Regulators in the USA have expanded the black box warning on Sanofi-Aventis’ rheumatoid arthritis drug Arava to highlight the risk of severe liver damage.

The US Food and Drug Admininstration says the move is based agency received on a review of adverse event reports which identified 49 cases of severe liver injury in patients on Arava (leflunomide). These included 14 fatalities reported between August 2002 to May 2009, and 36 cases which required hospitalisation

The agency went on to say that the greatest risk occurred in patients taking other drugs that may cause liver damage while taking Arava and in those with pre-existing liver disease. The new warnings say these patients should not receive the drug and also state that liver enzymes should be monitored at least monthly for three months after the start of treatment.

The revised warning also notes that patients who experience itching, yellow eyes or skin, dark urine, loss of appetite, or light-coloured stool while taking leflunomide should contact a doctor right away. Arava previously carried a boxed warning that the drug was contraindicated in pregnant women and women of childbearing age who do not use reliable contraception.

The drug has been attacked in the past by groups like the consumer watchdog Public Citizen who had demanded Arava’s withdrawal from the market. Those pleas were rejected by the FDA some six years ago.