First-generation antipsychotic, diphenylbutylpiperidine derivative
ATC code: N05AG01 (Pimozide)
Brand names
Orap
Blocks postsynaptic dopamine D2 receptors in the striatum and mesolimbic system, plus 5-HT2A receptors and L-type calcium channels. Long half-life (about 55 hours) supports once-daily dosing. Metabolised by CYP3A4 and to a lesser extent CYP1A2; the main adverse risk is QT prolongation and dose-dependent sinus node suppression.
Second line
Pimozide is a second-line antipsychotic for Tourette syndrome in patients over 12 with severe motor or vocal tics when behavioural therapy and alpha-2 agonists (clonidine, guanfacine) failed. approved this indication in 1984. and AEMPS support use only after ECG screening with dose titrated by QTc. Long-term treatment requires weight and metabolic monitoring.
12 pairs found. Sorted from critical to minor.
Mechanism
Amiodarone is a moderate CYP3A4 inhibitor and the strongest clinical QT prolonger. Double torsades risk. Orap Section 4 + additive QT effect.
Symptoms
QT prolongation (amiodarone itself extends 30–50 ms), syncope, torsades de pointes.
Management
Combination contraindicated. For atrial fibrillation in a pimozide patient, use a beta-blocker for rate control or catheter ablation.
Mechanism
CYP3A4 inhibition by atazanavir raises pimozide – torsades de pointes.
Symptoms
QT prolongation, syncope.
Management
Combination contraindicated.
Mechanism
Clarithromycin is a strong CYP3A4 inhibitor. Pimozide is 80% metabolised by CYP3A4; concentration rises 5–7 fold during co-administration. Orap Section 4 strict contraindication – risk of QT prolongation, torsades de pointes and sudden cardiac death.
Symptoms
Within 3–7 days: palpitations, dizziness, syncope. ECG QTc above 500 ms, ventricular ectopy; in severe cases torsades de pointes progressing to ventricular fibrillation.
Management
Combination contraindicated. For infection in a pimozide patient use azithromycin (no CYP3A4 inhibition) or another antibiotic class (amoxicillin for typical pneumonia). If clarithromycin is needed, hold pimozide for the course and resume 7 days after the last dose.
Mechanism
Cobicistat is a strong CYP3A4 inhibitor (potency similar to ritonavir). Tybost Section 4.3 strict contraindication with pimozide.
Symptoms
QT prolongation, syncope, torsades de pointes.
Management
Combination contraindicated. For HIV, switch to a regimen without cobicistat (dolutegravir + 2 NRTIs).
Mechanism
Erythromycin is a moderate-to-strong CYP3A4 inhibitor. Pimozide concentration rises 3–5 fold, with additive QT prolongation (erythromycin itself is a QT prolonger). Orap Section 4 contraindication.
Symptoms
QT prolongation, syncope, torsades de pointes within 3–10 days.
Management
Combination contraindicated. Alternative: azithromycin or another class. If erythromycin is needed, hold pimozide for the course.
Mechanism
Itraconazole is the strongest clinical CYP3A4 inhibitor. Pimozide concentration rises 10+ fold; torsades de pointes risk is maximal. 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.
Mechanism
Ketoconazole is a strong CYP3A4 inhibitor. Pimozide rises 8-fold, QT extends past 500 ms. Orap Section 4.
Symptoms
Progressive QT prolongation within 5 days, torsades de pointes risk.
Management
Combination contraindicated. Alternative: terbinafine or fluconazole for limited infections (fluconazole is a weaker CYP3A4 inhibitor but still requires ECG monitoring).
Mechanism
Posaconazole is a strong CYP3A4 inhibitor. Pimozide rises, torsades risk. Orap Section 4 + Noxafil Section 4.3.
Symptoms
QT prolongation within 5 days.
Management
Combination contraindicated. Hold pimozide for the entire course.
Mechanism
Quinidine is a strong CYP2D6 inhibitor (secondary pimozide pathway) and itself a QT prolonger. Double torsades risk. Orap Section 4.
Symptoms
QT prolongation by day 3, syncope, torsades de pointes.
Management
Combination contraindicated. If antiarrhythmic is needed in a pimozide patient, discuss catheter ablation or rate control with a beta-blocker without QT effect.
Mechanism
Ritonavir is the strongest ARV CYP3A4 inhibitor. Pimozide concentration rises 15-fold. Orap Section 4 strict contraindication.
Symptoms
QT prolongation, syncope, torsades de pointes.
Management
Combination contraindicated. For HIV in a pimozide patient, switch ARV to a regimen without ritonavir or cobicistat (e.g., dolutegravir + 2 NRTIs).
Mechanism
Voriconazole is a strong CYP3A4 inhibitor and itself a QT prolonger. Double torsades risk. Orap Section 4.
Symptoms
QTc above 500 ms by day 2–3, syncope, torsades de pointes.
Management
Combination contraindicated. For invasive mycosis in a pimozide patient, hold pimozide during the voriconazole course and resume 7 days after.
Mechanism
Fluconazole is a moderate CYP3A4 inhibitor. Pimozide rises 2–3 fold. QT prolongation is clinically significant. recommends avoidance.
Symptoms
QT prolongation, dizziness within 5–7 days.
Management
If fluconazole is needed, ECG at baseline and every 3 days, reduce pimozide by 50%. Better: terbinafine for superficial infections.
Opens the checker prefilled with this drug. Pick the second one from your regimen.
Human pregnancy data are limited. Use only if benefit outweighs risk; FDA assigns category C due to rodent embryotoxicity.
Pimozide passes into breast milk. Breastfeeding during treatment is not recommended.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Pimozide is evaluated for the following indications with varying evidence strength: Tourette syndrome (evidence tier B). See the full indication matrix with dosing and citations above on this page.
Common side effects of Pimozide (≥ 1 in 100): Drowsiness, Dry mouth, Constipation, Tremor, Weight gain, Sedation. See the Safety section for uncommon and serious reactions.
FDA category C. Human pregnancy data are limited. Use only if benefit outweighs risk; FDA assigns category C due to rodent embryotoxicity.
Pimozide passes into breast milk. Breastfeeding during treatment is not recommended.
Pimozide is contraindicated in: Congenital long QT syndrome; Combination with QT-prolonging agents (amiodarone, sotalol, high-dose citalopram, moxifloxacin, ondansetron); Combination with strong CYP3A4 inhibitors (clarithromycin, erythromycin, itraconazole, ketoconazole, voriconazole, posaconazole, ritonavir, cobicistat); Severe depression with CNS depression; Parkinson disease. Full list in the Safety section.