Drug interactions
Hydrocodone + Nefazodone
Severity: Major
Hydrocodone and Nefazodone: 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
Nefazodone strongly inhibits CYP3A4, which can substantially increase hydrocodone exposure and risk of profound sedation and respiratory depression. Nefazodone also has serotonergic activity, adding a theoretical risk of serotonin syndrome.
What this interaction means in plain words
Hydrocodone and Nefazodone 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
Strong CYP3A4 inhibition reduces hydrocodone clearance, with additive serotonergic effects.
What to do
Avoid if possible, or start with a reduced hydrocodone dose and monitor closely for respiratory depression and serotonin toxicity. Reduce opioid dose again or monitor if nefazodone is 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 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 Nefazodone?
MediHelp rates the interaction as major. Hydrocodone and Nefazodone 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. Nefazodone strongly inhibits CYP3A4, which can substantially increase hydrocodone exposure and risk of profound sedation and respiratory depression. Nefazodone also has serotonergic activity, adding a theoretical risk of serotonin syndrome.
How serious is the interaction between Hydrocodone and Nefazodone?
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 if possible, or start with a reduced hydrocodone dose and monitor closely for respiratory depression and serotonin toxicity. Reduce opioid dose again or monitor if nefazodone is stopped.
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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