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Penicillamine (Cuprimine)
(pen-ih- SILL-ah-meen)
Pregnancy Category: D Cuprimine Depen (Rx)

Classification: Antirheumatic, heavy metal antagonist, to treat cystinuria

Action/Kinetics: A chelating agent for mercury, lead, iron, and copper; forms soluble complexes, thus decreasing toxic levels of the metal (e.g., copper in Wilson's disease). Anti-inflammatory activity may be due to its ability to inhibit T-lymphocyte function and therefore decrease cell-mediated immune response. May also protect lymphocytes from hydrogen peroxide generated at the site of inflammation by inhibiting release of lysosomal enzymes and oxygen radicals. Beneficial effects may not be seen for 2 to 3 months when used for rheumatoid arthritis. In cystinuria, is able to reduce excess cystine excretion, probably by disulfide interchange between penicillamine and cystine. This results in penicillamine-cysteine disulfide, which is a complex that is more soluble than cystine and is thus readily excreted. Well absorbed from the GI tract and excreted in urine. Food decreases the absorption of penicillamine over 50%. Peak plasma levels: 1-3 hr. About 80% is bound to plasma albumin. t 1/2: Approximately 2 hr. Metabolites are excreted through the urine.

Uses: Wilson's disease, cystinuria, and rheumatoid arthritis (severe active disease unresponsive to conventional therapy). Heavy metal antagonist. Investigational: Primary biliary cirrhosis. Scleroderma.

Contraindications: Pregnancy, lactation, penicillinase-related aplastic anemia or agranulocytosis, hypersensitivity to drug. Clients allergic to penicillin may cross-react with penicillamine. Renal insufficiency or history thereof.

Special Concerns: Use for juvenile rheumatoid arthritis has not been established. Clients older than 65 years may be at greater risk of developing hematologic side effects.

Side Effects: This drug manifests a large number of potentially serious side effects. Clients should be carefully monitored. GI: Altered taste perception (common), N&V, diarrhea, anorexia, GI pain, stomatitis, oral ulcerations, reactivation of peptic ulcer, glossitis, cheilosis, colitis, gingivostomatitis (rare). CNS: Tinnitus, myasthenia gravis, peripheral sensory and motor neuropathies (with or without muscle weakness), reversible optic neuritis, polyradiculopathy (rare). Hematologic: Thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia eosinophilia, monocytosis, red cell aplasia, thrombocytopenia, hemolytic anemia leukocytosis, thrombocytosis. Renal: Proteinuria, hematuria, nephrotic syndrome, Goodpasture's syndrome (a severe and ultimately fatal glomerulonephritis). Allergic: Rashes (common), lupus-like syndrome, drug fever, pruritus, pemphigoid-type symptoms (e.g., bullous lesions), arthralgia, lymphadenopathy, dermatoses, urticaria, thyroiditis, hypoglycemia, migratory polyarthralgia, polymyositis, allergic alveolitis. Respiratory: Obliterative bronchiolitis, pulmonary fibrosis, pneumonitis, bronchial asthma, interstitial pneumonitis. Dermatologic: Increased skin friability, excessive skin wrinkling, development of small white papules at venipuncture and surgical sites, alopecia or falling hair, lichen planus, dermatomyositis, nail disorders, toxic epidermal necrolysis cutaneous macular atrophy. Hepatic: Pancreatitis, hepatic dysfunction, intrahepatic cholestasis, toxic hepatitis (rare). Other: Thrombophlebitis, hyperpyrexia, polymyositis, mammary hyperplasia, renal vasculitis (may be fatal), hot flashes, lupus erythematosus-like syndrome.

Laboratory Test Alterations: Serum alkaline phosphatase, LDH. Positive thymol turbidity test and cephalin flocculation test.

Drug Interactions: Antacids / Effect of penicillamine due to absorption from GI tract Antimalarial drugs / Risk of blood dyscrasias and adverse renal effects Cytotoxic drugs / Risk of blood dyscrasias and adverse renal effects Digoxin / Penicillamine effect of digoxin Gold therapy / Risk of blood dyscrasias and adverse renal effects Iron salts / Effect of penicillamine due to absorption from GI tract

How Supplied: Capsule: 125 mg, 250 mg; Tablet: 250 mg

?Capsules, Tablets Rheumatoid arthritis.
Adults, individualized, initial: 125-250 mg/day. Dosage may be increased at 1- to 3-month intervals by 125- to 250-mg increments until adequate response is attained. Maximum: 500-750 mg/day. Up to 500 mg/day can be given as a single dose; higher dosages should be divided. Maintenance, individualized. Range: 500-750 mg/day. If the client is in remission for 6 or more months, a gradual stepwise decrease in dose of 125 or 250 mg/day at about 3-month intervals can be attempted.
Wilson's disease.
Dosage is usually calculated on the basis of the urinary excretion of copper. One gram of penicillamine promotes excretion of 2 mg of copper. Adults and adolescents, usual, initial: 250 mg q.i.d. Dosage may have to be increased to 2 g/day. A further increase does not produce additional excretion. Pediatric, 6 months--young children: 250 mg as a single dose given in fruit juice.
Antidote for heavy metals.
Adults: 0.5-1.5 g/day for 1-2 months; pediatric: 30-40 mg/kg/day (600-750 mg/m 2/day) for 1-6 months.
Individualized and based on excretion rate of cystine (100-200 mg/day in clients with no history of stones, below 100 mg with clients with history of stones or pain). Initiate at low dosage (250 mg/day) and increase gradually to minimum effective dosage. Adult, usual: 2 g/day (range: 1-4 g/day); pediatric: 7.5 mg/kg q.i.d. If divided in fewer than four doses, give larger dose at night.
Primary biliary cirrhosis.
Adults: 600-900 mg/day.

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