Didanosine, the second drug approved for the treatment of HIV infections and one of the oldest weapons in the AIDS armamentarium, has been found to produce rare cases of potentially fatal liver disease in patients taking it for long periods, the Food and Drug Administration announced Monday. Didanosine, marketed by Bristol-Myers Squibb under the brand names Videx and Videx EC (an extended release version), was approved by the FDA in 1991, joining AZT as the only drugs then approved to treat HIV. It is a reverse transcriptase inhibitor, blocking the action of the key enzyme used by HIV in replicating. It has limited value when used alone because the virus rapidly mutates to overcome it, and is thus generally used in drug cocktails.
In the 18 years since the drug has been on the market, the FDA has received 42 reports of a rare disorder called non-cirrhotic portal hypertension. It results when high blood pressure occurs in the portal vein--a major vein of the liver--causing the vein to enlarge and weaken. Once the vein wall is weakened, it can split open, leading to fatal bleeding. Non-cirrhotic means that the condition is not caused by cirrhosis of the liver, a consequence of alcohol abuse.
Of the 42 cases, 26 were males, 14 were females and no gender was reported for two. Their ages ranged from 10 to 66 years. All had been taking the drug for months or years before the condition developed. Four of the patients died from bleeding or organ failure. Eight patients were treated by surgical techniques to reinforce the vein or by a liver transplant. Only the three patients who had transplants fully recovered.
The FDA concluded that the benefits of the drug outweigh the risk, but is increasing the package warning to alert physicians and patients to the possibility that the problem will develop. The drug already has a box warning of an increased risk of lactic acidosis and hepatomegaly with steatosis, caused by damage to mitochondria in liver cells.
-- Thomas H. Maugh II