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IMPORTANT SAFETY INFORMATION

BOXED WARNING: PATIENTS CO-INFECTED WITH HEPATITIS B VIRUS (HBV) AND HIV-1: EMERGENCE OF LAMIVUDINE-RESISTANT HBV AND EXACERBATIONS OF HBV

All patients with HIV-1 should be tested for the presence of HBV prior to or when initiating DOVATO. Emergence of lamivudine-resistant HBV variants associated with lamivudine-containing antiretroviral regimens has been reported. If DOVATO is used in 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 have been reported in patients who are co-infected with HIV-1 and HBV and have discontinued lamivudine, a component of DOVATO. Closely monitor hepatic function in these patients and, if appropriate, initiate anti-HBV treatment.

CONTRAINDICATIONS

• Do not use DOVATO in patients with previous hypersensitivity reaction to dolutegravir or lamivudine
• Do not use DOVATO in patients receiving dofetilide

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reconstitution syndrome or hepatitis B reactivation, particularly in the setting where anti-hepatitis therapy was withdrawn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:

• 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 REACTIONS
The most common adverse reactions (incidence ≥2%, all grades) receiving DOVATO were headache (3%), nausea (2%), diarrhea (2%), insomnia (2%), and fatigue (2%).

DRUG INTERACTIONS

• Consult full Prescribing Information for DOVATO for more information on potentially significant drug interactions
• DOVATO is a complete regimen. Coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended
• Drugs that induce or inhibit CYP3A or UGT1A1 may affect the plasma concentrations of dolutegravir
• When coadministering DOVATO with carbamazepine or rifampin, take an additional TIVICAY (dolutegravir) 50-mg tablet, approximately 12 hours from the dose of DOVATO
• Administer DOVATO 2 hours before or 6 hours after taking polyvalent cation-containing antacids or laxatives, sucralfate, oral supplements containing iron or calcium, or buffered medications. Alternatively, DOVATO and supplements containing calcium or iron can be taken with food 

USE IN SPECIFIC POPULATIONS

• Pregnancy: There are insufficient human data on the use of DOVATO during pregnancy to definitively assess a drug-associated risk for birth defects and miscarriage. An Antiretroviral Pregnancy Registry has been established. Avoid use of DOVATO at the time of conception through the first trimester of pregnancy. If planning a pregnancy or if pregnancy is confirmed while taking DOVATO during the first trimester, if possible, switch to an alternative regimen
• Lactation: Breastfeeding is not recommended due to the potential for HIV-1 transmission, developing viral resistance in HIV-positive infants, and adverse reactions in a breastfed infant
• Females and Males of Reproductive Potential: Perform pregnancy testing before initiation of DOVATO. Advise individuals of childbearing potential to consistently use effective contraception while taking DOVATO
• Renal Impairment: DOVATO is not recommended for patients with creatinine clearance <50 mL/min  

INDICATION
DOVATO is indicated as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults with no antiretroviral treatment history and with no known substitutions associated with resistance to the individual components of DOVATO.

 

Please see full Prescribing Information, including Boxed Warning, for DOVATO.