Clozaril Medication Interactions: What Prescribers & Patients Need to Know

Clozaril (clozapine) has complex pharmacology and interacts with many other medications, both prescription and over-the-counter. Some interactions increase clozapine levels which can lead to toxicity, while others reduce clozapine levels and effectiveness. Careful management of medication regimen is required to limit risks and ensure safety.

CYP450 Enzyme Inhibition

Clozapine is metabolized by CYP1A2, CYP2D6, and CYP3A4 enzymes in the liver. Medications that inhibit these enzymes will increase clozapine levels in the blood. Examples include:

  • Fluvoxamine (antidepressant): Can increase clozapine levels up to 6-fold. Avoid combination if possible due to high toxicity risk. If essential, use lowest effective doses of both and monitor plasma clozapine levels closely.
  • Ketoconazole (antifungal): Increases clozapine levels by up to 50-90% via CYP3A4 inhibition. Monitor for toxicity or adjust clozapine dose if used long-term. Single-dose antifungals are less likely to significantly alter clozapine metabolism.
  • Ciprofloxacin (antibiotic): CYP1A2 inhibitor that can increase clozapine levels by up to 70%. Clozapine dose may need reduction if used concurrently to avoid toxicity. Plasma level monitoring is advisable.
  • Hormonal contraceptives: Estrogen in oral contraceptives is a weak CYP1A2 inhibitor. Clozapine dose adjustments are usually unnecessary but females starting or stopping birth control require monitoring.

CYP450 Enzyme Induction

Substances that induce hepatic enzymes can significantly lower clozapine plasma concentrations. Examples include:

  • Carbamazepine (mood stabilizer): Potent CYP1A2 inducer that reduces clozapine levels by up to 50-70%. May require up to doubling the clozapine dose to compensate but plasma level monitoring is essential due to variability between individuals.
  • Phenytoin (anticonvulsant): Like carbamazepine, phenytoin induces CYP1A2 and can decrease clozapine levels enough to reduce effectiveness. Dose increases will depend on degree of induction and should be guided by drug level testing.
  • St. John’s wort (herbal supplement): Also significantly lowers clozapine levels through CYP induction. Patients should avoid St. John’s wort due to risks of losing response to clozapine treatment.
  • Smoking: Polycyclic aromatic hydrocarbons in cigarette smoke strongly induce CYP1A2 enzymes. Smoking cessation causes clozapine levels to rise, often sharply. Clozapine dose reduction of up to 50% may be required with monitoring of plasma drug concentrations. Gradual titration is needed if resuming smoking.

In summary, clinicians must closely consider a patient’s complete medication and supplement regimen when prescribing clozapine and make adjustments as needed based on potential for significant interactions. Similarly, patients and caregivers need to understand the importance of routinely reporting any changes to the clozapine treatment team. Ongoing vigilance and management of both induction and inhibition effects on clozapine metabolism are paramount to maximizing safety and effectiveness. Monitoring of plasma levels in complex or unstable cases provides an additional safeguard given the possibility of individual variability and unpredictable responses. While adding to the overall monitoring burden, medication reviews and dose titrations based on changes represent a key strategy for optimizing clozapine treatment and limiting risks in certain patient subgroups.

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:


    • ANSM (Agence nationale de sécurité du médicament et des produits de santé):


    • AEMPS (Agencia Española de Medicamentos y Productos Sanitarios):


    • BfArM (Bundesinstitut für Arzneimittel und Medizinprodukte):


    For questions about your medication:

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


    • 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:

    Canada (French)

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


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


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


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


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


    • 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

Log In

Forgot password?

Forgot password?

Enter your account data and we will send you a link to reset your password.

Your password reset link appears to be invalid or expired.

Log in

Privacy Policy

Add to Collection

No Collections

Here you'll find all collections you've created before.