PenicillamineRx

Trade Names: Cuprimine, Depen

Synonyms: D-Penicillamine

Drug Class: Chelating agent, DMARD

Preparations
Capsules: 250 mg
Tablet: 250 mg (scored)

Dose: For RA (obsolete), 125-250 mg daily initially. Increase by 125-mg increments at 1- to 3-month intervals until usual maintenance dose of 375–750 mg/day is reached. Do not exceed maximum dose of 1 g/day.

Indications: RA, scleroderma, primary biliary cirrhosis, Wilson’s disease, cystinuria, lead poisoning

Mechanism of Action: In RA, mechanism is unknown but may be related to inhibition of T cell function.

Contraindications: Hypersensitivity to penicillamine, renal impairment, pregnancy

Precautions: Penicillamine has a high frequency of adverse effects, and most patients experience an adverse drug reaction.

Monitoring: CBC, differential, platelets, and urinalysis (for protein) should initially be done within 1–2 weeks and then monthly until therapeutic effect and a stable dose are achieved. The frequency of laboratory testing may be changed to every 4–8 weeks if the laboratory indices remain stable on repeat testing.

Pregnancy Risk: D

Adverse Effects
Common: Rash, hives, itching, altered (metallic) taste, proteinuria, arthralgia
Less common: Fever, hematologic toxicity (agranulocytosis, thrombocytopenia, leukopenia, aplastic anemia), glomerulonephritis, myasthenia gravis, Goodpasture syndrome, optic neuritis, hepatitis, lymphadenopathy, drug-induced lupus, pemphigus, inflammatory myositis, bronchiolitis obliterans, mouth ulcers

Drug Interactions: Antacids/iron/food: Significantly decreased absorption of penicillamine

Patient Instructions: Take on an empty stomach. Altered taste may occur. Regular laboratory monitoring is required. Do not become pregnant.

Comments: Penicillamine for RA is obsolete; it  has largely been replaced by methotrexate and other DMARDs. Most patients who took penicillamine for RA discontinued it within 1–2 years because of lack of efficacy or toxicity. Data suggesting benefits of penicillamine in scleroderma are largely based on retrospective studies. A controlled study found no difference between 125 mg on alternate days (a dose used as a substitute for placebo) and 750–1,000 mg/day.

Clinical Pharmacology: Absorption is 50%. When chronic treatment is stopped there is a prolonged elimination phase lasting 4-6 days. Elimination is primarily renal as unchanged drug.

Cost: $$$$

BIBLIOGRAPHY

Clements PJ, Furst DE, Wong WK, et al. High-dose versus low-dose D-penicillamine in early diffuse systemic sclerosis: analysis of a two-year, double-blind, randomized, controlled clinical trial. Arthritis Rheum 1999;42:1194–1203. PMID:10366112