Haloperidol × Pimozide

Both drugs prolong the QT interval. For haloperidol, there are reports of QTc prolongation, ventricular arrhythmias and sudden death, with higher risk at high doses, high plasma concentrations and parenteral, especially intravenous, use (haloperidol label). For pimozide, there are reports of QT prolongation, torsade de pointes, ventricular tachycardia and ventricular fibrillation at therapeutic doses (pimozide label). Both labels assume the effects add up, and each lists the other drug among contraindicated QT-prolonging drugs. There is also a kinetic side: haloperidol inhibits CYP2D6 (haloperidol label), this enzyme partly metabolises pimozide, and the Spanish pimozide label contraindicates CYP2D6 inhibitors (pimozide label). The labels cite no study of pimozide concentrations on haloperidol. Both drugs block dopamine D2 receptors, so motor side effects, hyperprolactinaemia and the risk of neuroleptic malignant syndrome add up.

QT prolongation causes no symptoms and shows only on the ECG; arrhythmia presents as palpitations, dizziness or syncope, and both labels report sudden death (haloperidol and pimozide labels). Double dopamine blockade brings tremor, rigidity, hypersalivation, bradykinesia, akathisia and acute dystonia (haloperidol label). Neuroleptic malignant syndrome usually starts with high fever, followed by muscle rigidity, unstable blood pressure and pulse, and altered consciousness (both labels).

The combination is contraindicated. The Spanish haloperidol label bans concomitant use with drugs that prolong the QT interval and names pimozide among the examples (haloperidol label, AEMPS). The Spanish pimozide label contraindicates any drug known to prolong QT as well as CYP2D6 inhibitors (pimozide label). The US pimozide label contraindicates other drugs that prolong the QT interval (pimozide label, FDA). The US haloperidol label is softer and only calls for particular caution with such drugs (haloperidol label, FDA), but the strictest document applies. Under the US label, pimozide in Tourette's disorder is meant for patients who cannot tolerate or do not respond to haloperidol (pimozide label, FDA): the two are replacements for each other, not partners. If a patient takes both, stop one of them. For each drug on its own: before starting haloperidol, take an ECG, correct potassium and magnesium and then monitor electrolytes; reduce the dose if QTc lengthens and stop haloperidol if QTc exceeds 500 ms (haloperidol label). On pimozide, take an ECG before the start and repeat it during treatment, and stop the drug if QT or QTc exceeds 500 ms (pimozide label).