FDA and Tibotec Therapeutics are alerting healthcare professionals about the risk of hepatotoxicity associated with the antiretroviral drug Prezista (darunavir). Prezista, co-administered with ritonavir and other antiretroviral agents, is used to treat certain patients with HIV-1. Some patients receiving the Prezista/ritonavir combination have experienced drug-induced hepatitis and liver injuries, a small number of them fatal. Most of these patients were taking multiple medications that can affect the liver or had other co-morbid conditions. Patients with underlying liver disease, such as chronic hepatitis B or C may be at increased risk for developing liver function abnormalities. It is not clear that the Prezista/ritonavir combination caused the adverse reactions. Still, clinicians should be alert to the signs and symptoms of liver toxicity in patients taking this drug combination. Appropriate hepatic lab tests should be done before starting the drug, and patients should be monitored during treatment according to HIV treatment guidelines. Elevated levels of ALT, AST and GGT may indicate liver injury. Patients with underlying chronic hepatitis or cirrhosis, or patients who have elevated transaminase levels before treatment, should be monitored more frequently. Consider interrupting or stopping the treatment if there is evidence of new or worsening liver dysfunction, including clinically significant elevation of liver enzymes, or symptoms such as fatigue, anorexia, nausea, jaundice, dark urine, liver tenderness, or hepatomegaly. Patients should be told to promptly seek medical attention if they experience these symptoms. Additional Information: FDA MedWatch Safety Alert. Prezista (darunavir). March 12, 2008. http://www.fda.gov/medwatch/safety/2008/safety08.htm#Prezista

Novartis is warning healthcare professionals that hepatic failure can occur in patients treated with Exjade(deferasirox). Exjade is used to treat tranfusional hemosiderosis, the chronic iron overload that can result from multiple blood transfusions. Cases of liver failure, some of them fatal, have been reported in patients treated with Exjade. Most of these cases occurred in patients over 55 years old who had significant comorbidities, including liver cirrhosis and multi-organ failure. Because of this, liver function should be monitored monthly, and if there is unexplained, persistent, or progressive increase in serum transaminase levels, Exjade treatment should be modified or interrupted. FDA Patient Safety News: March 2008 For more information, please see our website: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/psn/transcript.cfm?show=73#4

Biogen Idec and Elan Pharmaceuticals are warning healthcare professionals about reports of clinically significant liver injury in patients taking Tysabri (natalizumab). Tysabri is a monoclonal antibody used to treat certain patients with relapsing forms of multiple sclerosis. Signs of liver injury, such as elevated total bilirubin and significantly elevated serum hepatic enzymes, have occurred as early as six days after the first dose of Tysabri. These signs can also occur for the first time even in patients who have taken multiple doses of Tysabri. Some patients had liver injury that recurred after rechallenge with the drug, which provides evidence that Tysabri caused the injury. The combination of elevated bilirubin and transaminase levels without evidence of obstruction is an important indicator that a medication may be causing severe liver injury. This could lead to death or the need for a liver transplant in some patients. Therefore Tysabri should be discontinued in patients with jaundice or other evidence of significant liver injury. Patients should also be told that Tysabri may cause liver injury and advised to contact their doctors if they develop symptoms of hepatotoxicity such as jaundice, fatigue, nausea, vomiting and dark urine. Additional Information: FDA MedWatch Safety Alert. Tysabri (natalizumab). February 27, 2008. http://www.fda.gov/medwatch/safety/2008/safety08.htm#Tysabri

FDA and Tibotec Therapeutics are alerting healthcare professionals about the risk of hepatotoxicity associated with the antiretroviral drug Prezista (darunavir). Prezista, co-administered with ritonavir and other antiretroviral agents, is used to treat certain patients with HIV-1. Some patients receiving the Prezista/ritonavir combination have experienced drug-induced hepatitis and liver injuries, a small number of them fatal. Most of these patients were taking multiple medications that can affect the liver or had other co-morbid conditions. Patients with underlying liver disease, such as chronic hepatitis B or C may be at increased risk for developing liver function abnormalities. It is not clear that the Prezista/ritonavir combination caused the adverse reactions. Still, clinicians should be alert to the signs and symptoms of liver toxicity in patients taking this drug combination. Appropriate hepatic lab tests should be done before starting the drug, and patients should be monitored during treatment according to HIV treatment guidelines. Elevated levels of ALT, AST and GGT may indicate liver injury. Patients with underlying chronic hepatitis or cirrhosis, or patients who have elevated transaminase levels before treatment, should be monitored more frequently. Consider interrupting or stopping the treatment if there is evidence of new or worsening liver dysfunction, including clinically significant elevation of liver enzymes, or symptoms such as fatigue, anorexia, nausea, jaundice, dark urine, liver tenderness, or hepatomegaly. Patients should be told to promptly seek medical attention if they experience these symptoms. FDA Patient Safety News: May 2008 For more information, please see our website: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/psn/transcript.cfm?show=75#6

Biogen Idec and Elan Pharmaceuticals are warning healthcare professionals about reports of clinically significant liver injury in patients taking Tysabri (natalizumab). Tysabri is a monoclonal antibody used to treat certain patients with relapsing forms of multiple sclerosis. Signs of liver injury, such as elevated total bilirubin and significantly elevated serum hepatic enzymes, have occurred as early as six days after the first dose of Tysabri. These signs can also occur for the first time even in patients who have taken multiple doses of Tysabri. Some patients had liver injury that recurred after rechallenge with the drug, which provides evidence that Tysabri caused the injury. The combination of elevated bilirubin and transaminase levels without evidence of obstruction is an important indicator that a medication may be causing severe liver injury. This could lead to death or the need for a liver transplant in some patients. Therefore Tysabri should be discontinued in patients with jaundice or other evidence of significant liver injury. Patients should also be told that Tysabri may cause liver injury and advised to contact their doctors if they develop symptoms of hepatotoxicity such as jaundice, fatigue, nausea, vomiting and dark urine. FDA Patient Safety News: May 2008 For more information, please see our website: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/psn/transcript.cfm?show=75#3

Biogen Idec has notified healthcare professionals about safety changes in the labeling for Avonex (interferon beta-1a), which is used to treat relapsing forms of MS. The labeling now warns that severe hepatic injury, including hepatic failure, hepatitis, and elevated serum hepatic enzyme levels, have been reported in patients on Avonex. Patients have also experienced asymptomatic elevation of hepatic transaminases, and this recurred in some patients when they were rechallenged with Avonex. In some cases, these events occurred when the patient was taking other drugs that are associated with hepatic injury. The company says consider the potential for injury when Avonex is used in combination with other hepatotoxic products such as alcohol, or when new agents are added to the regimen of patients already on Avonex. The company also says that patients on Avonex should be monitored for signs of hepatic injury.