Drug · FAERS side-effect profile with label screen
Methadone Hydrochloride side effects: what 10,755 FDA adverse event reports show
Drug class
Not stated in label
Brand names
Methadone Hydrochloride
openFDA label
Who reports
10,755 reports · 86% serious · 3,019 with death outcome · 48% female
openFDA FAERS counts, all years, deduplication not applied
Used for
Methadone hydrochloride tablets is indicated for the: Management of severe and persistent pain that requires an opioid analgesic and that cannot be adequately treated with alternative options, including immediate-release opioids. Limitations of Use Bec.
FDA label, Indications and Usage
What it is
Methadone hydrochloride is chemically described as 6-(dimethylamino)-4,4-diphenyl-3-hepatanone hydrochloride. Methadone hydrochloride USP is a white powder.
FDA label, Description section
Boxed warning
SERIOUS AND LIFE-THREATENING RISKS FROM USE OF METHADONE HYDROCHLORIDE TABLETS A ddiction, Abuse, and Misuse Because the use of methadone hydrochloride tablets exposes patients and other users to the risks of opioid .
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 1Labeled adverse reaction 1Labeled (related wording) 9Likely indication confounding 1Reporting / coding artifact 5Lab value / disease marker 3Not in label — unassessed 20
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 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.
- 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. 977 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 |
|---|---|---|---|---|---|---|
| Malignant cranial nerve neoplasm | 16 | 3,076.2 1,396.3–6,777.3ROR 3,080.8 · χ² 17,754 / p <1e-300 | 488.7 EB05 318.9 · IC025 +4.2 3/3 methods agree | Not in label — unassessed | serious n=16 | no trial data cached |
| Retro-orbital neoplasm | 16 | 831.4 462.7–1,494.1ROR 832.7 · χ² 8,694 / p <1e-300 | 342.5 EB05 223.6 · IC025 +4.1 3/3 methods agree | Not in label — unassessed | serious n=16 | no trial data cached |
| Vision abnormal neonatal | 112 | 703.7 567.2–873.1ROR 711.1 · χ² 57,022 / p <1e-300 | 473.5 EB05 404.4 · IC025 +7.0 3/3 methods agree | Not in label — unassessed | serious n=112 · 100% consumer | no trial data cached |
| Neonatal hypoacusis | 41 | 412.7 294.7–578.0ROR 414.3 · χ² 13,527 / p <1e-300 | 293.4 EB05 225.5 · IC025 +5.5 3/3 methods agree | Not in label — unassessed | serious n=41 · 100% consumer | no trial data cached |
| Postmortem blood drug level abnormal | 18 | 272.5 166.4–446.3ROR 273.0 · χ² 4,030 / p <1e-300 | 190.8 EB05 127.7 · IC025 +4.2 3/3 methods agree | Lab value / disease marker | serious n=18 | no trial data cached |
| Phyllodes tumour | 10 | 270.8 139.7–524.8ROR 271.0 · χ² 2,125 / p <1e-300 | 163.9 EB05 95.1 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious n=10 | no trial data cached |
| Congenital nystagmus | 24 | 249.4 163.1–381.5ROR 250.0 · χ² 5,039 / p <1e-300 | 188.0 EB05 133.0 · IC025 +4.6 3/3 methods agree | Labeled (related wording) related wording | serious n=24 · 100% clinician | no trial data cached |
| Strabismus congenital | 15 | 225.3 132.0–384.5ROR 225.6 · χ² 2,801 / p <1e-300 | 160.9 EB05 103.5 · IC025 +3.9 3/3 methods agree | Labeled (related wording) related wording | serious n=15 | no trial data cached |
| Drug withdrawal syndrome neonatal | 1,431 | 206.4 196.1–217.2ROR 237.9 · χ² 264,131 / p <1e-300 | 186.0 EB05 178.1 · IC025 +7.4 3/3 methods agree | Labeled (related wording) related wording | serious PRR 123.7 | no trial data cached |
| Substance abuser | 20 | 204.5 129.0–324.2ROR 204.9 · χ² 3,480 / p <1e-300 | 157.4 EB05 107.6 · IC025 +4.3 3/3 methods agree | Not in label — unassessed | serious n=20 · 100% clinician | no trial data cached |
| Learning disability | 465 | 184.0 167.6–201.9ROR 192.2 · χ² 77,077 / p <1e-300 | 166.8 EB05 154.5 · IC025 +7.0 3/3 methods agree | Not in label — unassessed | serious n=465 · 100% consumer | no trial data cached |
| Neuroblastoma recurrent | 16 | 168.1 100.9–280.1ROR 168.3 · χ² 2,293 / p <1e-300 | 130.9 EB05 85.4 · IC025 +3.9 3/3 methods agree | Not in label — unassessed | serious n=16 | no trial data cached |
| Developmental delay | 508 | 115.3 105.6–125.8ROR 121.0 · χ² 54,214 / p <1e-300 | 108.4 EB05 100.7 · IC025 +6.5 3/3 methods agree | Not in label — unassessed | serious PRR 73.9 · 98% consumer | no trial data cached |
| Radiation associated pain | 10 | 97.1 51.5–183.2ROR 97.2 · χ² 816 / p 8e-180 | 79.0 EB05 45.9 · IC025 +3.0 3/3 methods agree | Not in label — unassessed | serious n=10 | no trial data cached |
| Muscle tone disorder | 14 | 90.6 53.0–154.9ROR 90.7 · χ² 1,101 / p 1e-241 | 77.7 EB05 49.2 · IC025 +3.6 3/3 methods agree | Labeled (related wording) related wording | serious n=14 | no trial data cached |
| Substance use | 64 | 84.5 65.8–108.4ROR 85.0 · χ² 4,976 / p <1e-300 | 79.1 EB05 64.1 · IC025 +5.2 3/3 methods agree | Reporting / coding artifact | serious n=62 | no trial data cached |
| Accidental poisoning | 55 | 82.7 63.2–108.3ROR 83.2 · χ² 4,180 / p <1e-300 | 77.3 EB05 61.6 · IC025 +5.1 3/3 methods agree | Not in label — unassessed | serious n=55 | no trial data cached |
| Sudden infant death syndrome | 19 | 77.4 48.9–122.4ROR 77.5 · χ² 1,305 / p 5e-286 | 69.5 EB05 47.0 · IC025 +3.9 3/3 methods agree | Not in label — unassessed | serious n=19 | no trial data cached |
| Multiple drug overdose accidental | 14 | 60.6 35.6–103.2ROR 60.7 · χ² 739 / p 5e-163 | 54.7 EB05 34.6 · IC025 +3.4 3/3 methods agree | Labeled (related wording) related wording | serious n=14 | no trial data cached |
| Myocardial fibrosis | 25 | 59.7 40.1–88.9ROR 59.8 · χ² 1,343 / p 2e-294 | 55.6 EB05 39.6 · IC025 +4.1 3/3 methods agree | Not in label — unassessed | serious n=25 · ♀ 17% (drug 48%) · 100% clinician | no trial data cached |
| Toxicologic test abnormal | 18 | 59.0 36.9–94.2ROR 59.1 · χ² 940 / p 1e-206 | 54.1 EB05 36.2 · IC025 +3.7 3/3 methods agree | Reporting / coding artifact | serious n=18 | no trial data cached |
| Substance use disorder | 89 | 58.1 47.1–71.6ROR 58.5 · χ² 4,790 / p <1e-300 | 55.8 EB05 46.7 · IC025 +5.1 3/3 methods agree | Labeled adverse reaction exact term | serious n=89 | no trial data cached |
| Bradypnoea | 71 | 52.9 41.8–67.0ROR 53.3 · χ² 3,471 / p <1e-300 | 50.9 EB05 41.7 · IC025 +4.9 3/3 methods agree | Not in label — unassessed | serious n=71 · 99% clinician | no trial data cached |
| Visceral congestion | 13 | 52.6 30.3–91.3ROR 52.7 · χ² 591 / p 6e-131 | 47.9 EB05 29.8 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious n=13 | no trial data cached |
| Drug diversion | 148 | 51.7 44.0–60.8ROR 52.4 · χ² 7,120 / p <1e-300 | 50.1 EB05 43.7 · IC025 +5.2 3/3 methods agree | Reporting / coding artifact | serious n=111 | no trial data cached |
| Substance dependence | 15 | 44.6 26.8–74.5ROR 44.7 · χ² 584 / p 3e-129 | 41.5 EB05 26.7 · IC025 +3.3 3/3 methods agree | Labeled (related wording) related wording | serious n=15 | no trial data cached |
| Premature labour | 111 | 38.7 32.1–46.6ROR 39.1 · χ² 3,956 / p <1e-300 | 37.7 EB05 32.2 · IC025 +4.7 3/3 methods agree | Not in label — unassessed | serious n=111 · ♀ 100% (drug 48%) · 100% clinician | no trial data cached |
| Toxic leukoencephalopathy | 14 | 38.3 22.6–65.1ROR 38.4 · χ² 463 / p 5e-103 | 35.9 EB05 22.7 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious n=14 | no trial data cached |
| Foetal exposure during pregnancy | 1,455 | 35.5 33.9–37.3ROR 40.9 · χ² 48,102 / p <1e-300 | 34.9 EB05 33.4 · IC025 +5.0 3/3 methods agree | Reporting / coding artifact | serious PRR 23.6 | no trial data cached |
| Miosis | 131 | 32.6 27.4–38.7ROR 33.0 · χ² 3,914 / p <1e-300 | 31.9 EB05 27.6 · IC025 +4.6 3/3 methods agree | Not in label — unassessed | serious PRR 22.8 · ♀ 22% (drug 48%) · 98% clinician | no trial data cached |
| Multiple drug overdose intentional | 49 | 29.7 22.4–39.4ROR 29.8 · χ² 1,311 / p 3e-287 | 29.0 EB05 22.8 · IC025 +4.0 3/3 methods agree | Labeled (related wording) related wording | serious n=49 · 100% clinician | no trial data cached |
| Torsade de pointes | 115 | 28.9 24.1–34.7ROR 29.2 · χ² 3,028 / p <1e-300 | 28.4 EB05 24.3 · IC025 +4.4 3/3 methods agree | Labeled (related wording) related wording | serious PRR 19.2 · 94% clinician | no trial data cached |
| Thyroxine increased | 10 | 28.0 15.0–52.3ROR 28.1 · χ² 231 / p 2e-52 | 26.3 EB05 15.0 · IC025 +2.5 3/3 methods agree | Lab value / disease marker | serious n=10 | no trial data cached |
| Respiratory depression | 167 | 26.9 23.1–31.3ROR 27.3 · χ² 4,084 / p <1e-300 | 26.5 EB05 23.3 · IC025 +4.4 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 18.3 | no trial data cached |
| Multiple drug overdose | 65 | 25.5 20.0–32.5ROR 25.6 · χ² 1,485 / p <1e-300 | 25.0 EB05 20.3 · IC025 +4.0 3/3 methods agree | Labeled (related wording) related wording | serious n=65 | no trial data cached |
| Electrocardiogram qt corrected interval prolonged | 10 | 24.8 13.3–46.2ROR 24.8 · χ² 202 / p 3e-46 | 23.3 EB05 13.1 · IC025 +2.5 3/3 methods agree | Lab value / disease marker | serious n=10 | no trial data cached |
| Drug use disorder | 100 | 23.8 19.6–29.0ROR 24.0 · χ² 2,138 / p <1e-300 | 23.5 EB05 19.8 · IC025 +4.1 3/3 methods agree | Likely indication confounding term in indications; also in warnings | serious PRR 16.3 · 95% clinician | no trial data cached |
| Substance-induced psychotic disorder | 26 | 23.2 15.8–34.1ROR 23.2 · χ² 523 / p 4e-116 | 22.6 EB05 16.2 · IC025 +3.4 3/3 methods agree | Not in label — unassessed | serious n=26 · ♀ 0% (drug 48%) | no trial data cached |
| Substance abuse | 93 | 22.5 18.3–27.5ROR 22.7 · χ² 1,866 / p <1e-300 | 22.1 EB05 18.6 · IC025 +4.0 3/3 methods agree | Reporting / coding artifact | serious PRR 16.4 · ♀ 21% (drug 48%) | no trial data cached |
| Cardiopulmonary failure | 44 | 22.1 16.5–29.8ROR 22.2 · χ² 858 / p 8e-189 | 21.7 EB05 16.8 · IC025 +3.6 3/3 methods agree | Not in label — unassessed | serious n=44 · ♀ 27% (drug 48%) · 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 |
|---|---|---|---|---|---|---|
| Foetal exposure during pregnancy | 1,455 | 35.5 33.9–37.3ROR 40.9 · χ² 48,102 / p <1e-300 | 34.9 EB05 33.4 · IC025 +5.0 3/3 methods agree | Reporting / coding artifact | serious PRR 23.6 | no trial data cached |
| Drug withdrawal syndrome neonatal | 1,431 | 206.4 196.1–217.2ROR 237.9 · χ² 264,131 / p <1e-300 | 186.0 EB05 178.1 · IC025 +7.4 3/3 methods agree | Labeled (related wording) related wording | serious PRR 123.7 | no trial data cached |
| Toxicity to various agents | 1,144 | 13.4 12.7–14.1ROR 14.8 · χ² 13,098 / p <1e-300 | 13.3 EB05 12.6 · IC025 +3.6 3/3 methods agree | Not in label — unassessed | serious PRR 8.8 | no trial data cached |
| Drug dependence | 1,027 | 12.4 11.7–13.1ROR 13.6 · χ² 10,746 / p <1e-300 | 12.3 EB05 11.7 · IC025 +3.5 3/3 methods agree | Reporting / coding artifact | serious PRR 8.4 · 82% consumer | no trial data cached |
| Overdose | 941 | 8.5 8.0–9.0ROR 9.2 · χ² 6,258 / p <1e-300 | 8.4 EB05 8.0 · IC025 +3.0 3/3 methods agree | Reporting / coding artifact | serious PRR 7.0 | no trial data cached |
| Drug abuse | 791 | 18.6 17.4–19.9ROR 20.0 · χ² 13,082 / p <1e-300 | 18.4 EB05 17.4 · IC025 +4.1 3/3 methods agree | Reporting / coding artifact | serious PRR 12.5 · 94% clinician | no trial data cached |
| Death | 582 | 1.3 1.2–1.4ROR 1.3 · χ² 46 / p 6e-12 | 1.3 EB05 1.2 · IC025 +0.3 | Outcome field, not a reaction boxed warning mentions mortality | serious PRR 0.9 | no trial data cached |
| Pain | 552 | 1.7 1.6–1.9ROR 1.8 · χ² 182 / p 1e-41 | 1.7 EB05 1.6 · IC025 +0.7 | Labeled — boxed warning exact term | serious PRR 1.1 · ♀ 83% (drug 48%) | no trial data cached |
| Dependence | 534 | 18.9 17.4–20.5ROR 19.8 · χ² 8,976 / p <1e-300 | 18.7 EB05 17.4 · IC025 +4.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 12.6 · 98% consumer | no trial data cached |
| Maternal exposure during pregnancy | 532 | 11.8 10.9–12.8ROR 12.4 · χ² 5,250 / p <1e-300 | 11.7 EB05 10.9 · IC025 +3.4 3/3 methods agree | Reporting / coding artifact | serious PRR 6.3 · ♀ 99% (drug 48%) · 92% clinician | no trial data cached |
| Developmental delay | 508 | 115.3 105.6–125.8ROR 121.0 · χ² 54,214 / p <1e-300 | 108.4 EB05 100.7 · IC025 +6.5 3/3 methods agree | Not in label — unassessed | serious PRR 73.9 · 98% consumer | no trial data cached |
| Learning disability | 465 | 184.0 167.6–201.9ROR 192.2 · χ² 77,077 / p <1e-300 | 166.8 EB05 154.5 · IC025 +7.0 3/3 methods agree | Not in label — unassessed | serious n=465 · 100% consumer | no trial data cached |
| Anxiety | 435 | 3.0 2.7–3.3ROR 3.1 · χ² 575 / p 2e-127 | 3.0 EB05 2.7 · IC025 +1.4 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 1.5 · ♀ 83% (drug 48%) | no trial data cached |
| Exposure during pregnancy | 392 | 12.4 11.2–13.6ROR 12.8 · χ² 4,068 / p <1e-300 | 12.3 EB05 11.3 · IC025 +3.4 3/3 methods agree | Reporting / coding artifact | serious PRR 2.4 · ♀ 99% (drug 48%) · 98% clinician | no trial data cached |
| Emotional distress | 384 | 6.2 5.6–6.8ROR 6.4 · χ² 1,665 / p <1e-300 | 6.1 EB05 5.6 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 2.3 · ♀ 90% (drug 48%) | 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.
- Vision abnormal neonatal — n=112, PRR 703.7
- Neonatal hypoacusis — n=41, PRR 412.7
- Substance abuser — n=20, PRR 204.5
- Learning disability — n=465, PRR 184.0
- Developmental delay — n=508, PRR 115.3
- Accidental poisoning — n=55, PRR 82.7
- Myocardial fibrosis — n=25, PRR 59.7
- Bradypnoea — n=71, PRR 52.9
- Premature labour — n=111, PRR 38.7
- Miosis — n=131, PRR 32.6
✓ A hand-written Bradford Hill causality assessment exists for this drug: Methadone ↔ QT prolongation / torsades.
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 Methadone?
In FDA FAERS, the most frequently co-reported reaction terms for Methadone are drug withdrawal syndrome neonatal, toxicity to various agents, pain, dependence, developmental delay, learning disability. 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 Methadone have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF METHADONE HYDROCHLORIDE TABLETS A ddiction, Abuse, and Misuse Because the use of methadone hydrochloride tablets exposes patients and other users to the risks of opioid .
Do FAERS signals prove that Methadone 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 4a44bde6-c348-4316-b0e0-c24b407cb823, effective 20251231; matched on
openfda.generic_name.exact:"METHADONE") - 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, 1,017 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.