Cabotegravir Sodium
FDA Drug Information • Also known as: Vocabria
- Brand Names
- Vocabria
- Dosage Form
- POWDER
- Product Type
- BULK INGREDIENT
Description
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
What Is Cabotegravir Sodium Used For?
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.Dosage and Administration
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...Side Effects (Adverse Reactions)
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...Drug Interactions
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...Contraindications
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 )Pregnancy and Breastfeeding
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,...
Overdosage
10 OVERDOSAGE There is no known specific treatment for overdose with VOCABRIA. If overdose occurs, monitor the patient and apply standard supportive treatment as required as well as observation of the clinical status of the individual. As cabotegravir is highly bound to plasma proteins, it is unlikely that it will be significantly removed by dialysis.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING Each VOCABRIA tablet contains 30 mg of cabotegravir and is a white, oval, film-coated, biconvex tablet debossed with “SV CTV” on one side. Bottle of 30 tablets with child-resistant closure NDC 49702-248-13. Store below 30°C (86°F).
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.