For treatment-naïve and virologically suppressed adults with HIV-1. See Full Indication.
The information below gives an overview of the potential risks and side effects of DOVATO as observed in GEMINI 1 & 2, Study of Test And Treat (STAT), and TANGO clinical trials, including warnings and precautions, drug-related adverse events, and discontinuation rates due to adverse events.
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
- 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
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 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reconstitution syndrome or hepatitis B reactivation, particularly in the setting where anti-hepatitis therapy was withdrawn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.
GEMINI 1 & 2 TRIALS:
Drug-Related Adverse Events and Discontinuation Rates in Treatment-Naïve Adults Through 144 Weeks
Significantly Lower Rate of Drug-Related Adverse Events vs DTG + TDF/FTC at 144 Weeks*
GEMINI 1 & 2—Pooled Analysis, n (%)1,2
Based on participants reporting drug-related AEs (all Grades: DOVATO arm [20% at 144 weeks]; DTG + TDF/FTC arm [27% at 144 weeks]).1 The clinical significance is unknown.
†Includes fatigue, asthenia, and malaise.2
AE=adverse event, DTG=dolutegravir; FTC=emtricitabine; TDF=tenofovir disoproxil fumarate.
STAT-RAPID INITIATION TRIAL:
Drug-Related Adverse Events Regardless of Treatment Regimen and Discontinuation Rates
Drug-Related Adverse Events at 48 Weeks
STAT—CHARACTERISTIC, % (n)2
The safety population is the same as the ITT—all enrolled participants who received at least 1 dose of DOVATO.
- 2% (n=2) of participants had serious AEs¶
- Rates of discontinuation due to adverse events through 24 weeks: Of the 11% (n=15) of participants who discontinued the study, 9% (n=12) were lost to follow-up or withdrew consent and 2% (n=3) due to physician decision. Data were not available for 4% (n=5) of participants
§All AEs were grade 2.
||One AE leading to discontinuation occurred (rash), and the event resolved.
¶Two serious AEs occurred (cellulitis, streptococcal bacteremia). No fatal serious AEs occurred. AEs were coded using MedDRA v23.1
SAE=serious adverse event.
TANGO TRIAL:
Drug-Related Adverse Events and Discontinuation Rates Through 144 Weeks2,3
1 participant was excluded for receiving a TDF-containing regimen instead of a TAF-containing regimen.
TAF=tenofovir alafenamide fumarate.
References:
- Cahn P, Madero JS, Arribas JR, et al. Durable efficacy of dolutegravir (DTG) plus lamivudine (3TC) in antiretroviral treatment-naïve adults with HIV-1 infection—3-year results from the GEMINI studies. Poster P018 presented at: HIV Glasgow 2020; October 5-8, 2020; Virtual.
- Data on file, ViiV Healthcare.
- van Wyk J, Ait-Khaled M, Santos J, et al. Metabolic health outcomes at week 144 in the TANGO study, comparing a switch to DTG/3TC versus maintenance of TAF-based regimens. Poster PEB164 presented at: 11th IAS Conference on HIV Science; July 18-21, 2021; Virtual.
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