Amiodarone-Induced Neutropenia: An Uncommon Side Effect of a Common Drug

Amiodarone is widely used as an antiarrhythmic agent for the treatment of both supraventricular and ventricular arrhythmias in various inpatient as well as outpatient settings. Classified as a class III antiarrhythmic agent, it acts mainly by inhibition of potassium channels in the cardiac muscle. Adverse effects are quite common and usually involve pulmonary, gastrointestinal, endocrine, dermatologic, or neuromuscular systems. Although hematologic side effects including thrombocytopenia have also been reported, amiodarone-induced neutropenia is quite rare. We present a case of amiodarone-induced neutropenia in a 66-year-old Caucasian gentleman. He presented to our hospital with cardiac arrest due to ventricular-fibrillation and had received amiodarone as a part of his therapy. His hospital course was complicated by neutropenia which was found to have a clear temporal relation with amiodarone. His initial white blood cell count was 6400/mm3 with an absolute neutrophil count (ANC) of 4800/mm3. His ANC started to downtrend and reached a nadir of 400/mm3 at day six of therapy. This improved significantly after stopping amiodarone, without any change in other medications. Given the rapid improvement of his neutropenia with the discontinuation of amiodarone, further workup with a bone marrow biopsy was not performed. Severe selective neutropenia, also known as agranulocytosis, is a life-threatening condition due to increased risk of severe infections. Antiarrhythmic agents such as tocainamide, procainamide, and flecainide are generally known to cause agranulocytosis. The mechanism of agranulocytosis or neutropenia is thought to be mediated by either immune-mediated destruction or direct and indirect toxicity to myeloid precursors. Although amiodarone has been in use for over 20 years in the management of tachyarrhythmias, agranulocytosis as a direct side effect of amiodarone therapy has been rarely reported. It is important to keep in mind this rare but potentially life-threatening adverse effect of amiodarone when initiating therapy.