Antipsychotic (diphenylbutylpiperidine neuroleptic)
Pimozide is an antipsychotic medicine used to treat tics in Tourette syndrome, in patients who do not respond to other therapies. It should be used with caution, with ECG monitoring, because it can affect the heart rhythm.
Also known as: Pimozida, Orap
Ketoconazole + pimozide: ketoconazole reduces pimozide metabolism (CYP3A4), increasing its levels and the risk of ventricular arrhythmias (QT prolongation) (QUADRO 2).
Pimozide is metabolised by CYP3A4 and prolongs the QT interval; ketoconazole, a strong inhibitor of that enzyme, markedly increases its plasma concentration, with a high risk of severe ventricular arrhythmias, including torsades de pointes. QUADRO 2 of Annex 7 flags the combination on the list of interactions increasing arrhythmia risk, and the combination is contraindicated in the labels of both drugs. Pimozide is used in tic disorders and resistant psychotic disorders, and oral ketoconazole in systemic mycoses — situations where an alternative is mandatory: another antipsychotic without relevant interaction or another antifungal (fluconazole has weaker CYP3A4 inhibition, but requires evaluation). No safe dose is documented for the combination; after accidental exposure, monitor ECG (QTc), potassium and magnesium.
Ketoconazole + pimozide: ketoconazole (strong CYP3A4 inhibitor) increases pimozide levels — high risk of torsades de pointes; contraindicated combination.
Pimozide is susceptible to CYP3A4 inhibitors and prolongs the QT interval — the inhibition of metabolism by ketoconazole increases levels and the arrhythmia risk (QUADRO 2, Pimozide/Azole antifungals: "Pimozide: reduced metabolism").
Monitor ECG (QT interval) and signs of pimozide toxicity.
Syncope, palpitations, torsades de pointes in a patient on ketoconazole + pimozide.
Avoid the combination (risk of torsades de pointes); use an alternative antipsychotic if needed.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 7, QUADRO 2 (Pimozide; Azole antifungals)
No documented food or drink interactions.
FDA label (Drug Interactions): pimozide prolongs the QT interval; an additive effect is anticipated with other QT-prolonging drugs (phenothiazines, tricyclic antidepressants, class Ia/III antiarrhythmics, macrolides, moxifloxacin, mefloquine, tacrolimus, ziprasidone, among others) — do not administer with these drugs.
Contraindicated with QT-prolonging drugs; monitor ECG, potassium and magnesium before and during treatment.
DailyMed/FDA (NIH/NLM) — Pimozide (ANI), Drug Interactions: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4e954fc2-fdff-486c-beb6-2b8ace717081
FDA label (Drug Interactions/WARNINGS): pimozide prolongs the QT interval — contraindicated in patients with congenital long QT syndrome or other QT-prolonging factors.
Contraindicated in congenital long QT syndrome; monitor ECG before and during treatment.
DailyMed/FDA (NIH/NLM) — Pimozide (ANI), Drug Interactions: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4e954fc2-fdff-486c-beb6-2b8ace717081
FDA label (PREGNANCY, Teratogenic Effects): reproduction studies in rats and rabbits (up to 8× the maximum human dose) with no evidence of teratogenicity; in rats, the dose resulted in decreased pregnancies and retarded fetal development (inhibition/delay of implantation).
No teratogenicity in animals, but decreased pregnancies in rats; use only if benefit justifies risk.
No specific breastfeeding data in the label; assess risk/benefit.
Not applicable (no specific contraception requirements in the label).
DailyMed/FDA (NIH/NLM) — approved Pimozide label (ANI), PREGNANCY section: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4e954fc2-fdff-486c-beb6-2b8ace717081 ; Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 2, Drugs and Breastfeeding: The manufacturer recommends avoiding, unless its use is essential; there is no useful information.
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Antipsychotic (diphenylbutylpiperidine): dopaminergic D2 antagonist — reduces tics in Tourette syndrome; prolongs the QT interval (additive effect with other QT-prolonging drugs) (FDA label).
Dopaminergic D2 receptor blockade; QT prolongation (cardiac potassium channel blockade).
Oral absorption; the label does not quantify bioavailability (tablet use).
Metabolism mainly by CYP3A4 (also CYP1A2 and CYP2D6); poor CYP2D6 metabolisers (5-10% of the population) have higher concentrations (Pharmacogenomics).
Long elimination half-life (approximately 50 hours).
