Naldemedine side effects: what 1,619 FDA adverse event reports show

Naldemedine · Symproic · 47 reaction terms · 797 drug–reaction co-reports · data 2026-09-14

Drug class

Opioid antagonist

FDA label, Indications wording

Brand names

Symproic

openFDA label

Who reports

1,619 reports · 74% serious · 457 with death outcome · 46% female

openFDA FAERS counts, all years, deduplication not applied

Used for

SYMPROIC is indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation.

FDA label, Indications and Usage

What it is

SYMPROIC (naldemedine), an opioid antagonist, contains naldemedine tosylate as the active ingredient.

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 28 strongest signals

Labeled (related wording) 1Reporting / coding artifact 1Lab value / disease marker 1Not in label — unassessed 25

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.
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. 19 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
Interstitial lung disease	79	21.2 17.1–26.3ROR 22.2 · χ² 1,502 / p <1e-300	21.1 EB05 17.5 · IC025 +3.9 3/3 methods agree	Not in label — unassessed	serious PRR 16.6	no trial data cached
Cytokine release syndrome	31	21.1 14.9–29.9ROR 21.5 · χ² 573 / p 5e-127	20.8 EB05 15.3 · IC025 +3.4 3/3 methods agree	Not in label — unassessed	serious PRR 16.6 · 100% clinician	no trial data cached
Hepatic function abnormal	51	17.8 13.6–23.4ROR 18.4 · χ² 794 / p 4e-175	17.7 EB05 13.9 · IC025 +3.5 3/3 methods agree	Not in label — unassessed	serious PRR 14.1 · 92% clinician	no trial data cached
Delirium	43	16.1 12.0–21.7ROR 16.5 · χ² 595 / p 9e-132	15.9 EB05 12.2 · IC025 +3.3 3/3 methods agree	Not in label — unassessed	serious PRR 12.8	no trial data cached
Malignant neoplasm progression	96	12.2 10.1–14.8ROR 12.9 · χ² 981 / p 1e-215	12.1 EB05 10.1 · IC025 +3.2 3/3 methods agree	Reporting / coding artifact	serious PRR 9.7	no trial data cached
Disseminated intravascular coagulation	12	11.0 6.3–19.4ROR 11.1 · χ² 99 / p 1e-23	9.3 EB05 5.1 · IC025 +2.0 3/3 methods agree	Not in label — unassessed	serious PRR 8.6	no trial data cached
Adrenal insufficiency	10	10.8 5.8–20.1ROR 10.9 · χ² 80 / p 2e-19	8.7 EB05 4.6 · IC025 +1.8 3/3 methods agree	Not in label — unassessed	serious PRR 8.5	no trial data cached
Ileus	10	10.5 5.7–19.5ROR 10.6 · χ² 77 / p 9e-19	8.4 EB05 4.5 · IC025 +1.8 3/3 methods agree	Not in label — unassessed	serious PRR 8.3	no trial data cached
Sinus tachycardia	11	10.1 5.6–18.1ROR 10.1 · χ² 81 / p 1e-19	8.2 EB05 4.5 · IC025 +1.8 3/3 methods agree	Not in label — unassessed	serious PRR 8.0	no trial data cached
Neutrophil count decreased	31	9.9 7.0–14.1ROR 10.1 · χ² 240 / p 2e-54	9.3 EB05 6.6 · IC025 +2.5 3/3 methods agree	Lab value / disease marker	serious PRR 7.8 · 94% clinician	no trial data cached
Metastases to liver	13	9.6 5.6–16.5ROR 9.7 · χ² 92 / p 5e-22	8.0 EB05 4.7 · IC025 +1.9 3/3 methods agree	Not in label — unassessed	serious PRR 7.5	no trial data cached
Febrile neutropenia	48	9.4 7.1–12.4ROR 9.7 · χ² 353 / p 6e-79	9.0 EB05 6.9 · IC025 +2.6 3/3 methods agree	Not in label — unassessed	serious PRR 7.3 · ♀ 21% (drug 46%) · 98% clinician	no trial data cached
Metastases to bone	11	8.7 4.8–15.7ROR 8.8 · χ² 68 / p 1e-16	6.9 EB05 4.0 · IC025 +1.7 3/3 methods agree	Not in label — unassessed	serious PRR 6.9	no trial data cached
Toxic epidermal necrolysis (severe skin peeling reaction)	10	8.6 4.6–15.9ROR 8.6 · χ² 60 / p 5e-15	6.7 EB05 3.7 · IC025 +1.6 3/3 methods agree	Not in label — unassessed	serious PRR 6.7	no trial data cached
Altered state of consciousness	13	7.8 4.5–13.4ROR 7.9 · χ² 71 / p 2e-17	6.4 EB05 3.9 · IC025 +1.7 3/3 methods agree	Not in label — unassessed	serious PRR 6.1	no trial data cached
Lung neoplasm malignant	24	7.5 5.1–11.2ROR 7.6 · χ² 130 / p 3e-30	6.7 EB05 4.7 · IC025 +2.0 3/3 methods agree	Not in label — unassessed	serious PRR 5.9 · 100% clinician	no trial data cached
Multiple organ dysfunction syndrome	14	6.5 3.9–11.0ROR 6.5 · χ² 60 / p 5e-15	5.5 EB05 3.4 · IC025 +1.5 3/3 methods agree	Not in label — unassessed	serious PRR 5.1	no trial data cached
Hyperkalaemia (high potassium)	17	6.3 3.9–10.1ROR 6.4 · χ² 71 / p 2e-17	5.5 EB05 3.6 · IC025 +1.6 3/3 methods agree	Not in label — unassessed	serious PRR 5.0	no trial data cached
Drug-induced liver injury	15	6.3 3.8–10.4ROR 6.4 · χ² 62 / p 2e-15	5.4 EB05 3.4 · IC025 +1.6 3/3 methods agree	Not in label — unassessed	serious PRR 5.0	no trial data cached
Stevens-johnson syndrome (severe blistering skin reaction)	10	5.8 3.1–10.8ROR 5.8 · χ² 35 / p 1e-9	4.7 EB05 2.7 · IC025 +1.2 3/3 methods agree	Not in label — unassessed	serious PRR 4.6	no trial data cached
Pancreatic carcinoma	13	5.8 3.4–10.0ROR 5.8 · χ² 47 / p 4e-12	4.9 EB05 3.0 · IC025 +1.4 3/3 methods agree	Not in label — unassessed	serious PRR 4.5	no trial data cached
Electrocardiogram qt prolonged	16	5.8 3.5–9.4ROR 5.8 · χ² 58 / p 1e-14	5.0 EB05 3.3 · IC025 +1.5 3/3 methods agree	Not in label — unassessed	serious PRR 4.6	no trial data cached
Cerebral infarction	10	5.3 2.9–9.8ROR 5.3 · χ² 31 / p 1e-8	4.3 EB05 2.5 · IC025 +1.1 3/3 methods agree	Not in label — unassessed	serious PRR 4.1	no trial data cached
Neoplasm malignant	27	5.2 3.6–7.6ROR 5.3 · χ² 89 / p 2e-21	4.8 EB05 3.5 · IC025 +1.6 3/3 methods agree	Not in label — unassessed	serious PRR 4.2 · 100% clinician	no trial data cached
Pneumonitis	10	4.8 2.6–8.9ROR 4.8 · χ² 26 / p 1e-7	4.0 EB05 2.4 · IC025 +0.9 3/3 methods agree	Not in label — unassessed	serious PRR 3.5	no trial data cached
Neoplasm progression	12	4.4 2.5–7.8ROR 4.5 · χ² 29 / p 5e-8	3.8 EB05 2.4 · IC025 +1.0 3/3 methods agree	Not in label — unassessed	serious PRR 4.8	no trial data cached
Myelosuppression	10	3.8 2.1–7.1ROR 3.8 · χ² 18 / p 1e-5	3.3 EB05 2.0 · IC025 +0.7	Not in label — unassessed	serious PRR 3.0	no trial data cached
Drug withdrawal syndrome	25	3.7 2.5–5.4ROR 3.7 · χ² 46 / p 7e-12	3.4 EB05 2.5 · IC025 +1.1 3/3 methods agree	Labeled (related wording) related wording	serious PRR 1.7 · ♀ 72% (drug 46%)	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
Malignant neoplasm progression	96	12.2 10.1–14.8ROR 12.9 · χ² 981 / p 1e-215	12.1 EB05 10.1 · IC025 +3.2 3/3 methods agree	Reporting / coding artifact	serious PRR 9.7	no trial data cached
Interstitial lung disease	79	21.2 17.1–26.3ROR 22.2 · χ² 1,502 / p <1e-300	21.1 EB05 17.5 · IC025 +3.9 3/3 methods agree	Not in label — unassessed	serious PRR 16.6	no trial data cached
Hepatic function abnormal	51	17.8 13.6–23.4ROR 18.4 · χ² 794 / p 4e-175	17.7 EB05 13.9 · IC025 +3.5 3/3 methods agree	Not in label — unassessed	serious PRR 14.1 · 92% clinician	no trial data cached
Febrile neutropenia	48	9.4 7.1–12.4ROR 9.7 · χ² 353 / p 6e-79	9.0 EB05 6.9 · IC025 +2.6 3/3 methods agree	Not in label — unassessed	serious PRR 7.3 · ♀ 21% (drug 46%) · 98% clinician	no trial data cached
Delirium	43	16.1 12.0–21.7ROR 16.5 · χ² 595 / p 9e-132	15.9 EB05 12.2 · IC025 +3.3 3/3 methods agree	Not in label — unassessed	serious PRR 12.8	no trial data cached
Neutrophil count decreased	31	9.9 7.0–14.1ROR 10.1 · χ² 240 / p 2e-54	9.3 EB05 6.6 · IC025 +2.5 3/3 methods agree	Lab value / disease marker	serious PRR 7.8 · 94% clinician	no trial data cached
Cytokine release syndrome	31	21.1 14.9–29.9ROR 21.5 · χ² 573 / p 5e-127	20.8 EB05 15.3 · IC025 +3.4 3/3 methods agree	Not in label — unassessed	serious PRR 16.6 · 100% clinician	no trial data cached
Neoplasm malignant	27	5.2 3.6–7.6ROR 5.3 · χ² 89 / p 2e-21	4.8 EB05 3.5 · IC025 +1.6 3/3 methods agree	Not in label — unassessed	serious PRR 4.2 · 100% clinician	no trial data cached
Drug withdrawal syndrome	25	3.7 2.5–5.4ROR 3.7 · χ² 46 / p 7e-12	3.4 EB05 2.5 · IC025 +1.1 3/3 methods agree	Labeled (related wording) related wording	serious PRR 1.7 · ♀ 72% (drug 46%)	no trial data cached
Lung neoplasm malignant	24	7.5 5.1–11.2ROR 7.6 · χ² 130 / p 3e-30	6.7 EB05 4.7 · IC025 +2.0 3/3 methods agree	Not in label — unassessed	serious PRR 5.9 · 100% clinician	no trial data cached
Hyperkalaemia (high potassium)	17	6.3 3.9–10.1ROR 6.4 · χ² 71 / p 2e-17	5.5 EB05 3.6 · IC025 +1.6 3/3 methods agree	Not in label — unassessed	serious PRR 5.0	no trial data cached
Electrocardiogram qt prolonged	16	5.8 3.5–9.4ROR 5.8 · χ² 58 / p 1e-14	5.0 EB05 3.3 · IC025 +1.5 3/3 methods agree	Not in label — unassessed	serious PRR 4.6	no trial data cached
Drug-induced liver injury	15	6.3 3.8–10.4ROR 6.4 · χ² 62 / p 2e-15	5.4 EB05 3.4 · IC025 +1.6 3/3 methods agree	Not in label — unassessed	serious PRR 5.0	no trial data cached
Multiple organ dysfunction syndrome	14	6.5 3.9–11.0ROR 6.5 · χ² 60 / p 5e-15	5.5 EB05 3.4 · IC025 +1.5 3/3 methods agree	Not in label — unassessed	serious PRR 5.1	no trial data cached
Pancreatic carcinoma	13	5.8 3.4–10.0ROR 5.8 · χ² 47 / p 4e-12	4.9 EB05 3.0 · IC025 +1.4 3/3 methods agree	Not in label — unassessed	serious PRR 4.5	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.

Interstitial lung disease — n=79, PRR 21.2
Cytokine release syndrome — n=31, PRR 21.1
Hepatic function abnormal — n=51, PRR 17.8
Delirium — n=43, PRR 16.1
Febrile neutropenia — n=48, PRR 9.4
Lung neoplasm malignant — n=24, PRR 7.5
Neoplasm malignant — n=27, PRR 5.2

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 Naldemedine?

In FDA FAERS, the most frequently co-reported reaction terms for Naldemedine are interstitial lung disease, hepatic function abnormal, febrile neutropenia, delirium, neutrophil count decreased, cytokine release syndrome. 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 Naldemedine have an FDA boxed warning?

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

Do FAERS signals prove that Naldemedine 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 b1a1256c-a1eb-4abe-ab1e-30e4711afd16, effective 20250725; matched on openfda.generic_name.exact:"NALDEMEDINE")
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, 47 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.