RISKS AND SIDE
EFFECTS OF DOVATO
RISKS AND SIDE
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 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reconstitution syndrome or hepatitis B reactivation, particularly in the setting where anti-hepatitis therapy was withdrawn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.
GEMINI 1 & 2 TRIALS:
Drug-Related Adverse Events and Discontinuation Rates in Treatment-Naive 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
|Drug-related AEs||DOVATO (n=716)||DTG + TDF/FTC (n=717)|
|All grades||146 (20%)||192 (27%)|
|Grades 2 to 5||58 (8%)||69 (10%)|
|Patients reporting drug-related AEs (all Grades) with ≥2% frequency|
|Headache||21 (3%)||30 (4%)|
|Nausea||14 (2%)||40 (6%)|
|Diarrhea||15 (2%)||21 (3%)|
|Insomnia||15 (2%)||20 (3%)|
|Dizziness||8 (1%)||14 (2%)|
|Fatigue†||12 (2%)||13 (2%)|
|Anxiety||11 (2%)||6 (<1%)|
|AEs leading to withdrawal||31 (4%)||33 (5%)|
Based on patients 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 24 Weeks
STAT—CHARACTERISTIC, % (n)2
|Patients reporting drug-related adverse events||(n=131)|
|All grades||7% (9)|
|Grades 2 to 5||2% (2)‡|
|Adverse events occurring in >5% of patients|
|AEs leading to withdrawal||<1% (1)§|
- 2% (n=2) of patients had serious AEs||
- Rates of discontinuation due to adverse events through 24 weeks: Of the 11% (n=15) of patients 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 patients
‡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.
Drug-Related Adverse Events and Discontinuation Rates Through 96 Weeks2,3
1 participant was excluded for receiving a TDF-containing regiment instead of a TAF-containing regimen.
- 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. Presented at: HIV Glasgow 2020; October 5-8, 2020; Virtual. Poster P018.
- Data on file, ViiV Healthcare.
- 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.