Cuprimine


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penicillamine

(pen-i-sill-a-meen) ,

Cuprimine

(trade name),

Depen

(trade name)

Classification

Therapeutic: antidotes
Pharmacologic: chelating agents
Pregnancy Category: D

Indications

Progressive rheumatoid arthritis resistant to conventional therapy.Management of copper deposition in Wilson’s disease.Management of recurrent cystine calculi.Adjunct in the treatment of heavy metal poisoning.

Action

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.

Therapeutic effects

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

Pharmacokinetics

Absorption: Well absorbed after oral administration.
Distribution: Crosses the placenta.
Metabolism and 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).

Time/action profile

ROUTEONSETPEAKDURATION
PO (antirheumatic)2–3 mounknown1–3 mo
PO (Wilson’s disease)1–3 mounknownunknown

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Cross-sensitivity with penicillin may exist; Patients currently receiving gold salts, antimalarials, antineoplastics, oxyphenbutazone, or phenylbutazone; Concurrent use of iron supplements; Obstetric: Pregnancy (penicillamine should be avoided in pregnant patients with rheumatoid arthritis or cystinuria); Obstetric: Lactation.
Use Cautiously in: Renal impairment (increased risk of adverse renal reactions in patients with rheumatoid arthritis); History of aplastic anemia due to penicillamine; Patients requiring surgery (may impair wound healing); Geriatric: Geriatric patients (increased risk of hematologic toxicity, skin rash and taste abnormality; dose reduction recommended); Obstetric: Pregnancy (for patients with Wilson’s disease, limit daily dose to <1 g. If cesarean section is planned, decrease daily dose to 250 mg for last 6 wk of pregnancy and until incision is healed).

Adverse Reactions/Side Effects

Ear, Eye, Nose, Throat

  • blurred vision
  • eye pain

Respiratory

  • coughing
  • shortness of breath
  • wheezing

Gastrointestinal

  • altered taste
  • anorexia
  • cholestatic jaundice
  • diarrhea
  • drug-induced pancreatitis
  • dyspepsia
  • epigastric pain
  • hepatic dysfunction
  • nausea
  • oral ulceration
  • vomiting

Genitourinary

  • proteinuria (most frequent)

Dermatologic

  • pemphigus (most frequent)
  • ecchymoses
  • hives
  • itching
  • rashes
  • wrinkling

Hematologic

  • aplastic anemia (life-threatening)
  • anemia
  • eosinophilia
  • leukopenia
  • thrombocytopenia
  • thrombocytosis

Musculoskeletal

  • arthralgia
  • migratory polyarthritis

Neurologic

  • myasthenia gravis syndrome

Miscellaneous

  • Goodpasture’s syndrome (glomerulonephritis and intra-alveolar hemorrhage) (life-threatening)
  • allergic reactions (most frequent)
  • fever
  • lymphadenopathy
  • systemic lupus erythematosus–like syndrome

Interactions

Drug-Drug interaction

Increased risk of adverse hematologic effects with antineoplastics, immunosuppressants, or gold salts (avoid concurrent use).Concurrent administration of iron supplements decreases absorption of penicillamine.May decrease serum digoxin levels.May increase requirements for pyridoxine (vitamin B6).

Route/Dosage

Oral (Adults) Antirheumatic—125–250 mg/day as a single dose; may be slowly increased up to 1.5 g/day.Chelating agent (Wilson’s disease)—250 mg qid. Antiurolithic—500 mg 4 times daily.
Oral (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.

Availability

Capsules: 125 mg, 250 mg
Tablets: 250 mg

Nursing implications

Nursing assessment

  • Monitor intake and output and daily weight, and assess for edema during therapy. Notify physician or other health care professional if edema or weight gain occurs.
    • Monitor patient for allergic reactions (rash, fever). Discontinue treatment and reinstitute at lower dose (250 mg/day), increasing gradually. Prednisone 20 mg/day may be administered for the first few weeks of therapy to decrease severity of reactions. Antihistamines may be used to control pruritus.
  • Arthritis: Assess pain and range of motion periodically during therapy.
  • Cystinuria: X-ray examinations for renal calculi should be monitored annually for stone formation.
  • Lab Test Considerations: Monitor CBC with differential, platelet counts, and urinalysis (especially for protein and cells) at least every 2 wk during the first 6 mo of therapy or after dose ↑ and monthly thereafter. May cause leukopenia, anemia, and thrombocytopenia. Discontinue therapy if WBC <3500/mm3, neutrophils <2000/mm3, monocytes <500/mm3, platelet count <100,000/mm3, or if hematuria occurs.
    • Monitor liver function tests every 6 mo during the first 18 mo of therapy.
    • May cause a positive ANA test result.
    • May cause hypoglycemia.
    • Arthritis: Monitor 24-hr urinary protein levels every 1–2 wk in patients with moderate proteinuria.
    • Wilson’s disease: Monitor urinary copper levels before and soon after initiation of therapy and every 3 mo during continued therapy.
    • Cystinuria: Monitor urinary cystine levels. Urinary cystine excretion should be maintained at <100 mg in patients with a history of pain or calculi or at 100–200 mg in patients without a history of calculi.

Potential Nursing Diagnoses

Acute pain (Indications)

Implementation

  • Do not confuse penicillamine with penicillin.
  • Oral: Administer on an empty stomach, at least 1 hr before or 2 hr after meals. Other medications should be administered at least 1 hr apart from penicillamine to maximize absorption.
    • Do not administer concurrently with products containing iron.
    • Penicillamine increases the daily requirements for pyridoxine. Supplemental doses of pyridoxine 25 mg/day (vitamin B) may be required in patients with impaired nutrition.
  • Arthritis: Dose adjustments may be required every 2–3 mo during therapy.
    • If no improvement is seen after 3–4 mo of therapy with doses of 1–1.5 g daily, medication should be discontinued.
  • Wilson’s Disease: Sulfurated potash (10–40 mg) may be administered with meals to minimize copper absorption.

Patient/Family Teaching

  • 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.
    • 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.

Evaluation/Desired Outcomes

  • Decreased pain and increased range of motion in patients with rheumatoid arthritis.
  • Prevention and treatment of symptoms of Wilson’s disease.
  • Prevention and treatment of renal calculi in patients with excessive urinary cystine levels.

Cuprimine

(kŭp′rə-mēn′)
A trademark for the drug penicillamine.

Cuprimine

a trademark for a chelating agent used in treating poisoning by heavy metals (D-penicillamine).

Penicillamine (Cuprimine, Depen)

A drug used to treat medical problems (such as excess copper in the body and rheumatoid arthritis) and to prevent kidney stones. It is also sometimes prescribed to remove excess lead from the body.
Mentioned in: Lead Poisoning