Drug · FAERS side-effect profile with label screen
Levoleucovorin Injection side effects: what 2,976 FDA adverse event reports show
Drug class
Folate analog
FDA label, Indications wording
Who reports
2,976 reports · 99% serious · 505 with death outcome · 39% female
openFDA FAERS counts, all years, deduplication not applied
Used for
Levoleucovorin injection is a folate analog. Levoleucovorin injection rescue is indicated after high-dose methotrexate therapy in osteosarcoma. Levoleucovorin injection is also indicated to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosage of folic acid antagonists.
FDA label, Indications and Usage
What it is
Levoleucovorin is the levo isomeric form of racemic d,l-leucovorin, present as the calcium salt. Levoleucovorin is the pharmacologically active isomer of leucovorin [(6-S)-leucovorin]. Levoleucovorin Injection contain levoleucovorin calcium, which is one of several active, chemically reduced derivatives of folic acid.
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 adverse reaction 4Labeled (related wording) 3Reporting / coding artifact 2Lab value / disease marker 2Not in label — unassessed 29
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.
- 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. 46 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 |
|---|---|---|---|---|---|---|
| Myelosuppression | 127 | 26.4 22.3–31.3ROR 27.5 · χ² 3,071 / p <1e-300 | 26.2 EB05 22.6 · IC025 +4.3 3/3 methods agree | Not in label — unassessed | serious PRR 15.1 | no trial data cached |
| Neutrophil count decreased | 131 | 22.9 19.3–27.0ROR 23.9 · χ² 2,712 / p <1e-300 | 22.7 EB05 19.6 · IC025 +4.1 3/3 methods agree | Lab value / disease marker | serious PRR 15.1 | no trial data cached |
| Hypomagnesaemia | 35 | 17.8 12.8–24.8ROR 18.0 · χ² 538 / p 3e-119 | 17.6 EB05 13.1 · IC025 +3.3 3/3 methods agree | Not in label — unassessed | serious PRR 10.7 · 97% clinician | no trial data cached |
| Interstitial lung disease | 116 | 17.0 14.2–20.3ROR 17.6 · χ² 1,725 / p <1e-300 | 16.9 EB05 14.4 · IC025 +3.7 3/3 methods agree | Not in label — unassessed | serious PRR 9.9 | no trial data cached |
| Diarrhoea haemorrhagic | 22 | 16.6 10.9–25.2ROR 16.7 · χ² 306 / p 7e-69 | 16.1 EB05 11.0 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious PRR 10.3 · ♀ 91% (drug 39%) · 100% clinician | no trial data cached |
| Colon cancer | 33 | 15.6 11.1–21.9ROR 15.8 · χ² 436 / p 4e-97 | 15.3 EB05 11.3 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious PRR 9.2 · 100% clinician | no trial data cached |
| Thrombotic microangiopathy | 18 | 13.1 8.3–20.8ROR 13.2 · χ² 189 / p 2e-43 | 12.2 EB05 7.6 · IC025 +2.5 3/3 methods agree | Not in label — unassessed | serious PRR 7.6 | no trial data cached |
| Disseminated intravascular coagulation | 26 | 13.0 8.9–19.1ROR 13.1 · χ² 276 / p 3e-62 | 12.4 EB05 8.6 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious PRR 7.6 | no trial data cached |
| Anaphylactic shock | 45 | 12.4 9.3–16.6ROR 12.6 · χ² 460 / p 3e-102 | 12.1 EB05 9.2 · IC025 +3.0 3/3 methods agree | Not in label — unassessed | serious PRR 7.2 · 100% clinician | no trial data cached |
| Hepatic cytolysis | 20 | 11.5 7.5–17.9ROR 11.6 · χ² 182 / p 8e-42 | 10.6 EB05 6.8 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 6.7 · 100% clinician | no trial data cached |
| Malignant neoplasm progression | 161 | 11.2 9.6–13.0ROR 11.7 · χ² 1,483 / p <1e-300 | 11.0 EB05 9.7 · IC025 +3.2 3/3 methods agree | Reporting / coding artifact | serious PRR 6.6 | no trial data cached |
| Metastases to liver | 25 | 10.1 6.8–14.9ROR 10.1 · χ² 195 / p 1e-44 | 9.2 EB05 6.3 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 5.9 · 100% clinician | no trial data cached |
| Neuropathy peripheral (nerve damage in hands/feet) | 131 | 9.8 8.3–11.6ROR 10.2 · χ² 1,026 / p 2e-225 | 9.6 EB05 8.3 · IC025 +3.0 3/3 methods agree | Labeled (related wording) related wording | serious PRR 6.6 · 93% clinician | no trial data cached |
| Altered state of consciousness | 28 | 9.2 6.3–13.3ROR 9.2 · χ² 196 / p 1e-44 | 8.4 EB05 6.0 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 5.4 · ♀ 16% (drug 39%) · 100% clinician | no trial data cached |
| Posterior reversible encephalopathy syndrome | 12 | 8.9 5.1–15.6ROR 8.9 · χ² 76 / p 1e-18 | 7.2 EB05 4.2 · IC025 +1.8 3/3 methods agree | Not in label — unassessed | serious PRR 5.2 | no trial data cached |
| Folliculitis | 13 | 8.9 5.2–15.3ROR 8.9 · χ² 83 / p 4e-20 | 7.3 EB05 4.4 · IC025 +1.8 3/3 methods agree | Not in label — unassessed | serious PRR 6.1 | no trial data cached |
| Mucosal inflammation | 32 | 8.7 6.1–12.2ROR 8.7 · χ² 209 / p 1e-47 | 8.0 EB05 5.8 · IC025 +2.4 3/3 methods agree | Labeled (related wording) related wording | serious PRR 5.4 · 100% clinician | no trial data cached |
| Febrile neutropenia | 80 | 8.5 6.9–10.6ROR 8.7 · χ² 525 / p 2e-116 | 8.2 EB05 6.8 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious PRR 5.0 · 98% clinician | no trial data cached |
| Hepatic encephalopathy | 11 | 8.3 4.6–15.0ROR 8.3 · χ² 64 / p 8e-16 | 6.6 EB05 3.8 · IC025 +1.6 3/3 methods agree | Not in label — unassessed | serious PRR 4.9 | no trial data cached |
| Rash maculo-papular | 25 | 8.0 5.4–11.8ROR 8.0 · χ² 145 / p 1e-33 | 7.2 EB05 5.0 · IC025 +2.1 3/3 methods agree | Not in label — unassessed | serious PRR 5.1 · 100% clinician | no trial data cached |
| Cerebral infarction | 27 | 7.8 5.3–11.3ROR 7.8 · χ² 153 / p 2e-35 | 7.1 EB05 5.0 · IC025 +2.1 3/3 methods agree | Not in label — unassessed | serious PRR 4.5 · 96% clinician | no trial data cached |
| Ascites | 31 | 7.4 5.2–10.6ROR 7.5 · χ² 166 / p 2e-38 | 6.8 EB05 5.0 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious PRR 4.4 · 90% clinician | no trial data cached |
| Metastases to lung | 12 | 7.3 4.2–12.9ROR 7.4 · χ² 59 / p 6e-15 | 6.0 EB05 3.6 · IC025 +1.6 3/3 methods agree | Not in label — unassessed | serious PRR 4.3 | no trial data cached |
| Proteinuria | 19 | 7.1 4.5–11.1ROR 7.1 · χ² 94 / p 2e-22 | 6.2 EB05 4.1 · IC025 +1.8 3/3 methods agree | Not in label — unassessed | serious PRR 4.6 | no trial data cached |
| Oesophagitis | 11 | 7.1 3.9–12.8ROR 7.1 · χ² 52 / p 3e-13 | 5.7 EB05 3.3 · IC025 +1.5 3/3 methods agree | Not in label — unassessed | serious PRR 4.6 | no trial data cached |
| Melaena (black stool) | 22 | 7.0 4.6–10.7ROR 7.1 · χ² 108 / p 1e-25 | 6.2 EB05 4.3 · IC025 +1.9 3/3 methods agree | Not in label — unassessed | serious PRR 4.2 · ♀ 14% (drug 39%) · 95% clinician | no trial data cached |
| Ileus | 12 | 6.9 3.9–12.1ROR 6.9 · χ² 55 / p 8e-14 | 5.6 EB05 3.4 · IC025 +1.5 3/3 methods agree | Not in label — unassessed | serious PRR 4.0 | no trial data cached |
| Peritonitis | 20 | 6.8 4.4–10.5ROR 6.8 · χ² 93 / p 2e-22 | 6.0 EB05 4.1 · IC025 +1.8 3/3 methods agree | Not in label — unassessed | serious PRR 4.0 · 95% clinician | no trial data cached |
| Neutropenia (low neutrophils (infection-fighting cells)) | 129 | 6.7 5.7–7.9ROR 7.0 · χ² 625 / p 3e-138 | 6.6 EB05 5.7 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 4.1 · 97% clinician | no trial data cached |
| Stomatitis (mouth sores) | 57 | 6.6 5.1–8.6ROR 6.7 · χ² 267 / p 2e-60 | 6.3 EB05 5.0 · IC025 +2.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 5.7 · 95% clinician | no trial data cached |
| Splenomegaly | 11 | 6.6 3.7–12.0ROR 6.6 · χ² 47 / p 3e-12 | 5.3 EB05 3.2 · IC025 +1.4 3/3 methods agree | Not in label — unassessed | serious PRR 4.3 | no trial data cached |
| Skin disorder | 31 | 6.6 4.6–9.3ROR 6.6 · χ² 141 / p 8e-33 | 6.0 EB05 4.4 · IC025 +2.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 6.4 · 100% clinician | no trial data cached |
| Intestinal obstruction | 33 | 6.2 4.4–8.7ROR 6.3 · χ² 139 / p 2e-32 | 5.7 EB05 4.3 · IC025 +1.9 3/3 methods agree | Not in label — unassessed | serious PRR 3.7 · 94% clinician | no trial data cached |
| Pneumonia aspiration | 21 | 5.9 3.9–9.1ROR 6.0 · χ² 81 / p 9e-20 | 5.3 EB05 3.7 · IC025 +1.7 3/3 methods agree | Not in label — unassessed | serious PRR 3.5 · 100% clinician | no trial data cached |
| Device related infection | 13 | 5.9 3.5–10.2ROR 6.0 · χ² 49 / p 2e-12 | 5.0 EB05 3.1 · IC025 +1.4 3/3 methods agree | Reporting / coding artifact | serious PRR 3.3 | no trial data cached |
| Leukopenia (low white blood cells) | 41 | 5.8 4.3–7.9ROR 5.9 · χ² 158 / p 1e-36 | 5.5 EB05 4.2 · IC025 +1.9 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.5 · 100% clinician | no trial data cached |
| Palmar-plantar erythrodysaesthesia syndrome | 19 | 5.7 3.7–9.0ROR 5.8 · χ² 70 / p 4e-17 | 5.1 EB05 3.4 · IC025 +1.6 3/3 methods agree | Not in label — unassessed | serious PRR 4.2 | no trial data cached |
| White blood cell count decreased | 86 | 5.6 4.5–6.9ROR 5.7 · χ² 321 / p 5e-72 | 5.4 EB05 4.5 · IC025 +2.1 3/3 methods agree | Labeled (related wording) related wording | serious PRR 4.6 | no trial data cached |
| Blood alkaline phosphatase increased | 19 | 5.4 3.4–8.4ROR 5.4 · χ² 64 / p 8e-16 | 4.8 EB05 3.3 · IC025 +1.5 3/3 methods agree | Lab value / disease marker | serious PRR 3.6 | no trial data cached |
| Decreased appetite (loss of appetite) | 170 | 5.2 4.5–6.0ROR 5.4 · χ² 574 / p 3e-127 | 5.1 EB05 4.5 · IC025 +2.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 4.6 · 98% 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 |
|---|---|---|---|---|---|---|
| Decreased appetite (loss of appetite) | 170 | 5.2 4.5–6.0ROR 5.4 · χ² 574 / p 3e-127 | 5.1 EB05 4.5 · IC025 +2.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 4.6 · 98% clinician | no trial data cached |
| Malignant neoplasm progression | 161 | 11.2 9.6–13.0ROR 11.7 · χ² 1,483 / p <1e-300 | 11.0 EB05 9.7 · IC025 +3.2 3/3 methods agree | Reporting / coding artifact | serious PRR 6.6 | no trial data cached |
| Neuropathy peripheral (nerve damage in hands/feet) | 131 | 9.8 8.3–11.6ROR 10.2 · χ² 1,026 / p 2e-225 | 9.6 EB05 8.3 · IC025 +3.0 3/3 methods agree | Labeled (related wording) related wording | serious PRR 6.6 · 93% clinician | no trial data cached |
| Neutrophil count decreased | 131 | 22.9 19.3–27.0ROR 23.9 · χ² 2,712 / p <1e-300 | 22.7 EB05 19.6 · IC025 +4.1 3/3 methods agree | Lab value / disease marker | serious PRR 15.1 | no trial data cached |
| Neutropenia (low neutrophils (infection-fighting cells)) | 129 | 6.7 5.7–7.9ROR 7.0 · χ² 625 / p 3e-138 | 6.6 EB05 5.7 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 4.1 · 97% clinician | no trial data cached |
| Myelosuppression | 127 | 26.4 22.3–31.3ROR 27.5 · χ² 3,071 / p <1e-300 | 26.2 EB05 22.6 · IC025 +4.3 3/3 methods agree | Not in label — unassessed | serious PRR 15.1 | no trial data cached |
| Interstitial lung disease | 116 | 17.0 14.2–20.3ROR 17.6 · χ² 1,725 / p <1e-300 | 16.9 EB05 14.4 · IC025 +3.7 3/3 methods agree | Not in label — unassessed | serious PRR 9.9 | no trial data cached |
| White blood cell count decreased | 86 | 5.6 4.5–6.9ROR 5.7 · χ² 321 / p 5e-72 | 5.4 EB05 4.5 · IC025 +2.1 3/3 methods agree | Labeled (related wording) related wording | serious PRR 4.6 | no trial data cached |
| Febrile neutropenia | 80 | 8.5 6.9–10.6ROR 8.7 · χ² 525 / p 2e-116 | 8.2 EB05 6.8 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious PRR 5.0 · 98% clinician | no trial data cached |
| Platelet count decreased | 58 | 3.8 3.0–5.0ROR 3.9 · χ² 119 / p 4e-28 | 3.7 EB05 3.0 · IC025 +1.5 3/3 methods agree | Labeled (related wording) related wording | serious PRR 2.7 | no trial data cached |
| Stomatitis (mouth sores) | 57 | 6.6 5.1–8.6ROR 6.7 · χ² 267 / p 2e-60 | 6.3 EB05 5.0 · IC025 +2.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 5.7 · 95% clinician | no trial data cached |
| Disease progression | 56 | 3.3 2.6–4.3ROR 3.4 · χ² 90 / p 1e-21 | 3.3 EB05 2.6 · IC025 +1.3 3/3 methods agree | Reporting / coding artifact | serious PRR 2.2 · 94% clinician | no trial data cached |
| Thrombocytopenia (low platelets) | 51 | 3.2 2.5–4.2ROR 3.3 · χ² 76 / p 1e-18 | 3.1 EB05 2.5 · IC025 +1.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 1.9 · 100% clinician | no trial data cached |
| Anaphylactic shock | 45 | 12.4 9.3–16.6ROR 12.6 · χ² 460 / p 3e-102 | 12.1 EB05 9.2 · IC025 +3.0 3/3 methods agree | Not in label — unassessed | serious PRR 7.2 · 100% clinician | no trial data cached |
| Infusion related reaction (reaction during infusion) | 43 | 4.6 3.4–6.2ROR 4.6 · χ² 117 / p 1e-27 | 4.4 EB05 3.4 · IC025 +1.6 3/3 methods agree | Not in label — unassessed | serious PRR 3.3 · 100% clinician | 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.
- Myelosuppression — n=127, PRR 26.4
- Hypomagnesaemia — n=35, PRR 17.8
- Interstitial lung disease — n=116, PRR 17.0
- Diarrhoea haemorrhagic — n=22, PRR 16.6
- Colon cancer — n=33, PRR 15.6
- Disseminated intravascular coagulation — n=26, PRR 13.0
- Anaphylactic shock — n=45, PRR 12.4
- Hepatic cytolysis — n=20, PRR 11.5
- Metastases to liver — n=25, PRR 10.1
- Altered state of consciousness — n=28, PRR 9.2
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 Levoleucovorin?
In FDA FAERS, the most frequently co-reported reaction terms for Levoleucovorin are decreased appetite, neuropathy peripheral, neutrophil count decreased, neutropenia, myelosuppression, interstitial lung disease. 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 Levoleucovorin have an FDA boxed warning?
No. The FDA label retrieved for Levoleucovorin has no boxed warning; see the label's Warnings and Precautions for the recognised risks.
Do FAERS signals prove that Levoleucovorin 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 c003aaed-89c3-d6a6-0d34-18851b7e1255, effective 20171231; matched on
openfda.generic_name.exact:"LEVOLEUCOVORIN") - 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, 86 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.