• Progressive rheumatoid arthritis resistant to conventional therapy.
• Management of copper deposition in Wilson’s disease.
• Management of recurrent cystine calculi.

Unlabeled Uses:

• Adjunct in the treatment of heavy metal poisoning.

Contraindicated in:

• Hypersensitivity
• Cross-sensitivity with penicillin may exist
• Patients currently receiving gold salts, antimalarials, or antineoplastics
• Concurrent use of iron supplements
• OB: Should be avoided in pregnant women with rheumatoid arthritis or cystinuria
• Lactation: Lactation.

Use Cautiously in:

• Renal impairment (↑ risk of adverse renal reactions in patients with rheumatoid arthritis)
• History of aplastic anemia due to penicillamine
• Patients requiring surgery (may impair wound healing)
• OB: For pregnant women with Wilson’s disease, limit daily dose to <1 g. If Cesarean section is planned, ↓ daily dose to 250 mg for last 6 wk of pregnancy and until incision is healed
• Geri: ↑ risk of hematologic toxicity, skin rash and taste abnormality in older adults; dose ↓ recommended).

Derm: pemphigus, ecchymoses, hives, itching, rash, wrinkling.

EENT: blurred vision, eye pain.

GI: altered taste, anorexia, cholestatic jaundice, diarrhea, dyspepsia, epigastric pain, hepatic impairment, nausea, oral ulceration, PANCREATITIS, vomiting.

GU: proteinuria.

Hemat: leukopenia, anemia, APLASTIC ANEMIA, eosinophilia, thrombocytopenia, thrombocytosis.

MS: arthralgia, migratory polyarthritis.

Neuro: myasthenia gravis syndrome.

Resp: coughing, shortness of breath, wheezing.
Misc: allergic reactions, GOODPASTURE’S SYNDROME (GLOMERULONEPHRITIS AND INTRA-ALVEOLAR HEMORRHAGE), fever, lymphadenopathy, systemic lupus erythematosus–like syndrome.

Drug-Drug:

• ↑ risk of adverse hematologic effects with antineoplastics, immunosuppressants, or gold salts; avoid concurrent use.
• Concurrent administration of iron supplements ↓ absorption of penicillamine.
• May ↓ serum digoxin levels.

Drug-Food:

• May ↑ requirements for pyridoxine (vitamin B₆).

(Generic available)

• Capsules: 250 mg;
• Tablets: 250 mg;

• PO (Adults): Antirheumatic: 125–250 mg/day as a single dose; may be slowly ↑ up to 1.5 g/day.Chelating agent (Wilson’s disease): 250 mg 4 times daily. Antiurolithic: 500 mg 4 times daily.
• PO (Children >6 mo): Chelating agent (Wilson’s disease): 250 mg/day as a single dose; older children may receive the adult dose. Antiurolithic: 7.5 mg/kg 4 times daily.

Cuprimine, Depen

• Antirheumatic effect, probably resulting from enhanced lymphocyte function.
• Chelates heavy metals, including copper, mercury, lead, and iron, into complexes that are excreted by the kidneys.
• Forms a soluble complex with cystine that is readily excreted by the kidneys.

• Decreased disease progression in rheumatoid arthritis.
• Decreased copper deposition in Wilson’s disease.
• Decreased cystine renal calculi formation.

Therapeutic Classification: antidotes, antirheumatics (DMARD), antiurolithics

Pharmacologic Classification: chelating agents

Absorption: Well absorbed after oral administration.

Distribution: Crosses the placenta.

Metabolism/Excretion: Some excreted in urine as heavy metal–penicillamine complex, some excreted in urine as cystine-penicillamine complex, some metabolized by the liver.

Half-life: 1–7.5 hr (4–6 days during long-term use).

• Instruct patient to take penicillamine as directed. If on once-daily schedule, take missed doses as soon as remembered unless remembered the next day; if on twice-daily schedule, take missed doses as soon as remembered unless almost time for next dose; if on more than twice-daily dosing schedule, take missed doses within 1 hr or omit. Do not double doses.
  • Consult health care professional before discontinuation of therapy, as interruption of therapy may cause sensitivity reactions when therapy is resumed. Therapy should be resumed starting with smaller dose and increasing gradually.
  • Inform patient that penicillamine may alter taste acuity, which may be restored by administration of copper 5–10 mg daily. Cupric sulfate 4% solution 5–10 drops may be mixed in fruit juice and taken twice daily. This is contraindicated in patients with Wilson’s disease.
  • Advise patient to notify health care professional of medication regimen before surgery or treatment. Dose of penicillamine should be reduced until wound healing is complete.
  • Instruct patient to notify health care professional of skin rash, unusual bleeding or bruising, sore throat, exertional dyspnea, unexplained coughing or wheezing, fever, chills, or any unusual effects.
  • May be teratogenic. Advise females or reproductive potential to use effective contraception during therapy and to notify health care professional if pregnancy is planned or suspected or if breastfeeding. If penicillamine is administered during pregnancy to patients with Wilson's disease, recommended daily dose be limited to 750 mg. If cesarean section is planned, reduce daily dose to 250 mg, but not lower, for last 6 wk of pregnancy and postoperatively until wound healing is complete.
  • Emphasize the importance of follow-up exams to check progress.
• Wilson’s Disease: Advise patient to discuss dietary restrictions with health care professional. A low-copper diet may be required. Chocolate, nuts, shellfish, mushrooms, liver, molasses, broccoli, and cereals enriched with copper should be avoided. If drinking water contains >100 mcg/liter of copper, distilled or demineralized water should be used.
• Cystinuria: Advise patient to maintain a fluid intake of at least 2000–3000 mL/day, with increased fluids at night.
  • Advise patient to discuss dietary restrictions with health care professional. Low-methionine diet may be required to minimize cystine production but is contraindicated in growing children or pregnancy because of low protein content.

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