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reconstitution syndrome or hepatitis B reactivation, particularly in the setting where anti-hepatitis therapy was withdrawn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:
- Alternative treatments to DOVATO 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 DOVATO and counsel 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 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 Through 96 Weeks
Significantly Lower Rate of Drug-Related Adverse Events vs DTG + TDF/FTC at 96 Weeks*
GEMINI 1 & 2—POOLED ANALYSIS, % (n)1,2
|Patients reporting drug-related adverse events||DOVATO (n=716)||DTG + TDF/FTC (n=717)|
|All grades||20% (140)||25% (179)|
|Grades 2 to 5||7% (50)||8% (57)|
|Patients reporting drug-related adverse events (all grades) with ≥2% frequency†|
|Headache||3% (21)||4% (30)|
|Nausea||2% (14)||5% (39)|
|Diarrhea||2% (15)||3% (19)|
|Insomnia||2% (15)||3% (19)|
|Fatigue‡||2% (12)||2% (13)|
|Anxiety||2% (11)||1% (5)|
|Dizziness||1% (8)||2% (13)|
|AEs leading to withdrawal||3%||3%|
*The clinical significance is unknown.
- Rates of discontinuation due to adverse events through 96 weeks: 3% in each arm
- Most common adverse events leading to discontinuation were psychiatric disorders (1% of patients in both treatment arms through 96 weeks)
Based on patients reporting drug-related adverse events (all grades): DOVATO arm (20%); DTG + TDF/FTC arm (25%).
Includes fatigue, asthenia, and malaise.
AEs=adverse events; DTG=dolutegravir; TDF=tenofovir disoproxil fumarate; FTC=emtricitabine.
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||DOVATO (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 bacterermia). No fatal serious AEs occurred.
Drug-Related Adverse Events and Discontinuation Rates Through 48 Weeks3
Overall Adverse Events Were Comparable Across Both Arms at 48 Weeks
(n=369), n (%)
(n=372), n (%)
|Patients reporting drug-related AEs, all grades#||45 (12%)||5 (1%)|
|Patients reporting any drug-related AEs, grades 2 to 5||17 (5%)||3 (1%)|
|Grades 2 to 5 (occurring in ≥0.5% of patients)|
|Constipation||2 (1%)||1 (<1%)|
|AEs leading to withdrawal||13 (4%)||2 (1%)|
|Drug-related AEs leading to withdrawal||9 (2%)||1 (<1%)|
All drug-related AEs are Grade 2 or less.
- Cahn P, Madero JS, Arribas JR, et al. Durable efficacy of dolutegravir plus lamivudine in antiretroviral treatment-naïve adults with HIV-1 infection: 96-week results from the GEMINI-1 and GEMINI-2 randomized clinical trials. J Acquir Immune Defic Syndr. 2020;83(3):310-318. doi:10.1097/QAI.0000000000002275.
- Data on file, ViiV Healthcare.
- 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;ciz1243. doi:10.1093/cid/ciz1243.