Constipation Can Lead to Serious Bowel Problems. https://www.fda.gov/safety/medical-product-safety-information/clozaril-fazaclo-odt-versacloz-clozapine-drug-safety-communication-fda-strengthens-warning-untreated
  19. 19.0 19.1 Osorio L Clozapine and Cancer Risk: New Data. Medscape. May 12, 2022 https://www.medscape.com/viewarticle/973902
    Tiihonen J, et al. Long-term treatment with clozapine and other antipsychotic drugs and the risk of haematological malignancies in people with schizophrenia: a nationwide case-control and cohort study in Finland. Lancet Psychiatry. 2022 May;9(5):353-362 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35334224

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