Raltegravir is an integrase inhibitor, the first of a new class of antiviral agents active against the human immunodeficiency virus (HIV) that targets the viral integrase. Raltegravir is used in combination with other antiretroviral agents in the treatment of HIV infection, but has had limited use. Raltegravir has not been linked convincingly to serum aminotransferase elevations during therapy or to episodes of acute, clinically apparent liver injury.
Raltegravir (ral teg' ra vir) is relatively new antiretroviral drug that targets the HIV integrase, one of the three enzymes involved in viral replication. Raltegravir blocks the binding site of the HIV integrase and prevents the strand transfer activity and integration of the provirus into the host genome. Raltegravir has both in vitro and in vivo activity against HIV, and several randomized controlled trials have shown that it leads to significant decline in HIV RNA levels and rises in peripheral CD4 T cell counts. Raltegravir was given accelerated approval for use in HIV infection in the United States in 2007 and is currently used an increasing proportion of antiretroviral regimens. Raltegravir is available as 400 mg tablets under the brand name Isentress. The recommended dose regimen is 400 mg twice daily in combination with other classes of antiretroviral agents. Common side effects include diarrhea, headache, nausea and fever.
In large clinical trials, therapy with raltegravir was associated with alanine aminotransferase (ALT) elevations in up to 10% and elevations of greater than 5 times the upper limit of normal (ULN) in 3% to 4% of patients, but these rates were similar to those in comparator groups receiving matched background optimized antiretroviral therapy without raltegravir. These elevations have not been associated with clinical symptoms and generally do not require dose modification. There have been no published reports of clinically apparent cases of liver injury attributed to raltegravir, but it has had limited use. The product label for raltegravir mentions hepatitis and hepatic failure as a potential adverse reactions, but without specific details. Raltegravir has also been linked to instances of Stevens Johnson syndrome, which can be accompanied by hepatic involvement. Finally, initiation of antiretroviral therapy with raltegravir can result in the immune reconstitution syndrome which may cause a worsening or flare of an accompanying chronic hepatitis B or C in coinfected individuals.
Mechanism of Injury
Raltegravir is metabolized by the liver and undergoes glucuronidation as a part of its metabolic clearance. It does not have an effect on the CYP 450 system.
Outcome and Management
If raltegravir hepatotoxicity occurs, it must be very rare.
Other Drugs in the Subclass, Integrase Strand Transfer Inhibitors: Dolutegravir, Elvitegravir
REPRESENTATIVE TRADE NAMES
Raltegravir – Isentress®
Product labeling at DailyMed, National Library of Medicine, NIH
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References updated: 10 February 2014
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