Cabotegravir/rilpivirine

From WikiProjectMed
Jump to navigation Jump to search

Cabotegravir/rilpivirine
Cabotegravir (GSK744).svg
Rilpivirine (TMC278).svg
Combination of
CabotegravirIntegrase strand transfer inhibitor (INSTI)
RilpivirineNon-nucleoside reverse transcriptase inhibitor (NNRTI)
Clinical data
Trade namesCabenuva
AHFS/Drugs.comMultum Consumer Information
MedlinePlusa621009
License data
Pregnancy
category
  • AU: B1
Routes of
administration
Intramuscular
ATC code
  • None
Legal status
Legal status
Identifiers
KEGG

Cabotegravir/rilpivirine, sold under the brand name Cabenuva, is a co-packaged antiretroviral medication for the treatment of HIV/AIDS.[3][4][5][6][7] It contains cabotegravir and rilpivirine in a package with two separate injection vials.[3][4][6]

The most common adverse reactions include injection site reactions, fever or feeling hot (pyrexia), fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness and rash.[3][4][8]

The co-packaged medication was approved for medical use in the United States in January 2021.[4][8][9] It is the first FDA-approved injectable, complete regimen for HIV-infected adults that is administered once a month.[4][5] It is also approved for use in Canada.[1] In the European Union, the two medications are approved separately.[10][11][12]

Medical uses

Cabotegravir/rilpivirine is indicated 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.[3][4] 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.[13]

Contraindications and 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, phenytoin and phenobarbital.[3]

Adverse 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,[12] fatigue, musculoskeletal pain, nausea, sleep disorders, and dizziness.[3]

Pharmacology

Cabotegravir is an integrase strand transfer inhibitor. Rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI).[3]

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.[4][5][8] 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.[4] Trials were conducted at 223 sites in 24 countries including the United States.[8]

In Trial 1, participants who were never treated for the infection before, received an approved therapy for 20 weeks.[8] 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.[8] Participants and the health providers knew which treatments have been given.[8]

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.[8] Participants and the health providers knew which treatments have been given.[8]

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.[13] The two medicines are the first antiretrovirals that come in a long-acting injectable formulation.[13] This means that instead of daily pills, people receive intramuscular injections monthly or every two months.[13] Rilpivirine and cabotegravir were approved for medical use in the European Union in December 2020, as two separate medications.[11][12]

In January 2021, the U.S. Food and Drug Administration (FDA) granted the approval of Cabenuva to ViiV Healthcare.[4][8]

The combination was approved for medical use in Australia in February 2021.[14][15]

References

  1. ^ a b "Cabenuva Product information". Health Canada. 25 April 2012. Retrieved 22 January 2021.
  2. ^ "Summary Basis of Decision (SBD) for Vocabria/Cabenuva". Health Canada. 23 October 2014. Retrieved 29 May 2022.
  3. ^ a b c d e f g h "Cabenuva- cabotegravir and rilpivirine kit". DailyMed. Retrieved 13 February 2021.
  4. ^ a b c d e f g h i j "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. Retrieved 21 January 2021. Public Domain This article incorporates text from this source, which is in the public domain.
  5. ^ a b c d "Cabenuva and Vocabria approved for HIV infection". U.S. Food and Drug Administration (FDA). 27 January 2021. Retrieved 27 January 2021. Public Domain This article incorporates text from this source, which is in the public domain.
  6. ^ a b "ViiV Healthcare announces FDA approval of Cabenuva (cabotegravir, rilpivirine), the first and only complete long-acting regimen for HIV treatment". ViiV Healthcare. 21 January 2021. Retrieved 21 January 2021 – via Business Wire.
  7. ^ Howe ZW, Norman S, Lueken AF, Huesgen E, Farmer EK, Jarrell K, et al. (August 2021). "Therapeutic review of cabotegravir/rilpivirine long-acting antiretroviral injectable and implementation considerations at an HIV specialty clinic". Pharmacotherapy. 41 (8): 686–699. doi:10.1002/phar.2605. PMID 34130357. S2CID 235451020.
  8. ^ a b c d e f g h i j "Drug Trials Snapshot: Cabenuva". U.S. Food and Drug Administration (FDA). 20 January 2021. Retrieved 17 February 2021. Public Domain This article incorporates text from this source, which is in the public domain.
  9. ^ "Drug Approval Package: Cabotegravir". U.S. Food and Drug Administration (FDA). 3 March 2021. Retrieved 14 September 2021.
  10. ^ "Janssen Announces European Commission Authorisation of the First Complete Long-Acting Injectable HIV Treatment in Europe" (Press release). Janssen. Retrieved 22 January 2021 – via Business Wire.
  11. ^ a b "Rekambys EPAR". European Medicines Agency (EMA). 13 October 2020. Retrieved 4 January 2021.
  12. ^ a b c "Vocabria EPAR". European Medicines Agency (EMA). 5 January 2021. Retrieved 5 January 2021.
  13. ^ a b c d "First long-acting injectable antiretroviral therapy for HIV recommended approval". European Medicines Agency (EMA) (Press release). 16 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.
  14. ^ "Australian Public Assessment Report for Cabotegravir sodium and cabotegravir/rilpivirine" (PDF). Therapeutic Goods Administration (TGA). Australian Government Department of Health. May 2021.
  15. ^ "TGA eBS - Product and Consumer Medicine Information Licence".

External links

  • "Cabotegravir". Drug Information Portal. U.S. National Library of Medicine.
  • "Rilpivirine". Drug Information Portal. U.S. National Library of Medicine.
  • 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