Penicillamine in Rheumatoid Arthritis: Adverse Effects

Abstract

The use of penicillamine in rheumatoid arthritis (RA) is limited by the incidence of adverse effects, some o f which are potentially hazardous. However, adverse effects are dose-related and the advantages and disadvantages of different fixed and flexible dose regimes are discussed. The incidence of adverse effects is significantly greater in patients previously treated with gold who developed toxicity to that drug-no such increase king found in gold treated patients whose only reason for stopping gold was ineffectiveness. Rashes which develop after several months of treatment are variants of pemphigus and their variouS presentations are described. Fatal reactions, fortunately rare, are predominantly associated with aplasia of the bone marrow. Monthly haemtological checks coupled with meticulous charting of the results may reveal trends as well as numerical changes and serve as an early warning of marrow damage. 1 017 014o/ 1 Retween mealsScand J Rheumatol Downloaded from informahealthcare.com by Nyu Medical Center on 11/03/14For personal use only.

Low‐Dose D‐Penicillamine Therapy in Rheumatoid Arthritis

“…We did not find any significant difference in the number of patients withdrawn for skin lesions among the 3 groups in this study; the overall withdrawal rate was 4% among the D-penicillamine patients. The rashes in our subjects occurred throughout the trial, but were more frequent in the first 2 months, which supports the reports of others (7,29,30).…”

“…Skin rashes are considered the most common side effect of D-penicillamine (7,13) and have resulted in about 10% of withdrawals in some trials (29,30). We did not find any significant difference in the number of patients withdrawn for skin lesions among the 3 groups in this study; the overall withdrawal rate was 4% among the D-penicillamine patients.…”

“…Limiting its general use is the high incidence of side effects, which range from dysgeusia and rash to proteinuria, leukopenia, thrombocytopenia, and aplastic anemia (7). Additionally, a constellation of syndromes, including membranous glomerulopathy (8), myasthenia gravis (9, lo), pemphigus (1 l), and others (10,12) infrequently develops in patients treated with D-penicillamine.…”

“…Early studies used 1,500 mg/day (l), and subsequent investigators have reported efficacy with reduced toxicity for 600 mg/day (2,6). Later, respected clinicians claimed that doses as low as 125, 250, and 500 mg of Dpenicillamine per day were effective (7,15,16). It has been stated that a 375 mg dose is unquestionably effective and that 150 mg daily appears to be effective in some patients (7), yet no controlled studies have been reported to establish this as fact.…”

“…Later, respected clinicians claimed that doses as low as 125, 250, and 500 mg of Dpenicillamine per day were effective (7,15,16). It has been stated that a 375 mg dose is unquestionably effective and that 150 mg daily appears to be effective in some patients (7), yet no controlled studies have been reported to establish this as fact. In order to explore and define these issues, we undertook a controlled, double-blind study to compare the efficacy, tolerability, and safety of daily doses of 125 mg Dpenicillamine per day, 500 mg D-penicillamine per day, and placebo in patients with active RA.…”