Cabotegravir

Warning

H400 (100%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]；H410 (100%): Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]

P273, P391, and P501 (click each P-code to see the statement)

The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

In large clinical trials, switching antiretroviral therapy of HIV infection to the combination of parenteral injections of long acting cabotegravir and rilpivirine was associated with alanine aminotransferase (ALT) elevations in up to 7% of patients, but levels above 5 times the upper limit of normal (ULN) arose in only 1% to 2% of subjects. The elevations were typically transient, asymptomatic, and rarely required dose modification or discontinuation. While clinically apparent liver injury with jaundice was reported to occur in early studies, there were no such cases in the large, preregistration trials of long acting, parenteral cabotegravir and rilpivirine used for treatment of HIV infection or in the large trials of long acting cabotegravir used as prophylaxis against acquiring HIV infection. The use of injections every 4 or 8 weeks has been found to improve compliance and to be preferable to daily oral therapy by many patients requiring long term antiretroviral therapy. Since approval of cabotegravir for use as maintenance therapy and for prophylaxis against HIV infection, there have been no case reports of clinically apparent hepatotoxicity associated with its use.；Interestingly, in the large preregistration trials of parenteral cabotegravir and rilpivirine as replacement therapy of HIV infection, cases of acute hepatitis A, B and C were reported as adverse events, occurring largely in patients who had been switched to the parenteral regimen compared to control subjects who were continued on oral agents. The reasons for these differences were unclear. Importantly, neither cabotegravir or rilpivirine have activity against hepatitis B virus (HBV), and one possibility has been that reactivation of hepatitis B may occur after withdrawal of oral antiretroviral agents that have activity against HBV, such as tenofovir, emtricitabine, and lamivudine. For this reason, patients starting long- acting parenteral regimens of cabotegravir and rilpivirine should be screened for hepatitis B virus markers and potential risks of stopping agents with activity against HBV should be considered. In addition, persons with HIV without protective antibodies to HAV and HBV should be offered hepatitis A and B virus vaccination.；Likelihood score: E* (unproven but suspected cause of clinically apparent liver injury).

J - Antiinfectives for systemic use；J05 - Antivirals for systemic use；J05A - Direct acting antivirals；J05AJ - Integrase inhibitors；J05AJ04 - Cabotegravir

QJ - Antiinfectives for systemic use；QJ05 - Antivirals for systemic use；QJ05A - Direct acting antivirals；QJ05AJ - Integrase inhibitors；QJ05AJ04 - Cabotegravir

Cabotegravir is an inhibitor of HIV integrase, which reduces viral replication. It has a long duration of action as the oral tablet is given daily and the intramuscular suspension is given monthly. Patients should be counselled regarding the risk of hypersensitivity, hepatotoxicity, and depression.

HMH0132Z1Q

CABOTEGRAVIR

Mechanisms of Action [MoA] - HIV Integrase Inhibitors

Established Pharmacologic Class [EPC] - Human Immunodeficiency Virus Integrase Strand Transfer Inhibitor

Mechanisms of Action [MoA] - Organic Anion Transporter 1 Inhibitors

Mechanisms of Action [MoA] - Organic Anion Transporter 3 Inhibitors