Oxycodone and fentanyl are metabolised mainly by CYP3A4. When a patient on either starts a strong CYP3A4 inhibitor, such as clarithromycin or an azole antifungal, opioid exposure can rise and cause sedation or respiratory depression. The reverse also applies: stopping an inhibitor, or starting an inducer such as rifampicin, can lower opioid effect and precipitate pain or withdrawal.
Ask about every new medicine, including short antibiotic courses and over-the-counter products, and check an interaction resource before co-prescribing. Warn patients and carers about drowsiness and slow breathing.
- Check CYP3A4 interactions whenever a patient on oxycodone or fentanyl starts a new drug.
- Watch for drowsiness and slow breathing after starting an inhibitor.
- Expect reduced effect after starting an inducer such as rifampicin.
- Review doses when the interacting drug is stopped.
Why it matters
A short antibiotic course can change opioid exposure enough to cause harm.
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