APRETUDE

What it is

APRETUDE contains cabotegravir, available as film-coated tablets and prolonged-release suspension for injection. The tablet formulation contains 30 mg cabotegravir as cabotegravir sodium. The injection formulation contains 600 mg cabotegravir as cabotegravir free acid in a 3 mL vial. Cabotegravir inhibits HIV integrase by binding to the integrase active site and blocking the strand transfer step of retroviral deoxyribonucleic acid integration which is essential for the HIV replication cycle.

Approved indications

— Pre-exposure prophylaxis in at-risk adults and adolescents (at least 12 years of age) and weighing at least 35 kg to reduce the risk of sexually acquired HIV-1 infection. — Oral lead-in with APRETUDE tablets to assess tolerability of cabotegravir prior to administration of cabotegravir injections or as short-term oral PrEP in individuals who will miss planned dosing with cabotegravir injections.

Dosing overview

For oral lead-in, APRETUDE tablets are recommended for approximately one month (at least 28 days) at a dose of 30 mg once daily prior to the initiation of APRETUDE injection. The recommended initial APRETUDE injection dose is a single 3 mL (600 mg) intramuscular injection, followed one month later by a second 3 mL (600 mg) intramuscular injection, then a single 3 mL (600 mg) intramuscular injection administered every 2 months. Individuals may be given injections up to 7 days before or after the scheduled dosing date.

Key safety warnings

APRETUDE is not always effective in preventing HIV-1 acquisition and the time to onset of protection after commencing APRETUDE is unknown. Individuals should be re-confirmed to be HIV-negative at frequent intervals, in line with local guidelines but at no more than 3 month intervals, while taking APRETUDE for pre-exposure prophylaxis. There is a potential risk of developing resistance to APRETUDE if an individual acquires HIV-1 either before or during administration of APRETUDE, or following discontinuation of APRETUDE; to minimise this risk, it is essential to clinically reassess individuals for risk of HIV acquisition and to frequently test to confirm HIV negative status. Hypersensitivity reactions have been reported in association with integrase inhibitors, characterised by rash, constitutional findings and sometimes organ dysfunction, including liver injury; discontinue APRETUDE and other suspected agents immediately should signs or symptoms of hypersensitivity develop. Hepatotoxicity has been reported in a limited number of individuals receiving APRETUDE with or without known pre-existing hepatic disease; clinical and laboratory monitoring should be considered and APRETUDE should be discontinued if hepatotoxicity is confirmed. Residual concentrations of cabotegravir injection may remain in the systemic circulation of individuals for prolonged periods (up to 12 months or longer).

Contraindications

APRETUDE is contraindicated in individuals with an unknown or a positive HIV-1 status or with known hypersensitivity to cabotegravir or to any of the excipients in the tablets or the injection formulation. APRETUDE is contraindicated in individuals receiving rifampicin, rifapentine, phenytoin, phenobarbital, carbamazepine and oxcarbazepine.

PBS listing

No PBS listing information is provided in the source documents.

Regulatory history

APRETUDE was first listed on the ARTG on 2022-08-11 for both the 600 mg/3 mL prolonged-release suspension for injection and the 30 mg film-coated tablet formulations. The AusPAR approval date was 2022-08-08. This medicinal product is subject to additional monitoring in Australia, which will allow quick identification of new safety information.