Drug interactions
Fosphenytoin + Methadone
Severity: Major
Fosphenytoin 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
Fosphenytoin, through its active metabolite phenytoin, induces hepatic enzymes that metabolise methadone, lowering methadone concentrations. Patients on methadone maintenance can develop opioid withdrawal symptoms and loss of analgesic effect. If phenytoin is stopped, methadone levels may rise and cause toxicity.
What this interaction means in plain words
Fosphenytoin 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.
Fosphenytoin belongs to Central Nervous System; Methadone belongs to Musculoskeletal.
Why it happens
Phenytoin induces CYP3A4 and CYP2B6 (and other enzymes), increasing methadone clearance.
What to do
Monitor for withdrawal symptoms and titrate methadone upward as needed when fosphenytoin is started. Reduce the methadone dose again and watch for sedation and respiratory depression if the anticonvulsant is discontinued.
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 Fosphenytoin
- Dronedarone + Fosphenytoin Contraindicated
- Fosphenytoin + Ledipasvir-sofosbuvir Contraindicated
- Fosphenytoin + Lorlatinib Contraindicated
- Fosphenytoin + Lurasidone Contraindicated
- Fosphenytoin + Ranolazine Contraindicated
- Fosphenytoin + Sofosbuvir-velpatasvir-voxilaprevir Contraindicated
Frequently asked questions
Can I take Fosphenytoin with Methadone?
MediHelp rates the interaction as major. Fosphenytoin 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. Fosphenytoin, through its active metabolite phenytoin, induces hepatic enzymes that metabolise methadone, lowering methadone concentrations. Patients on methadone maintenance can develop opioid withdrawal symptoms and loss of analgesic effect. If phenytoin is stopped, methadone levels may rise and cause toxicity.
How serious is the interaction between Fosphenytoin 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: Monitor for withdrawal symptoms and titrate methadone upward as needed when fosphenytoin is started. Reduce the methadone dose again and watch for sedation and respiratory depression if the anticonvulsant is discontinued.
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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