Itraconazole is the strongest clinical CYP3A4 inhibitor. Pimozide concentration rises 10+ fold; torsades de pointes risk is maximal. FDA Orap Section 4 strict contraindication.
Symptoms
QT prolongation by day 3, syncope, torsades de pointes.
Management
Combination contraindicated. Alternative antifungal: terbinafine for superficial infections. For systemic infections, hold pimozide one week before itraconazole and resume 2 weeks after.
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.