RISKS AND SIDE EFFECTS
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reconstitution syndrome or hepatitis B reactivation, particularly in the setting where anti-hepatitis therapy was withdrawn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:
- Avoid use of DOVATO at the time of conception through the first trimester due to the risk of neural tube defects
- Perform pregnancy testing before use of DOVATO and advise that consistent use of effective contraception is recommended while using DOVATO in individuals of childbearing potential
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 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.
Adverse Drug Reactions
Pooled Analysis Through 48 Weeks From GEMINI 1 & 21,2
|Treatment-emergent ADRs (all grades) with ≥2% frequency, % (n)
||DOVATO (n=716)||DTG + TDF/FTC (n=717)|
|Headache||3% (21)||4% (30)|
|Nausea||2% (14)||5% (39)|
|Diarrhea||2% (14)||3% (19)|
|Insomnia||2% (13)||3% (18)|
|Fatigue*||2% (11)||2% (12)|
|Dizziness||1% (8)||2% (13)|
|Drug-related AEs, % (n)¹|
|All grades||18% (126)||24% (169)|
|Grades 2 to 5||6% (42)||7% (47)|
*Includes fatigue, asthenia, and malaise.
DTG=dolutegravir; TDF=tenofovir disoproxil fumarate; FTC=emtricitabine.
Pooled Analysis Through 48 Weeks From GEMINI 1 & 2
Patients who discontinued due to AEs1
DTG + TDF/FTC
- Most common AEs leading to discontinuation were psychiatric disorders (<1% of patients in both treatment arms)
ADR=adverse drug reaction; AEs=adverse events; DTG=dolutegravir; FTC=emtricitabine; TDF=tenofovir disoproxil fumarate.
- Cahn P, Sierra Madero J, Arribas J, et al; and GEMINI study team. Dolutegravir plus lamivudine versus dolutegravir plus tenofovir disoproxil fumarate and emtricitabine in antiretroviral-naïve adults with HIV-1 infection (GEMINI-1 and GEMINI-2): week 48 results from two multicentre, double-blind, randomised, non-inferiority, phase 3 trials. Lancet. 2019;393(10167):143-155.
- Data on file. ViiV Healthcare group of companies. Research Triangle Park, NC.