Penicillamine

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.

of penicillamine in rheumatoid arthritis is unknown although it appears to suppress disease activity. Unlike cytotoxic immunosuppressants, penicillamine markedly lowers IgM rheumatoid factor but produces no significant depression in absolute levels of serum immunoglobulins. Also unlike cytotoxic immunosuppressants which act on both, penicillamine in vitro depresses T-cell activity but not B-cell activity. In vitro, penicillamine dissociates macroglobulins (rheumatoid factor) although the relationship of the activity to its effect in rheumatoid arthritis is not known. In rheumatoid arthritis, the onset of therapeutic response to CUPRIMINE may not be seen for 2 or 3 months. In those patients who respond, however, the first evidence of suppression of symptoms such as pain, tenderness, and swelling is generally apparent within 3 months.

In all patients receiving penicillamine, it is important that CUPRIMINE be given on an empty stomach, at least one hour before meals or two hours after meals, and at least one hour apart from any other drug, food, or milk. Because penicillamine increases the requirement for pyridoxine, patients may require a daily supplement of pyridoxine. Wilson’s Disease Optimal dosage can be determined by measurement of urinary copper excretion and the determination of free copper in the serum. The urine must be collected in copper-free glassware, and should be quantitatively analyzed for copper before and soon after initiation of therapy with CUPRIMINE. Determination of 24-hour urinary copper excretion is of greatest value in the first week of therapy with penicillamine.

Except for the treatment of Wilson’s disease or certain patients with cystinuria, use of penicillamine during pregnancy is contraindicated. Although breast milk studies have not been reported in animals or humans, mothers on therapy with penicillamine should not nurse their infants. Patients with a history of penicillamine-related aplastic anemia or agranulocytosis should not be restarted on penicillamine. Because of its potential for causing renal damage, penicillamine should not be administered to rheumatoid arthritis patients with a history or other evidence of renal insufficiency.

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. 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.

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. 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, and drug eruptions, which may be accompanied by fever, arthralgia, or lymphadenopathy have occurred. Some patients may show a lupus erythematosus-like syndrome similar to drug-induced lupus produced by other pharmacological agents. Urticaria and exfoliative dermatitis have occurred.

Store at 20° to 25°C (68° to 77°F).