Cabenuva Prescribing Guidelines
NDC Code(s): 49702-238-01, 49702-240-15, 49702-243-02, 49702-245-01, 49702-249-02, 49702-253-15
Packager: ViiV Healthcare Company
Category: HUMAN PRESCRIPTION DRUG LABEL
DEA Schedule: None
Marketing Status: New Drug Application
Drug Label Information
Updated February 27, 2023
HIGHLIGHTS OF PRESCRIBING INFORMATION
Initial U.S. Approval: 2021
INDICATIONS AND USAGE
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)
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)
CONTRAINDICATIONS
- 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
- Hypersensitivity reactions have been reported with rilpivirine-containing regimens and in association with integrase inhibitors. 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)
ADVERSE REACTIONS
The most common adverse reactions (Grades 1 to 4) observed in ≥2% of subjects receiving CABENUVA were injection site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, and rash. (6.1)
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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)
USE IN SPECIFIC POPULATIONS
- Pregnancy: After oral use of rilpivirine, exposures were generally lower during pregnancy compared with the postpartum period. (8.1)
- Lactation: Breastfeeding is not recommended due to the potential for HIV-1 transmission. (8.2) See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
CLOSE
TABLE OF CONTENTS
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
2.1 Dosage and Administration Overview
2.2 Adherence to CABENUVA
2.3 Recommended 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
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
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
2.6 Dosing Recommendations When Switching from Monthly to Every-2-Month Intramuscular Injections
2.7 Dosing Recommendations When Switching from Every-2-Month to Monthly Intramuscular Injections
2.8 Recommended Dosing Schedule for Missed Injections
2.9 Administration Instructions for Injections
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Hypersensitivity Reactions
5.2 Post-Injection Reactions
5.3 Hepatotoxicity
5.4 Depressive Disorders
5.5 Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions
5.6 Long-Acting Properties and Potential Associated Risks with CABENUVAs
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
6.2 Postmarketing Experience
7 DRUG INTERACTIONS
7.1 Concomitant Use with Other Antiretroviral Medicines
7.2 Use of Other Antiretroviral Drugs after Discontinuation of CABENUVA
7.3 Potential for Other Drugs to Affect CABENUVA
7.4 Established and Other Potentially Significant Drug Interactions
7.5 Drugs without Clinically Significant Interactions
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Lactation
8.4 Pediatric Use
8.5 Geriatric Use
8.6 Renal Impairment
8.7 Hepatic Impairment
10 OVERDOSAGE
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
12.4 Microbiology
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
14 CLINICAL STUDIES
14.1 Clinical Trials in Adults
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
- 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)].
Table 1. Recommended Dosing Schedule with Optional Oral Lead-in or Direct to Injection for Monthly Injection
Drug | Optional Oral Lead-ina (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 1b | 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) |
Table 2. Recommended Dosing Schedule with Optional Oral Lead-in or Direct to Injection for Every-2-Month Injection
Drug | Optional Oral Lead-ina (at Least 28 Days) | Intramuscular (Gluteal) Injectionsb |
---|---|---|
Month (at Least 28 Days) Prior to Starting Injections | Initiate Injectionsc at Month 1, Month 2, and then Every 2 Months Onwards (Starting at Month 4) | |
Cabotegravir | 30 mg once daily with a meal | 600 mg (3 mL) |
Rilpivirine | 25 mg once daily with a meal | 900 mg (3 mL) |
b For the every-2-month injection dosing schedule in adults, Initiation Injections are injections administered at Month 1 and Month 2 and Continuation Injections are injections administered every 2 months onwards (starting Month 4).
2.6 Dosing Recommendations When Switching from Monthly to Every-2-Month Intramuscular Injections
Time since Last Injection | Recommendation |
---|---|
Less than or equal to 2 months | Resume with 400-mg (2-mL) cabotegravir and 600-mg (2-mL) rilpivirine gluteal intramuscular monthly injections as soon as possible. |
Greater than 2 months | Re-initiate the patient with 600-mg (3-mL) cabotegravir and 900-mg (3‑mL) rilpivirine gluteal intramuscular injections then continue to follow the 400‑mg (2‑mL) cabotegravir and 600-mg (2-mL) rilpivirine gluteal intramuscular monthly injection dosing schedule. |
If a scheduled every-2-month injection visit is missed or delayed by more than 7 days and oral therapy has not been taken in the interim, clinically reassess the patient to determine if resumption of injection dosing remains appropriate [see Warnings and Precautions (5.6)]. If the every-2‑month dosing schedule will be continued, see TABLE 4 for dosing recommendations.
Missed Injection Visit | Time since Last Injection | Recommendation |
---|---|---|
Injection 2 (Month 2) | Less than or equal to 2 months | Resume with 600-mg (3-mL) cabotegravir and 900‑mg (3‑mL) rilpivirine intramuscular injections as soon as possible, then continue to follow the every-2-month injection dosing schedule. |
Greater than 2 months | Re-initiate the patient with 600-mg (3-mL) cabotegravir and 900-mg (3‑mL) rilpivirine intramuscular injections, followed by the second initiation injection dose 1 month later. Then continue to follow the every-2-month injection dosing schedule thereafter. | |
Injection 3 or later (Month 4 onwards) | Less than or equal to 3 months | Resume with 600-mg (3-mL) cabotegravir and 900‑mg (3‑mL) rilpivirine intramuscular injections as soon as possible and continue with the every‑2‑month injection dosing schedule. |
Greater than 3 months | Re-initiate the patient with 600-mg (3-mL) cabotegravir and 900-mg (3‑mL) rilpivirine intramuscular injections, followed by the second initiation injection dose 1 month later. Then continue with the every-2-month injection dosing schedule thereafter. |
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)
- 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)]:
- Anticonvulsants: Carbamazepine, oxcarbazepine, phenobarbital, phenytoin
- Antimycobacterials: Rifabutin, rifampin, rifapentine
- Glucocorticoid (systemic): Dexamethasone (more than a single-dose treatment)
- Herbal product: St John’s wort (Hypericum perforatum)
5 WARNINGS AND PRECAUTIONS
4 CONTRAINDICATIONS
6 ADVERSE REACTIONS
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 reactionsb | 83% | 37% | 0 | 0 |
Pyrexia c | 8% | 2% | 0 | 0 |
Fatigue d | 5% | 1% | <1% | <1% |
Headache | 4% | <1% | <1% | <1% |
Musculoskeletal paine | 3% | 1% | <1% | 0 |
Nausea | 3% | <1% | 1% | <1% |
Sleep disorders f | 2% | <1% | <1% | 0 |
Dizziness | 2% | <1% | <1% | 0 |
Rashg | 2% | <1% | 0 | 0 |
Injection Site Reactions | FLAIR and ATLAS | ATLAS-2M | |
---|---|---|---|
Cabotegravir plus Rilpivirine Once Monthly (n = 591) | Cabotegravir plus Rilpivirine Once Every 2 Months (n = 522) | Cabotegravir plus Rilpivirine Once Monthly (n = 523) | |
Any injection site reaction | 83% | 75% | 75% |
Pain/discomfort | 79% | 73% | 71% |
Nodules | 14% | 10% | 17% |
Induration | 12% | 8% | 7% |
Swelling | 8% | 6% | 5% |
Erythema | 4% | 2% | 3% |
Pruritus | 4% | 5% | 5% |
Bruising/discoloration | 3% | 2% | 2% |
Warmth | 2% | 1% | 2% |
Hematoma | 2% | <1% | 3% |
Laboratory Parameter | FLAIR and ATLAS | ATLAS-2M | ||
---|---|---|---|---|
Cabotegravir plus Rilpivirine Once Monthly (n = 591) | Current Antiretroviral Regimen (n = 591) | Cabotegravir plus Rilpivirine Once Every 2 Months (n = 522) | Cabotegravir plus Rilpivirine Once Monthly (n = 523) | |
ALT (≥5.0 x ULN) | 2% | <1% | <1% | <1% |
AST (≥5.0 x ULN) | 2% | <1% | <1% | <1% |
Total bilirubin (≥2.6 x ULN) | <1% | <1% | <1% | <1% |
Creatine phosphokinase (≥10.0 x ULN) | 8% | 4% | 3% | 4% |
Lipase (≥3.0 x ULN) | 5% | 3% | 3% | 2% |
7 DRUG INTERACTIONS
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 Rifapentine |
↓Cabotegravir ↓Rilpivirine | |
Antimycobacterial: Rifabutin | ↓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: Methadonea | ↔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. |
a See Clinical Pharmacology (12.3) for magnitude of interaction.
8 USE IN SPECIFIC POPULATIONS
- Trials in adults [see Clinical Studies (14.1)]
- MOCHA (NCT03497676) trial in adolescents
10 OVERDOSAGE
11 DESCRIPTION


12 CLINICAL PHARMACOLOGY
Table 9. Pharmacokinetic Properties of the Components of CABENUVA
Cabotegravir | Rilpivirine | |
---|---|---|
Absorptiona | ||
Tmax (days), median | 7 | 3 to 4 |
Distribution | ||
% Bound to human plasma proteins | >99.8 | 99.7 |
Blood-to-plasma ratio | 0.52 | 0.7 |
CSF-to-plasma concentration ratio (median [range])b | 0.003 (0.002 to 0.004) | 0.01 (BLQ to 0.02) |
Elimination | ||
t1/2 (weeks) meanc | 5.6 to 11.5 | 13 to 28 |
Metabolism | ||
Metabolic pathways | UGT1A1 UGT1A9 (minor) | CYP3A |
Excretion | ||
Major route of elimination | Metabolism | Metabolism |
% of dose excreted as total 14C (unchanged drug) in urined | 27 (0) | 6 (<1) |
% of dose excreted as total 14C (unchanged drug) in fecesd | 59 (47) | 85 (26) |
Drug | Dosing Phase | Dosage Regimen | Geometric Mean (5th, 95th Percentile)a | ||
---|---|---|---|---|---|
AUC(0-tau)b (mcg•h/mL) | Cmax (mcg/mL) | Ctaub (mcg/mL) | |||
Cabotegravir | Oral lead-inc | 30 mg once daily | 145 (93.5, 224) | 8.0 (5.3, 11.9) | 4.6 (2.8, 7.5) |
Initial injection (after oral lead-in)d | 600 mg IM initial dose | 1,591 (714; 3,245) | 8.0 (5.3, 11.9) | 1.5 (0.65, 2.9 | |
Initial injection (direct to injection)e | 600 mg IM initial dose | — | 1.89 (0.438, 5.69) | 1.43 (0.403, 3.90) | |
Monthly injectionf | 400 mg IM monthly | 2,415 (1,494; 3,645) | 4.2 (2.5, 6.5) | 2.8 (1.7, 4.6) | |
Every-2-month injectionf | 600 mg IM every 2 months | 3,764 (2,431; 5,857) | 4.0 (2.3, 6.8) | 1.6 (0.8, 3.0) | |
Drug | Dosing Phase | Dosage Regimen | Geometric Mean (5th, 95th Percentile)a | ||
AUC(0-tau)b (ng•h/mL) | Cmax (ng/mL) | Ctaub (ng/mL) | |||
Rilpivirine | Oral lead-inc,g | 25 mg once daily | 2,083 (1,125; 3,748) | 116 (48.6, 244) | 79.4 (31.8, 177) |
Initial injection (after oral lead-in)d | 900 mg IM initial dose | 44,842 (21,712; 87,575) | 144 (93.9, 221) | 41.9 (21.7, 78.9) | |
Initial injection (direct to injection)e | 900 mg IM initial dose | — | 68 (27.5, 220) | 48.9 (17.7, 138) | |
Monthly injectionf | 600 mg IM monthly | 68,324 (39,042; 118,111) | 121 (68.1, 210) | 85.8 (49.6, 147) | |
Every-2-month injectionf | 900 mg IM every 2 months | 132,450 (76,638; 221,783) | 138 (80.6, 228) | 68.9 (38.0, 119) |
Drug | Dosing Phase | Dosage Regimen | Geometric Mean (5th, 95th Percentile)a | |||
---|---|---|---|---|---|---|
AUC(0-tau)b (mcg•h/mL) | Cmax (mcg/mL) | Ctau (mcg/mL) | ||||
Cabotegravir | Oral lead-inc | 30 mg once daily | 193 (106, 346) | 14.4 (8.02, 25.5) | 5.79 (2.48, 12.6) | |
Initial injectiond | 600 mg IM initial dose | 2,123 (881; 4,938) | 11.2 (5.63, 21.5) | 1.84 (0.64, 4.52) | ||
Every-2-month injection e | 600 mg IM every 2-months | 4,871 (2,827; 8,232) | 7.23 (3.76, 14.1) | 2.01 (0.64, 4.73) | ||
Every-1-month injectione | 400 mg IM every 1 month | 3,222 (1,879; 5,406) | 7.88 (4.41, 13.8) | 3.65 (1.63, 7.49) | ||
Every-2-months injectione | 600 mg IM every 2 months | 4,871 (2,827; 8,232) | 7.23 (3.76, 14.1) | 2.01 (0.64, 4.73) | ||
Drug | Dosing Phase | Dosage Regimen | Geometric Mean (5th, 95th Percentile) | |||
AUC(0-tau)b (ng•h/mL) | Cmax (ng/mL) | Ctau (ng/mL) | ||||
Rilpivirine | Oral lead-inc | 25 mg PO once daily | 2,389 (1,259; 4,414) | 144 (80.8, 234) | 82.5 (37.5, 167) | |
Initial injectiond | 900 mg IM initial dose | 41,515 (19,301; 82,646) | 156 (93.4, 246) | 39.7 (20.0, 78.2) | ||
Every-1-month injectione | 600 mg IM every month | 74,717 (40,243; 136,114) | 128 (67.8, 233) | 97.3 (51.1, 175) | ||
Every-2-months injectione | 900 mg IM every 2 months | 114,139 (61,432; 206,214) | 111 (57.6, 212) | 63.1 (32.9, 117) |
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 | ||
---|---|---|---|---|---|
Cmax | AUC | Ctau or C24 |
Etravirine 200 mg twice daily |
30 mg once daily |
12 |
1.04 (0.99, 1.09) |
1.01 (0.96, 1.06) |
1.00 (0.94, 1.06) |
Rifabutin 300 mg once daily |
30 mg once daily |
12 |
0.83 (0.76, 0.90) |
0.77 (0.74, 0.83) |
0.74 (0.70, 0.78) |
Rifampin 600 mg once daily |
30-mg single dose |
15 |
0.94 (0.87, 1.02) |
0.41 (0.36, 0.46) |
0.50 (0.44, 0.57 |
Rilpivirine 25 mg once daily |
30 mg once daily |
11 |
1.05 (0.96, 1.15) |
1.12 (1.05, 1.19) |
1.14 (1.04, 1.24) |
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 | ||
---|---|---|---|---|---|
Cmax | AUC | Ctau or C24 | |||
Acetaminophen 500-mg single dose |
150 mg once dailya |
16 |
1.09 (1.01 to 1.18) |
1.16 (1.10 to 1.22) |
1.26 (1.16 to 1.38) |
Atorvastatin
40 mg once daily |
150 mg once dailya |
16 |
0.91 (0.79 to 1.06) |
0.90 (0.81 to 0.99) |
0.90 (0.84 to 0.96) |
Chlorzoxazone 500-mg single dose taken 2 hours after rilpivirine |
150 mg once dailya |
14 |
1.79 (1.56 to 2.06) |
2.30
(1.98 to 2.67) |
2.78
(2.39 to 3.24) |
Didanosine 400 mg once daily delayed-release capsules taken 2 hours before rilpivirine |
150 mg once dailya |
21 |
1.00 (0.90 to 1.10) |
1.00 (0.95 to 1.06) |
1.00 (0.92 to 1.09) |
Ethinyl estradiol/norethindrone 0.035 mg once daily/1 mg once daily |
25 mg once daily |
15 | ↔b | ↔b | ↔b |
Ketoconazole 400 mg once daily |
150 mg once dailyb |
15 |
1.30
(1.13 to 1.48) |
1.49 (1.31 to 1.70) |
1.76 (1.57 to 1.97) |
Lopinavir/ritonavir 400/100 mg twice daily (soft gel capsule) |
150 mg once dailya |
15 |
0.96 (0.88 to 1.05) |
0.99 (0.89 to 1.10) |
0.89 (0.73 to 1.08) |
Methadone 60 to 100 mg once daily, individualized dose |
25 mg once daily | 12 | ↔b | ↔b | ↔b |
Raltegravir 400 mg twice daily |
25 mg once daily |
23 |
1.12 (1.04 to 1.20) |
1.12 (1.05 to 1.19) |
1.03 (0.96 to 1.12) |
Rifabutin 300 mg once daily |
25 mg once daily |
18 |
0.69 (0.62 to 0.76) |
0.58 (0.52 to 0.65) |
0.52 (0.46 to 0.59) |
Rifabutin 300 mg once daily |
50 mg once daily |
18 |
1.43 (1.30 to 1.56) |
1.16 (1.06 to 1.26) |
0.93 (0.85 to 1.01) |
(reference arm for comparison was 25 mg once-daily rilpivirine administered alone) | |||||
Rifampin 600 mg once daily |
150 mg once dailya |
16 |
0.31 (0.27 to 0.36) |
0.20 (0.18 to 0.23) |
0.11 (0.10 to 0.13) |
Sildenafil 50-mg single dose |
75 mg once dailya |
16 |
0.92 (0.85 to 0.99) |
0.98 (0.92 to 1.05) |
1.04 (0.98 to 1.09) |
Tenofovir disoproxil fumarate 300 mg once daily |
150 mg once dailya |
16 |
0.96 (0.81 to 1.13) |
1.01 (0.87 to 1.18) |
0.99 (0.83 to 1.16) |
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 | ||
---|---|---|---|---|---|
Cmax | AUC | Ctau or C24 | |||
Ethinyl estradiol 0.03 mg once daily |
30 mg once daily |
19 |
0.92 (0.83, 1.03) |
1.02 (0.97, 1.08) |
1.00 (0.92, 1.10) |
Levonorgestrel 0.15 mg once daily |
30 mg once daily |
19 |
1.05 (0.96, 1.15) |
1.12 (1.07, 1.18) |
1.07 (1.01, 1.15) |
Midazolam 3 mg |
30 mg once daily |
12 |
1.09 (0.94, 1.26) |
1.10 (0.95, 1.26) |
NA |
Rilpivirine 25 mg once daily |
30 mg once daily |
11 |
0.96 (0.85, 1.09) |
0.99 (0.89, 1.09) |
0.92 (0.79, 1.07) |
Coadministered Drug(s) and Dose(s) | Dose of Rilpivirine | n | Geometric Mean Ratio (90% CI) of Coadministered Drug Pharmacokinetic Parameters with/without EDURANT No Effect = 1.00 | ||
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Cmax | AUC | Cmin | |||
Acetaminophen 500-mg single dose |
150 mg once dailya |
16 |
0.97 (0.86 to 1.10) |
0.91 (0.86 to 0.97) |
NA |
Atorvastatin 40 mg once daily |
150 mg once dailya |
16 |
1.35 (1.08 to 1.68) |
1.04 (0.97 to 1.12) |
0.85 (0.69 to 1.03) |
2-hydroxy-atorvastatin |
1.58 (1.33 to 1.87) |
1.39 (1.29 to 1.50) |
1.32 (1.10 to 1.58) |
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4-hydroxy-atorvastatin |
1.28 (1.15 to 1.43) |
1.23 (1.13 to 1.33) |
NA | ||
Chlorzoxazone 500-mg single dose taken 2 hours after rilpivirine |
150 mg once dailya |
16 |
0.98 (0.85 to 1.13) |
1.03 (0.95 to 1.13) |
NA |
Darunavir/ritonavir 800/100 mg once daily |
150 mg once dailya |
15 |
0.90 (0.81 to 1.00) |
0.89 (0.81 to 0.99) |
0.89 (0.68 to 1.16) |
Didanosine 400 mg once daily delayed-release capsules taken 2 hours before rilpivirine |
150 mg once dailya |
13 |
0.96 (0.80 to 1.14) |
1.12 (0.99 to 1.27) |
NA |
Digoxin 0.5-mg single dose |
25 mg once daily |
22 |
1.06 (0.97 to 1.17) |
0.98 (0.93 to 1.04)c |
NA |
Ethinyl estradiol 0.035 mg once daily |
25 mg once daily |
17 |
1.17 (1.06 to 1.30) |
1.14 (1.10 to 1.19) |
1.09 (1.03 to 1.16) |
Norethindrone 1 mg once daily |
0.94 (0.83 to 1.06) |
0.89 (0.84 to 0.94) |
0.99 (0.90 to 1.08) |
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Ketoconazole 400 mg once daily |
150 mg once dailya |
14 |
0.85 (0.80 to 0.90) |
0.76 (0.70 to 0.82) |
0.34 (0.25 to 0.46) |
Lopinavir/ritonavir 400/100 mg twice daily (soft gel capsule) |
150 mg once dailya |
15 |
0.96 (0.88 to 1.05) |
0.99 (0.89 to 1.10) |
0.89 (0.73 to 1.08) |
Methadone 60 to 100 mg once daily, individualized dose |
25 mg once daily |
13 | |||
R(‑) methadone |
0.86 (0.78 to 0.95) |
0.84 (0.74 to 0.95) |
0.78 (0.67 to 0.91) |
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S(+) methadone |
0.87 (0.78 to 0.97) |
0.84 (0.74 to 0.96) |
0.79 (0.67 to 0.92) |
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Metformin 850-mg single dose |
25 mg once daily |
20 |
1.02 (0.95 to -1.10) |
0.97 (0.90 to 1.06)b |
NA |
Raltegravir 400 mg twice daily |
25 mg once daily |
23 |
1.10 (0.77 to 1.58) |
1.09 (0.81 to 1.47) |
1.27 (1.01 to 1.60) |
Rifampin 600 mg once daily |
150 mg once dailya |
16 |
1.02 (0.93 to 1.12) |
0.99 (0.92 to 1.07) |
NA |
25-desacetylrifampin |
1.00 (0.87 to 1.15) |
0.91 (0.77 to 1.07) |
NA | ||
Sildenafil 50-mg single dose |
75 mg once dailya |
16 |
0.93 (0.80 to 1.08) |
0.97 (0.87 to 1.08) |
NA |
N-desmethyl-sildenafil |
0.90 (0.80 to 1.02) |
0.92 (0.85 to 0.99)c |
NA | ||
Tenofovir disoproxil fumarate 300 mg once daily |
150 mg once dailya |
16 |
1.19 (1.06 to 1.34) |
1.23 (1.16 to 1.31) |
1.24 (1.10 to 1.38) |
FLAIR CAB+RPV N = 283 | FLAIR CAR N = 283 | ATLAS CAB+RPV N = 308 | ATLAS CAR N = 308 | ATLAS-2M Q4W N = 523 | ATLAS-2M Q8W N = 522 | |
---|---|---|---|---|---|---|
Total confirmed virologic failures | 5 | 4 | 3 | 4 | 2 | 9 |
Subtype A1b | 4/8 (50%) | 1/4 (25%) | 1/17 (6%) | 0/21 (0%) | 0/30 (0%) | 4/31 (13%) |
+L74Ic | 4/5 (80%) | 1/3 (33%) | 1/16 (6%) | 0/19 (0%) | 2/28 (0%) | 3/26 (12%) |
-L74I | 0/3 (0%) | 0/1 (0%) | 0/1 (0%) | 0/2 (0%) | 0/2 (0%) | 1/5 (20%) |
Other subtypes | 2/268 (0.7%) | 3/272 (1%) | 2/240 (0.8%) | 4/252 (1.6%) | 2/409 (0.5%) | 5/415 (1.2%) |
+L74Ic | 0/49 (0%) | 1/43 (2.3%) | 1/29 (3%) | 1/39 (2.6%) | 0/42 (0%) | 2/48 (4%) |
-L74I | 0/219 (2.5%) | 2/229 (0.9%) | 1/211 (0.5%) | 3/213 (1.4%) | 2/367 (0.5%) | 3/367 (0.8%) |
Missing data | 7 | 7 | 51 | 35 | 84 | 76 |
With NNRTI RASd | NA | NA | 3/78 (4%) | 2/83 (2%) | 1/128 (0.8%) | 7/117 (6%) |
Without NNRTI RAS | NA | NA | 0/179 (0%) | 2/190 (1%) | 1/310 (0.3%) | 2/327 (0.6%) |
Missing data | NA | NA | 51 | 35 | 84 | 76 |
13 NONCLINICAL TOXICOLOGY
14 CLINICAL STUDIES
- Trial 201584 (FLAIR [NCT02938520]), (n = 629): HIV-1–infected, antiretroviral treatment (ART)-naive subjects received a dolutegravir INSTI-containing regimen for 20 weeks (either dolutegravir/abacavir/lamivudine or dolutegravir plus 2 other NRTIs if subjects were HLA-B*5701 positive). Subjects who were virologically suppressed (HIV-1 RNA) < 50 copies/mL, n = 566) were then randomized (1:1) to receive either a cabotegravir plus rilpivirine regimen or remain on the current antiretroviral regimen. Subjects randomized to receive cabotegravir plus rilpivirine initiated treatment with daily oral lead-in dosing with one 30-mg VOCABRIA (cabotegravir) tablet plus one 25-mg EDURANT (rilpivirine) tablet for at least 4 weeks followed by monthly injections with CABENUVA for an additional 44 weeks [see Dosage and Administration (2.2, 2.3)].
- Trial 201585 (ATLAS [NCT02951052]), (n = 616): HIV-1–infected, ART-experienced, virologically-suppressed (for at least 6 months; median prior treatment duration was 4.3 years) subjects (HIV-1 RNA <50 copies/mL) were randomized and received either a cabotegravir plus rilpivirine regimen or remained on their current antiretroviral regimen. Subjects randomized to receive cabotegravir plus rilpivirine initiated treatment with daily oral lead-in dosing with one 30-mg VOCABRIA (cabotegravir) tablet plus one 25-mg EDURANT (rilpivirine) tablet for at least 4 weeks followed by monthly injections with CABENUVA for an additional 44 weeks [see Dosage and Administration (2.2, 2.3)].
Virologic Outcomes | FLAIR Monthly Dosing | ATLAS Monthly Dosing | ||
---|---|---|---|---|
CAB plus RPV (n = 283) | CAR (n = 283) | CAB plus RPV (n = 308) | CAR (n = 308) | |
HIV-1 RNA ≥50 copies/mLa | 2% | 2% | 2% | 1% |
Treatment difference | -0.4% (95% CI: -2.8%, 2.1%) | 0.7% (95% CI: -1.2%, 2.5%) | ||
HIV-1 RNA <50 copies/mL | 94% | 93% | 93% | 95% |
No virologic data at Week 48 window | 4% | 4% | 6% | 4% |
Discontinued due to adverse event or death | 3% | <1% | 4% | 2% |
Discontinued for other reasons | 1% | 4% | 2% | 2% |
Missing data during window but on study | 0 | 0 | 0 | 0 |
Baseline Factors | FLAIR Monthly Dosing | ATLAS Monthly Dosing | ||
---|---|---|---|---|
CAB plus RPV (N = 283) n/N (%) | CAR (N = 283) n/N (%) | CAB plus RPV (N = 308) n/N (%) | CAR (N = 308) n/N (%) | |
Baseline CD4+ (cells/mm3) | ||||
<350 | 0/19 | 1/27 (4%) | 0/23 | 1/27 (4%) |
≥350 to <500 | 3/64 (5%) | 0/60 | 2/56 (4%) | 0/60 |
≥500 | 3/200 (2%) | 6/196 (3%) | 3/299 (1%) | 2/224 (<1%) |
Gender | ||||
Male | 3/220 (1%) | 6/219 (3%) | 3/209 (1%) | 3/204 (1%) |
Female | 3/63 (5%) | 1/64 (2%) | 2/99 (2%) | 0/104 |
Race | ||||
White | 6/216 (3%) | 5/201 (2%) | 3/214 (1%) | 2/207 (<1%) |
African American/African Heritage | 0/47 | 2/56 (4%) | 2/62 (3%) | 1/77 (1%) |
Asian/Other | 0/20 | 0/24 | 0/32 | 0/24 |
Body mass index | ||||
<30 kg/m2 | 3/243 (1%) | 7/246 (3%) | 3/248 (1%) | 1/242 (<1%) |
≥30 kg/m2 | 3/40 (8%) | 0/37 | 2/60 (3%) | 2/66 (3%) |
Age (years) | ||||
<50 | 5/250 (2%) | 6/254 (2%) | 4/242 (2%) | 2/212 (<1%) |
≥50 | 1/33 (3%) | 1/29 (3%) | 1/66 (2%) | 1/96 (1%) |
Baseline antiviral therapy at randomization | ||||
Protease inhibitor-containing regimen | 0 | 0 | 1/51 (2%) | 0/54 |
Integrase inhibitor-containing regimen | 6/283 (2%) | 7/283 (2%) | 0/102 | 2/99 (2%) |
Non-nucleoside reverse transcriptase inhibitor-containing regimen | 0 | 0 | 4/155 (3%) | 1/155 (<1%) |
- Trial 207966 (ATLAS-2M [NCT03299049]), (n = 1,045): HIV-1–infected, ART‑experienced, virologically suppressed subjects, including 504 subjects from the ATLAS trial (randomized to CAB plus RPV [n = 253] or CAR [n = 251]; prior exposure to cabotegravir plus rilpivirine [n = 391]), were randomized and received a cabotegravir plus rilpivirine regimen administered as injection doses of cabotegravir 400 mg plus rilpivirine 600 mg either monthly or cabotegravir 600 mg plus rilpivirine 900 mg every 2 months. Subjects without prior exposure to cabotegravir plus rilpivirine initiated treatment with daily oral lead-in dosing with one 30-mg VOCABRIA (cabotegravir) tablet plus one 25-mg EDURANT (rilpivirine) tablet for at least 4 weeks followed by monthly or every-2-month injections with CABENUVA for an additional 44 weeks.
Virologic Outcomes | Cabotegravir plus Rilpivirine | |
---|---|---|
Every-2-Month Dosing n = 522 | Monthly Dosing n = 523 | |
HIV-1 RNA ≥50 copies/mLa | 2% | 1% |
Treatment difference | 0.8 (95% CI: -0.6%, 2.2%) | |
HIV-1 RNA <50 copies/mL | 94% | 94% |
No virologic data at Week 48 window | 4% | 6% |
Discontinued study due to adverse event or death | 2% | 3% |
Discontinued for other reasons | 2% | 3% |
Missing data during window but on study | 0 | 0 |
Baseline Factors | Cabotegravir plus Rilpivirine | |
---|---|---|
Every-2-Month Dosing (N = 522) n/N (%) |
Monthly Dosing (N = 523) n/N (%) |
|
Baseline CD4+ (cells/mm3) | ||
<350 | 1/35 (3%) | 1/27 (4%) |
≥350 to <500 | 1/96 (1%) | 0/89 |
≥500 | 7/391 (2%) | 4/407 (1%) |
Gender | ||
Male | 4/385 (1%) | 5/380 (1%) |
Female | 5/137 (4%) | 0/143 |
Race | ||
White | 5/370 (1%) | 5/393 (1%) |
Black/African American Asian/Other | 4/101 (4%) 0/51 | 0/90 0/40 |
Body mass index | ||
<30 kg/m2 | 3/409 (1%) | 3/425 (1%) |
≥30 kg/m2 | 6/113 (5%) | 2/98 (2%) |
Age (years) | ||
<35 | 4/137 (3%) | 1/145 (1%) |
35 to <50 | 3/242 (1%) | 2/239 (1%) |
≥50 | 2/143 (1%) | 2/139 (1%) |
Prior exposure to cabotegravir plus rilpivirine | ||
None | 5/327 (2%) | 5/327 (2%) |
1 to 24 Weeks | 3/69 (4%) | 0/68 |
>24 Weeks | 1/126 (1%) | 0/128 |
Baseline third-agent class | ||
Protease inhibitor-containing regimen | 1/40 (3%) | 1/30 (3%) |
Integrase inhibitor-containing regimen | 3/136 (2%) | 2/141 (1%) |
NNRTI-containing regimen | 1/151 (1%) | 2/156 (1%) |
Cabotegravir plus rilpivirine | 4/195 (2%) | 0/196 |
16 HOW SUPPLIED/STORAGE AND HANDLING
- 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
- 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.
17 PATIENT COUNSELING INFORMATION
PATIENT PACKAGE INSERT
PATIENT INFORMATION | |
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CABENUVA [KAB-en-ew-vah] | |
(cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension) | |
co-packaged for intramuscular use | |
What is CABENUVA? CABENUVA is a prescription medicine that is used without other human immunodeficiency virus-1 (HIV-1) medicines to treat HIV-1 infection in people 12 years of age and older who weigh at least 77 pounds (35 kg) to replace their current HIV-1 medicines when their healthcare provider determines that they meet certain requirements. HIV-1 is the virus that causes acquired immune deficiency syndrome (AIDS). CABENUVA contains 2 different medicines:
It is not known if CABENUVA is safe and effective in children younger than 12 years of age or weighing less than 77 pounds (35 kg). |
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Do not receive CABENUVA if you:
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Before you receive CABENUVA, tell your healthcare provider about all your medical conditions, including if you:
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Some medicines interact with CABENUVA. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine. You can ask your healthcare provider or pharmacist for a list of medicines that interact with CABENUVA. Do not start taking a new medicine without telling your healthcare provider. Your healthcare provider can tell you if it is safe to take CABENUVA with other medicines. |
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How will I receive CABENUVA?
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What are the possible side effects of CABENUVA? CABENUVA may cause serious side effects including:
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The most common side effects of CABENUVA include: | |
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These are not all the possible side effects of CABENUVA. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1‑800‑FDA‑1088. | |
General information about the safe and effective use of CABENUVA.
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. You can ask your healthcare provider or pharmacist for information about CABENUVA that is written for health professionals. |
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What are the ingredients in CABENUVA?
Cabotegravir extended-release injectable suspension: Active ingredient: cabotegravir Inactive ingredients: mannitol, polyethylene glycol (PEG) 3350, polysorbate 20, and Water for Injection. Rilpivirine extended-release injectable suspension: Active ingredient: rilpivirine Inactive ingredients: citric acid monohydrate, poloxamer 338, Water for Injection, glucose monohydrate to ensure isotonicity, sodium dihydrogen phosphate monohydrate, and sodium hydroxide to adjust pH. |
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Manufactured for: ViiV Healthcare Durham, NC 27701 |
by: GlaxoSmithKline Durham, NC 27701 and Janssen Pharmaceuticals Titusville, NJ 08560 |
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. The maker of this brand is not affiliated with and does not endorse the ViiV Healthcare group of companies or its products. ©2023 ViiV Healthcare group of companies or its licensor. CBN:5PIL For more information, go to WWW.CABENUVA.COM or call 1-877-844-8872. |
INSTRUCTIONS FOR USE
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Overview:
A complete dose of CABENUVA requires two injections: 400 mg (2 mL) of cabotegravir and 600 mg (2 mL) of rilpivirine. Cabotegravir and rilpivirine are suspensions that do not need further dilution or reconstitution. The preparation steps for both medicines are the same. Cabotegravir and rilpivirine are for gluteal intramuscular use only. Each injection must be administered to separate gluteal intramuscular sites (on opposite sides or at least 2 cm apart). The administration order is not important. Note: The ventrogluteal site is recommended. |
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Storage information | |||||
Store in refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze. |
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Prior to administration: | |||||
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Your pack contains: | |||||
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You will also need: | |||||
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Preparation: | |||||
1. Inspect the vial. | |||||
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Note: The Cabotegravir vial has a brown tint to the glass. Do not use if the expiration date has passed. |
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Wait 15 minutes | |||||
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3. Shake the vial vigorously. | |||||
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Remove the vial cap. | |||||
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Do not allow anything to touch the rubber stopper after wiping it. |
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5. Peel open the vial adapter. | |||||
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Note: Keep the adapter in place in its packaging for the next step. |
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6. Attach the vial adapter. | |||||
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See Figure F. |
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7. Prepare the syringe. | |||||
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8. Attach the syringe. | |||||
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See Figure H. |
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9. Slowly draw up the dose. | |||||
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10. Unscrew the syringe. | |||||
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Unscrew the syringe from the vial adapter, holding the vial adapter as shown. See Figure J. Note: Keep the syringe upright to avoid leakage. Check that the suspension looks uniform and milky white. | ||||
11. Prepare the injection site. | |||||
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Injection: | |||||
12. Prepare the injection site. | |||||
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Note: For gluteal intramuscular use only. Do not inject intravenously. |
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13. Remove the cap. | |||||
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14. Remove extra liquid from the syringe. | |||||
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Note: Clean the injection site with an alcohol wipe. Allow the skin to air dry before continuing. |
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15. Stretch the skin. | |||||
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Use the z-track injection technique to minimize medicine leakage from the injection site.
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16. Insert the needle. | |||||
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17. Inject the dose of medicine. | |||||
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18. Assess the injection site. | |||||
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Do not massage the area. |
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19. Make the needle safe. | |||||
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See Figure S. |
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After injection: | |||||
20. Dispose safely. | |||||
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Repeat for 2nd medicine. | |||||
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Questions and Answers | |||||
1. How long can the medicines be left out of the refrigerator?
It is best to inject the medicines as soon as they reach room temperature. However, the vials may sit in the carton at room temperature (maximum temperature of 25°C [77°F]) for up to 6 hours; do not put back into the refrigerator. If not used within 6 hours, the medicines must be discarded. 2. How long can the medicines be left in the syringes? It is best to inject the (room temperature) medicines as soon as possible after drawing them up. However, the medicines can remain in the syringes for up to 2 hours before injection. 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. 3. Why do I need to inject air into the vials? Injecting 1 mL of air into the vials makes it easier to draw up the medicines into the syringes. Without the air, some liquid may flow back into the vials unintentionally, leaving less medicine than intended in the syringes. 4. Does the order in which I give the medicines matter? No, the order is unimportant. 5. Is it safe to warm the vials up to room temperature more quickly? It is best to let the vials come to room temperature naturally. However, you can use the warmth of your hands to speed up the warm-up time, but make sure the vials do not get above 25°C (77°F). Do not use any other heating methods. |
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Manufactured for:
ViiV Healthcare Durham, NC 27701 |
by: GlaxoSmithKline Durham, NC 27701 and Janssen Pharmaceuticals Titusville, NJ 08560 |
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Trademarks are owned by or licensed to the ViiV Healthcare group of companies.
©2023 ViiV Healthcare group of companies or its licensor. CBN:4IFU2 |
This Instructions for Use has been approved by the U.S. Food and Drug Administration. Â Â Revised: 2/2023
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Overview:
A complete dose of CABENUVA requires two injections: 600 mg (3 mL) of cabotegravir and 900 mg (3 mL) of rilpivirine. Cabotegravir and rilpivirine are suspensions that do not need further dilution or reconstitution. The preparation steps for both medicines are the same. Cabotegravir and rilpivirine are for gluteal intramuscular use only. Each injection must be administered to separate gluteal intramuscular sites (on opposite sides or at least 2 cm apart). The administration order is not important. Note: The ventrogluteal site is recommended. |
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Storage information | |||||
Store in refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze. |
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Prior to administration: | |||||
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Your pack contains: | |||||
Consider the patient’s build and use medical judgment to select an appropriate injection needle length. |
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You will also need: | |||||
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Preparation: | |||||
1. Inspect the vial. | |||||
![]() |
Note: The Cabotegravir vial has a brown tint to the glass. Do not use if the expiration date has passed. |
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Wait 15 minutes | |||||
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3. Shake the vial vigorously. | |||||
![]() |
|
||||
Remove the vial cap. | |||||
![]() |
Do not allow anything to touch the rubber stopper after wiping it. |
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5. Peel open the vial adapter. | |||||
![]() |
Note: Keep the adapter in place in its packaging for the next step. |
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6. Attach the vial adapter. | |||||
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See Figure F. |
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7. Prepare the syringe. | |||||
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8. Attach the syringe. | |||||
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See Figure H. |
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9. Slowly draw up the dose. | |||||
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10. Unscrew the syringe. | |||||
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Unscrew the syringe from the vial adapter, holding the vial adapter as shown. See Figure J. Note: Keep the syringe upright to avoid leakage. Check that the suspension looks uniform and milky white. | ||||
11. Prepare the injection site. | |||||
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Injection: | |||||
12. Prepare the injection site. | |||||
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Note: For gluteal intramuscular use only. Do not inject intravenously. |
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13. Remove the cap. | |||||
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14. Remove extra liquid from the syringe. | |||||
![]() |
Note: Clean the injection site with an alcohol wipe. Allow the skin to air dry before continuing. |
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15. Stretch the skin. | |||||
![]() |
Use the z-track injection technique to minimize medicine leakage from the injection site.
|
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16. Insert the needle. | |||||
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17. Inject the dose of medicine. | |||||
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18. Assess the injection site. | |||||
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Do not massage the area. |
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19. Make the needle safe. | |||||
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See Figure S. |
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After injection: | |||||
20. Dispose safely. | |||||
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Repeat for 2nd medicine. | |||||
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Questions and Answers | |||||
1. How long can the medicine be left out of the refrigerator?
It is best to inject the medicines as soon as they reach room temperature. However, the vials may sit in the carton at room temperature (maximum temperature of 25°C [77°F]) for up to 6 hours; do not put back into the refrigerator. If not used within 6 hours, the medicines must be discarded. 2. How long can the medicines be left in the syringes? It is best to inject the (room temperature) medicines as soon as possible after drawing them up. However, the medicines can remain in the syringes for up to 2 hours before injection. 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. 3. Why do I need to inject air into the vials? Injecting 1 mL of air into the vials makes it easier to draw up the medicines into the syringes. Without the air, some liquid may flow back into the vials unintentionally, leaving less medicine than intended in the syringes. 4. Does the order in which I give the medicines matter? No, the order is unimportant. 5. Is it safe to warm the vials up to room temperature more quickly? It is best to let the vials come to room temperature naturally. However, you can use the warmth of your hands to speed up the warm-up time, but make sure the vials do not get above 25°C (77°F). Do not use any other heating methods. |
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Manufactured for:
ViiV Healthcare Durham, NC 27701 |
by: GlaxoSmithKline Durham, NC 27701 and Janssen Pharmaceuticals Titusville, NJ 08560 |
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Trademarks are owned by or licensed to the ViiV Healthcare group of companies.
©2023 ViiV Healthcare group of companies or its licensor. CBN:5IFU3 |
PRINCIPAL DISPLAY PANEL
NDC 49702-253-15
CABENUVA
Cabotegravir extended-release
injectable suspension
400 mg/2 mL
(200 mg/mL)
co-packaged with
Rilpivirine extended-release
injectable suspension
600 mg/2 mL
(300 mg/mL)
Rx Only
For gluteal intramuscular use only.
Healthcare Professional administration only.
- 1 Cabotegravir single-dose vial
- 1 Rilpivirine single-dose vial
- 2 Vial adapters
- 2 Syringes
- 2 Injection needles (23 gauge, 1 ½ inch)
- 2 Syringe labels
- Prescribing Information
- Patient Information
- Instructions for Use
Store in refrigerator at 2°C to 8°C (36°F to 46°F).
Do not freeze.
Discard unused portion.
Prior to administration, bring vials to room temperature (not to exceed 25°C (77°F). Vials may remain at room temperature for up to 6 hours. If not used within 6 hours, they must be discarded.
400 mg/600 mg Kit
Cabotegravir – Made in Singapore
Rilpivirine – Made in Belgium
©2019 ViiV Healthcare group of companies or its licensor.
62000000045124 Rev. 12/19

PRINCIPAL DISPLAY PANEL
NDC 49702-240-15
CABENUVA
Cabotegravir extended-release
injectable suspension
600 mg/3 mL
(200 mg/mL)
co-packaged with
Rilpivirine extended-release
injectable suspension
900 mg/3 mL
(300 mg/mL)
Rx Only
For gluteal intramuscular use only.
Healthcare Professional administration only.
- 1 Cabotegravir single-dose vial
- 1 Rilpivirine single-dose vial
- 2 Vial adapters
- 2 Syringes
- 2 Injection needles (23 gauge, 1 ½ inch)
- 2 Syringe labels
- Prescribing Information
- Patient Information
- Instructions for Use
Store in refrigerator at 2°C to 8°C (36°F to 46°F).
Do not freeze.
Discard unused portion.
Prior to administration, bring vials to room temperature (not to exceed 25°C (77°F). Vials may remain at room temperature for up to 6 hours. If not used within 6 hours, they must be discarded.
600 mg/900 mg Kit
Cabotegravir – Made in Singapore
Rilpivirine – Made in Belgium
©2019 ViiV Healthcare group of companies or its licensor.
62000000045131 Rev. 12/19

INGREDIENTS AND APPEARANCE
CABENUVA cabotegravir and rilpivirine kit |
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---|---|---|---|---|---|
PRODUCT INFORMATION | |||||
Product Type | HUMAN PRESCRIPTION DRUG | Item Code (Source) | NDC:49702-253 | ||
PACKAGING | |||||
# | Item Code | Package Description | Marketing Start Date | Marketing End Date | |
1 | NDC:49702-253-15 | 1 in 1 CARTON; Type 0: Not a Combination Product | 01/21/2021 | ||
QUANTITY OF PARTS | |||||
Part # | Package Quantity | Total Product Quantity | |||
Part 1 | 1 VIAL | 1 mL | |||
Part 2 | 1 VIAL | 1 ML | |||
Part 1 of 2 CABOTEGRAVIR cabotegravir injection, suspension, extended release |
|||||
PRODUCT INFORMATION | |||||
Item Code (Source) | NDC:49702-245 | ||||
Route of Administration | INTRAMUSCULAR | ||||
ACTIVE INGREDIENT/ACTIVE MOIETY | |||||
Ingredient Name | Basis of Strength | Strength | |||
CABOTEGRAVIR (UNII: HMH0132Z1Q) (CABOTEGRAVIR - UNII:HMH0132Z1Q) |
CABOTEGRAVIR |
200 mg in 1 mL |
|||
INACTIVE INGREDIENTS | |||||
Ingredient Name | Strength | ||||
MANNITOL (UNII: 3OWL53L36A) | |||||
POLYSORBATE 20 (UNII: 7T1F30V5YH) | |||||
POLYETHYLENE GLYCOL 3350 (UNII: G2M7P15E5P) | |||||
WATER (UNII: 059QF0KO0R) | |||||
PRODUCT CHARACTERISTICS | |||||
Color | WHITE (white to light pink) | Score | |||
Shape | Size | ||||
Flavor | Imprint Code | ||||
Contains | |||||
PACKAGING | |||||
# | Item Code | Package Description | Marketing Start Date | Marketing End Date | |
1 | NDC:49702-245-01 | 2 mL in 1 VIAL; Type 0: Not a Combination Product | |||
MARKETING INFORMATION | |||||
Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date | ||
NDA | NDA212888 | 01/21/2021 | |||
PRODUCT INFORMATION | |
---|---|
Item Code (Source) | Route of Administration |
NDC:49702-249 | INTRAMUSCULAR |
ACTIVE INGREDIENT/ACTIVE MOIETY | ||
---|---|---|
Ingredient Name | Basis of Strength | Strength |
RILPIVIRINE (UNII: FI96A8X663) (RILPIVIRINE - UNII:FI96A8X663) | RILPIVIRINE | 300 mg in 1 mL |
INACTIVE INGREDIENTS | |
---|---|
Ingredient Name | Strength |
POLOXAMER 338 (UNII: F75JV2T505) | |
CITRIC ACID MONOHYDRATE (UNII: 2968PHW8QP) | |
DEXTROSE MONOHYDRATE (UNII: LX22YL083G) | |
SODIUM PHOSPHATE, MONOBASIC, MONOHYDRATE (UNII: 593YOG76RN) | |
SODIUM HYDROXIDE (UNII: 55X04QC32I) | |
WATER (UNII: 059QF0KO0R) |
PACKAGING | ||||
---|---|---|---|---|
# | Item Code | Package Description | Marketing Start Date | Marketing End Date |
1 | NDC:49702-249-02 | 2 mL in 1 VIAL; Type 0: Not a Combination Product |
MARKETING INFORMATION | |||||
---|---|---|---|---|---|
Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date | ||
NDA | NDA212888 | 01/21/2021 |
MARKETING INFORMATION | |||||
---|---|---|---|---|---|
Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date | ||
NDA | NDA212888 | 01/21/2021 |
cabotegravir and rilpivirine kit
PRODUCT INFORMATION | |
---|---|
Product Type | Item Code (Source) |
HUMAN PRESCRIPTION DRUG | NDC:49702-240 |
PACKAGING | ||||
---|---|---|---|---|
# | Item Code | Package Description | Marketing Start Date | Marketing End Date |
1 | NDC:49702-240-15 | 1 in 1 CARTON; Type 0: Not a Combination Product | 01/21/2021 |
QUANTITY OF PARTS | ||
---|---|---|
Part # | Package Quantity | Total Product Quantity |
Part 1 | 0 VIAL | 1 mL |
Part 2 | 0 VIAL | 1 mL |
PRODUCT INFORMATION | |
---|---|
Item Code (Source) | Route of Administration |
NDC:49702-238 | INTRAMUSCULAR |
ACTIVE INGREDIENT/ACTIVE MOIETY | ||
---|---|---|
Ingredient Name | Basis of Strength | Strength |
CABOTEGRAVIR (UNII: HMH0132Z1Q) (CABOTEGRAVIR - UNII:HMH0132Z1Q) | CABOTEGRAVIR | 200 mg in 1 mL |
INACTIVE INGREDIENTS | |
---|---|
Ingredient Name | Strength |
MANNITOL (UNII: 3OWL53L36A) | |
POLYSORBATE 20 (UNII: 7T1F30V5YH) | |
POLYETHYLENE GLYCOL 3350 (UNII: G2M7P15E5P) | |
WATER (UNII: 059QF0KO0R) |
PRODUCT CHARACTERISTICS | |||||
---|---|---|---|---|---|
Color | WHITE (white to light pink) | Score | |||
Shape | Size | ||||
Flavor | Imprint Code | ||||
Contains |
PACKAGING | ||||
---|---|---|---|---|
# | Item Code | Package Description | Marketing Start Date | Marketing End Date |
1 | NDC:49702-238-01 | 3 mL in 1 VIAL; Type 0: Not a Combination Product |
MARKETING INFORMATION | |||||
---|---|---|---|---|---|
Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date | ||
NDA | NDA212888 | 01/21/2021 |
PRODUCT INFORMATION | |
---|---|
Item Code (Source) | Route of Administration |
NDC:49702-243 | INTRAMUSCULAR |
ACTIVE INGREDIENT/ACTIVE MOIETY | ||
---|---|---|
Ingredient Name | Basis of Strength | Strength |
RILPIVIRINE (UNII: FI96A8X663) (RILPIVIRINE - UNII:FI96A8X663) | RILPIVIRINE | 300 mg in 1 mL |
INACTIVE INGREDIENTS | |
---|---|
Ingredient Name | Strength |
POLOXAMER 338 (UNII: F75JV2T505) | |
CITRIC ACID MONOHYDRATE (UNII: 2968PHW8QP) | |
DEXTROSE MONOHYDRATE (UNII: LX22YL083G) | |
SODIUM PHOSPHATE, MONOBASIC, MONOHYDRATE (UNII: 593YOG76RN) | |
SODIUM HYDROXIDE (UNII: 55X04QC32I) | |
WATER (UNII: 059QF0KO0R) |
PACKAGING | ||||
---|---|---|---|---|
# | Item Code | Package Description | Marketing Start Date | Marketing End Date |
1 | NDC:49702-243-02 | 3 mL in 1 VIAL; Type 0: Not a Combination Product |
MARKETING INFORMATION | |||||
---|---|---|---|---|---|
Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date | ||
NDA | NDA212888 | 01/21/2021 |
MARKETING INFORMATION | |||||
---|---|---|---|---|---|
Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date | ||
NDA | NDA212888 | 01/21/2021 |
ESTABLISHMENT | |||||
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Name | Address | ID/FEI |