HIV Drug Has Liver Risks, FDA WarnsFeb 2, 2010 | Parker Waichman LLP
The U.S. Food and Drug Administration (FDA) just issued a safety announcement alerting healthcare professionals and patients about a rare, but serious liver complication known as non-cirrhotic portal hypertension occurring in some patients using Videx or Videx EC (didanosine). Didanosine is an antiretroviral medication used to treat the Human Immunodeficiency Virus (HIV) infection. Videx was the first approved didanosine medication; Videx EC is a delayed-release version of Videx. Bristol-Myers Squibb markets both.
Didanosine is a prescription medication in the nucleoside analogues class of medications used with other drugs to treat patients infected with HIV, the virus that causes AIDS, and works by reducing the growth of HIV. Didanosine helps the body maintain its supply of immune cells called CD4 cells, which are critical for fighting HIV and other infections.
Non-cirrhotic portal hypertension—portal hypertension not caused by cirrhosis of the liver—is rare in the United States. The disorder occurs when blood flow in the major vein in the liver—the portal vein—slows. This slowed blood flow can lead to the development of severely enlarged esophageal veins (varices) in the gastrointestinal system. Because esophageal varices are thin and portal hypertension increases the pressure of blood flow in these veins, esophageal varices can break open, resulting in serious bleeding and, in some cases, death.
The FDA became aware of these adverse events through adverse event reports submitted to FDA's Adverse Event Reporting System (AERS), and has since revised the didanosine drug label to include information about non-cirrhotic portal hypertension. The FDA believes the clinical benefits of didanosine for certain patients with HIV continue to outweigh its potential risks; however, the decision to use this drug must be made on an individual basis between the treating physician and the patient.
The FDA is advising physicians to continue monitoring patients for the development of portal hypertension and esophageal varices. Of note, didanosine already has a Boxed Warning for lactic acidosis and hepatomegaly with steatosis and, other liver adverse events such as lactic acidosis, hepatomegaly with steatosis, and liver failure have been reported with the use of didanosine alone and in combination with other antiviral drugs.
Of the 42 post-marketing cases of non-cirrhotic portal hypertension in patients using didanosine 26 were males; 14 were females; and, in two, no gender was specified. The ages ranged from 10 years to 66 years. Duration of didanosine treatment ranged from months to years before development of non-cirrhotic portal hypertension.
Patients required banding/ligation of esophageal varices, transjugular intrahepatic portosystemic shunt (TIPSS) procedure, or liver transplantation; four patients died. Some deaths were due to bleeding or liver failure after the condition developed. In one case, a combination of multi-organ failure, cerebral hemorrhage, sepsis, and lactic acidosis caused the death.
Videx/Videx EC does not cure HIV infection, may not prevent development of HIV-related illnesses, and may not prevent the spread of HIV to other people.