Vocabria

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.

2 DOSAGE AND ADMINISTRATION • One tablet of VOCABRIA 30 mg taken orally once daily in combination with 1 tablet of EDURANT 25 mg taken orally once daily with a meal: • for approximately 1 month if oral lead-in is used for HIV-1 treatment. ( 2.1 ) • for up to 2 months to replace up to 2 consecutive missed monthly injections of CABENUVA ( 2.2 ) Refer to 2.1 for dosing recommendations for missed injections. ( 2.1 ) • HIV-1 Screening: Screen all individuals for HIV-1 infection prior to initiating VOCABRIA and APRETUDE for HIV-1 PrEP and at least once every 3 months while taking APRETUDE. ( 2.2 ) • One tablet of VOCABRIA 30 mg taken orally once daily for approximately 1 month if oral lead-in is used for HIV-1 PrEP. Refer to 2.2 for dosing recommendations for missed injections. ( 2.2 ) 2.1 Treatment of HIV-1 Infection in Adults and Adolescents 12 Years of Age and Older and Weighing at Least 35 kg Oral Lead-In Dosing to Assess Tolerability of Cabotegravir Consult the prescribing information for CABENUVA (cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension) before initiating VOCABRIA to ensure therapy with CABENUVA is appropriate. See full prescribing information for CABENUVA. Oral lead-in may be used to assess the tolerability of cabotegravir prior to the initiation of CABENUVA. The recommended oral lead-in daily dose is one 30-mg tablet of VOCABRIA with one 25-mg tablet of EDURANT for approximately 1 month (at least 28 days). The last oral dose should be taken on the same day injections with CABENUVA are started. Take VOCABRIA once daily with EDURANT at approximately the same time each day with a meal [see Clinical Pharmacology ( 12.3 )] . Because VOCABRIA is indicated in combination with EDURANT tablets, the prescribing information for EDURANT should also be consulted. Recommended Oral Dosing to Replace Planned Missed Injections of CABENUVA Planned Missed Injections for Patients on the Monthly Dosing Schedule: If a patient plans to miss a monthly scheduled injection of CABENUVA by more than 7 days, take daily oral therapy for up to 2 months to replace missed injection visits. For oral therapy with VOCABRIA and EDURANT, the recommended oral daily dose is one 30‑mg tablet of VOCABRIA and one 25-mg tablet of EDURANT. Take VOCABRIA with EDURANT at approximately the same time each day with a meal. The first dose of oral therapy should be taken 1 month (+/-7 days) after the last injection dose of CABENUVA and continued until the day injection dosing is restarted. For oral therapy with VOCABRIA and EDURANT of durations greater than 2 months, an alternative oral regimen is recommended. See full prescribing information for CABENUVA to resume monthly injection dosing. Planned Missed Injections for Patients on the Every-2-Month Dosing Schedule: If a patient plans to miss a scheduled every-2-month injection of CABENUVA by more than 7 days, take daily oral therapy for up to 2 months to replace 1 missed scheduled every-2-month injection. For oral therapy with VOCABRIA and EDURANT of durations greater than 2 months, the recommended oral daily dose is one 30-mg tablet of VOCABRIA and one 25-mg tablet of EDURANT. Take VOCABRIA with EDURANT at approximately the same time each day with a meal. The first dose of oral therapy should be taken approximately 2 months after the last injection dose of CABENUVA and continued until the day injection dosing is restarted. For oral therapy with VOCABRIA and EDURANT of durations greater than 2 months, an alternative oral regimen is recommended. See full prescribing information for CABENUVA to resume every-2-month injection dosing. 2.2 HIV-1 Pre-Exposure Prophylaxis in Adults and Adolescents Weighing at Least 35 kg HIV-1 Screening for Individuals for HIV-1 Pre-Exposure Prophylaxis Individuals must be tested for HIV-1 infection prior to initiating VOCABRIA and APRETUDE for HIV-1 PrEP, and with each subsequent injection of APRETUDE, using a test approved or cleared by the FDA for the diagnosis of acute or primary HIV-1 infection. If an antigen/antibody-specific test is used and provides negative results, then such negative results should be confirmed using an RNA-specific assay, even if the results of the RNA-assay are available after VOCABRIA or APRETUDE administration [see Contraindications ( 4 ), Warnings and Precautions ( 5.1 )] . Oral Lead-In Dosing to Assess Tolerability of Cabotegravir for HIV-1 Pre-Exposure Prophylaxis Consult the prescribing information for APRETUDE before initiating VOCABRIA to ensure use of APRETUDE is appropriate. See full prescribing information for APRETUDE. Oral lead-in may be used to assess the tolerability of cabotegravir prior to the initiation of APRETUDE. The recommended oral daily dose is one 30-mg tablet of VOCABRIA for approximately 1 month (at least 28 days). Following oral lead-in, start initiation injection of APRETUDE on the last day of oral lead-in or within 3 days. Oral Dosing to Replace a Planned Missed Injection of APRETUDE (One Every-2-Month Injection) If an individual plans to miss a scheduled injection of APRETUDE by more than 7 days, take daily oral VOCABRIA to replace one every-2-month injection visit. The recommended oral daily dose is one 30-mg tablet of VOCABRIA. The first dose of oral VOCABRIA should be taken approximately 2 months after the last injection dose of APRETUDE. Restart injection with APRETUDE on the day oral dosing completes or within 3 days. See full prescribing information for APRETUDE to resume every-2-month injection dosing.

4 CONTRAINDICATIONS Treatment of HIV-1 Infection VOCABRIA is contraindicated in patients: • with previous hypersensitivity reaction to cabotegravir [see Warnings and Precautions ( 5.2 )] . • receiving the following coadministered drugs for which significant decreases in cabotegravir plasma concentrations may occur due to uridine diphosphate glucuronosyltransferase (UGT)1A1 enzyme induction, which may result in loss of virologic response [see Drug Interactions ( 7.2 , 7.3 ), Clinical Pharmacology ( 12.3 )] : o Anticonvulsants: Carbamazepine, oxcarbazepine, phenobarbital, phenytoin o Antimycobacterials: Rifampin, rifapentine Prior to initiation of VOCABRIA, note that use of CABENUVA (cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension) with rifabutin is contraindicated. Since VOCABRIA is taken in combination with EDURANT tablets, the prescribing information for EDURANT should be consulted for additional contraindications. HIV-1 Pre-Exposure Prophylaxis VOCABRIA is contraindicated in individuals: • with unknown or positive HIV-1 status [see Warnings and Precautions ( 5.1 )] . • with previous hypersensitivity reaction to cabotegravir [see Warnings and Precautions ( 5.2 )] . • receiving the following coadministered drugs for which significant decreases in cabotegravir plasma concentrations may occur due to UGT1A1 enzyme induction, which may result in loss of efficacy [see Drug Interactions ( 7.2 , 7.3 ), Clinical Pharmacology ( 12.3 )] : o Anticonvulsants: Carbamazepine, oxcarbazepine, phenobarbital, phenytoin o Antimycobacterials: Rifampin, rifapentine • Previous hypersensitivity reaction to cabotegravir. ( 4 ) • Coadministration with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin, and rifapentine. ( 4 ) • Positive HIV-1 status for HIV-1 PrEP. ( 4 )

5 WARNINGS AND PRECAUTIONS • HIV-1 PrEP: Comprehensive management to reduce the risk of HIV-1 acquisition. ( 5.1 ) • Serious or severe hypersensitivity reactions have been reported with cabotegravir and include Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Discontinue VOCABRIA immediately if signs or symptoms of hypersensitivity reactions develop. ( 5.2 ) • Hepatotoxicity has been reported in patients receiving cabotegravir. Monitoring of liver chemistries is recommended when VOCABRIA is used for HIV-1 treatment. Clinical and laboratory monitoring should be considered when VOCABRIA is used for HIV-1 PrEP. Discontinue VOCABRIA if hepatotoxicity is suspected. ( 5.3 ) • Depressive disorders have been reported with VOCABRIA when used with EDURANT for HIV-1 treatment. Prompt evaluation is recommended for depressive symptoms. ( 5.4 ) • Risks Associated with Combination Treatment: Review the prescribing information for EDURANT for information on rilpivirine prior to initiation of VOCABRIA in combination with EDURANT. ( 5.6 ) 5.1 Comprehensive Management to Reduce the Risk of HIV-1 Infection When VOCABRIA is Used for HIV-1 Pre-Exposure Prophylaxis Use of VOCABRIA for HIV-1 PrEP should be part of a comprehensive prevention strategy including adherence to the dosing schedule and safer sex practices, including condoms, to reduce the risk of sexually transmitted infections (STIs). VOCABRIA is not always effective in preventing HIV-1 acquisition [see Clinical Studies ( 14.2 )] . The time from initiation of VOCABRIA for HIV-1 PrEP to maximal protection against HIV-1 infection is unknown. Risk for HIV-1 acquisition includes behavioral, biological, or epidemiologic factors including, but not limited to, condomless sex, past or current STIs, self-identified HIV risk, having sexual partners of unknown HIV-1 viremic status, or sexual activity in a high prevalence area or network. Counsel individuals on the use of other prevention measures (e.g., consistent and correct condom use; knowledge of partner(s)’ HIV-1 status, including viral suppression status; regular testing for STIs that can facilitate HIV-1 transmission). Inform individuals about and support their efforts in reducing sexual risk behavior. VOCABRIA for HIV-1 PrEP to reduce the risk of acquiring HIV-1 should be used only in individuals confirmed to be HIV-1 negative [see Contraindications ( 4 )] . HIV-1 resistance substitutions may emerge in individuals with undiagnosed HIV-1 infection who are taking only VOCABRIA, because VOCABRIA alone does not constitute a complete regimen for HIV-1 treatment [see Microbiology ( 12.4 )] ; therefore, care should be taken to minimize the risk of initiating or continuing VOCABRIA before confirming the individual is HIV-1 negative. • Prior to initiating VOCABRIA for HIV-1 PrEP, ask seronegative individuals about recent (in past month) potential exposure events (e.g., condomless sex or condom breaking during sex with a partner of unknown HIV-1 status or unknown viremic status, a recent STI), and evaluate for current or recent signs or symptoms consistent with acute HIV-1 infection (e.g., fever, fatigue, myalgia, skin rash). • If recent (<1 month) exposures to HIV-1 are suspected or clinical symptoms consistent with acute HIV-1 infection are present, use a test approved or cleared by the FDA as an aid in the diagnosis of acute or primary HIV-1 infection. Testing should be repeated prior to each injection of APRETUDE and upon diagnosis of any other STIs [see Dosage and Administration ( 2.2 )]. • If an HIV-1 test indicates possible HIV-1 infection, or if symptoms consistent with acute HIV-1 infection develop following an exposure event, additional HIV testing to determine HIV status is needed. If an individual has confirmed HIV-1 infection, then the individual must be transitioned to a complete HIV-1 treatment regimen. Counsel individuals without HIV-1 to strictly adhere to the recommended dosing schedule for VOCABRIA in order to reduce the risk of HIV-1 acquisition and the potential development of resistance [see Dosage and Administration ( 2.2 ), Microbiology ( 12.4 )] . Some individuals, such as adolescents, may benefit from frequent visits and counseling to support adherence to the dosing schedule [see Use in Specific Populations ( 8.4 ), Microbiology ( 12.4 ), Clinical Studies ( 14.2 )] . 5.2 Hypersensitivity Reactions Serious or severe hypersensitivity reactions have been reported with cabotegravir and include Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) [see Adverse Reactions ( 6.2 )] . Administration of oral lead-in dosing was used in clinical studies to help identify participants who may be at risk of a hypersensitivity reaction. Remain vigilant and discontinue VOCABRIA if a hypersensitivity reaction is suspected [see Dosage and Administration ( 2.2 ), Contraindications ( 4 ), Adverse Reactions ( 6 )] . Discontinue VOCABRIA 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, mucosal involvement [oral blisters or lesions], conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema, difficulty breathing). Clinical status, including liver transaminases, should be monitored and appropriate therapy initiated. 5.3 Hepatotoxicity Hepatotoxicity has been reported in a limited number of patients receiving cabotegravir with or without known pre-existing hepatic disease or identifiable risk factors [see Adverse Reactions ( 6.1 )] . When VOCABRIA is Used for Treatment HIV-1 Infection Patients with underlying liver disease or marked elevations in transaminases prior to treatment with VOCABRIA may be at increased risk for worsening or development of transaminase elevations. Monitoring of liver chemistries is recommended and treatment with VOCABRIA should be discontinued if hepatotoxicity is suspected. When VOCABRIA is Used for HIV-1 Pre-Exposure Prophylaxis Clinical and laboratory monitoring should be considered and VOCABRIA should be discontinued if hepatotoxicity is suspected, and individuals managed as clinically indicated. 5.4 Depressive Disorders When VOCABRIA is Used for Treatment HIV-1 Infection Depressive disorders (including depressed mood, depression, mood altered, mood swings, suicidal ideation/suicide attempt) have been reported with VOCABRIA when used with EDURANT for treatment of HIV-1 infection [see Adverse Reactions ( 6.1 )] . Promptly evaluate patients with depressive symptoms to assess whether the symptoms are related to VOCABRIA and to determine whether the risks of continued therapy outweigh the benefits. When VOCABRIA is Used for HIV-1 Pre-Exposure Prophylaxis Depressive disorders (including depression, depressed mood, persistent depressive disorder, suicidal ideation/suicide attempt) have been reported with VOCABRIA [see Adverse Reactions ( 6.1 )] . Promptly evaluate individuals with depressive symptoms to assess whether the symptoms are related to VOCABRIA and to determine whether the risks of continued therapy outweigh the benefits. 5.5 Risk of Adverse Reactions, Loss of Efficacy, or Reduced Concentration Due to Drug Interactions The concomitant use of VOCABRIA and other drugs may result in known or potentially significant drug interactions, some of which may lead to adverse events, loss of efficacy from VOCABRIA when used for treatment of HIV-1 infection or HIV-1 PrEP, and possible development of viral resistance [see Contraindications ( 4 ), Drug Interactions ( 7.2 , 7.3 )] . See Table 1 for steps to prevent or manage these possible and known significant drug interactions, including dosing recommendations. Consider the potential for drug interactions prior to and during use of VOCABRIA; review concomitant medications during use of VOCABRIA [see Drug Interactions ( 7.3 )] . 5.6 Risks Associated with Combination Treatment VOCABRIA is indicated for use in combination with EDURANT (rilpivirine) for treatment of HIV-1 infection [see Indications and Usage ( 1.1 ), Dosage and Administration ( 2.1 )] . Review the prescribing information for EDURANT for information on rilpivirine prior to initiation of VOCABRIA in combination with EDURANT.

7 DRUG INTERACTIONS • Refer to the full prescribing information for important drug interactions with VOCABRIA. ( 4 , 5.5 , 7 ) • VOCABRIA in combination with EDURANT is a complete regimen for HIV-1 treatment. Coadministration with other antiretroviral medications for PrEP is not recommended. ( 7.1 ) • Drugs that induce uridine diphosphate glucuronosyltransferase (UGT)1A1 may decrease the plasma concentrations of cabotegravir. ( 4 , 7.2 , 7.3 ) 7.1 Concomitant Use with Other Antiretroviral Medicines VOCABRIA in combination with EDURANT (rilpivirine) is a complete regimen for the treatment of HIV-1 infection. Refer to the prescribing information for EDURANT for relevant information on rilpivirine. Coadministration of VOCABRIA with other antiretroviral medications for PrEP is not recommended [see Drug Interactions ( 7.4 ), Clinical Pharmacology ( 12.3 )] . Prior to initiating dosing with VOCABRIA, the prescribing information for CABENUVA (cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension) or APRETUDE should be consulted to ensure use of CABENUVA or APRETUDE will be appropriate for either the treatment of HIV-1 infection or HIV-1 PrEP, respectively. 7.2 Potential for Other Drugs to Affect VOCABRIA Cabotegravir is primarily metabolized by UGT1A1 with some contribution from UGT1A9. Drugs that are strong inducers of UGT1A1 or UGT1A9 are expected to decrease cabotegravir plasma concentrations and may result in loss of efficacy; therefore, coadministration of VOCABRIA with these drugs is contraindicated [see Contraindications ( 4 )] . Coadministration of oral cabotegravir with polyvalent cation-containing products may lead to decreased absorption of cabotegravir [see Drug Interactions ( 7.3 )] . 7.3 Established and Other Potentially Significant Drug Interactions Information regarding potential drug interactions with cabotegravir are provided in Table 1 . These recommendations are based on either drug interaction trials or predicted interactions due to the expected magnitude of the interaction and potential for loss of efficacy [see Contraindications ( 4 ), Warnings and Precautions ( 5.5 ), Clinical Pharmacology ( 12.3 )] . Table 1 includes potentially significant interactions but is not all inclusive. Refer to the prescribing information for EDURANT (rilpivirine) for established or potentially significant interactions that should be considered during concomitant administration of VOCABRIA and EDURANT for HIV-1 treatment. Table 1. Drug Interactions with VOCABRIA ↓ = Decrease; PrEP = Pre-exposure prophylaxis. a Rifabutin can be coadministered with cabotegravir; however, it is contraindicated with CABENUVA for HIV-1 treatment. Dosage modification is recommended with APRETUDE for HIV-1 PrEP. Concomitant Drug Class: Drug Name Effect on Concentration Clinical Comment Antacids containing polyvalent cations (e.g., aluminum or magnesium hydroxide, calcium carbonate) ↓Cabotegravir Administer antacid products at least 2 hours before or 4 hours after taking VOCABRIA. Anticonvulsants: Carbamazepine Oxcarbazepine Phenobarbital Phenytoin ↓Cabotegravir Coadministration is contraindicated with VOCABRIA due to potential for loss of efficacy and development of resistance [see Contraindications ( 4 )] . Antimycobacterials a : Rifampin Rifapentine ↓Cabotegravir Antimycobacterial: Rifabutin ↓Cabotegravir Dose modification is not required for VOCABRIA. Dose modification is recommended for APRETUDE for HIV-1 PrEP. Coadministration is contraindicated with CABENUVA for HIV-1 treatment. 7.4 Drugs without Clinically Significant Interactions with Cabotegravir Based on drug interaction study results, the following drugs can be coadministered with cabotegravir without a dose adjustment: etravirine, midazolam, oral contraceptives containing levonorgestrel and ethinyl estradiol, rifabutin, and rilpivirine [see Clinical Pharmacology ( 12.3 )] . Prior to initiating oral therapy, note that use of CABENUVA (cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension) with rifabutin is contraindicated for the treatment of HIV-1 infection. Dosage modification is recommended when APRETUDE is used with rifabutin for HIV-1 PrEP.

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 )] .

8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to VOCABRIA during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263. Risk Summary There are insufficient human data on the use of VOCABRIA during pregnancy to adequately assess a drug-associated risk of birth defects and miscarriage. Discuss the benefit-risk of using VOCABRIA with individuals of childbearing potential or during pregnancy. The APR has been established to monitor for birth defects following prenatal exposure to antiretrovirals. The rate of miscarriage is not reported in the APR. The background risk for major birth defects and miscarriage for the indicated population is unknown. The background rate for major birth defects in a United States (U.S.) reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP) is 2.7%. The estimated background rate of miscarriage in clinically recognized pregnancies in the U.S. general population is 15% to 20%. The APR uses the MACDP as the U.S. reference population for birth defects in the general population. The MACDP evaluates mothers and infants from a limited geographic area and does not include outcomes for births that occurred at <20 weeks’ gestation. In animal reproduction studies with oral cabotegravir, a delay in the onset of parturition and increased stillbirths and neonatal deaths were observed in a rat pre- and postnatal development study at >28 times the exposure at the recommended human dose (RHD). No evidence of adverse developmental outcomes was observed with oral cabotegravir in rats or rabbits (>28 times or similar to the exposure at the RHD, respectively) given during organogenesis (see Data ) . Data Animal Data: Cabotegravir was administered orally to pregnant rats at 0, 0.5, 5, or 1,000 mg/kg/day from 15 days before cohabitation, during cohabitation, and from Gestation Days 0 to 17. There were no effects on fetal viability when fetuses were delivered by caesarean, although a minor decrease in fetal body weight was observed at 1,000 mg/kg/day (>28 times the exposure in humans at the RHD). No drug-related fetal toxicities were observed at 5 mg/kg/day (approximately 13 times the exposure in humans at the RHD), and no drug-related fetal malformations were observed at any dose. Cabotegravir was administered orally to pregnant rabbits at 0, 30, 500, or 2,000 mg/kg/day from Gestation Days 7 to 19. No drug-related fetal toxicities were observed at 2,000 mg/kg/day (approximately 0.7 times the exposure in humans at the RHD). In a rat pre- and postnatal development study, cabotegravir was administered orally to pregnant rats at 0, 0.5, 5, or 1,000 mg/kg/day from Gestation Day 6 to Lactation Day 21. A delay in the onset of parturition and increases in the number of stillbirths and neonatal deaths by Lactation Day 4 were observed at 1,000 mg/kg/day (>28 times the exposure in humans at the RHD); there were no alterations to growth and development of surviving offspring. In a cross-fostering study, similar incidences of stillbirths and early postnatal deaths were observed when rat pups born to cabotegravir-treated mothers were nursed from birth by control mothers. There was no effect on neonatal survival of control pups nursed from birth by cabotegravir-treated mothers. A lower dose of 5 mg/kg/day (13 times the exposure at the RHD) was not associated with delayed parturition or neonatal mortality in rats. Studies in pregnant rats showed that cabotegravir crosses the placenta and can be detected in fetal tissue.