RUKOBIA

What it is

RUKOBIA contains fostemsavir trometamol 600 mg as the active ingredient. It is an extended release tablet presented as a beige, film-coated, biconvex, oval tablet. Fostemsavir is a prodrug that is hydrolysed to the active moiety, temsavir, upon cleavage of a phosphonooxymethyl group in vivo. Temsavir binds directly to the gp120 subunit within the HIV-1 envelope glycoprotein gp160 and selectively inhibits the interaction between the virus and cellular CD4 receptors, thereby preventing viral entry into, and infection of, host cells. This medicinal product is subject to additional monitoring in Australia, which will allow quick identification of new safety information.

Approved indications

— Treatment in combination with other antiretroviral agents of heavily treatment-experienced adults with multidrug-resistant human immunodeficiency virus-1 (HIV-1) infection for whom it is otherwise not possible to construct a suppressive antiviral regimen due to resistance, intolerance or safety considerations.

Dosing overview

The recommended dosage of fostemsavir is 600 mg orally twice daily. Fostemsavir can be taken with or without food, and tablets should be swallowed whole and should not be chewed, crushed or split. Therapy should be initiated by a physician experienced in the management of HIV infection.

Key safety warnings

In HIV-infected patients with severe immune deficiency at the time of initiation of antiretroviral therapy, an inflammatory reaction to asymptomatic or residual opportunistic infections may arise and cause serious clinical conditions or aggravation of symptoms, typically within the first few weeks or months of initiation of therapy. Relevant examples are cytomegalovirus retinitis, generalised and/or focal mycobacterial infections and Pneumocystis jiroveci pneumonia. Any inflammatory symptoms must be evaluated without delay and treatment initiated when necessary. A supratherapeutic dose of fostemsavir has been shown to significantly prolong the QTc interval of the electrocardiogram. Fostemsavir should be used with caution in patients with a history of QT interval prolongation, when co-administered with a drug with a known risk of Torsade de Pointes, or in patients with relevant pre-existing cardiac disease. Elderly patients may be more susceptible to drug-induced QT interval prolongation. Monitoring of liver chemistries is recommended in patients with hepatitis B and/or C coinfection. Particular diligence should be applied in initiating or maintaining effective hepatitis B therapy when starting fostemsavir therapy in HIV-hepatitis B co-infected patients. Patients receiving fostemsavir or any other antiretroviral therapy may still develop opportunistic infections and other complications of HIV infection. Therefore, patients should remain under close clinical observation by physicians experienced in the treatment of these associated HIV diseases.

Contraindications

Fostemsavir is contraindicated in patients who have demonstrated hypersensitivity to fostemsavir or any components of formulations of fostemsavir. Fostemsavir is contraindicated in combination with strong CYP3A inducers including, but not limited to: carbamazepine, phenytoin (anticonvulsants), mitotane (antineoplastic), enzalutamide (androgen receptor inhibitor), rifampicin (antimycobacterial) and St John's wort (Hypericum perforatum, herbal supplement).

Regulatory history

RUKOBIA fostemsavir 600 mg extended release tablet was first listed on the ARTG on 14 July 2021. The TGA approved RUKOBIA (fostemsavir trometamol) 600 mg extended release tablets on 9 July 2021 for the treatment of heavily treatment-experienced adults with multidrug-resistant human immunodeficiency virus-1 (HIV-1) infection. The clinical data package supported the efficacy and safety of fostemsavir in heavily treatment-experienced adults with multidrug-resistant HIV-1 infection, with the pivotal BRIGHTE study demonstrating significant virologic response and CD4+ cell count increases in patients with limited treatment options.