Drug interactions
Fentanyl + Hydrocodone
Severity: Major
Fentanyl and Hydrocodone: 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 analgesia and also additive respiratory depression, sedation and risk of overdose. Duplicate opioid therapy rarely has clear benefit.
What this interaction means in plain words
Fentanyl and Hydrocodone 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; Hydrocodone belongs to Musculoskeletal.
Why it happens
Additive mu-opioid receptor agonist effects.
What to do
Avoid concurrent use unless intentionally managing breakthrough pain under supervision, using the lowest doses for the shortest time. Monitor for respiratory depression and 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 Fentanyl
- Alvimopan + Fentanyl Contraindicated
- Fentanyl + Isocarboxazid Contraindicated
- Fentanyl + Olanzapine / samidorphan Contraindicated
- Fentanyl + Phenelzine Contraindicated
- Fentanyl + Tranylcypromine Contraindicated
- Alfentanil + Fentanyl Major
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 Fentanyl with Hydrocodone?
MediHelp rates the interaction as major. Fentanyl and Hydrocodone 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 analgesia and also additive respiratory depression, sedation and risk of overdose. Duplicate opioid therapy rarely has clear benefit.
How serious is the interaction between Fentanyl and Hydrocodone?
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 concurrent use unless intentionally managing breakthrough pain under supervision, using the lowest doses for the shortest time. Monitor for respiratory depression and consider naloxone availability.
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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