Information for Healthcare Professionals
· Be aware that didanosine use has been associated with the development of non-cirrhotic portal hypertension.
· Discuss with patients the clinical benefits and potential risks, including the risk of non-cirrhotic portal hypertension, with the use of didanosine.
· Continue to monitor patients for the development of portal hypertension and oesophageal varices.
· Be aware that didanosine already has a Boxed Warning for lactic acidosis and hepatomegaly with steatosis.
· Didanosine in combination with other antiretroviral agents as well as hydroxyurea or ribavirin has been associated with the development of liver toxicity.
Data Summary
The FDA's decision to revise the drug label for didanosine is based on post-marketing reports of patients developing non-cirrhotic portal hypertension while using didanosine. 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 2 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.
· Definitive cases of non-cirrhotic portal hypertension were confirmed by biopsy and had no alternative etiology for the diagnosis.
Medical interventions described in the reported cases included:
· Banding/ligation of oesophageal varices in 8 patients.
· Transjugular intrahepatic portosystemic shunt procedure in 3 patients.
· Liver transplantation in 3 patients.
There were 4 deaths total in the 42 reported cases. The cause of death in the 4 patients was due to:
· Haemorrhage from oesophageal varices in 2 patients.
· Progressive liver failure in 1 patient.
· A combination of multi-organ failure, cerebral haemorrhage, sepsis, and lactic acidosis in 1 patient.
The only patients who have been reported as fully recovered are the 3 non-cirrhotic portal hypertension patients who received a liver transplant.
A causal association is difficult to determine from postmarketing reports alone. However, based on the number of well-documented cases and exclusion of other causes of portal hypertension such as alcohol-related cirrhosis or hepatitis C, the FDA concludes there is an association between use of didanosine and development of non-cirrhotic portal hypertension.
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SOURCE: US Food and Drug Administration
ROCKVILLE, Md -- January 29, 2010 -- The US Food and Drug Administration (FDA) is alerting healthcare professionals about a rare, but serious, complication in the liver known as non-cirrhotic portal hypertension in patients using didanosine (Videx or Videx EC).
The FDA became aware of cases of non-cirrhotic portal hypertension through adverse event reports submitted to the FDA's Adverse Event Reporting System (AERS). Based on these reports, the FDA has revised the didanosine drug label to include information about non-cirrhotic portal hypertension to help ensure the safe use of this drug.
The FDA believes the clinical benefits of didanosine for certain patients with HIV continue to outweigh its potential risks. The decision to use this drug, however, must be made on an individual basis between the treating physician and the patient.
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