Major
Haloperidol × Ketoconazole
First-generation antipsychotics. Butyrophenone derivatives×Systemic antimycotics. Imidazole derivatives
Mechanism
Ketoconazole is a potent CYP3A4 inhibitor – the main haloperidol metabolic route. Haloperidol plasma levels rise 2- to 3-fold. Ketoconazole itself prolongs QT; effects add up.
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Severe cases: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia and hypomagnesaemia.
Management
Avoid the combination. Alternative antifungals: terbinafine or echinocandins. Alternative antipsychotics: olanzapine or aripiprazole.
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.