Fatal Lung Toxic Effects Related to Dronedarone Use FREE

Dronedarone is a derivative of amiodarone that aimed to reduce the extracardiac adverse effects while preserving its antiarrhythmic effects for treatment of atrial fibrillation (AF).¹ In the ATHENA trial (A Placebo-Controlled, Double-Blind, Parallel Arm Trial to Assess the Efficacy of Dronedarone 400 mg bid for the Prevention of Cardiovascular Hospitalization or Death from Any Cause in Patients with Atrial Fibrillation/Atrial Flutter),² dronedarone reduced cardiovascular hospitalization and death in patients with nonpermanent atrial fibrillation (AF) with other cardiovascular risk factors. However, an experimental study³ suggested that dronedarone might have toxic effects on the lung greater than or equal to amiodarone. We describe 2 cases of fatal and near-fatal lung toxic effects associated with dronedarone use.

A 72-year-old woman was hospitalized with progressive dyspnea for 3 weeks. She had symptomatic paroxysmal AF, and amiodarone was initiated 2 years ago. Ten months before admission, she was enrolled into the ATHENA trial,² in which amiodarone therapy was stopped for 1 month prior to switching to dronedarone. At the time of admission, she had already been using dronedarone for 9 months. Chest radiography on admission showed bilateral diffuse pulmonary infiltrates, and thoracic computed tomography revealed diffuse ground glass opacities involving both lungs (Figure, A and B). Treatment with empirical board-spectrum antibiotics failed, and she developed progressive respiratory failure necessitating mechanical ventilation 20 days later. All microbiological examination findings were negative. Trans-bronchial biopsy revealed features compatible to bronchiolitis obliterans with organizing pneumonia (BOOP) described in amiodarone-induced lung toxic effects (Figure, C).⁴ Pulse methylprednisolone therapy was tried, but she subsequently died 4 days later.

An 83-year-old man with history of hypertension and diabetes mellitus presented with new-onset AF. He was treated initially with 6 days of intravenous and then 4 days of oral amiodarone (a total of 4.6 g), which was subsequently switched to oral dronedarone for 4 days. He was transferred to our hospital for management of AF. On admission, dronedarone therapy was stopped, but he developed progressive dyspnea 2 days later. Chest radiography and thoracic computed tomography revealed diffuse ground glass opacities over both lungs, compatible with BOOP (Figure, D and E). Treatment with broad-spectrum antibiotics failed, and he developed respiratory failure necessitating mechanical ventilation. All the microbiological investigation findings were negative. His condition improved with pulse methylprednisolone therapy, and he was successfully weaned off from the ventilator.

Although it is arguable that both patients were treated with amiodarone before switching to dronedarone, the temporal sequence of their onset of respiratory symptoms as well as similar radiological features would suggest that dronedarone may in fact play an important role in the pathogenesis. Furthermore, the lung toxic effects appear to occur both after the short- and long-term exposure to dronedarone. Our observations suggest that serial monitoring of chest radiography is needed in patients receiving dronedarone, especially in those with prior exposure to amiodarone.