1 INDICATIONS AND USAGE HIV-1 Treatment: VOCABRIA is an HIV-1 integrase strand transfer inhibitor (INSTI) indicated in combination with EDURANT (rilpivirine) for short-term treatment of HIV-1 infection in adults and adolescents 12 years of age and older and weighing at least 35 kg who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine.

( 1.1 ) HIV-1 Pre-Exposure Prophylaxis: VOCABRIA is indicated for short-term pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in adults and adolescents weighing at least 35 kg who are at risk for HIV-1 acquisition.

Individuals must have a negative HIV-1 test prior to initiating VOCABRIA for HIV-1 PrEP.

( 1.2 ) VOCABRIA may be used as: • oral lead-in to assess the tolerability of cabotegravir prior to administration of CABENUVA (cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension) for HIV-1 treatment or APRETUDE (cabotegravir extended-release injectable suspension) for HIV-1 PrEP.

( 1.1 , 1.2 ) • oral therapy for patients who will miss planned injection dosing with CABENUVA for HIV-1 treatment or APRETUDE for HIV-1 PrEP.

( 1.1 , 1.2 ) 1.1 Treatment of HIV-1 Infection VOCABRIA is indicated in combination with EDURANT (rilpivirine) tablets for short-term treatment of HIV-1 infection in adults and adolescents 12 years of age and older and weighing at least 35 kg who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine, for use as [see Microbiology ( 12.4 ), Clinical Studies ( 14.1 )] : • oral lead-in to assess the tolerability of cabotegravir prior to administration of cabotegravir extended-release injectable suspension, a component of CABENUVA (cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension).

• oral therapy for patients who will miss planned injection dosing with CABENUVA.

1.2 HIV-1 Pre-Exposure Prophylaxis VOCABRIA is indicated for short-term pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in adults and adolescents weighing at least 35 kg who are at risk for HIV-1 acquisition.

Individuals must have a negative HIV-1 test prior to initiating VOCABRIA for HIV-1 PrEP.

VOCABRIA may be used as [see Dosage and Administration ( 2.2 ), Contraindications ( 4 ), Warnings and Precautions ( 5.1 ), Clinical Studies ( 14.2 )] : • oral lead-in to assess the tolerability of cabotegravir prior to administration of APRETUDE (cabotegravir extended-release injectable suspension).

• oral PrEP for patients who will miss planned injection dosing with APRETUDE.

6 ADVERSE REACTIONS The following adverse reactions are described below and in other sections of the labeling: • Hypersensitivity reactions [see Warnings and Precautions ( 5.2 )] • Hepatotoxicity [see Warnings and Precautions ( 5.3 )] • Depressive disorders [see Warnings and Precautions ( 5.4 )] • In patients with HIV-1, the most common adverse reactions observed in at least 3 participants receiving VOCABRIA were fatigue, headache, diarrhea, nausea, dizziness, abnormal dreams, anxiety, insomnia, abdominal discomfort, abdominal distension, and asthenia.

( 6.1 ) • In individuals without HIV-1 receiving VOCABRIA, the most common adverse reactions reported in ≥1% were headache, diarrhea, nausea, dizziness, upper respiratory tract infection, somnolence, fatigue, abnormal dreams, and abdominal pain.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact ViiV Healthcare at 1-877-844-8872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

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 with rates in the clinical trials of another drug and may not reflect rates observed in practice.

See full prescribing information for CABENUVA (cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension) for additional safety information.

Since VOCABRIA is taken in combination with EDURANT tablets, the prescribing information for EDURANT (rilpivirine) should be consulted for relevant information on rilpivirine.

Adverse Reactions of VOCABRIA in Clinical Trials for the Treatment of HIV-1 Infection Clinical Trials Experience in Adults: The safety assessment of VOCABRIA for oral lead-in therapy prior to therapy with CABENUVA is based on the analysis of 48-week data from virologically suppressed participants with HIV-1 infection in 3 international, multicenter, open-label trials, where 590 of 1,182 participants received oral lead-in within the pivotal trials FLAIR and ATLAS (pooled analysis) and 655 of 1,045 participants received oral lead-in within ATLAS-2M [see Clinical Studies ( 14.1 )] .

Adverse reactions were reported following exposure to VOCABRIA tablets and EDURANT tablets administered in combination as oral lead-in therapy (median time exposure: 5.3 weeks).

Adverse reactions included those attributable to the oral formulation of cabotegravir and rilpivirine administered as a combination regimen.

Refer to the prescribing information for EDURANT for other adverse reactions associated with oral rilpivirine.

The most common adverse reactions during the oral lead-in period in the pooled analyses of FLAIR and ATLAS at Week 48 were headache, nausea, abnormal dreams, anxiety, and insomnia, all of which occurred in at least 3 participants with an incidence ≤1%.

The most common adverse reactions during the oral lead-in period for ATLAS-2M were fatigue, diarrhea, headache, nausea, dizziness, abdominal discomfort, abdominal distension, insomnia, and asthenia, all of which occurred in at least 3 participants across both arms, with an incidence ≤2%.

During the oral lead-in period for FLAIR and ATLAS, 6 (1%) participants discontinued due to adverse events, including asthenia, myalgia, depression suicidal, and headache.

During the oral lead-in period for ATLAS-2M, 4 (<1%) participants discontinued due to adverse events, including asthenia, skin lesion, fatigue, transaminases increased, and depression.

In the extension phase of the FLAIR study at Week 124, the overall safety profile was consistent with that observed at Week 48 and when injection therapy with CABENUVA was initiated directly without the oral lead-in phase.

Clinical Trial Experience in Adolescents: Based on data from the Week 24 analysis of the MOCHA study in 144 adolescents (aged 12 to younger than 18 years and weighing ≥35 kg), the safety profile of oral cabotegravir and oral rilpivirine administered in combination during the oral lead-in period in adolescents was consistent with the safety profile established with cabotegravir plus rilpivirine in adults.

Adverse Reactions of VOCABRIA in Clinical Trials for HIV-1 Pre-Exposure Prophylaxis Clinical Trial Experience in Adults: In trial HPTN 083, adverse reactions were reported while participants were on blinded study product following exposure to VOCABRIA tablets as oral lead-in for HIV-1 PrEP (median time exposure: 4.1 weeks).

The most common adverse reactions reported at ≥1% during the oral lead-in period were diarrhea (4% and 4%), nausea (3% and 5%), dizziness (2% and 2%), headache (2% and 2%), fatigue (1% and 2%), and abnormal dreams (1% and 2%) for VOCABRIA and TRUVADA (emtricitabine and tenofovir disoproxil fumarate), respectively.

During the oral lead-in period, 24 (1%) participants receiving VOCABRIA discontinued due to adverse events, including increased alanine aminotransferase, increased aspartate aminotransferase, suicide attempt, and dizziness, which were observed in ≥2 participants.

In Trial HPTN 084, adverse reactions were reported while participants were on blinded study product following exposure to VOCABRIA tablets as oral lead-in for HIV-1 PrEP (median time exposure: 4.1 weeks).

The most common adverse reactions reported at ≥1% during the oral lead-in period were headache (6% and 7%), nausea (3% and 7%), dizziness (3% and 4%), diarrhea (2% and 4%), upper respiratory tract infection (2% and 2%), somnolence (2% and 1%), fatigue (1% and 2%), abdominal pain (1% and 1%), vomiting (<1% and 3%), decreased appetite (<1% and 2%), and pruritus (<1% and 1%) for VOCABRIA and TRUVADA, respectively.

During the oral lead-in period, 4 (<1%) participants receiving VOCABRIA discontinued due to adverse events of increased alanine aminotransferase (n = 3) and sleep disorders (n = 1).

Clinical Trials Experience in Adolescents: In adolescents receiving VOCABRIA for HIV-1 PrEP, the safety data were comparable to the safety data reported in adults receiving VOCABRIA for HIV-1 PrEP [see Use in Specific Populations ( 8.4 )] .

Less Common Adverse Reactions The following select adverse reactions (regardless of severity) occurred in <1% of participants receiving VOCABRIA in clinical trials for the treatment of HIV-1 infection or for HIV-1 PrEP.

Psychiatric Disorders: Suicidal ideation, and suicide attempt (these events were observed primarily in participants with a pre‑existing history of depression or other psychiatric illness).

6.2 Postmarketing Experience The following adverse reactions have been identified during postmarketing use of VOCABRIA or cabotegravir-containing regimens.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Immune System Disorders Hypersensitivity reactions (including angioedema and urticaria) [see Warnings and Precautions ( 5.2 )] .

Skin and Subcutaneous Tissue Disorders Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) [see Warnings and Precautions ( 5.2 )] .