Setmelanotide side effects: what 270 FDA adverse event reports show

Setmelanotide · Imcivree · 16 reaction terms · 210 drug–reaction co-reports · data 2026-09-14

Drug class

Melanocortin 4 Receptor Agonist

FDA label (Established Pharmacologic Class)

Brand names

Imcivree

openFDA label

Who reports

270 reports · 64% serious · 4 with death outcome · 66% female

openFDA FAERS counts, all years, deduplication not applied

Used for

IMCIVREE is indicated to reduce excess body weight and maintain weight reduction long term in adults and pediatric patients aged [ see Dosage and Administration (2.1) ]: 4 years and older with acquired hypothalamic obesity (HO) 2 years and older with s.

FDA label, Indications and Usage

What it is

IMCIVREE contains setmelanotide acetate, a melanocortin 4 (MC4) receptor agonist. Setmelanotide is an 8 amino acid cyclic peptide analog of endogenous melanocortin peptide α‑MSH (alpha-melanocyte stimulating hormone).

FDA label, Description section

Boxed warning

None in the current label

How to read this page. FAERS is a spontaneous-reporting system: counts are not incidence rates and a signal is not proof of causation. Each reaction below is run through an automated screen — is the term in the FDA label (known), in the indications (the disease being treated), an administrative/coding term, or none of these (unlabeled)? That screen is mechanical text matching, not a causality assessment. The 30 hand-written Bradford Hill assessments are on the causality assessment page. Not medical advice.

Causality screen of the 13 strongest signals

Labeled (related wording) 8Reporting / coding artifact 2Not in label — unassessed 3

What the badges mean

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. 3 further terms are in the interactive explorer. Reaction links open the term's cross-drug page.

Show: hide coding/lab/outcome terms hide indication terms unlabeled only hide PRR-only

Reaction	Reports	PRR 95% CI · ROR · χ²/p	EBGM EB05 · IC025	Label screen	Serious-only & strata	Trial cross-check
Hunger	17	98.3 62.0–155.8ROR 104.8 · χ² 1,540 / p <1e-300	88.7 EB05 58.6 · IC025 +3.9 3/3 methods agree	Not in label — unassessed	serious n=14	no trial data cached
Injection site nodule	13	92.0 54.1–156.4ROR 96.6 · χ² 1,080 / p 3e-237	81.3 EB05 50.6 · IC025 +3.5 3/3 methods agree	Labeled (related wording) related wording	serious n=8	no trial data cached
Increased appetite	17	70.3 44.4–111.4ROR 75.0 · χ² 1,093 / p 5e-240	65.3 EB05 43.2 · IC025 +3.7 3/3 methods agree	Not in label — unassessed	serious PRR 87.2	no trial data cached
Skin discolouration	35	59.2 43.5–80.6ROR 67.9 · χ² 1,947 / p <1e-300	57.4 EB05 43.1 · IC025 +4.5 3/3 methods agree	Not in label — unassessed	serious PRR 61.5 · ♀ 90% (drug 66%)	no trial data cached
Intentional dose omission	15	42.6 26.1–69.7ROR 45.1 · χ² 569 / p 4e-126	40.6 EB05 26.1 · IC025 +3.3 3/3 methods agree	Reporting / coding artifact	serious PRR 52.7	no trial data cached
Product dose omission in error	14	40.5 24.3–67.5ROR 42.7 · χ² 501 / p 3e-111	38.5 EB05 24.4 · IC025 +3.2 3/3 methods agree	Reporting / coding artifact	serious PRR 103.1	no trial data cached
Injection site irritation	5	30.7 12.9–73.2ROR 31.3 · χ² 116 / p 3e-27	26.4 EB05 9.9 · IC025 +1.5 3/3 methods agree	Labeled (related wording) related wording	serious n=3	no trial data cached
Injection site pruritus	22	25.7 17.2–38.3ROR 27.9 · χ² 499 / p 8e-111	25.2 EB05 17.5 · IC025 +3.3 3/3 methods agree	Labeled (related wording) related wording	serious PRR 104.1	no trial data cached
Injection site urticaria	6	19.2 8.7–42.4ROR 19.6 · χ² 86 / p 8e-21	16.0 EB05 5.9 · IC025 +1.6 3/3 methods agree	Labeled (related wording) related wording	serious n=5	no trial data cached
Injection site bruising	18	17.7 11.3–27.7ROR 18.9 · χ² 269 / p 1e-60	17.2 EB05 11.2 · IC025 +2.8 3/3 methods agree	Labeled (related wording) related wording	serious PRR 37.7	no trial data cached
Injection site erythema (redness where injected)	21	13.2 8.8–19.9ROR 14.2 · χ² 226 / p 2e-51	12.5 EB05 8.2 · IC025 +2.6 3/3 methods agree	Labeled (related wording) related wording	serious PRR 45.2	no trial data cached
Injection site mass	6	12.6 5.7–27.9ROR 12.9 · χ² 53 / p 1e-13	9.0 EB05 3.7 · IC025 +1.3 3/3 methods agree	Labeled (related wording) related wording	serious PRR 40.5	no trial data cached
Injection site swelling	11	11.3 6.3–20.1ROR 11.7 · χ² 93 / p 2e-22	9.4 EB05 5.0 · IC025 +1.9 3/3 methods agree	Labeled (related wording) related wording	serious PRR 30.0	no trial data cached

Trial evidence (ClinicalTrials.gov)

Trial cross-check not yet run for this drug (ClinicalTrials.gov pull covers the 800 most-reported drugs first).

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
Skin discolouration	35	59.2 43.5–80.6ROR 67.9 · χ² 1,947 / p <1e-300	57.4 EB05 43.1 · IC025 +4.5 3/3 methods agree	Not in label — unassessed	serious PRR 61.5 · ♀ 90% (drug 66%)	no trial data cached
Injection site pruritus	22	25.7 17.2–38.3ROR 27.9 · χ² 499 / p 8e-111	25.2 EB05 17.5 · IC025 +3.3 3/3 methods agree	Labeled (related wording) related wording	serious PRR 104.1	no trial data cached
Injection site erythema (redness where injected)	21	13.2 8.8–19.9ROR 14.2 · χ² 226 / p 2e-51	12.5 EB05 8.2 · IC025 +2.6 3/3 methods agree	Labeled (related wording) related wording	serious PRR 45.2	no trial data cached
Injection site bruising	18	17.7 11.3–27.7ROR 18.9 · χ² 269 / p 1e-60	17.2 EB05 11.2 · IC025 +2.8 3/3 methods agree	Labeled (related wording) related wording	serious PRR 37.7	no trial data cached
Increased appetite	17	70.3 44.4–111.4ROR 75.0 · χ² 1,093 / p 5e-240	65.3 EB05 43.2 · IC025 +3.7 3/3 methods agree	Not in label — unassessed	serious PRR 87.2	no trial data cached
Hunger	17	98.3 62.0–155.8ROR 104.8 · χ² 1,540 / p <1e-300	88.7 EB05 58.6 · IC025 +3.9 3/3 methods agree	Not in label — unassessed	serious n=14	no trial data cached
Intentional dose omission	15	42.6 26.1–69.7ROR 45.1 · χ² 569 / p 4e-126	40.6 EB05 26.1 · IC025 +3.3 3/3 methods agree	Reporting / coding artifact	serious PRR 52.7	no trial data cached
Product dose omission in error	14	40.5 24.3–67.5ROR 42.7 · χ² 501 / p 3e-111	38.5 EB05 24.4 · IC025 +3.2 3/3 methods agree	Reporting / coding artifact	serious PRR 103.1	no trial data cached
Injection site nodule	13	92.0 54.1–156.4ROR 96.6 · χ² 1,080 / p 3e-237	81.3 EB05 50.6 · IC025 +3.5 3/3 methods agree	Labeled (related wording) related wording	serious n=8	no trial data cached
Injection site swelling	11	11.3 6.3–20.1ROR 11.7 · χ² 93 / p 2e-22	9.4 EB05 5.0 · IC025 +1.9 3/3 methods agree	Labeled (related wording) related wording	serious PRR 30.0	no trial data cached
Injection site mass	6	12.6 5.7–27.9ROR 12.9 · χ² 53 / p 1e-13	9.0 EB05 3.7 · IC025 +1.3 3/3 methods agree	Labeled (related wording) related wording	serious PRR 40.5	no trial data cached
Injection site urticaria	6	19.2 8.7–42.4ROR 19.6 · χ² 86 / p 8e-21	16.0 EB05 5.9 · IC025 +1.6 3/3 methods agree	Labeled (related wording) related wording	serious n=5	no trial data cached
Injection site irritation	5	30.7 12.9–73.2ROR 31.3 · χ² 116 / p 3e-27	26.4 EB05 9.9 · IC025 +1.5 3/3 methods agree	Labeled (related wording) related wording	serious n=3	no trial data cached
Injection site induration	4	24.0 9.1–63.4ROR 24.3 · χ² 67 / p 2e-16	17.9 EB05 4.7 · IC025 +1.0 3/3 methods agree	Labeled (related wording) related wording	serious n=3	no trial data cached
Intentional self-injury	3	11.5 3.7–35.6ROR 11.7 · χ² 19 / p 5e-6	5.8 EB05 1.9 · IC025 +0.1	Reporting / coding artifact	serious PRR 10.5	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.

Skin discolouration — n=35, PRR 59.2

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 Setmelanotide?

In FDA FAERS, the most frequently co-reported reaction terms for Setmelanotide are skin discolouration, injection site pruritus, injection site erythema, injection site bruising, increased appetite, hunger. 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 Setmelanotide have an FDA boxed warning?

No. The FDA label retrieved for Setmelanotide has no boxed warning; see the label's Warnings and Precautions for the recognised risks.

Do FAERS signals prove that Setmelanotide 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 70c3ccf7-4df0-4c75-ba07-fede9970c8d9, effective 20260401; matched on openfda.generic_name.exact:"SETMELANOTIDE")
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, field patient.drug.openfda.generic_name.exact, 16 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.