Bosentan side effects: what 50,101 FDA adverse event reports show

Bosentan · 1,227 reaction terms · 165,284 drug–reaction co-reports · data 2026-09-14

Drug class

Endothelin receptor antagonist

FDA label, Indications wording

Who reports

50,101 reports · 85% serious · 15,952 with death outcome · 73% female

openFDA FAERS counts, all years, deduplication not applied

Used for

1. INDICATIONS AND USAGE Bosentan is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1): in adults to improve exercise ability and to decrease clinical worsening. Studies establishing effectiveness included predominantly.

FDA label, Indications and Usage

What it is

11. DESCRIPTION Bosentan, an endothelin receptor antagonist that belongs to a class of highly substituted pyrimidine derivatives, with no chiral centers. It is designated chemically as 4-tert-.

FDA label, Description section

Boxed warning

RISKS OF HEPATOTOXICITY and EMBRYO-FETALTOXICITY Because of the risks of hepatotoxicity and birth defects, bosentan tablets for oral suspension is available only through a restricted program called the Bosentan REMS Program. Under the Bosentan REMS, prescribers, patients, and pharmacies must enroll in the program [see Warnings and Precautions (5.3) ] .

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 adverse reaction 2Labeled (related wording) 1Likely indication confounding 3Reporting / coding artifact 2Lab value / disease marker 3Not in label — unassessed 29

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. 1,187 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
Balloon atrial septostomy	28	576.7 324.9–1,023.6ROR 577.0 · χ² 6,467 / p <1e-300	207.0 EB05 150.3 · IC025 +4.9 3/3 methods agree	Not in label — unassessed	serious n=28 · 100% clinician	not reported in cached trials
Patent ductus arteriosus repair	22	377.6 211.7–673.4ROR 377.8 · χ² 4,117 / p <1e-300	168.8 EB05 117.5 · IC025 +4.5 3/3 methods agree	Likely indication confounding shares a disease stem with the indications wording	serious n=22 · 100% clinician	not reported in cached trials
Heart and lung transplant	41	194.1 133.9–281.4ROR 194.3 · χ² 5,223 / p <1e-300	124.7 EB05 95.8 · IC025 +5.2 3/3 methods agree	Not in label — unassessed	serious n=41 · ♀ 47% (drug 73%) · 90% clinician	not reported in cached trials
Pulmonary hypertensive crisis	76	167.4 128.3–218.5ROR 167.7 · χ² 8,821 / p <1e-300	115.9 EB05 95.6 · IC025 +5.7 3/3 methods agree	Likely indication confounding shares a disease stem with the indications wording	serious n=76	not reported in cached trials
Atrial septal defect repair	46	154.1 109.8–216.1ROR 154.2 · χ² 4,980 / p <1e-300	107.5 EB05 83.9 · IC025 +5.2 3/3 methods agree	Not in label — unassessed	serious n=46 · 100% clinician	not reported in cached trials
Pulmonary vein stenosis	25	113.2 72.7–176.2ROR 113.2 · χ² 2,093 / p <1e-300	83.5 EB05 59.5 · IC025 +4.4 3/3 methods agree	Not in label — unassessed	serious n=25	not reported in cached trials
Right-to-left cardiac shunt	39	87.8 62.1–124.0ROR 87.9 · χ² 2,687 / p <1e-300	70.2 EB05 53.5 · IC025 +4.7 3/3 methods agree	Not in label — unassessed	serious n=39 · 92% clinician	not reported in cached trials
Systemic sclerosis	38	87.4 61.6–124.1ROR 87.5 · χ² 2,608 / p <1e-300	69.9 EB05 53.1 · IC025 +4.7 3/3 methods agree	Not in label — unassessed	serious n=38 · 100% clinician	not reported in cached trials
Right ventricular failure	1,141	80.6 75.7–85.8ROR 82.5 · χ² 74,981 / p <1e-300	67.5 EB05 64.3 · IC025 +5.9 3/3 methods agree	Not in label — unassessed	serious PRR 46.1 · 91% clinician	NCT00303459: 6/159 (3.8%) on Bosentan; 8/174 (4.6%) control (serious AE)
Pulmonary arterial hypertension	2,291	78.1 74.8–81.6ROR 81.8 · χ² 146,616 / p <1e-300	65.8 EB05 63.5 · IC025 +6.0 3/3 methods agree	Likely indication confounding term in indications; also in warnings	serious PRR 45.3	NCT00303459: 25/159 (15.7%) on Bosentan; 28/174 (16.1%) control (serious AE)
Endarterectomy	30	64.0 43.6–94.1ROR 64.1 · χ² 1,557 / p <1e-300	53.8 EB05 39.5 · IC025 +4.3 3/3 methods agree	Not in label — unassessed	serious n=31 · 90% clinician	not reported in cached trials
Biopsy liver	51	58.7 43.8–78.7ROR 58.7 · χ² 2,481 / p <1e-300	50.6 EB05 40.0 · IC025 +4.6 3/3 methods agree	Not in label — unassessed	serious n=51 · 100% clinician	not reported in cached trials
Walking distance test abnormal	47	58.0 42.7–78.7ROR 58.0 · χ² 2,257 / p <1e-300	50.0 EB05 39.1 · IC025 +4.6 3/3 methods agree	Reporting / coding artifact	serious n=41	not reported in cached trials
Pulmonary arterial pressure increased	192	55.6 47.9–64.6ROR 55.8 · χ² 9,026 / p <1e-300	48.9 EB05 43.4 · IC025 +5.2 3/3 methods agree	Lab value / disease marker	serious n=179	not reported in cached trials
Catheter management	104	54.4 44.4–66.8ROR 54.5 · χ² 4,771 / p <1e-300	47.8 EB05 40.6 · IC025 +5.0 3/3 methods agree	Reporting / coding artifact	serious n=101 · 95% clinician	not reported in cached trials
Pulmonary veno-occlusive disease	80	54.3 43.0–68.5ROR 54.4 · χ² 3,650 / p <1e-300	47.6 EB05 39.4 · IC025 +4.8 3/3 methods agree	Labeled adverse reaction exact term	serious n=80 · 95% clinician	not reported in cached trials
Right ventricular systolic pressure increased	35	52.4 36.9–74.5ROR 52.5 · χ² 1,521 / p <1e-300	45.5 EB05 34.2 · IC025 +4.3 3/3 methods agree	Lab value / disease marker	serious n=32 · 100% clinician	not reported in cached trials
Cor pulmonale	106	51.6 42.2–63.2ROR 51.7 · χ² 4,630 / p <1e-300	45.6 EB05 38.8 · IC025 +4.9 3/3 methods agree	Not in label — unassessed	serious n=104 · 93% clinician	NCT00303459: 1/159 (0.6%) on Bosentan; 1/174 (0.6%) control (serious AE)
Cor pulmonale chronic	20	49.9 31.4–79.4ROR 50.0 · χ² 812 / p 6e-179	43.0 EB05 29.4 · IC025 +3.7 3/3 methods agree	Not in label — unassessed	serious n=17	NCT00303459: 1/159 (0.6%) on Bosentan; 1/174 (0.6%) control (serious AE)
Transplant evaluation	54	49.4 37.3–65.5ROR 49.5 · χ² 2,245 / p <1e-300	43.6 EB05 34.7 · IC025 +4.5 3/3 methods agree	Not in label — unassessed	serious n=54 · 100% clinician	not reported in cached trials
Hepatic congestion	100	48.6 39.5–59.8ROR 48.7 · χ² 4,126 / p <1e-300	43.2 EB05 36.6 · IC025 +4.8 3/3 methods agree	Labeled (related wording) related wording	serious n=99 · 93% clinician	not reported in cached trials
Tracheostomy malfunction	21	47.3 30.1–74.2ROR 47.3 · χ² 812 / p 6e-179	41.0 EB05 28.3 · IC025 +3.7 3/3 methods agree	Not in label — unassessed	serious n=20	not reported in cached trials
Lung transplant	347	45.1 40.3–50.3ROR 45.4 · χ² 13,439 / p <1e-300	40.6 EB05 37.2 · IC025 +5.1 3/3 methods agree	Not in label — unassessed	serious n=347 · 94% clinician	NCT00391443: 1/209 (0.5%) control (serious AE)
Heart transplant	80	40.8 32.5–51.4ROR 40.9 · χ² 2,792 / p <1e-300	36.9 EB05 30.6 · IC025 +4.6 3/3 methods agree	Not in label — unassessed	serious n=80 · ♀ 48% (drug 73%)	not reported in cached trials
Pulmonary arterial pressure abnormal	24	38.0 25.0–57.8ROR 38.0 · χ² 758 / p 3e-167	34.0 EB05 24.1 · IC025 +3.7 3/3 methods agree	Lab value / disease marker	serious n=23 · 100% clinician	not reported in cached trials
Scleroderma renal crisis	30	36.6 25.2–53.1ROR 36.6 · χ² 921 / p 2e-202	33.0 EB05 24.2 · IC025 +3.8 3/3 methods agree	Not in label — unassessed	serious n=30 · 100% clinician	not reported in cached trials
Catheter site discharge	88	36.3 29.2–45.2ROR 36.4 · χ² 2,746 / p <1e-300	33.2 EB05 27.8 · IC025 +4.5 3/3 methods agree	Not in label — unassessed	serious n=79	not reported in cached trials
Catheter removal	28	35.7 24.3–52.5ROR 35.7 · χ² 838 / p 2e-184	32.3 EB05 23.4 · IC025 +3.8 3/3 methods agree	Not in label — unassessed	serious n=26 · 100% clinician	not reported in cached trials
Crest syndrome	18	34.2 21.1–55.3ROR 34.2 · χ² 505 / p 4e-112	30.7 EB05 20.5 · IC025 +3.3 3/3 methods agree	Not in label — unassessed	serious n=17	NCT00303459: 1/174 (0.6%) control (serious AE)
Catheter site erythema	156	33.6 28.6–39.6ROR 33.7 · χ² 4,536 / p <1e-300	31.1 EB05 27.2 · IC025 +4.6 3/3 methods agree	Not in label — unassessed	serious n=132	not reported in cached trials
Catheter site inflammation	41	33.5 24.4–46.1ROR 33.5 · χ² 1,166 / p 8e-256	30.7 EB05 23.6 · IC025 +4.0 3/3 methods agree	Not in label — unassessed	serious n=34	not reported in cached trials
Catheter site pruritus	63	32.4 25.1–41.9ROR 32.4 · χ² 1,748 / p <1e-300	29.9 EB05 24.2 · IC025 +4.2 3/3 methods agree	Not in label — unassessed	serious n=51	not reported in cached trials
Pulmonary hypertension	1,468	31.5 29.9–33.2ROR 32.5 · χ² 40,346 / p <1e-300	29.4 EB05 28.1 · IC025 +4.8 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 20.1	NCT00391443: 2/406 (0.5%) on Bosentan (serious AE)
Finger amputation	51	31.3 23.6–41.6ROR 31.3 · χ² 1,363 / p 1e-298	28.9 EB05 22.8 · IC025 +4.1 3/3 methods agree	Not in label — unassessed	serious n=49	NCT00303459: 1/159 (0.6%) on Bosentan (serious AE)
Catheter site swelling	64	31.3 24.3–40.3ROR 31.3 · χ² 1,715 / p <1e-300	28.9 EB05 23.4 · IC025 +4.2 3/3 methods agree	Not in label — unassessed	serious n=59	not reported in cached trials
Scleroderma	252	31.0 27.3–35.3ROR 31.2 · χ² 6,783 / p <1e-300	28.9 EB05 26.0 · IC025 +4.6 3/3 methods agree	Not in label — unassessed	serious n=245	not reported in cached trials
Pulmonary artery dilatation	23	29.7 19.5–45.3ROR 29.7 · χ² 568 / p 6e-126	27.2 EB05 19.1 · IC025 +3.4 3/3 methods agree	Not in label — unassessed	serious n=23 · 100% clinician	not reported in cached trials
Cardioversion	92	29.3 23.7–36.1ROR 29.3 · χ² 2,319 / p <1e-300	27.3 EB05 22.9 · IC025 +4.2 3/3 methods agree	Not in label — unassessed	serious n=92 · 96% clinician	not reported in cached trials
Dyspnoea exacerbated	34	29.1 20.6–41.2ROR 29.1 · χ² 836 / p 4e-184	26.9 EB05 20.1 · IC025 +3.7 3/3 methods agree	Not in label — unassessed	serious n=30 · 100% clinician	not reported in cached trials
Therapeutic embolisation	20	28.3 18.0–44.5ROR 28.3 · χ² 468 / p 5e-104	26.0 EB05 17.7 · IC025 +3.3 3/3 methods agree	Not in label — unassessed	serious n=20	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 Bosentan 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 (8 of 40 signal terms matched).

NCT00391443 — BUILD 3: Bosentan Use in Interstitial Lung Disease (N=616, PHASE3; 161 AE terms posted; arms: Placebo; Bosentan)
NCT00303459 — Effects of the Combination of Bosentan and Sildenafil Versus Sildenafil Monotherapy on Pulmonary Arterial Hype (N=334, PHASE4; 265 AE terms posted; arms: Bosentan; Placebo)

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
Death	9,321	4.6 4.5–4.7ROR 5.4 · χ² 26,788 / p <1e-300	4.5 EB05 4.5 · IC025 +2.1 3/3 methods agree	Outcome field, not a reaction	serious PRR 3.1	NCT00303459: 1/159 (0.6%) on Bosentan; 1/174 (0.6%) control (serious AE)
Dyspnoea (shortness of breath)	6,001	4.5 4.4–4.6ROR 5.0 · χ² 16,473 / p <1e-300	4.4 EB05 4.3 · IC025 +2.1 3/3 methods agree	Not in label — unassessed	serious PRR 3.7	NCT00391443: 6/406 (1.5%) on Bosentan (serious AE)
Pneumonia (lung infection)	2,698	3.5 3.4–3.6ROR 3.7 · χ² 4,884 / p <1e-300	3.5 EB05 3.4 · IC025 +1.7 3/3 methods agree	Labeled (related wording) related wording	serious PRR 2.4	NCT00391443: 16/406 (3.9%) on Bosentan; 10/209 (4.8%) control (serious AE)
Pulmonary arterial hypertension	2,291	78.1 74.8–81.6ROR 81.8 · χ² 146,616 / p <1e-300	65.8 EB05 63.5 · IC025 +6.0 3/3 methods agree	Likely indication confounding term in indications; also in warnings	serious PRR 45.3	NCT00303459: 25/159 (15.7%) on Bosentan; 28/174 (16.1%) control (serious AE)
Fatigue (tiredness)	2,258	1.2 1.2–1.3ROR 1.2 · χ² 90 / p 1e-21	1.2 EB05 1.2 · IC025 +0.2	Labeled — boxed warning exact term	serious PRR 1.1	NCT00391443: 46/406 (11.3%) on Bosentan; 15/209 (7.2%) control
Headache	2,227	1.5 1.4–1.6ROR 1.5 · χ² 368 / p 2e-82	1.5 EB05 1.4 · IC025 +0.5	Labeled adverse reaction exact term	serious PRR 1.5	NCT00391443: 44/406 (10.8%) on Bosentan; 22/209 (10.5%) control
Nausea	2,067	1.1 1.1–1.1ROR 1.1 · χ² 18 / p 1e-5	1.1 EB05 1.1 · IC025 +0.1	Labeled — boxed warning exact term	serious PRR 1.1	NCT00391443: 27/406 (6.7%) on Bosentan; 15/209 (7.2%) control
Diarrhoea (diarrhea)	2,001	1.3 1.2–1.4ROR 1.3 · χ² 144 / p 1e-33	1.3 EB05 1.3 · IC025 +0.3	Not in label — unassessed	serious PRR 1.2	NCT00303459: 19/159 (11.9%) on Bosentan; 19/174 (10.9%) control
Condition aggravated	1,873	2.6 2.5–2.7ROR 2.7 · χ² 1,867 / p <1e-300	2.6 EB05 2.5 · IC025 +1.3 3/3 methods agree	Reporting / coding artifact	serious PRR 2.6	not reported in cached trials
Dizziness	1,767	1.5 1.4–1.6ROR 1.5 · χ² 287 / p 1e-64	1.5 EB05 1.4 · IC025 +0.5	Not in label — unassessed	serious PRR 1.4	NCT00391443: 1/406 (0.2%) on Bosentan; 1/209 (0.5%) control (serious AE)
Malaise (feeling unwell)	1,706	1.6 1.6–1.7ROR 1.6 · χ² 418 / p 3e-93	1.6 EB05 1.6 · IC025 +0.6	Not in label — unassessed	serious PRR 1.4	not reported in cached trials
Fall	1,570	2.0 1.9–2.1ROR 2.0 · χ² 770 / p 9e-170	2.0 EB05 1.9 · IC025 +0.9	Not in label — unassessed	serious PRR 1.5	NCT00391443: 1/406 (0.2%) on Bosentan; 1/209 (0.5%) control (serious AE)
Cough	1,554	2.3 2.2–2.4ROR 2.4 · χ² 1,190 / p 5e-261	2.3 EB05 2.2 · IC025 +1.1 3/3 methods agree	Not in label — unassessed	serious PRR 2.1	NCT00391443: 1/406 (0.2%) on Bosentan; 1/209 (0.5%) control (serious AE)
Vomiting	1,539	1.4 1.3–1.4ROR 1.4 · χ² 160 / p 6e-37	1.4 EB05 1.3 · IC025 +0.4	Labeled — boxed warning exact term	serious PRR 1.2	NCT00391443: 1/406 (0.2%) on Bosentan (serious AE)
Pulmonary hypertension	1,468	31.5 29.9–33.2ROR 32.5 · χ² 40,346 / p <1e-300	29.4 EB05 28.1 · IC025 +4.8 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 20.1	NCT00391443: 2/406 (0.5%) on Bosentan (serious AE)

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.

Balloon atrial septostomy — n=28, PRR 576.7
Heart and lung transplant — n=41, PRR 194.1
Atrial septal defect repair — n=46, PRR 154.1
Pulmonary vein stenosis — n=25, PRR 113.2
Right-to-left cardiac shunt — n=39, PRR 87.8
Systemic sclerosis — n=38, PRR 87.4
Right ventricular failure — n=1,141, PRR 80.6 (also seen in trial arm)
Endarterectomy — n=30, PRR 64.0
Biopsy liver — n=51, PRR 58.7
Cor pulmonale — n=106, PRR 51.6 (also seen in trial arm)

✓ A hand-written Bradford Hill causality assessment exists for this drug: Bosentan ↔ Hepatotoxicity.

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 Bosentan?

In FDA FAERS, the most frequently co-reported reaction terms for Bosentan are dyspnoea, pneumonia, pulmonary arterial hypertension, fatigue, headache, nausea. 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 Bosentan have an FDA boxed warning?

Yes. The current FDA label carries a boxed warning: RISKS OF HEPATOTOXICITY and EMBRYO-FETALTOXICITY Because of the risks of hepatotoxicity and birth defects, bosentan tablets for oral suspension is available only through a restricted program called the Bosentan REMS Program. Under the Bosentan REMS, prescribers, patients, and pharmacies must enroll in the program [see Warnings and Precautions (5.3) ] .

Do FAERS signals prove that Bosentan 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 540b6f6a-79f3-4681-8c2a-268cf7cecbc9, effective 20251103; matched on openfda.generic_name.exact:"BOSENTAN")
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, 1,227 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 BOSENTAN, 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.