Important Safety Information

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

WARNINGS AND PRECAUTIONS

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reconstitution syndrome or hepatitis B reactivation, particularly in the setting where anti-hepatitis therapy was withdrawn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:

Fatal cases have been reported with the use of nucleoside analogues, including abacavir and lamivudine. Discontinue TRIUMEQ if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity develop, including hepatomegaly and steatosis in the absence of marked transaminase elevations.

Embryofetal Toxicity:

• Alternative treatments to TRIUMEQ should be considered at the time of conception through the first trimester of pregnancy due to the risk of neural tube defects
• Perform pregnancy testing before use of TRIUMEQ and counsel that consistent use of effective contraception is recommended while using TRIUMEQ in adolescents and adults of childbearing potential

Adverse Reactions or Loss of Virologic Response Due to Drug Interactions with concomitant use of TRIUMEQ and other drugs may occur (see Contraindications and Drug Interactions).

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)

ADVERSE REACTIONS

The most common adverse reactions (incidence ≥2%, Grades 2-4) in treatment-naïve adults receiving TRIUMEQ were insomnia (3%), headache (2%), and fatigue (2%).

DRUG INTERACTIONS

• Consult the full Prescribing Information for TRIUMEQ for more information on potentially significant drug interactions
• Drugs that induce or inhibit CYP3A or UGT1A1 may affect plasma concentrations of dolutegravir
• Administer TRIUMEQ 2 hours before or 6 hours after taking polyvalent cation-containing antacids or laxatives, sucralfate, oral supplements containing iron or calcium, or buffered medications. Alternatively, when taken with food, TRIUMEQ and supplements containing calcium or iron can be taken at the same time

USE IN SPECIFIC POPULATIONS

• Pregnancy: There are insufficient human data on the use of TRIUMEQ during pregnancy to definitively assess a drug-associated risk for birth defects and miscarriage. An Antiretroviral Pregnancy Registry has been established. If planning a pregnancy or if pregnancy is confirmed while taking TRIUMEQ during the first trimester, assess the risks and benefits of continuing TRIUMEQ versus switching to another antiretroviral regimen. For individuals actively trying to become pregnant, initiation of TRIUMEQ is not recommended unless there is no suitable alternative
• Lactation: Breastfeeding is not recommended due to the potential for HIV-1 transmission, developing viral resistance in HIV-positive infants, and adverse reactions in a breastfed infant
• Females and Males of Reproductive Potential: Perform pregnancy testing before initiation of TRIUMEQ. Advise individuals of childbearing potential to consistently use effective contraception while taking TRIUMEQ
• Impaired Renal Function: TRIUMEQ is not recommended in patients with creatinine clearance <50 mL/min
• Impaired Hepatic Function: If a dose reduction of abacavir is required for patients with mild hepatic impairment, then the individual components of TRIUMEQ should be used

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