Alprazolam × Haloperidol

Both drugs depress the central nervous system (CNS). The alprazolam SmPC warns that with antipsychotics the depressant effect can increase, up to respiratory depression, coma and death, and the haloperidol SmPC says haloperidol can enhance the effect of hypnotics and sedatives. The haloperidol SmPC also lists alprazolam among CYP3A4 inhibitors that may raise haloperidol levels, usually by 20–40% and in some cases by up to 100%. Higher haloperidol levels raise the risk of its adverse effects, including QT prolongation on the electrocardiogram.

Drowsiness, slowed reactions, poor coordination and confusion. Marked central nervous system depression can lead to slowed breathing and coma (alprazolam SmPC). In older people, sedation and muscle weakness raise the risk of falls, often with serious consequences (alprazolam SmPC). Haloperidol can cause a fast heart rate and a drop in blood pressure on standing, and QT prolongation carries a risk of ventricular arrhythmias (haloperidol SmPC).

The combination is not prohibited, but the alprazolam SmPC requires limiting the dose and duration of its use with antipsychotics, and haloperidol is one of them. The US Food and Drug Administration (FDA) alprazolam label likewise requires limiting the alprazolam dose and duration with any central nervous system depressant. Alprazolam is given for as short a time as possible, no longer than 2–4 weeks without reassessment, and older or debilitated patients start at a lower dose. In chronic respiratory insufficiency the alprazolam dose is reduced, and in severe respiratory insufficiency or sleep apnoea syndrome alprazolam is contraindicated (alprazolam SmPC). Before haloperidol is started, a baseline electrocardiogram (ECG) is recorded and potassium and magnesium are corrected. With alprazolam the patient is watched for stronger or longer haloperidol effects and the haloperidol dose is reduced if needed; haloperidol is stopped if the QTc interval exceeds 500 ms (haloperidol SmPC).