ons (6.1)]. In some cases, the elevations in transaminases were consistentwith immune reconstitution syndrome or HBV reactivation particularly in the setting where antihepatitistherapy was withdrawn. Cases of hepatic toxicity, including elevated serum liverbiochemistries, hepatitis, and acute liver failure, have also been reported in patients receiving a
dolutegravir-containing regimen who had no pre-existing hepatic disease or other identifiable risk factors.
Drug-induced liver injury leading to liver transplant has been reported withTRIUMEQ (abacavir, dolutegravir, and lamivudine). Monitoring for hepatotoxicity is
recommended.
5.4 Embryo-Fetal Toxicity
Preliminary data from an observational study showed that dolutegravir, a component ofDOVATO, was associated with increased risk of neural tube defects when administered at thetime of conception and in early pregnancy. As there is limited understanding of reported types ofneural tube defects associated with dolutegravir use and because the date of conception may notbe determined with precision, avoid use of DOVATO at the time of conception through the firsttrimester of pregnancy [see Use in Specific Populations (8.1)].
If there are plans to become pregnant or if pregnancy is confirmed within the first trimester whileon DOVATO, if possible, switch to an alternative regimen.
Perform pregnancy testing before initiation of DOVATO in individuals of childbearing potentialto exclude use of DOVATO during the first trimester of pregnancy [see Dosage andAdministration (2.1)].
Advise individuals of childbearing potential to consistently use effective contraception [see Usein Specific Populations (8.1, 8.3)].
5.5 Lactic Acidosis and Severe Hepatomegaly with Steatosis
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reportedwith the use of nucleoside analogues, including lamivudine (a component of DOVATO). Amajority of these cases have been in women. Female sex and obesity may be risk factors for thedevelopment of lactic acidosis and severe hepatomegaly with steatosis in patients treated withantiretroviral nucleoside analogues. Monitor closely when administering DOVATO to anypatient with known risk factors for liver disease. Treatment with DOVATO should be suspendedin any patient who develops clinical or laboratory findings suggestive of lactic acidosis or
pronounced hepatotoxicity, which may include hepatomegaly and steatosis even in the absenceof marked transaminase elevations.
5.6 Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions
The coadministration of DOVATO and other drugs may result in known or potentially
significant drug interactions, some of which may lead to [see Contraindications (4), DrugInteractions (7.4)]:
• Loss of therapeutic effect of DOVATO and possible development of resistance.
• Possible clinically significant adverse reactions from greater exposures of coadministereddrugs.
See Table 5 for steps to prevent or manage these possible and known significant druginteractions, including dosing recommendations.
Consider the potential for druginteractions prior to and during therapy with DOVATO; review coadministered drugs during therapy withDOVATO; and monitor for the adverse reactions associated with the coadministered drugs.
5.7 Immune Reconstitution Syndrome
Immune reconstitution syndrome has been report |
