26 January 2011
The European Medicines Agency (EMA) has become aware of two reports of severe liver injury in patients treated with dronedaroneq (Multaq ®) and has recommended that changes be made to the medicine’s prescribing information to ensure that patients’ liver function is tested before initiation of treatment, closely monitored during treatment, and treatment is stopped if there are signs of potential liver damage.
Prescribers should identify those patients currently receiving dronedarone and contact them within the next month to ensure liver function tests are performed as described in the regimen below. Treatment should be stopped in a patient’s with raised levels of alanine aminotransferase i.e. more than 3xULN. A liver function test should be performed before a patient commences treatment with dronedarone and at regular intervals thereafter. Prescribing managers may wish to take steps to ensure prescribers are aware of this urgent regulatory action.
Dronedarone was marketed in 2010 for use in adult clinically stable patients with a history of, or current non-permanent atrial fibrillation (AF) to prevent recurrence of AF or to lower ventricular rate. As part of its routine monitoring of the drug, the licensing agency has become aware of reports of severe liver injury in patients treated with the medicine. These include two cases of liver failure requiring a transplant, reported in December 2010. The two cases occurred 4.5 and 6 months after starting treatment in patients with normal liver function before treatment. Both patients were taking other medication but a causal relationship with dronedarone could not be excluded.
Urgent regulatory action is to be taken to help manage the possible risk of severe liver complications. The Committee for Medicinal Products for Human Use (CHMP) has agreed that the company should provide a letter to healthcare professionals explaining the changes to be made to ensure that a patient’s liver function is monitored before initiation of treatment and whilst they are receiving dronedarone.
What are the new licensing recommendations for prescribers?
- Before starting treatment with dronedarone, doctors should perform liver function tests. Tests should be repeated monthly for six months, at months 9 and 12, and periodically thereafter.
- Contact patients who are currently receiving the drug within the next month so that liver function tests can be performed. Thereafter, they should carry out further tests as described above depending on when treatment was started.
- Stop treatment with dronedarone in patients with raised levels of the liver enzyme alanine aminotransferase (more than three times above the upper limit of normal). Appropriate investigation and close observation of patients should continue until the enzyme levels return to normal.
Patients are advised to immediately report to their doctor any symptoms that could indicate liver injury (such as sustained new-onset abdominal pain, loss of appetite, nausea, vomiting, fever, tiredness, jaundice, dark urine or itching).
The CHMP is to assess all available data concerning the possible risks of liver injury associated with the use of dronedarone and their impact on its benefit-risk balance and will announce its conclusions once a final opinion is reached.
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