Drug interactions
Hydrocodone + Phenobarbital
Severity: Major
Hydrocodone 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 adds to the CNS and respiratory depressant effects of opioids, risking profound sedation, coma and death. As a CYP3A4 inducer, it may also lower hydrocodone levels over time, and exposure may rise sharply when phenobarbital is stopped.
What this interaction means in plain words
Hydrocodone 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, plus phenobarbital induction of CYP3A4 affecting hydrocodone clearance.
What to do
Avoid or limit to the lowest doses and shortest duration, monitoring sedation and respiratory rate. Reassess hydrocodone dosing when phenobarbital is started or 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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Other interactions of Hydrocodone
- Alvimopan + Hydrocodone Contraindicated
- Bupropion-naltrexone + Hydrocodone Contraindicated
- Hydrocodone + Isocarboxazid Contraindicated
- Hydrocodone + Olanzapine / samidorphan Contraindicated
- Hydrocodone + Phenelzine Contraindicated
- Alfentanil + Hydrocodone Major
Frequently asked questions
Can I take Hydrocodone with Phenobarbital?
MediHelp rates the interaction as major. Hydrocodone 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 adds to the CNS and respiratory depressant effects of opioids, risking profound sedation, coma and death. As a CYP3A4 inducer, it may also lower hydrocodone levels over time, and exposure may rise sharply when phenobarbital is stopped.
How serious is the interaction between Hydrocodone 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: Avoid or limit to the lowest doses and shortest duration, monitoring sedation and respiratory rate. Reassess hydrocodone dosing when phenobarbital is started or discontinued.
What other medicines interact with Hydrocodone?
MediHelp also lists interactions of Hydrocodone with, for example, Alvimopan, Bupropion-naltrexone, Isocarboxazid. The full list is on the Hydrocodone page.
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