For virologically suppressed individuals 12 years or older weighing at least 35 kg with HIV-1. See Full Indication.

Dosing and Drug
Interactions of
Every-2-Month CABENUVA

Every-2-month CABENUVA is administered as 2 intramuscular injections by a healthcare professional every 2 months. Adherence to the dosing schedule is strongly recommended.

Recommended Every-2-Month Dosing Schedule

Starting patients on every-2-month CABENUVA injections

Before initiation of CABENUVA, ensure patients agree to the required every-2-month dosing schedule, and counsel patients about the importance of adherence to scheduled dosing visits. Patients who miss a scheduled injection visit should be clinically reassessed to ensure resumption of therapy remains appropriate.

EVERY-2-MONTH DOSING SCHEDULE

Adherence to the every-2-month dosing schedule is strongly recommended. Setting a consistent injection date, the Target Treatment Date, can help keep your patients on track
CABENUVA has dosing flexibility, allowing for injections to be given up to 7 days before or after the Target Treatment Date

IM=intramuscular; LA=long-acting.

Starting patients with oral lead-in

If you would like to assess tolerability, prescribe 2 tablets (1 x 30-mg cabotegravir tablet and 1 x 25-mg rilpivirine tablet) to be taken once daily with a meal for 1 month (at least 28 days).

EVERY-2-MONTH DOSING WITH ORAL LEAD-IN

FLAIR 124-Week: Extension Phase
At Week 124, the safety profile of CABENUVA, when initiated without the oral lead-in phase, was consistent with the overall safety profile observed at Week 48.*

At 4 weeks post-first injection, plasma concentrations of cabotegravir and rilpivirine were similar among patients who started with injections and patients who started with oral lead-in^†

*FLAIR is a phase 3, international, randomized, noninferiority trial in virologically suppressed (HIV-1 RNA <50 copies/mL) adults >18 years of age with HIV-1 (N=566). Patients were randomized to receive either once-monthly CABENUVA after 1 month of oral lead-in with cabotegravir plus rilpivirine, or continue ABC/DTG/3TC or DTG plus 2 NRTIs if HLA-B*5701-positive. Median age was 34 years and 7% of patients had CD4+ cell count <350 cells/mm³. The extension phase of FLAIR from Week 100 to Week 124 examined the efficacy, safety, and pharmacokinetics when initiating patients to CABENUVA with or without oral lead-in.

†For cabotegravir, the geometric mean minimum plasma concentration 4 weeks after CABENUVA administration was 1.43 µg/ml for patients who started with injections vs 1.5 µg/ml for patients who started with oral lead-in. For rilpivirine, the geometric mean minimum plasma concentration 4 weeks after CABENUVA administration was 48.9 ng/mL for patients who started with injections vs 41.9 ng/mL for patients who started with oral lead-in.

Drug-drug interaction recommendations do not vary based on dosing schedule.

Drug-drug Interactions

Recommendations are based on drug-drug interactions observed after oral administration of cabotegravir and rilpivirine or predicted interactions due to the expected magnitude of the interaction and potential loss of virologic response

Concomitant drug class Drug name	Effect on concentration	Recommendation
Anticonvulsants: Carbamazepine Oxcarbazepine Phenobarbital Phenytoin	↓ Cabotegravir ↓ Rilpivirine	Coadministration with CABENUVA is contraindicated due to potential for loss of virologic response and development of resistance.
Antimycobacterials: Rifampin Rifapentine Rifabutin	↓ Cabotegravir ↓ 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 associated with risk of Torsade de Pointes. Where possible, consider alternatives such as azithromycin, which increases rilpivirine concentrations less.
Narcotic analgesic: Methadone	↔︎ Cabotegravir ↔︎ Rilpivirine	No dose adjustment required when starting coadministration with CABENUVA. Clinical monitoring is recommended as methadone maintenance therapy may need to be adjusted in some patients.

↑ = Increase, ↓ = Decrease, ↔︎ = No Change

Switching Recommendations

Switching from once-monthly to every-2-month dosing

RECOMMENDATIONS WHEN SWITCHING FROM ONCE-MONTHLY TO EVERY-2-MONTH DOSING OF CABENUVA

Once-Monthly Dosing Schedule

Every-2-month dosing calendar

Setting a consistent injection date, the Target Treatment Date, can help keep your patients on track. It is recommended that patients receive their monthly injection on the same date each month, making the Target Treatment Date fall between the 1st and 28th of each month.

CABENUVA has dosing flexibility, allowing for continuation injections to be given up to 7 days before or 7 days after the Target Treatment Date.1

Scheduling every-2-month injections

Before initiation of clinician-administered CABENUVA, ensure patients agree to the required every-2-month dosing schedule and counsel patients about the importance of adherence to scheduled dosing visits. Talk to your patients about their availability to attend regular injection visits.

For every-2-month dosing of CABENUVA, 2 intramuscular injections are administered by a healthcare professional every 2 months. Adherence to the dosing schedule is strongly recommended.

Setting a consistent every-2-month injection date, the Target Treatment Date, can help keep your patients on track. It is recommended that patients receive their every-2-month injection on the same date every other month, making the Target Treatment Date fall between the 1st and 28th day of every 2 months to help ensure consistency every 2 months.

The dosing flexibility of every-2-month CABENUVA, allows for continuation injections to be given up to 7 days before or 7 days after the Target Treatment Date, which is referred to as the dosing window.

Create a Treatment Plan

Missed Injections

Continuing every-2-month CABENUVA after missed injections

Adherence to the dosing schedule is strongly recommended. Patients who miss a scheduled injection visit should be clinically reassessed to ensure resumption of therapy remains appropriate.

Planned Missed Injections

If a patient plans to miss a scheduled injection visit by more than 7 days:
- Any fully suppressive oral antiretroviral regimen may be used until injections are resumed, or
- Oral cabotegravir (30-mg tablet) in combination with rilpivirine (25-mg tablet) once daily may be used for up to 2 consecutive months to cover a planned missed injection visit
The first doses of oral therapy should be taken approximately 2 months after the last injection dose of CABENUVA and continued until the day injection dosing is restarted

RESTARTING AFTER PLANNED MISSED INJECTIONS

Unplanned Missed Injections

RESTARTING AFTER UNPLANNED MISSED INJECTIONS

Dosing and administration guide

Download this guide to receive information on:

CABENUVA dosing kits and storage
The CABENUVA dosing schedule
Administering the initiation and continuation injections
Managing missed injections
Injection considerations to share with your patients

Download

Alternative Site for Administration (ASA)

For practices that are not yet equipped to administer CABENUVA injections or prefer to have injections administered to patients off-site, an ASA may be an appropriate option.

Download

What is an ASA?

An ASA is a flexible option for patients to receive CABENUVA injections outside of the prescribing physician’s office. Additionally, ViiVConnect may help you locate an ASA. Please indicate your ASA request on the CABENUVA Enrollment Form.

How to ﬁnd an ASA for your patient

Find an ASA nearby with the CABENUVA ASA Locator Tool located on the ViiVConnect website. Enter the ZIP code or use your location to search for injection facilities within a selected search radius. Inclusion of facilities in this ASA Locator does not imply a referral, recommendation, or endorsement by ViiV Healthcare.

Is your facility interested in becoming an ASA?

If you would like to list your facility on the CABENUVA ASA Locator Tool, download and complete the agreement form on the ASA Locator page.

Drug-drug interactions

Recommendations are based on drug-drug interactions observed after oral administration of cabotegravir or rilpivirine or predicted interactions due to the expected magnitude of the interaction and potential for loss of virologic response¹

Concomitant drug class¹ Drug name	Effect on concentration1	Recommendation1
Anticonvulsants: Carbamazepine Oxcarbazepine Phenobarbital Phenytoin	↓ Cabotegravir ↓ Rilpivirine	Coadministration with CABENUVA is contraindicated due to potential for loss of virologic response and development of resistance.
Antimycobacterials: Rifampin Rifapentine Rifabutin	↓ Cabotegravir ↓ Rilpivirine ↔︎ Rifabutin
Glucocorticoid (systemic): Dexamethasone (more than a single-dose treatment)	↓ Rilpivirine
Herbal product: St John’s wort (Hypericum perforatum)	↓ Rilpivirine
Macrolide or ketolide antibiotics: Clarithromycin Erythromycin Telithromycin	↔︎Cabotegravir ↑ Rilpivirine	Use with caution. Where possible, consider alternatives such as azithromycin (which does not include rilpivirine concentrations).
Narcotic analgesic: Methadone	↔︎ Cabotegravir ↔︎ Rilpivirine	No dose adjustment required. Clinical monitoring is recommended as methadone maintenance therapy may need to be adjusted in some patients.

No interactions related to absorption from the GI tract and no food restrictions with CABENUVA

↑ = Increase, ↓ = Decrease, ↔︎ = No Change

GI=gastrointestinal.

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ARROW

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

Do not use CABENUVA in patients with previous hypersensitivity reaction to cabotegravir or rilpivirine

Do not use CABENUVA in patients receiving carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, systemic dexamethasone (>1 dose), and St John’s wort

WARNINGS AND PRECAUTIONS

Hypersensitivity Reactions:

Hypersensitivity reactions, including cases of drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported during postmarketing experience with rilpivirine-containing regimens. 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

Serious or severe hypersensitivity reactions have been reported in association with other integrase inhibitors and could occur with CABENUVA

Discontinue CABENUVA immediately if signs or symptoms of hypersensitivity reactions develop. Clinical status, including liver transaminases, should be monitored and appropriate therapy initiated. Cabotegravir and rilpivirine oral lead-in may be used to help identify patients who may be at risk of a hypersensitivity reaction

Post-Injection Reactions:

Serious post-injection reactions (reported in less than 1% of subjects) 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 pain (e.g., back and chest). These events may have been associated with accidental intravenous administration and began to resolve within a few minutes after the injection

Carefully follow the Instructions for Use when preparing and administering CABENUVA. The suspensions should be injected slowly via intramuscular injection and avoid accidental intravenous administration. Observe patients briefly (approximately 10 minutes) after the injection. If a post-injection reaction occurs, monitor and treat as clinically indicated

Hepatotoxicity:

Hepatotoxicity has been reported in patients receiving cabotegravir or rilpivirine with or without known pre-existing hepatic disease or identifiable risk factors

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

Depressive Disorders:

Depressive disorders (including depressed mood, depression, major depression, mood altered, mood swings, dysphoria, negative thoughts, suicidal ideation or attempt) have been reported with CABENUVA or the individual products

Promptly evaluate patients with depressive symptoms

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 (see Contraindications and Drug Interactions)

Rilpivirine doses 3 and 12 times higher than the recommended oral dosage can prolong the QTc interval

CABENUVA should be used with caution in combination with drugs with a known risk of Torsade de Pointes

Long-Acting Properties and Potential Associated Risks with CABENUVA:

Residual concentrations of cabotegravir and rilpivirine may remain in the systemic circulation of patients for prolonged periods (up to 12 months or longer). Select appropriate patients who agree to the required monthly or every-2-month injection dosing schedule because non-adherence could lead to loss of virologic response and development of resistance

To minimize the potential risk of developing viral resistance, it is essential to initiate an alternative, fully suppressive antiretroviral regimen no later than 1 month after the final injection doses of CABENUVA when dosed monthly and no later than 2 months after the final injections of CABENUVA when dosed every 2 months. If virologic failure is suspected, switch the patient to an alternative regimen as soon as possible

ADVERSE REACTIONS

The most common adverse reactions in adults (incidence ≥2%, all grades) treated with CABENUVA were injection site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, and rash

The safety of CABENUVA in adolescents is expected to be similar to adults

DRUG INTERACTIONS

Refer to the applicable full Prescribing Information for important drug interactions with CABENUVA, VOCABRIA (cabotegravir), or EDURANT (rilpivirine)

Because CABENUVA is a complete regimen, coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended

Drugs that are strong inducers of UGT1A1 or UGT1A9 are expected to decrease the plasma concentrations of cabotegravir. Drugs that induce or inhibit CYP3A may affect the plasma concentrations of rilpivirine

CABENUVA should be used with caution in combination with drugs with a known risk of Torsade de Pointes

USE IN SPECIFIC POPULATIONS

Pregnancy: There are insufficient human data on the use of CABENUVA during pregnancy to adequately assess a drug-associated risk for birth defects and miscarriage. Discuss the benefit-risk of using CABENUVA during pregnancy and conception and consider that cabotegravir and rilpivirine are detected in systemic circulation for up to 12 months or longer after discontinuing injections of CABENUVA. An Antiretroviral Pregnancy Registry has been established

Lactation: The CDC recommends that HIV‑1−infected mothers in the United States not breastfeed their infants to avoid risking postnatal transmission of HIV-1 infection. Breastfeeding is also not recommended due to the potential for developing viral resistance in HIV-positive infants, adverse reactions in a breastfed infant, and detectable cabotegravir and rilpivirine concentrations in systemic circulation for up to 12 months or longer after discontinuing injections of CABENUVA

INDICATION

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.

Please see full Prescribing Information for CABENUVA.

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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.

Please see full Prescribing Information for CABENUVA.

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CBRWCNT210044 December 2021

Produced in USA.

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Dosing and Drug Interactions of Every-2-Month CABENUVA