5.1 Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions

The concomitant use of VITEKTA and other drugs may result in known or potentially significant drug interactions, some of which may lead to [see Drug Interactions (7)]:

• Loss of therapeutic effect of VITEKTA and possible development of resistance
• Possible clinically significant adverse reactions from greater exposures of concomitant drugs or elvitegravir.

See Table 4 for steps to prevent or manage these possible and known significant drug interactions, including dosing recommendations [see Drug Interactions (7)]. Consider the potential for drug interactions prior to and during VITEKTA therapy; review concomitant medications during VITEKTA therapy; and monitor for the adverse reactions associated with the concomitant drugs.

5.2 Use with Other Antiretroviral Agents

Use of VITEKTA in combination with the fixed dose combination STRIBILD is not recommended, because elvitegravir is a component of STRIBILD.

VITEKTA is indicated for use in combination with a protease inhibitor coadministered with ritonavir and with other antiretroviral drug(s). VITEKTA in combination with a protease inhibitor and cobicistat is not recommended because dosing recommendations for such combinations have not been established and may result in suboptimal plasma concentrations of VITEKTA and/or the protease inhibitor, leading to loss of therapeutic effect and development of resistance.

5.3 Immune Reconstitution Syndrome

Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy. During the initial phase of combination antiretroviral treatment, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further eva luation and treatment.

Autoimmune disorders (such as Graves' disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of treatment.

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety assessment of VITEKTA is primarily based on data from a controlled clinical trial, Study 145, in which 712 HIV-1 infected, antiretroviral treatment-experienced adults received VITEKTA (N=354) or raltegravir (N=358), each administered with a background regimen consisting of a fully active protease inhibitor coadministered with ritonavir and with other antiretroviral drug(s) for at least 96 weeks.

The proportion of subjects who discontinued study treatment due to adverse events, regardless of severity, was 3% in the VITEKTA group and 4% in the raltegravir group. The most common adverse reaction (all Grades, incidence greater than or equal to 5%) in subjects receiving VITEKTA in Study 145 was diarrhea. See also Table 2 for the frequency of adverse reactions occurring in at least 2% of subjects in any treatment group in Study 145.