Cabotegravir Sodium

Q: How should I take Cabotegravir Sodium?

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 VO

Q: What should I know before taking Cabotegravir Sodium?

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

Q: Is Cabotegravir Sodium available over the counter?

Cabotegravir Sodium is a prescription medication. You will need a valid prescription from a licensed healthcare provider.

Prescription

Nama merek: Vocabria

Bentuk Sediaan

Tablet

Rute Pemberian

ORAL

Produsen

ViiV Healthcare Company

About This Medication

11 DESCRIPTION VOCABRIA contains cabotegravir, as cabotegravir sodium, an HIV integrase strand transfer inhibitor (INSTI). The chemical name of cabotegravir sodium is sodium ( 3S,11aR )-N-[(2,4-difluorophenyl)methyl]-6-hydroxy-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydro[1,3]oxazolo[3,2-a]pyrido [1,2-d]pyrazine-8-carboxamide. The empirical formula is C 19 H 16 F 2 N 3 NaO 5 and the molecular weight is 427.34 g/mol. It has the following structural formula: Cabotegravir sodium is a white to almost white crystalline solid that is slightly soluble in water. Each immediate-release film-coated tablet of VOCABRIA for oral administration contains 30 mg of cabotegravir (equivalent to 31.62 mg cabotegravir sodium) and the inactive ingredients: hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate. The tablet film-coating contains hypromellose, polyethylene glycol, and titanium dioxide. Cabotegravir sodium chemical structure

Bahan Aktif

Bahan	Kekuatan
Cabotegravir Sodium	-

Indikasi & Penggunaan

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.

Cara kerja

12.1 Mechanism of Action Cabotegravir is an HIV-1 antiretroviral drug [see Microbiology ( 12.4 )] .

Dosis & Cara Pemberian

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.

Side Effects Overview

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 )] .

Peringatan & Tindakan Pencegahan

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.

Kontraindikasi

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 )

Farmakokinetik

12.3 Pharmacokinetics Absorption, Distribution, and Elimination The pharmacokinetic properties of cabotegravir are provided in Table 2 . The multiple-dose pharmacokinetic parameters are provided in Table 3 . Table 2. Pharmacokinetic Properties of Cabotegravir CSF = Cerebrospinal fluid. a Geometric mean ratio (fed/fasted) in pharmacokinetic parameters and 90% confidence interval. High‑calorie/high-fat meal = 870 kcal, 53% fat. b Dosing in mass balance studies: single-dose oral administration of [ 14 C] cabotegravir. Absorption T max (h), median 3 Effect of high-fat meal (relative to fasting): 1.14 AUC (0-inf) ratio a (1.02, 1.28) Distribution % Bound to human plasma proteins >99.8 Blood-to-plasma ratio 0.52 CSF-to-plasma concentration ratio (median [range]) b 0.003 (0.002 to 0.004) Elimination t 1/2 (h), mean 41 Metabolism Metabolic pathways UGT1A1 UGT1A9 (minor) Excretion Major route of elimination Metabolism % of dose excreted as total 14 C (unchanged drug) in urine b 27 (0) % of dose excreted as total 14 C (unchanged drug) in feces b 59 (47) Table 3. Multiple-Dose Pharmacokinetic Parameters of Oral Cabotegravir in Adults a Pharmacokinetic parameter values were based on individual post-hoc estimates from the final population pharmacokinetic model for participants receiving 30 mg of oral cabotegravir once daily in FLAIR and ATLAS trials. b tau is dosing interval: 24 hours for oral cabotegravir. Parameter Geometric Mean (5 th , 95 th Percentile) a C max (mcg/mL) 8.0 (5.3, 11.9) AUC (0-tau) (mcg•h/mL) b 145 (93.5, 224) C tau (mcg/mL) b 4.6 (2.8, 7.5) Specific Populations No clinically significant differences in the pharmacokinetics of cabotegravir were observed based on age, sex, race/ethnicity, body mass index, or UGT1A1 polymorphisms. The effect of hepatitis B and C virus co-infection on the pharmacokinetics of cabotegravir is unknown. Renal Impairment: No clinically significant differences in the pharmacokinetics of cabotegravir are expected with mild, moderate, or severe renal impairment. Cabotegravir has not been studied in patients with end-stage renal disease not on dialysis. As cabotegravir is >99% protein bound, dialysis is not expected to alter exposures of cabotegravir [see Use in Specific Populations ( 8.6 )] . Hepatic Impairment: No clinically significant differences in the pharmacokinetics of cabotegravir are expected in mild to moderate (Child-Pugh A or B) hepatic impairment. The effect of severe hepatic impairment (Child-Pugh C) on the pharmacokinetics of cabotegravir has not been studied [see Use in Specific Populations ( 8.7 )] . Gender: Population pharmacokinetic analyses revealed no clinically relevant effect of gender on the exposure of cabotegravir. In addition, no clinically relevant differences in plasma cabotegravir concentrations were observed in PrEP studies by gender, including cisgender men and transgender women (+/-hormone use). Therefore, no dose adjustment is necessary based on gender. Geriatric Patients: No dose adjustment is required in elderly individuals. There are limited data available on the use of cabotegravir in individuals aged 65 years and older. In general, caution should be exercised in administration of cabotegravir in elderly individuals, reflecting greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy [see Use in Specific Populations ( 8.5 )] . Pediatric Patients: Population pharmacokinetic analyses revealed no clinically relevant differences in exposure between adolescent participants (weighing ≥35 kg) and adult participants with and without HIV-1 from the cabotegravir development program; therefore, no dosage adjustment is needed for adolescents weighing ≥35 kg ( Table 4 ). Table 4. Pharmacokinetic Parameters following Once-Daily Oral Cabotegravir in Adolescents Aged 12 to Younger than 18 Years (≥35 kg) a Pharmacokinetic parameter values were based on individual post-hoc estimates from population pharmacokinetic models in both adolescents with HIV-1 (n = 147) weighing 35.2 to 98.5 kg and adolescents without HIV-1 (n = 62) weighing 39.9 to 167 kg. b tau is dosing interval: 24 hours for oral administration. Parameter Geometric Mean (5 th , 95 th Percentile) a C max (mcg/mL) 10.7 (7.36, 16.6) AUC (0-tau) (mcg•h/mL) b 203 (136, 320) C tau (mcg/mL) b 6.43 (4.15, 10.5) Drug Interaction Studies Cabotegravir is not a clinically relevant inhibitor of the following enzymes and transporters: cytochrome P450 (CYP)1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4; UGT1A1, 1A3, 1A4, 1A6, 1A9, 2B4, 2B7, 2B15, and 2B17; P-glycoprotein (P-gp); breast cancer resistance protein (BCRP); bile salt export pump (BSEP); organic cation transporter (OCT)1, OCT2; organic anion transporter polypeptide (OATP)1B1, OATP1B3; multidrug and toxin extrusion transporter (MATE) 1, MATE 2-K; and multidrug resistance protein (MRP)2 or MRP4. In vitro, cabotegravir inhibited renal OAT1 (IC 50 = 0.81 microM) and OAT3 (IC 50 = 0.41 microM). Based on physiologically based pharmacokinetic (PBPK) modeling, cabotegravir may increase the AUC of OAT1/3 substrates up to approximately 80%. In vitro, cabotegravir did not induce CYP1A2, CYP2B6, or CYP3A4. Simulations using PBPK modeling show that no clinically significant interaction is expected during coadministration of cabotegravir with drugs that inhibit UGT1A1. In vitro, cabotegravir was not a substrate of OATP1B1, OATP1B3, OATP2B1, or OCT1. Cabotegravir is a substrate of P-gp and BCRP in vitro; however, because of its high permeability, no alteration in cabotegravir absorption is expected with coadministration of P-gp or BCRP inhibitors. The effects of coadministered drugs on the exposure of cabotegravir are summarized in Table 5 , and the effects of cabotegravir on the exposure of coadministered drugs are summarized in Table 6 . Table 5. Effect of Coadministered Drugs on the Pharmacokinetics of Cabotegravir n = Maximum number of participants with data, CI = Confidence Interval. Coadministered Drug(s) and Dose(s) Dose of Cabotegravir n Geometric Mean Ratio (90% CI) of Cabotegravir Pharmacokinetic Parameters with/without Coadministered Drugs No Effect = 1.00 C max AUC C tau or C 24 Etravirine 30 mg 12 1.04 1.01 1.00 200 mg twice daily once daily (0.99, 1.09) (0.96, 1.06) (0.94, 1.06) Rifabutin 30 mg 12 0.83 0.79 0.74 300 mg once daily once daily (0.76, 0.90) (0.74, 0.83) (0.70, 0.78) Rifampin 30-mg 15 0.94 0.41 0.50 600 mg once daily single dose (0.87, 1.02) (0.36, 0.46) (0.44, 0.57) Rilpivirine 30 mg 11 1.05 1.12 1.14 25 mg once daily once daily (0.96, 1.15) (1.05, 1.19) (1.04, 1.24) Table 6. Effect of Cabotegravir on the Pharmacokinetics of Coadministered Drugs n = Maximum number of participants with data, CI = Confidence Interval, NA = Not available. Coadministered Drug(s) and Dose(s) Dose of Cabotegravir n Geometric Mean Ratio (90% CI) of Pharmacokinetic Parameters of Coadministered Drug with/without Cabotegravir No Effect = 1.00 C max AUC C tau or C 24 Ethinyl estradiol 30 mg 19 0.92 1.02 1.00 0.03 mg once daily once daily (0.83, 1.03) (0.97, 1.08) (0.92, 1.10) Levonorgestrel 30 mg 19 1.05 1.12 1.07 0.15 mg once daily once daily (0.96, 1.15) (1.07, 1.18) (1.01, 1.15) Midazolam 30 mg 12 1.09 1.10 NA 3 mg once daily (0.94, 1.26) (0.95, 1.26) Rilpivirine 30 mg 11 0.96 0.99 0.92 25 mg once daily once daily (0.85, 1.09) (0.89, 1.09) (0.79, 1.07)

Frequently Asked Questions

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: …

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 ) • …

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 …

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: …

Cabotegravir Sodium is a prescription medication. You will need a valid prescription from a licensed healthcare provider.

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References & Data Sources

• DailyMed — Cabotegravir Sodium drug label (National Library of Medicine)
• openFDA — Cabotegravir Sodium label data (U.S. Food & Drug Administration)
• RxNorm — RXCUI 2475199 (NLM Normalized Drug Names)
• NDC Directory — Cabotegravir Sodium (FDA National Drug Code)

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Sumber data: DailyMed (NLM), openFDA, MFDS