Penicillamine

Indications

Penicillamine is used for: Wilson's Disease

Adult Dose

Wilson's Disease 250 mg PO QID; dosage range 500-1500 mg/day Pregnancy: Not to exceed 500-750 mg/day Planned cesarean section: Reduce dose to 250 mg/day for the last 6 weeks of pregnancy and postoperatively until wound healing completed Dosing considerations Adjust dose to achieve urinary copper excretion of 0.5-1 mg/day Free copper levels in serum: Maintain at <10 mcg/dL Arsenic Poisoning 100 mg/kg/day PO divided q6hr x5 days If used for chronic arsenic poisoning, endpoint: 24 hours urinary arsenic <50 mcg/L Rheumatoid Arthritis Initial: 125-250 mg/day PO Maintenance: May be increased by 125-250 mg/day q1-3Months up to 500-750 mg/day, may be increased further if no response and patient tolerates Lead Poisoning 1-1.5 g qDay PO or divided BID-TID x1-6 months

Child Dose

Lead Poisoning Considered 3rd-line therapy 20-40 mg/kg/day PO divided q8hr Wilson's Disease 20 mg/kg/day PO divided q12hr Cystinuria 30 mg/kg/day PO divided BID/QID; not to exceed 1 g/day Juvenile Rheumatoid Arthritis 1st step (2 months): 5 mg/kg PO qDay x2 months 2nd step (4 months): 10 mg/kg PO qDay x4 months

Renal Dose

Administration

Usually given with 10-25 mg/day pyridoxine Take on empty stomach; last dose given at least 3 hr after evening meal

Contra Indications

Penicillin allergy, discontinue if immune reactions History of penicillamine-related aplastic anemia, agranulocytosis Renal insufficiency (avoid if CrCl <50 mL/min) Concurrency with gold salts, antimalarials, immunosuppressants, phenylbutazone

Precautions

Antacids, digoxin and iron (PO) decr levels and/or activity Reactive airway disease Associated with obliterative bronchiolitis Increases the body's requirement for pyridoxine Potential for development of (reversible) myasthenia gravis and other neurologic symptoms

Pregnancy-Lactation

Pregnancy & Lactation Pregnancy Category: D; allowed only in Wilson's: not to exceed 750 mg/d; contraindicated for rheumatoid arthritis and cystinuria Lactation: little information available, mfr states do not nurse

Interactions

Adverse Effects

Side effects of Penicillamine : >10% Worsening neurologic symptoms (10-50% pts with Wilson's disease) Adverse effects requiring discontinuation of treatment Discontinued in 20-30% of pts with Wilson's disease Diarrhea (17%) Taste alteration (12%) 1-10% Proteinuria (6%) Rash (early and late 5%) Thrombocytopenia (4-5%) Leukopenia (2-5%) Frequency Not Defined Nausea/vomiting Fever Anorexia Pemphigus Oral lichenoid reaction Myasthemia gravis Neuropathy Optic neuritisTinnitus Goodpasture's syndrome Renal failure positive ANA Hepatitis Pancreatitis Hemolytic anemia

Mechanism of Action

Chelates gold, copper, mercury, and arsenic Cystinuria: forms disulfide bonds with cysteine and facilitates excretion of cysteine-penicillamine complex rather than cystine Rheumatoid arthris: unknown; depresses T-cell activity in vitro