Rekambys Adverse Reactions

Summary of the safety profile: The most frequently reported ARs from every 1 month dosing studies were injection site reactions (up to 84%), headache (up to 12%) and pyrexia (10%).
The most frequently reported ARs from every 2 months dosing were injection site reactions (76%), headache (7%) and pyrexia (7%).
Tabulated summary of adverse reactions: The ARs identified for rilpivirine and/or cabotegravir are listed by system organ class (SOC) and frequency (see Table 11). Frequencies are defined as very common (≥1/10), common (≥1/100 to <1/10) and uncommon (≥1/1,000 to <1/100). (See Table 11.)

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Description of selected adverse reactions: Local Injection Site Reactions (ISRs): Up to 1% of subjects discontinued treatment with rilpivirine and cabotegravir injections because of ISRs.
Injection site reactions were generally mild (Grade 1, 70% - 75% of subjects) or moderate (Grade 2, 27% - 36% of subjects). 3-4% of subjects experienced severe (Grade 3) ISRs. The median duration of ISR events was 3 days. The percentage of subjects reporting ISRs decreased over time.
Weight increased: At the Week 48 time point, subjects in Phase 3 Studies FLAIR and ATLAS, who received rilpivirine plus cabotegravir gained a median of 1.5 kg in weight; subjects continuing on their current antiretroviral regimen (CAR) group gained a median of 1.0 kg (pooled analysis).
In the individual studies FLAIR and ATLAS, the median weight gains in the rilpivirine plus cabotegravir arms were 1.3 kg and 1.8 kg respectively, compared to 1.5 kg and 0.3 kg in the CAR arms.
At the 48 week timepoint, in ATLAS-2M the median weight gain in both the monthly and every 2 months rilpivirine+cabotegravir dosing arms was 1.0 kg.
Changes in laboratory chemistry: Elevated transaminases (ALT/AST) were observed in subjects receiving rilpivirine plus cabotegravir during the clinical studies. These elevations were primarily attributed to acute viral hepatitis. A few subjects on oral rilpivirine plus oral cabotegravir treatment had transaminase elevations attributed to suspected drug-related hepatotoxicity; these changes were reversible upon discontinuation of treatment.
Small, non-progressive increases in total bilirubin (without clinical jaundice) were observed with treatment with rilpivirine plus cabotegravir. These changes are not considered clinically relevant as they likely reflect competition between cabotegravir and unconjugated bilirubin for a common clearance pathway (UGT1A1).
Elevated lipases were observed during clinical trials with rilpivirine plus cabotegravir. Grade 3 and 4 lipase increases occurred at a higher incidence with rilpivirine plus cabotegravir compared with CAR. These elevations were generally asymptomatic and did not lead to rilpivirine plus cabotegravir discontinuation. One case of fatal pancreatitis with Grade 4 lipase and confounding factors (including history of pancreatitis) has been reported in study ATLAS-2M for which the causality to the injection regimen could not be ruled out.
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.