Drug interactions
Hydrocodone + Nirmatrelvir / ritonavir
Severity: Major
Hydrocodone and Nirmatrelvir / ritonavir: major interaction.
Last updated Sources: US FDA label
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
Ritonavir in this combination strongly inhibits CYP3A4 and can markedly increase hydrocodone exposure. The result may be excessive sedation and life-threatening respiratory depression.
What this interaction means in plain words
Hydrocodone and Nirmatrelvir / ritonavir 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
Ritonavir is a strong CYP3A4 inhibitor that reduces hydrocodone clearance.
What to do
Reduce the hydrocodone dose or use an alternative analgesic during the short antiviral course, and monitor for respiratory depression and sedation. Readjust the opioid dose after the course is completed.
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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References
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 Nirmatrelvir / ritonavir?
MediHelp rates the interaction as major. Hydrocodone and Nirmatrelvir / ritonavir 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. Ritonavir in this combination strongly inhibits CYP3A4 and can markedly increase hydrocodone exposure. The result may be excessive sedation and life-threatening respiratory depression.
How serious is the interaction between Hydrocodone and Nirmatrelvir / ritonavir?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Reduce the hydrocodone dose or use an alternative analgesic during the short antiviral course, and monitor for respiratory depression and sedation. Readjust the opioid dose after the course is completed.
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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