oval, biconvex, white, film-coated tablets, debossed with “SV 137” on oneface. Each tablet contains 50 mg of dolutegravir and 300 mg oflamivudine.
4 CONTRAINDICATIONS
DOVATO is contraindicated in patients:
• with prior hypersensitivity reaction to dolutegravir [see Warnings and Precautions (5.2)] orlamivudine.
• receiving dofetilide, due to the potential for increased dofetilide plasma concentrations andthe risk for serious and/or life-threatening events [see DrugInteractions (7.2)].
5 WARNINGS AND PRECAUTIONS
5.1 Patients Co-infected with HIV-1 and HBV: Emergence of Lamivudine-Resistant
HBV and the Risk of Posttreatment Exacerbations of HBV
All patients with HIV-1 should be tested for the presence of HBV prior to or when initiatingDOVATO.
Emergence of Lamivudine-Resistant HBV
Safety and efficacy of lamivudine have not been established for treatment of chronic HBV insubjects dually infected with HIV-1 and HBV. Emergence of HBV variants associated withresistance to lamivudine has been reported in HIV-1–infected subjects who have receivedlamivudine-containing antiretroviral regimens in the presence of concurrent infection with HBV.
If a decision is made to administer DOVATO to 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 in Patients Co-infected with HIV-1 and HBVSevere acute exacerbations of HBV have been reported in patients who are co-infected with
HIV-1 and HBV and have discontinued products containing lamivudine, and may occur withdiscontinuation of DOVATO. Patients who are co-infected with HIV-1 and HBV who
discontinue DOVATO should be closely monitored with both clinical and laboratory follow-upfor at least several months after stopping treatment with DOVATO. If appropriate, initiation ofanti-HBV therapy may be warranted, especially in patients with advanced liver disease orcirrhosis, since posttreatment exacerbation of hepatitis may lead to hepatic decompensation andliver failure.
5.2 Hypersensitivity Reactions
Hypersensitivity reactions have been reported with the use of dolutegravir, a component ofDOVATO, and were characterized by rash, constitutional findings, and sometimes organdysfunction, including liver injury. These events were reported in <1% of subjects receivingdolutegravir in Phase 3 clinical trials.
Discontinue DOVATO immediately if signs or symptoms of hypersensitivity reactions develop(including, but not limited to, severe rash or rash accompanied by fever, general malaise, fatigue,muscle or joint aches, blisters or peeling of the skin, oral blisters or lesions, conjunctivitis, facialedema, hepatitis, eosinophilia, angioedema, difficulty breathing). Clinical status, including liveraminotransferases, should be monitored and appropriate therapy initiated. Delay in stopping
treatment with DOVATO or other suspect agents after the onset of hypersensitivity may result ina life-threatening reaction [see Contraindications (4)].
5.3 Hepatotoxicity
Hepatic adverse events have been reported in patients receiving a dolutegravir-containingregimen [see Adverse Reactions (6.1)]. Patients with underlying hepatitis B or C may be atincreased risk for worsening or development of transaminase elevations with use of DOVATO[see Adverse Reacti |
