Cabenuva
cabotegravir and rilpivirine · Kit
Uses
1 INDICATIONS AND USAGE CABENUVA is indicated as a complete regimen for the treatment of HIV-1 infection in adults and adolescents 12 years of age and older and weighing at least 35 kg to replace the current antiretroviral regimen in those 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 [see Microbiology ( 12.4 ), Clinical Studies ( 14.1 )] . CABENUVA, a 2-drug co-packaged product of cabotegravir, an HIV-1 integrase strand transfer inhibitor (INSTI), and rilpivirine, an HIV-1 non‑nucleoside reverse transcriptase inhibitor (NNRTI), is indicated as a complete regimen for the treatment of HIV-1 infection in adults and adolescents 12 years of age and older and weighing at least 35 kg to replace the current antiretroviral regimen in those 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 )
Dosage and administration
• Refer to full prescribing information for detailed information on dosage and administration recommendations. ( 2 )
• Prior to initiating treatment with CABENUVA, oral lead-in dosing may be considered to assess the tolerability of cabotegravir and rilpivirine with the recommended dosage used for approximately 1 month. ( 2.3 )
• For gluteal intramuscular injection only. ( 2.4 , 2.5 , 2.9 )
• Recommended Monthly Dosing Schedule: Initiate injections of CABENUVA (600 mg of cabotegravir and 900 mg of rilpivirine) on the last day of current antiretroviral therapy or oral lead-in and continue with injections of CABENUVA (400 mg of cabotegravir and 600 mg of rilpivirine) every month thereafter. ( 2.4 )
• Recommended Every-2-Month Dosing Schedule: Initiate injections of CABENUVA (600 mg of cabotegravir and 900 mg of rilpivirine) on the last day of current antiretroviral therapy or oral lead-in for 2 consecutive months and continue with injections of CABENUVA every 2 months thereafter. ( 2.5 ) 2.1 Dosage and Administration Overview
• CABENUVA contains cabotegravir extended-release injectable suspension in a single-dose vial and rilpivirine extended-release injectable suspension in a single-dose vial [see Dosage Forms and Strengths ( 3 )] .
• CABENUVA must be administered by a healthcare provider by gluteal intramuscular injection [see Dosage and Administration ( 2.9 )] .
• CABENUVA may be initiated with oral cabotegravir and oral rilpivirine prior to the intramuscular injections or the patient may proceed directly to injection of CABENUVA without an oral lead-in [see Dosage and Administration ( 2.3 )] .
• CABENUVA can be injected monthly or every 2 months [see Dosage and Administration ( 2.4 , 2.5 )] . Healthcare providers should discuss these 2 dosing options with the patient prior to starting CABENUVA and decide which injection dosing frequency would be the most appropriate option for the patient [see Adverse Reactions ( 6.1 ), Microbiology ( 12.4 ), Clinical Studies ( 14.1 )] . 2.2 Adherence to CABENUVA Prior to starting CABENUVA, healthcare providers should carefully select patients who agree to the required monthly or every‑2-month injection dosing schedule and counsel patients about the importance of adherence to scheduled dosing visits to help maintain viral suppression and reduce the risk of viral rebound and potential development of resistance with missed doses [see Dosage and Administration ( 2.1 ), Warnings and Precautions ( 5.6 ), Microbiology ( 12.4 )] . 2.3 Optional Oral Lead-In Dosing to Assess Tolerability of CABENUVA in Adults and Adolescents 12 Years of Age and Older and Weighing at Least 35 kg The healthcare provider and patient may decide to use an oral lead-in with oral cabotegravir and oral rilpivirine prior to the initiation of CABENUVA to assess the tolerability of cabotegravir and rilpivirine, or the healthcare provider and patient may proceed directly to injection of CABENUVA without the use of an oral lead-in. If oral lead-in is used, the recommended oral lead-in daily dose is one 30-mg tablet of VOCABRIA (cabotegravir) and one 25-mg tablet of EDURANT (rilpivirine) taken with a meal for approximately 1 month (at least 28 days), followed by intramuscular initiation injections of CABENUVA. See Tables 1 and 2 for recommended oral lead-in and monthly or every-2-month intramuscular injection dosing schedule for CABENUVA [see Dosage and Administration ( 2.4 , 2.5 )] . 2.4 Recommended Monthly Gluteal Intramuscular Injection Dosing with CABENUVA in Adults and Adolescents 12 Years of Age and Older and Weighing at Least 35 kg Initiation Injections (CABENUVA 600-mg/900-mg Kit) Initiate injections on the last day of current antiretroviral therapy or oral lead-in, if used [see Dosage and Administration ( 2.3 )] . The recommended initiation injection doses of CABENUVA are a single 600-mg (3-mL) intramuscular injection of cabotegravir and a single 900-mg (3-mL) intramuscular injection of rilpivirine. Administer cabotegravir and rilpivirine at separate gluteal injection sites (on opposite sides or at least 2 cm apart) during the same visit [see Dosage and Administration ( 2.9 )] . Continuation injections should be initiated a month after the initiation injections. Continuation Injections (CABENUVA 400-mg/600-mg Kit) After the initiation injections, the recommended monthly continuation injection doses of CABENUVA are a single 400-mg (2-mL) intramuscular injection of cabotegravir and a single 600-mg (2-mL) intramuscular injection of rilpivirine at each visit ( Table 1 ). Administer cabotegravir and rilpivirine at separate gluteal injection sites (on opposite sides or at least 2 cm apart) during the same visit [see Dosage and Administration ( 2.9 )] . Patients may be given CABENUVA up to 7 days before or after the date the patient is scheduled to receive monthly injections. Table 1. Recommended Dosing Schedule with Optional Oral Lead-In or Direct to Injection for Monthly Injection a The optional oral therapy should be continued until the day the first injection is administered. b Given on the last day of current antiretroviral therapy or oral lead-in if used. Drug Optional Oral Lead-In a (at Least 28 Days) Intramuscular (Gluteal) Initiation Injections (One-Time Dosing) Intramuscular (Gluteal) Continuation Injections (Once-Monthly Dosing) Month (at Least 28 Days) Prior to Starting Injections Initiate Injections at Month 1 b One Month after Initiation Injection and Monthly Onwards Cabotegravir 30 mg once daily with a meal 600 mg (3 mL) 400 mg (2 mL) Rilpivirine 25 mg once daily with a meal 900 mg (3 mL) 600 mg (2 mL) 2.5 Recommended Every-2-Month Gluteal Intramuscular Injection Dosing with CABENUVA in Adults and Adolescents 12 Years of Age and Older and Weighing at Least 35 kg Initiation Injections (CABENUVA 600-mg/900-mg Kit) Initiate injections on the last day of current antiretroviral therapy or oral lead-in, if used [see Dosage and Administration ( 2.3 )] .
Dosage forms and strengths
Injection:
• Kit of single-dose vials of 400 mg/2 mL (200 mg/mL) of cabotegravir extended-release injectable suspension and 600 mg/2 mL (300 mg/mL) of rilpivirine extended-release injectable suspension. ( 3 )
• Kit of single-dose vials of 600 mg/3 mL (200 mg/mL) of cabotegravir extended-release injectable suspension and 900 mg/3 mL (300 mg/mL) of rilpivirine extended-release injectable suspension. ( 3 ) Injection:
• Kit of single-dose vials of 400 mg/2 mL (200 mg/mL) of cabotegravir extended-release injectable suspension and 600 mg/2 mL (300 mg/mL) of rilpivirine extended-release injectable suspension. ( 3 )
• Kit of single-dose vials of 600 mg/3 mL (200 mg/mL) of cabotegravir extended-release injectable suspension and 900 mg/3 mL (300 mg/mL) of rilpivirine extended-release injectable suspension. ( 3 )
Contraindications
4 CONTRAINDICATIONS CABENUVA is contraindicated in patients:
• with previous hypersensitivity reaction to cabotegravir or rilpivirine [see Warnings and Precautions ( 5.1 )] .
• receiving the following coadministered drugs for which significant decreases in cabotegravir and/or rilpivirine plasma concentrations may occur due to uridine diphosphate glucuronosyltransferase (UGT)1A1 and/or cytochrome P450 (CYP)3A enzyme induction, which may result in loss of virologic response [see Drug Interactions ( 7 ), Clinical Pharmacology ( 12.3 )] : o Anticonvulsants: Carbamazepine, oxcarbazepine, phenobarbital, phenytoin o Antimycobacterials: Rifabutin, rifampin, rifapentine o Glucocorticoid (systemic): Dexamethasone (more than a single-dose treatment) o Herbal product: St John’s wort ( Hypericum perforatum )
• Previous hypersensitivity reaction to cabotegravir or rilpivirine. ( 4 )
• Coadministration with drugs where significant decreases in cabotegravir and/or rilpivirine plasma concentrations may occur, which may result in loss of virologic response. ( 4 )
Warnings and precautions
• Serious or severe hypersensitivity reactions have been reported with cabotegravir- and rilpivirine-containing regimens. Reactions associated with cabotegravir include Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Reactions associated with rilpivirine-containing regimens include cases of drug reaction with eosinophilia and systemic symptoms (DRESS). Discontinue CABENUVA immediately if signs or symptoms of hypersensitivity reactions develop. ( 5.1 )
• Serious post-injection reactions with rilpivirine were reported. Monitor and treat as clinically indicated. ( 5.2 )
• Hepatotoxicity has been reported in patients receiving cabotegravir or rilpivirine. Monitoring of liver chemistries is recommended. Discontinue CABENUVA if hepatotoxicity is suspected. ( 5.3 )
• Depressive disorders have been reported with CABENUVA. Prompt evaluation is recommended for depressive symptoms. ( 5.4 )
• Residual concentrations of cabotegravir and rilpivirine may remain in the systemic circulation of patients up to 12 months or longer. It is essential to initiate an alternative, fully suppressive antiretroviral regimen no later than 1 month after the final injections of CABENUVA when dosed monthly and no later than 2 months after the final injections when dosed every 2 months. If virologic failure is suspected, prescribe an alternative regimen as soon as possible. ( 5.6 ) 5.1 Hypersensitivity Reactions Serious or severe hypersensitivity reactions have been reported with cabotegravir- and rilpivirine-containing regimens. Reactions associated with cabotegravir include Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) [see Adverse Reactions ( 6.2 )] . Reactions associated with rilpivirine-containing regimens include cases of drug reaction with eosinophilia and systemic symptoms (DRESS) [see Adverse Reactions ( 6.1 , 6.2 )] . While some skin reactions were accompanied by constitutional symptoms such as fever, other skin reactions were associated with organ dysfunctions, including elevations in hepatic serum biochemistries. Administration of cabotegravir and rilpivirine oral lead-in dosing was used in clinical studies to help identify patients who may be at risk of a hypersensitivity reaction [see Dosage and Administration ( 2.3 ), Contraindications ( 4 )] . Remain vigilant and discontinue CABENUVA if a hypersensitivity reaction is suspected [see Contraindications ( 4 ), Adverse Reactions ( 6 )] . Discontinue CABENUVA 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. For information regarding the long-acting properties of CABENUVA, [see Warnings and Precautions ( 5.6 )] . Administer oral lead-in dosing prior to administration of CABENUVA to help identify patients who may be at risk of a hypersensitivity reaction [see Dosage and Administration ( 2.3 ), Contraindications ( 4 )] . 5.2 Post-Injection Reactions In clinical trials, serious post-injection reactions were reported within minutes after the injection of rilpivirine. These events included symptoms such as dyspnea, bronchospasm, agitation, abdominal cramping, rash/urticaria, dizziness, flushing, sweating, oral numbness, changes in blood pressure, and pain (e.g., back and chest). These events were reported in <1% of participants and began to resolve within minutes after the injection, with some patients receiving supportive care. These events may have been associated with accidental intravenous administration during the intramuscular injection procedure [see Adverse Reactions ( 6.1 )] . Carefully follow the Instructions for Use when preparing and administering CABENUVA. The suspensions should be injected slowly via intramuscular injection, and care should be taken to avoid accidental intravenous administration [see Dosage and Administration ( 2.9 )] . Observe patients briefly (approximately 10 minutes) after the injection. If a patient experiences a post-injection reaction, monitor and treat as clinically indicated. 5.3 Hepatotoxicity Hepatotoxicity has been reported in patients receiving cabotegravir or rilpivirine with or without known pre-existing hepatic disease or identifiable risk factors [see Adverse Reactions ( 6.1 )] . Patients with underlying liver disease or marked elevations in transaminases prior to treatment may be at increased risk for worsening or development of transaminase elevations. Monitoring of liver chemistries is recommended and treatment with CABENUVA should be discontinued if hepatotoxicity is suspected. For information regarding the long-acting properties of CABENUVA, [see Warnings and Precautions ( 5.6 )] . 5.4 Depressive Disorders Depressive disorders (including depressed mood, depression, major depression, mood altered, mood swings, dysphoria, negative thoughts, suicidal ideation, suicide attempt) have been reported with CABENUVA or the individual drug products [see Adverse Reactions ( 6.1 )] . Promptly evaluate patients with depressive symptoms to assess whether the symptoms are related to CABENUVA and to determine whether the risks of continued therapy outweigh the benefits. 5.5 Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions The concomitant use of CABENUVA and other drugs may result in known or potentially significant drug interactions, some of which may lead to adverse events, loss of virologic response of CABENUVA, and possible development of viral resistance [see Contraindications ( 4 ), Drug Interactions ( 7.4 )] .
Side effects
The following adverse reactions are described below and in other sections of the labeling:
• Hypersensitivity reactions [see Warnings and Precautions ( 5.1 )]
• Post-injection reactions [see Warnings and Precautions ( 5.2 )]
• Hepatotoxicity [see Warnings and Precautions ( 5.3 )]
• Depressive disorders [see Warnings and Precautions ( 5.4 )] The most common adverse reactions (Grades 1 to 4) observed in ≥2% of participants receiving CABENUVA were injection site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, and rash. ( 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. Clinical Trials Experience in Adults The safety assessment of CABENUVA is based on the analysis of pooled 48-week data from 1,182 virologically suppressed participants with HIV-1 infection in 2 international, multicenter, open-label pivotal trials, FLAIR and ATLAS, and 1,045 virologically suppressed participants from the ATLAS-2M trial [see Clinical Studies ( 14.1 )] . Additional safety information from other ongoing or earlier clinical trials in the cabotegravir and rilpivirine program have been considered in assessing the overall safety profile of CABENUVA. Adverse reactions were reported following exposure to CABENUVA extended-release injectable suspensions (median time exposure at the time of analysis: 54 weeks in FLAIR and ATLAS, and 64 weeks in ATLAS-2M) and data from VOCABRIA (cabotegravir) tablets and EDURANT (rilpivirine) tablets administered in combination as oral lead-in therapy (median time exposure: 5.3 weeks in FLAIR and ATLAS, and 5.6 weeks in ATLAS-2M). Adverse reactions included those attributable to both the oral and injectable formulations of cabotegravir and rilpivirine administered as a combination regimen. Refer to the prescribing information for EDURANT (rilpivirine) for other adverse reactions associated with oral rilpivirine. The most common adverse reactions regardless of severity reported in ≥2% of adult participants from FLAIR and ATLAS at Week 48 are presented in Table 5 . Selected laboratory abnormalities are included in Table 7 . At Week 96, the overall safety profile for FLAIR was consistent with that observed at Week 48, with no new safety findings identified. 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. Overall, 4% of participants in the group receiving CABENUVA and 2% of participants in the control group in FLAIR and ATLAS discontinued due to adverse events. Non-injection-site-related adverse events leading to discontinuation and occurring in more than 1 participant were headache, diarrhea, hepatitis A, and acute hepatitis B (all with an incidence <1%). In ATLAS-2M, 2% of participants in both treatment groups discontinued due to adverse events. Non-injection-site–related adverse events leading to discontinuation and occurring in more than 1 participant in ATLAS-2M were fatigue, pyrexia, headache, presyncope, acute hepatitis B, hyperhidrosis, and abnormal dreams that occurred with an incidence of ≤1% in either treatment group. Table 5. Adverse Reactions a (Grades 1 to 4) Reported in at Least 2% of Participants with HIV-1 Infection in FLAIR and ATLAS Trials (Week 48 Pooled Analyses) a Adverse reactions defined as “treatment-related” as assessed by the investigator. b See Injection-Associated Adverse Reactions for additional information. c Pyrexia: includes pyrexia, feeling hot, chills, influenza-like illness, body temperature increased. d Fatigue: includes fatigue, malaise, asthenia. e Musculoskeletal pain: includes musculoskeletal pain, musculoskeletal discomfort, back pain, myalgia, pain in extremity. f Sleep disorders: includes insomnia, poor quality sleep, somnolence. g Rash: includes erythema, pruritus, pruritus generalized, purpura, rash, rash- erythematous, generalized, macular. Adverse Reactions Cabotegravir plus Rilpivirine Once Monthly (n = 591) Current Antiretroviral Regimen (n = 591) All Grades At Least Grade 2 All Grades At Least Grade 2 Injection site reactions b 83% 37% 0 0 Pyrexia c 8% 2% 0 0 Fatigue d 5% 1% <1% <1% Headache 4% <1% <1% <1% Musculoskeletal pain e 3% 1% <1% 0 Nausea 3% <1% 1% <1% Sleep disorders f 2% <1% <1% 0 Dizziness 2% <1% <1% 0 Rash g 2% <1% 0 0 In ATLAS-2M, the type and frequency of adverse reactions reported in participants receiving CABENUVA once monthly or CABENUVA once every 2 months for 48 weeks were similar. Differences between treatment arms were reported for the types of injection-associated adverse reactions (see Injection-Associated Adverse Reactions for additional information). Injection-Associated Adverse Reactions: Local Injection Site Reactions (ISRs): In the 3 Phase 3 studies, FLAIR, ATLAS, and ATLAS‑2M, the most frequent adverse reactions associated with the intramuscular administration of CABENUVA were ISRs. In the pooled analysis of FLAIR and ATLAS, 83% of participants reported any injection site reaction with the monthly dosing regimen, with 1% of participants who discontinued treatment with CABENUVA because of ISRs. After 14,682 injections, 3,663 ISRs were reported. The severity of ISRs was generally mild (Grade 1: 75% of participants) or moderate (Grade 2: 36% of participants). Four percent (4%) of participants experienced severe (Grade 3) ISRs, and no participant experienced Grade 4 ISRs. The median duration of overall ISR events was 3 days.
Drug interactions
• Refer to the full prescribing information for important drug interactions with CABENUVA. ( 4 , 5.5 , 7 )
• Because CABENUVA is a complete regimen, coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended. ( 7.1 )
• Drugs that induce uridine diphosphate glucuronosyltransferase (UGT)1A1 or cytochrome P450 (CYP)3A4 may decrease the plasma concentrations of the components of CABENUVA. ( 4 , 7.3 , 7.4 )
• CABENUVA should be used with caution in combination with drugs with a known risk of Torsade de Pointes. ( 7.3 , 7.4 ) 7.1 Concomitant Use with Other Antiretroviral Medicines Because CABENUVA is a complete regimen, coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended [see Indications and Usage ( 1 )] . 7.2 Use of Other Antiretroviral Drugs after Discontinuation of CABENUVA Residual concentrations of cabotegravir and rilpivirine may remain in the systemic circulation of patients for prolonged periods (up to 12 months or longer). These residual concentrations are not expected to affect the exposures of antiretroviral drugs that are initiated after discontinuation of CABENUVA [see Warnings and Precautions ( 5.6 ), Drug Interactions ( 7.4 ), Clinical Pharmacology ( 12.3 )] . 7.3 Potential for Other Drugs to Affect CABENUVA Refer to the prescribing information for VOCABRIA (cabotegravir) and EDURANT (rilpivirine) for additional drug interaction information related to oral cabotegravir and oral rilpivirine, respectively. Cabotegravir 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 virologic response; therefore, coadministration of CABENUVA with these drugs is contraindicated [see Contraindications ( 4 )] . Rilpivirine Rilpivirine is primarily metabolized by CYP3A. Coadministration of CABENUVA and drugs that induce CYP3A may result in decreased plasma concentrations of rilpivirine and loss of virologic response and possible resistance to rilpivirine or to the class of NNRTIs [see Contraindications ( 4 ), Drug Interactions ( 7.4 )]. Coadministration of CABENUVA and drugs that inhibit CYP3A may result in increased plasma concentrations of rilpivirine [see Drug Interactions ( 7.4 ), Clinical Pharmacology ( 12.3 )] . QT-Prolonging Drugs: At mean steady-state C max values 4.4- and 11.6-fold higher than those with the recommended 600‑mg dose of rilpivirine extended-release injectable suspension, rilpivirine may prolong the QTc interval [see Clinical Pharmacology ( 12.2 )] . CABENUVA should be used with caution in combination with drugs with a known risk of Torsade de Pointes [see Warnings and Precautions ( 5.5 ), Drug Interactions ( 7.4 )] . 7.4 Established and Other Potentially Significant Drug Interactions Refer to the prescribing information for VOCABRIA (cabotegravir) and EDURANT (rilpivirine) for additional drug interaction information related to oral cabotegravir and oral rilpivirine, respectively. Information regarding potential drug interactions with cabotegravir and rilpivirine is provided in Table 8 . These recommendations are based on either drug interaction trials following oral administration of cabotegravir or rilpivirine or predicted interactions due to the expected magnitude of the interaction and potential for loss of virologic response [see Contraindications ( 4 ), Warnings and Precautions ( 5.5 ), Clinical Pharmacology ( 12.3 )] . Table 8 includes potentially significant interactions but is not all inclusive. Table 8. Drug Interactions with CABENUVA ↑ = Increase, ↓ = Decrease, ↔ = No change. a See Clinical Pharmacology ( 12.3 ) for magnitude of interaction. Concomitant Drug Class: Drug Name Effect on Concentration Clinical Comment Anticonvulsants: Carbamazepine Oxcarbazepine Phenobarbital Phenytoin ↓Cabotegravir ↓Rilpivirine Coadministration is contraindicated with CABENUVA due to potential for loss of virologic response and development of resistance [see Contraindications ( 4 )] . Antimycobacterials: Rifampin a Rifapentine ↓Cabotegravir ↓Rilpivirine Antimycobacterial: Rifabutin a ↓Cabotegravir ↔Rifabutin ↓Rilpivirine Glucocorticoid (systemic): Dexamethasone (more than a single-dose treatment) ↓Rilpivirine Herbal product: St John’s wort ( Hypericum perforatum ) ↓Rilpivirine Macrolide or ketolide antibiotics: Azithromycin Clarithromycin Erythromycin ↔Cabotegravir ↑Rilpivirine Macrolides are expected to increase concentrations of rilpivirine and are associated with a risk of Torsade de Pointes [see Warnings and Precautions ( 5.5 )] . Where possible, consider alternatives, such as azithromycin, which increases rilpivirine concentrations less than other macrolides. Narcotic analgesic: Methadone a ↔Cabotegravir ↓Methadone ↔Rilpivirine No dose adjustment of methadone is required when starting coadministration of methadone with CABENUVA. However, clinical monitoring is recommended as methadone maintenance therapy may need to be adjusted in some patients. 7.5 Drugs without Clinically Significant Interactions Cabotegravir Based on drug interaction study results, the following drugs can be coadministered with cabotegravir (non-antiretrovirals and rilpivirine) or given after discontinuation of cabotegravir (antiretrovirals and non-antiretrovirals) without a dose adjustment: etravirine, midazolam, oral contraceptives containing levonorgestrel and ethinyl estradiol, and rilpivirine [see Clinical Pharmacology ( 12.3 )] .
Use in specific populations
• Pregnancy: After oral use of rilpivirine, exposures were generally lower during pregnancy compared with the postpartum period. ( 8.1 ) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to CABENUVA 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 CABENUVA during pregnancy to adequately assess a drug-associated risk of birth defects and miscarriage. Discuss the benefit-risk of using CABENUVA with individuals of childbearing potential or during pregnancy. Cabotegravir and rilpivirine are detected in systemic circulation for up to 12 months or longer after discontinuing injections of CABENUVA; therefore, consideration should be given to the potential for fetal exposure during pregnancy [see Warnings and Precautions ( 5.6 ), Drug Interactions ( 7.2 )] . Cabotegravir use in pregnant individuals has not been evaluated. Available data from the APR show no difference in the overall risk of birth defects for rilpivirine compared with the background rate for major birth defects of 2.7% in a United States (U.S.) reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP) (see Data ). 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 U.S. reference population of the 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 ). No adverse developmental outcomes were observed when rilpivirine was administered orally at exposures 15 (rats) and 70 (rabbits) times the exposure in humans at the RHD (see Data ). Clinical Considerations Lower exposures with oral rilpivirine were observed during pregnancy. Viral load should be monitored closely if the patient remains on CABENUVA during pregnancy. Cabotegravir and rilpivirine are detected in systemic circulation for up to 12 months or longer after discontinuing injections of CABENUVA; therefore, consideration should be given to the potential for fetal exposure during pregnancy [see Warnings and Precautions ( 5.6 ), Drug Interactions ( 7.2 )] . Data Human Data: Rilpivirine: Based on prospective reports to the APR of over 580 exposures to oral rilpivirine-containing regimens during the first trimester of pregnancy and over 200 during second/third trimester of pregnancy, the prevalence of birth defects in live births was 1.5% (95% CI: 0.7% to 2.9%) and 1.5% (95% CI: 0.3% to 4.2%) following first and second/third trimester exposures, respectively, compared with the background birth defect rate of 2.7% in the U.S. reference population of the MACDP. In a clinical trial, total oral rilpivirine exposures were generally lower during pregnancy compared with the postpartum period. Refer to the prescribing information for EDURANT (rilpivirine) for additional information on rilpivirine. Animal Data: Cabotegravir: 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. Rilpivirine: Rilpivirine was administered orally to pregnant rats (40, 120, or 400 mg/kg/day) and rabbits (5, 10, or 20 mg/kg/day) through organogenesis (on Gestation Days 6 through 17 and 6 through 19, respectively).
Pregnancy
8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to CABENUVA 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 CABENUVA during pregnancy to adequately assess a drug-associated risk of birth defects and miscarriage. Discuss the benefit-risk of using CABENUVA with individuals of childbearing potential or during pregnancy. Cabotegravir and rilpivirine are detected in systemic circulation for up to 12 months or longer after discontinuing injections of CABENUVA; therefore, consideration should be given to the potential for fetal exposure during pregnancy [see Warnings and Precautions ( 5.6 ), Drug Interactions ( 7.2 )] . Cabotegravir use in pregnant individuals has not been evaluated. Available data from the APR show no difference in the overall risk of birth defects for rilpivirine compared with the background rate for major birth defects of 2.7% in a United States (U.S.) reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP) (see Data ). 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 U.S. reference population of the 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 ). No adverse developmental outcomes were observed when rilpivirine was administered orally at exposures 15 (rats) and 70 (rabbits) times the exposure in humans at the RHD (see Data ). Clinical Considerations Lower exposures with oral rilpivirine were observed during pregnancy. Viral load should be monitored closely if the patient remains on CABENUVA during pregnancy. Cabotegravir and rilpivirine are detected in systemic circulation for up to 12 months or longer after discontinuing injections of CABENUVA; therefore, consideration should be given to the potential for fetal exposure during pregnancy [see Warnings and Precautions ( 5.6 ), Drug Interactions ( 7.2 )] . Data Human Data: Rilpivirine: Based on prospective reports to the APR of over 580 exposures to oral rilpivirine-containing regimens during the first trimester of pregnancy and over 200 during second/third trimester of pregnancy, the prevalence of birth defects in live births was 1.5% (95% CI: 0.7% to 2.9%) and 1.5% (95% CI: 0.3% to 4.2%) following first and second/third trimester exposures, respectively, compared with the background birth defect rate of 2.7% in the U.S. reference population of the MACDP. In a clinical trial, total oral rilpivirine exposures were generally lower during pregnancy compared with the postpartum period. Refer to the prescribing information for EDURANT (rilpivirine) for additional information on rilpivirine. Animal Data: Cabotegravir: 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. Rilpivirine: Rilpivirine was administered orally to pregnant rats (40, 120, or 400 mg/kg/day) and rabbits (5, 10, or 20 mg/kg/day) through organogenesis (on Gestation Days 6 through 17 and 6 through 19, respectively).
Pediatric use
8.4 Pediatric Use The safety and effectiveness of CABENUVA have been established in adolescents aged 12 to younger than 18 years and weighing at least 35 kg, which is supported by the following:
• Trials in adults [see Clinical Studies ( 14.1 )]
• MOCHA (NCT03497676) trial in adolescents, in which virologically suppressed adolescents with HIV-1 (aged 12 to younger than 18 years and weighing at least 35 kg) received either cabotegravir or rilpivirine in addition to their background antiretroviral regimen (cohort 1), or cabotegravir plus rilpivirine as a complete regimen (cohort 2) [see Adverse Reactions ( 6.1 ), Clinical Pharmacology ( 12.3 ), Clinical Studies ( 14.2 )] . The safety and efficacy in adolescents (aged 12 to younger than 18 years and weighing at least 35 kg) were similar to that in adults and there was no clinically significant change in exposure for the components of CABENUVA [see Adverse Reactions ( 6.1 )] . The efficacy of CABENUVA in adolescents is extrapolated from adults with support from pharmacokinetic analyses showing similar drug exposure and additional supportive efficacy data from the MOCHA study [see Clinical Pharmacology ( 12.3 ), Clinical Studies ( 14.2 )] . The safety, efficacy, and pharmacokinetics of CABENUVA have not been established in pediatric patients younger than 12 years of age or weighing <35 kg.
Geriatric use
8.5 Geriatric Use Clinical trials of CABENUVA did not include sufficient numbers of participants aged 65 years and older to determine whether they respond differently from younger participants. In general, caution should be exercised in administration of CABENUVA in elderly patients, reflecting greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy [see Clinical Pharmacology ( 12.3 )] .
Overdosage
There is no known specific treatment for overdose with cabotegravir or rilpivirine. If overdose occurs, monitor the patient and apply standard supportive treatment as required, including monitoring of vital signs and ECG (QT interval) as well as observation of the clinical status of the patient. As both cabotegravir and rilpivirine are highly bound to plasma proteins, it is unlikely that either would be significantly removed by dialysis. Consider the prolonged exposure to cabotegravir and rilpivirine (components of CABENUVA) following an injection when assessing treatment needs and recovery [see Warnings and Precautions ( 5.6 )] .
Description
11 DESCRIPTION CABENUVA contains cabotegravir extended-release injectable suspension, an HIV INSTI, co-packaged with rilpivirine extended-release injectable suspension, an HIV NNRTI. Cabotegravir The chemical name for cabotegravir is ( 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 17 F 2 N 3 O 5 and the molecular weight is 405.35 g/mol. It has the following structural formula: Cabotegravir extended-release injectable suspension is a white to light pink free-flowing suspension for intramuscular injection in a sterile single-dose vial. Each vial contains 2 mL or 3 mL of the following: cabotegravir 200 mg/mL and the inactive ingredients mannitol (35 mg/mL), polyethylene glycol (PEG) 3350 (20 mg/mL), polysorbate 20 (20 mg/mL), and Water for Injection. The vial stoppers are not made with natural rubber latex. Rilpivirine The chemical name for rilpivirine is 4-[[4-[[4-[(E)-2-cyanoethenyl]-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile. Its molecular formula is C 22 H 18 N 6 and its molecular weight is 366.42. Rilpivirine has the following structural formula: Rilpivirine extended-release injectable suspension is a white to off-white suspension for intramuscular injection. Each sterile single-dose vial contains 2 mL or 3 mL of the following: rilpivirine 300 mg/mL and the following inactive ingredients: citric acid monohydrate (1 mg/mL), dextrose to ensure isotonicity, monobasic sodium phosphate (1.74 mg/mL), poloxamer 338 (50 mg/mL), sodium hydroxide to adjust pH, and Water for Injection. The vial stoppers are not made with natural rubber latex. Cabotegravir chemical structure Rilpivirine chemical structure
Mechanism of action
12.1 Mechanism of Action CABENUVA contains 2 long-acting HIV-1 antiretroviral drugs, cabotegravir and rilpivirine [see Microbiology ( 12.4 )] .
How supplied
How Supplied CABENUVA is supplied in 2 dosing kits. Each kit contains 1 vial of cabotegravir extended‑release injectable suspension and 1 vial of rilpivirine extended-release injectable suspension, co‑packaged as follows: CABENUVA 400-mg/600-mg Kit (NDC 49702-253-15) containing:
• One single-dose vial of cabotegravir extended-release injectable suspension containing 400 mg/2 mL (200 mg/mL) of cabotegravir.
• One single-dose vial of rilpivirine extended-release injectable suspension containing 600 mg/2 mL (300 mg/mL) of rilpivirine CABENUVA 600-mg/900-mg Kit (NDC 49702-240-15) containing:
• One single-dose vial of cabotegravir extended-release injectable suspension containing 600 mg/3 mL (200 mg/mL) of cabotegravir.
• One single-dose vial of rilpivirine extended-release injectable suspension containing 900 mg/3 mL (300 mg/mL) of rilpivirine. Each dosing kit also contains 2 syringes, 2 syringe labels, 2 vial adapters, and 2 needles for intramuscular injection (23-gauge, 1½ inch). The vial stoppers are not made with natural rubber latex. Storage and Handling Store CABENUVA in the refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton until ready to use. Do not freeze. Do not mix with any other product or diluent. Prior to administration, vials should be brought to room temperature (not to exceed 25°C [77°F]). Vials may remain in the carton at room temperature for up to 6 hours; do not put back into the refrigerator. If not used within 6 hours, they must be discarded. Once the suspensions have been drawn into the respective syringes, the injections should be administered as soon as possible, but may remain in the syringes for up to 2 hours. The filled syringes should not be placed in the refrigerator. If the medicines remain in the syringes for more than 2 hours, the filled syringes and needles must be discarded [see Dosage and Administration ( 2.9 )] .
Patient information
Advise the patient to read the FDA-approved patient labeling (Patient Information). Hypersensitivity Reactions Advise patients to immediately contact their healthcare provider if they develop a rash. Instruct patients to immediately stop taking CABENUVA and seek medical attention if they develop a rash associated with any of the following symptoms, as it may be a sign of a more serious reaction such as Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) or drug reaction with eosinophilia and systemic symptoms (DRESS): fever; generally ill feeling; extreme tiredness; muscle or joint aches; blisters; oral blisters or lesions; eye inflammation; facial swelling; swelling of the eyes, lips, tongue, or mouth; difficulty breathing; and/or signs and symptoms of liver problems (e.g., yellowing of the skin or whites of the eyes; dark or tea-colored urine; pale-colored stools or bowel movements; nausea; vomiting; loss of appetite; or pain, aching, or sensitivity on the right side below the ribs). Advise patients that if hypersensitivity occurs, they will be closely monitored, laboratory tests will be ordered, and appropriate therapy will be initiated [see Warnings and Precautions ( 5.1 )] . Adverse Reactions Following Injections Advise patients that injection site reactions have been reported in the majority of patients receiving CABENUVA. These local reactions typically consist of one or more of the following: pain, erythema, tenderness, pruritus, and local swelling. Systemic reactions have also been reported, such as fever, musculoskeletal pain, and sciatica pain [see Adverse Reactions ( 6.1 )] . Serious post-injection reactions were reported within minutes after the injection of rilpivirine, including dyspnea, bronchospasm, agitation, abdominal cramping, rash/urticaria, dizziness, flushing, sweating, oral numbness, changes in blood pressure, and back pain (e.g., back and chest). These events began to resolve within minutes after the injection. Advise patients that they will be observed briefly (approximately 10 minutes) after the injection. If they experience a post-injection reaction, they will be monitored and appropriate treatment administered [see Warnings and Precautions ( 5.2 )] . Hepatotoxicity Inform patients that hepatotoxicity has been reported with cabotegravir and rilpivirine, components of CABENUVA [see Warnings and Precautions ( 5.3 ), Adverse Reactions ( 6.1 )] . Inform patients that monitoring for liver transaminases is recommended. Depressive Disorders Inform patients that depressive disorders (including depressed mood, depression, major depression, mood altered, mood swings, unusual mood, negative thoughts, suicidal ideation, suicide attempt) have been reported with at least one of the components of CABENUVA. Advise patients to seek prompt medical evaluation if they experience depressive symptoms [see Warnings and Precautions ( 5.4 ), Adverse Reactions ( 6.1 )] . Drug Interactions Inform patients that CABENUVA may interact with other drugs; therefore, advise patients to report to their healthcare provider the use of any other prescription or nonprescription medication or herbal products, including St. John’s wort. CABENUVA is an extended-release injectable that may be systemically present for 12 months or longer. These residual concentrations are not expected to affect the exposures of antiretroviral drugs that are initiated after discontinuation of CABENUVA [see Contraindications ( 4 ), Drug Interactions ( 7 )] . Adherence to CABENUVA Counsel patients about the importance of continued medication adherence and scheduled visits to help maintain viral suppression and to reduce risk of loss of virologic response and development of resistance [see Dosage and Administration ( 2.1 ), Warnings and Precautions ( 5.6 )] . Two Options for Dosing Frequency Advise the patient that CABENUVA can be injected monthly or every 2 months after oral lead‑in with cabotegravir and rilpivirine to assess tolerability. Discuss the two injection dosing frequency options with the patient prior to starting CABENUVA and decide which injection dosing frequency would be the most appropriate option for the patient [see Dosage and Administration ( 2.1 )]. Missed Dose Inform patients that CABENUVA can remain in the body for up to 12 months or longer after receiving their last injection. Advise patients that they should contact their healthcare provider if they miss or plan to miss a scheduled injection visit and that oral therapy with VOCABRIA and EDURANT may be used up to 2 months to replace missed injection visits, or any other fully suppressive oral antiretroviral regimen may be used until injections are resumed. Advise patients that if they stop treatment with CABENUVA, they will need to take other medicines to treat their HIV-1 infection [see Dosage and Administration ( 2.2 , 2.8 ), Warnings and Precautions ( 5.6 )] . Pregnancy Registry Inform patients that there is an antiretroviral pregnancy registry to monitor fetal outcomes in those exposed to CABENUVA during pregnancy. Patients who are of reproductive potential should be informed of the long duration of exposure of CABENUVA and that there is very limited clinical experience in human pregnancy [see Warnings and Precautions ( 5.6 ), Use in Specific Populations ( 8.1 )] . Lactation Inform individuals with HIV-1 infection that the potential risks of breastfeeding include: (1) HIV-1 transmission (in HIV-1–negative infants), (2) developing viral resistance (in HIV-1–positive infants), and (3) adverse reactions in a breastfed infant similar to those seen in adults [see Use in Specific Populations ( 8.2 )] . CABENUVA and VOCABRIA are trademarks owned by or licensed to the ViiV Healthcare group of companies. The other brand listed is a trademark owned by or licensed to its respective owner and is not a trademark owned by or licensed to the ViiV Healthcare group of companies.
Label text from the FDA structured product label by ViiV Healthcare Company (revised Nov 26, 2025). Long sections are shortened; the complete label is on DailyMed.
Cabenuva NDC products (3)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 49702-240 | Kit | ViiV Healthcare Company | NDA |
| 49702-253 | Kit | ViiV Healthcare Company | NDA |
| 49702-266 | Kit | ViiV Healthcare Company | NDA |
Frequently asked questions
What is Cabenuva used for?
1 INDICATIONS AND USAGE CABENUVA is indicated as a complete regimen for the treatment of HIV-1 infection in adults and adolescents 12 years of age and older and weighing at least 35 kg to replace the current antiretroviral regimen in those 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…
What are the side effects of Cabenuva?
The following adverse reactions are described below and in other sections of the labeling: • Hypersensitivity reactions [see Warnings and Precautions ( 5.1 )] • Post-injection reactions [see Warnings and Precautions ( 5.2 )] • Hepatotoxicity [see Warnings and Precautions ( 5.3 )] • Depressive disorders [see Warnings and Precautions ( 5.4 )] The most common adverse reactions (Grades 1 to 4)… See the full label for the complete list.
Who makes Cabenuva?
Cabenuva is listed by 1 labeler in the FDA NDC directory, including ViiV Healthcare Company.