Azithromycin/chloroquine/tacrolimus

Author Information

An event is serious (based on the ICH definition) when the patient outcome is:

• * death

• * life-threatening

• * hospitalisation

• * disability

• * congenital anomaly

• * other medically important event

• * Drug interaction

A 43-year-old man developed atrial fibrillation, ventricular tachycardia (VT), wide complex tachycardia (WCT) and cardiac arrest during treatment with off-label chloroquine for COVID-19 and following concomitant administration of azithromycin for COVID-19 and tacrolimus as immunosuppressant therapy [routes and time to reactions onset not stated].

The man, who had hypertension and chronic renal disease due to non-specific glomerulonephritis, presented to the emergency department with intermittent fever, dry cough and progressive dyspnea since a week. Six months before, he underwent, kidney transplant from a cadaveric donor. Additionally, he had a history of tertiary hyperparathyroidism and underwent parathyroidectomy. He had been receiving nifedipine, metoprolol, mycophenolic acid, prednisone, calcium carbonate, calcitriol and tacrolimus 1mg twice daily. Physical examination showed tachycardia, shortness of breath and a peripheral capillary oxygen saturation level of 83%. Further investigations were significant with infectious aetiology. An ECG showed sinus tachycardia. Chest x-ray showed bilateral ground glass image. Thereafter, he was found to be positive for COVID-19 infection. A QTc of baseline ECG was normal and a validated risk score to predict QT interval prolongation in hospitalised patients was at low risk. Therefore, he was started on an off-label treatment with chloroquine 500mg twice on day 1, then 500mg daily on days 2-5 plus azithromycin 500mg daily on day 1, then 250mg daily on days 2-5). On day 4 of the therapy, he developed a fast-WCT with heart beats of 180 beats/minute.

The man was treated with IV amiodarone 300mg. It was not possible to record the complete 12 lead ECG, but only a DII rhythm strip was recorded. A close inspection demonstrated possible atrio-ventricular dissociation, which suggests the diagnosis of VT. The rhythm was following the cardioversion; however, after 5 minutes of initiation of amiodarone, the rhythm was observed with a DII rhythm strip that demonstrated an irregular rhythm, QRS 110ms at 100 beats/min on an average with biphasic T waves with ST-segment depression, without organized atrial activity significant with atrial fibrillation. There was no evidence of prolonged QT interval. During arrhythmia episodes, troponin I was 0.2 ng/dL. On the same day before arrhythmia episodes, laboratory investigations were not relevant to the event. Following 50 minutes of pharmacological cardioversion, he developed cardiac arrest and died without any response to cardiopulmonary resuscitation.