Fluconazole and Percocet (Oxycodone/Acetaminophen) Interaction: Dosage and Precautions
When using fluconazole and Percocet (oxycodone/acetaminophen) together, reduce the oxycodone dose by 30-50% due to the inhibition of CYP3A4 metabolism by fluconazole, which can significantly increase oxycodone plasma concentrations and risk of respiratory depression.
Mechanism of Interaction
Fluconazole is a moderate inhibitor of the CYP3A4 enzyme system, which is responsible for metabolizing oxycodone 1. When administered together:
- Fluconazole increases plasma concentrations of oxycodone by inhibiting its metabolism
- This interaction can lead to increased opioid effects and potential toxicity
- The acetaminophen component of Percocet is not significantly affected by this interaction
Dosage Recommendations
Fluconazole Dosing
- For most fungal infections:
Percocet (Oxycodone/Acetaminophen) Dosing Adjustments
- Initial dose reduction of oxycodone by 30-50% when starting fluconazole 1
- Monitor closely for signs of opioid toxicity (sedation, respiratory depression)
- Titrate dose based on pain control and side effects
- Low-dose combinations (oxycodone 5 mg with acetaminophen 325 mg) are often effective for moderate pain 4
Monitoring Recommendations
Monitor for Opioid Toxicity
- Respiratory rate and depth
- Level of sedation
- Pupil size
- Blood pressure and heart rate
- Mental status changes
Timing of Monitoring
- Most critical during first 24-48 hours after starting combination
- Reassess every 24-48 hours during concurrent therapy
- Be especially vigilant when changing doses of either medication
Special Populations and Considerations
Renal Impairment
- Fluconazole requires dose adjustment in renal impairment 5
- For patients with creatinine clearance <50 mL/min, reduce fluconazole dose by 50%
- Oxycodone and acetaminophen both require dose reduction in severe renal impairment
Hepatic Impairment
- Both medications require dose reduction in hepatic impairment
- Monitor liver function tests if treatment extends beyond 7-10 days 3
- Acetaminophen daily dose should not exceed 2000 mg in patients with hepatic impairment
Elderly Patients
- Start with lower doses of both medications
- Increased sensitivity to CNS effects of opioids
- Higher risk of adverse effects from drug interactions
Precautions and Contraindications
Absolute Contraindications
- Known hypersensitivity to either medication
- Severe respiratory depression
- Severe bronchial asthma in unmonitored settings
Relative Contraindications
- Sleep apnea
- Concurrent use of other CNS depressants
- History of substance abuse
- Pregnancy (fluconazole should be avoided except in severe fungal infections) 1
Alternative Approaches
If Interaction Cannot Be Avoided
- Consider using non-opioid analgesics when possible
- For fungal infections, consider topical antifungals for localized infections
- For systemic infections requiring fluconazole, consider alternative pain management strategies
Pain Management Alternatives
- NSAIDs (if not contraindicated)
- Acetaminophen alone
- Non-pharmacological pain management techniques
Follow-up and Duration of Therapy
- Reassess need for continued opioid therapy regularly
- For fungal infections, follow guideline-recommended durations based on infection type 2, 3
- Monitor for resolution of both pain and fungal infection
Key Pitfalls to Avoid
- Failing to recognize the interaction and not reducing oxycodone dose initially
- Overlooking signs of opioid toxicity during combination therapy
- Not adjusting doses in patients with renal or hepatic impairment
- Continuing combination therapy longer than necessary
- Abrupt discontinuation of opioid therapy after prolonged use
By following these recommendations, clinicians can safely manage patients requiring both fluconazole and Percocet while minimizing the risk of adverse effects from this significant drug interaction.