Drug interactions
Nirmatrelvir / ritonavir + Oxycodone
Severity: Major
Nirmatrelvir / ritonavir and Oxycodone: 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
Ritonavir strongly inhibits CYP3A4, the main route of oxycodone clearance, so oxycodone exposure rises substantially. This raises the risk of excessive sedation and potentially fatal respiratory depression, particularly in the first days of coadministration and again after the antiviral is stopped.
What this interaction means in plain words
Nirmatrelvir / ritonavir and Oxycodone 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 inhibition of hepatic and intestinal CYP3A4 reduces oxycodone metabolism to noroxycodone.
What to do
Reduce the oxycodone dose or choose a non-CYP3A4-dependent analgesic during the 5-day antiviral course, and monitor for sedation and respiratory depression. Re-evaluate dosing when ritonavir is discontinued because oxycodone levels will fall.
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 Oxycodone
- Alvimopan + Oxycodone Contraindicated
- Calcium / magnesium / potassium / sodium oxybates + Oxycodone Contraindicated
- Isocarboxazid + Oxycodone Contraindicated
- Olanzapine / samidorphan + Oxycodone Contraindicated
- Oxycodone + Phenelzine Contraindicated
- Oxycodone + Sodium oxybate Contraindicated
Frequently asked questions
Can I take Nirmatrelvir / ritonavir with Oxycodone?
MediHelp rates the interaction as major. Nirmatrelvir / ritonavir and Oxycodone 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 strongly inhibits CYP3A4, the main route of oxycodone clearance, so oxycodone exposure rises substantially. This raises the risk of excessive sedation and potentially fatal respiratory depression, particularly in the first days of coadministration and again after the antiviral is stopped.
How serious is the interaction between Nirmatrelvir / ritonavir and Oxycodone?
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 oxycodone dose or choose a non-CYP3A4-dependent analgesic during the 5-day antiviral course, and monitor for sedation and respiratory depression. Re-evaluate dosing when ritonavir is discontinued because oxycodone levels will fall.
What other medicines interact with Oxycodone?
MediHelp also lists interactions of Oxycodone with, for example, Alvimopan, Calcium / magnesium / potassium / sodium oxybates, Isocarboxazid. The full list is on the Oxycodone page.
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