Drug interactions
Clozapine + Methadone
Severity: Major
Clozapine and Methadone: major interaction.
Last updated Sources: US FDA label
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 can prolong the QT interval, and clozapine also causes sedation, respiratory depression (especially with opioids) and orthostatic hypotension. The combination raises the risk of arrhythmia and CNS or respiratory depression.
What this interaction means in plain words
Clozapine and Methadone can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for.
Clozapine belongs to Central Nervous System; Methadone belongs to Musculoskeletal.
Why it happens
Additive QT prolongation and additive CNS and respiratory depression.
What to do
Obtain a baseline ECG, correct electrolytes, and monitor the ECG after dose changes. Watch closely for sedation, hypotension and respiratory depression.
What to ask your pharmacist
- Does the benefit of taking both outweigh the risk in my case?
- Do I need any blood test, ECG or other check while on both?
- What early warning signs should I watch for, and what should I do if they appear?
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References
Other interactions of Methadone
- Alvimopan + Methadone Contraindicated
- Calcium / magnesium / potassium / sodium oxybates + Methadone Contraindicated
- Droperidol + Methadone Contraindicated
- Ibutilide + Methadone Contraindicated
- Isocarboxazid + Methadone Contraindicated
- Lefamulin + Methadone Contraindicated
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 Methadone?
MediHelp rates the interaction as major. Clozapine and Methadone can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for. Both drugs can prolong the QT interval, and clozapine also causes sedation, respiratory depression (especially with opioids) and orthostatic hypotension. The combination raises the risk of arrhythmia and CNS or respiratory depression.
How serious is the interaction between Clozapine and Methadone?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Obtain a baseline ECG, correct electrolytes, and monitor the ECG after dose changes. Watch closely for sedation, hypotension and respiratory depression.
What other medicines interact with Methadone?
MediHelp also lists interactions of Methadone with, for example, Alvimopan, Calcium / magnesium / potassium / sodium oxybates, Droperidol. The full list is on the Methadone page.
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