Ziv-Aflibercept side effects: what 1,303 FDA adverse event reports show

Ziv-Aflibercept · Zaltrap · 36 reaction terms · 841 drug–reaction co-reports · data 2026-09-14

Drug class

Vascular Endothelial Growth Factor Inhibitor

FDA label (Established Pharmacologic Class) · compare the class

Brand names

Zaltrap

openFDA label

Who reports

1,303 reports · 94% serious · 207 with death outcome · 41% female

openFDA FAERS counts, all years, deduplication not applied

Used for

ZALTRAP, in combination with fluorouracil, leucovorin, irinotecan-(FOLFIRI), is indicated for the treatment of patients with metastatic colorectal cancer (mCRC) that is resistant to or has progressed following an oxaliplatin-containing regimen. ZALTRAP.

FDA label, Indications and Usage

What it is

Ziv-aflibercept is a vascular endothelial growth factor inhibitor. It is a recombinant fusion protein consisting of Vascular Endothelial Growth Factor (VEGF)-binding portions from the extracellular domains of human VEGF Receptors 1 and 2 fused to the Fc portion of the human IgG1.

FDA label, Description section

Boxed warning

None in the current 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 24 strongest signals

Labeled adverse reaction 11Labeled (related wording) 2Reporting / coding artifact 1Not in label — unassessed 10

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.
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.
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. 12 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
Proteinuria	64	54.8 43.1–69.6ROR 57.6 · χ² 3,319 / p <1e-300	53.8 EB05 43.6 · IC025 +4.9 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 33.5 · 98% clinician	no trial data cached
Hypertensive crisis	22	31.8 21.0–48.1ROR 32.3 · χ² 624 / p 4e-138	31.0 EB05 21.5 · IC025 +3.5 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 19.6 · ♀ 95% (drug 41%) · 100% clinician	no trial data cached
Mucosal inflammation	33	20.4 14.6–28.6ROR 20.9 · χ² 590 / p 2e-130	20.2 EB05 15.0 · IC025 +3.4 3/3 methods agree	Labeled (related wording) related wording	serious PRR 12.9 · 97% clinician	no trial data cached
Ileus	15	19.6 11.9–32.5ROR 19.9 · χ² 247 / p 6e-56	19.0 EB05 11.9 · IC025 +2.7 3/3 methods agree	Not in label — unassessed	serious PRR 12.2	no trial data cached
Intestinal perforation	13	18.6 10.8–32.0ROR 18.8 · χ² 200 / p 1e-45	17.8 EB05 10.5 · IC025 +2.6 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 11.5	no trial data cached
Posterior reversible encephalopathy syndrome	11	18.6 10.3–33.5ROR 18.8 · χ² 166 / p 3e-38	17.5 EB05 9.6 · IC025 +2.4 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 11.4	no trial data cached
Palmar-plantar erythrodysaesthesia syndrome	26	17.9 12.2–26.2ROR 18.3 · χ² 398 / p 7e-89	17.6 EB05 12.5 · IC025 +3.1 3/3 methods agree	Not in label — unassessed	serious PRR 13.5 · 100% clinician	no trial data cached
Hyperbilirubinaemia	11	17.2 9.5–31.0ROR 17.3 · χ² 152 / p 3e-35	16.0 EB05 8.5 · IC025 +2.3 3/3 methods agree	Not in label — unassessed	serious PRR 10.8	no trial data cached
Ejection fraction decreased	15	15.5 9.4–25.7ROR 15.7 · χ² 189 / p 2e-43	14.7 EB05 8.8 · IC025 +2.5 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 10.5	no trial data cached
Neutropenia (low neutrophils (infection-fighting cells))	105	12.5 10.4–15.0ROR 13.5 · χ² 1,104 / p 3e-242	12.4 EB05 10.5 · IC025 +3.2 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 7.8 · 96% clinician	no trial data cached
Neutrophil count decreased	29	11.5 8.0–16.5ROR 11.8 · χ² 269 / p 1e-60	10.9 EB05 7.7 · IC025 +2.7 3/3 methods agree	Labeled (related wording) related wording	serious PRR 7.7 · 100% clinician	no trial data cached
Stomatitis (mouth sores)	43	11.4 8.5–15.3ROR 11.8 · χ² 399 / p 4e-89	11.0 EB05 8.4 · IC025 +2.8 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 10.1 · 95% clinician	no trial data cached
Metastases to liver	12	11.0 6.3–19.4ROR 11.1 · χ² 100 / p 1e-23	9.3 EB05 5.2 · IC025 +2.0 3/3 methods agree	Not in label — unassessed	serious PRR 6.8	no trial data cached
Rectal haemorrhage	28	10.5 7.2–15.1ROR 10.7 · χ² 230 / p 2e-52	9.8 EB05 6.8 · IC025 +2.5 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 6.4 · 93% clinician	no trial data cached
Hypertension (high blood pressure)	137	10.4 8.9–12.2ROR 11.5 · χ² 1,166 / p 7e-256	10.3 EB05 8.9 · IC025 +3.0 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 7.4 · 96% clinician	no trial data cached
Bone marrow failure	13	10.2 6.0–17.6ROR 10.3 · χ² 99 / p 1e-23	8.6 EB05 5.0 · IC025 +2.0 3/3 methods agree	Not in label — unassessed	serious PRR 6.3	no trial data cached
Neurotoxicity	11	10.2 5.7–18.4ROR 10.3 · χ² 82 / p 6e-20	8.3 EB05 4.6 · IC025 +1.8 3/3 methods agree	Not in label — unassessed	serious PRR 6.3	no trial data cached
Febrile neutropenia	40	9.7 7.2–13.2ROR 10.0 · χ² 305 / p 1e-68	9.2 EB05 6.9 · IC025 +2.6 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 6.0 · 98% clinician	no trial data cached
Ascites	17	9.3 5.8–14.9ROR 9.4 · χ² 118 / p 9e-28	8.1 EB05 5.1 · IC025 +2.1 3/3 methods agree	Not in label — unassessed	serious PRR 5.8	no trial data cached
Oral herpes	10	8.3 4.5–15.4ROR 8.3 · χ² 57 / p 2e-14	6.5 EB05 3.6 · IC025 +1.5 3/3 methods agree	Not in label — unassessed	serious PRR 11.9	no trial data cached
Intestinal obstruction	19	8.2 5.2–12.8ROR 8.3 · χ² 113 / p 1e-26	7.1 EB05 4.7 · IC025 +2.0 3/3 methods agree	Not in label — unassessed	serious PRR 5.1	no trial data cached
Dysphonia	28	7.7 5.3–11.1ROR 7.9 · χ² 157 / p 2e-36	7.0 EB05 5.0 · IC025 +2.2 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 8.3 · 100% clinician	no trial data cached
Oral pain	10	7.2 3.9–13.3ROR 7.2 · χ² 47 / p 3e-12	5.6 EB05 3.2 · IC025 +1.4 3/3 methods agree	Not in label — unassessed	serious PRR 8.1	no trial data cached
Disease progression	49	6.7 5.1–8.8ROR 6.9 · χ² 233 / p 8e-53	6.3 EB05 5.0 · IC025 +2.2 3/3 methods agree	Reporting / coding artifact	serious PRR 4.6 · 92% clinician	no trial data cached

Trial evidence (ClinicalTrials.gov)

Trial cross-check not yet run for this drug (ClinicalTrials.gov pull covers the 800 most-reported drugs first).

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
Hypertension (high blood pressure)	137	10.4 8.9–12.2ROR 11.5 · χ² 1,166 / p 7e-256	10.3 EB05 8.9 · IC025 +3.0 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 7.4 · 96% clinician	no trial data cached
Neutropenia (low neutrophils (infection-fighting cells))	105	12.5 10.4–15.0ROR 13.5 · χ² 1,104 / p 3e-242	12.4 EB05 10.5 · IC025 +3.2 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 7.8 · 96% clinician	no trial data cached
Proteinuria	64	54.8 43.1–69.6ROR 57.6 · χ² 3,319 / p <1e-300	53.8 EB05 43.6 · IC025 +4.9 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 33.5 · 98% clinician	no trial data cached
Disease progression	49	6.7 5.1–8.8ROR 6.9 · χ² 233 / p 8e-53	6.3 EB05 5.0 · IC025 +2.2 3/3 methods agree	Reporting / coding artifact	serious PRR 4.6 · 92% clinician	no trial data cached
Stomatitis (mouth sores)	43	11.4 8.5–15.3ROR 11.8 · χ² 399 / p 4e-89	11.0 EB05 8.4 · IC025 +2.8 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 10.1 · 95% clinician	no trial data cached
Febrile neutropenia	40	9.7 7.2–13.2ROR 10.0 · χ² 305 / p 1e-68	9.2 EB05 6.9 · IC025 +2.6 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 6.0 · 98% clinician	no trial data cached
Mucosal inflammation	33	20.4 14.6–28.6ROR 20.9 · χ² 590 / p 2e-130	20.2 EB05 15.0 · IC025 +3.4 3/3 methods agree	Labeled (related wording) related wording	serious PRR 12.9 · 97% clinician	no trial data cached
Neutrophil count decreased	29	11.5 8.0–16.5ROR 11.8 · χ² 269 / p 1e-60	10.9 EB05 7.7 · IC025 +2.7 3/3 methods agree	Labeled (related wording) related wording	serious PRR 7.7 · 100% clinician	no trial data cached
Dysphonia	28	7.7 5.3–11.1ROR 7.9 · χ² 157 / p 2e-36	7.0 EB05 5.0 · IC025 +2.2 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 8.3 · 100% clinician	no trial data cached
Rectal haemorrhage	28	10.5 7.2–15.1ROR 10.7 · χ² 230 / p 2e-52	9.8 EB05 6.8 · IC025 +2.5 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 6.4 · 93% clinician	no trial data cached
Palmar-plantar erythrodysaesthesia syndrome	26	17.9 12.2–26.2ROR 18.3 · χ² 398 / p 7e-89	17.6 EB05 12.5 · IC025 +3.1 3/3 methods agree	Not in label — unassessed	serious PRR 13.5 · 100% clinician	no trial data cached
Hypertensive crisis	22	31.8 21.0–48.1ROR 32.3 · χ² 624 / p 4e-138	31.0 EB05 21.5 · IC025 +3.5 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 19.6 · ♀ 95% (drug 41%) · 100% clinician	no trial data cached
Intestinal obstruction	19	8.2 5.2–12.8ROR 8.3 · χ² 113 / p 1e-26	7.1 EB05 4.7 · IC025 +2.0 3/3 methods agree	Not in label — unassessed	serious PRR 5.1	no trial data cached
Ascites	17	9.3 5.8–14.9ROR 9.4 · χ² 118 / p 9e-28	8.1 EB05 5.1 · IC025 +2.1 3/3 methods agree	Not in label — unassessed	serious PRR 5.8	no trial data cached
Ejection fraction decreased	15	15.5 9.4–25.7ROR 15.7 · χ² 189 / p 2e-43	14.7 EB05 8.8 · IC025 +2.5 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 10.5	no trial data cached

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.

Palmar-plantar erythrodysaesthesia syndrome — n=26, PRR 17.9

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 Ziv-Aflibercept?

In FDA FAERS, the most frequently co-reported reaction terms for Ziv-Aflibercept are hypertension, neutropenia, proteinuria, stomatitis, febrile neutropenia, mucosal inflammation. 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 Ziv-Aflibercept have an FDA boxed warning?

No. The FDA label retrieved for Ziv-Aflibercept has no boxed warning; see the label's Warnings and Precautions for the recognised risks.

Do FAERS signals prove that Ziv-Aflibercept 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 f6725df6-50ee-4b0a-b900-d02ba634395d, effective 20251006; matched on openfda.generic_name.exact:"ZIV-AFLIBERCEPT")
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, 36 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.