Drug · FAERS side-effect profile with label screen
Sacubitril and Valsartan side effects: what 115,375 FDA adverse event reports show
Drug class
Angiotensin 2 Receptor Blocker
FDA label (Established Pharmacologic Class) · compare the class
Who reports
115,375 reports · 51% serious · 14,147 with death outcome · 36% female
openFDA FAERS counts, all years, deduplication not applied
Used for
Sacubitril and valsartan tablets are a combination of sacubitril, a neprilisin inhibitor, and valsartan, an angiotensin II receptor blocker, and sacubitril and valsartan tablets are indicated: • to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure.
FDA label, Indications and Usage
What it is
Sacubitril and valsartan tablets is a combination of a neprilysin inhibitor and an angiotensin II receptor blocker. Sacubitril and valsartan contains a complex comprised of anionic forms of Sacubitril, Valsartan and sodium cations in the ratio of 1:1:3, respectively.
FDA label, Description section
Boxed warning
FETAL TOXICITY • When pregnancy is detected, discontinue Sacubitril and valsartan tablets as soon as possible. (5.1) • Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. (5.1) WARNING: FETAL TOXICITY See full prescribing information for complete boxed warning .
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 13Reporting / coding artifact 1Lab value / disease marker 6Not in label — unassessed 16
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). 1,176 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 |
|---|---|---|---|---|---|---|
| Device inappropriate shock delivery | 36 | 168.9 107.1–266.5ROR 169.0 · calibrated p 9e-9 ✓ | 83.5 EB05 63.0 · IC025 +4.8 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: only this drug | Reporting / coding artifact | serious n=36 · ♀ 0% (drug 36%) | not reported in cached trials |
| Throat clearing | 1,549 | 130.2 122.0–139.0ROR 131.9 · calibrated p 1e-8 ✓ | 75.6 EB05 72.5 · IC025 +6.1 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: only this drug | Not in label — unassessed | serious n=464 · 96% consumer | not reported in cached trials |
| Ejection fraction abnormal | 428 | 97.2 86.4–109.4ROR 97.6 · calibrated p 1e-7 ✓ | 63.1 EB05 58.2 · IC025 +5.7 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: only this drug | Likely indication confounding term in indications | serious n=168 · 82% consumer | not reported in cached trials |
| N-terminal prohormone brain natriuretic peptide increased | 242 | 37.8 32.9–43.4ROR 37.9 · calibrated p 8e-5 ✓ | 31.3 EB05 28.1 · IC025 +4.7 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: only this drug | Lab value / disease marker | serious n=223 | not reported in cached trials |
| Left ventricular enlargement | 43 | 37.0 26.7–51.4ROR 37.1 · calibrated p 1e-4 ✓ | 30.5 EB05 23.6 · IC025 +4.0 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: only this drug | Likely indication confounding shares a disease stem with the indications wording | serious n=41 · ♀ 0% (drug 36%) · 100% clinician | not reported in cached trials |
| Ejection fraction decreased | 2,494 | 34.6 33.1–36.1ROR 35.3 · calibrated p 1e-4 ✓ | 29.1 EB05 28.2 · IC025 +4.8 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: PRR 41.7 (38.1–45.6) | Likely indication confounding term in indications | age-adj. PRR 34.1 · serious PRR 27.7 · 75% consumer | not reported in cached trials |
| Ventricular enlargement | 27 | 32.8 21.7–49.4ROR 32.8 · calibrated p 3e-4 ✓ | 27.4 EB05 19.7 · IC025 +3.6 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: only this drug | Likely indication confounding shares a disease stem with the indications wording | serious n=27 · ♀ 0% (drug 36%) | not reported in cached trials |
| Inferior vena cava dilatation | 32 | 32.6 22.4–47.5ROR 32.6 · calibrated p 3e-4 ✓ | 27.3 EB05 20.3 · IC025 +3.7 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: only this drug | Not in label — unassessed | serious n=32 · ♀ 0% (drug 36%) · 100% clinician | not reported in cached trials |
| Ejection fraction | 86 | 31.2 24.8–39.3ROR 31.3 · calibrated p 3e-4 ✓ | 26.6 EB05 22.2 · IC025 +4.2 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: only this drug | Likely indication confounding term in indications | serious n=20 · 88% consumer | not reported in cached trials |
| Cardiac dysfunction | 524 | 30.3 27.6–33.2ROR 30.4 · calibrated p 2e-4 ✓ | 26.0 EB05 24.2 · IC025 +4.5 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: only this drug | Likely indication confounding shares a disease stem with the indications wording | serious n=520 · 86% consumer | not reported in cached trials |
| Cardiac failure chronic | 606 | 30.1 27.6–32.8ROR 30.2 · calibrated p 3e-4 ✓ | 25.9 EB05 24.2 · IC025 +4.5 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: PRR 14.9 (13.1–16.9) | Not in label — unassessed | serious n=605 | NCT03066804: 21/1,280 (1.6%) on Sacubitril and Valsartan (serious AE) |
| Brain natriuretic peptide abnormal | 27 | 25.9 17.3–38.8ROR 25.9 · calibrated p 9e-4 ✓ | 22.4 EB05 16.1 · IC025 +3.4 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: only this drug | Lab value / disease marker | serious n=19 | not reported in cached trials |
| Chronic left ventricular failure | 43 | 25.1 18.2–34.5ROR 25.1 · calibrated p 9e-4 ✓ | 21.9 EB05 16.9 · IC025 +3.6 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: only this drug | Likely indication confounding term in indications | serious n=42 | NCT03066804: 1/1,280 (0.1%) on Sacubitril and Valsartan (serious AE) |
| Left atrial enlargement | 63 | 24.3 18.7–31.6ROR 24.3 · calibrated p 9e-4 ✓ | 21.4 EB05 17.3 · IC025 +3.8 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: only this drug | Not in label — unassessed | serious n=60 | not reported in cached trials |
| Weight fluctuation | 1,141 | 22.3 20.9–23.7ROR 22.5 · calibrated p 0.001 ✓ | 19.9 EB05 18.9 · IC025 +4.2 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: PRR 69.8 (59.2–82.4) | Not in label — unassessed | serious n=396 · 91% consumer | not reported in cached trials |
| Blood potassium increased | 1,411 | 17.2 16.3–18.2ROR 17.4 · calibrated p 0.004 ✓ | 15.8 EB05 15.1 · IC025 +3.9 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: PRR 19.8 (18.1–21.7) | Labeled (related wording) related wording | serious PRR 11.8 | NCT03066804: 26/1,280 (2.0%) on Sacubitril and Valsartan |
| Low cardiac output syndrome | 29 | 17.2 11.7–25.2ROR 17.2 · calibrated p 0.005 ✓ | 15.5 EB05 11.1 · IC025 +3.0 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: only this drug | Not in label — unassessed | serious n=29 · 100% clinician | not reported in cached trials |
| Left ventricular dilatation | 41 | 16.1 11.7–22.2ROR 16.1 · calibrated p 0.006 ✓ | 14.7 EB05 11.2 · IC025 +3.2 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: only this drug | Likely indication confounding shares a disease stem with the indications wording | serious n=40 | not reported in cached trials |
| Concomitant disease aggravated | 504 | 16.1 14.7–17.6ROR 16.1 · calibrated p 0.005 ✓ | 14.8 EB05 13.8 · IC025 +3.7 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: PRR 22.7 (19.3–26.6) | Not in label — unassessed | serious n=356 | not reported in cached trials |
| Blood pressure systolic decreased | 368 | 16.0 14.4–17.8ROR 16.1 · calibrated p 0.005 ✓ | 14.8 EB05 13.5 · IC025 +3.7 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: PRR 17.5 (14.8–20.8) | Lab value / disease marker | serious n=247 | not reported in cached trials |
| Brain natriuretic peptide increased | 250 | 16.0 14.0–18.2ROR 16.0 · calibrated p 0.005 ✓ | 14.7 EB05 13.2 · IC025 +3.6 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: PRR 20.1 (16.2–25.0) | Lab value / disease marker | serious n=201 | not reported in cached trials |
| Prescribed underdose | 1,586 | 15.6 14.8–16.4ROR 15.8 · calibrated p 0.006 ✓ | 14.4 EB05 13.9 · IC025 +3.8 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: PRR 52.7 (46.5–59.7) | Not in label — unassessed | age-adj. PRR 16.5 · serious PRR 11.3 | not reported in cached trials |
| Cardiorenal syndrome | 43 | 14.7 10.8–20.1ROR 14.8 · calibrated p 0.009 ✓ | 13.5 EB05 10.3 · IC025 +3.1 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: only this drug | Likely indication confounding shares a disease stem with the indications wording | serious n=43 · ♀ 0% (drug 36%) · 100% clinician | not reported in cached trials |
| Dizziness postural | 684 | 13.9 12.8–15.0ROR 13.9 · calibrated p 0.009 ✓ | 12.9 EB05 12.1 · IC025 +3.6 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: PRR 29.4 (25.3–34.2) | Not in label — unassessed | serious n=283 · 80% consumer | not reported in cached trials |
| Fluid imbalance | 48 | 13.2 9.8–17.7ROR 13.2 · calibrated p 0.013 ✓ | 12.1 EB05 9.3 · IC025 +3.0 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: only this drug | Not in label — unassessed | serious n=23 · 100% consumer | not reported in cached trials |
| Dyspnoea paroxysmal nocturnal | 50 | 13.2 9.9–17.5ROR 13.2 · calibrated p 0.014 ✓ | 12.1 EB05 9.4 · IC025 +3.0 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: only this drug | Not in label — unassessed | serious n=47 · ♀ 0% (drug 36%) · 100% clinician | not reported in cached trials |
| Orthopnoea | 212 | 12.9 11.2–14.8ROR 12.9 · calibrated p 0.013 ✓ | 12.0 EB05 10.7 · IC025 +3.3 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: PRR 11.0 (9.0–13.3) | Not in label — unassessed | serious n=195 | not reported in cached trials |
| Dilated cardiomyopathy | 57 | 11.8 9.0–15.5ROR 11.8 · calibrated p 0.020 ✓ | 10.9 EB05 8.6 · IC025 +2.9 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: only this drug | Likely indication confounding shares a disease stem with the indications wording | serious n=57 | not reported in cached trials |
| Systolic dysfunction | 64 | 11.7 9.1–15.1ROR 11.7 · calibrated p 0.020 ✓ | 10.8 EB05 8.6 · IC025 +2.9 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: PRR 28.1 (17.3–45.6) | Likely indication confounding term in indications | serious n=63 | not reported in cached trials |
| Glycosylated haemoglobin decreased | 95 | 11.5 9.3–14.1ROR 11.5 · calibrated p 0.021 ✓ | 10.7 EB05 8.9 · IC025 +3.0 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: only this drug | Lab value / disease marker | serious n=23 · 80% consumer | not reported in cached trials |
| Cardiac output decreased | 52 | 11.4 8.6–15.1ROR 11.4 · calibrated p 0.023 ✓ | 10.4 EB05 8.1 · IC025 +2.8 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: only this drug | Lab value / disease marker | serious n=47 | not reported in cached trials |
| Ischaemic cardiomyopathy | 181 | 11.2 9.7–13.0ROR 11.2 · calibrated p 0.022 ✓ | 10.5 EB05 9.3 · IC025 +3.1 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: PRR 14.5 (11.5–18.2) | Likely indication confounding shares a disease stem with the indications wording | serious n=181 | not reported in cached trials |
| Hypotension (low blood pressure) | 11,577 | 11.1 10.9–11.3ROR 12.2 · calibrated p 0.016 ✓ | 10.5 EB05 10.3 · IC025 +3.4 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: PRR 17.1 (16.7–17.6) | Labeled — boxed warning exact term | age-adj. PRR 9.1 · serious PRR 6.5 | NCT03066804: 6/1,280 (0.5%) on Sacubitril and Valsartan (serious AE) |
| Asthma-chronic obstructive pulmonary disease overlap syndrome | 30 | 11.1 7.6–16.0ROR 11.1 · calibrated p 0.027 ✓ | 9.8 EB05 7.0 · IC025 +2.6 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: only this drug | Not in label — unassessed | serious n=30 · ♀ 0% (drug 36%) · 100% clinician | not reported in cached trials |
| Heart failure with reduced ejection fraction | 26 | 10.9 7.3–16.2ROR 10.9 · calibrated p 0.029 ✓ | 9.6 EB05 6.6 · IC025 +2.5 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: only this drug | Likely indication confounding shares a disease stem with the indications wording | serious n=26 | not reported in cached trials |
| Cardiac failure (heart failure) | 4,514 | 10.8 10.5–11.1ROR 11.2 · calibrated p 0.022 ✓ | 10.2 EB05 10.0 · IC025 +3.3 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: PRR 14.9 (14.2–15.6) | Labeled (related wording) related wording | age-adj. PRR 10.1 · serious PRR 11.5 | NCT03066804: 21/1,280 (1.6%) on Sacubitril and Valsartan (serious AE) |
| Jugular vein distension | 32 | 10.7 7.5–15.3ROR 10.7 · calibrated p 0.030 ✓ | 9.5 EB05 6.9 · IC025 +2.6 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: only this drug | Not in label — unassessed | serious n=31 · 100% clinician | not reported in cached trials |
| Heart valve incompetence | 158 | 10.5 9.0–12.3ROR 10.5 · calibrated p 0.028 ✓ | 9.9 EB05 8.6 · IC025 +3.0 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: PRR 31.2 (22.6–42.9) | Not in label — unassessed | serious n=105 · 80% consumer | not reported in cached trials |
| Hypoacusis | 2,357 | 10.5 10.1–10.9ROR 10.7 · calibrated p 0.025 ✓ | 10.0 EB05 9.6 · IC025 +3.2 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: PRR 41.6 (37.9–45.6) | Not in label — unassessed | age-adj. PRR 3.2 · serious PRR 5.1 · 89% consumer | not reported in cached trials |
| Decreased activity | 584 | 10.4 9.6–11.3ROR 10.5 · calibrated p 0.028 ✓ | 9.9 EB05 9.2 · IC025 +3.2 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: PRR 25.0 (21.4–29.1) | Labeled (related wording) related wording | age-adj. PRR 12.3 · serious PRR 8.2 · 89% 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 | 8,483 | 9.08.8–9.2 | signal |
| Arrhythmia / qt | 3,403 | 3.23.1–3.3 | signal |
| Myocardial infarction | 2,990 | 2.72.6–2.8 | signal |
| Kidney injury | 5,600 | 2.22.2–2.3 | signal |
| Stroke | 2,225 | 1.61.6–1.7 | raised |
| Hyponatraemia | 683 | 1.51.4–1.7 | raised |
| Fall / fracture | 2,959 | 1.41.4–1.5 | raised |
| Hyperglycaemia / diabetes | 2,345 | 1.21.2–1.3 | raised |
| Anaphylaxis / angioedema | 758 | 1.11.0–1.2 | raised |
| Hypoglycaemia | 556 | 1.11.0–1.1 | no difference |
| Depression | 1,263 | 0.80.8–0.9 | lower than other drugs |
| Serious infection | 3,052 | 0.70.7–0.7 | lower than other drugs |
| Anaemia | 1,001 | 0.60.6–0.6 | lower than other drugs |
| Venous thromboembolism | 708 | 0.60.6–0.6 | lower than other drugs |
| Malignancy | 1,046 | 0.50.5–0.5 | lower than other drugs |
| Gi bleeding | 504 | 0.50.5–0.5 | lower than other drugs |
Trial evidence (ClinicalTrials.gov)
✓ Trial adverse-event data found on ClinicalTrials.gov
Largest completed trials with posted results that list Sacubitril and Valsartan 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 (5 of 40 signal terms matched).
- NCT03066804 — A Randomized, Double-blind Controlled Study Comparing LCZ696 to Medical Therapy for Comorbidities in HFpEF Pat (N=2572, PHASE3; 280 AE terms posted; arms: Sacubitril/Valsartan (LCZ696); Individualized Medical Therapy (IMT); Total)
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 |
|---|---|---|---|---|---|---|
| Hypotension (low blood pressure) | 11,577 | 11.1 10.9–11.3ROR 12.2 · calibrated p 0.016 ✓ | 10.5 EB05 10.3 · IC025 +3.4 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: PRR 17.1 (16.7–17.6) | Labeled — boxed warning exact term | age-adj. PRR 9.1 · serious PRR 6.5 | NCT03066804: 6/1,280 (0.5%) on Sacubitril and Valsartan (serious AE) |
| Death | 9,146 | 1.9 1.9–2.0ROR 2.0 · calibrated p 0.955 | 1.9 EB05 1.9 · IC025 +0.9 vs other Angiotensin 2 Receptor Blockers: PRR 17.3 (16.8–17.9) | Outcome field, not a reaction boxed warning mentions mortality | age-adj. PRR 1.7 · serious PRR 2.2 · 70% consumer | NCT03066804: 2/1,280 (0.2%) on Sacubitril and Valsartan (serious AE) |
| Dyspnoea (shortness of breath) | 8,999 | 2.9 2.9–3.0ROR 3.1 · calibrated p 0.599 | 2.9 EB05 2.8 · IC025 +1.5 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: PRR 7.6 (7.4–7.8) | Not in label — unassessed | age-adj. PRR 3.1 · serious PRR 2.7 · 73% consumer | NCT03066804: 1/1,280 (0.1%) on Sacubitril and Valsartan (serious AE) |
| Dizziness | 8,718 | 3.2 3.2–3.3ROR 3.4 · calibrated p 0.509 | 3.2 EB05 3.1 · IC025 +1.6 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: PRR 7.6 (7.4–7.8) | Labeled adverse reaction exact term | age-adj. PRR 3.2 · serious PRR 2.6 · 75% consumer | NCT03066804: 1/1,280 (0.1%) on Sacubitril and Valsartan (serious AE) |
| Fatigue (tiredness) | 8,713 | 2.1 2.0–2.1ROR 2.1 · calibrated p 0.984 | 2.0 EB05 2.0 · IC025 +1.0 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: PRR 6.6 (6.5–6.8) | Not in label — unassessed | age-adj. PRR 2.2 · serious PRR 1.9 · 80% consumer | NCT03066804: 1/1,284 (0.1%) on Sacubitril and Valsartan (serious AE) |
| Cough | 7,867 | 5.2 5.1–5.3ROR 5.5 · calibrated p 0.183 | 5.1 EB05 5.0 · IC025 +2.3 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: PRR 10.7 (10.4–11.0) | Labeled adverse reaction exact term | age-adj. PRR 4.7 · serious PRR 3.4 · 84% consumer | NCT03066804: 1/1,284 (0.1%) on Sacubitril and Valsartan (serious AE) |
| Wrong technique in product usage process | 7,322 | 6.8 6.6–7.0ROR 7.2 · calibrated p 0.091 | 6.6 EB05 6.5 · IC025 +2.7 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: PRR 47.3 (44.8–50.0) | Reporting / coding artifact | age-adj. PRR 7.0 · serious PRR 15.3 · 71% consumer | not reported in cached trials |
| Weight decreased (weight loss) | 5,209 | 3.4 3.3–3.5ROR 3.6 · calibrated p 0.472 | 3.4 EB05 3.3 · IC025 +1.7 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: PRR 8.3 (8.0–8.5) | Not in label — unassessed | age-adj. PRR 3.3 · serious PRR 2.2 · 85% consumer | not reported in cached trials |
| Cardiac failure (heart failure) | 4,514 | 10.8 10.5–11.1ROR 11.2 · calibrated p 0.022 ✓ | 10.2 EB05 10.0 · IC025 +3.3 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: PRR 14.9 (14.2–15.6) | Labeled (related wording) related wording | age-adj. PRR 10.1 · serious PRR 11.5 | NCT03066804: 21/1,280 (1.6%) on Sacubitril and Valsartan (serious AE) |
| Malaise (feeling unwell) | 4,463 | 1.9 1.8–1.9ROR 1.9 · calibrated p 0.881 | 1.8 EB05 1.8 · IC025 +0.8 vs other Angiotensin 2 Receptor Blockers: PRR 5.4 (5.2–5.6) | Not in label — unassessed | age-adj. PRR 1.6 · serious PRR 1.5 · 78% consumer | NCT03066804: 1/1,284 (0.1%) on Sacubitril and Valsartan (serious AE) |
| Asthenia (weakness) | 3,818 | 1.9 1.8–1.9ROR 1.9 · calibrated p 0.878 | 1.8 EB05 1.8 · IC025 +0.8 vs other Angiotensin 2 Receptor Blockers: PRR 4.4 (4.3–4.6) | Not in label — unassessed | age-adj. PRR 1.7 · serious PRR 1.6 · 75% consumer | not reported in cached trials |
| Weight increased (weight gain) | 3,510 | 2.9 2.8–3.0ROR 3.0 · calibrated p 0.642 | 2.9 EB05 2.8 · IC025 +1.5 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: PRR 9.3 (8.9–9.8) | Not in label — unassessed | age-adj. PRR 3.8 · serious PRR 2.4 · 78% consumer | not reported in cached trials |
| Blood pressure decreased | 3,181 | 9.1 8.8–9.4ROR 9.3 · calibrated p 0.041 ✓ | 8.7 EB05 8.5 · IC025 +3.1 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: PRR 13.9 (13.2–14.7) | Labeled — boxed warning synonym match | age-adj. PRR 7.5 · serious PRR 6.8 | not reported in cached trials |
| Product dose omission issue | 2,850 | 1.8 1.8–1.9ROR 1.8 · calibrated p 0.858 | 1.8 EB05 1.8 · IC025 +0.8 vs other Angiotensin 2 Receptor Blockers: PRR 14.3 (13.5–15.1) | Reporting / coding artifact | age-adj. PRR 2.4 · serious PRR 2.8 · 88% consumer | not reported in cached trials |
| Myocardial infarction (heart attack) | 2,782 | 2.9 2.8–3.0ROR 3.0 · calibrated p 0.642 | 2.9 EB05 2.8 · IC025 +1.5 3/3 methods agree vs other Angiotensin 2 Receptor Blockers: PRR 7.7 (7.4–8.1) | Not in label — unassessed | age-adj. PRR 2.4 · serious PRR 3.2 · 78% consumer | NCT03066804: 2/1,280 (0.2%) on Sacubitril and Valsartan (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.
- Throat clearing — n=1,549, PRR 130.2
- Inferior vena cava dilatation — n=32, PRR 32.6
- Cardiac failure chronic — n=606, PRR 30.1 (also seen in trial arm)
- Left atrial enlargement — n=63, PRR 24.3
- Weight fluctuation — n=1,141, PRR 22.3
- Low cardiac output syndrome — n=29, PRR 17.2
- Concomitant disease aggravated — n=504, PRR 16.1
- Prescribed underdose — n=1,586, PRR 15.6
- Dizziness postural — n=684, PRR 13.9
- Fluid imbalance — n=48, PRR 13.2
✓ A hand-written Bradford Hill causality assessment exists for this drug: Valsartan ↔ Acute kidney injury.
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 Sacubitril and Valsartan?
In FDA FAERS, the most frequently co-reported reaction terms for Sacubitril and Valsartan are hypotension, dyspnoea, dizziness, fatigue, cough, weight decreased. 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 Sacubitril and Valsartan have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: FETAL TOXICITY • When pregnancy is detected, discontinue Sacubitril and valsartan tablets as soon as possible. (5.1) • Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. (5.1) WARNING: FETAL TOXICITY See full prescribing information for complete boxed warning .
Do FAERS signals prove that Sacubitril and Valsartan 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 103c39e2-f3c8-40fc-a57e-3af018fb4af4, effective 20250626; matched on
openfda.generic_name.exact:"SACUBITRIL AND VALSARTAN") - 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, 1,216 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
SACUBITRIL, 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.