Moderate
Amitriptyline × ritonavir
Tricyclic antidepressants (TCA)×HIV protease inhibitor / pharmacokinetic booster
Mechanism
Ritonavir is a strong CYP2D6 and CYP3A4 inhibitor. Amitriptyline is metabolised by both. TCA AUC rises 2–3-fold, amplifying anticholinergic effects and QT prolongation.
Symptoms
Dry mouth, constipation, urinary retention, accommodation disturbance, tachycardia. In older patients: delirium and confusion risk. QT prolongation with torsades risk.
Management
Avoid in HIV-therapy patients. For neuropathic pain, alternatives: gabapentin or pregabalin. For depression: sertraline or escitalopram. If unavoidable, begin amitriptyline at 5 mg at bedtime and do not exceed 25 mg/day; check ECG at 1 and 2 weeks.
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.