Major

Fluconazole × Methadone

Antifungals, triazole derivatives×Synthetic opioid, full mu-receptor agonist

Mechanism

Fluconazole inhibits CYP3A4 and CYP2B6 – the main methadone metabolism enzymes. Methadone concentration rises by 35% with QT prolongation. Methadone alone prolongs QT above 80 mg/day; fluconazole amplifies this.

Symptoms

Drowsiness, respiratory depression (rate below 12/min), miosis, ECG QTc above 500 ms. Severe cases: fatal arrhythmia.

Management

Reduce methadone by 25% when starting fluconazole, ECG before and after. With methadone above 80 mg/day or QT risk factors, choose an alternative antifungal (isavuconazole, terbinafine for superficial infections).

Check the full regimen, not just this pair

Opens the checker with these two drugs prefilled. Add the rest of the regimen and recompute additive risks.

Open checker

Sources

FDA: Dolophine (methadone) prescribing information (2014)

← All interactions

Major

Fluconazole × Methadone

Antifungals, triazole derivatives×Synthetic opioid, full mu-receptor agonist

Mechanism

Symptoms

Drowsiness, respiratory depression (rate below 12/min), miosis, ECG QTc above 500 ms. Severe cases: fatal arrhythmia.

Management

Check the full regimen, not just this pair

Opens the checker with these two drugs prefilled. Add the rest of the regimen and recompute additive risks.

Open checker

Sources

FDA: Dolophine (methadone) prescribing information (2014)

← All interactions