The Importance of Blood Monitoring with Clozaril

Clozaril (clozapine) is the only medication that requires routine blood monitoring to detect a rare but serious side effect known as agranulocytosis, a sharp drop in white blood cells which increases the risk of dangerous infections. As such, regular blood tests are mandatory to ensure this potentially life-threatening complication is identified early.

Agranulocytosis Risk

Clozaril causes agranulocytosis by suppressing the bone marrow’s production of granulocytes, a type of white blood cell (WBC) that fights infection. The incidence is 0.8% with weekly monitoring, but increases to 3% without monitoring. Agranulocytosis usually occurs within 6 months, although it can develop at any time throughout treatment.

Clozaril Risk Evaluation and Mitigation Strategy (REMS)

Due to risks, Clozaril has a strict REMS program including:

  • Baseline WBC and absolute neutrophil count (ANC) before starting Clozaril. Normal ranges are 3.5-11 x 10^9 cells/L and 2.0-7.5 x 10^9 cells/L respectively.
  • Weekly blood tests for 18 weeks, then biweekly up to 1 year. After 1 year and stable, monitoring reduces to monthly but must continue lifelong.
  • Immediately stop Clozaril if WBC <3.0 or ANC <1.5. Do not rechallenge.
  • Withhold Clozaril and repeat bloods if WBC 3.0-3.5 or ANC 1.5-2.0. May restart after levels increase if approved by the Novartis Clozaril National Registry.
  • Reduce dose or withhold Clozaril if WBC >15.0 or ANC >11.0 to avoid toxicity. Resume at a lower dose once levels decrease to within range.
  • Report results to registry within 2 weeks to continue accessing Clozaril. Alert registry immediately if out of range values.
  • Educate patients and caregivers on risks and importance of blood monitoring compliance. Intervening at the Earliest Signs
    Prompt intervention is critical once reduced blood cell counts are detected to avoid infection and serious complications. Options include:
  • Immediately stop Clozaril and do not rechallenge if neutrophil count <1,500 cells/μL or lowers over successive tests. The risk of agranulocytosis is too high.
  • Granulocyte colony stimulating factor (G-CSF) to stimulate bone marrow if levels 1,000-1,500 cells/μL. Temporarily withhold Clozaril, then may restart at lower dose if levels rise and remain stable. However, recurrence risk with rechallenge is high.
  • Prophylactic antibiotics and very close monitoring if levels marginally reduced but still over 1,500 cells/μL. Withhold Clozaril at discretion of prescribing psychiatrist based on clinical status.
  • Hospitalization for isolation and management may be required, especially if fever or other signs of infection are present along with reduced WBCs. IV antibiotics will be administered and all drugs with potential bone marrow toxicity ceased.

In summary, routine blood cell count monitoring remains the only way to mitigate risks with Clozaril and avoid delaying identification and treatment of agranulocytosis or related complications. Strict compliance with the REMS program is essential to accessing this vital medication and ensuring patient safety is maximized based on close clinical supervision and early medical intervention where required.


There are various forms of drugs available, such as tablets or liquids, and each may have a separate patient information leaflet (PIL) for different doses. It is important to refer to the PIL for the specific form and dose of the drug that you have been prescribed.

You can search for further information and PILs on websites such as:

  • The British National Formulary (BNF)
  • Electronic medicines compendium (emc)
  • The National Library of Medicine's DailyMed
  • The Food and Drug Administration (FDA) 
  • Different drug forms like tablets or liquids have specific patient information leaflets (PIL) for various doses. Refer to the PIL for your prescribed drug form and dose.

    Search for PILs on websites like:

    France

    • ANSM (Agence nationale de sécurité du médicament et des produits de santé): ansm.sante.fr

    Spain

    • AEMPS (Agencia Española de Medicamentos y Productos Sanitarios): aemps.gob.es

    Germany

    • BfArM (Bundesinstitut für Arzneimittel und Medizinprodukte): bfarm.de

    Italy

    For questions about your medication:

    • Consult your doctor, a healthcare professional, or a pharmacist

    France

    • Contact SOS Médecins: 3624
    • For mental health support, contact SOS Suicide: 01 45 39 40 00

    Belgium (French)

    Switzerland (French)

    • La Main Tendue: 143
    • Website: 143.ch

    Canada (French)

    • Centre de prévention du suicide du Québec: 1 866 APPELLE (1 866 277-3553)
    • Website: cpsquebec.ca

    Spain

    • Contact emergency number: 112
    • For mental health support, contact Teléfono de la Esperanza: 717 003 717

    Germany

    • Contact emergency number: 112
    • For mental health support, contact Telefonseelsorge: 0800 111 0 111 or 0800 111 0 222

    Italy

    • Contact emergency number: 112
    • For mental health support, contact Telefono Amico: 199 284 284

    Netherlands

    • Contact emergency number: 112
    • For mental health support, contact 113 Zelfmoordpreventie: 0800 0113

    Portugal

    • Contact emergency number: 112
    • For mental health support, contact Sos Voz Amiga: 21 354 45 45, 91 280 26 69, or 96 352 46 60

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