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THE SAFETY OF APRETUDE HAS BEEN INVESTIGATED IN >3,500 STUDY PARTICIPANTS GLOBALLY[1–3]

APRETUDE is generally well tolerated with low discontinuation rates

In HIV Prevention Trials Network (HPTN) 083, which included >2,000 cisgender men and transgender women who have sex with men, 5.7% (n=130/2,282) discontinued due to adverse events (AEs).[4]

Grade 2+ AEs occured in:[3]

0%
of participants in the APRETUDE arm (n=2,106/2,280)
0%
of participants in the tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) arm (n=2,116/2,282)

APRETUDE demonstrated a similar AE profile to TDF/FTC (excluding injection site reactions [ISRs])[3]

Adapted from Landovitz RJ et al. 2021.

APRETUDE is generally well tolerated with low discontinuation rates

In HPTN 084, which included >1,500 cisgender women, 1.1% (n=17/1,614) receiving APRETUDE discontinued due to AEs.[2]

Grade 2+ AEs occured in:[3]

0%
of participants in 
the APRETUDE arm (n=1,487/1,614)
0%
of participants in 
the TDF/FTC arm 
(n=1,486/1,610)

APRETUDE demonstrated a similar AE profile to TDF/FTC (excluding ISRs)[2]

Adapted from Delany-Moretlwe S et al. 2022.

82% (n=1,740/2,117) of participants receiving APRETUDE experienced at least one ISR, most of which were mild to moderate:[1,3]

  • 80% of ISRs were grade 1 or 2
  • No grade 4 reactions were reported
  • 2.4% (n=50/2,117) of participants discontinued APRETUDE as a result of ISRs
  • The median duration of overall ISR events was 4 days
  • The proportion of individuals reporting ISRs at each visit, and the severity, decreased over time

No new safety concerns were identified in the 12-month unblinded phase of HPTN 083.[3]

38% (n=577/1,519) of participants receiving APRETUDE experienced at least one ISR, most of which were mild to moderate:[1,2]

  • 0% of participants discontinued APRETUDE as a results of ISRs
  • The median duration of overall ISR events was 8 days
  • The proportion of individuals reporting ISRs at each visit, and the severity, decreased over time

No new safety concerns were identified in the 12-month unblinded phase of HPTN 084.[5]

Drug interactions (based on studies with oral cabotegravir)[1]

WARNINGS AND PRECAUTIONS[1]

  • Overall HIV-1 infection prevention strategy

    • Apretude may not always be effective in preventing HIV-1 infection Cabotegravir concentrations associated with significant antiviral activity are achieved and maintained within hours after initiation of oral lead-in and within 7 days from the first injection (without oral lead-in). The exact time from initiation of Apretude for HIV-1 PrEP to maximal protection against HIV-1 infection is unknown.
    • APRETUDE should be used for pre-exposure prophylaxis (PrEP) as part of an overall HIV-1 infection prevention strategy including the use of other HIV-1 prevention measures (e.g., knowledge of HIV-1 status, regular testing for other sexually transmitted infections, condom use)

  • Potential risk of resistance

    • There is a potential risk of developing resistance to cabotegravir if an individual acquires HIV-1 either before or during administration of APRETUDE, or following discontinuation of APRETUDE
    • To minimise this, it is essential to clinically reassess individuals for risk of HIV acquisition and to frequently test to confirm HIV-negative status. Individuals who are diagnosed with HIV-1 should immediately begin antiretroviral therapy
    • APRETUDE alone does not constitute a complete regimen for the treatment of HIV-1, and HIV-1 resistance mutations have emerged in some individuals with undetected HIV-1 infection who were only taking APRETUDE
    • Alternative forms of PrEP should be considered following discontinuation of APRETUDE for those individuals at continuing risk of HIV acquisition and initiated within 2 months of the final APRETUDE injection
    • APRETUDE should only be used to reduce the risk of acquiring HIV-1 in individuals confirmed to be HIV negative (see contraindications). Individuals should be re-confirmed to be HIV negative at each subsequent injection of APRETUDE
    • If clinical symptoms consistent with acute viral infection are present and recent (<1 month) exposures to HIV-1 are suspected, HIV-1 status should be re-confirmed
    • A combined antigen/antibody test as well as an HIV-ribonucleic acid (RNA)-based test should both be negative. Prescribers are advised to perform both tests, even if the result of the HIV-RNA-based test will become available after the APRETUDE injection. If a combined testing strategy including both tests is not available, ensure testing follows local guidelines

  • Importance of adherence

    • Individuals should be counselled periodically to strictly adhere to the recommended APRETUDE dosing schedule in order to reduce the risk of HIV-1 acquisition and the potential development of resistance

  • Long-acting properties of APRETUDE

    • Residual concentrations of APRETUDE may remain in the systemic circulation of individuals for prolonged periods (up to 12 months or longer), therefore, physicians should take the prolonged release characteristics of APRETUDE into consideration when the medicinal product is discontinued and alternative non-long-acting forms of PrEP are taken, as long as or at any time the risk of acquiring HIV is present in the months after discontinuation of APRETUDE

  • Hypersensitivity reactions

    • Hypersensitivity reactions have been reported in association with integrase inhibitors including APRETUDE. These reactions were characterised by rash, constitutional findings, and sometimes organ dysfunction, including liver injury 
    • APRETUDE and other suspected medicinal products should be discontinued immediately, should signs or symptoms of hypersensitivity develop (including, but not limited to, severe rash, or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial oedema, hepatitis, eosinophilia, or angioedema). Clinical status, including liver aminotransferases, should be monitored and appropriate therapy initiated

  • Hepatotoxicity

    • Hepatotoxicity has been reported in a limited number of individuals receiving cabotegravir with or without known pre-existing hepatic disease. Administration of cabotegravir oral lead-in was used in clinical studies to help identify individuals who may be at risk of hepatotoxicity.
    • Clinical and laboratory monitoring are recommended and Apretude should be discontinued if hepatotoxicity is confirmed, and individuals managed as clinically indicated.

  • Adolescents

    • Suicidal ideation and suicide attempts have been reported with APRETUDE, particularly in those with pre-existing psychiatric illness
    • Although clinical studies did not show an increased incidence of psychiatric illness in adolescents compared to adult subjects, given the vulnerability of the adolescent population, adolescents should be counselled before prescribing, and periodically while receiving APRETUDE, and managed as clinically indicated

  • Contraindications

    APRETUDE is contraindicated in individuals:

    • With hypersensitivity to the active substance, or to any of the following excipients: mannitol (E421), polysorbate 20 (E432), macrogol (E1521), water for injections
    • Receiving rifampicin, rifapentine, phenytoin, phenobarbital, carbamazepine, or oxcarbazepine
    • With unknown or positive HIV-1 status

Please refer to the Summary of Product Characteristics for a full list of adverse events, serious adverse events and prescribing considerations.

Considerations for APRETUDE during pregnancy or breastfeeding[1]

Women of childbearing potential should be counselled about prolonged release characteristics of cabotegravir injection. If a woman plans a pregnancy, the benefits and the risks of starting/continuing PrEP with Apretude should be discussed

APRETUDE injection is not recommended during pregnancy unless the expected benefit justifies the potential risk to the foetus. APRETUDE has been detected in systemic circulation for up to 12 months or longer after an injection, therefore, consideration should be given to the potential for foetal exposure during pregnancy.[1]

It is expected that APRETUDE will be secreted into human milk based on animal data, although this has not been confirmed in humans. APRETUDE may be present in human milk for up to 12 months or longer after the last APRETUDE injection. It is recommended that women breastfeed only if the expected benefit justifies the potential risk to 
the infant.[1]

Dosing and administration of APRETUDE

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AE, adverse event; HIV-1, human immunodeficiency virus type 1; HPTN, HIV Prevention Trials Network; ISR, injection site reaction; PrEP, pre-exposure prophylaxis; 
RNA, ribonucleic acid; TDF/FTC, tenofovir disoproxil fumarate/emtricitabine.

References:

  1. APRETUDE (cabotegravir) Summary of Product Characteristics (SmPC).
  2. Delany-Moretlwe S et al. Lancet. 2022;399(10337):1779–1789.
  3. Landovitz RJ et al. N Engl J Med. 2021;385(7):595–608.
  4. Landovitz RJ et al. N Engl J Med. 2021;385(7):595–608. (Suppl Appendix).
  5. Mascolini M. Presentation at the 24th International AIDS Conference. 29 July–2 August 2022. Montreal, Canada.

PM-GB-CBT-WCNT-240004 November 2024

Prescribing Information

Adverse event reporting

Adverse events should be reported. Reporting forms and information can be found at https://yellowcard.mhra.gov.uk/ or search for MHRA Yellowcard in the Google Play or Apple App store. Adverse events should also be reported to GSK via the GSK Reporting Tool or on 0800 221441.

If you are from outside the UK, you can report adverse events to GSK/ViiV by selecting your region and market, here.