Drug interactions
Clozapine + Codeine
Severity: Moderate
Clozapine and Codeine: moderate interaction.
Last updated
For healthcare professionals — reference only. This page is a brief summary, not medical advice and not a substitute for official labeling or clinical judgement. Always verify before prescribing or dispensing.
Summary
Both drugs cause sedation and can depress respiration, and clozapine also carries a risk of circulatory collapse, so the combination may increase CNS depression. Clozapine is only a weak CYP2D6 inhibitor, so any loss of codeine analgesia is probably small.
What this interaction means in plain words
Clozapine and Codeine can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken.
Clozapine belongs to Central Nervous System; Codeine belongs to Musculoskeletal.
Why it happens
Additive CNS depression; clozapine is a weak CYP2D6 substrate/inhibitor that may slightly reduce conversion of codeine to morphine.
What to do
Start codeine at a low dose and monitor for excessive sedation, hypotension and respiratory depression. Reassess analgesic response if pain control is inadequate.
What to ask your pharmacist
- Should I take them at different times of day?
- Does the dose of either medicine need to change?
- Is there anything I should avoid, such as alcohol or certain foods, while on both?
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Other interactions of Codeine
- Alvimopan + Codeine Contraindicated
- Codeine + Isocarboxazid Contraindicated
- Codeine + Olanzapine / samidorphan Contraindicated
- Codeine + Phenelzine Contraindicated
- Codeine + Tranylcypromine Contraindicated
- Alfentanil + Codeine Major
Other interactions of Clozapine
- Clozapine + Deferiprone Contraindicated
- Clozapine + Irinotecan Contraindicated
- Clozapine + Pimozide Contraindicated
- Clozapine + Thioridazine Contraindicated
- Acalabrutinib + Clozapine Major
- Adagrasib + Clozapine Major
Frequently asked questions
Can I take Clozapine with Codeine?
MediHelp rates the interaction as moderate. Clozapine and Codeine can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken. Both drugs cause sedation and can depress respiration, and clozapine also carries a risk of circulatory collapse, so the combination may increase CNS depression. Clozapine is only a weak CYP2D6 inhibitor, so any loss of codeine analgesia is probably small.
How serious is the interaction between Clozapine and Codeine?
MediHelp rates it moderate, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Start codeine at a low dose and monitor for excessive sedation, hypotension and respiratory depression. Reassess analgesic response if pain control is inadequate.
What other medicines interact with Codeine?
MediHelp also lists interactions of Codeine with, for example, Alvimopan, Isocarboxazid, Olanzapine / samidorphan. The full list is on the Codeine page.
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