Interactions between Clozapine and other drugs

Potential to increase Clozapine levels

Antiviral treatments for COVID-19 disease
- Paxlovid® is contraindicated in people taking clozapine, with the risk of serious clozapine toxicity.

SSRIs for example:
- fluvoxamine (very large effect)
- fluoxetine
- paroxetine
- sertraline (large doses)
Ciprofloxacin
Cimetidine
some macrolide antibiotics including:
- erythromycin
- clarithromycin
- azithromycin
caffeine (large doses)

Potential to decrease Clozapine levels

Carbamazepine
Rifampicin
St Johns Wort
Omeprazole
Phenytoin
Phenobarbitone

Potential to depress bone marrow

Carbamazepine
Trimethoprim/sulfamethoxazole
Nitrofurantoin
Cytotoxic medication
Immunosuppressant medication

Potential to depress respiration

Benzodiazepines, especially large parenteral doses or at start of therapy

Potential for anticholinergic side effects

For example constipation, urinary retention, delirium

Anticholinergic TCAs for example
- amitriptyline
- dothiepin
Anticholinergic antipsychotics for example
- chlorpromazine
- pericyazine
- quetiapine
EPSE medication for example
- benzhexol
- benztropine
- biperiden
sedating antihistamines for example
- diphenhydramine
- cyproheptadine
- promethazine
- trimeprazine
gastrointestinal antispasmodics for example
- atropine
- hyoscine

Potential for hypotension

Antihypertensives
TCAs
Some antipsychotics for example
- chlorpromazine
- pericyazine
- trifluoperazine
- risperidone (initially)
- quetiapine (initially)

Potential for changes due to smoking

Starting or stopping smoking can cause dramatic changes in clozapine blood levels

Prescription medications used for smoking cessation have been associated with destabilisation of mental state in some patients. Consider a strategic approach in consultation with a psychiatrist. Clozapine levels must be monitored in people ceasing smoking to avoid clozapine toxicity. Refer to the Clozapine Management Clinical Guideline (CMCG) (PDF 3.95MB) for required monitoring.

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Last updated: 15 Mar 2023

SA Health

Interactions between Clozapine and other drugs

Potential to increase Clozapine levels

Potential to decrease Clozapine levels

Potential to depress bone marrow

Potential to depress respiration

Potential for anticholinergic side effects

Potential for hypotension

Potential for changes due to smoking

Acknowledgement of Country

Interactions between Clozapine and other drugs

Potential to increase Clozapine levels

Potential to decrease Clozapine levels

Potential to depress bone marrow

Potential to depress respiration

Potential for anticholinergic side effects

Potential for hypotension

Potential for changes due to smoking

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