No

Chelating Agent

Treatment of Wilson's disease, cystinuria, adjunct in the treatment of rheumatoid arthritis; lead, mercury, copper, and possibly gold poisoning. ( Note: Oral DMSA is preferable for lead or mercury poisoning); primary biliary cirrhosis; as adjunctive therapy following initial treatment with calcium EDTA or BAL

D

Hypersensitivity to penicillamine or components; renal insufficiency; patients with previous penicillamine-related aplastic anemia or agranulocytosis; concomitant administration with other hematopoietic-depressant drugs (eg, gold, immunosuppressants, antimalarials, phenylbutazone)

Cross-sensitivity with penicillin is possible; therefore, should be used cautiously in patients with a history of penicillin allergy. Patients on penicillamine for Wilson's disease or cystinuria should receive pyridoxine supplementation 25 mg/day; once instituted for Wilson's disease or cystinuria, continue treatment on a daily basis; interruptions of even a few days have been followed by hypersensitivity with reinstitution of therapy. Penicillamine has been associated with fatalities due to agranulocytosis, aplastic anemia, thrombocytopenia, Goodpasture's syndrome, and myasthenia gravis; patients should be warned to report promptly any symptoms suggesting toxicity; approximately 33% of patients will experience an allergic reaction; since toxicity may be dose related, it is recommended not to exceed 750 mg/day in elderly.

>10%:

Dermatologic: Rash, urticaria, itching (44% to 50%)

Gastrointestinal: Hypogeusia (25% to 33%)

Neuromuscular & skeletal: Arthralgia

1% to 10%:

Cardiovascular: Edema of the face, feet, or lower legs

Central nervous system: Fever, chills

Gastrointestinal: Weight gain, sore throat

Genitourinary: Bloody or cloudy urine

Hematologic: Aplastic or hemolytic anemia, leukopenia (2%), thrombocytopenia (4%)

Miscellaneous: White spots on lips or mouth, positive ANA

<1%: Fatigue, toxic epidermal necrolysis, pemphigus, increased friability of the skin, iron deficiency, nausea, vomiting, anorexia, pancreatitis, cholestatic jaundice, hepatitis, myasthenia gravis syndrome, weakness, optic neuritis, tinnitus, nephrotic syndrome, coughing, wheezing, SLE-like syndrome, spitting of blood, allergic reactions, lymphadenopathy

Symptoms of overdose include nausea and vomiting

Following GI decontamination, treatment is supportive

Decreased effect with iron and zinc salts, antacids (magnesium, calcium, aluminum) and food

Decreased effect/levels of digoxin

Increased effect of gold, antimalarials, immunosuppressants, phenylbutazone (hematologic, renal toxicity)

Store in tight, well-closed containers

Chelates with lead, copper, mercury and other heavy metals to form stable, soluble complexes that are excreted in urine; depresses circulating IgM rheumatoid factor, depresses T-cell but not B-cell activity; combines with cystine to form a compound which is more soluble, thus cystine calculi are prevented

Absorption: Oral: 40% to 70%

Metabolism: Small amounts of hepatic metabolism

Protein binding: 80% bound to albumin

Half-life: 1.7-3.2 hours

Time to peak serum concentration: Within 2 hours

Elimination: Primarily (30% to 60%) in urine as unchanged drug

Oral:

Children: Initial: 3 mg/kg/day ( less than or equal to 250 mg/day) for 3 months, then 6 mg/kg/day ( less than or equal to 500 mg/day) in divided doses twice daily for 3 months to a maximum of 10 mg/kg/day in 3-4 divided doses

Adults: 125-250 mg/day, may increase dose at 1- to 3-month intervals up to 1-1.5 g/day

Wilson's disease (doses titrated to maintain urinary copper excretion >1 mg/day):

Infants <6 months: 250 mg/dose once daily

Children <12 years: 250 mg/dose 2-3 times/day

Adults: 250 mg 4 times/day

Cystinuria:

Children: 30 mg/kg/day in 4 divided doses

Adults: 1-4 g/day in divided doses every 6 hours

Lead poisoning (continue until blood lead level is <60 mg/dL): Children and Adults: 25-35 mg/kg/d, administered in 3-4 divided doses; initiating treatment at 25% of this dose and gradually increasing to the full dose over 2-3 weeks may minimize adverse reactions

Primary biliary cirrhosis: 250 mg/day to start, increase by 250 mg every 2 weeks up to a maintenance dose of 1 g/day, usually given 250 mg 4 times/day

Arsenic poisoning: Children: 100 mg/kg/day in divided doses every 6 hours for 5 days; maximum: 1 g/day

Dosing adjustment/comments in renal impairment: Cl_cr <50 mL/minute: Avoid use

Should be administered at least 1 hour before a meal on an empty stomach; do not administer with milk; iron and zinc may decrease drug action; increase dietary intake of pyridoxine; for Wilson's disease, decrease copper in diet and omit chocolate, nuts, shellfish, mushrooms, liver, raisins, broccoli, and molasses; for lead poisoning, decrease calcium in diet

Urinalysis, CBC with differential, platelet count, liver function tests; weekly measurements of urinary and blood concentration of the intoxicating metal is indicated (3 months has been tolerated)

May cause drowsiness

May cause aplastic anemia; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

Take this medication exactly as directed; do not increase dose without consulting prescriber. Capsules may be opened and contents mixed in 15-30 mL of chilled fruit juice or puree; do not take with milk or milk products. Avoid alcohol or excess intake of vitamin A. It is preferable to take penicillamine on empty stomach (1 hour before or 2 hours after meals). Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake).

Lead poisoning: Decrease dietary calcium.

Cystinuria: Take with large amounts of water.

You may experience anorexia, nausea, vomiting (frequent small meals, frequent mouth care, sucking lozenges, or chewing gum may help). Report persistent fever or chills, unhealed sores, white spots or sores in mouth or vaginal area, extreme fatigue, or signs of infection; breathlessness, difficulty breathing, or unusual cough; unusual bruising/bleeding; blood in urine, stool, mouth, or vomitus; swollen face or extremities; skin rash or itching; muscle pain or cramping; or pain on urination. Pregnancy/breast-feeding precautions: Do not get pregnant while taking this medication; use appropriate barrier contraceptives. Do not breast-feed.

For patients who cannot swallow, contents of capsules may be administered in 15-30 mL of chilled puréed fruit or fruit juice; patients should be warned to report promptly any symptoms suggesting toxicity

Capsule: 125 mg, 250 mg

Tablet: 250 mg

A 50 mg/mL suspension may be made by mixing twenty 250 mg capsules with 1 g carboxymethylcellulose, 50 g sucrose, 100 mg citric acid, parabens, and purified water to a total volume of 100 mL; cherry flavor may be added. Stability is 30 days refrigerated.

Adelman HM, Winters PR, Mahan CS, et al, "D-Penicillamine-Induced Myasthenia Gravis; Diagnosis Obscured by Coexisting Chronic Obstructive Pulmonary Disease," Am J Med Sci, 1995, 309(4):191-3.

Andonopoulos AP, Terzis E, and Tsibri E, "D-Penicillamine Induced Myasthenia Gravis in Rheumatoid Arthritis: An Unpredictable Common Occurrence?" Clin Rheumatol, 1994, 13(4):586-8.

Aronow R and Fleschmann LE, "Mercury Poisoning in Children," Clin Pediatr (Phila), 1976, 15(10):936-45.

Kandola L, Swannell AJ, and Hunter A, "Acquired Sideroblastic Anaemia Associated With Penicillamine Therapy for Rheumatoid Arthritis," Ann Rheum Dis, 1995, 54(6):529-30.

Lyle WH, "Penicillamine in Metal Poisoning," J Rheumatol Suppl, 1981, 7:96-9.

Multz CV, "Cholestatic Hepatitis Caused by Penicillamine," JAMA, 1981, 246(6):674-5.

Negishi M, Matsuda A, Kaga S, et al, "A Case of Agranulocytosis Which Occurred Several Hours After the Readministration of D-Penicillamine Accompanied by Shivering-Chillness," Arerugi, 1995, 44(2):96-9.

Rosa FW, "Teratogen Update. Penicillamine," Teratology, 1986, 33(1):127-31.

Smith DB and Gallagher BB, "The Effect of Penicillamine on Seizure Threshold. The Role of Pyridoxine," Arch Neurol, 1970, 23(1):59-62.

Stein HB, Patterson AC, Offer RC, et al, "Adverse Effects of D-Penicillamine in Rheumatoid Arthritis," Ann Intern Med, 1980, 92:24-9.