Drug interactions
Fentanyl + Phenobarbital
Severity: Major
Fentanyl and Phenobarbital: 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
Phenobarbital and fentanyl both depress the CNS, so together they raise the risk of profound sedation, respiratory depression and death. Phenobarbital is also a CYP3A4 inducer and may reduce fentanyl concentrations with prolonged use, and withdrawal of the inducer can then cause fentanyl accumulation.
What this interaction means in plain words
Fentanyl and Phenobarbital 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.
Why it happens
Additive CNS depression and CYP3A4 induction by phenobarbital increasing fentanyl clearance.
What to do
Use the lowest effective doses and monitor for sedation and respiratory depression. Adjust the fentanyl dose when phenobarbital is started or stopped.
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 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 Phenobarbital?
MediHelp rates the interaction as major. Fentanyl and Phenobarbital 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. Phenobarbital and fentanyl both depress the CNS, so together they raise the risk of profound sedation, respiratory depression and death. Phenobarbital is also a CYP3A4 inducer and may reduce fentanyl concentrations with prolonged use, and withdrawal of the inducer can then cause fentanyl accumulation.
How serious is the interaction between Fentanyl and Phenobarbital?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Use the lowest effective doses and monitor for sedation and respiratory depression. Adjust the fentanyl dose when phenobarbital is started or stopped.
What other medicines interact with Fentanyl?
MediHelp also lists interactions of Fentanyl with, for example, Alvimopan, Isocarboxazid, Olanzapine / samidorphan. The full list is on the Fentanyl page.
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