DOVATO is indicated as a complete regimen to treat HIV-1 infection in adults with no antiretroviral (ARV) treatment history or to replace the current ARV regimen in those whoare virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable ARV regimen with no history of treatment failure and no known resistance to any component of DOVATO.
IMPORTANT SAFETY INFORMATION
BOXED WARNING: PATIENTS CO-INFECTED WITH HEPATITIS B VIRUS (HBV) AND HIV-1: EMERGENCE OF LAMIVUDINE-RESISTANT HBV AND EXACERBATIONS OF HBV
All patients with HIV-1 should be tested for the presence of HBV prior to or when initiating DOVATO. Emergence of lamivudine-resistant HBV variants associated with lamivudine-containing antiretroviral regimens has been reported. If DOVATO is used in patients co-infected with HIV-1 and HBV, additional treatment should be considered for appropriate treatment of chronic HBV; otherwise, consider an alternative regimen.
Severe acute exacerbations of HBV have been reported in patients who are co-infected with HIV-1 and HBV and have discontinued lamivudine, a component of DOVATO. Closely monitor hepatic function in these patients and, if appropriate, initiate anti-HBV treatment.
- Do not use DOVATO in patients with previous hypersensitivity reaction to dolutegravir or lamivudine
- Do not use DOVATO in patients receiving dofetilide
Warnings and precautions
- Hypersensitivity reactions have been reported with dolutegravir and were characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury
- Discontinue DOVATO immediately if signs or symptoms of severe skin or 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
- 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 DOVATO. 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
- Monitoring for hepatotoxicity is recommended
Embryo Fetal Toxicity:
- Assess the risks and benefits of DOVATO and discuss with the patient to determine if an alternative treatment should be considered at the time of conception through the first trimester of pregnancy due to the risk of neural tube defects
- Pregnancy testing is recommended before initiation of DOVATO. Individuals of childbearing potential should be counseled on the consistent use of effective contraception
Lactic Acidosis and Severe Hepatomegaly With Steatosis:
Fatal cases have been reported with the use of nucleoside analogs, including lamivudine. Discontinue DOVATO if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity develop, including hepatomegaly and steatosis in the absence of marked transaminase elevations.
Adverse Reactions or Loss of Virologic Response Due to Drug Interactions with concomitant use of DOVATO 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 DOVATO.
The most common adverse reactions (incidence ≥2%, all grades) with DOVATO were headache (3%), nausea (2%), diarrhea (2%), insomnia (2%), fatigue (2%), and anxiety (2%).
- Consult full Prescribing Information for DOVATO for more information on potentially significant drug interactions
- DOVATO is a complete regimen. Coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended
- Drugs that induce or inhibit CYP3A or UGT1A1 may affect the plasma concentrations of dolutegravir
- Administer DOVATO 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, DOVATO and supplements containing calcium or iron can be taken with food
Please see additional Important Safety Information continued on right.
References: 1. van Wyk J, Ajana F, Bisshop F, et al. Efficacy and safety of switching to dolutegravir/lamivudine fixed-dose 2-drug regimen vs continuing a tenofovir alafenamide–based 3- or 4-drug regimen for maintenance of virologic suppression in adults living with human immunodeficiency virus type 1: phase 3, randomized, noninferiority TANGO study. Clin Infect Dis. 2020;71(8):1920-1929. doi:10.1093/cid/ciz1243
2. Data on file, ViiV Healthcare.
3. van Wyk J, Ajana F, Bisshop F, et al. Switching to DTG/3TC fixed-dose combination (FDC) is non-inferior to continuing a TAF-based regimen (TBR) in maintaining virologic suppression through 96 weeks (TANGO study). Presented at: HIV Glasgow 2020; October 5-8, 2020; Virtual.Slides O441.
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