Penicillamine

Indications

Penicillamine is used for: Wilson's Disease, Arsenic Poisoning, Rheumatoid Arthritis, Lead Poisoning, Cystinuria

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 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 Cystine calculi; Cystinuria Adult: 1-4 g daily in 4 divided doses. Usual dose: 2 g/day. If 4 equal doses are not possible, give largest dose at bedtime. Doses adjusted to limit cystine excretion to 100-200 mg/day (<100 mg/day with history of stone formation). Patients should receive pyridoxine supplementation 25 mg/day. Elderly: Doses titrated to maintain urinary copper excretion >2 mg/day. Patients should receive pyridoxine supplementation 25 mg/day. Up to 20 mg/kg/day or 750 mg/day.

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

Renal impairment: CrCl (ml/min) Dosage Recommendation <50 Avoid

Administration

Usually given with 10-25 mg/day pyridoxine Should be taken on an empty stomach. Take on an empty stomach 1 hr before or 2 hr after meals, & at least 1 hr apart from any other drug, food, milk, antacid, Zn- or Fe-containing prep.

Contra Indications

Lupus erythematosus, severe thrombocytopenia, aplastic anaemia, history of D-penicillamine-induced agranulocytosis; pregnancy and lactation.

Precautions

Wilson's disease and cystinuria (25 mg/day) continued on a daily basis once instituted; renal impairment; penicillin allergy; monitor urine for proteinuria and haematuria, blood and platelet counts regularly. Consider withdrawal if platelets fall <120000/mm3 or white blood cells <2500/mm3 or if 3 successive falls within reference range (restart at reduced dose when levels are within reference range); withdraw permanently if leucopenia or thrombocytopenia reoccur. Regularly monitor renal and hepatic function (every 6 mth). Monitor body temperature twice weekly during 1st month of therapy, then every 2 wk for 5 mth, then monthly. Counsel patient to report sore throat, fever, infection, non-specific illness, unexplained bleeding or bruising, pupura, mouth ulcers or rashes. In cystinuria, maintain adequate fluid intake (1 pint of fluid before bed and 1 pint of fluid during night). Caution in patients who have had previous adverse reactions to gold. Penicillamine serum levels may be decreased if taken with food, take 1 hr before meals and at bedtime. For patients who cannot swallow, dissolve tablet or capsule contents in 15-30 ml of chilled puree or fruit juice; do not administer with milk. Avoid oral iron within 2 hr of dose. In Wilson's disease, decrease copper in diet (<1-2 mg/day). In lead poisoning, decrease calcium in diet. Lactation: little information available, mfr states do not nurse

Pregnancy-Lactation

Pregnancy Category: D; allowed only in Wilson's: not to exceed 750 mg/d; contraindicated for rheumatoid arthritis and cystinuria

Interactions

Antacids, iron and zinc interfere with the absorption of penicillamine. Concomitant use of NSAIDs may increase risk of renal damage. May increase levodopa levels. May reduce serum digoxin levels. Potentially Fatal: May increase risk of bone marrow suppression with clozapine, co-trimoxazole, nitrofurantoin, olanzapine, thiamazole, gold, chloroquine, hydroxychloroquine or immunosuppressive treatment.

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

Penicillamine is a chelating agent which aids the removal of heavy-metal ions including copper, lead, arsenic and mercury from the body by forming complexes that are readily excreted by the kidney. It interacts with cystine to form a more soluble compound reducing urinary concentration of cystine and prevents renal calculi development. In rheumatoid arthritis, it depresses circulating IgM rheumatoid factor and T-cell activity (but not B-cell activity).