From the Guidelines
Penicillamine is not a first-line treatment for rheumatoid arthritis and should only be considered when other disease-modifying antirheumatic drugs (DMARDs) have failed, due to its potential for significant side effects and the availability of safer alternatives. The use of penicillamine in treating rheumatoid arthritis is based on its ability to reduce inflammation and slow joint damage, as seen in studies such as 1. However, its efficacy is modest, with approximately 40% of patients responding to treatment, and it is often reserved for cases where the combination of NSAIDs and steroids fails or when a reduction in steroid use is desired. Some key points to consider when using penicillamine for rheumatoid arthritis include:
- Starting with a low dose of 125-250 mg daily and gradually increasing to 500-750 mg daily, divided into multiple doses, taken on an empty stomach
- Monitoring for common side effects such as rash, altered taste, decreased appetite, nausea, and more serious adverse effects like proteinuria, blood disorders, and autoimmune conditions
- Regular monitoring of complete blood counts, urinalysis, and kidney and liver function tests every 2-4 weeks initially, then every 1-3 months
- Avoiding taking penicillamine with food, antacids, or iron supplements to ensure optimal absorption It's worth noting that newer DMARDs with better safety profiles have become available, making penicillamine a less common choice for treating rheumatoid arthritis, as supported by studies such as 1.
From the FDA Drug Label
Penicillamine interferes with the formation of cross-links between tropocollagen molecules and cleaves them when newly formed The mechanism of action of penicillamine in rheumatoid arthritis is unknown, although it appears to suppress disease activity. Unlike cytotoxic immunosuppressants, penicillamine markedly lowers IgM rheumatoid factor but produces no significant depression in absolute levels of serum immunoglobulins Also unlike cytotoxic immunosuppressants, which act on both, penicillamine in vitro depresses T-cell activity but not B-cell activity. In rheumatoid arthritis, the onset of therapeutic response to DEPEN may not be seen for two or three months.
The role of penicillamine in treating rheumatoid arthritis is to suppress disease activity, although the exact mechanism of action is unknown. Penicillamine has been shown to:
- Lower IgM rheumatoid factor
- Depress T-cell activity but not B-cell activity
- Interfere with the formation of cross-links between tropocollagen molecules The onset of therapeutic response may take two or three months 2.
From the Research
Role of Penicillamine in Treating Rheumatoid Arthritis
Penicillamine is used as a second-line agent in the treatment of rheumatoid arthritis due to its effectiveness in reducing the degree of synovitis, rheumatoid factor, and immune complexes in serum and synovial fluid 3. The drug has been shown to induce healing of erosive lesions after two to three years of treatment, as evidenced by roentgenographic improvements 3.
Mechanism of Action and Benefits
The exact mechanism of action of penicillamine in rheumatoid arthritis is not fully understood, but it is believed to involve modulation of the immune system, potentially through the induction of autoimmune side effects in some patients 3. Benefits of penicillamine treatment include:
- Decrease in synovitis
- Reduction in rheumatoid factor and immune complexes
- Healing of erosive lesions
- Improvement in clinical symptoms
Adverse Effects and Limitations
Despite its benefits, the use of penicillamine is limited by its toxicity, with common adverse effects including:
- Proteinuria (7-13%) 4, 5
- Skin rashes (5-9%) 4, 5
- Gastrointestinal events (5%) 4
- Thrombocytopenia or leucopenia (2-5%) 4, 5
- Autoimmune syndromes (rare) 4, 3 These adverse effects often require cessation of therapy, with only 30-40% of patients still taking the drug at 2 years 4.
Dosage and Administration
Studies suggest that the daily dose of penicillamine should be as low as possible, with increases made at infrequent intervals only, and with due regard to the likelihood of further improvement in relation to an increased risk of adverse reactions 6, 7. A flexible prescribing policy, starting with a low dose and increasing only if response is poor, may be more successful in the long term, with lower average maintenance doses and fewer withdrawals due to adverse reactions 7.