Drug · FAERS side-effect profile with label screen
Macitentan side effects: what 68,750 FDA adverse event reports show
Drug class
Endothelin Receptor Antagonist
FDA label (Established Pharmacologic Class) · compare the class
Who reports
68,750 reports · 71% serious · 12,527 with death outcome · 75% female
openFDA FAERS counts, all years, deduplication not applied
Used for
Macitentan tablets are an endothelin receptor antagonist (ERA) indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) in adults to reduce the risks of disease progression and hospitalization for PAH ( 1.1 ). 1.1 Pulmonary Art.
FDA label, Indications and Usage
What it is
Macitentan tablets are an endothelin receptor antagonist.
FDA label, Description section
Boxed warning
EMBRYO-FETAL TOXICITY Macitentan tablets are contraindicated for use during pregnancy because it may cause fetal harm based on animal data [see Contraindications ( 4.1), Warnings and Precautions ( 5.1 )], Use in Specific Populations (8.1 )].
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 1Labeled (related wording) 3Likely indication confounding 2Reporting / coding artifact 4Lab value / disease marker 5Not in label — unassessed 25
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 (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, for the 300 most-reported drugs, adjusted for age band), and flags pairs whose reports are unusually skewed by sex or come mostly from consumers. Each row also shows the PRR against the other drugs of the same FDA class, which removes most confounding by the condition being treated, and a calibrated p-value: on validation, known non-causes average an ROR of about 2, so significance is judged against that empirical null (✓ = p < 0.05 after calibration). 1,200 further terms are in the interactive explorer. Reaction links open the term's cross-drug page.
Show:
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Catheter management | 335 | 180.5 157.7–206.7ROR 181.4 · calibrated p 1e-9 ✓ | 112.3 EB05 102.6 · IC025 +6.4 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 17.7 (14.6–21.5) | Reporting / coding artifact | serious n=318 · 94% clinician | not reported in cached trials |
| Device wireless communication issue | 84 | 154.4 118.7–200.9ROR 154.6 · calibrated p 6e-9 ✓ | 100.0 EB05 83.3 · IC025 +5.6 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 12.2 (8.6–17.1) | Reporting / coding artifact | 100% consumer | not reported in cached trials |
| Catheter site rash | 143 | 141.9 116.3–173.1ROR 142.2 · calibrated p 1e-8 ✓ | 95.4 EB05 83.0 · IC025 +5.9 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 12.2 (9.4–15.9) | Not in label — unassessed | serious n=119 | not reported in cached trials |
| Catheter site irritation | 101 | 141.4 111.6–179.1ROR 141.6 · calibrated p 1e-8 ✓ | 94.7 EB05 80.2 · IC025 +5.7 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 15.8 (11.2–22.2) | Not in label — unassessed | serious n=85 | not reported in cached trials |
| Catheter site pruritus | 276 | 140.6 121.9–162.2ROR 141.2 · calibrated p 9e-9 ✓ | 95.4 EB05 86.3 · IC025 +6.2 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 10.2 (8.5–12.2) | Not in label — unassessed | serious n=230 | not reported in cached trials |
| Catheter site scab | 32 | 135.0 89.0–204.9ROR 135.1 · calibrated p 4e-8 ✓ | 88.6 EB05 65.7 · IC025 +4.7 3/3 methods agree vs other Endothelin Receptor Antagonists: only this drug | Not in label — unassessed | serious n=28 · ♀ 100% (drug 75%) · 100% clinician | not reported in cached trials |
| Transplant evaluation | 149 | 125.7 103.9–152.2ROR 126.0 · calibrated p 2e-8 ✓ | 87.9 EB05 76.7 · IC025 +5.8 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 8.6 (6.8–10.9) | Not in label — unassessed | serious n=147 · 93% clinician | not reported in cached trials |
| Pulmonary endarterectomy | 43 | 125.1 87.6–178.5ROR 125.1 · calibrated p 5e-8 ✓ | 85.3 EB05 66.0 · IC025 +5.0 3/3 methods agree vs other Endothelin Receptor Antagonists: only this drug | Not in label — unassessed | serious n=43 · 100% clinician | not reported in cached trials |
| Device maintenance issue | 161 | 121.8 101.4–146.3ROR 122.1 · calibrated p 3e-8 ✓ | 86.0 EB05 75.4 · IC025 +5.8 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 12.0 (9.4–15.3) | Reporting / coding artifact | serious n=53 · 86% consumer | not reported in cached trials |
| Catheter site warmth | 41 | 113.7 79.4–162.9ROR 113.8 · calibrated p 1e-7 ✓ | 79.7 EB05 61.3 · IC025 +4.9 3/3 methods agree vs other Endothelin Receptor Antagonists: only this drug | Not in label — unassessed | serious n=33 | not reported in cached trials |
| Catheter site vesicles | 49 | 104.9 75.7–145.2ROR 104.9 · calibrated p 2e-7 ✓ | 75.7 EB05 59.5 · IC025 +5.0 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 8.4 (5.6–12.5) | Not in label — unassessed | serious n=41 · ♀ 100% (drug 75%) | not reported in cached trials |
| Atrial septal defect repair | 43 | 102.2 72.3–144.5ROR 102.3 · calibrated p 2e-7 ✓ | 74.1 EB05 57.3 · IC025 +4.8 3/3 methods agree vs other Endothelin Receptor Antagonists: only this drug | Likely indication confounding shares a disease stem with the indications wording | serious n=43 · 100% clinician | not reported in cached trials |
| Cardiac output increased | 41 | 96.0 67.5–136.4ROR 96.0 · calibrated p 3e-7 ✓ | 70.6 EB05 54.3 · IC025 +4.8 3/3 methods agree vs other Endothelin Receptor Antagonists: only this drug | Lab value / disease marker | serious n=31 | not reported in cached trials |
| Cardiac failure high output | 56 | 93.7 69.4–126.5ROR 93.8 · calibrated p 3e-7 ✓ | 70.0 EB05 55.9 · IC025 +5.0 3/3 methods agree vs other Endothelin Receptor Antagonists: only this drug | Labeled (related wording) related wording | serious n=56 · 100% clinician | not reported in cached trials |
| Endarterectomy | 53 | 93.4 68.6–127.1ROR 93.5 · calibrated p 3e-7 ✓ | 69.7 EB05 55.3 · IC025 +5.0 3/3 methods agree vs other Endothelin Receptor Antagonists: only this drug | Not in label — unassessed | serious n=50 · 100% clinician | not reported in cached trials |
| Pulmonary arterial wedge pressure increased | 40 | 92.9 65.2–132.4ROR 92.9 · calibrated p 4e-7 ✓ | 68.9 EB05 52.8 · IC025 +4.7 3/3 methods agree vs other Endothelin Receptor Antagonists: only this drug | Lab value / disease marker | serious n=34 · 100% clinician | not reported in cached trials |
| Pulmonary arterial hypertension | 3,291 | 89.0 85.6–92.4ROR 93.4 · calibrated p 2e-7 ✓ | 68.8 EB05 66.8 · IC025 +6.0 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 7.5 (7.2–7.9) | Likely indication confounding term in indications; also in warnings | age-adj. PRR 83.0 · serious PRR 55.6 | NCT00660179: 48/250 (19.2%) on Macitentan; 56/249 (22.5%) control (serious AE) |
| Walking distance test abnormal | 83 | 83.4 65.4–106.4ROR 83.5 · calibrated p 6e-7 ✓ | 64.6 EB05 53.7 · IC025 +5.2 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 8.8 (6.4–12.1) | Reporting / coding artifact | serious n=55 | not reported in cached trials |
| Pulmonary arterial pressure abnormal | 59 | 78.6 59.0–104.6ROR 78.6 · calibrated p 1e-6 ✓ | 61.3 EB05 49.2 · IC025 +4.9 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 10.5 (7.1–15.6) | Lab value / disease marker | serious n=47 | not reported in cached trials |
| Pulmonary arterial pressure increased | 331 | 77.3 68.5–87.2ROR 77.7 · calibrated p 8e-7 ✓ | 61.4 EB05 56.1 · IC025 +5.6 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 8.8 (7.5–10.2) | Lab value / disease marker | serious n=290 | not reported in cached trials |
| Catheter site erythema | 417 | 75.7 68.0–84.3ROR 76.2 · calibrated p 9e-7 ✓ | 60.5 EB05 55.8 · IC025 +5.7 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 9.7 (8.4–11.3) | Not in label — unassessed | serious n=335 | not reported in cached trials |
| Oxygen consumption increased | 470 | 75.7 68.4–83.7ROR 76.2 · calibrated p 9e-7 ✓ | 60.5 EB05 56.0 · IC025 +5.7 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 7.6 (6.7–8.6) | Lab value / disease marker | serious n=381 | not reported in cached trials |
| Catheter site discharge | 214 | 73.5 63.3–85.4ROR 73.7 · calibrated p 1e-6 ✓ | 58.9 EB05 52.6 · IC025 +5.5 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 8.0 (6.6–9.7) | Not in label — unassessed | serious n=179 | not reported in cached trials |
| Right ventricular failure | 1,292 | 68.1 64.2–72.4ROR 69.4 · calibrated p 2e-6 ✓ | 55.7 EB05 53.2 · IC025 +5.7 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 8.0 (7.4–8.6) | Labeled (related wording) related wording | serious PRR 44.8 | NCT00660179: 21/250 (8.4%) on Macitentan; 40/249 (16.1%) control (serious AE) |
| Pulmonary veno-occlusive disease | 125 | 66.6 54.9–80.9ROR 66.8 · calibrated p 2e-6 ✓ | 54.3 EB05 46.7 · IC025 +5.2 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 10.4 (8.0–13.6) | Labeled — boxed warning exact term | serious n=124 · 92% clinician | not reported in cached trials |
| Infusion site infection | 396 | 64.4 57.8–71.8ROR 64.8 · calibrated p 3e-6 ✓ | 53.1 EB05 48.8 · IC025 +5.5 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 6.2 (5.4–7.1) | Labeled (related wording) related wording | serious n=191 | NCT00660179: 3/250 (1.2%) on Macitentan; 1/249 (0.4%) control (serious AE) |
| Catheterisation cardiac abnormal | 44 | 59.4 43.0–82.0ROR 59.4 · calibrated p 8e-6 ✓ | 48.7 EB05 37.8 · IC025 +4.5 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 8.9 (5.8–13.7) | Not in label — unassessed | serious n=29 | NCT00667823: 2/550 (0.4%) on Macitentan (serious AE) |
| Vascular device occlusion | 54 | 58.2 43.5–77.9ROR 58.2 · calibrated p 8e-6 ✓ | 48.1 EB05 38.3 · IC025 +4.6 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 9.4 (6.3–14.0) | Not in label — unassessed | serious n=52 | not reported in cached trials |
| Paracentesis | 99 | 58.0 46.8–72.0ROR 58.1 · calibrated p 6e-6 ✓ | 48.4 EB05 40.9 · IC025 +5.0 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 12.4 (9.0–17.1) | Not in label — unassessed | serious n=94 · 100% clinician | not reported in cached trials |
| Infusion site discharge | 271 | 57.3 50.3–65.2ROR 57.5 · calibrated p 6e-6 ✓ | 48.1 EB05 43.5 · IC025 +5.3 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 7.0 (5.9–8.2) | Not in label — unassessed | serious n=82 · 71% consumer | not reported in cached trials |
| Catheter site swelling | 145 | 57.0 47.7–68.1ROR 57.1 · calibrated p 7e-6 ✓ | 47.8 EB05 41.6 · IC025 +5.1 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 11.2 (8.7–14.5) | Not in label — unassessed | serious n=112 | not reported in cached trials |
| Right ventricular enlargement | 46 | 51.8 37.9–70.8ROR 51.8 · calibrated p 2e-5 ✓ | 43.6 EB05 34.0 · IC025 +4.4 3/3 methods agree vs other Endothelin Receptor Antagonists: only this drug | Not in label — unassessed | serious n=44 | not reported in cached trials |
| Catheter site pain | 368 | 51.5 46.1–57.5ROR 51.8 · calibrated p 1e-5 ✓ | 44.0 EB05 40.4 · IC025 +5.2 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 11.2 (9.6–13.2) | Not in label — unassessed | serious n=292 | not reported in cached trials |
| Infusion site warmth | 170 | 50.1 42.6–58.9ROR 50.2 · calibrated p 1e-5 ✓ | 42.9 EB05 37.7 · IC025 +5.0 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 7.9 (6.4–9.8) | Not in label — unassessed | serious n=57 | not reported in cached trials |
| Ventilation perfusion mismatch | 39 | 49.9 35.6–70.1ROR 50.0 · calibrated p 2e-5 ✓ | 42.1 EB05 32.2 · IC025 +4.3 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 6.5 (4.2–10.0) | Not in label — unassessed | serious n=35 · 100% clinician | not reported in cached trials |
| Infusion site irritation | 175 | 49.8 42.5–58.5ROR 50.0 · calibrated p 2e-5 ✓ | 42.7 EB05 37.6 · IC025 +5.0 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 7.7 (6.3–9.5) | Not in label — unassessed | serious n=63 · 72% consumer | not reported in cached trials |
| Right ventricular dilatation | 76 | 46.6 36.6–59.3ROR 46.6 · calibrated p 3e-5 ✓ | 40.1 EB05 33.1 · IC025 +4.6 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 17.7 (11.7–26.6) | Not in label — unassessed | serious n=74 · 91% clinician | not reported in cached trials |
| Abdominal cavity drainage | 55 | 45.4 34.2–60.3ROR 45.4 · calibrated p 3e-5 ✓ | 39.1 EB05 31.1 · IC025 +4.4 3/3 methods agree vs other Endothelin Receptor Antagonists: only this drug | Not in label — unassessed | serious n=55 · 100% clinician | not reported in cached trials |
| Mineral supplementation | 57 | 44.7 33.8–59.0ROR 44.7 · calibrated p 4e-5 ✓ | 38.6 EB05 30.9 · IC025 +4.4 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 15.1 (9.6–23.6) | Not in label — unassessed | serious n=50 · 100% clinician | not reported in cached trials |
| Infusion site induration | 181 | 44.4 38.0–51.9ROR 44.5 · calibrated p 3e-5 ✓ | 38.6 EB05 34.1 · IC025 +4.9 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 8.1 (6.6–9.9) | Not in label — unassessed | serious n=52 · 74% consumer | not reported in cached trials |
Clinical concept groups
MedDRA splits one clinical problem across several terms (e.g. "neutropenia", "neutrophil count decreased", "agranulocytosis"), which dilutes term-level signals. These rows count reports with any term in a concept group (an exact union, not a sum), compared with all other drugs. Groups are hand-built and listed in the methods.
| Concept | Reports | PRR 95% CI | Reading |
|---|---|---|---|
| Heart failure | 2,815 | 4.94.7–5.0 | signal |
| Anaemia | 2,873 | 2.92.8–3.0 | signal |
| Serious infection | 7,234 | 2.92.8–2.9 | signal |
| Gi bleeding | 1,261 | 2.12.0–2.2 | raised |
| Interstitial lung disease | 625 | 2.01.8–2.2 | raised |
| Arrhythmia / qt | 1,254 | 2.01.9–2.1 | raised |
| Fall / fracture | 2,367 | 1.91.8–2.0 | raised |
| Kidney injury | 1,999 | 1.31.3–1.4 | raised |
| Hyponatraemia | 328 | 1.21.1–1.4 | raised |
| Thrombocytopenia | 802 | 1.11.0–1.2 | raised |
| Venous thromboembolism | 787 | 1.11.0–1.2 | raised |
| Opportunistic infection | 435 | 1.00.9–1.1 | no difference |
| Stroke | 602 | 0.70.7–0.8 | lower than other drugs |
| Hypoglycaemia | 228 | 0.70.6–0.8 | lower than other drugs |
| Liver injury | 679 | 0.70.6–0.7 | lower than other drugs |
| Depression | 591 | 0.60.6–0.7 | lower than other drugs |
Trial evidence (ClinicalTrials.gov)
✓ Trial adverse-event data found on ClinicalTrials.gov
Largest completed trials with posted results that list Macitentan 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 (4 of 40 signal terms matched).
- NCT00660179 — Study of Macitentan (ACT-064992) on Morbidity and Mortality in Patients With Symptomatic Pulmonary Arterial Hy (N=742, PHASE3; 281 AE terms posted; arms: Placebo; ACT-064992 3 mg; ACT-064992 10 mg)
- NCT00667823 — Clinical Study to Assess the Long-term Safety and Tolerability of ACT 064992 in Patients With Symptomatic Pulm (N=550, PHASE3; 392 AE terms posted; arms: Macitentan 10 mg)
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 |
|---|---|---|---|---|---|---|
| Dyspnoea (shortness of breath) | 11,956 | 6.6 6.5–6.7ROR 7.7 · calibrated p 0.074 | 6.4 EB05 6.3 · IC025 +2.7 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 4.8 (4.7–4.9) | Not in label — unassessed | age-adj. PRR 6.2 · serious PRR 5.8 | NCT00660179: 2/250 (0.8%) on Macitentan; 1/249 (0.4%) control (serious AE) |
| Headache | 8,323 | 4.1 4.0–4.2ROR 4.5 · calibrated p 0.294 | 4.0 EB05 4.0 · IC025 +2.0 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 5.7 (5.6–5.9) | Labeled adverse reaction exact term | age-adj. PRR 4.0 · serious PRR 4.2 | NCT00660179: 1/242 (0.4%) on Macitentan (serious AE) |
| Death | 7,367 | 2.6 2.6–2.7ROR 2.8 · calibrated p 0.690 | 2.6 EB05 2.6 · IC025 +1.3 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 5.0 (4.8–5.1) | Outcome field, not a reaction | age-adj. PRR 3.1 · serious PRR 2.1 | NCT00660179: 1/250 (0.4%) on Macitentan (serious AE) |
| Diarrhoea (diarrhea) | 6,581 | 3.1 3.1–3.2ROR 3.4 · calibrated p 0.519 | 3.1 EB05 3.1 · IC025 +1.6 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 7.1 (6.9–7.3) | Not in label — unassessed | age-adj. PRR 2.8 · serious PRR 3.0 | NCT00660179: 1/250 (0.4%) on Macitentan (serious AE) |
| Nausea | 5,972 | 2.3 2.3–2.4ROR 2.4 · calibrated p 0.839 | 2.3 EB05 2.3 · IC025 +1.2 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 6.6 (6.4–6.8) | Labeled adverse reaction exact term | age-adj. PRR 2.3 · serious PRR 2.4 | NCT00660179: 1/250 (0.4%) on Macitentan (serious AE) |
| Fatigue (tiredness) | 5,041 | 2.0 1.9–2.0ROR 2.1 · calibrated p 0.977 | 2.0 EB05 1.9 · IC025 +0.9 vs other Endothelin Receptor Antagonists: PRR 5.2 (5.1–5.4) | Labeled adverse reaction exact term | age-adj. PRR 1.9 · serious PRR 2.1 | NCT00660179: 1/242 (0.4%) on Macitentan (serious AE) |
| Pneumonia (lung infection) | 4,550 | 4.3 4.2–4.5ROR 4.6 · calibrated p 0.286 | 4.3 EB05 4.2 · IC025 +2.1 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 4.8 (4.6–5.0) | Labeled (related wording) related wording | age-adj. PRR 4.1 · serious PRR 3.5 | NCT00660179: 1/250 (0.4%) on Macitentan (serious AE) |
| Dizziness | 4,533 | 2.8 2.7–2.9ROR 2.9 · calibrated p 0.654 | 2.8 EB05 2.7 · IC025 +1.4 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 4.7 (4.5–4.9) | Not in label — unassessed | age-adj. PRR 2.6 · serious PRR 2.8 | NCT00660179: 24/250 (9.6%) on Macitentan; 27/249 (10.8%) control |
| Hospitalisation | 4,110 | 8.4 8.2–8.7ROR 8.9 · calibrated p 0.048 ✓ | 8.2 EB05 8.0 · IC025 +3.0 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 18.9 (17.9–19.9) | Reporting / coding artifact | age-adj. PRR 8.3 · serious PRR 6.7 | not reported in cached trials |
| Cough | 3,940 | 4.3 4.2–4.5ROR 4.5 · calibrated p 0.291 | 4.3 EB05 4.2 · IC025 +2.0 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 6.4 (6.1–6.6) | Not in label — unassessed | age-adj. PRR 3.9 · serious PRR 3.9 | NCT00660179: 20/250 (8.0%) on Macitentan; 30/249 (12.0%) control |
| Fluid retention | 3,837 | 24.8 24.0–25.6ROR 26.2 · calibrated p 5e-4 ✓ | 23.0 EB05 22.4 · IC025 +4.5 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 5.3 (5.1–5.5) | Labeled — boxed warning exact term | age-adj. PRR 24.4 · serious PRR 21.9 | NCT00667823: 1/550 (0.2%) on Macitentan (serious AE) |
| Hypotension (low blood pressure) | 3,626 | 5.6 5.4–5.8ROR 5.9 · calibrated p 0.160 | 5.5 EB05 5.4 · IC025 +2.4 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 6.3 (6.1–6.6) | Labeled adverse reaction exact term | age-adj. PRR 4.9 · serious PRR 4.4 | NCT00660179: 1/250 (0.4%) on Macitentan; 3/249 (1.2%) control (serious AE) |
| Malaise (feeling unwell) | 3,595 | 2.5 2.4–2.6ROR 2.6 · calibrated p 0.777 | 2.5 EB05 2.4 · IC025 +1.3 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 5.2 (5.0–5.4) | Not in label — unassessed | age-adj. PRR 2.6 · serious PRR 2.5 | not reported in cached trials |
| Pulmonary arterial hypertension | 3,291 | 89.0 85.6–92.4ROR 93.4 · calibrated p 2e-7 ✓ | 68.8 EB05 66.8 · IC025 +6.0 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 7.5 (7.2–7.9) | Likely indication confounding term in indications; also in warnings | age-adj. PRR 83.0 · serious PRR 55.6 | NCT00660179: 48/250 (19.2%) on Macitentan; 56/249 (22.5%) control (serious AE) |
| Vomiting | 3,191 | 2.1 2.0–2.2ROR 2.1 · calibrated p 0.985 | 2.1 EB05 2.0 · IC025 +1.0 3/3 methods agree vs other Endothelin Receptor Antagonists: PRR 6.5 (6.2–6.8) | Labeled adverse reaction exact term | age-adj. PRR 2.1 · serious PRR 1.9 | NCT00660179: 1/250 (0.4%) on Macitentan (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.
- Catheter site rash — n=143, PRR 141.9
- Catheter site irritation — n=101, PRR 141.4
- Catheter site pruritus — n=276, PRR 140.6
- Catheter site scab — n=32, PRR 135.0
- Transplant evaluation — n=149, PRR 125.7
- Pulmonary endarterectomy — n=43, PRR 125.1
- Catheter site warmth — n=41, PRR 113.7
- Catheter site vesicles — n=49, PRR 104.9
- Endarterectomy — n=53, PRR 93.4
- Catheter site erythema — n=417, PRR 75.7
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 Macitentan?
In FDA FAERS, the most frequently co-reported reaction terms for Macitentan are dyspnoea, headache, diarrhoea, nausea, fatigue, pneumonia. 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 Macitentan have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: EMBRYO-FETAL TOXICITY Macitentan tablets are contraindicated for use during pregnancy because it may cause fetal harm based on animal data [see Contraindications ( 4.1), Warnings and Precautions ( 5.1 )], Use in Specific Populations (8.1 )].
Do FAERS signals prove that Macitentan 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 226049ba-9c76-0798-6725-ee027a041820, effective 20260611; matched on
openfda.generic_name.exact:"MACITENTAN") - 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, 1,240 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
MACITENTAN, results-bearing studies sorted by enrollment)
Page generated 2026-10-14. 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.