Haloperidol × Ziprasidone

Both drugs prolong the QT interval and the effects add up. The haloperidol label describes QTc prolongation, ventricular arrhythmias and sudden death, with higher risk at high doses, high plasma concentrations and parenteral, especially intravenous, use (4.4). Ziprasidone prolongs QT in a dose-related way. In the study cited in the FDA label, oral ziprasidone lengthened QTc by 9–14 ms more than haloperidol; after a second intramuscular injection ziprasidone added 12.8 ms and haloperidol 14.7 ms (Geodon, 5.3). There is no kinetic component. According to its label, ziprasidone does not change the concentrations of CYP2D6 or CYP3A4 substrates to a clinically relevant degree (Zeldox, 4.5).

QTc prolongation on the ECG, torsade de pointes, ventricular fibrillation, sudden death. Clinically this means palpitations, dizziness, syncope or seizures: the ziprasidone label names them as reasons to suspect a malignant arrhythmia and record an ECG (Zeldox, 4.4). The risk is higher with bradycardia, hypokalaemia and hypomagnesaemia, heart disease, a family history of QT prolongation, in CYP2D6 poor metabolisers with high haloperidol concentrations, and with intravenous haloperidol (both labels).

The combination is contraindicated: the AEMPS haloperidol label (sections 4.3 and 4.5) bars haloperidol with QT-prolonging drugs and names ziprasidone in the list. The ziprasidone label says it should not be given with QT-prolonging drugs (Zeldox, 4.4), and the FDA label says to avoid the combination (Geodon, 5.3). The second antipsychotic is not added on top of the first; one replaces the other. Before starting either drug, record a baseline ECG (haloperidol label, 4.4; ziprasidone label, 4.4 – in patients with heart disease) and correct potassium and magnesium (both labels). Decide on ECG monitoring during treatment (haloperidol label, 4.4). If QTc lengthens, reduce the haloperidol dose and stop it at QTc above 500 ms (haloperidol label, 4.4). Ziprasidone is also stopped at QTc above 500 ms (Zeldox, 4.4). Palpitations, dizziness, syncope or seizures in a patient taking both call for an ECG and an arrhythmia work-up (Zeldox, 4.4). Intravenous haloperidol adds risk on its own (haloperidol label, 4.4; FDA label).