Pimozide × Ziprasidone

Both antipsychotics prolong the QT interval. Ziprasidone does so dose-dependently, to a mild-to-moderate degree (ziprasidone label); in placebo-controlled trials QTc rose by about 10 ms at the highest recommended daily dose of 160 mg (ziprasidone label, FDA). For pimozide, there are reports of QT prolongation, torsade de pointes, ventricular tachycardia and ventricular fibrillation at therapeutic doses (pimozide label). No study of the pair exists, and both labels assume the effects add up (ziprasidone and pimozide labels). No kinetic contribution is expected: ziprasidone has little inhibitory effect on cytochrome enzymes, including CYP3A4 and CYP2D6, which metabolise pimozide (ziprasidone label). Both drugs block dopamine D2 receptors, so motor side effects and the risk of neuroleptic malignant syndrome also add up.

QT prolongation causes no symptoms and shows only on the ECG. The ziprasidone label names palpitations, dizziness, syncope or seizures as possible signs of a malignant arrhythmia (ziprasidone label); the pimozide label also reports sudden death and cardiac arrest (pimozide label). Double dopamine blockade presents as tremor, rigidity, akathisia and acute dystonia, and neuroleptic malignant syndrome as high fever, muscle rigidity, unstable blood pressure and pulse, and altered consciousness (both labels).

The combination is contraindicated. The Spanish ziprasidone label names pimozide in its contraindications (ziprasidone label, AEMPS). The US ziprasidone label lists pimozide among the drugs that should not be given with ziprasidone (ziprasidone label, FDA). The Spanish pimozide label contraindicates any drug known to prolong the QT interval and stresses that its list of examples is not exhaustive (pimozide label). The US pimozide label names ziprasidone outright (pimozide label, FDA). Do not prescribe the two drugs together. If a patient on one of them needs another antipsychotic, choose one that does not prolong the QT interval, because the ban in both labels covers that whole class (ziprasidone and pimozide labels). For each drug on its own: before starting ziprasidone, correct potassium and magnesium, and in patients with stable heart disease take an ECG (ziprasidone label); on pimozide, take an ECG before the start and repeat it during treatment (pimozide label). With palpitations, dizziness, syncope or seizures, take an ECG to look for arrhythmia (ziprasidone label), and stop the drug if QTc exceeds 500 ms (ziprasidone and pimozide labels).