Vocabria Adverse Reactions

Summary of the safety profile: Tablet: The most frequently reported adverse reaction (ARs) from monthly dosing studies were headache (up to 12%) and pyrexia⁴ (10%).
The most frequently reported ARs, considered by the investigator as causally related, from ATLAS-2M every 2 month dosing were headache (7%) and pyrexia⁴ (7%).
Suspension for injection: The most frequently reported adverse reactions (ARs) from monthly dosing studies were injection site reactions (up to 84%), headache (up to 12%) and pyrexia⁴ (10%).
The most frequently reported ARs from ATLAS-2M every 2 month dosing were injection site reactions (76%), headache (7%) and pyrexia⁴ (7%).
Tabulated list of adverse reactions: The ARs identified for cabotegravir and/or rilpivirine are listed in Table 15 by body system organ class and frequency. Frequencies are defined as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000). (See Table 15.)

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Suspension for injection: 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 Vocabria and rilpivirine injection regimen with Direct to Injection did not identify any new safety concerns related to omitting the oral lead-in phase (see Pharmacology: Pharmacodynamics under Actions).
Description of selected adverse reactions: Weight increased: At the Week 48 time point, subjects in studies FLAIR and ATLAS, who received Vocabria plus rilpivirine gained a median of 1.5 kg in weight; subjects continuing on their current antiretroviral therapy (CAR) gained a median of 1.0 kg (pooled analysis). In the individual studies FLAIR and ATLAS, the median weight gains in the Vocabria plus rilpivirine 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 2-monthly Vocabria plus rilpivirine dosing arms was 1.0 kg.
Changes in laboratory chemistries: Small, non-progressive increases in total bilirubin (without clinical jaundice) were observed with treatment with Vocabria plus rilpivirine. These changes are not considered clinically relevant as they likely reflect competition between cabotegravir and unconjugated bilirubin for a common clearance pathway (UGT1A1).
Elevated transaminases (ALT/AST) were observed in subjects receiving Vocabria plus rilpivirine during clinical studies. These elevations were primarily attributed to acute viral hepatitis. A few subjects on oral therapy had transaminase elevations attributed to suspected drug-related hepatotoxicity; these changes were reversible upon discontinuation of treatment (see Precautions).
Elevated lipases were observed during clinical trials with Vocabria plus rilpivirine; Grade 3 and 4 lipase increases occurred at a higher incidence with Vocabria plus rilpivirine compared with CAR. These elevations were generally asymptomatic and did not lead to Vocabria plus rilpivirine 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 causality to the injection regimen could not be ruled out.
Suspension for injection: Local injection site reactions (ISRs): Up to 1% of subjects discontinued treatment with Vocabria plus rilpivirine because of ISRs. When dosing monthly, up to 84% of subjects reported injection site reactions; out of 30393 injections, 6815 ISRs were reported. When dosing every 2 months, 76% of patients reported injection site reactions; out of 8470 injections, 2507 ISRs were reported.
The severity of reactions was 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 overall ISR events was 3 days. The percentage of subjects reporting ISRs decreased over time.