Drug interactions
Fentanyl + Methadone
Severity: Major
Fentanyl and Methadone: major 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
Two opioid agonists together produce additive central nervous system and respiratory depression, with profound sedation, hypotension, coma or death possible. Methadone's long and variable half-life makes accumulation and delayed toxicity a particular concern.
What this interaction means in plain words
Fentanyl 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.
Fentanyl belongs to Musculoskeletal; Methadone belongs to Musculoskeletal.
Why it happens
Additive mu-opioid receptor agonism causing pharmacodynamic CNS and respiratory depression.
What to do
Reserve the combination for patients without adequate alternatives, use the lowest doses for the shortest time, and monitor respiratory rate and sedation closely. Consider naloxone availability.
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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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 Fentanyl
- Alvimopan + Fentanyl Contraindicated
- Fentanyl + Isocarboxazid Contraindicated
- Fentanyl + Olanzapine / samidorphan Contraindicated
- Fentanyl + Phenelzine Contraindicated
- Fentanyl + Tranylcypromine Contraindicated
- Alfentanil + Fentanyl Major
Frequently asked questions
Can I take Fentanyl with Methadone?
MediHelp rates the interaction as major. Fentanyl 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. Two opioid agonists together produce additive central nervous system and respiratory depression, with profound sedation, hypotension, coma or death possible. Methadone's long and variable half-life makes accumulation and delayed toxicity a particular concern.
How serious is the interaction between Fentanyl 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: Reserve the combination for patients without adequate alternatives, use the lowest doses for the shortest time, and monitor respiratory rate and sedation closely. Consider naloxone availability.
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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