Penicillamine side effects: what 921 FDA adverse event reports show
Drug class
Antirheumatic Agent
Who reports
921 reports · 77% serious · 90 with death outcome · 70% female
Used for
Penicillamine capsules are indicated in the treatment of Wilson's disease, cystinuria, and in patients with severe, active rheumatoid arthritis who have failed to respond to an adequate trial of conventional therapy. Available evidence suggests that penicillamine capsules are not of value in ankylosing spondylitis.
What it is
DESCRIPTION Penicillamine is a chelating agent used in the treatment of Wilson's disease. It is also used to reduce cystine excretion in cystinuria and to treat patients with severe, active rheumatoid arthritis unresponsive to conventional therapy (see INDICATIONS ). It is 3-mercapto-D-valine.
Boxed warning
Physicians planning to use penicillamine should thoroughly familiarize themselves with its toxicity, special dosage considerations, and therapeutic benefits. Penicillamine should never be used casually. Each patient should remain constantly under the close supervision of the physician.
Causality screen of the 19 strongest signals
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.
- 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. 12 further terms are in the interactive explorer. Reaction links open the term's cross-drug page.
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Red blood cell sedimentation rate increased | 67 | 138.1 109.5–174.0ROR 148.8 · χ² 8,930 / p <1e-300 | 132.1 EB05 107.6 · IC025 +5.7 3/3 methods agree | Lab value / disease marker | serious PRR 116.7 · ♀ 100% (drug 70%) | no trial data cached |
| Vasculitis | 52 | 101.8 78.1–132.6ROR 107.8 · χ² 5,068 / p <1e-300 | 97.8 EB05 77.4 · IC025 +5.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 81.8 · ♀ 98% (drug 70%) · 98% clinician | no trial data cached |
| Proteinuria | 65 | 78.6 62.1–99.4ROR 84.5 · χ² 4,889 / p <1e-300 | 76.6 EB05 62.2 · IC025 +5.2 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 63.6 · ♀ 98% (drug 70%) · 97% clinician | no trial data cached |
| Cardiovascular disorder | 67 | 59.7 47.4–75.2ROR 64.2 · χ² 3,800 / p <1e-300 | 58.6 EB05 47.7 · IC025 +5.0 3/3 methods agree | Not in label — unassessed | serious PRR 48.0 · ♀ 100% (drug 70%) | no trial data cached |
| Inflammation | 111 | 49.2 41.3–58.6ROR 55.8 · χ² 5,198 / p <1e-300 | 48.7 EB05 41.6 · IC025 +5.0 3/3 methods agree | Not in label — unassessed | serious PRR 49.2 · ♀ 100% (drug 70%) | no trial data cached |
| Contraindicated product administered | 62 | 46.8 36.8–59.5ROR 50.1 · χ² 2,731 / p <1e-300 | 46.1 EB05 37.2 · IC025 +4.7 3/3 methods agree | Reporting / coding artifact | serious PRR 42.9 · ♀ 100% (drug 70%) | no trial data cached |
| Anaphylactic reaction (severe allergic reaction) | 77 | 31.9 25.7–39.5ROR 34.7 · χ² 2,276 / p <1e-300 | 31.6 EB05 26.1 · IC025 +4.4 3/3 methods agree | Not in label — unassessed | serious PRR 24.4 · ♀ 97% (drug 70%) | no trial data cached |
| Joint swelling | 144 | 27.2 23.4–31.6ROR 32.0 · χ² 3,623 / p <1e-300 | 27.1 EB05 23.6 · IC025 +4.4 3/3 methods agree | Not in label — unassessed | serious PRR 34.6 · ♀ 98% (drug 70%) | no trial data cached |
| Petechiae | 11 | 24.0 13.4–43.3ROR 24.3 · χ² 220 / p 4e-50 | 23.0 EB05 13.4 · IC025 +2.6 3/3 methods agree | Not in label — unassessed | serious PRR 21.8 | no trial data cached |
| Drug hypersensitivity | 180 | 21.1 18.5–24.0ROR 25.9 · χ² 3,451 / p <1e-300 | 21.0 EB05 18.6 · IC025 +4.1 3/3 methods agree | Not in label — unassessed | serious PRR 31.0 · ♀ 91% (drug 70%) | no trial data cached |
| Treatment failure | 69 | 19.1 15.2–24.0ROR 20.6 · χ² 1,170 / p 1e-256 | 19.0 EB05 15.5 · IC025 +3.7 3/3 methods agree | Reporting / coding artifact | serious PRR 27.5 · ♀ 100% (drug 70%) · 97% clinician | no trial data cached |
| Drug intolerance | 79 | 18.7 15.1–23.0ROR 20.3 · χ² 1,308 / p 1e-286 | 18.6 EB05 15.4 · IC025 +3.7 3/3 methods agree | Reporting / coding artifact | serious PRR 21.9 · ♀ 92% (drug 70%) · 94% clinician | no trial data cached |
| Pulmonary fibrosis | 15 | 17.8 10.8–29.5ROR 18.1 · χ² 222 / p 2e-50 | 17.2 EB05 10.5 · IC025 +2.7 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 13.5 | no trial data cached |
| Pain in jaw | 15 | 12.0 7.3–19.9ROR 12.2 · χ² 141 / p 8e-33 | 10.8 EB05 6.4 · IC025 +2.3 3/3 methods agree | Labeled (related wording) related wording | serious PRR 14.6 | no trial data cached |
| Dermatitis | 10 | 11.0 5.9–20.3ROR 11.1 · χ² 81 / p 1e-19 | 8.9 EB05 4.6 · IC025 +1.8 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 16.7 | no trial data cached |
| Musculoskeletal stiffness | 42 | 10.9 8.1–14.6ROR 11.4 · χ² 369 / p 2e-82 | 10.5 EB05 7.9 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious PRR 13.3 · ♀ 97% (drug 70%) · 95% clinician | no trial data cached |
| Rheumatoid arthritis | 53 | 10.7 8.2–13.8ROR 11.2 · χ² 456 / p 2e-101 | 10.3 EB05 8.1 · IC025 +2.8 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 9.8 · ♀ 98% (drug 70%) · 94% clinician | no trial data cached |
| Urticaria (hives) | 71 | 9.7 7.8–12.1ROR 10.4 · χ² 549 / p 9e-122 | 9.4 EB05 7.6 · IC025 +2.8 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 13.8 · ♀ 100% (drug 70%) | no trial data cached |
| Drug exposure during pregnancy | 14 | 9.2 5.5–15.5ROR 9.3 · χ² 95 / p 1e-22 | 7.7 EB05 4.7 · IC025 +1.9 3/3 methods agree | Reporting / coding artifact | serious PRR 7.1 | no trial data cached |
Trial evidence (ClinicalTrials.gov)
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 |
|---|---|---|---|---|---|---|
| Drug hypersensitivity | 180 | 21.1 18.5–24.0ROR 25.9 · χ² 3,451 / p <1e-300 | 21.0 EB05 18.6 · IC025 +4.1 3/3 methods agree | Not in label — unassessed | serious PRR 31.0 · ♀ 91% (drug 70%) | no trial data cached |
| Joint swelling | 144 | 27.2 23.4–31.6ROR 32.0 · χ² 3,623 / p <1e-300 | 27.1 EB05 23.6 · IC025 +4.4 3/3 methods agree | Not in label — unassessed | serious PRR 34.6 · ♀ 98% (drug 70%) | no trial data cached |
| Inflammation | 111 | 49.2 41.3–58.6ROR 55.8 · χ² 5,198 / p <1e-300 | 48.7 EB05 41.6 · IC025 +5.0 3/3 methods agree | Not in label — unassessed | serious PRR 49.2 · ♀ 100% (drug 70%) | no trial data cached |
| Drug intolerance | 79 | 18.7 15.1–23.0ROR 20.3 · χ² 1,308 / p 1e-286 | 18.6 EB05 15.4 · IC025 +3.7 3/3 methods agree | Reporting / coding artifact | serious PRR 21.9 · ♀ 92% (drug 70%) · 94% clinician | no trial data cached |
| Anaphylactic reaction (severe allergic reaction) | 77 | 31.9 25.7–39.5ROR 34.7 · χ² 2,276 / p <1e-300 | 31.6 EB05 26.1 · IC025 +4.4 3/3 methods agree | Not in label — unassessed | serious PRR 24.4 · ♀ 97% (drug 70%) | no trial data cached |
| Urticaria (hives) | 71 | 9.7 7.8–12.1ROR 10.4 · χ² 549 / p 9e-122 | 9.4 EB05 7.6 · IC025 +2.8 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 13.8 · ♀ 100% (drug 70%) | no trial data cached |
| Treatment failure | 69 | 19.1 15.2–24.0ROR 20.6 · χ² 1,170 / p 1e-256 | 19.0 EB05 15.5 · IC025 +3.7 3/3 methods agree | Reporting / coding artifact | serious PRR 27.5 · ♀ 100% (drug 70%) · 97% clinician | no trial data cached |
| Cardiovascular disorder | 67 | 59.7 47.4–75.2ROR 64.2 · χ² 3,800 / p <1e-300 | 58.6 EB05 47.7 · IC025 +5.0 3/3 methods agree | Not in label — unassessed | serious PRR 48.0 · ♀ 100% (drug 70%) | no trial data cached |
| Red blood cell sedimentation rate increased | 67 | 138.1 109.5–174.0ROR 148.8 · χ² 8,930 / p <1e-300 | 132.1 EB05 107.6 · IC025 +5.7 3/3 methods agree | Lab value / disease marker | serious PRR 116.7 · ♀ 100% (drug 70%) | no trial data cached |
| Proteinuria | 65 | 78.6 62.1–99.4ROR 84.5 · χ² 4,889 / p <1e-300 | 76.6 EB05 62.2 · IC025 +5.2 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 63.6 · ♀ 98% (drug 70%) · 97% clinician | no trial data cached |
| Contraindicated product administered | 62 | 46.8 36.8–59.5ROR 50.1 · χ² 2,731 / p <1e-300 | 46.1 EB05 37.2 · IC025 +4.7 3/3 methods agree | Reporting / coding artifact | serious PRR 42.9 · ♀ 100% (drug 70%) | no trial data cached |
| Rheumatoid arthritis | 53 | 10.7 8.2–13.8ROR 11.2 · χ² 456 / p 2e-101 | 10.3 EB05 8.1 · IC025 +2.8 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 9.8 · ♀ 98% (drug 70%) · 94% clinician | no trial data cached |
| Vasculitis | 52 | 101.8 78.1–132.6ROR 107.8 · χ² 5,068 / p <1e-300 | 97.8 EB05 77.4 · IC025 +5.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 81.8 · ♀ 98% (drug 70%) · 98% clinician | no trial data cached |
| Musculoskeletal stiffness | 42 | 10.9 8.1–14.6ROR 11.4 · χ² 369 / p 2e-82 | 10.5 EB05 7.9 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious PRR 13.3 · ♀ 97% (drug 70%) · 95% clinician | no trial data cached |
| Pain in jaw | 15 | 12.0 7.3–19.9ROR 12.2 · χ² 141 / p 8e-33 | 10.8 EB05 6.4 · IC025 +2.3 3/3 methods agree | Labeled (related wording) related wording | serious PRR 14.6 | 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.
- Cardiovascular disorder — n=67, PRR 59.7
- Inflammation — n=111, PRR 49.2
- Anaphylactic reaction — n=77, PRR 31.9
- Joint swelling — n=144, PRR 27.2
- Drug hypersensitivity — n=180, PRR 21.1
- Musculoskeletal stiffness — n=42, PRR 10.9
✓ A hand-written Bradford Hill causality assessment exists for this drug: Penicillamine ↔ Proteinuria / membranous nephropathy.
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 Penicillamine?
In FDA FAERS, the most frequently co-reported reaction terms for Penicillamine are drug hypersensitivity, joint swelling, inflammation, anaphylactic reaction, urticaria, cardiovascular disorder. 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 Penicillamine have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: Physicians planning to use penicillamine should thoroughly familiarize themselves with its toxicity, special dosage considerations, and therapeutic benefits. Penicillamine should never be used casually. Each patient should remain constantly under the close supervision of the physician.
Do FAERS signals prove that Penicillamine 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 01e79d8f-8c74-4f48-b761-9f225fabf93d, effective 20260723; matched on
openfda.generic_name.exact:"PENICILLAMINE") - 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, 31 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.