What are the potential interactions between fluconazole and Percocet (oxycodone/acetaminophen)?

Fluconazole and Percocet (Oxycodone/Acetaminophen) Interaction

Fluconazole significantly increases oxycodone plasma concentrations, requiring a 30-50% dose reduction of Percocet when used concurrently to prevent potentially life-threatening opioid toxicity. 1

Mechanism of Interaction

Fluconazole is a potent inhibitor of the cytochrome P450 enzyme system, particularly CYP3A4, which is the primary metabolic pathway for oxycodone. When administered together:

• Fluconazole blocks oxycodone metabolism, leading to:
  • Increased oxycodone plasma concentrations
  • Prolonged elimination half-life
  • Enhanced and prolonged opioid effects 1
• The acetaminophen component of Percocet is not significantly affected by this interaction

Clinical Consequences

This drug interaction can result in serious adverse effects:

• Respiratory depression (most concerning)
• Excessive sedation
• Hypotension
• Mental status changes
• Potentially fatal outcomes in severe cases 1

Management Recommendations

1. Dose Adjustment:

   • Reduce Percocet (oxycodone) dose by 30-50% when initiating fluconazole 1
   • Titrate slowly based on clinical response

2. Monitoring:

   • Monitor closely for signs of opioid toxicity:
     • Respiratory rate <12/min or shallow breathing
     • Excessive sedation
     • Pinpoint pupils
     • Mental status changes

3. Alternative Options:

   • Consider using an antifungal with less CYP3A4 inhibition if clinically appropriate
   • For pain management, consider opioids less dependent on CYP3A4 metabolism

Special Populations at Higher Risk

• Elderly patients: More susceptible due to age-related changes in drug metabolism and increased sensitivity to CNS depressants 1
• Patients with renal impairment: May experience more pronounced interactions due to decreased clearance of fluconazole

Patient Education

• Report increased drowsiness, confusion, or breathing difficulties immediately
• Avoid alcohol consumption which can compound CNS depression
• Do not adjust medication doses without consulting healthcare provider

Clinical Decision Algorithm

1. If fluconazole is essential:

   • Start with 30-50% reduced Percocet dose
   • Monitor for respiratory depression and sedation
   • Titrate dose slowly based on pain control and side effects

2. If Percocet is essential:

   • Consider alternative antifungal therapy if clinically appropriate
   • If fluconazole must be used, implement dose reduction and monitoring as above

3. If both medications are essential:

   • Consider hospitalization or close monitoring during initial co-administration in high-risk patients
   • Have naloxone readily available for emergency reversal of opioid effects

This interaction represents a significant clinical concern that requires proactive management to prevent potentially life-threatening complications.