Glucarpidase side effects: what 358 FDA adverse event reports show

Glucarpidase · Voraxaze · 11 reaction terms · 213 drug–reaction co-reports · data 2026-09-14

Drug class

Carboxypeptidase

FDA label (Established Pharmacologic Class)

Brand names

Voraxaze

openFDA label

Who reports

358 reports · 71% serious · 70 with death outcome · 39% female

openFDA FAERS counts, all years, deduplication not applied

Used for

VORAXAZE is indicated to reduce toxic plasma methotrexate concentration (greater than 1 micromole per liter) in adult and pediatric patients with delayed methotrexate clearance (plasma methotrexate concentrations greater than 2 standard deviations of the mean methotrexate excretion curve specific for the dose of methotrexate administered) due to impaired renal function.

FDA label, Indications and Usage

What it is

Glucarpidase is a carboxypeptidase produced by recombinant DNA technology in genetically modified Escherichia coli. Glucarpidase is a 390-amino acid homodimer protein with a molecular weight of 83 kDa. Each potency Unit corresponds to the enzymatic cleavage of 1 µmol/L of methotrexate per minute at 37°C.

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 9 strongest signals

Labeled (related wording) 1Reporting / coding artifact 3Not in label — unassessed 5

What the badges mean

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. 2 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
Rebound effect	31	160.5 114.6–224.8ROR 175.6 · χ² 4,746 / p <1e-300	145.9 EB05 107.7 · IC025 +4.9 3/3 methods agree	Not in label — unassessed	serious PRR 167.7	no trial data cached
Nephropathy toxic	13	68.4 40.1–116.7ROR 71.0 · χ² 797 / p 1e-175	62.4 EB05 38.8 · IC025 +3.4 3/3 methods agree	Not in label — unassessed	serious PRR 56.6	no trial data cached
Drug level increased	16	56.6 35.1–91.4ROR 59.2 · χ² 819 / p 2e-180	53.2 EB05 34.7 · IC025 +3.6 3/3 methods agree	Reporting / coding artifact	serious PRR 44.3	no trial data cached
Toxic epidermal necrolysis (severe skin peeling reaction)	14	54.4 32.6–91.0ROR 56.6 · χ² 682 / p 2e-150	50.8 EB05 32.2 · IC025 +3.4 3/3 methods agree	Not in label — unassessed	serious PRR 44.0	no trial data cached
Drug effect incomplete	33	52.5 37.9–72.7ROR 57.7 · χ² 1,618 / p <1e-300	51.0 EB05 38.0 · IC025 +4.3 3/3 methods agree	Reporting / coding artifact	serious PRR 121.5	no trial data cached
Mucosal inflammation	23	51.7 34.8–76.8ROR 55.2 · χ² 1,095 / p 3e-240	49.7 EB05 34.9 · IC025 +3.9 3/3 methods agree	Labeled (related wording) related wording	serious PRR 44.4 · 95% clinician	no trial data cached
Underdose	62	49.7 39.7–62.4ROR 59.9 · χ² 2,920 / p <1e-300	49.0 EB05 39.6 · IC025 +4.7 3/3 methods agree	Reporting / coding artifact	serious PRR 44.4	no trial data cached
Fluid overload	7	27.8 13.3–57.9ROR 28.3 · χ² 155 / p 7e-36	25.5 EB05 12.3 · IC025 +2.0 3/3 methods agree	Not in label — unassessed	serious PRR 29.1	no trial data cached
Prescribed underdose	6	17.6 8.0–39.0ROR 17.9 · χ² 78 / p 5e-19	14.3 EB05 5.2 · IC025 +1.5 3/3 methods agree	Not in label — unassessed	serious PRR 16.2	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
Underdose	62	49.7 39.7–62.4ROR 59.9 · χ² 2,920 / p <1e-300	49.0 EB05 39.6 · IC025 +4.7 3/3 methods agree	Reporting / coding artifact	serious PRR 44.4	no trial data cached
Drug effect incomplete	33	52.5 37.9–72.7ROR 57.7 · χ² 1,618 / p <1e-300	51.0 EB05 38.0 · IC025 +4.3 3/3 methods agree	Reporting / coding artifact	serious PRR 121.5	no trial data cached
Rebound effect	31	160.5 114.6–224.8ROR 175.6 · χ² 4,746 / p <1e-300	145.9 EB05 107.7 · IC025 +4.9 3/3 methods agree	Not in label — unassessed	serious PRR 167.7	no trial data cached
Mucosal inflammation	23	51.7 34.8–76.8ROR 55.2 · χ² 1,095 / p 3e-240	49.7 EB05 34.9 · IC025 +3.9 3/3 methods agree	Labeled (related wording) related wording	serious PRR 44.4 · 95% clinician	no trial data cached
Drug level increased	16	56.6 35.1–91.4ROR 59.2 · χ² 819 / p 2e-180	53.2 EB05 34.7 · IC025 +3.6 3/3 methods agree	Reporting / coding artifact	serious PRR 44.3	no trial data cached
Toxic epidermal necrolysis (severe skin peeling reaction)	14	54.4 32.6–91.0ROR 56.6 · χ² 682 / p 2e-150	50.8 EB05 32.2 · IC025 +3.4 3/3 methods agree	Not in label — unassessed	serious PRR 44.0	no trial data cached
Nephropathy toxic	13	68.4 40.1–116.7ROR 71.0 · χ² 797 / p 1e-175	62.4 EB05 38.8 · IC025 +3.4 3/3 methods agree	Not in label — unassessed	serious PRR 56.6	no trial data cached
Fluid overload	7	27.8 13.3–57.9ROR 28.3 · χ² 155 / p 7e-36	25.5 EB05 12.3 · IC025 +2.0 3/3 methods agree	Not in label — unassessed	serious PRR 29.1	no trial data cached
Prescribed underdose	6	17.6 8.0–39.0ROR 17.9 · χ² 78 / p 5e-19	14.3 EB05 5.2 · IC025 +1.5 3/3 methods agree	Not in label — unassessed	serious PRR 16.2	no trial data cached
Hepatocellular injury	4	16.5 6.2–43.7ROR 16.7 · χ² 44 / p 2e-11	10.6 EB05 3.2 · IC025 +0.8 3/3 methods agree	Not in label — unassessed	serious PRR 13.3	no trial data cached
Therapy change	4	24.3 9.2–64.4ROR 24.6 · χ² 68 / p 1e-16	18.2 EB05 4.7 · IC025 +1.0 3/3 methods agree	Reporting / coding artifact	serious n=2	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.

Rebound effect — n=31, PRR 160.5

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 Glucarpidase?

In FDA FAERS, the most frequently co-reported reaction terms for Glucarpidase are rebound effect, mucosal inflammation, toxic epidermal necrolysis, nephropathy toxic, fluid overload, prescribed underdose. 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 Glucarpidase have an FDA boxed warning?

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

Do FAERS signals prove that Glucarpidase 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 acaef5a6-b740-40e3-8ffe-74a75c74745c, effective 20241127; matched on openfda.generic_name.exact:"GLUCARPIDASE")
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, 11 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.