Wednesday, March 30, 2011

Multaq Liver Damage ? Update for April 2011

Sanofi-AventisImage via Wikipedia
Multaq (dronedarone) is a popular antiarrhythmia drug manufactured and marketed by Sanofi – Aventis SA, has been linked by the US FDA to acute liver damage, severe liver toxicity, acute hepatic failure, acute liver failure and other complications and damage of the liver and hepatic system, often requiring surgery and in acute cases, a liver transplant.

Multaq is used to treat abnormal heart rhythm in patients who have had an abnormal heart rhythm (atrial fibrillation or atrial flutter) during the past 6 months. Multaq (dronedarone) is said to reduce the risk of patient hospitalization for these heart arrhythmia problems. Since the FDA’s approval of Multaq in July 2009 until October 2010, almost a half a million Multaq prescriptions have been dispensed.  During that same time, approximately 147,000 patients filled Multaq prescriptions at retail pharmacies in the United States on an outpatient basis. In addition to outpatient Multaq prescriptions filled at retail pharmacies, a significant number of Multaq prescriptions have been filled and dispensed in hospital settings on an inpatient basis.

As of late January of 2011: 857 people reported to have side effects when taking Multaq. Among them, 21 people (2.45%) have Abnormal Liver Function Test Results. In this study of Multaq users, 21 people tested abnormal for liver function while taking Multaq. The length of Multaq use as well as gender and age of the users, and severity of the abnormal liver function test were included.

From the FDA site:

FDA has received several case reports of hepatocellular liver injury and hepatic failure in patients treated with dronedarone, including two post-marketing reports of acute hepatic failure requiring transplantation. Because these reactions are reported voluntarily from a treatment population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The two cases of acute hepatic failure requiring transplantation occurred at 4.5 and 6 months after initiation of dronedarone in patients with previously normal hepatic serum enzymes. Both patients were female and approximately 70 years of age. In the first case, the patient had underlying intermittent atrial fibrillation, arterial hypertension and stable coronary artery disease. She was treated with dronedarone for 4.5 months. Two weeks prior to hospitalization she reported increased exhaustion and tiredness. One week prior to admission she discontinued dronedarone, and at the time of admission she was noted to have jaundice, coagulopathy, transaminitis and hyperbilirubinemia, which progressed to hepatic encephalopathy over the next nine days. A pre-transplant workup did not reveal another etiology of liver failure. In the second case, the patient had a medical history of paroxysmal atrial fibrillation and Sjogren's syndrome. Following 6 months of treatment with dronedarone she developed weakness, abdominal pain, coagulopathy, transaminitis and hyperbilirubinemia.

She was transplanted 1 month later; no alternative etiology for liver failure was identified in the transplant work-up. In both cases, the explanted liver showed evidence of extensive hepatocellular necrosis.
Multaq (dronedarone) is approved to reduce the risk of cardiovascular hospitalization in patients with paroxysmal or persistent atrial fibrillation (AF) or atrial flutter (AFL), with a recent history of AF/AFL and associated cardiovascular risk factors (age >70, hypertension, diabetes, prior cerebrovascular accident, left atrial diameter ≥ 50 mm or left ventricular ejection fraction <40%) who are in sinus rhythm or who will be cardioverted.

Dronedarone is contraindicated in patients with NYHA Class IV heart failure or NYHA Class II - III heart failure with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic. In a placebo-controlled study in patients with severe heart failure requiring recent hospitalization or referral to a specialized heart failure clinic for worsening symptoms (the ANDROMEDA Study), patients given dronedarone had a greater than two-fold increase in mortality. Such patients should not be given dronedarone.