Azithromycin × Sertraline

Both drugs prolong the QT interval. Sertraline does so in a concentration-dependent way: at twice the maximum recommended dose the largest mean increase was 10 ms (sertraline label of the US Food and Drug Administration, FDA). Azithromycin, like other macrolides, prolongs cardiac repolarisation and the QT interval, which carries a risk of torsades de pointes (azithromycin SmPC). The effects add up.

QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.

The US Food and Drug Administration (FDA) label of sertraline says to avoid drugs known to prolong the QT interval; its examples include antibiotics such as the macrolide erythromycin (sertraline FDA label). The US azithromycin label asks prescribers to weigh the risk of QT prolongation in patients who already take such drugs (azithromycin FDA label). European SmPCs allow the combination with caution: azithromycin is used carefully in patients with QT prolongation, low potassium or magnesium, clinically relevant bradycardia, arrhythmia, severe heart failure and in older people, and sertraline in heart disease, low potassium or magnesium, a family history of QT prolongation and bradycardia (azithromycin and sertraline SmPCs). Avoid the combination where possible; if azithromycin is still needed, assess these risk factors before starting.