Cabotegravir
Clinical data | |
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Trade names | Vocabria, Apretude |
Other names | S/GSK1265744, GSK744 |
AHFS/Drugs.com | Monograph |
MedlinePlus | a621010 |
License data |
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Pregnancy category | |
intramuscular | |
ATC code | |
Legal status | |
Legal status | |
UGT1A1 | |
Metabolites | glucuronide |
Elimination half-life | tablets: 41 hours injection: 5.6–11.5 weeks |
Excretion | 47% via feces, 27% via urine |
Identifiers | |
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Cabotegravir, sold under the brand name Vocabria among others, is a
It is an integrase inhibitor with a carbamoyl pyridone structure similar to that of dolutegravir.[14]
In December 2021, the U.S. Food and Drug Administration approved cabotegravir for pre-exposure prophylaxis (PrEP) in at-risk people under the brand name Apretude.[15] In September 2023, it was approved for pre-exposure prophylaxis in the European Union.[11]
Medical uses
Cabotegravir in combination with
The two medicines are the first antiretroviral drugs that come in a long-acting injectable formulation.[16]
Cabotegravir (Apretude) is indicated for use in at-risk people weighing at least 35 kilograms (77 lb) for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV.[15]
Contraindications and interactions
Cabotegravir must not be combined with the drugs
Adverse effects
The most common side effects of the injectable combination therapy with rilpivirine are reactions at the injection site (in up to 84% of patients) such as
Pharmacology
Mechanism of action
Cabotegravir is an
Pharmacokinetics
When taken by mouth, cabotegravir reaches highest blood plasma levels after three hours. Taking the drug together with food slightly increases its concentrations in the blood, but this is not clinically relevant. After injection into the muscle, cabotegravir is slowly absorbed into the bloodstream, reaching its highest blood plasma levels after about seven days.[13]
Over 99% of the substance are bound to
Elimination has only been studied for oral administration: Most of the drug is eliminated via the faeces in unchanged form (47%). It is not known how much of this amount comes from the bile, and how much was not absorbed in the first place. (The bile actually contains the glucuronide, but this could be broken up again in the gut lumen to give the parent substance that is observed in the faeces.) To a lesser extent it is excreted via the urine (27%), almost exclusively as the glucuronide.[13]
Pharmacogenomics
UGT1A1
Chemistry
Cabotegravir is a white to off-white, crystalline powder that is practically insoluble in
Formulation
In studies, the agent was packaged into nanoparticles (GSK744LAP) conferring a biological half-life of 21 to 50 days[citation needed] following a single dose. The marketed injection achieves its long half-life not via nanoparticles but with a suspension of the free cabotegravir acid. The tablets contain cabotegravir sodium salt.[21]
History
Cabotegravir was examined in the clinical trials HPTN 083 and HPTN 084.[22][23]
Society and culture
Legal status
In 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Vocabria intended for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in combination with rilpivirine injection.[24] The EMA also recommended marketing authorization be given for rilpivirine and cabotegravir injections to be used together for the treatment of people with HIV-1 infection.[16] Cabotegravir was approved for medical use in the European Union in December 2020.[9]
In December 2021, the U.S. Food and Drug Administration (FDA) approved cabotegravir for pre-exposure prophylaxis.[15] The FDA granted the approval of Apretude to Viiv.[15]
Zimbabwe became the first African country to approve the drug in October 2022.[25]
Names
Cabotegravir is the United States Adopted Name (USAN)[26] and the international nonproprietary name (INN).[27]
Research
Pre-exposure prophylaxis
In 2020, results for some studies were released showing success in using injectable cabotegravir for long-acting pre-exposure prophylaxis (PrEP) with greater efficacy than the emtricitabine/tenofovir combination being widely used for PrEP at the time.[28][29]
The safety and efficacy of cabotegravir to reduce the risk of acquiring HIV were evaluated in two randomized, double-blind trials that compared cabotegravir to emtricitabine/tenofovir, a once daily oral medication for HIV PrEP.[15] Trial 1 included HIV-uninfected men and transgender women who have sex with men and have high-risk behavior for HIV infection.[15] Trial 2 included uninfected cisgender women at risk of acquiring HIV.[15]
In Trial 1, 4,566 cisgender men and transgender women who have sex with men received either cabotegravir or emtricitabine/tenofovir.[15] The trial measured the rate of HIV infections among trial participants taking daily cabotegravir followed by cabotegravir injections every two months compared to daily oral emtricitabine/tenofovir.[15] The trial showed participants who took cabotegravir had 69% less risk of getting infected with HIV when compared to participants who took emtricitabine/tenofovir.[15]
In Trial 2, 3,224 cisgender women received either cabotegravir or emtricitabine/tenofovir.[15] The trial measured the rate of HIV infections in participants who took oral cabotegravir and injections of cabotegravir compared to those who took emtricitabine/tenofovir orally.[15] The trial showed participants who took cabotegravir had 90% less risk of getting infected with HIV when compared to participants who took emtricitabine/tenofovir.[15]
References
- ^ a b c "Vocabria (cabotegravir) film-coated tablets Product Information". TGA eBS. 12 June 2021. Archived from the original on 13 June 2021. Retrieved 12 June 2021.
- ^ a b "Vocabria". Therapeutic Goods Administration (TGA). 26 February 2021. Archived from the original on 9 September 2021. Retrieved 8 September 2021.
- FDA. Retrieved 22 October 2023.
- ^ "Summary for ARTG Entry: 323721 VOCABRIA cabotegravir (as sodium) 30 mg film-coated tablet, bottle". Therapeutic Goods Administration. The Government of Australia. 13 August 2021.[permanent dead link]
- ^ "Vocabria Product information". Health Canada. 25 April 2012. Archived from the original on 24 February 2021. Retrieved 22 January 2021.
- ^ a b c d e f g "Vocabria- cabotegravir sodium tablet, film coated". DailyMed. Archived from the original on 15 June 2021. Retrieved 12 June 2021.
- ^ a b "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. This article incorporates text from this source, which is in the public domain.
- ^ "Apretude- cabotegravir kit". DailyMed. Archived from the original on 25 December 2021. Retrieved 24 December 2021.
- ^ a b "Vocabria EPAR". European Medicines Agency (EMA). 13 October 2020. Archived from the original on 14 July 2021. Retrieved 22 January 2021. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
- ^ "Vocabria Product information". Union Register of medicinal products. Archived from the original on 5 March 2023. Retrieved 3 March 2023.
- ^ a b "Apretude EPAR". European Medicines Agency. 20 September 2023. Archived from the original on 6 October 2023. Retrieved 20 September 2023.
- ^ "Apretude Product information". Union Register of medicinal products. 20 September 2023. Archived from the original on 6 October 2023. Retrieved 1 October 2023.
- ^ a b c d e f g h i "Vocabria: EPAR – Product information" (PDF). European Medicines Agency. 5 January 2021. Archived (PDF) from the original on 10 April 2021. Retrieved 23 February 2021.
- S2CID 184399045.
- ^ a b c d e f g h i j k l m "FDA Approves First Injectable Treatment for HIV Pre-Exposure Prevention". U.S. Food and Drug Administration (FDA) (Press release). 20 December 2021. Archived from the original on 22 April 2022. Retrieved 21 December 2021. This article incorporates text from this source, which is in the public domain.
- ^ a b c "First long-acting injectable antiretroviral therapy for HIV recommended approval" (Press release). European Medicines Agency (EMA). 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.
- ^ "Cabenuva- cabotegravir and rilpivirine kit". DailyMed. Archived from the original on 15 June 2021. Retrieved 12 June 2021.
- ^ "Edurant- rilpivirine hydrochloride tablet, film coated". DailyMed. Archived from the original on 28 October 2020. Retrieved 12 June 2021.
- ^ "Rilpivirine Monograph for Professionals". Drugs.com. 24 September 2020. Archived from the original on 10 April 2021. Retrieved 12 June 2021.
- S2CID 182950312.
- ^ a b "Vocabria: EPAR – Public assessment report" (PDF). European Medicines Agency. 5 January 2021. Archived (PDF) from the original on 10 April 2021. Retrieved 24 February 2021.
- ^ "HPTN083 — Prevention Now". HIV Prevention Trials Network. Archived from the original on 27 July 2018. Retrieved 2 December 2017.
- ^ "HPTN084 — Prevention Now". HIV Prevention Trials Network. Archived from the original on 27 July 2018. Retrieved 2 December 2017.
- ^ "Vocabria: Pending EC decision". European Medicines Agency (EMA). 16 October 2020. Archived from the original on 1 January 2021. Retrieved 16 October 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
- ^ Chingono N (20 October 2022). "Zimbabwe becomes first African nation to approve HIV prevention drug". The Guardian. Archived from the original on 7 February 2023. Retrieved 21 October 2022.
- ^ "Adopted USANs" (PDF). American Medical Association. Retrieved 19 September 2014.
- hdl:10665/331088.
- ^ Ryan G (7 July 2020). "Injectable PrEP Is Even More Effective Than Daily Truvada". Poz. Archived from the original on 13 June 2021. Retrieved 9 November 2020.
- ^ Ryan G (9 November 2020). "For Women, Injectable Cabotegravir Is More Effective Than Truvada as PrEP". Poz. Archived from the original on 8 May 2021. Retrieved 9 November 2020.