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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-.

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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet].

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Last Update: January 30, 2018.



Raltegravir is an integrase inhibitor, the first of the 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. 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 in an increasing proportion of antiretroviral regimens. Raltegravir is available as 400 mg tablets generically and 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 were not associated with clinical symptoms and generally did not require dose modification. There have been no published reports of clinically apparent cases of liver injury attributed to raltegravir. Nevertheless, 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 and drug hypersensitivity reactions, 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.

Likelihood score: E* (unproven but suspected cause of clinically apparent liver injury).

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

Serum enzyme elevations during raltegravir therapy are not uncommon but are generally mild to moderate in severity and often are attributable to other agents taken in combination with raltegravir. Nevertheless, aminotransaferase elevations above 5 times the ULN, if confirmed, warrant dose interruption and evaluation for other causes of acute liver injury. There is no information about the cross sensitivity to liver injury among the various HIV integrase inhibitors, but some degree of cross reactivity should be expected.

Drug Class: Antiviral Agents

Other Drugs in the Subclass, Integrase Strand Transfer Inhibitors: Bictegravir, Cabotegravir, Dolutegravir, Elvitegravir



Raltegravir – Isentress®


Antiviral Agents


Product labeling at DailyMed, National Library of Medicine, NIH


Raltegravir 518048-05-0 C20-H21-F-N6-O5 image 135216344 in the ncbi pubchem database


References updated: 30 January 2018

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    (Among 192 adults with HIV and either HBV or HCV coinfection who were started on antiretroviral therapy and monitored under "real life" conditions, ALT and AST elevations above 5 times ULN occurred in 10 patients [5%], but all were self limited and none required discontinuation of therapy for this reason).
  • Cahn P, Kaplan R, Sax PE, Squires K, Molina JM, Avihingsanon A, Ratanasuwan W, et al. ONCEMRK Study Group. Raltegravir 1200 mg once daily versus raltegravir 400 mg twice daily, with tenofovir disoproxil fumarate and emtricitabine, for previously untreated HIV-1 infection: a randomised, double-blind, parallel-group, phase 3, non-inferiority trial. Lancet HIV. 2017;4(11):e486–e494. [PubMed: 28918877]
    (Among 802 adults with HIV infection treated with once or twice daily raltegravir for 48 weeks, efficacy and tolerability were similar in the two groups, while ALT elevations above 2.5 times ULN occurred in 2.5% of patiients on once vs 0.8% on twice daily raltegravir).


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