Summary of the safety profile The most frequently reported ARs were injection site reactions, headache, and pyrexia. Tabulated summary of adverse reactions The ARs identified for rilpivirine and/or cabotegravir are listed by system organ class (SOC) and frequency (see Table 7).
Frequencies are defined as very common (≥ 1/10), common (≥ 1/100 to < 1/10) and uncommon (≥ 1/1,000 to < 1/100). Table 7 Tabulated summary of adverse reactions1 MedDRA System Organ Class (SOC) Frequency Category ARs for rilpivirine + cabotegravir regimen Blood and lymphatic system disorders Common decreased white blood cell count2, decreased haemoglobin2, decreased platelet count2 Immune System Disorders Uncommon immune reactivation syndrome2 Metabolism and nutrition disorders Very common increased total cholesterol (fasted)2, increased LDL cholesterol (fasted)2 Common decreased appetite2, increased triglycerides (fasted)2 Psychiatric disorders Common depression, anxiety, abnormal dreams, insomnia, sleep disorder2, depressed mood2 Nervous system disorders Very common headache 13 Common dizziness Uncommon somnolence, vasovagal reactions (in response to injections) Gastrointestinal disorders Very common increased pancreatic amylase2 Common nausea, vomiting, abdominal pain3, flatulence, diarrhoea, abdominal discomfort2, dry mouth2, increased lipase2 Hepatobiliary disorders Uncommon hepatotoxicity Skin and subcutaneous tissue disorders Common rash4 Musculoskeletal and connective tissue disorders Common myalgia General disorders and administrative site conditions Very common injection site reactions (pain and discomfort, nodule, induration), pyrexia5 Common injection site reactions (swelling, erythema, pruritus, bruising, warmth, haematoma), fatigue, asthenia, malaise Uncommon injection site reactions (cellulitis, abscess, anaesthesia, haemorrhage, discolouration) Investigations Common weight increased Uncommon transaminase increased, blood bilirubin increased 1 The frequency of the identified ARs are based on all reported occurrences of the events and are not limited to those considered at least possibly related by the investigator.
2 Additional adverse reactions seen with oral rilpivirine in other studies. 3 Abdominal pain includes the following grouped MedDRA preferred term: abdominal pain, upper abdominal pain. 4 Rash includes the following grouped MedDRA preferred terms: rash, rash erythematous, rash generalised, rash macular, rash maculo-papular, rash morbilliform, rash papular, rash pruritic.
5 Pyrexia includes the following grouped MedDRA preferred terms: pyrexia, feeling hot, body temperature increased. The majority of pyrexia events were reported within one week of injections. The overall safety profile at week 96 and week 124 in the FLAIR study was consistent with that observed at week 48, with no new safety findings identified.
In the extension phase of the FLAIR study, initiating the rilpivirine plus cabotegravir injection regimen without oral lead-in (direct to injection) was not associated with any new safety concerns related to omitting the oral lead-in phase.
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. 0 kg (pooled analysis). 3 kg in the CAR arms. 0 kg. 14 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. Paediatric population Based on data from the week 16 (Cohort 1; n=25) and week 24 (Cohort 2; n=144) analyses of the MOCHA study (IMPAACT 2017), no new safety concerns were identified in adolescents (aged at least 12 years and weighing 35 kg or more) when compared with the safety profile established in adults.
Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the […]