An 8-year-old boy who had received a bone marrow transplant due to relapse of acute lymphoblastic leukemia was admitted for veno-occlusive disease. He also developed acute kidney injury and was dialysis dependent. His condition was gradually stabilized but he subsequently developed invasive pulmonary aspergillosis with multiple aspergillomas involving both lungs. He was then given oral posaconazole 300 mg twice daily and intravenous liposomal amphotericin B (Ambisome) 90 mg (3 mg/kg) daily infused through a Hickman catheter over one hour. The tip of the central catheter was located at the junction between superior vena cava (SVC) and right atrium (RA). However, he developed feeding intolerance with severe abdominal pain requiring temporary suspension of enteral feeding. Posaconazole was switched to intravenous voriconazole 210 mg every 12 hours. Five days after the co-administration of voriconazole and amphotericin B infusion, he developed an attack of non-sustained wide complex tachycardia lasting for 24 seconds after infusion of voriconazole and amphotericin B. Thirty seconds later, there were three similar attacks lasting for 15, 2 and 4 seconds, respectively with an interval duration of 1 second in between. He was asymptomatic during the attacks. He was receiving continuous renal replacement therapy at that juncture. An electrocardiogram performed immediately after the event failed to capture the ventricular tachycardia. It showed a QT interval of 0.42 seconds. Few days later, the asymptomatic ventricular ectopics appeared again during amphotericin B infusion. There were no other pro-arrhythmic medications, and the tacrolimus level was 5.3 µg/L. Voriconazole was then switched back to oral posaconazole as his enteral feeding was re-established and the administration duration of amphotericin B was lengthened to two hours, with no recurrence of arrthymias.

Several antifungal agents of triazole class are arrhythmogenic but ventricular tachycardia has only been rarely reported [1,2]. The underlying mechanism probably involves both direct blockage of hERG potassium channel and inhibition of channel trafficking, as demonstrated with ketoconazole [3]. The development of ventricular arrhythmia and hyperkalemia after rapid infusion of amphotericin B has been previously reported in those with impaired renal function [4]. The infusion through a central catheter located at SVC-RA junction appeared to increase the risk of inducing arrhythmia [5].

Although, there is no drug interaction between voriconazole and amphotericin B, the arrhythmogenic properties of both agents increase the risk of developing cardiac arrhythmia, if co-administered. A rapid infusion rate, the presence of acute kidney injury with low glomerular filtration rate, electrolyte disturbances and administration through a central catheter near the SVC-RA junction – all appeared to have increased the risk of cardiac toxicity in this child. Our experience suggests that amphotericin B-associated ventricular arrhythmias may be managed with a slower infusion rate and avoidance of co-infusion with other anti-fungal agents.

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2. Dewan P, Gomber S, Arora V. Ventricular tachycardia: A rare side effect of voriconazole. Indian J Pediatr. 2017;842:152-3.

3. Cubeddu LX. Drug-induced Inhibition and trafficking disruption of ion channels: Pathogenesis of QT abnormalities and drug-induced fatal arrhythmias. Curr Cardiol Rev.　2016;12:141-54.

4. Craven PC, Gremillion DH. Risk factors of ventricular fibrillation during rapid amphotericin B infusion. Antimicrob Agents Chemother.　1985;27:868-71.

5. Chongtham DS,　Singh MM,　Ram T. Amphotericin B induced ventricular arrhythmia and its relation to central venous line. J Postgrad Med. 2001;47:282.