Fam-Trastuzumab Deruxtecan-Nxki side effects: what 10,020 FDA adverse event reports show

Fam-Trastuzumab Deruxtecan-Nxki · Enhertu · 844 reaction terms · 26,314 drug–reaction co-reports · data 2026-09-14

Drug class

Her2-directed antibody and topoisomerase inhibitor conjugate

FDA label, Indications wording

Brand names

Enhertu

openFDA label

Who reports

10,020 reports · 75% serious · 2,575 with death outcome · 88% female

openFDA FAERS counts, all years, deduplication not applied

Used for

ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for: HER2-Positive Early Breast Cancer as neoadjuvant treatment of adult patients with HER2-positive (IHC 3+ or ISH+) Stage II or III breast cancer, as determined by an FDA-authorized test followed by a taxane, trastuzumab, and pertuzumab (THP).

FDA label, Indications and Usage

What it is

Fam-trastuzumab deruxtecan-nxki is a HER2-directed antibody and topoisomerase inhibitor conjugate. Fam-trastuzumab deruxtecan-nxki is an antibody-drug conjugate (ADC) composed of three compone.

FDA label, Description section

Boxed warning

INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY Interstitial Lung Disease (ILD) and pneumonitis, including severe, life-threatening, and fatal cases, have been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms.

FDA 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 40 strongest signals

Labeled — boxed warning 3Labeled adverse reaction 5Labeled (related wording) 11Reporting / coding artifact 2Lab value / disease marker 2Not in label — unassessed 17

What the badges mean

Labeled — boxed warning The term (or its clinical synonym) appears in the FDA boxed warning: causality is regulator-recognised and considered serious.
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.
Lab value / disease marker A laboratory result, investigation or disease-activity marker (antibody positive, CRP abnormal, swollen joint count) not described in the label. These usually mirror the monitored disease or testing protocol rather than a drug effect; not screened further.
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. 804 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
Nail bed inflammation	25	178.5 118.7–268.5ROR 179.0 · χ² 3,900 / p <1e-300	146.3 EB05 104.2 · IC025 +4.6 3/3 methods agree	Not in label — unassessed	serious n=25	no trial data cached
Kl-6 increased	11	113.5 61.9–208.2ROR 113.6 · χ² 1,059 / p 2e-232	91.1 EB05 54.3 · IC025 +3.2 3/3 methods agree	Not in label — unassessed	serious n=10	no trial data cached
Nasal mucosal disorder	25	93.5 62.6–139.5ROR 93.7 · χ² 2,100 / p <1e-300	83.9 EB05 59.8 · IC025 +4.4 3/3 methods agree	Not in label — unassessed	serious n=25	no trial data cached
Radiation necrosis	24	92.1 61.2–138.5ROR 92.3 · χ² 1,983 / p <1e-300	82.6 EB05 58.4 · IC025 +4.3 3/3 methods agree	Not in label — unassessed	serious n=22 · 96% clinician	no trial data cached
Pseudocirrhosis	12	79.4 44.6–141.2ROR 79.5 · χ² 820 / p 1e-180	68.5 EB05 41.8 · IC025 +3.3 3/3 methods agree	Not in label — unassessed	serious n=10	no trial data cached
Streptococcal sepsis	27	48.4 33.1–70.9ROR 48.5 · χ² 1,179 / p 1e-258	45.9 EB05 33.1 · IC025 +4.0 3/3 methods agree	Not in label — unassessed	serious n=27	no trial data cached
Interstitial lung disease	1,020	45.1 42.5–47.9ROR 50.1 · χ² 43,118 / p <1e-300	44.1 EB05 41.9 · IC025 +5.3 3/3 methods agree	Labeled — boxed warning exact term	serious PRR 30.8 · 97% clinician	no trial data cached
Lymphangiosis carcinomatosa	22	45.1 29.6–68.8ROR 45.2 · χ² 886 / p 7e-195	42.6 EB05 29.7 · IC025 +3.8 3/3 methods agree	Not in label — unassessed	serious n=22 · 100% clinician	no trial data cached
Metastases to meninges	45	42.8 31.9–57.5ROR 43.0 · χ² 1,761 / p <1e-300	41.3 EB05 32.1 · IC025 +4.4 3/3 methods agree	Labeled adverse reaction exact term	serious n=45 · 91% clinician	no trial data cached
Metastases to central nervous system	257	42.8 37.9–48.4ROR 43.9 · χ² 10,251 / p <1e-300	41.9 EB05 37.7 · IC025 +5.1 3/3 methods agree	Labeled (related wording) related wording	serious PRR 32.6	no trial data cached
Metastases to skin	18	37.4 23.5–59.6ROR 37.5 · χ² 591 / p 7e-131	35.5 EB05 23.8 · IC025 +3.4 3/3 methods agree	Labeled (related wording) related wording	serious n=18	no trial data cached
Hemianopia	17	36.2 22.4–58.5ROR 36.3 · χ² 538 / p 3e-119	34.4 EB05 22.7 · IC025 +3.3 3/3 methods agree	Not in label — unassessed	serious n=17	no trial data cached
Pneumonitis	401	31.5 28.6–34.7ROR 32.8 · χ² 11,646 / p <1e-300	31.0 EB05 28.5 · IC025 +4.7 3/3 methods agree	Labeled — boxed warning exact term	serious PRR 21.5	no trial data cached
Pseudomonal sepsis	26	31.3 21.3–46.1ROR 31.4 · χ² 722 / p 2e-159	30.3 EB05 21.7 · IC025 +3.6 3/3 methods agree	Not in label — unassessed	serious n=26	no trial data cached
Eastern cooperative oncology group performance status worsened	18	30.7 19.3–48.9ROR 30.8 · χ² 481 / p 6e-107	29.4 EB05 19.7 · IC025 +3.3 3/3 methods agree	Labeled (related wording) related wording	serious n=17	no trial data cached
Metastases to pleura	15	30.6 18.4–50.9ROR 30.6 · χ² 394 / p 5e-88	29.1 EB05 18.7 · IC025 +3.1 3/3 methods agree	Labeled (related wording) related wording	serious n=14	no trial data cached
Lung opacity	35	28.8 20.7–40.2ROR 28.9 · χ² 900 / p 5e-198	28.1 EB05 21.1 · IC025 +3.8 3/3 methods agree	Labeled adverse reaction exact term	serious n=29 · 91% clinician	no trial data cached
Cell death	27	28.8 19.7–42.1ROR 28.9 · χ² 687 / p 8e-152	27.9 EB05 20.1 · IC025 +3.6 3/3 methods agree	Labeled (related wording) related wording	serious n=27 · 100% clinician	no trial data cached
Pulmonary toxicity	80	24.1 19.4–30.0ROR 24.3 · χ² 1,730 / p <1e-300	23.7 EB05 19.7 · IC025 +4.0 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 17.4 · 92% clinician	no trial data cached
Ocular toxicity	11	22.0 12.1–39.8ROR 22.0 · χ² 198 / p 3e-45	20.8 EB05 11.8 · IC025 +2.5 3/3 methods agree	Not in label — unassessed	serious n=8	no trial data cached
Pneumocystis jirovecii infection	11	20.1 11.1–36.5ROR 20.2 · χ² 180 / p 3e-41	18.9 EB05 10.6 · IC025 +2.4 3/3 methods agree	Labeled (related wording) related wording	serious n=11	no trial data cached
Excessive eye blinking	14	20.0 11.8–33.8ROR 20.0 · χ² 232 / p 1e-52	19.1 EB05 11.7 · IC025 +2.7 3/3 methods agree	Not in label — unassessed	serious n=14	no trial data cached
Vascular device infection	42	19.6 14.5–26.6ROR 19.7 · χ² 718 / p 2e-158	19.3 EB05 14.8 · IC025 +3.5 3/3 methods agree	Labeled (related wording) related wording	serious n=42 · 90% clinician	no trial data cached
Ventricular dysfunction	24	19.5 13.1–29.1ROR 19.5 · χ² 399 / p 4e-89	19.0 EB05 13.3 · IC025 +3.1 3/3 methods agree	Labeled — boxed warning exact term	serious n=24 · 100% clinician	no trial data cached
Disease progression	1,077	19.3 18.2–20.4ROR 21.5 · χ² 18,579 / p <1e-300	19.1 EB05 18.2 · IC025 +4.1 3/3 methods agree	Reporting / coding artifact	serious PRR 14.9 · 93% clinician	no trial data cached
Metastases to lymph nodes	58	18.2 14.1–23.6ROR 18.3 · χ² 921 / p 2e-202	18.0 EB05 14.4 · IC025 +3.5 3/3 methods agree	Not in label — unassessed	serious n=57	no trial data cached
Pneumocystis jirovecii pneumonia	86	18.2 14.7–22.4ROR 18.3 · χ² 1,365 / p 4e-299	17.9 EB05 15.0 · IC025 +3.7 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 13.9 · 100% clinician	no trial data cached
Metastases to liver	134	16.1 13.6–19.1ROR 16.3 · χ² 1,871 / p <1e-300	15.9 EB05 13.8 · IC025 +3.6 3/3 methods agree	Not in label — unassessed	serious PRR 12.4	no trial data cached
Ejection fraction decreased	117	15.8 13.2–19.0ROR 16.0 · χ² 1,600 / p <1e-300	15.7 EB05 13.4 · IC025 +3.6 3/3 methods agree	Lab value / disease marker	serious PRR 9.3 · 96% clinician	no trial data cached
Cardiac dysfunction	26	15.0 10.2–22.0ROR 15.0 · χ² 323 / p 2e-72	14.5 EB05 10.1 · IC025 +2.9 3/3 methods agree	Labeled (related wording) related wording	serious n=25 · 92% clinician	no trial data cached
Myelosuppression	234	14.5 12.8–16.4ROR 14.8 · χ² 2,909 / p <1e-300	14.4 EB05 12.9 · IC025 +3.6 3/3 methods agree	Not in label — unassessed	serious PRR 11.1 · 99% clinician	no trial data cached
Therapy change	63	13.8 10.7–17.6ROR 13.8 · χ² 728 / p 1e-160	13.5 EB05 10.9 · IC025 +3.2 3/3 methods agree	Reporting / coding artifact	serious n=39	no trial data cached
Gastrointestinal toxicity	30	13.4 9.4–19.2ROR 13.4 · χ² 330 / p 4e-74	12.9 EB05 9.2 · IC025 +2.9 3/3 methods agree	Labeled (related wording) related wording	serious n=23 · 97% clinician	no trial data cached
Paronychia	27	13.1 9.0–19.2ROR 13.2 · χ² 289 / p 5e-65	12.6 EB05 8.7 · IC025 +2.8 3/3 methods agree	Not in label — unassessed	serious n=27	no trial data cached
Metastases to lung	71	12.9 10.3–16.3ROR 13.0 · χ² 766 / p 6e-169	12.7 EB05 10.3 · IC025 +3.2 3/3 methods agree	Labeled (related wording) related wording	serious PRR 9.9	no trial data cached
Ascites	169	12.1 10.4–14.0ROR 12.3 · χ² 1,700 / p <1e-300	12.0 EB05 10.5 · IC025 +3.3 3/3 methods agree	Not in label — unassessed	serious PRR 9.3	no trial data cached
Varicose vein	29	11.7 8.2–16.9ROR 11.8 · χ² 273 / p 1e-61	11.1 EB05 7.8 · IC025 +2.7 3/3 methods agree	Not in label — unassessed	serious n=28	no trial data cached
Radiation pneumonitis	11	10.8 6.0–19.5ROR 10.8 · χ² 88 / p 4e-21	8.8 EB05 4.8 · IC025 +1.9 3/3 methods agree	Labeled adverse reaction exact term	serious n=11	no trial data cached
Metastases to bone	79	10.1 8.1–12.6ROR 10.2 · χ² 640 / p 2e-141	9.9 EB05 8.1 · IC025 +2.9 3/3 methods agree	Labeled (related wording) related wording	serious PRR 7.8	no trial data cached
Tumour marker increased	23	10.0 6.7–15.1ROR 10.1 · χ² 178 / p 8e-41	9.1 EB05 6.1 · IC025 +2.4 3/3 methods agree	Lab value / disease marker	serious n=14	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
Nausea	1,219	3.2 3.1–3.4ROR 3.5 · χ² 1,952 / p <1e-300	3.2 EB05 3.1 · IC025 +1.6 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 2.7	no trial data cached
Death	1,213	2.9 2.8–3.1ROR 3.2 · χ² 1,626 / p <1e-300	2.9 EB05 2.8 · IC025 +1.5 3/3 methods agree	Outcome field, not a reaction boxed warning mentions mortality	serious PRR 2.3	no trial data cached
Disease progression	1,077	19.3 18.2–20.4ROR 21.5 · χ² 18,579 / p <1e-300	19.1 EB05 18.2 · IC025 +4.1 3/3 methods agree	Reporting / coding artifact	serious PRR 14.9 · 93% clinician	no trial data cached
Interstitial lung disease	1,020	45.1 42.5–47.9ROR 50.1 · χ² 43,118 / p <1e-300	44.1 EB05 41.9 · IC025 +5.3 3/3 methods agree	Labeled — boxed warning exact term	serious PRR 30.8 · 97% clinician	no trial data cached
Off label use (used outside approved label)	797	1.9 1.8–2.1ROR 2.0 · χ² 367 / p 5e-82	1.9 EB05 1.8 · IC025 +0.8	Reporting / coding artifact	serious PRR 1.4	no trial data cached
Fatigue (tiredness)	797	2.1 2.0–2.3ROR 2.2 · χ² 506 / p 2e-112	2.1 EB05 2.0 · IC025 +1.0 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 1.5	no trial data cached
Diarrhoea (diarrhea)	575	1.9 1.7–2.0ROR 1.9 · χ² 240 / p 2e-54	1.9 EB05 1.7 · IC025 +0.8	Labeled adverse reaction exact term	serious PRR 1.7	no trial data cached
Vomiting	560	2.5 2.3–2.7ROR 2.6 · χ² 514 / p 4e-114	2.5 EB05 2.3 · IC025 +1.2 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 1.9	no trial data cached
Pneumonitis	401	31.5 28.6–34.7ROR 32.8 · χ² 11,646 / p <1e-300	31.0 EB05 28.5 · IC025 +4.7 3/3 methods agree	Labeled — boxed warning exact term	serious PRR 21.5	no trial data cached
Decreased appetite (loss of appetite)	382	3.5 3.1–3.8ROR 3.6 · χ² 670 / p 4e-148	3.4 EB05 3.2 · IC025 +1.6 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 3.2	no trial data cached
Asthenia (weakness)	381	2.1 1.9–2.3ROR 2.2 · χ² 229 / p 6e-52	2.1 EB05 1.9 · IC025 +0.9	Labeled adverse reaction exact term	serious PRR 2.0	no trial data cached
No adverse event	365	4.3 3.9–4.8ROR 4.4 · χ² 932 / p 7e-205	4.3 EB05 3.9 · IC025 +1.9 3/3 methods agree	Reporting / coding artifact	serious PRR 0.4	no trial data cached
Alopecia (hair loss)	347	3.7 3.3–4.1ROR 3.8 · χ² 685 / p 3e-151	3.7 EB05 3.4 · IC025 +1.7 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 2.7	no trial data cached
Dyspnoea (shortness of breath)	321	1.2 1.1–1.3ROR 1.2 · χ² 10 / p 1e-3	1.2 EB05 1.1 · IC025 +0.1	Labeled — boxed warning exact term	serious PRR 1.1	no trial data cached
Intentional product use issue	259	6.2 5.5–7.0ROR 6.3 · χ² 1,120 / p 7e-246	6.1 EB05 5.5 · IC025 +2.4 3/3 methods agree	Reporting / coding artifact	serious PRR 6.7 · 95% clinician	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.

Nail bed inflammation — n=25, PRR 178.5
Nasal mucosal disorder — n=25, PRR 93.5
Radiation necrosis — n=24, PRR 92.1
Streptococcal sepsis — n=27, PRR 48.4
Lymphangiosis carcinomatosa — n=22, PRR 45.1
Pseudomonal sepsis — n=26, PRR 31.3
Metastases to lymph nodes — n=58, PRR 18.2
Metastases to liver — n=134, PRR 16.1
Myelosuppression — n=234, PRR 14.5
Paronychia — n=27, PRR 13.1

✓ A hand-written Bradford Hill causality assessment exists for this drug: Trastuzumab ↔ Cardiotoxicity / heart failure.

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 Fam-Trastuzumab Deruxtecan-Nxki?

In FDA FAERS, the most frequently co-reported reaction terms for Fam-Trastuzumab Deruxtecan-Nxki are nausea, interstitial lung disease, fatigue, diarrhoea, vomiting, pneumonitis. 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 Fam-Trastuzumab Deruxtecan-Nxki have an FDA boxed warning?

Yes. The current FDA label carries a boxed warning: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY Interstitial Lung Disease (ILD) and pneumonitis, including severe, life-threatening, and fatal cases, have been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms.

Do FAERS signals prove that Fam-Trastuzumab Deruxtecan-Nxki 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 7e67e73e-ddf4-4e4d-8b50-09d7514910b6, effective 20260515; matched on openfda.generic_name.exact:"FAM-TRASTUZUMAB DERUXTECAN-NXKI")
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, 844 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.