Drug · FAERS side-effect profile with label screen
Methylene Blue side effects: what 1,550 FDA adverse event reports show
Drug class
Oxidation-reduction agent
FDA label, Indications wording
Who reports
1,550 reports · 93% serious · 250 with death outcome · 55% female
openFDA FAERS counts, all years, deduplication not applied
Used for
Methylene Blue Injection is indicated for the treatment of pediatric and adult patients with acquired methemoglobinemia. Methylene Blue Injection is an oxidation-reduction agent indicated for the treatment of pediatric and adult patients with acquired methemoglobinemia.
FDA label, Indications and Usage
What it is
Methylene blue is an oxidation-reduction agent.
FDA label, Description section
Boxed warning
SEROTONIN SYNDROME WITH CONCOMITANT USE OF SEROTONERGIC DRUGS AND OPIOIDS Methylene blue injection may cause serious or fatal serotonergic syndrome when used in combination with serotonergic drugs and opioids. Avoid .
FDA 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 — boxed warning 6Labeled (related wording) 1Reporting / coding artifact 4Lab value / disease marker 3Not in label — unassessed 26
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 (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. 26 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 |
|---|---|---|---|---|---|---|
| Serotonin syndrome | 469 | 340.1 314.9–367.3ROR 487.2 · χ² 154,437 / p <1e-300 | 327.2 EB05 303.1 · IC025 +7.8 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 206.0 · 97% clinician | no trial data cached |
| Blood potassium increased | 62 | 51.9 40.6–66.3ROR 54.0 · χ² 3,034 / p <1e-300 | 50.9 EB05 41.1 · IC025 +4.8 3/3 methods agree | Lab value / disease marker | serious PRR 41.4 · ♀ 96% (drug 55%) · 95% clinician | no trial data cached |
| Blood lactate dehydrogenase increased | 60 | 51.1 39.8–65.5ROR 53.1 · χ² 2,888 / p <1e-300 | 50.1 EB05 40.4 · IC025 +4.7 3/3 methods agree | Lab value / disease marker | serious PRR 33.4 · ♀ 100% (drug 55%) · 95% clinician | no trial data cached |
| Cardiogenic shock | 51 | 48.5 37.0–63.6ROR 50.1 · χ² 2,319 / p <1e-300 | 47.5 EB05 37.6 · IC025 +4.6 3/3 methods agree | Not in label — unassessed | serious PRR 29.2 · 98% clinician | no trial data cached |
| Encephalopathy | 82 | 45.4 36.8–56.1ROR 47.9 · χ² 3,512 / p <1e-300 | 44.8 EB05 37.3 · IC025 +4.8 3/3 methods agree | Not in label — unassessed | serious PRR 28.0 · 96% clinician | no trial data cached |
| Mydriasis | 41 | 43.4 32.1–58.7ROR 44.6 · χ² 1,652 / p <1e-300 | 42.5 EB05 32.6 · IC025 +4.3 3/3 methods agree | Not in label — unassessed | serious PRR 34.5 · ♀ 92% (drug 55%) | no trial data cached |
| Shock | 64 | 38.0 29.9–48.4ROR 39.6 · χ² 2,268 / p <1e-300 | 37.6 EB05 30.4 · IC025 +4.5 3/3 methods agree | Not in label — unassessed | serious PRR 23.5 · ♀ 22% (drug 55%) · 95% clinician | no trial data cached |
| Blood creatine phosphokinase increased | 72 | 33.4 26.6–41.8ROR 35.0 · χ² 2,227 / p <1e-300 | 33.0 EB05 27.1 · IC025 +4.4 3/3 methods agree | Lab value / disease marker | serious PRR 22.9 · ♀ 97% (drug 55%) · 94% clinician | no trial data cached |
| Muscle rigidity | 28 | 31.8 22.0–45.9ROR 32.3 · χ² 802 / p 8e-177 | 31.1 EB05 22.6 · IC025 +3.7 3/3 methods agree | Not in label — unassessed | serious PRR 21.9 · 96% clinician | no trial data cached |
| Drug interaction | 358 | 30.6 27.9–33.5ROR 39.5 · χ² 10,272 / p <1e-300 | 30.5 EB05 27.9 · IC025 +4.7 3/3 methods agree | Reporting / coding artifact | serious PRR 21.1 · 96% clinician | no trial data cached |
| Lactic acidosis | 60 | 25.3 19.8–32.5ROR 26.3 · χ² 1,378 / p <1e-300 | 25.1 EB05 20.2 · IC025 +4.0 3/3 methods agree | Not in label — unassessed | serious PRR 15.6 · 96% clinician | no trial data cached |
| Ileus | 22 | 24.2 16.0–36.7ROR 24.6 · χ² 466 / p 1e-103 | 23.7 EB05 16.5 · IC025 +3.3 3/3 methods agree | Not in label — unassessed | serious PRR 15.0 · ♀ 0% (drug 55%) · 95% clinician | no trial data cached |
| Multiple organ dysfunction syndrome | 46 | 22.3 16.8–29.7ROR 23.0 · χ² 916 / p 2e-201 | 22.1 EB05 17.2 · IC025 +3.7 3/3 methods agree | Not in label — unassessed | serious PRR 13.7 · 91% clinician | no trial data cached |
| Intentional overdose | 100 | 21.3 17.6–25.7ROR 22.6 · χ² 1,913 / p <1e-300 | 21.1 EB05 17.9 · IC025 +3.9 3/3 methods agree | Reporting / coding artifact | serious PRR 13.6 · 100% clinician | no trial data cached |
| Metabolic acidosis | 49 | 21.0 15.9–27.6ROR 21.6 · χ² 912 / p 1e-200 | 20.8 EB05 16.3 · IC025 +3.6 3/3 methods agree | Not in label — unassessed | serious PRR 13.0 · ♀ 24% (drug 55%) · 98% clinician | no trial data cached |
| Chromaturia | 33 | 19.8 14.1–27.7ROR 20.2 · χ² 570 / p 3e-126 | 19.5 EB05 14.5 · IC025 +3.4 3/3 methods agree | Not in label — unassessed | serious PRR 16.3 · 90% clinician | no trial data cached |
| Respiratory depression | 17 | 18.8 11.7–30.1ROR 19.0 · χ² 268 / p 1e-60 | 18.2 EB05 11.8 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious PRR 11.9 | no trial data cached |
| Circulatory collapse | 21 | 16.6 10.9–25.4ROR 16.8 · χ² 293 / p 6e-66 | 16.2 EB05 10.9 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious PRR 10.3 · ♀ 81% (drug 55%) · 100% clinician | no trial data cached |
| Coma | 58 | 16.5 12.8–21.2ROR 17.1 · χ² 829 / p 2e-182 | 16.3 EB05 13.1 · IC025 +3.4 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 10.2 · 100% clinician | no trial data cached |
| Bradycardia (slow heart rate) | 62 | 15.8 12.4–20.2ROR 16.4 · χ² 846 / p 3e-186 | 15.7 EB05 12.6 · IC025 +3.4 3/3 methods agree | Not in label — unassessed | serious PRR 10.1 · ♀ 33% (drug 55%) · 98% clinician | no trial data cached |
| Alanine aminotransferase increased | 67 | 14.8 11.7–18.7ROR 15.4 · χ² 848 / p 1e-186 | 14.6 EB05 11.9 · IC025 +3.3 3/3 methods agree | Labeled (related wording) related wording | serious PRR 10.4 · ♀ 95% (drug 55%) · 94% clinician | no trial data cached |
| Hypotension (low blood pressure) | 207 | 14.0 12.3–15.9ROR 16.0 · χ² 2,506 / p <1e-300 | 13.9 EB05 12.4 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | serious PRR 10.0 · 97% clinician | no trial data cached |
| Myoclonus | 12 | 13.6 7.8–24.0ROR 13.7 · χ² 128 / p 6e-30 | 12.2 EB05 6.6 · IC025 +2.2 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 8.9 | no trial data cached |
| Depressed level of consciousness | 39 | 13.4 9.8–18.2ROR 13.7 · χ² 435 / p 8e-97 | 13.1 EB05 9.8 · IC025 +3.0 3/3 methods agree | Not in label — unassessed | serious PRR 8.5 · 97% clinician | no trial data cached |
| Hypothermia | 10 | 13.3 7.2–24.8ROR 13.4 · χ² 102 / p 3e-24 | 11.4 EB05 5.7 · IC025 +2.0 3/3 methods agree | Not in label — unassessed | serious PRR 8.3 | no trial data cached |
| Rhabdomyolysis (muscle breakdown) | 41 | 13.3 9.9–18.0ROR 13.7 · χ² 456 / p 2e-101 | 13.1 EB05 9.9 · IC025 +3.0 3/3 methods agree | Not in label — unassessed | serious PRR 8.3 · ♀ 13% (drug 55%) · 95% clinician | no trial data cached |
| Generalised tonic-clonic seizure | 16 | 13.2 8.1–21.6ROR 13.4 · χ² 169 / p 6e-39 | 12.2 EB05 7.3 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 8.3 | no trial data cached |
| Mental status changes | 27 | 13.2 9.0–19.1ROR 13.4 · χ² 291 / p 1e-65 | 12.7 EB05 8.8 · IC025 +2.8 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 9.0 · 92% clinician | no trial data cached |
| Drug ineffective for unapproved indication | 52 | 12.6 9.7–16.5ROR 13.0 · χ² 546 / p 4e-121 | 12.4 EB05 9.7 · IC025 +3.0 3/3 methods agree | Reporting / coding artifact | serious PRR 17.1 · 98% clinician | no trial data cached |
| Acute respiratory distress syndrome | 15 | 11.5 6.9–19.0ROR 11.6 · χ² 133 / p 4e-31 | 10.2 EB05 6.0 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious PRR 7.1 | no trial data cached |
| Toxicity to various agents | 140 | 11.3 9.6–13.2ROR 12.3 · χ² 1,313 / p 1e-287 | 11.2 EB05 9.7 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious PRR 7.2 · 98% clinician | no trial data cached |
| Hyperkalaemia (high potassium) | 29 | 11.2 7.8–16.1ROR 11.4 · χ² 261 / p 6e-59 | 10.6 EB05 7.5 · IC025 +2.6 3/3 methods agree | Not in label — unassessed | serious PRR 7.1 · ♀ 11% (drug 55%) · 93% clinician | no trial data cached |
| Agitation | 61 | 11.2 8.8–14.3ROR 11.6 · χ² 559 / p 8e-124 | 10.9 EB05 8.7 · IC025 +2.9 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 9.1 · ♀ 86% (drug 55%) | no trial data cached |
| Neurotoxicity | 14 | 10.9 6.5–18.4ROR 11.0 · χ² 116 / p 2e-27 | 9.4 EB05 5.5 · IC025 +2.1 3/3 methods agree | Not in label — unassessed | serious PRR 6.8 | no trial data cached |
| Sinus tachycardia | 11 | 10.5 5.8–18.9ROR 10.6 · χ² 85 / p 1e-20 | 8.6 EB05 4.7 · IC025 +1.9 3/3 methods agree | Not in label — unassessed | serious PRR 6.6 | no trial data cached |
| Delirium | 26 | 10.2 7.0–14.9ROR 10.3 · χ² 206 / p 4e-47 | 9.4 EB05 6.5 · IC025 +2.5 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 6.4 · 100% clinician | no trial data cached |
| Leukocytosis | 13 | 9.7 5.7–16.7ROR 9.8 · χ² 93 / p 2e-22 | 8.1 EB05 4.7 · IC025 +1.9 3/3 methods agree | Not in label — unassessed | serious PRR 6.1 | no trial data cached |
| Cardiac arrest (heart stopping) | 59 | 9.6 7.5–12.4ROR 10.0 · χ² 450 / p 4e-100 | 9.3 EB05 7.4 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious PRR 5.9 · 95% clinician | no trial data cached |
| Post procedural complication | 13 | 9.1 5.3–15.7ROR 9.2 · χ² 86 / p 8e-21 | 7.6 EB05 4.5 · IC025 +1.9 3/3 methods agree | Reporting / coding artifact | serious PRR 6.1 | no trial data cached |
| Hypoxia (low oxygen) | 23 | 8.9 5.9–13.3ROR 9.0 · χ² 153 / p 2e-35 | 8.0 EB05 5.4 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious PRR 5.6 · 100% 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 |
|---|---|---|---|---|---|---|
| Serotonin syndrome | 469 | 340.1 314.9–367.3ROR 487.2 · χ² 154,437 / p <1e-300 | 327.2 EB05 303.1 · IC025 +7.8 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 206.0 · 97% clinician | no trial data cached |
| Drug interaction | 358 | 30.6 27.9–33.5ROR 39.5 · χ² 10,272 / p <1e-300 | 30.5 EB05 27.9 · IC025 +4.7 3/3 methods agree | Reporting / coding artifact | serious PRR 21.1 · 96% clinician | no trial data cached |
| Hypotension (low blood pressure) | 207 | 14.0 12.3–15.9ROR 16.0 · χ² 2,506 / p <1e-300 | 13.9 EB05 12.4 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | serious PRR 10.0 · 97% clinician | no trial data cached |
| Toxicity to various agents | 140 | 11.3 9.6–13.2ROR 12.3 · χ² 1,313 / p 1e-287 | 11.2 EB05 9.7 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious PRR 7.2 · 98% clinician | no trial data cached |
| Overdose | 106 | 6.6 5.5–8.0ROR 7.0 · χ² 505 / p 3e-112 | 6.5 EB05 5.5 · IC025 +2.4 3/3 methods agree | Reporting / coding artifact | serious PRR 5.1 · ♀ 26% (drug 55%) · 96% clinician | no trial data cached |
| Intentional overdose | 100 | 21.3 17.6–25.7ROR 22.6 · χ² 1,913 / p <1e-300 | 21.1 EB05 17.9 · IC025 +3.9 3/3 methods agree | Reporting / coding artifact | serious PRR 13.6 · 100% clinician | no trial data cached |
| Encephalopathy | 82 | 45.4 36.8–56.1ROR 47.9 · χ² 3,512 / p <1e-300 | 44.8 EB05 37.3 · IC025 +4.8 3/3 methods agree | Not in label — unassessed | serious PRR 28.0 · 96% clinician | no trial data cached |
| Blood creatine phosphokinase increased | 72 | 33.4 26.6–41.8ROR 35.0 · χ² 2,227 / p <1e-300 | 33.0 EB05 27.1 · IC025 +4.4 3/3 methods agree | Lab value / disease marker | serious PRR 22.9 · ♀ 97% (drug 55%) · 94% clinician | no trial data cached |
| Alanine aminotransferase increased | 67 | 14.8 11.7–18.7ROR 15.4 · χ² 848 / p 1e-186 | 14.6 EB05 11.9 · IC025 +3.3 3/3 methods agree | Labeled (related wording) related wording | serious PRR 10.4 · ♀ 95% (drug 55%) · 94% clinician | no trial data cached |
| Shock | 64 | 38.0 29.9–48.4ROR 39.6 · χ² 2,268 / p <1e-300 | 37.6 EB05 30.4 · IC025 +4.5 3/3 methods agree | Not in label — unassessed | serious PRR 23.5 · ♀ 22% (drug 55%) · 95% clinician | no trial data cached |
| Bradycardia (slow heart rate) | 62 | 15.8 12.4–20.2ROR 16.4 · χ² 846 / p 3e-186 | 15.7 EB05 12.6 · IC025 +3.4 3/3 methods agree | Not in label — unassessed | serious PRR 10.1 · ♀ 33% (drug 55%) · 98% clinician | no trial data cached |
| Blood potassium increased | 62 | 51.9 40.6–66.3ROR 54.0 · χ² 3,034 / p <1e-300 | 50.9 EB05 41.1 · IC025 +4.8 3/3 methods agree | Lab value / disease marker | serious PRR 41.4 · ♀ 96% (drug 55%) · 95% clinician | no trial data cached |
| Agitation | 61 | 11.2 8.8–14.3ROR 11.6 · χ² 559 / p 8e-124 | 10.9 EB05 8.7 · IC025 +2.9 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 9.1 · ♀ 86% (drug 55%) | no trial data cached |
| Lactic acidosis | 60 | 25.3 19.8–32.5ROR 26.3 · χ² 1,378 / p <1e-300 | 25.1 EB05 20.2 · IC025 +4.0 3/3 methods agree | Not in label — unassessed | serious PRR 15.6 · 96% clinician | no trial data cached |
| Blood lactate dehydrogenase increased | 60 | 51.1 39.8–65.5ROR 53.1 · χ² 2,888 / p <1e-300 | 50.1 EB05 40.4 · IC025 +4.7 3/3 methods agree | Lab value / disease marker | serious PRR 33.4 · ♀ 100% (drug 55%) · 95% 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.
- Cardiogenic shock — n=51, PRR 48.5
- Encephalopathy — n=82, PRR 45.4
- Mydriasis — n=41, PRR 43.4
- Shock — n=64, PRR 38.0
- Muscle rigidity — n=28, PRR 31.8
- Lactic acidosis — n=60, PRR 25.3
- Ileus — n=22, PRR 24.2
- Multiple organ dysfunction syndrome — n=46, PRR 22.3
- Metabolic acidosis — n=49, PRR 21.0
- Chromaturia — n=33, PRR 19.8
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 Methylene Blue?
In FDA FAERS, the most frequently co-reported reaction terms for Methylene Blue are serotonin syndrome, hypotension, toxicity to various agents, encephalopathy, blood creatine phosphokinase increased, alanine aminotransferase increased. 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 Methylene Blue have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: SEROTONIN SYNDROME WITH CONCOMITANT USE OF SEROTONERGIC DRUGS AND OPIOIDS Methylene blue injection may cause serious or fatal serotonergic syndrome when used in combination with serotonergic drugs and opioids. Avoid .
Do FAERS signals prove that Methylene Blue 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 2566ce72-9d19-42e5-80f9-8fc4612b1eff, effective 20250127; matched on
openfda.generic_name.exact:"METHYLENE BLUE") - 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, 66 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.