Drug interactions
Cimetidine + Methadone
Severity: Major
Cimetidine and Methadone: major interaction.
Last updated Sources: UK SmPC
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
Cimetidine can raise methadone concentrations by inhibiting its hepatic metabolism, increasing sedation, respiratory depression and potentially QT prolongation. Case reports describe opioid toxicity after cimetidine initiation.
What this interaction means in plain words
Cimetidine 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.
Cimetidine belongs to Gastrointestinal Tract; Methadone belongs to Musculoskeletal.
Why it happens
Cimetidine inhibits CYP3A4 and CYP2D6/2B6 pathways that metabolize methadone.
What to do
Prefer famotidine; if cimetidine is used, monitor for sedation, respiratory depression and QTc, and reduce methadone dose as needed.
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 Cimetidine
- Cimetidine + Dofetilide Contraindicated
- Cimetidine + Fezolinetant Contraindicated
- Alfentanil + Cimetidine Major
- Atazanavir + Cimetidine Major
- Carmustine + Cimetidine Major
- Cimetidine + Citalopram Major
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
Frequently asked questions
Can I take Cimetidine with Methadone?
MediHelp rates the interaction as major. Cimetidine 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. Cimetidine can raise methadone concentrations by inhibiting its hepatic metabolism, increasing sedation, respiratory depression and potentially QT prolongation. Case reports describe opioid toxicity after cimetidine initiation.
How serious is the interaction between Cimetidine 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: Prefer famotidine; if cimetidine is used, monitor for sedation, respiratory depression and QTc, and reduce methadone dose as needed.
What other medicines interact with Cimetidine?
MediHelp also lists interactions of Cimetidine with, for example, Dofetilide, Fezolinetant, Alfentanil. The full list is on the Cimetidine page.
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