Penicillamine

INDICATIONS CUPRIMINE is indicated in the treatment of Wilson’s disease, cystinuria, and in patients with severe, active rheumatoid arthritis who have failed to respond to an adequate trial of conventional therapy. Available evidence suggests that CUPRIMINE is not of value in ankylosing spondylitis. Wilson’s Disease Wilson’s disease (hepatolenticular degeneration) occurs in individuals who have inherited an autosomal-recessive defect that leads to an accumulation of copper far in excess of metabolic requirements. The excess copper is deposited in several organs and tissues, and eventually produces pathological effects primarily in the liver, where damage progresses to postnecrotic cirrhosis, and in the brain, where degeneration is widespread.

ADVERSE REACTIONS Penicillamine is a drug with a high incidence of untoward reactions, some of which are potentially fatal. Therefore, it is mandatory that patients receiving penicillamine therapy remain under close medical supervision throughout the period of drug administration (see WARNINGS and PRECAUTIONS ). Reported incidences (%) for the most commonly occurring adverse reactions in rheumatoid arthritis patients are noted, based on 17 representative clinical trials reported in the literature (1270 patients). Allergic Generalized pruritus, early and late rashes (5%), pemphigus (see WARNINGS ), and drug eruptions, which may be accompanied by fever, arthralgia, or lymphadenopathy have occurred (see WARNINGS and PRECAUTIONS ).

Pregnancy Penicillamine can cause fetal harm when administered to a pregnant woman. Penicillamine has been shown to be teratogenic in rats when given in doses six times higher than the highest dose recommended for human use. Skeletal defects, cleft palates, and fetal toxicity (resorptions) have been reported. There are no controlled studies on the use of penicillamine in pregnant women.

Physicians planning to use penicillamine should thoroughly familiarize themselves with its toxicity, special dosage considerations, and therapeutic benefits. Penicillamine should never be used casually. Each patient should remain constantly under the close supervision of the physician. Patients should be warned to report promptly any symptoms suggesting toxicity. WARNINGS The use of penicillamine has been associated with fatalities due to certain diseases such as aplastic anemia, agranulocytosis, thrombocytopenia, Goodpasture’s syndrome, and myasthenia gravis. Because of the potential for serious hematological and renal adverse reactions to occur at any time, routine urinalysis, white and differential blood cell count, hemoglobin determination, and direct platelet count must be done twice weekly, together with monitoring of the patient’s skin, lymph nodes, and body temperature, during the first month of therapy, every two weeks for the next 5 months, and monthly thereafter. CONTRAINDICATIONS Except for the treatment of Wilson’s disease or certain patients with cystinuria, use of penicillamine during pregnancy is contraindicated (see WARNINGS ). Although breast milk studies have not been reported in animals or humans, mothers on therapy with penicillamine should not nurse their infants.