Liver Injury Linked to Darunavir (Prezista)

By Michael Smith
ROCKVILLE, Md., March 21 -- The anti-HIV drug darunavir (Prezista) may be associated with liver toxicity, the FDA and the drug's maker warned today.
The warning emerged from 24 cases of liver injury, including some fatalities, identified in postmarketing reports of darunavir use, according to the FDA and Tibotec Therapeutics, of East Bridgewater, N.J.
"While causality is not firmly established, an association between (darunavir) and hepatotoxicity is suspected," the FDA said.
The company has sent a Dear Healthcare Professional letter to doctors, and the prescribing information and the package insert have been changed to reflect the warning.
The prescribing information and package insert now advise:
Physicians should undertake appropriate hepatic laboratory testing before and after starting patients on the drug.
Patients should seek medical attention if they have unexplained fatigue, anorexia, nausea, jaundice, abdominal pain, or dark urine.
Doctors should consider interrupting or discontinuing darunavir if there's evidence of new or worsening liver injury.
Darunavir is a protease inhibitor approved for the treatment of HIV in antiretroviral treatment-experienced adult patients. It is given with ritonavir (Norvir), which is known to be associated with liver toxicity.
In general, antiretroviral medications are associated with liver enzyme elevations.
The FDA said it is possible that darunavir is related to liver adverse events in 24 cases, including hepatic failure, hepatic necrosis, cirrhosis, hepatitis, jaundice and increased liver function tests.
In all cases, patients were taking other drugs or had underlying medical conditions that may have contributed, the agency said. In nine of the 24 cases, the patient reported co-infection with hepatitis B or C.
The agency highlighted five cases, which it said were "among the most convincing cases from clinical trials and post-marketing reports:"
A biopsy-proven drug-induced liver injury in a patient with a history of alcohol use.
Acute hepatitis with elevated liver enzymes in a patient co-infected with chronic hepatitis B. The condition abated when darunavir and other antiretrovirals were stopped and recurred when they were restarted.
Two cases of biopsy-proven drug-induced liver injury in patients not co-infected with hepatitis B or C.
Acute hepatitis with a drug-induced hypersensitivity reaction in a patient with chronic hepatitis B. All anti-retrovirals were stopped and restarted except darunavir, and the hepatitis did not recur.