Risks and Side Effects

BOXED WARNING: HYPERSENSITIVITY REACTIONS AND EXACERBATIONS OF HEPATITIS B VIRUS (HBV):

Hypersensitivity Reactions:

  • Serious and sometimes fatal hypersensitivity reactions have occurred with abacavir-containing products
  • Hypersensitivity to abacavir is a multi-organ clinical syndrome
  • Patients who carry the HLA‐B*5701 allele are at a higher risk of experiencing a hypersensitivity reaction to abacavir, although hypersensitivity reactions have occurred in patients who do not carry the HLA‐B*5701 allele
  • TRIUMEQ is contraindicated in patients with a prior hypersensitivity reaction to abacavir and in HLA‐B*5701-positive patients. All patients should be screened for the HLA‐B*5701 allele prior to initiating therapy or reinitiation of therapy with TRIUMEQ unless patients have a previously documented HLA‐B*5701 allele assessment
  • Discontinue TRIUMEQ as soon as hypersensitivity reaction is suspected. Regardless of HLA‐B*5701 status, permanently discontinue TRIUMEQ if hypersensitivity cannot be ruled out, even when other diagnoses are possible
  • Following a hypersensitivity reaction to TRIUMEQ, NEVER restart TRIUMEQ or any other abacavir-containing product

Exacerbations of Hepatitis B:

  • Severe acute exacerbations of HBV have been reported in patients who are co-infected with HBV and HIV-1 and have discontinued lamivudine, a component of TRIUMEQ. Monitor hepatic function closely in these patients and, if appropriate, initiate anti-hepatitis B treatment

CONTRAINDICATIONS

  • Do not use TRIUMEQ in patients who have the HLA-B*5701 allele
  • Do not use TRIUMEQ in patients with previous hypersensitivity reaction to abacavir, dolutegravir, or lamivudine
  • Do not use TRIUMEQ in patients receiving dofetilide
  • Do not use TRIUMEQ in patients with moderate or severe hepatic impairment

Hypersensitivity Reactions:

  • Hypersensitivity reactions have been reported with dolutegravir and were characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury
  • Clinically, it is not possible to determine whether a hypersensitivity reaction with TRIUMEQ would be caused by abacavir or dolutegravir
  • Discontinue TRIUMEQ immediately if signs or symptoms of hypersensitivity reactions develop, as a delay in stopping treatment may result in a life-threatening reaction. Clinical status, including liver aminotransferases, should be monitored and appropriate therapy initiated

Hepatotoxicity:

  • Hepatic adverse events have been reported, including cases of hepatic toxicity (elevated serum liver biochemistries, hepatitis, and acute liver failure), in patients receiving a dolutegravir-containing regimen without pre-existing hepatic disease or other identifiable risk factors
  • Patients with underlying hepatitis B or C or marked elevations in transaminases prior to treatment may be at increased risk for worsening or development of transaminase elevations with use of TRIUMEQ. In some cases, the elevations in transaminases were consistent with immune reconstitution syndrome or hepatitis B reactivation, particularly in the setting where anti-hepatitis therapy was withdrawn
  • Drug-induced liver injury leading to liver transplant has been reported with TRIUMEQ
  • Monitoring for hepatotoxicity is recommended

Lactic Acidosis and Severe Hepatomegaly with Steatosis:

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues, including abacavir and lamivudine. Female sex and obesity may be risk factors in patients treated with nucleoside analogues.

Embryofetal Toxicity:

  • Avoid use of dolutegravir, a component of TRIUMEQ, at the time of conception through the first trimester due to the risk of neural tube defects
  • Perform pregnancy testing before use of dolutegravir and advise that consistent use of effective contraception is recommended while using dolutegravir in adolescents and adults of childbearing potential

Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions:

The concomitant use of TRIUMEQ and other drugs may result in known or potentially significant drug interactions (see Contraindications and Drug Interactions)

Use with Interferon- and Ribavirin-based Regimens:

Hepatic decompensation, some fatal, has occurred in HIV-1/hepatitis C virus (HCV) co-infected patients receiving combination antiretroviral therapy and interferon alfa with or without ribavirin. Patients receiving interferon alfa, with or without ribavirin, and TRIUMEQ should be closely monitored.

Immune Reconstitution Syndrome,

including the occurrence of autoimmune disorders with variable time to onset, has been reported with the use of TRIUMEQ.

Myocardial Infarction (MI):

  • Several observational studies have reported an association with the use of abacavir and the risk of MI; meta-analyses of randomized controlled clinical trials did not show increased risk. To date, there is no established biological mechanism to explain a potential increase in risk. In totality, the available data show inconsistency; therefore, evidence for a causal relationship between abacavir and the risk of MI is inconclusive
  • The underlying risk of coronary heart disease should be considered when prescribing antiretroviral therapies, including abacavir, and action taken to minimize all modifiable risk factors (eg, hypertension, hyperlipidemia, diabetes mellitus, smoking)

SINGLE—Grades 2 to 4 treatment-emergent adverse drug reactions (≥2% frequency)

*Includes pooled terms: rash, rash generalized, rash macular, rash maculopapular, rash pruritic, and drug eruption.

TDF/FTC=tenofovir/emtricitabine.

ARIA—Grades 2 to 4 treatment-emergent adverse drug reactions (≥2% frequency)1

*Includes rash, rash generalized, rash maculopapular, rash papular, and rash pruritic.

TDF/FTC=tenofovir/emtricitabine.

 

  • Direct comparisons across trials should not be made due to differing trial designs

Please see full Prescribing Information, including Boxed Warning and Medication Guide, for TRIUMEQ.

Reference

  1. Data on file. ViiV Healthcare group of companies. Research Triangle Park, NC.