Cabotegravir and Rilpivirine side effects: what 6,074 FDA adverse event reports show
Drug class
Hiv-1 integrase strand transfer inhibitor (insti)
Label matched
Cabotegravir (Apretude)
Who reports
6,074 reports · 20% serious · 113 with death outcome · 30% female
Used for
APRETUDE is indicated for pre‑exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in adults and adolescents weighing at least 35 kg who are at risk for HIV-1 acquisition. Individuals must have a negative HIV-1 test prior.
What it is
APRETUDE contains cabotegravir extended-release injectable suspension, an HIV INSTI.
Boxed warning
RISK OF DRUG RESISTANCE WITH USE OF APRETUDE FOR HIV-1 PRE‑EXPOSURE PROPHYLAXIS (PrEP) IN UNDIAGNOSED HIV-1 INFECTION Individuals must be tested for HIV-1 infection prior to initiating APRETUDE or oral cabotegravir, .
Causality screen of the 38 strongest signals
What the badges mean
- Labeled adverse reaction The exact term appears in the label's warnings or adverse-reactions sections: a known, expected effect. The FAERS signal confirms the label rather than discovering anything.
- Labeled (related wording) The label describes this effect under different wording (e.g. 'neutropenia' for 'neutrophil count decreased'). Treated as known.
- Reporting / coding artifact An administrative, monitoring or exposure term (product issue, off-label use, 'test normal', overdose...). Not a biological reaction; a high PRR here reflects how reports are coded.
- Not in label — unassessed Not found in the label text, not an artifact pattern. This is a genuine candidate for a formal causality assessment (Bradford Hill / WHO-UMC); it has NOT had one here.
Strongest disproportionality signals
Flagged terms (PRR ≥ 2, χ² ≥ 4, n ≥ 10), ranked by PRR; infinite PRRs (no comparator reports) excluded. The EBGM column is a second, shrinkage-based estimate (MGPS) with its 5th percentile EB05 and the BCPNN IC025; a pair flagged by PRR alone is marked PRR-only and should be read as fragile. The strata column recomputes the PRR on serious reports only and flags pairs whose reports are unusually skewed by sex or come mostly from consumers rather than clinicians. 57 further terms are in the interactive explorer. Reaction links open the term's cross-drug page.
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Injection site nodule | 189 | 60.1 52.2–69.3ROR 62.0 · χ² 10,746 / p <1e-300 | 58.8 EB05 52.1 · IC025 +5.4 3/3 methods agree | Labeled (related wording) related wording | serious n=15 | no trial data cached |
| Product complaint | 204 | 28.3 24.7–32.4ROR 29.2 · χ² 5,308 / p <1e-300 | 28.0 EB05 24.9 · IC025 +4.5 3/3 methods agree | Reporting / coding artifact | 97% clinician | no trial data cached |
| Nodule | 73 | 19.3 15.4–24.3ROR 19.5 · χ² 1,243 / p 1e-272 | 19.1 EB05 15.7 · IC025 +3.7 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 7.2 · 95% clinician | no trial data cached |
| Injection site discomfort | 38 | 12.7 9.2–17.4ROR 12.8 · χ² 396 / p 2e-88 | 12.3 EB05 9.2 · IC025 +2.9 3/3 methods agree | Labeled (related wording) related wording | serious n=3 | no trial data cached |
| Product administered at inappropriate site | 60 | 11.4 8.8–14.6ROR 11.5 · χ² 557 / p 2e-123 | 11.1 EB05 8.8 · IC025 +3.0 3/3 methods agree | Reporting / coding artifact | serious n=6 | no trial data cached |
| Wrong technique in device usage process | 129 | 9.7 8.2–11.5ROR 9.9 · χ² 999 / p 1e-219 | 9.5 EB05 8.2 · IC025 +2.9 3/3 methods agree | Reporting / coding artifact | serious n=18 · 94% clinician | no trial data cached |
| Exposure during pregnancy | 172 | 9.5 8.2–11.0ROR 9.8 · χ² 1,304 / p 7e-286 | 9.4 EB05 8.2 · IC025 +3.0 3/3 methods agree | Reporting / coding artifact | serious PRR 3.2 · ♀ 100% (drug 30%) · 99% clinician | no trial data cached |
| Product administration error | 51 | 8.8 6.7–11.6ROR 8.9 · χ² 344 / p 4e-77 | 8.4 EB05 6.5 · IC025 +2.6 3/3 methods agree | Reporting / coding artifact | serious PRR 7.4 · 90% clinician | no trial data cached |
| Product dose omission issue | 703 | 8.5 7.9–9.1ROR 9.5 · χ² 4,697 / p <1e-300 | 8.5 EB05 7.9 · IC025 +3.0 3/3 methods agree | Reporting / coding artifact | serious PRR 8.0 | no trial data cached |
| Injection site induration | 29 | 7.7 5.4–11.1ROR 7.7 · χ² 162 / p 2e-37 | 7.0 EB05 5.1 · IC025 +2.2 3/3 methods agree | Labeled (related wording) related wording | serious n=2 | no trial data cached |
| Product storage error | 185 | 7.4 6.4–8.5ROR 7.6 · χ² 1,012 / p 2e-222 | 7.2 EB05 6.4 · IC025 +2.6 3/3 methods agree | Reporting / coding artifact | serious PRR 2.5 · 93% clinician | no trial data cached |
| Injection site mass | 78 | 7.3 5.8–9.1ROR 7.4 · χ² 416 / p 8e-93 | 7.0 EB05 5.8 · IC025 +2.4 3/3 methods agree | Labeled (related wording) related wording | serious PRR 16.1 | no trial data cached |
| Injection site pain (pain where injected) | 622 | 7.1 6.5–7.6ROR 7.7 · χ² 3,265 / p <1e-300 | 7.0 EB05 6.6 · IC025 +2.7 3/3 methods agree | Labeled (related wording) related wording | serious PRR 16.7 | no trial data cached |
| Product preparation error | 33 | 5.5 3.9–7.7ROR 5.5 · χ² 116 / p 2e-27 | 5.1 EB05 3.8 · IC025 +1.8 3/3 methods agree | Reporting / coding artifact | serious n=1 · 91% clinician | no trial data cached |
| Sciatica | 22 | 4.8 3.1–7.2ROR 4.8 · χ² 62 / p 2e-15 | 4.4 EB05 3.0 · IC025 +1.4 3/3 methods agree | Not in label — unassessed | serious PRR 4.3 | no trial data cached |
| Product dispensing error | 30 | 4.7 3.3–6.8ROR 4.8 · χ² 85 / p 2e-20 | 4.4 EB05 3.3 · IC025 +1.5 3/3 methods agree | Reporting / coding artifact | serious n=1 | no trial data cached |
| Injection site warmth | 28 | 4.7 3.2–6.8ROR 4.7 · χ² 77 / p 8e-19 | 4.4 EB05 3.2 · IC025 +1.5 3/3 methods agree | Labeled (related wording) related wording | serious n=5 | no trial data cached |
| Treatment failure | 106 | 4.4 3.7–5.4ROR 4.5 · χ² 280 / p 4e-63 | 4.4 EB05 3.7 · IC025 +1.8 3/3 methods agree | Reporting / coding artifact | serious PRR 7.1 · 92% clinician | no trial data cached |
| Abscess | 20 | 4.3 2.8–6.7ROR 4.3 · χ² 48 / p 3e-12 | 4.0 EB05 2.7 · IC025 +1.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 6.3 | no trial data cached |
| Gait inability | 41 | 4.3 3.1–5.8ROR 4.3 · χ² 99 / p 1e-23 | 4.1 EB05 3.1 · IC025 +1.5 3/3 methods agree | Not in label — unassessed | serious PRR 8.4 | no trial data cached |
| Poor quality product administered | 12 | 4.0 2.3–7.1ROR 4.0 · χ² 24 / p 4e-7 | 3.6 EB05 2.2 · IC025 +0.9 3/3 methods agree | Labeled (related wording) related wording | – | no trial data cached |
| Injection site swelling | 86 | 3.9 3.2–4.8ROR 3.9 · χ² 183 / p 5e-42 | 3.8 EB05 3.2 · IC025 +1.6 3/3 methods agree | Labeled (related wording) related wording | serious PRR 13.8 | no trial data cached |
| Incorrect route of product administration | 18 | 3.7 2.3–5.8ROR 3.7 · χ² 33 / p 6e-9 | 3.4 EB05 2.3 · IC025 +1.0 3/3 methods agree | Reporting / coding artifact | serious PRR 3.6 | no trial data cached |
| Exposure via skin contact | 24 | 3.6 2.4–5.4ROR 3.7 · χ² 44 / p 2e-11 | 3.4 EB05 2.4 · IC025 +1.1 3/3 methods agree | Reporting / coding artifact | serious n=1 · 100% clinician | no trial data cached |
| Inappropriate schedule of product administration | 185 | 3.6 3.1–4.1ROR 3.7 · χ² 347 / p 1e-77 | 3.6 EB05 3.2 · IC025 +1.6 3/3 methods agree | Reporting / coding artifact | serious PRR 6.5 | no trial data cached |
| Presyncope (near-fainting) | 24 | 3.4 2.3–5.1ROR 3.4 · χ² 38 / p 3e-10 | 3.2 EB05 2.3 · IC025 +1.0 3/3 methods agree | Not in label — unassessed | serious PRR 5.4 | no trial data cached |
| Psychotic disorder | 29 | 3.4 2.3–4.9ROR 3.4 · χ² 46 / p 6e-12 | 3.2 EB05 2.4 · IC025 +1.1 3/3 methods agree | Not in label — unassessed | serious PRR 10.8 · ♀ 0% (drug 30%) | no trial data cached |
| Injection site reaction | 67 | 3.4 2.6–4.3ROR 3.4 · χ² 109 / p 9e-26 | 3.3 EB05 2.7 · IC025 +1.3 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 6.1 | no trial data cached |
| Mass | 13 | 3.2 1.9–5.5ROR 3.2 · χ² 17 / p 2e-5 | 2.9 EB05 1.8 · IC025 +0.6 | Not in label — unassessed | serious PRR 4.2 | no trial data cached |
| Injection site discolouration | 11 | 3.0 1.7–5.5ROR 3.1 · χ² 13 / p 1e-4 | 2.8 EB05 1.7 · IC025 +0.5 | Labeled (related wording) related wording | serious n=2 | no trial data cached |
| Hepatitis c | 10 | 2.8 1.5–5.2ROR 2.8 · χ² 10 / p 8e-4 | 2.6 EB05 1.5 · IC025 +0.3 | Labeled (related wording) related wording | serious PRR 8.8 | no trial data cached |
| Liver function test increased | 16 | 2.6 1.6–4.2ROR 2.6 · χ² 14 / p 1e-4 | 2.5 EB05 1.6 · IC025 +0.5 | Not in label — unassessed | serious PRR 3.0 | no trial data cached |
| Circumstance or information capable of leading to medication error | 24 | 2.5 1.6–3.7ROR 2.5 · χ² 19 / p 5e-6 | 2.4 EB05 1.7 · IC025 +0.6 | Labeled (related wording) related wording | serious n=1 | no trial data cached |
| Musculoskeletal pain | 37 | 2.4 1.7–3.3ROR 2.4 · χ² 29 / p 3e-8 | 2.4 EB05 1.8 · IC025 +0.7 | Not in label — unassessed | serious PRR 3.7 | no trial data cached |
| Muscle tightness | 11 | 2.3 1.3–4.2ROR 2.3 · χ² 7 / p 0.004 | 2.2 EB05 1.3 · IC025 +0.1 | Not in label — unassessed | serious PRR 3.6 | no trial data cached |
| Influenza like illness (flu-like illness) | 54 | 2.2 1.7–2.9ROR 2.3 · χ² 36 / p 9e-10 | 2.2 EB05 1.8 · IC025 +0.7 | Labeled (related wording) related wording | serious PRR 1.3 | no trial data cached |
| Treatment noncompliance | 32 | 2.0 1.4–2.9ROR 2.0 · χ² 16 / p 4e-5 | 2.0 EB05 1.5 · IC025 +0.4 | Reporting / coding artifact | serious PRR 2.3 | no trial data cached |
| Drug resistance | 15 | 2.0 1.2–3.3ROR 2.0 · χ² 7 / p 0.005 | 2.0 EB05 1.3 · IC025 +0.1 | Reporting / coding artifact | serious PRR 3.5 | no trial data cached |
Trial evidence (ClinicalTrials.gov)
Most frequently reported reactions
By raw co-report count, regardless of disproportionality. Common terms here are often the illness itself or generic outcomes.
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Product dose omission issue | 703 | 8.5 7.9–9.1ROR 9.5 · χ² 4,697 / p <1e-300 | 8.5 EB05 7.9 · IC025 +3.0 3/3 methods agree | Reporting / coding artifact | serious PRR 8.0 | no trial data cached |
| Injection site pain (pain where injected) | 622 | 7.1 6.5–7.6ROR 7.7 · χ² 3,265 / p <1e-300 | 7.0 EB05 6.6 · IC025 +2.7 3/3 methods agree | Labeled (related wording) related wording | serious PRR 16.7 | no trial data cached |
| Off label use (used outside approved label) | 435 | 1.7 1.6–1.9ROR 1.8 · χ² 137 / p 7e-32 | 1.7 EB05 1.6 · IC025 +0.6 | Reporting / coding artifact | serious PRR 0.8 · 96% clinician | no trial data cached |
| Pain | 287 | 1.6 1.4–1.8ROR 1.6 · χ² 66 / p 2e-16 | 1.6 EB05 1.5 · IC025 +0.5 | Labeled adverse reaction exact term | serious PRR 1.6 | no trial data cached |
| Product complaint | 204 | 28.3 24.7–32.4ROR 29.2 · χ² 5,308 / p <1e-300 | 28.0 EB05 24.9 · IC025 +4.5 3/3 methods agree | Reporting / coding artifact | 97% clinician | no trial data cached |
| Injection site nodule | 189 | 60.1 52.2–69.3ROR 62.0 · χ² 10,746 / p <1e-300 | 58.8 EB05 52.1 · IC025 +5.4 3/3 methods agree | Labeled (related wording) related wording | serious n=15 | no trial data cached |
| Inappropriate schedule of product administration | 185 | 3.6 3.1–4.1ROR 3.7 · χ² 347 / p 1e-77 | 3.6 EB05 3.2 · IC025 +1.6 3/3 methods agree | Reporting / coding artifact | serious PRR 6.5 | no trial data cached |
| Product storage error | 185 | 7.4 6.4–8.5ROR 7.6 · χ² 1,012 / p 2e-222 | 7.2 EB05 6.4 · IC025 +2.6 3/3 methods agree | Reporting / coding artifact | serious PRR 2.5 · 93% clinician | no trial data cached |
| Exposure during pregnancy | 172 | 9.5 8.2–11.0ROR 9.8 · χ² 1,304 / p 7e-286 | 9.4 EB05 8.2 · IC025 +3.0 3/3 methods agree | Reporting / coding artifact | serious PRR 3.2 · ♀ 100% (drug 30%) · 99% clinician | no trial data cached |
| Wrong technique in device usage process | 129 | 9.7 8.2–11.5ROR 9.9 · χ² 999 / p 1e-219 | 9.5 EB05 8.2 · IC025 +2.9 3/3 methods agree | Reporting / coding artifact | serious n=18 · 94% clinician | no trial data cached |
| Incorrect dose administered | 112 | 1.7 1.4–2.1ROR 1.7 · χ² 33 / p 5e-9 | 1.7 EB05 1.5 · IC025 +0.5 | Reporting / coding artifact | serious PRR 2.2 | no trial data cached |
| Treatment failure | 106 | 4.4 3.7–5.4ROR 4.5 · χ² 280 / p 4e-63 | 4.4 EB05 3.7 · IC025 +1.8 3/3 methods agree | Reporting / coding artifact | serious PRR 7.1 · 92% clinician | no trial data cached |
| Product use issue | 105 | 1.9 1.6–2.3ROR 1.9 · χ² 47 / p 5e-12 | 1.9 EB05 1.6 · IC025 +0.6 | Reporting / coding artifact | serious PRR 1.2 | no trial data cached |
| Depression | 103 | 1.5 1.3–1.9ROR 1.6 · χ² 20 / p 5e-6 | 1.5 EB05 1.3 · IC025 +0.3 | Labeled — boxed warning synonym match | serious PRR 2.7 | no trial data cached |
| Injection site swelling | 86 | 3.9 3.2–4.8ROR 3.9 · χ² 183 / p 5e-42 | 3.8 EB05 3.2 · IC025 +1.6 3/3 methods agree | Labeled (related wording) related wording | serious PRR 13.8 | no trial data cached |
Unlabeled candidate signals
These flagged terms were not found in the FDA label text and do not match an artifact pattern. They are the pairs that would merit a structured assessment (temporality, dose-response, biological plausibility, consistency across databases, trial or cohort evidence). The screen has not done that; string-matching misses label wording, and a strong PRR can still be stimulated reporting, co-medication, or the disease itself.
- Sciatica — n=22, PRR 4.8
- Gait inability — n=41, PRR 4.3
- Presyncope — n=24, PRR 3.4
- Psychotic disorder — n=29, PRR 3.4
- Musculoskeletal pain — n=37, PRR 2.4
Want to assess one of these properly? The runbook describes the Bradford Hill / trial-evidence workflow used on the assessment page, and handoff_top1000_signals.csv lists the strongest unassessed pairs across all drugs.
Common questions
What are the most reported side effects of Cabotegravir and Rilpivirine?
In FDA FAERS, the most frequently co-reported reaction terms for Cabotegravir and Rilpivirine are injection site pain, pain, injection site nodule, depression, injection site swelling. These are report counts, not rates: FAERS has no denominator, reporting is voluntary and uneven, and a term can be reported because of the illness being treated rather than the drug.
Does Cabotegravir and Rilpivirine have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: RISK OF DRUG RESISTANCE WITH USE OF APRETUDE FOR HIV-1 PRE‑EXPOSURE PROPHYLAXIS (PrEP) IN UNDIAGNOSED HIV-1 INFECTION Individuals must be tested for HIV-1 infection prior to initiating APRETUDE or oral cabotegravir, .
Do FAERS signals prove that Cabotegravir and Rilpivirine causes these side effects?
No. A disproportionality signal (PRR, ROR) means a reaction is reported more often with this drug than with others in the database. That can reflect a real effect, but also the disease being treated, stimulated reporting after news or litigation, co-medications, or how reports are coded. Causality needs temporality, dose-response, biological plausibility, consistency across data sources and, ideally, trial or cohort evidence. This page screens each term against the FDA label and ClinicalTrials.gov results; it does not establish causation.
Sources & methods
- FDA label via openFDA (set ID 4338428e-43d4-4e02-ac9d-bd98e738a7da, effective 20250411; matched on
openfda.generic_name.exact:"CABOTEGRAVIR") - Bayesian shrinkage measures computed offline over all 1,317,300 cached pairs: BCPNN information component (IC, with Norén closed-form IC025) and MGPS empirical-Bayes geometric mean (EBGM, EB05) with a two-component gamma prior fitted by maximum marginal likelihood (α₁=0.57, β₁=0.02, α₂=1.42, β₂=0.70, w=0.17); unstratified
- FAERS pair statistics from the OpenPV build of 2026-09-14 (openFDA
count=aggregation, fieldpatient.drug.openfda.generic_name.exact, 95 reaction terms, min 3 co-reports); PRR/ROR with 95% CI, chi-square with Yates correction - Serious-only and stratified counts (serious:1, patient.patientsex, primarysource.qualification) from openFDA count queries; serious-only PRR uses the drug serious report total and the term global serious total (N_serious=11,882,979); strata shown only when n ≥ 20
- Seriousness and sex counts from openFDA
count=serious,patient.patientsex,seriousnessdeath
Page generated 2026-10-08. Label and PubChem text are retrieved automatically and may lag the current label; always check the current prescribing information. OpenPV is a beta research tool of the Open Source Medicine Foundation.