Belzutifan side effects: what 1,573 FDA adverse event reports show
Drug class
Hypoxia-inducible Factor Inhibitor
Brand names
Welireg
Who reports
1,573 reports · 70% serious · 150 with death outcome · 36% female
Used for
WELIREG is a hypoxia-inducible factor inhibitor indicated: von Hippel-Lindau (VHL) disease for treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery.
What it is
Belzutifan is an inhibitor of hypoxia-inducible factor-2α (HIF-2α).
Boxed warning
EMBRYO-FETAL TOXICITY Exposure to WELIREG during pregnancy can cause embryo-fetal harm. Verify pregnancy status prior to the initiation of WELIREG. Advise patients of these risks and the need for effective non-hormonal contraception.
Causality screen of the 17 strongest signals
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 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.
- 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. 11 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 |
|---|---|---|---|---|---|---|
| Hypoxia (low oxygen) | 146 | 55.7 47.7–65.1ROR 61.3 · χ² 7,772 / p <1e-300 | 55.1 EB05 48.0 · IC025 +5.3 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 44.5 · 92% clinician | no trial data cached |
| Malignant neoplasm progression | 208 | 27.3 24.0–31.0ROR 31.3 · χ² 5,253 / p <1e-300 | 27.2 EB05 24.2 · IC025 +4.4 3/3 methods agree | Reporting / coding artifact | serious PRR 22.4 · 94% clinician | no trial data cached |
| Wound infection | 19 | 23.3 14.9–36.5ROR 23.6 · χ² 384 / p 9e-86 | 22.8 EB05 15.4 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious PRR 20.7 | no trial data cached |
| Anaemia (low red blood cells) | 283 | 19.8 17.8–22.0ROR 23.9 · χ² 5,070 / p <1e-300 | 19.7 EB05 17.9 · IC025 +4.1 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 14.0 | no trial data cached |
| Hospice care | 14 | 19.0 11.3–32.0ROR 19.1 · χ² 220 / p 4e-50 | 18.2 EB05 11.1 · IC025 +2.6 3/3 methods agree | Not in label — unassessed | serious PRR 3.2 | no trial data cached |
| Therapy partial responder | 18 | 15.9 10.1–25.3ROR 16.1 · χ² 237 / p 7e-54 | 15.3 EB05 9.8 · IC025 +2.7 3/3 methods agree | Reporting / coding artifact | serious PRR 14.2 | no trial data cached |
| Oxygen saturation decreased | 47 | 11.2 8.5–14.9ROR 11.6 · χ² 429 / p 1e-95 | 10.9 EB05 8.4 · IC025 +2.9 3/3 methods agree | Lab value / disease marker | serious PRR 6.1 | no trial data cached |
| Therapy change | 7 | 9.7 4.6–20.3ROR 9.7 · χ² 46 / p 5e-12 | 6.9 EB05 3.3 · IC025 +1.3 3/3 methods agree | Reporting / coding artifact | serious n=3 | no trial data cached |
| Therapy interrupted | 47 | 9.1 6.9–12.0ROR 9.3 · χ² 331 / p 3e-74 | 8.6 EB05 6.7 · IC025 +2.6 3/3 methods agree | Reporting / coding artifact | serious PRR 4.7 · ♀ 59% (drug 36%) · 86% consumer | no trial data cached |
| Transfusion | 7 | 8.9 4.2–18.6ROR 8.9 · χ² 41 / p 6e-11 | 6.3 EB05 3.1 · IC025 +1.2 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 6.6 | no trial data cached |
| Pneumonitis | 17 | 8.4 5.2–13.5ROR 8.5 · χ² 103 / p 1e-24 | 7.2 EB05 4.6 · IC025 +2.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 7.2 | no trial data cached |
| Haemoglobin decreased | 59 | 7.6 6.0–9.8ROR 7.9 · χ² 336 / p 3e-75 | 7.3 EB05 5.8 · IC025 +2.4 3/3 methods agree | Labeled — boxed warning synonym match | serious PRR 3.3 | no trial data cached |
| Myocarditis | 6 | 7.1 3.2–15.7ROR 7.1 · χ² 25 / p 2e-7 | 4.9 EB05 2.4 · IC025 +0.9 3/3 methods agree | Not in label — unassessed | serious PRR 5.9 | no trial data cached |
| Cholecystitis | 6 | 6.7 3.0–15.0ROR 6.8 · χ² 24 / p 5e-7 | 4.7 EB05 2.3 · IC025 +0.8 3/3 methods agree | Not in label — unassessed | serious PRR 5.6 | no trial data cached |
| Metastases to bone | 8 | 6.5 3.3–13.0ROR 6.5 · χ² 32 / p 7e-9 | 4.9 EB05 2.7 · IC025 +1.1 3/3 methods agree | Not in label — unassessed | serious PRR 4.8 | no trial data cached |
| Proteinuria | 9 | 6.4 3.3–12.2ROR 6.4 · χ² 36 / p 1e-9 | 5.0 EB05 2.8 · IC025 +1.2 3/3 methods agree | Not in label — unassessed | serious PRR 5.9 | no trial data cached |
| Palmar-plantar erythrodysaesthesia syndrome | 7 | 4.0 1.9–8.4ROR 4.0 · χ² 13 / p 2e-4 | 3.3 EB05 1.8 · IC025 +0.4 | Not in label — unassessed | serious PRR 3.8 | no trial data cached |
Trial evidence (ClinicalTrials.gov)
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 |
|---|---|---|---|---|---|---|
| Anaemia (low red blood cells) | 283 | 19.8 17.8–22.0ROR 23.9 · χ² 5,070 / p <1e-300 | 19.7 EB05 17.9 · IC025 +4.1 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 14.0 | no trial data cached |
| Malignant neoplasm progression | 208 | 27.3 24.0–31.0ROR 31.3 · χ² 5,253 / p <1e-300 | 27.2 EB05 24.2 · IC025 +4.4 3/3 methods agree | Reporting / coding artifact | serious PRR 22.4 · 94% clinician | no trial data cached |
| Hypoxia (low oxygen) | 146 | 55.7 47.7–65.1ROR 61.3 · χ² 7,772 / p <1e-300 | 55.1 EB05 48.0 · IC025 +5.3 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 44.5 · 92% clinician | no trial data cached |
| Haemoglobin decreased | 59 | 7.6 6.0–9.8ROR 7.9 · χ² 336 / p 3e-75 | 7.3 EB05 5.8 · IC025 +2.4 3/3 methods agree | Labeled — boxed warning synonym match | serious PRR 3.3 | no trial data cached |
| Therapy interrupted | 47 | 9.1 6.9–12.0ROR 9.3 · χ² 331 / p 3e-74 | 8.6 EB05 6.7 · IC025 +2.6 3/3 methods agree | Reporting / coding artifact | serious PRR 4.7 · ♀ 59% (drug 36%) · 86% consumer | no trial data cached |
| Oxygen saturation decreased | 47 | 11.2 8.5–14.9ROR 11.6 · χ² 429 / p 1e-95 | 10.9 EB05 8.4 · IC025 +2.9 3/3 methods agree | Lab value / disease marker | serious PRR 6.1 | no trial data cached |
| Wound infection | 19 | 23.3 14.9–36.5ROR 23.6 · χ² 384 / p 9e-86 | 22.8 EB05 15.4 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious PRR 20.7 | no trial data cached |
| Therapy partial responder | 18 | 15.9 10.1–25.3ROR 16.1 · χ² 237 / p 7e-54 | 15.3 EB05 9.8 · IC025 +2.7 3/3 methods agree | Reporting / coding artifact | serious PRR 14.2 | no trial data cached |
| Pneumonitis | 17 | 8.4 5.2–13.5ROR 8.5 · χ² 103 / p 1e-24 | 7.2 EB05 4.6 · IC025 +2.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 7.2 | no trial data cached |
| Hospice care | 14 | 19.0 11.3–32.0ROR 19.1 · χ² 220 / p 4e-50 | 18.2 EB05 11.1 · IC025 +2.6 3/3 methods agree | Not in label — unassessed | serious PRR 3.2 | no trial data cached |
| Proteinuria | 9 | 6.4 3.3–12.2ROR 6.4 · χ² 36 / p 1e-9 | 5.0 EB05 2.8 · IC025 +1.2 3/3 methods agree | Not in label — unassessed | serious PRR 5.9 | no trial data cached |
| Metastases to bone | 8 | 6.5 3.3–13.0ROR 6.5 · χ² 32 / p 7e-9 | 4.9 EB05 2.7 · IC025 +1.1 3/3 methods agree | Not in label — unassessed | serious PRR 4.8 | no trial data cached |
| Renal cancer | 7 | 1.9 0.9–4.1ROR 1.9 · χ² 2 / p 0.065 | 1.8 EB05 1.0 · IC025 -0.4 PRR-only: not supported by EBGM or IC | Labeled (related wording) related wording | serious PRR 0.2 | no trial data cached |
| Palmar-plantar erythrodysaesthesia syndrome | 7 | 4.0 1.9–8.4ROR 4.0 · χ² 13 / p 2e-4 | 3.3 EB05 1.8 · IC025 +0.4 | Not in label — unassessed | serious PRR 3.8 | no trial data cached |
| Transfusion | 7 | 8.9 4.2–18.6ROR 8.9 · χ² 41 / p 6e-11 | 6.3 EB05 3.1 · IC025 +1.2 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 6.6 | no trial data cached |
Unlabeled candidate signals
Every screened signal with n ≥ 20 was either labeled, an indication term, or an artifact pattern — no unlabeled candidate stood out in the top signals.
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 Belzutifan?
In FDA FAERS, the most frequently co-reported reaction terms for Belzutifan are anaemia, hypoxia, haemoglobin decreased, oxygen saturation decreased, wound infection, pneumonitis. 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 Belzutifan have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: EMBRYO-FETAL TOXICITY Exposure to WELIREG during pregnancy can cause embryo-fetal harm. Verify pregnancy status prior to the initiation of WELIREG. Advise patients of these risks and the need for effective non-hormonal contraception.
Do FAERS signals prove that Belzutifan 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 13e15ee0-d679-4fa9-9430-e2e2170474da, effective 20260612; matched on
openfda.generic_name.exact:"BELZUTIFAN") - 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, 28 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
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.