Drug interactions
Methadone + Primidone
Severity: Major
Methadone and Primidone: 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
Primidone, and its metabolite phenobarbital, induce hepatic enzymes and can lower methadone concentrations, possibly precipitating opioid withdrawal or loss of analgesia. Both drugs also cause sedation, so effects may add together as the interaction evolves, and stopping primidone later may cause methadone levels to rise.
What this interaction means in plain words
Methadone and Primidone 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.
Methadone belongs to Musculoskeletal; Primidone belongs to Central Nervous System.
Why it happens
Phenobarbital-mediated induction of CYP3A4 and CYP2B6 increases methadone clearance, with additive CNS depression.
What to do
Monitor for withdrawal symptoms and adjust the methadone dose upward as needed when primidone is started. Reduce methadone and watch for oversedation if primidone is withdrawn.
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 Primidone
- Lorlatinib + Primidone Contraindicated
- Lurasidone + Primidone Contraindicated
- Primidone + Ranolazine Contraindicated
- Primidone + Sofosbuvir-velpatasvir-voxilaprevir Contraindicated
- Primidone + Voriconazole Contraindicated
- Abiraterone + Primidone Major
Frequently asked questions
Can I take Methadone with Primidone?
MediHelp rates the interaction as major. Methadone and Primidone 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. Primidone, and its metabolite phenobarbital, induce hepatic enzymes and can lower methadone concentrations, possibly precipitating opioid withdrawal or loss of analgesia. Both drugs also cause sedation, so effects may add together as the interaction evolves, and stopping primidone later may cause methadone levels to rise.
How serious is the interaction between Methadone and Primidone?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Monitor for withdrawal symptoms and adjust the methadone dose upward as needed when primidone is started. Reduce methadone and watch for oversedation if primidone is withdrawn.
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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