Nirogacestat side effects: what 826 FDA adverse event reports show

Nirogacestat · Ogsiveo · 28 reaction terms · 386 drug–reaction co-reports · data 2026-09-14

Drug class

Gamma Secretase Inhibitor

FDA label (Established Pharmacologic Class)

Brand names

Ogsiveo

openFDA label

Who reports

826 reports · 29% serious · 8 with death outcome · 66% female

openFDA FAERS counts, all years, deduplication not applied

Used for

OGSIVEO is indicated for adult patients with progressing desmoid tumors who require systemic treatment. OGSIVEO is a gamma secretase inhibitor indicated for adult patients with progressing desmoid tumors who require systemic treatment. ( 1 )

FDA label, Indications and Usage

What it is

OGSIVEO oral tablets contain nirogacestat (as nirogacestat hydrobromide), a gamma (ɣ) secretase inhibitor. Nirogacestat hydrobromide is chemically known as (S)-2-(((S)-6,8-Difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino)propan-2-yl)-1H-imidazol-4-yl) pentanamide dihydrobromide.

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 23 strongest signals

Labeled adverse reaction 4Reporting / coding artifact 4Not in label — unassessed 15

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.
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. 5 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
Product dose omission in error	42	39.2 29.2–52.6ROR 41.2 · χ² 1,525 / p <1e-300	38.5 EB05 29.7 · IC025 +4.2 3/3 methods agree	Reporting / coding artifact	serious PRR 81.3 · 100% consumer	no trial data cached
Amenorrhoea (missed periods)	17	25.5 15.9–40.8ROR 26.0 · χ² 376 / p 4e-84	24.8 EB05 16.4 · IC025 +3.1 3/3 methods agree	Not in label — unassessed	serious PRR 48.3	no trial data cached
Dry throat	10	24.7 13.3–45.7ROR 25.0 · χ² 204 / p 1e-46	23.4 EB05 13.2 · IC025 +2.5 3/3 methods agree	Not in label — unassessed	serious n=1	no trial data cached
Stomatitis (mouth sores)	59	24.4 19.0–31.2ROR 26.1 · χ² 1,301 / p 4e-285	24.2 EB05 19.4 · IC025 +3.9 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 23.7 · 78% consumer	no trial data cached
Folliculitis	8	19.4 9.7–38.7ROR 19.6 · χ² 122 / p 1e-28	17.5 EB05 8.0 · IC025 +2.0 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 17.2	no trial data cached
Intentional dose omission	19	17.4 11.2–27.1ROR 17.8 · χ² 278 / p 1e-62	16.9 EB05 11.1 · IC025 +2.8 3/3 methods agree	Reporting / coding artifact	serious PRR 15.1	no trial data cached
Brain fog	10	17.2 9.3–31.8ROR 17.4 · χ² 136 / p 8e-32	15.7 EB05 8.0 · IC025 +2.2 3/3 methods agree	Not in label — unassessed	serious PRR 13.3	no trial data cached
Insurance issue	9	15.2 7.9–29.1ROR 15.3 · χ² 105 / p 5e-25	13.2 EB05 6.2 · IC025 +2.0 3/3 methods agree	Not in label — unassessed	serious PRR 28.0	no trial data cached
Thirst	10	14.0 7.6–26.0ROR 14.2 · χ² 108 / p 1e-25	12.2 EB05 6.1 · IC025 +2.0 3/3 methods agree	Not in label — unassessed	serious PRR 10.5	no trial data cached
Epistaxis (nosebleed)	37	12.4 9.0–16.9ROR 12.9 · χ² 376 / p 4e-84	12.0 EB05 8.9 · IC025 +2.9 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 9.9	no trial data cached
Neoplasm progression	17	12.1 7.6–19.4ROR 12.4 · χ² 163 / p 1e-37	11.1 EB05 6.8 · IC025 +2.4 3/3 methods agree	Not in label — unassessed	serious PRR 23.8	no trial data cached
Cyst	6	12.1 5.4–26.8ROR 12.2 · χ² 50 / p 6e-13	8.5 EB05 3.6 · IC025 +1.3 3/3 methods agree	Not in label — unassessed	serious PRR 21.2	no trial data cached
Hot flush (hot flashes)	35	11.6 8.4–16.1ROR 12.1 · χ² 330 / p 4e-74	11.2 EB05 8.2 · IC025 +2.8 3/3 methods agree	Not in label — unassessed	serious PRR 10.2 · ♀ 97% (drug 66%) · 77% consumer	no trial data cached
Ocular discomfort	5	11.5 4.8–27.6ROR 11.6 · χ² 38 / p 3e-10	7.5 EB05 3.0 · IC025 +1.0 3/3 methods agree	Not in label — unassessed	serious n=2	no trial data cached
Rash maculo-papular	10	11.3 6.1–20.9ROR 11.4 · χ² 84 / p 3e-20	9.2 EB05 4.8 · IC025 +1.8 3/3 methods agree	Not in label — unassessed	serious PRR 10.1	no trial data cached
Intestinal perforation	5	11.1 4.6–26.7ROR 11.2 · χ² 37 / p 7e-10	7.2 EB05 2.9 · IC025 +1.0 3/3 methods agree	Not in label — unassessed	serious PRR 22.5	no trial data cached
Impaired driving ability	5	11.0 4.6–26.4ROR 11.1 · χ² 36 / p 1e-9	7.1 EB05 2.9 · IC025 +1.0 3/3 methods agree	Not in label — unassessed	serious PRR 11.8	no trial data cached
Skin cancer	9	10.5 5.5–20.0ROR 10.6 · χ² 68 / p 9e-17	8.1 EB05 4.2 · IC025 +1.7 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 19.1	no trial data cached
Therapy cessation	16	7.8 4.8–12.7ROR 8.0 · χ² 89 / p 2e-21	6.7 EB05 4.3 · IC025 +1.9 3/3 methods agree	Reporting / coding artifact	serious PRR 11.0	no trial data cached
Underdose	20	6.9 4.4–10.6ROR 7.0 · χ² 94 / p 1e-22	6.0 EB05 4.1 · IC025 +1.8 3/3 methods agree	Reporting / coding artifact	serious PRR 31.5 · 80% consumer	no trial data cached
Cytokine release syndrome	5	6.6 2.7–15.7ROR 6.6 · χ² 18 / p 9e-6	4.4 EB05 2.1 · IC025 +0.6 3/3 methods agree	Not in label — unassessed	serious PRR 13.3	no trial data cached
Peritonitis	5	6.0 2.5–14.5ROR 6.1 · χ² 16 / p 3e-5	4.1 EB05 2.0 · IC025 +0.5	Not in label — unassessed	serious PRR 12.2	no trial data cached
Skin irritation	8	4.4 2.2–8.7ROR 4.4 · χ² 18 / p 1e-5	3.6 EB05 2.0 · IC025 +0.7	Not in label — unassessed	serious n=3	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
Stomatitis (mouth sores)	59	24.4 19.0–31.2ROR 26.1 · χ² 1,301 / p 4e-285	24.2 EB05 19.4 · IC025 +3.9 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 23.7 · 78% consumer	no trial data cached
Product dose omission in error	42	39.2 29.2–52.6ROR 41.2 · χ² 1,525 / p <1e-300	38.5 EB05 29.7 · IC025 +4.2 3/3 methods agree	Reporting / coding artifact	serious PRR 81.3 · 100% consumer	no trial data cached
Epistaxis (nosebleed)	37	12.4 9.0–16.9ROR 12.9 · χ² 376 / p 4e-84	12.0 EB05 8.9 · IC025 +2.9 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 9.9	no trial data cached
Hot flush (hot flashes)	35	11.6 8.4–16.1ROR 12.1 · χ² 330 / p 4e-74	11.2 EB05 8.2 · IC025 +2.8 3/3 methods agree	Not in label — unassessed	serious PRR 10.2 · ♀ 97% (drug 66%) · 77% consumer	no trial data cached
Underdose	20	6.9 4.4–10.6ROR 7.0 · χ² 94 / p 1e-22	6.0 EB05 4.1 · IC025 +1.8 3/3 methods agree	Reporting / coding artifact	serious PRR 31.5 · 80% consumer	no trial data cached
Intentional dose omission	19	17.4 11.2–27.1ROR 17.8 · χ² 278 / p 1e-62	16.9 EB05 11.1 · IC025 +2.8 3/3 methods agree	Reporting / coding artifact	serious PRR 15.1	no trial data cached
Neoplasm progression	17	12.1 7.6–19.4ROR 12.4 · χ² 163 / p 1e-37	11.1 EB05 6.8 · IC025 +2.4 3/3 methods agree	Not in label — unassessed	serious PRR 23.8	no trial data cached
Amenorrhoea (missed periods)	17	25.5 15.9–40.8ROR 26.0 · χ² 376 / p 4e-84	24.8 EB05 16.4 · IC025 +3.1 3/3 methods agree	Not in label — unassessed	serious PRR 48.3	no trial data cached
Therapy cessation	16	7.8 4.8–12.7ROR 8.0 · χ² 89 / p 2e-21	6.7 EB05 4.3 · IC025 +1.9 3/3 methods agree	Reporting / coding artifact	serious PRR 11.0	no trial data cached
Rash maculo-papular	10	11.3 6.1–20.9ROR 11.4 · χ² 84 / p 3e-20	9.2 EB05 4.8 · IC025 +1.8 3/3 methods agree	Not in label — unassessed	serious PRR 10.1	no trial data cached
Thirst	10	14.0 7.6–26.0ROR 14.2 · χ² 108 / p 1e-25	12.2 EB05 6.1 · IC025 +2.0 3/3 methods agree	Not in label — unassessed	serious PRR 10.5	no trial data cached
Brain fog	10	17.2 9.3–31.8ROR 17.4 · χ² 136 / p 8e-32	15.7 EB05 8.0 · IC025 +2.2 3/3 methods agree	Not in label — unassessed	serious PRR 13.3	no trial data cached
Dry throat	10	24.7 13.3–45.7ROR 25.0 · χ² 204 / p 1e-46	23.4 EB05 13.2 · IC025 +2.5 3/3 methods agree	Not in label — unassessed	serious n=1	no trial data cached
Skin cancer	9	10.5 5.5–20.0ROR 10.6 · χ² 68 / p 9e-17	8.1 EB05 4.2 · IC025 +1.7 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 19.1	no trial data cached
Insurance issue	9	15.2 7.9–29.1ROR 15.3 · χ² 105 / p 5e-25	13.2 EB05 6.2 · IC025 +2.0 3/3 methods agree	Not in label — unassessed	serious PRR 28.0	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.

Hot flush — n=35, PRR 11.6

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 Nirogacestat?

In FDA FAERS, the most frequently co-reported reaction terms for Nirogacestat are stomatitis, epistaxis, hot flush, neoplasm progression, amenorrhoea, rash maculo-papular. 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 Nirogacestat have an FDA boxed warning?

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

Do FAERS signals prove that Nirogacestat 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 f172e6ff-3190-41b0-b95a-58a7ef9e9e1e, effective 20260901; matched on openfda.generic_name.exact:"NIROGACESTAT")
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, 28 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.