Causality assessment · Expected pharmacological effect

Ambrisentan and Fluid retention: is the FAERS signal real?

n=5,470 co-reports · PRR 20.3 · ROR 21.2

Ambrisentan side-effect profile All assessments See in the full list

A written Bradford Hill assessment of one drug–event pair. The grade is a judgement about the signal, not a statement that this drug causes this event in any one person; FAERS counts are reports, not rates.

Expected pharmacological effect

Ambrisentan ↔ Fluid retention

n=5,470 co-reports · PRR 20.3 · ROR 21.2

Ambrisentan is an endothelin-receptor antagonist for pulmonary arterial hypertension; peripheral oedema and fluid retention are its most common adverse effect (5,470 co-reports, PRR 20.3), reflecting vasodilation and sodium retention rather than heart failure in most cases. The effect is dose-related and, at higher exposure, can progress to decompensated heart failure, so the label requires caution in left-ventricular dysfunction and monthly liver monitoring for hepatotoxicity.

Regulatory basis: ambrisentan (Letairis) prescribing information — peripheral oedema and fluid retention.

Bradford Hill viewpoint	Status	Note
Temporality (necessary)	met	Fluid retention appears over weeks
Strength	met	PRR 20.3, large
Consistency	met	Reproduced across the ERA class
Specificity	partial	Shared with other endothelin antagonists
Biological gradient	met	Dose-related
Plausibility	met	Consistent with vasodilation and sodium retention
Coherence	met	Fits the mechanism
Experiment	met	ERA trials showed the excess
Analogy	met	Analogous to bosentan oedema

This table is this page's own qualitative read of the literature cited above, not an automated or citation-gated assessment — see the note at the bottom of this page.

✓ Trial evidence found — A Long Term Study of Ambrisentan in Pulmonary Arterial Hypertension Subjects Having Completed AMB-320 (NCT00423748) or AMB-321 (NCT00423202) (NCT00578786)

Adverse event	Ambrisentan 2.5 mg (n=43) · Ambrisentan 5 mg (n=146) · Ambrisentan 10 mg (n=194)
Oedema peripheral	1/43	0/146	2/194
Fluid retention	0/43	2/146	10/194
Oedema peripheal	13/43	53/146	101/194

Post-marketing signal terms appear in this trial's posted adverse-event tables; per-arm counts shown as affected/at-risk. View on ClinicalTrials.gov →