Sample Cabenuva Protocol and Clinician Reference Guide

By: Mandy Moncayo, PharmD Candidate¹, Caitlan Apping, PharmD Candidate¹, Sheila Montalvo, PharmD, BCPS², Elizabeth Sherman, PharmD, AAHIVP^{1,2, 3}

1. Nova Southeastern University College of Pharmacy, Ft. Lauderdale, Florida
2. Memorial Healthcare System, Hollywood, Florida
3. South Florida – Southeast AIDS Education and Training Center, Miami, Florida

Introduction

The U.S. Food and Drug Administration approved Cabenuva (cabotegravir and rilpivirine, injectable formulation) and Vocabria (cabotegravir, tablet formulation) on January 21, 2021. Cabenuva is the first complete long-acting antiretroviral treatment regimen for those with HIV-1 who are virologically suppressed on their current antiretroviral regimen. Cabenuva is co-packaged into a kit containing cabotegravir extended-release injectable suspension with rilpivirine extended-release injectable suspension. This document represents a sample protocol for the use of Cabenuva in clinical practice and is intended to help guide the clinician through the process of initial patient selection, drug product acquisition, and drug administration. Clinicians should amend this sample protocol template for their own clinic populations and as new information on the drug becomes available.

Patient Selection

• HIV-1 infection
• Virologically suppressed (e.g. HIV-1 RNA < 50 copies/mL for ≥3 months) on current regimen
• No history of treatment failure with a previous regimen from the development of resistance mutation(s)
• No known or suspected resistance to cabotegravir or rilpivirine, based on known NNRTI or INSTI resistance mutations (except for K103N mutation – this mutation is allowed)
• Women of childbearing potential should utilize effective contraception and not plan to become pregnant, per DHHS guideline recommendations. In clinical trials, the following forms of contraception were allowed: subdermal implant, intrauterine device or intrauterine system, combined estrogen/progesterone oral contraceptive, injectable progesterone, percutaneous contraceptive patches, contraceptive vaginal ring, or vasectomy for partner. In clinical trials, participants who became pregnant were switched from Cabenuva to an alternate oral ARV regimen for the remainder of their pregnancies.
• ● For patients taking acid-reducing medications
  • a. Since oral rilpivirine is contraindicated with proton pump inhibitors (PPIs), PPIs should be stopped before the oral lead-in period and should remain stopped during the entire duration of the oral lead-in
  • b. Since injectable rilpivirine does not interact with PPIs, PPI use can resume once monthly injections start
  • c. Oral rilpivirine requires dose separation from H2-receptor antagonists and antacids. Oral cabotegravir requires dose separation from antacids.
    • i. H-receptor antagonists: Administer H2-receptor antagonist at least 12 hours before or at least 4 hours after oral rilpivirine
    • ii. Antacids (e.g. aluminum or magnesium hydroxide, calcium carbonate): Administer antacid at least 2 hours before or at least 4 hours after oral rilpivirine and oral cabotegravir
• If co-infected with hepatitis B, patient must be on effective hepatitis B treatment before starting Cabenuva
  • a. There are no foreseeable drug-drug interactions between Cabenuva and hepatitis B or C medications
• Cannot be currently taking the following medications that are contraindicated with Cabenuva:
  • a. Anticonvulsants
    • i. Carbamazepine
    • ii. Oxcarbazepine
    • iii. Phenobarbital
    • iv. Phenytoin
  • b. Antimycobacterials
    • i. Rifabutin
    • ii. Rifampin
    • iii. Rifapentine
  • c. Glucocorticoids (systemic)
    • i. Dexamethasone (more than a single-dose treatment)
  • d. Herbal product
    • i. St. John’s wort
• History of good adherence and engagement in care with an understanding of the commitment needed to be adherent to monthly healthcare provider administered injections
• Sign the ViiVConnect Enrollment and Patient Authorization & Release Form
  • a. https://www.viivconnect.com/content/dam/cf-viiv/viiv-connect/master/pdf/CABENUVA_Enrollment_Form.pdf 
• Agree to the exact date for starting the oral lead-in therapy, in order to facilitate scheduling subsequent injection appointments
  • a. Patients must understand that the first injection needs to occur on their last day of oral therapy
• No dose adjustment is required for patients with mild, moderate, or severe renal impairment. Cabenuva has not been studied in patients with end stage renal disease, including those receiving dialysis.

Oral Lead-In Period

• Prior to starting monthly injections, patient initiates oral lead-in therapy:
  • a. 30 mg Vocabria (cabotegravir, tablet formulation) and 25 mg Edurant (rilpivirine, tablet formulation) taken once daily with a full meal (e.g., at least 500 calories) for at least 28 days
  • b. Oral lead-in therapy is ONLY available through TheraCom Pharmacy – TheraCom will supply both cabotegravir and rilpivirine pills for the lead-in period. See Appendix A for TheraCom Pharmacy contact information.
• An initial 30 day supply of oral cabotegravir (Vocabria) and oral rilpivirine (Edurant) in separate bottles will be provided for FREE, regardless of insurance, from TheraCom Pharmacy
  • a. The free oral lead-in can be mailed to the patient or to the clinic
  • b. The patient must talk to their provider before starting the oral lead-in therapy so that subsequent monthly injection appointments can be scheduled
• The purpose of the oral lead-in period is to assess for tolerability before starting the long-acting injections
• The most common adverse reactions during the oral-lead in period are headache, nausea, abnormal dreams, anxiety and insomnia
  • a. Advise patients to stop taking the oral lead-in and call the clinic immediately if they experience a hypersensitivity reaction (i.e., rash associated with any of the following symptoms: fever, malaise, tiredness, muscle or joint ache, blisters, swelling or inflammation, difficulty breathing, any symptoms of liver problems)
• The clinic should submit the ViiVConnect Enrollment Form to start a patient on Cabenuva
  • a. The patient will need to sign the ViiVConnect Enrollment Form
  • b. How long does it take from the time the ViiVConnect form is submitted until the patient receives the medication? After submitting the form, it takes 24-28 hours for a benefits investigation, then another 24 hours to approve, and then 3-4 days for shipping and receipt. The oral lead-in will only ship if it is covered by insurance.
  • c. A printable form can be found online at:
    • i. https://www.viivconnect.com/content/dam/cf-viiv/viiv-connect/master/pdf/CABENUVA_Enrollment_Form.pdf 
    •  ii. ViiV fax number: 1-844-208-7676
  • d. The form can also be completed online through the ViiVConnect Portal if the clinician has created a free login
    • i. Direct link to the ViiVConnect Portal: https://www.viivconnectportal.com/viivprovider/s/login/ 
• The ViiVConnect Enrollment Form will serve as the prescription for the oral lead-in. It will be sent directly from ViiV to TheraCom Pharmacy

Monthly Injections

• Each injection appointment will need to factor in an extra 25 minutes for 1) the vials need 15 minutes to come to room temperature before drawing them into the syringe for injection, and 2) the patient should be observed after the injection for 10 minutes to ensure no adverse reactions
• Initiation injection doses (loading dose):
  • a. Single dose of 600 mg cabotegravir (3 mL) AND
  • b. Single dose of 900 mg rilpivirine (3 mL)
  • c. It is given on the last day of oral lead-in therapy
• Continuation injection doses:
  • a. Single dose of 400 mg cabotegravir (2 mL) AND
  • b. Single dose 600 mg rilpivirine (2 mL)
  • c. It is given every month after the initial injection doses
• The time window for scheduling monthly injection appointments is seven days before to seven days after the target treatment date
• Cabenuva injections are delivered into the gluteus muscle
  • a. Each injection needs to be delivered as two separate injections in separate ventrogluteal sites (on opposite sides or 2 cm apart) during the same visit
  • b. It is recommended to administer the injections on opposite sides to reduce injection site pain due to the large volume being injected
  • c. The dorsogluteal site is another injection site option, however, the ventrogluteal site is recommended
  • d. There are insufficient data in patients with gluteal fillers of implants
• Preparation and Administration Instructions
  • a. See package insert; page 39: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/212888s000lbl.pdf 
  • b. Injections are stored at standard refrigeration (2°C to 8°C; 36°F to 46°F). Cabenuva needs to be brought to room temperature (removed from the refrigerator for ≥15 minutes) prior to injection and are stable at room temperature for up to six hours. If not used within six hours, the medication must be discarded. Cabotegravir and rilpivirine can remain in syringes for up to two hours before injecting. If two hours are exceeded, the medication, syringes, and needles must be discarded.
• Patients should be observed in the clinic for 10 minutes after receiving the injections for the emergence of any post-injection reactions
  • a. The most common injection-related adverse events during the clinical trials included injection site reactions, headache, pyrexia, increased body temperature, asthenia, and malaise
• Injection Kit Contents
  • a. 1 vial of cabotegravir
  • b. 1 vial of rilpivirine
  • c. 2 vial adaptors
  • d. 2 syringes
  • e. 2 syringe labels
  • f. 2 needles for intramuscular injection: 23-gauge, 1½ inch needle
• Syringes and needles for IM injections are included in the kit. However, alternate needles (not included in the kit) can be used. For cabotegravir, a 21-25 gauge needle can be used. For rilpivirine, a 21-23 gauge needle can be used.
• For those individuals who are obese (greater than 30 kg/m2), a 2 inch needle (not included in kit) should be used to ensure that injections are administered intramuscularly as opposed to subcutaneously (e.g. www.fisherhealthcare.com/2inchsafetyneedle)
• The vial stoppers are not made with natural rubber latex, so the injections are safe for persons with latex allergies
• If a patient plans to miss a scheduled injection dose by more than seven days, restart on daily oral therapy (also known as bridging) to replace up to 2 consecutive monthly injections
  • a. The daily oral regimen is 30 mg Vocabria (cabotegravir, tablet formulation) and 25 mg Edurant (rilpivirine, tablet formulation) taken once daily with a full meal (e.g., at least 500 calories)
  • b. The oral therapy should begin 1 month from the patient’s last injection dose and continue until injection dosing is restarted
  • c. If the patient misses ≤ 2 months of injections, restart on the maintenance injection doses
  • d. If the patient misses > 2 months of injections, restart on the initiation injection dose (loading dose) for 1 month then continue with maintenance injection doses
• If a patient misses or delays injection therapy by more than seven days and does not take oral therapy, reassess the patient’s determination to continue therapy
• The clinic will need to send a prescription for oral bridging therapy when needed for planned missed injection doses
  • a. Oral cabotegravir (Vocabria) is only available through TheraCom Pharmacy. It may take a few days to ship and arrive. See Appendix A for TheraCom Pharmacy contact information.
  • b. TheraCom will not provide oral rilpivirine (Edurant) for bridging therapy. Edurant is available at a retail pharmacy and will require a separate prescription.
  • c. Advise the patient to maintain oral bridging therapy with BOTH Vocabria and Edurant
• If Cabenuva is discontinued, an alternate ART regimen must be started no later than one month after the final injection of Cabenuva. Residual concentrations of Cabenuva may remain in systemic circulation of patients up to 12 months or longer. These residual concentrations are not expected to affect the exposures of ARVs initiated after the discontinuation of Cabenuva

Coverage

• Insurance Bridge Program
  • ViiV provides coverage of Cabenuva at no cost up to 12 months for eligible commercially insured patients waiting on coverage determinations
  • Coverage by ViiV will end when either the primary insurance comes to a coverage determination or at the end of 12 months
  • Excludes Medicare, Medicaid, ADAP, Tricare, and VA enrollees
  • Submitting the ViiVConnect Patient Enrollment Form is the first step to begin this process. Once the patient is enrolled, ViiV will check the status of coverage each month.
  • Link to more information on the Insurance Bridge Program: https://www.viivconnect.com/content/dam/cf-viiv/viiv-connect/master/pdf/CABENUVA_Bridge_Program_Brochure.pdf
• Patient Assistance Program (PAP)
  • For PAP patients, the drug is covered but the cost to administer the injections is not covered
  • Eligible patients MUST:
    • Live in one of the 50 states, the District of Columbia, or Puerto Rico
    • Have a household income ≤ 500% of the federal poverty level based on household size
    • Not be eligible for Medicaid or Puerto Rico’s Government Health Plan, Mi Salud (Puerto Rico applicants who qualify for Puerto Rico’s Government Health Plan must have documentation of denial of coverage through Mi Salud before applying to ViiV Healthcare PAP)
  • And either:
    • Have no prescription drug coverage OR
    • Have a Medicare Part B, Medicare Part D, or Medicare Advantage Plan and have spent at least $600 or more on out-of-pocket prescription expenses during the calendar year OR
    • Have a private insurance plan limited to generic-only coverage, outpatient use only, or therapeutic exclusion (non-coverage) of drug
  • Patients must fill out Section 8: PATIENT ASSISTANCE PROGRAM (PAP) of the ViiVConnect Enrollment Form for Cabenuva
  • Patients must re-apply for PAP every year
  • Direct link for PAP information and frequently asked questions:
    https://www.viivconnect.com/injectable/patient-assistance-program/ 
• Patient Savings Program (PSP)
  • Helps eligible, enrolled patients with out-of-pocket costs towards Cabenuva including administration fees, deductibles, co-pays, or coinsurance
  • Offers up to $13,000 in assistance for up to 12 months
  • Does not cover doctor’s fees for office visits needed for injections
  • Patients may be eligible if:
    • They have commercial insurance that provides coverage for Cabenuva under medical or pharmacy benefits
    • They are residents of the US (including District of Columbia and Puerto Rico)
  • Patients are NOT eligible if:
    • They are enrolled in a state or federal government-funded medical or prescription insurance plan such as Medicare, Medicaid, VA, or TRICARE
  • ○ PSP is card-free
    • Patients will not receive a card
    • PSP numbers will be stored on a virtual card and sent directly to any provider who needs them
    • If needed, PSP numbers can be accessed by calling ViiVConnect at 1-844-588-3288
  • Once the ViiVConnect Enrollment Form is submitted and processed, a ViiVConnect Access Coordinator will contact the provider to inform of the patient’s eligibility for PSP
  • Direct link to PSP information and to enroll patients online: https://www.viivconnect.com/injectable/patient-savings-program/ 

Acquisition

• The free 30-day oral lead-in of both Vocabria and Edurant is provided by TheraCom Pharmacy only one time at the beginning of therapy
• ViivConnect is available to confirm insurance coverage for the patient to ensure the patient will be able to access injections
  • To begin this process, submit an enrollment form to ViivConnect (www.viicconnect.com) 
  • The enrollment form can be used as a prescription for the oral lead-in and injections
  • If the patient is accessing therapy through a pharmacy, ViivConnect will triage this prescription to the respective pharmacy once coverage is confirmed
  • ViivConnect enrollment is not required to receive the free oral lead-in therapy or for access to Cabenuva
• Monthly injections are available through 14 specialty pharmacies and/or from 6 specialty distributors (see Appendix B for a link to the complete list of all pharmacies and distributors).
• Oral therapy used to replace planned missed injections (also known as bridging therapy) will require two separate prescriptions to different pharmacies
  • Vocabria is only available from TheraCom Pharmacy. The clinician must send a prescription for Vocabria directly to TheraCom to obtain the bridging supply. TheraCom Pharmacy will not dispense Edurant after the initial one-time oral lead-in at the beginning of therapy.
  • The cost of Edurant for oral bridging will be incurred by the patient. ViiV will not supply Edurant for oral bridging therapy for free. Viiv covers the cost of Vocabria for oral bridging.
  • Edurant is available at most retail pharmacies. The clinician must provide a prescription for Edurant to the patient’s pharmacy.
  • Patients must be instructed to begin oral bridging therapy when they have received both medications
• Ordering Cabenuva injections through a specialty pharmacy
  • Performed if the patient’s insurance covers Cabenuva under pharmacy benefits
  • Must order within the specialty pharmacy network
  • Specialty pharmacy processes the claim and ships product to the provider for administration. Monthly shipment schedules must be coordinated between the clinic and the specialty pharmacy.
  • Patients pay any copays or coinsurance directly to the specialty pharmacy
    • Patients enrolled in ViivConnect may use their virtual co-pay card supplied by ViivConnect, that is sent directly to the pharmacy, to assist with out-of-pocket costs
• Ordering Cabenuva injections through a specialty distributor (“Buy and Bill”)
  • Performed if the patient’s insurance covers Cabenuva under medical benefits
  • Buy and Bill allows the clinic to manage the entire acquisition process
  • The clinic purchases Cabenuva directly from the distributor
  • The clinic stores and tracks its inventory of Cabenuva
  • The clinic submits reimbursements claims to payers
  • The clinic collects the copay or coinsurance from each patient
• Direct link for list of specialty pharmacies and specialty distributors: https://www.viivconnect.com/content/dam/cf-viiv/viiv-connect/master/pdf/CABENUVA_ViiVConnect_SP-SD_List_Lbnd.pdf 

Appendices

Contact Information

• ViiVConnect Access Coordinator Phone Number: 1-844-588-3288
• TheraCom Pharmacy
  • Address
    • 345 International Blvd Ste 200 Brooks, KY 40109
  • ViiV Team @ TheraCom
    • Phone: 1-844-276-6299
    • Fax: 1-833-904-1881

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