D-Penicillamine

# D-Penicillamine ## Overview D-Penicillamine is a chelating agent and disease-modifying antirheumatic drug (DMARD). It chelates metals (copper, mercury, lead) and reduces cystine excretion. Use requires careful dose titration and close monitoring for toxicity. ## Primary Indications - Wilson's disease (copper chelation) - Cystinuria (reduces cystine stone formation) - Active rheumatoid arthritis (after failure of other DMARDs) - Heavy metal poisoning (lead, mercury) – typically not first-line ## Adult Dosing - **Wilson's disease:** 250 mg 4 times daily (total 1 g/day). Increase gradually from 250 mg/day. Usual range 750 mg–1.5 g/day. Maximum 2 g/day. - **Cystinuria:** Start 250 mg/day, titrate to maintain urinary cystine <200–300 mg/L. Usual 1–3 g/day in 3–4 divided doses. Maximum 4 g/day (rare). - **Rheumatoid arthritis:** Start 125–250 mg/day. Increase by 125–250 mg every 1–3 months as tolerated. Usual maintenance 500–750 mg/day. Maximum 1.5 g/day. ## Pediatric Dosing - **Wilson's disease:** 20 mg/kg/day (range 15–25 mg/kg/day) in 3–4 divided doses. Maximum 2 g/day. Exact titration per local protocol. - **Cystinuria:** 30 mg/kg/day in 4 divided doses (range 20–50 mg/kg/day). Maximum 4 g/day. - **Rheumatoid arthritis (juvenile idiopathic arthritis):** Not well-established; use per specialist and local protocol. Start low (3–5 mg/kg/day) with slow titration. - **Heavy metal poisoning:** Dosing varies by protocol; consult toxicology/poison center. ## Dose Adjustments - **Renal impairment:** Avoid if CrCl <50 mL/min. Dose reduce if CrCl 50–80 mL/min (use 50% of usual dose). Monitor carefully. - **Hepatic impairment:** No specific adjustment, but monitor liver function due to potential hepatotoxicity. - **During pregnancy:** Contraindicated for rheumatoid arthritis; may continue in Wilson's disease at lowest effective dose (risk of copper deficiency to fetus). Discuss with specialist. - **Toxicity interruption:** Hold drug for significant proteinuria, bone marrow suppression, or severe rash. Rechallenge only after full resolution and under expert guidance. ## Contraindications - Hypersensitivity to penicillamine - Previous penicillamine-induced aplastic anemia, agranulocytosis, or thrombocytopenia - Systemic lupus erythematosus (SLE) – may exacerbate - Lactation (relative; avoid if possible, especially for rheumatoid arthritis) - Concomitant gold salts, antimalarials, immunosuppressants (except corticosteroids) – increased risk of toxicity ## Adverse Effects - **Bone marrow suppression:** Leukopenia, thrombocytopenia, aplastic anemia (monitor CBC) - **Renal:** Proteinuria, hematuria (can progress to nephrotic syndrome) - **Autoimmune:** Drug-induced lupus, myasthenia gravis, pemphigus, Goodpasture's syndrome - **Dermatologic:** Rash (common), pruritus, urticaria, elastosis perforans serpiginosa - **GI:** Dysgeusia (metallic taste), nausea, anorexia - **Other:** Hepatotoxicity, interstitial pneumonitis, fever, lymphadenopathy, pyridoxine deficiency (supplement recommended) ## Key Drug Interactions - **Antacids, iron, zinc, calcium, magnesium:** Decrease absorption. Separate by at least 2 hours (4 hours for iron). - **Myelosuppressants (e.g., azathioprine, cyclophosphamide):** Additive toxicity – avoid combination. - **Other chelators (e.g., dimercaprol, EDTA):** Enhanced metal depletion – use only under expert guidance. - **Digoxin:** Increased digoxin levels (mechanism unclear) – monitor levels. ## Monitoring - **Baseline and then every 2 weeks (first 6 months), then monthly:** CBC with differential, urinalysis for protein/hematuria, liver function tests. - **Wilson's disease also:** Serum copper, ceruloplasmin, 24-hour urinary copper. - **Cystinuria also:** Urinary cystine, stone surveillance. - **Rheumatoid arthritis also:** Clinical response, acute phase reactants. - **Periodic:** Renal function (serum creatinine), pyridoxine status (if long-term). ## Clinical Pearls - **Start low, go slow:** Titrate to minimize adverse effects. Rapid dose escalation increases toxicity. - **Empty stomach:** Give 1 hour before or 2 hours after meals. Do not take with milk, antacids, or iron. - **Pyridoxine (vitamin B6):** Supplement with 25–50 mg daily to prevent deficiency (penicillamine can bind and deplete B6). - **For Wilson's disease:** Lifelong therapy needed. Do not stop abruptly – may cause fatal copper rebound. - **Taste alteration:** Metallic taste often resolves in 2–3 months; do not stop therapy for this alone. - **Toxicity education:** Warn patients to report fever, sore throat, easy bruising/bleeding, rash, or swelling immediately. - **Pregnancy:** In Wilson's disease, continue penicillamine throughout pregnancy at the lowest effective dose. In rheumatoid arthritis, contraindicated. --- *This information is for educational purposes only. Always verify dosing, indications, and safety with current prescribing references and local clinical protocols. Consult a clinical pharmacist or specialist before initiating or adjusting therapy.*