Drug · FAERS side-effect profile with label screen

Leucovorin side effects: what 19,003 FDA adverse event reports show

Leucovorin Calcium · 1,159 reaction terms · 71,262 drug–reaction co-reports · data 2026-09-14

Drug class

Not stated in label

Label matched

Leucovorin Calcium (Leucovorin Calcium)

closest FDA label found for this product string; brand list suppressed because the label is a related product, not an exact match

Who reports

19,003 reports · 90% serious · 2,533 with death outcome · 45% female

openFDA FAERS counts, all years, deduplication not applied

Used for

Leucovorin calcium rescue is indicated after high dose methotrexate therapy in osteosarcoma. Leucovorin calcium is also indicated to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent over dosages of folic acid antagonists. Leucovorin calcium is indicated in the treatment of megaloblastic anemias due to folic acid deficiency when oral therapy is not feasible.

FDA label, Indications and Usage

What it is

DESCRIPTION Leucovorin is one of several active, chemically reduced derivatives of folic acid. It is useful as an antidote to drugs which act as folic acid antagonists. Also known as folinic a.

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 40 strongest signals

Labeled (related wording) 1Likely indication confounding 1Reporting / coding artifact 3Lab value / disease marker 6Not in label — unassessed 29

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.
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 flags pairs whose reports are unusually skewed by sex or come mostly from consumers rather than clinicians. 1,119 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
Monocyte chemotactic protein-1 increased	19	1,292.0 664.5–2,512.1ROR 1,293.3 · χ² 10,622 / p <1e-300	370.3 EB05 250.5 · IC025 +4.4 3/3 methods agree	Lab value / disease marker	serious n=19	no trial arm names this drug
Lymphoid tissue hypoplasia	32	302.8 204.7–447.8ROR 303.3 · χ² 7,295 / p <1e-300	207.8 EB05 154.1 · IC025 +5.1 3/3 methods agree	Not in label — unassessed	serious n=32	no trial arm names this drug
Alpha tumour necrosis factor increased	19	279.4 168.8–462.4ROR 279.6 · χ² 3,975 / p <1e-300	182.1 EB05 123.2 · IC025 +4.3 3/3 methods agree	Lab value / disease marker	serious n=19	no trial arm names this drug
Thymus hypoplasia	32	252.3 171.8–370.5ROR 252.7 · χ² 6,299 / p <1e-300	182.8 EB05 135.6 · IC025 +5.0 3/3 methods agree	Not in label — unassessed	serious n=32	no trial arm names this drug
Nipple swelling	35	176.3 123.4–251.9ROR 176.6 · χ² 5,100 / p <1e-300	140.4 EB05 105.5 · IC025 +5.0 3/3 methods agree	Not in label — unassessed	serious n=35 · ♀ 0% (drug 45%)	no trial arm names this drug
Teratogenicity	28	112.4 76.2–165.8ROR 112.6 · χ² 2,702 / p <1e-300	95.5 EB05 69.4 · IC025 +4.6 3/3 methods agree	Not in label — unassessed	serious n=28 · 100% clinician	no trial arm names this drug
Central nervous system lupus	18	99.9 61.7–161.9ROR 100.0 · χ² 1,525 / p <1e-300	83.7 EB05 56.0 · IC025 +3.9 3/3 methods agree	Not in label — unassessed	serious n=18	no trial arm names this drug
Neutropenia neonatal	15	78.5 46.5–132.5ROR 78.5 · χ² 999 / p 2e-219	67.3 EB05 43.3 · IC025 +3.6 3/3 methods agree	Not in label — unassessed	serious n=15	no trial arm names this drug
Sleep disorder therapy	12	75.9 42.3–136.3ROR 76.0 · χ² 761 / p 1e-167	64.1 EB05 39.1 · IC025 +3.2 3/3 methods agree	Reporting / coding artifact	serious n=12	no trial arm names this drug
Laryngeal dyspnoea	13	68.0 38.8–119.1ROR 68.0 · χ² 746 / p 2e-164	58.8 EB05 36.6 · IC025 +3.3 3/3 methods agree	Not in label — unassessed	serious n=13	no trial arm names this drug
Non-cirrhotic portal hypertension	21	67.6 43.5–105.0ROR 67.7 · χ² 1,235 / p 6e-271	60.4 EB05 41.7 · IC025 +4.0 3/3 methods agree	Not in label — unassessed	serious n=21 · 100% clinician	no trial arm names this drug
Colorectal cancer metastatic	130	66.5 55.7–79.3ROR 66.9 · χ² 7,839 / p <1e-300	62.2 EB05 53.7 · IC025 +5.4 3/3 methods agree	Likely indication confounding shares a disease stem with the indications wording	serious n=130 · 94% clinician	no trial arm names this drug
Anastomotic complication	19	63.2 39.8–100.4ROR 63.3 · χ² 1,042 / p 8e-229	56.6 EB05 38.3 · IC025 +3.8 3/3 methods agree	Reporting / coding artifact	serious n=19	no trial arm names this drug
Congenital aplasia	15	60.2 35.8–101.3ROR 60.3 · χ² 773 / p 2e-170	53.5 EB05 34.4 · IC025 +3.5 3/3 methods agree	Not in label — unassessed	serious n=15	no trial arm names this drug
Disseminated aspergillosis	24	59.5 39.5–89.7ROR 59.6 · χ² 1,254 / p 7e-275	54.2 EB05 38.3 · IC025 +4.0 3/3 methods agree	Not in label — unassessed	serious n=24	no trial arm names this drug
Oesophageal atresia	28	51.5 35.3–75.3ROR 51.6 · χ² 1,277 / p 5e-280	47.8 EB05 34.7 · IC025 +4.1 3/3 methods agree	Not in label — unassessed	serious n=28 · 100% clinician	no trial arm names this drug
Portal venous gas	15	49.0 29.2–82.2ROR 49.0 · χ² 630 / p 3e-139	44.5 EB05 28.6 · IC025 +3.4 3/3 methods agree	Not in label — unassessed	serious n=15	no trial arm names this drug
Mycobacterium chelonae infection	31	48.5 33.8–69.4ROR 48.5 · χ² 1,334 / p 2e-292	45.2 EB05 33.4 · IC025 +4.2 3/3 methods agree	Not in label — unassessed	serious n=31	no trial arm names this drug
Secondary immunodeficiency	50	48.2 36.3–63.9ROR 48.3 · χ² 2,167 / p <1e-300	45.4 EB05 35.8 · IC025 +4.5 3/3 methods agree	Labeled (related wording) related wording	serious n=50	no trial arm names this drug
Rectal cancer metastatic	14	46.4 27.2–79.3ROR 46.5 · χ² 554 / p 8e-123	42.2 EB05 26.7 · IC025 +3.3 3/3 methods agree	Not in label — unassessed	serious n=14	no trial arm names this drug
Analgesic therapy	12	44.9 25.2–79.9ROR 44.9 · χ² 453 / p 8e-101	40.6 EB05 24.7 · IC025 +3.0 3/3 methods agree	Reporting / coding artifact	serious n=12	no trial arm names this drug
Interleukin level increased	20	42.9 27.5–67.1ROR 43.0 · χ² 748 / p 6e-165	39.9 EB05 27.3 · IC025 +3.6 3/3 methods agree	Lab value / disease marker	serious n=20 · 90% clinician	no trial arm names this drug
Subretinal fluid	37	40.1 28.9–55.6ROR 40.1 · χ² 1,322 / p 1e-289	38.0 EB05 28.8 · IC025 +4.1 3/3 methods agree	Not in label — unassessed	serious n=37 · 100% clinician	no trial arm names this drug
Anastomotic leak	24	39.4 26.2–59.2ROR 39.4 · χ² 830 / p 9e-183	37.0 EB05 26.2 · IC025 +3.8 3/3 methods agree	Not in label — unassessed	serious n=23 · ♀ 23% (drug 45%) · 91% clinician	no trial arm names this drug
Pseudomonal sepsis	57	36.9 28.3–48.0ROR 37.0 · χ² 1,890 / p <1e-300	35.3 EB05 28.3 · IC025 +4.3 3/3 methods agree	Not in label — unassessed	serious n=57	no trial arm names this drug
Minimal residual disease	14	33.9 19.9–57.7ROR 33.9 · χ² 402 / p 8e-90	31.6 EB05 20.0 · IC025 +3.1 3/3 methods agree	Not in label — unassessed	serious n=14	no trial arm names this drug
Rectal perforation	16	33.7 20.5–55.4ROR 33.7 · χ² 461 / p 2e-102	31.6 EB05 20.6 · IC025 +3.2 3/3 methods agree	Not in label — unassessed	serious n=15	no trial arm names this drug
Overlap syndrome	20	32.9 21.1–51.4ROR 33.0 · χ² 570 / p 2e-126	31.1 EB05 21.3 · IC025 +3.4 3/3 methods agree	Not in label — unassessed	serious n=20	no trial arm names this drug
Klebsiella test positive	18	31.3 19.6–50.0ROR 31.3 · χ² 484 / p 1e-107	29.6 EB05 19.8 · IC025 +3.3 3/3 methods agree	Lab value / disease marker	serious n=17	no trial arm names this drug
Catheter related infection	28	31.0 21.3–45.1ROR 31.0 · χ² 760 / p 1e-167	29.6 EB05 21.5 · IC025 +3.7 3/3 methods agree	Not in label — unassessed	serious n=27	no trial arm names this drug
Colon cancer metastatic	43	30.3 22.4–41.1ROR 30.4 · χ² 1,159 / p 3e-254	29.2 EB05 22.6 · IC025 +4.0 3/3 methods agree	Not in label — unassessed	serious n=44	no trial arm names this drug
Reversible posterior leukoencephalopathy syndrome	21	30.0 19.5–46.3ROR 30.1 · χ² 545 / p 6e-121	28.6 EB05 19.7 · IC025 +3.4 3/3 methods agree	Not in label — unassessed	serious n=20 · ♀ 70% (drug 45%) · 100% clinician	no trial arm names this drug
Granulocyte count decreased	47	29.9 22.4–39.9ROR 29.9 · χ² 1,249 / p 9e-274	28.8 EB05 22.5 · IC025 +4.0 3/3 methods agree	Lab value / disease marker	serious n=47	no trial arm names this drug
Malignant ascites	20	29.5 18.9–46.0ROR 29.6 · χ² 509 / p 5e-113	28.1 EB05 19.2 · IC025 +3.4 3/3 methods agree	Not in label — unassessed	serious n=19	no trial arm names this drug
Drug clearance decreased	31	27.8 19.5–39.7ROR 27.9 · χ² 756 / p 1e-166	26.8 EB05 19.7 · IC025 +3.7 3/3 methods agree	Lab value / disease marker	serious n=31	no trial arm names this drug
Foetal disorder	20	26.7 17.2–41.6ROR 26.8 · χ² 459 / p 5e-102	25.5 EB05 17.4 · IC025 +3.3 3/3 methods agree	Not in label — unassessed	serious n=20	no trial arm names this drug
Dilated cardiomyopathy	21	25.5 16.5–39.3ROR 25.5 · χ² 459 / p 3e-102	24.4 EB05 16.8 · IC025 +3.3 3/3 methods agree	Not in label — unassessed	serious n=21 · 100% clinician	no trial arm names this drug
Diffuse alveolar damage	25	24.4 16.4–36.3ROR 24.4 · χ² 526 / p 8e-117	23.5 EB05 16.7 · IC025 +3.4 3/3 methods agree	Not in label — unassessed	serious n=25 · 100% clinician	no trial arm names this drug
Stenotrophomonas infection	29	24.4 16.9–35.2ROR 24.4 · χ² 614 / p 8e-136	23.6 EB05 17.2 · IC025 +3.5 3/3 methods agree	Not in label — unassessed	serious n=29 · ♀ 0% (drug 45%) · 100% clinician	no trial arm names this drug
Peritoneal disorder	14	24.1 14.2–41.0ROR 24.2 · χ² 282 / p 2e-63	22.9 EB05 14.3 · IC025 +2.8 3/3 methods agree	Not in label — unassessed	serious n=14	no trial arm names this drug

Trial evidence (ClinicalTrials.gov)

ClinicalTrials.gov returned results-bearing trials mentioning Leucovorin only as a background or rescue medication (NCT01190930, NCT02883049); no trial listing it as the tested intervention was cached, so no trial cross-check is shown.

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
Diarrhoea (diarrhea)	1,799	3.1 3.0–3.2ROR 3.3 · χ² 2,618 / p <1e-300	3.1 EB05 3.0 · IC025 +1.5 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 3.2 · 90% clinician	no trial arm names this drug
Nausea	1,389	1.9 1.8–2.0ROR 2.0 · χ² 660 / p 7e-146	1.9 EB05 1.9 · IC025 +0.9	Labeled adverse reaction exact term	serious PRR 2.2	no trial arm names this drug
Vomiting	1,136	2.7 2.5–2.8ROR 2.8 · χ² 1,217 / p 6e-267	2.7 EB05 2.5 · IC025 +1.3 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 2.4 · 92% clinician	no trial arm names this drug
Neutropenia (low neutrophils (infection-fighting cells))	1,094	9.0 8.5–9.5ROR 9.5 · χ² 7,732 / p <1e-300	8.9 EB05 8.5 · IC025 +3.1 3/3 methods agree	Not in label — unassessed	serious PRR 5.3 · 95% clinician	no trial arm names this drug
Pyrexia (fever)	1,012	3.2 3.0–3.4ROR 3.4 · χ² 1,580 / p <1e-300	3.2 EB05 3.1 · IC025 +1.6 3/3 methods agree	Not in label — unassessed	serious PRR 2.5 · 91% clinician	no trial arm names this drug
Off label use (used outside approved label)	953	1.2 1.1–1.3ROR 1.2 · χ² 37 / p 7e-10	1.2 EB05 1.1 · IC025 +0.2	Reporting / coding artifact	serious PRR 1.4	no trial arm names this drug
Fatigue (tiredness)	874	1.2 1.2–1.3ROR 1.3 · χ² 42 / p 4e-11	1.2 EB05 1.2 · IC025 +0.2	Labeled adverse reaction exact term	serious PRR 1.4	no trial arm names this drug
Disease progression	770	7.2 6.8–7.8ROR 7.5 · χ² 4,136 / p <1e-300	7.2 EB05 6.8 · IC025 +2.7 3/3 methods agree	Reporting / coding artifact	serious PRR 5.2 · 96% clinician	no trial arm names this drug
Drug ineffective (drug did not work)	718	0.6 0.6–0.6ROR 0.6 · χ² 202 / p 5e-46	0.6 EB05 0.6 · IC025 -0.9 PRR-only: not supported by EBGM or IC	Reporting / coding artifact	serious PRR 1.0	no trial arm names this drug
Dyspnoea (shortness of breath)	711	1.4 1.3–1.5ROR 1.4 · χ² 79 / p 4e-19	1.4 EB05 1.3 · IC025 +0.3	Not in label — unassessed	serious PRR 1.2	no trial arm names this drug
Asthenia (weakness)	676	2.0 1.8–2.1ROR 2.0 · χ² 335 / p 4e-75	2.0 EB05 1.9 · IC025 +0.9	Not in label — unassessed	serious PRR 1.7	no trial arm names this drug
Abdominal pain	666	3.2 2.9–3.4ROR 3.2 · χ² 994 / p 2e-218	3.2 EB05 3.0 · IC025 +1.5 3/3 methods agree	Not in label — unassessed	serious PRR 2.5 · 92% clinician	no trial arm names this drug
Febrile neutropenia	652	11.0 10.2–11.8ROR 11.3 · χ² 5,854 / p <1e-300	10.8 EB05 10.2 · IC025 +3.3 3/3 methods agree	Not in label — unassessed	serious PRR 6.4 · 95% clinician	no trial arm names this drug
Thrombocytopenia (low platelets)	623	6.2 5.7–6.7ROR 6.4 · χ² 2,708 / p <1e-300	6.1 EB05 5.7 · IC025 +2.5 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 3.8 · 95% clinician	no trial arm names this drug
Anaemia (low red blood cells)	603	3.5 3.2–3.8ROR 3.6 · χ² 1,078 / p 1e-236	3.5 EB05 3.3 · IC025 +1.7 3/3 methods agree	Likely indication confounding term in indications; also in warnings	serious PRR 2.4 · 92% clinician	no trial arm names this drug

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.

Lymphoid tissue hypoplasia — n=32, PRR 302.8
Thymus hypoplasia — n=32, PRR 252.3
Nipple swelling — n=35, PRR 176.3
Teratogenicity — n=28, PRR 112.4
Non-cirrhotic portal hypertension — n=21, PRR 67.6
Disseminated aspergillosis — n=24, PRR 59.5
Oesophageal atresia — n=28, PRR 51.5
Mycobacterium chelonae infection — n=31, PRR 48.5
Subretinal fluid — n=37, PRR 40.1
Anastomotic leak — n=24, PRR 39.4

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 Leucovorin?

In FDA FAERS, the most frequently co-reported reaction terms for Leucovorin are diarrhoea, nausea, vomiting, neutropenia, pyrexia, fatigue. 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 Leucovorin have an FDA boxed warning?

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

Do FAERS signals prove that Leucovorin 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 1cb701ca-2478-4268-9d69-80293965d59d, effective 20220601; matched on openfda.generic_name.exact:"LEUCOVORIN CALCIUM")
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, 1,159 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 LEUCOVORIN, results-bearing studies sorted by enrollment)

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.