CABENUVA

What it is

Cabenuva contains cabotegravir prolonged-release suspension for injection and rilpivirine prolonged-release suspension for injection. It is available in two strengths: cabotegravir 400 mg/2 mL plus rilpivirine 600 mg/2 mL, or cabotegravir 600 mg/3 mL plus rilpivirine 900 mg/3 mL. Cabotegravir prolonged-release suspension is a white to light pink suspension, and rilpivirine prolonged-release suspension is a white to off-white suspension. This medicinal product is subject to additional monitoring in Australia, which will allow quick identification of new safety information.

Approved indications

— Treatment of Human Immunodeficiency Virus type 1 (HIV-1) infection in adults who are virologically suppressed (HIV-1 RNA <50 copies per mL) and have no known or suspected resistance to either cabotegravir or rilpivirine.

Dosing overview

Dosing for Cabenuva consists of three distinct phases: an optional oral lead-in with cabotegravir and rilpivirine tablets, initiation injections, and continuation injections. When used for oral lead-in, cabotegravir 30 mg tablet and rilpivirine 25 mg tablet, co-administered once daily, should be used for approximately one month (at least 28 days) prior to initiation of Cabenuva injections. In the clinical trial ATLAS 2M, a higher rate of confirmed virological failure was seen with the 2 monthly injection schedule (1.5%) as compared to the 1 monthly schedule (0.4%).

Key safety warnings

To minimise the risk of developing viral resistance, an alternative, fully suppressive antiretroviral regimen must be adopted no later than one month after the final injection doses of Cabenuva when dosed monthly and no later than two months after the final injection doses when dosed every 2 months. If virologic failure is suspected, an alternative regimen should be adopted as soon as possible. Hypersensitivity reactions have been reported with integrase inhibitors, characterised by rash, constitutional findings and sometimes organ dysfunction including liver injury. Cabenuva should be discontinued immediately, along with other suspected medicinal products, should signs or symptoms of hypersensitivity develop including severe rash, or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial oedema, hepatitis, eosinophilia or angioedema. Serious post-injection reactions were reported within minutes after injection of rilpivirine, including symptoms such as dyspnoea, bronchospasm, agitation, abdominal cramping, rash/urticaria, dizziness, flushing, sweating, oral numbness, changes in blood pressure and pain. These events were uncommon, began to resolve after injection, and some patients received supportive care. These events may have been associated with accidental intravenous administration during the intramuscular injection procedure. The suspension should be injected slowly, and care should be taken to avoid accidental intravenous administration. Patients should be observed briefly (approximately 10 minutes) after injection. Hepatotoxicity has been reported in a limited number of patients receiving cabotegravir with or without known pre-existing hepatic disease. Monitoring of liver chemistries is recommended and treatment with Cabenuva should be discontinued if hepatotoxicity is suspected.

Contraindications

Cabenuva is contraindicated in patients with known hypersensitivity to cabotegravir or rilpivirine or to any of the excipients. Cabenuva is contraindicated in combination with anticonvulsants (phenytoin, phenobarbital, carbamazepine and oxcarbazepine), antimycobacterials (rifabutin, rifampicin, rifapentine), systemic glucocorticoids dexamethasone (except as a single dose treatment), and St John's wort (Hypericum perforatum).

Regulatory history

Cabenuva was approved on 2021-02-10 for treatment of human immunodeficiency virus type 1 infection in adults who are virologically suppressed (HIV-1 RNA <50 copies/mL) and have no known or suspected resistance to either cabotegravir or rilpivirine. The product was first listed on the Australian Register of Therapeutic Goods on 2021-02-23, with two registered formulations: cabotegravir 600 mg/3 mL plus rilpivirine 900 mg/3 mL (ARTG 323783), and cabotegravir 400 mg/2 mL plus rilpivirine 600 mg/2 mL (ARTG 323784). The Pharmaceutical Benefits Scheme Advisory Committee did not recommend Cabenuva for listing in March 2021.