Moderate
Amitriptyline × Fluconazole
Tricyclic antidepressants (TCA)×Antifungals, triazole derivatives
Mechanism
Fluconazole weakly blocks CYP2C19 and CYP3A4 – amitriptyline metabolic routes. TCA plasma levels may rise with prolonged fluconazole courses.
Symptoms
Worsening anticholinergic symptoms (dry mouth, constipation, urinary retention), drowsiness, tachycardia. QT prolongation on ECG at fluconazole doses ≥200 mg.
Management
For short fluconazole courses (up to 7 days), no special adjustment. For prolonged systemic therapy (>14 days), reduce amitriptyline by 25% temporarily. Alternative antifungals: terbinafine for dermatophytosis or echinocandins.