Linaclotide side effects: what 26,520 FDA adverse event reports show
Drug class
Guanylate Cyclase-C Agonist
Brand names
Linzess
Who reports
26,520 reports · 36% serious · 1,064 with death outcome · 73% female
Used for
LINZESS is indicated for the treatment of: • irritable bowel syndrome with constipation (IBS-C) in adults and pediatric patients 7 years of age and older • chronic idiopathic constipation (CIC) in adults • functional constipation (FC) in pediatric pati.
What it is
LINZESS (linaclotide) is a guanylate cyclase-C (GC-C) agonist. Linaclotide is a 14-amino acid peptide with the following chemical name: L-cysteinyl-L-cysteinyl-L-glutamyl-L-tyrosyl-L-cysteinyl.
Boxed warning
RISK OF SERIOUS DEHYDRATION IN PEDIATRIC PATIENTS LESS THAN 2 YEARS OF AGE LINZESS is contraindicated in patients less than 2 years of age; in nonclinical studies in neonatal mice, administration of a single, clinica.
Causality screen of the 40 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.
- Likely indication confounding The term appears in the label's indications: reports probably describe the disease being treated (or its progression), not a drug effect. Classic confounding by indication.
- 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. 1,083 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 |
|---|---|---|---|---|---|---|
| Therapeutic product effect increased | 38 | 27.2 19.7–37.6ROR 27.2 · χ² 902 / p 2e-198 | 26.0 EB05 19.8 · IC025 +3.8 3/3 methods agree | Reporting / coding artifact | 100% consumer | not reported in cached trials |
| Gastrointestinal motility disorder | 170 | 26.2 22.5–30.5ROR 26.3 · χ² 3,957 / p <1e-300 | 25.3 EB05 22.2 · IC025 +4.3 3/3 methods agree | Not in label — unassessed | serious n=47 · 92% consumer | not reported in cached trials |
| Faeces hard | 117 | 24.5 20.4–29.5ROR 24.6 · χ² 2,538 / p <1e-300 | 23.7 EB05 20.3 · IC025 +4.1 3/3 methods agree | Not in label — unassessed | serious n=29 · 89% consumer | not reported in cached trials |
| Infrequent bowel movements | 70 | 22.8 18.0–28.9ROR 22.8 · χ² 1,396 / p <1e-300 | 22.1 EB05 18.0 · IC025 +3.9 3/3 methods agree | Not in label — unassessed | serious n=12 · 91% consumer | not reported in cached trials |
| Bowel movement irregularity | 176 | 18.7 16.1–21.7ROR 18.8 · χ² 2,857 / p <1e-300 | 18.2 EB05 16.1 · IC025 +3.9 3/3 methods agree | Not in label — unassessed | serious n=27 · 92% consumer | not reported in cached trials |
| Dyschezia | 68 | 18.2 14.3–23.1ROR 18.3 · χ² 1,064 / p 1e-233 | 17.7 EB05 14.4 · IC025 +3.6 3/3 methods agree | Not in label — unassessed | serious n=22 · 100% consumer | not reported in cached trials |
| Faecal volume increased | 10 | 15.3 8.2–28.7ROR 15.3 · χ² 118 / p 1e-27 | 13.4 EB05 6.6 · IC025 +2.1 3/3 methods agree | Lab value / disease marker | – | not reported in cached trials |
| Anal incontinence | 167 | 15.1 13.0–17.6ROR 15.2 · χ² 2,144 / p <1e-300 | 14.8 EB05 13.0 · IC025 +3.6 3/3 methods agree | Not in label — unassessed | serious n=56 · 84% consumer | not reported in cached trials |
| Rectal tenesmus | 23 | 15.0 10.0–22.7ROR 15.0 · χ² 282 / p 1e-63 | 14.3 EB05 9.7 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | ♀ 52% (drug 73%) · 100% consumer | not reported in cached trials |
| Therapeutic response increased | 17 | 14.6 9.1–23.6ROR 14.6 · χ² 199 / p 2e-45 | 13.6 EB05 8.4 · IC025 +2.6 3/3 methods agree | Reporting / coding artifact | – | not reported in cached trials |
| Gastrointestinal hypomotility | 40 | 14.4 10.5–19.7ROR 14.4 · χ² 477 / p 4e-106 | 13.9 EB05 10.5 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious n=33 · 100% consumer | not reported in cached trials |
| Rectal prolapse | 21 | 14.0 9.1–21.5ROR 14.0 · χ² 236 / p 1e-53 | 13.1 EB05 8.6 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious n=21 | not reported in cached trials |
| Cervical radiculopathy | 12 | 13.4 7.6–23.7ROR 13.4 · χ² 124 / p 5e-29 | 11.7 EB05 6.3 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious n=11 | not reported in cached trials |
| Volvulus | 36 | 12.4 8.9–17.2ROR 12.4 · χ² 360 / p 2e-80 | 11.8 EB05 8.7 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious n=32 | not reported in cached trials |
| Abnormal faeces | 119 | 11.6 9.7–13.9ROR 11.7 · χ² 1,129 / p 7e-248 | 11.4 EB05 9.7 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious n=16 · 89% consumer | not reported in cached trials |
| Defaecation urgency | 100 | 11.5 9.4–14.0ROR 11.5 · χ² 934 / p 2e-205 | 11.2 EB05 9.4 · IC025 +3.1 3/3 methods agree | Labeled adverse reaction exact term | serious n=18 · ♀ 52% (drug 73%) · 91% consumer | not reported in cached trials |
| Gastrointestinal sounds abnormal | 70 | 11.4 9.0–14.4ROR 11.4 · χ² 645 / p 2e-142 | 11.0 EB05 8.9 · IC025 +3.0 3/3 methods agree | Not in label — unassessed | serious n=13 · 94% consumer | not reported in cached trials |
| Impaired gastric emptying | 180 | 11.3 9.8–13.1ROR 11.4 · χ² 1,658 / p <1e-300 | 11.1 EB05 9.8 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious PRR 18.9 · 81% consumer | not reported in cached trials |
| Rebound acid hypersecretion | 43 | 11.2 8.3–15.2ROR 11.2 · χ² 385 / p 5e-86 | 10.7 EB05 8.1 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious n=43 | not reported in cached trials |
| Product packaging quantity issue | 153 | 11.2 9.6–13.2ROR 11.3 · χ² 1,396 / p <1e-300 | 11.0 EB05 9.6 · IC025 +3.2 3/3 methods agree | Reporting / coding artifact | 87% consumer | not reported in cached trials |
| Gastric dilatation | 22 | 10.6 6.9–16.1ROR 10.6 · χ² 179 / p 5e-41 | 9.5 EB05 6.3 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | 100% consumer | not reported in cached trials |
| Chronic kidney disease-mineral and bone disorder | 14 | 10.4 6.1–17.6ROR 10.4 · χ² 108 / p 1e-25 | 8.8 EB05 5.2 · IC025 +2.1 3/3 methods agree | Not in label — unassessed | serious n=14 | not reported in cached trials |
| Flatulence (gas) | 703 | 9.9 9.2–10.7ROR 10.2 · χ² 5,581 / p <1e-300 | 9.8 EB05 9.2 · IC025 +3.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 6.3 · 92% consumer | NCT00730171: 34/607 (5.6%) on Linaclotide |
| Therapeutic product effect variable | 47 | 9.8 7.4–13.1ROR 9.9 · χ² 360 / p 1e-80 | 9.3 EB05 7.2 · IC025 +2.7 3/3 methods agree | Reporting / coding artifact | serious n=8 · 100% consumer | not reported in cached trials |
| Product dispensing error | 266 | 9.8 8.7–11.0ROR 9.9 · χ² 2,064 / p <1e-300 | 9.6 EB05 8.7 · IC025 +3.0 3/3 methods agree | Reporting / coding artifact | serious n=17 | not reported in cached trials |
| Drug effect variable | 14 | 9.7 5.8–16.5ROR 9.8 · χ² 100 / p 7e-24 | 8.2 EB05 4.9 · IC025 +2.0 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Nephrogenic anaemia | 56 | 9.6 7.4–12.5ROR 9.6 · χ² 416 / p 8e-93 | 9.1 EB05 7.2 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious n=56 | not reported in cached trials |
| Hyperparathyroidism secondary | 30 | 9.5 6.6–13.6ROR 9.5 · χ² 216 / p 3e-49 | 8.7 EB05 6.2 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious n=30 | not reported in cached trials |
| Postural orthostatic tachycardia syndrome | 15 | 9.1 5.5–15.2ROR 9.1 · χ² 100 / p 1e-23 | 7.7 EB05 4.7 · IC025 +2.0 3/3 methods agree | Not in label — unassessed | serious n=14 | not reported in cached trials |
| Abdominal distension (bloating) | 1,170 | 9.0 8.5–9.5ROR 9.4 · χ² 8,243 / p <1e-300 | 8.9 EB05 8.5 · IC025 +3.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 6.0 · 87% consumer | not reported in cached trials |
| Obstructive sleep apnoea syndrome | 15 | 8.6 5.2–14.3ROR 8.6 · χ² 92 / p 5e-22 | 7.2 EB05 4.5 · IC025 +1.9 3/3 methods agree | Not in label — unassessed | serious n=15 | not reported in cached trials |
| Dry age-related macular degeneration | 11 | 7.9 4.4–14.3ROR 7.9 · χ² 59 / p 7e-15 | 6.3 EB05 3.6 · IC025 +1.6 3/3 methods agree | Not in label — unassessed | serious n=11 | not reported in cached trials |
| Physical product label issue | 11 | 7.5 4.2–13.6ROR 7.5 · χ² 55 / p 5e-14 | 6.0 EB05 3.5 · IC025 +1.5 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Constipation | 1,998 | 7.4 7.1–7.7ROR 7.9 · χ² 10,982 / p <1e-300 | 7.3 EB05 7.0 · IC025 +2.8 3/3 methods agree | Likely indication confounding term in indications; also in warnings | serious PRR 8.4 · 82% consumer | NCT00730171: 16/607 (2.6%) on Linaclotide |
| Functional gastrointestinal disorder | 32 | 7.4 5.2–10.4ROR 7.4 · χ² 168 / p 1e-38 | 6.7 EB05 4.9 · IC025 +2.1 3/3 methods agree | Labeled (related wording) related wording | serious n=20 · 80% consumer | not reported in cached trials |
| Product administration interrupted | 70 | 7.3 5.7–9.2ROR 7.3 · χ² 369 / p 1e-82 | 6.9 EB05 5.7 · IC025 +2.4 3/3 methods agree | Reporting / coding artifact | serious n=62 | not reported in cached trials |
| Pre-existing condition improved | 56 | 7.1 5.4–9.2ROR 7.1 · χ² 283 / p 7e-64 | 6.7 EB05 5.3 · IC025 +2.3 3/3 methods agree | Not in label — unassessed | serious n=32 | not reported in cached trials |
| Infusion site discharge | 15 | 7.0 4.2–11.6ROR 7.0 · χ² 70 / p 2e-17 | 5.9 EB05 3.7 · IC025 +1.7 3/3 methods agree | Not in label — unassessed | serious n=13 | not reported in cached trials |
| Cataplexy | 12 | 6.7 3.8–11.8ROR 6.7 · χ² 52 / p 3e-13 | 5.4 EB05 3.3 · IC025 +1.5 3/3 methods agree | Not in label — unassessed | serious n=12 | not reported in cached trials |
| Infusion site haemorrhage | 27 | 6.6 4.5–9.7ROR 6.6 · χ² 123 / p 9e-29 | 6.0 EB05 4.3 · IC025 +1.9 3/3 methods agree | Labeled (related wording) related wording | serious n=19 · ♀ 100% (drug 73%) | not reported in cached trials |
Trial evidence (ClinicalTrials.gov)
✓ Trial adverse-event data found on ClinicalTrials.gov
Largest completed trials with posted results that list Linaclotide as a study intervention. The right-hand column of the signal table shows whether each FAERS term was also recorded in these trials, with a real denominator (2 of 40 signal terms matched).
- NCT00730171 — An Open-label, Long-term Safety Study of Linaclotide in Patients With Chronic Constipation or Irritable Bowel (N=1743, PHASE3; 103 AE terms posted; arms: CC Safety Population: Total; IBS-C Safety Population: Total; Overall Safety Population: Total)
- NCT01880424 — A Phase 3, International, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Efficacy a (N=1722, PHASE3; 12 AE terms posted; arms: Linaclotide Arm; Placebo Arm)
Caveats: trial populations, doses and follow-up differ from the reporting population; AE terms are sponsor-coded and matched here by wording; absence from a trial list means the term was not reported above the sponsor's frequency threshold, not that it cannot occur.
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 |
|---|---|---|---|---|---|---|
| Diarrhoea (diarrhea) | 4,703 | 5.8 5.7–6.0ROR 6.9 · χ² 19,201 / p <1e-300 | 5.8 EB05 5.6 · IC025 +2.5 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 3.3 · 87% consumer | NCT00730171: 179/607 (29.5%) on Linaclotide |
| Drug ineffective (drug did not work) | 4,516 | 2.7 2.6–2.8ROR 3.1 · χ² 5,210 / p <1e-300 | 2.7 EB05 2.6 · IC025 +1.4 3/3 methods agree | Reporting / coding artifact | serious PRR 1.4 · 88% consumer | not reported in cached trials |
| Off label use (used outside approved label) | 3,345 | 3.1 3.0–3.2ROR 3.4 · χ² 4,803 / p <1e-300 | 3.0 EB05 3.0 · IC025 +1.5 3/3 methods agree | Reporting / coding artifact | serious PRR 1.5 · 86% consumer | not reported in cached trials |
| Constipation | 1,998 | 7.4 7.1–7.7ROR 7.9 · χ² 10,982 / p <1e-300 | 7.3 EB05 7.0 · IC025 +2.8 3/3 methods agree | Likely indication confounding term in indications; also in warnings | serious PRR 8.4 · 82% consumer | NCT00730171: 16/607 (2.6%) on Linaclotide |
| Nausea | 1,476 | 1.5 1.4–1.6ROR 1.5 · χ² 238 / p 6e-54 | 1.5 EB05 1.4 · IC025 +0.5 | Labeled adverse reaction exact term | serious PRR 2.3 | NCT00730171: 36/607 (5.9%) on Linaclotide |
| Fatigue (tiredness) | 1,171 | 1.2 1.1–1.3ROR 1.2 · χ² 37 / p 5e-10 | 1.2 EB05 1.1 · IC025 +0.2 | Not in label — unassessed | serious PRR 1.8 | not reported in cached trials |
| Abdominal distension (bloating) | 1,170 | 9.0 8.5–9.5ROR 9.4 · χ² 8,243 / p <1e-300 | 8.9 EB05 8.5 · IC025 +3.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 6.0 · 87% consumer | not reported in cached trials |
| Abdominal pain | 1,063 | 3.6 3.4–3.8ROR 3.7 · χ² 2,033 / p <1e-300 | 3.6 EB05 3.4 · IC025 +1.8 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.9 · 79% consumer | NCT00730171: 23/607 (3.8%) on Linaclotide |
| Headache | 1,040 | 1.3 1.2–1.4ROR 1.3 · χ² 80 / p 2e-19 | 1.3 EB05 1.2 · IC025 +0.3 | Labeled adverse reaction exact term | serious PRR 2.1 | NCT00730171: 1/1,119 (0.1%) on Linaclotide (serious AE) |
| Pain | 965 | 1.2 1.2–1.3ROR 1.2 · χ² 46 / p 6e-12 | 1.2 EB05 1.2 · IC025 +0.2 | Labeled adverse reaction exact term | serious PRR 1.9 | NCT00730171: 1/607 (0.2%) on Linaclotide (serious AE) |
| Abdominal pain upper | 942 | 3.6 3.4–3.9ROR 3.7 · χ² 1,808 / p <1e-300 | 3.6 EB05 3.4 · IC025 +1.7 3/3 methods agree | Labeled (related wording) related wording | serious PRR 3.4 · 85% consumer | NCT00730171: 23/607 (3.8%) on Linaclotide |
| Dizziness | 859 | 1.4 1.3–1.5ROR 1.4 · χ² 85 / p 1e-20 | 1.4 EB05 1.3 · IC025 +0.3 | Labeled — boxed warning exact term | serious PRR 1.9 · 72% consumer | not reported in cached trials |
| Inappropriate schedule of product administration | 775 | 3.5 3.2–3.7ROR 3.6 · χ² 1,370 / p 3e-300 | 3.5 EB05 3.3 · IC025 +1.7 3/3 methods agree | Reporting / coding artifact | serious PRR 2.8 · 87% consumer | not reported in cached trials |
| Fall | 718 | 1.7 1.6–1.8ROR 1.7 · χ² 213 / p 1e-48 | 1.7 EB05 1.6 · IC025 +0.6 | Not in label — unassessed | serious PRR 2.6 · 71% consumer | NCT00730171: 1/607 (0.2%) on Linaclotide (serious AE) |
| Flatulence (gas) | 703 | 9.9 9.2–10.7ROR 10.2 · χ² 5,581 / p <1e-300 | 9.8 EB05 9.2 · IC025 +3.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 6.3 · 92% consumer | NCT00730171: 34/607 (5.6%) on Linaclotide |
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.
- Gastrointestinal motility disorder — n=170, PRR 26.2
- Faeces hard — n=117, PRR 24.5
- Infrequent bowel movements — n=70, PRR 22.8
- Bowel movement irregularity — n=176, PRR 18.7
- Dyschezia — n=68, PRR 18.2
- Anal incontinence — n=167, PRR 15.1
- Rectal tenesmus — n=23, PRR 15.0
- Gastrointestinal hypomotility — n=40, PRR 14.4
- Rectal prolapse — n=21, PRR 14.0
- Volvulus — n=36, PRR 12.4
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 Linaclotide?
In FDA FAERS, the most frequently co-reported reaction terms for Linaclotide are diarrhoea, constipation, nausea, fatigue, abdominal distension, abdominal pain. 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 Linaclotide have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: RISK OF SERIOUS DEHYDRATION IN PEDIATRIC PATIENTS LESS THAN 2 YEARS OF AGE LINZESS is contraindicated in patients less than 2 years of age; in nonclinical studies in neonatal mice, administration of a single, clinica.
Do FAERS signals prove that Linaclotide 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 09beda19-56d6-4a56-afdc-9a77b70b2ef3, effective 20260521; matched on
openfda.generic_name.exact:"LINACLOTIDE") - 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, 1,123 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 - ClinicalTrials.gov API v2 (query
LINACLOTIDE, results-bearing studies sorted by enrollment)
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.