Cabotegravir/rilpivirine

Cabotegravir/rilpivirine
Combination of
CabotegravirIntegrase strand transfer inhibitor (INSTI)
RilpivirineNon-nucleoside reverse transcriptase inhibitor (NNRTI)
Names
Trade namesCabenuva
Clinical data
Main usesHIV/AIDS[1]
Side effectsInjection site reactions, fever, tiredness, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, rash[1]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • AU: B1
    Routes of
    use    		Intramuscular
    External links
    AHFS/Drugs.comMonograph
    MedlinePlusa621009
    Legal
    License data
    Legal status

    Cabotegravir/rilpivirine, sold under the brand name Cabenuva, is a co-packaged medication used to treat HIV/AIDS.[1] In those who are at least 12 years old, it is generally all the medications needed to treat the disease.[1] It is given by injection into a muscle.[1] It is packaged with two separate vials.[1]

    Common side effects include injection site reactions, fever, tiredness, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, and rash.[1] Other side effects may include allergic reactions, liver problems, and depression.[1] It contains cabotegravir, an HIV-1 integrase strand transfer inhibitor (INSTI), and rilpivirine, an HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI).[1]

    The combination was approved for medical use in Canada and Europe in 2020 and the United States in 2021.[4][1][2] In Europe, the two medications are approved separately.[5][6] In the United States it costs about 4,400 USD per month as of 2022.[7]

    Medical uses

    Cabotegravir/rilpivirine is used as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults to replace a current antiretroviral regimen in those who are virologically suppressed on a stable antiretroviral regimen with no history of treatment failure.[1][8] In the European Union, the combination is indicated for maintenance treatment of adults who have undetectable HIV levels in the blood (viral load less than 50 copies/mL) with their current antiretroviral treatment, and when the virus has not developed resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) and integrase strand transfer inhibitors.[9]

    Dosage

    It is given as an initial dose of 600 mg of cabotegravir and 900 mg of rilpivirine, followed by 400 mg of cabotegravir and 600 mg of rilpivirine once per month.[1] It may also be used at a dose of 600 mg of cabotegravir and 900 mg of rilpivirine every two months.[1]

    Side effects

    The most common side effects include reactions at the injection site (in up to 84% of patients) such as pain and swelling, as well as headache (up to 12%) and fever or feeling hot (in 10%). Less common side effects (under 10%) are depressive disorders, insomnia, rashes,[6] fatigue, musculoskeletal pain, nausea, sleep disorders, and dizziness.[1]

    Interactions

    Cabotegravir/rilpivirine must not be combined with drugs that induce the liver enzyme CYP3A4, because they accelerate the inactivation of rilpivirine, and/or the enzyme UGT1A1, because they accelerate the inactivation of cabotegravir. These mechanisms potentially result in loss of effectiveness. Examples for such drugs are rifampicin, rifapentine, carbamazepine, oxcarbazepine, eslicarbazepine acetate, phenytoin, primidone, phenobarbital and some glucocorticoids.[1]

    Pharmacology

    Further information: Cabotegravir § Pharmacology, Rilpivirine § Pharmacology, and Reverse-transcriptase inhibitor § Mechanism of action

    Cabotegravir is an integrase strand transfer inhibitor. Rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI).[1]

    History

    The safety and efficacy of cabotegravir/rilpivirine were established through two randomized, open-label, controlled clinical trials (Trial 1/NCT02938520 and Trial 2/NCT02951052) in 1,182 HIV-infected adults who were virologically suppressed (HIV-1 RNA less than 50 copies/milliliter) before initiation of treatment with cabotegravir/rilpivirine.[8][10][11] Participants in both trials continued to show virologic suppression at the conclusion of each study, and no clinically relevant change from baseline in CD4+ cell counts was observed.[8] Trials were conducted at 223 sites in 24 countries including the United States.[11]

    In Trial 1, participants who were never treated for the infection before, received an approved therapy for 20 weeks.[11] Those who did well after this treatment (who had HIV-1 RNA less than 50 copies/milliliter) were then randomized to receive either cabotegravir/rilpivirine (for the first four weeks they received tablets) or to remain on the same therapy for additional 44 weeks.[11] Participants and the health providers knew which treatments have been given.[11]

    In Trial 2, participants who were previously successfully treated for the infection (who had HIV-1 RNA less than 50 copies/milliliter), were randomized to receive either cabotegravir/rilpivirine (for the first four weeks they received tablets) or to remain on the same therapy for additional 44 weeks.[11] Participants and the health providers knew which treatments have been given.[11]

    In October 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended the granting of a marketing authorization for rilpivirine and cabotegravir, to be used together for the treatment of people with human immunodeficiency virus type 1 (HIV-1) infection.[9] The two medicines are the first antiretrovirals that come in a long-acting injectable formulation.[9] This means that instead of daily pills, people receive intramuscular injections monthly or every two months.[9] Rilpivirine and cabotegravir were approved for medical use in the European Union in December 2020, as two separate medications.[5][6]

    In January 2021, the U.S. Food and Drug Administration (FDA) granted the approval of Cabenuva to ViiV Healthcare.[8][11] It is the first FDA-approved injectable, complete regimen for HIV-infected adults that is administered once a month.[8][10]

    The combination was approved for medical use in Australia in February 2021.[12][13]

    References

    1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 "Cabenuva- cabotegravir and rilpivirine kit". DailyMed. Archived from the original on 15 June 2021. Retrieved 13 February 2021.
    2. 1 2 "Cabenuva Product information". Health Canada. 25 April 2012. Archived from the original on 14 May 2021. Retrieved 22 January 2021.
    3. ↑ "Summary Basis of Decision (SBD) for Vocabria/Cabenuva". Health Canada. 23 October 2014. Archived from the original on 30 May 2022. Retrieved 29 May 2022.
    4. ↑ "Janssen Announces European Commission Authorisation of the First Complete Long-Acting Injectable HIV Treatment in Europe" (Press release). Janssen. Archived from the original on 12 November 2021. Retrieved 22 January 2021 – via Business Wire.
    5. 1 2 "Rekambys EPAR". European Medicines Agency (EMA). 13 October 2020. Archived from the original on 8 January 2021. Retrieved 4 January 2021.
    6. 1 2 3 "Vocabria EPAR". European Medicines Agency (EMA). 5 January 2021. Archived from the original on 14 July 2021. Retrieved 5 January 2021.
    7. ↑ "Cabenuva Prices, Coupons, Copay & Patient Assistance". Drugs.com. Archived from the original on 22 April 2021. Retrieved 1 November 2022.
    8. 1 2 3 4 5 "FDA Approves First Extended-Release, Injectable Drug Regimen for Adults Living with HIV". U.S. Food and Drug Administration (FDA) (Press release). 21 January 2021. Archived from the original on 21 January 2021. Retrieved 21 January 2021. Public Domain This article incorporates text from this source, which is in the public domain.
    9. 1 2 3 4 "First long-acting injectable antiretroviral therapy for HIV recommended approval". European Medicines Agency (EMA) (Press release). 16 October 2020. Archived from the original on 17 October 2020. Retrieved 16 October 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
    10. 1 2 "Cabenuva and Vocabria approved for HIV infection". U.S. Food and Drug Administration (FDA). 27 January 2021. Archived from the original on 27 January 2021. Retrieved 27 January 2021. Public Domain This article incorporates text from this source, which is in the public domain.
    11. 1 2 3 4 5 6 7 8 "Drug Trials Snapshot: Cabenuva". U.S. Food and Drug Administration (FDA). 20 January 2021. Archived from the original on 28 July 2021. Retrieved 17 February 2021. Public Domain This article incorporates text from this source, which is in the public domain.
    12. ↑ "Australian Public Assessment Report for Cabotegravir sodium and cabotegravir/rilpivirine" (PDF). Therapeutic Goods Administration (TGA). Australian Government Department of Health. May 2021. Archived (PDF) from the original on 13 June 2021. Retrieved 23 October 2022.
    13. ↑ "TGA eBS - Product and Consumer Medicine Information Licence". Archived from the original on 13 June 2021. Retrieved 23 October 2022.
    Identifiers:
    • "Cabotegravir". Drug Information Portal. U.S. National Library of Medicine. Archived from the original on 29 January 2021. Retrieved 23 October 2022.
    • "Rilpivirine". Drug Information Portal. U.S. National Library of Medicine. Archived from the original on 19 May 2021. Retrieved 23 October 2022.
    • Clinical trial number NCT02938520 for "Study to Evaluate the Efficacy, Safety, and Tolerability of Long-acting Intramuscular Cabotegravir and Rilpivirine for Maintenance of Virologic Suppression Following Switch From an Integrase Inhibitor in HIV-1 Infected Therapy Naive Participants" at ClinicalTrials.gov
    • Clinical trial number NCT02951052 for "Study Evaluating the Efficacy, Safety, and Tolerability of Switching to Long-acting Cabotegravir Plus Long-acting Rilpivirine From Current Antiretroviral Regimen in Virologically Suppressed HIV-1-infected Adults" at ClinicalTrials.gov
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