Penicillamine

Mechanism-of-action class: Chelating Activity.

• 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.ICD-10: M06.9

• Except for the treatment of Wilson's disease or certain patients with cystinuria, use of penicillamine during pregnancy is contraindicated (see WARNINGS ). Although breast milk studies have not been reported in animals or humans, mothers on therapy with penicillamine should not nurse their infants.contraindicated

In all patients receiving penicillamine, it is important that penicillamine capsules be given on an empty stomach, at least one hour before meals or two hours after meals, and at least one hour apart from any other drug, food, or milk. Because penicillamine increases the requirement for pyridoxine, patients may require a daily supplement of pyridoxine (see PRECAUTIONS ). W i l s on 's Disease — Optimal dosage can be determined by measurement of urinary copper excretion and the determination of free copper in the serum. The urine must be collected in copper-free glassware, and should be quantitatively analyzed for copper before and soon after initiation of therapy with penicillamine capsules. Determination of 24-hour urinary copper excretion is of greatest value in the first week of therapy with penicillamine. In the absence of any drug reaction, a dose between 0.75 and 1.5 g that results in an initial 24-hour cupriuresis of over 2 mg should be continued for about three months, by which time the most reliable method of monitoring maintenance treatment is the determination of free copper in the serum. This equals the difference between quantitatively determined total copper and ceruloplasmin-copper. Adequately treated patients will usually have less than 10 mcg free copper/dL of serum. It is seldom necessary to exceed a dosage of 2 g/day. If the patient is intolerant to therapy with penicillamine capsules, alternative treatment is trientine hydrochloride.

The use of penicillamine has been associated with fatalities due to certain diseases such as aplastic anemia, agranulocytosis, thrombocytopenia, Goodpasture's syndrome, and myasthenia gravis. Because of the potential for serious hematological and renal adverse reactions to occur at any time, routine urinalysis, white and differential blood cell count, hemoglobin determination, and direct platelet count must be done twice weekly, together with monitoring of the patient's skin, lymph nodes and body temperature, during the first month of therapy, every two weeks for the next five months, and monthly thereafter. Patients should be instructed to report promptly the development of signs and symptoms of granulocytopenia and/or thrombocytopenia such as fever, sore throat, chills, bruising or bleeding. The above laboratory studies should then be promptly repeated. Leukopenia and thrombocytopenia have been reported to occur in up to five percent of patients during penicillamine therapy. Leukopenia is of the granulocytic series and may or may not be associated with an increase in eosinophils. A confirmed reduction in WBC below 3500/mm 3 mandates discontinuance of penicillamine therapy. Thrombocytopenia may be on an idiosyncratic basis, with decreased or absent megakaryocytes in the marrow, when it is part of an aplastic anemia. In other cases the thrombocytopenia is presumably on an immune basis since the number of megakaryocytes in the marrow has been reported to be normal or sometimes increased.

Penicillamine is a drug with a high incidence of untoward reactions, some of which are potentially fatal. Therefore, it is mandatory that patients receiving penicillamine therapy remain under close medical supervision throughout the period of drug administration (see WARNINGS and PRECAUTIONS ). Reported incidences (%) for the most commonly occurring adverse reactions in rheumatoid arthritis patients are noted, based on 17 representative clinical trials reported in the literature (1270 patients). Allergic — Generalized pruritus, early and late rashes (5%), pemphigus (see WARNINGS ), and drug eruptions which may be accompanied by fever, arthralgia, or lymphadenopathy have occurred (see WARNINGS and PRECAUTIONS ). Some patients may show a lupus erythematosus-like syndrome similar to drug-induced lupus produced by other pharmacological agents (see PRECAUTIONS ). Urticaria and exfoliative dermatitis have occurred. Thyroiditis has been reported; hypoglycemia in association with anti-insulin antibodies has been reported. These reactions are extremely rare. Some patients may develop a migratory polyarthralgia, often with objective synovitis (see DOSAGE AND ADMINISTRATION ). G a strointestinal — Anorexia, epigastric pain, nausea, vomiting, or occasional diarrhea may occur (17%). Isolated cases of reactivated peptic ulcer have occurred, as have hepatic dysfunction including hepatic failure, and pancreatitis. Intrahepatic cholestasis and toxic hepatitis have been reported rarely.

Pregnancy Pregnancy Category D (see WARNINGS , Pregnancy )

Metabolism

Penicillamine is absorbed rapidly but incompletely (40-70%) from the gastrointestinal tract, with wide inter-individual variations. Food, antacids, and iron reduce absorption of the drug.

• Dec 4, 1970NDANDA019853Valeant Pharms Intl
• Nov 8, 1978NDANDA019854Mylan Speciality Lp
• Jun 24, 2019ANDAANDA210976Watson Labs Inc
• Dec 23, 2019ANDAANDA211196Ph Health
• Dec 23, 2019ANDAANDA211231Ph Health
• Aug 4, 2020ANDAANDA211867Dr Reddys
• Nov 30, 2020ANDAANDA212933Lupin
• Dec 2, 2020ANDAANDA211735Granules

1. 1Drug Hypersensitivity17920%
2. 2Drug Ineffective17519%
3. 3Arthralgia14916%
4. 4Joint Swelling14416%
5. 5Inflammation11112%
6. 6Nausea9610%
7. 7Off Label Use9310%
8. 8Diarrhoea889.6%
9. 9Headache839.1%
10. 10Drug Intolerance798.6%
11. 11Hypersensitivity798.6%
12. 12Anaphylactic Reaction778.4%
13. 13Urticaria717.7%
14. 14Treatment Failure697.5%
15. 15Acute Kidney Injury687.4%

Recent PubMed references pinned to Penicillamine as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Evaluating miRNAs as predictive biomarkers for drug-induced autoimmune toxicity in D-penicillamine induced autoimmune diseases animal model.
  Journal of immunotoxicology · 2026 · Yuke R, Zhe Q, Di Z, et al.
  PMID 42008157DOI 10.1080/1547691X.2026.2622342
• Rare-earth cerium doped (NH(4))(2)V(3)O(8) with enhanced peroxidase mimics function for sensitively colorimetric detection of D-penicillamine.
  Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy · 2026 · Zhao A, Zhang X, Huang Y, et al.
  PMID 41955898DOI 10.1016/j.saa.2026.127850
• Targeted microwave sensitizers reprogram cancer-associated fibroblasts via nitric oxide delivery to potentiate hepatocellular carcinoma therapy.
  Journal of controlled release : official journal of the Controlled Release Society · 2026 · Ma S, Wang Q, Zhang Y, et al.
  PMID 41936879DOI 10.1016/j.jconrel.2026.114900
• Using inductively coupled plasma mass spectrometry for studying the association of gold nanoparticles with compounds of clinical interest.
  Talanta · 2026 · Karanasophonphun H, Siripinyanond A
  PMID 41905040DOI 10.1016/j.talanta.2026.129695
• Simple colorimetric detection of Cu(2+) in water and alcoholic beverages based on D-penicillamine-mediated laccase-like activity of PDA/MnO(x) nanoparticles.
  Food chemistry · 2026 · Hu M, Yue Z, Zhao F, et al.
  PMID 41865511DOI 10.1016/j.foodchem.2026.148918
• Evaluation of novel assays of non-ceruloplasmin copper to monitor chelation treatment in patients with Wilson disease.
  JHEP reports : innovation in hepatology · 2026 · Ott P, Sandahl T, Ala A, et al.
  PMID 41831608DOI 10.1016/j.jhepr.2026.101822
• The water-soluble red CsPbI(3) perovskite quantum dot "on-off-on" fluorescence sensor for the detection of Cu(2+) and D-penicillamine.
  Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy · 2026 · Pang M, Wang Y, Du Z, et al.
  PMID 41812495DOI 10.1016/j.saa.2026.127698
• Engineering MOF-Assembled Nanochannels for Enantioselective Detection and Separation of Chiral Drugs.
  Analytical chemistry · 2026 · Yu J, Xiang M, Li M, et al.
  PMID 41703944DOI 10.1021/acs.analchem.5c07686

The 10 most recently updated of 19 ClinicalTrials.gov registrations naming Penicillamine as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Trientine Tetrahydrochloride Administered Once a Day for the First Line Treatment of Wilson's Disease Patients.
  Not yet recruiting · Phase 3 · Interventional · 38 enrolled · Orphalan
  NCT07465718updated 2026-05-28
• Real World Evidence Study in Subjects With Wilson's Disease
  Completed · Observational · 50 enrolled · Orphalan
  NCT05783687updated 2026-04-06
• Off Treatment Urinary Copper Excretion in Wilson Disease, Pilot Study
  Recruiting · Observational · 30 enrolled · Yale University
  NCT07301216updated 2026-03-05
• Wilson's Disease Treated With D-Penicillamine: Characterization of Skin Damage Secondary to Treatment by Measuring Skin Elasticity
  Recruiting · Interventional · 120 enrolled · Centre Hospitalier Universitaire de Saint Etienne
  NCT06945081updated 2026-01-23
• International Wilson's Disease Patient Registry (iWilson Registry)
  Recruiting · Observational · 500 enrolled · Orphalan
  NCT05239858updated 2025-07-03
• Trientine Tetrahydrochloride (TETA 4HCL) for the Treatment of Wilson's Disease
  Completed · Phase 3 · Interventional · 77 enrolled · Orphalan
  NCT03539952updated 2025-07-02
• Study of ALXN1840 Versus Standard of Care in Pediatric Participants With Wilson Disease
  Terminated · Phase 3 · Interventional · 40 enrolled · Alexion Pharmaceuticals, Inc.
  NCT05047523updated 2024-10-23
• A Study to Assess Safety and Efficacy of ASP015K in Participants With Rheumatoid Arthritis (RA) Who Had an Inadequate Response or Intolerance to Methotrexate (MTX)
  Completed · Phase 3 · Interventional · 385 enrolled · Astellas Pharma China, Inc.
  NCT03660059updated 2024-10-21
• Efficacy and Safety of ALXN1840 Administered for 48 Weeks Versus Standard of Care in Participants With Wilson Disease
  Terminated · Phase 3 · Interventional · 214 enrolled · Alexion Pharmaceuticals, Inc.
  NCT03403205updated 2024-06-17
• Safety and Superiority of Penicillamine in Radiosensitization of Recurrent Head and Neck Cancer
  Unknown · Phase 2 · Interventional · 10 enrolled · Nanfang Hospital, Southern Medical University
  NCT06103617updated 2023-11-18

Frequently asked questions

How does Penicillamine work?

Mechanism-of-action class: Chelating Activity.

What is Penicillamine used for?

According to FDA labeling, Penicillamine carries indications including: 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.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Penicillamine?

Penicillamine is classified as Penicillamine and similar agents, Antirheumatic Agent, Chelating Activity, Decreased Immunologically Active Molecule Activity, Renal/Urological Activity Alteration.

What are the brand names for Penicillamine?

Penicillamine is marketed under brand names including Aagylur, Cuprimine, Depen.

What are the contraindications for Penicillamine?

Penicillamine labeling lists contraindications including: Except for the treatment of Wilson's disease or certain patients with cystinuria, use of penicillamine during pregnancy is contraindicated (see WARNINGS ). Although breast milk studies have not been reported in animals or humans, mothers on therapy with penicillamine should not nurse their infants.. Always consult the full prescribing information and a clinician.