ually requires discontinuation of penicillamine. Certain patients will develop a positive anti-nuclear antibody (ANA) test and some of these may show a lupus erythematosus-like syndrome similar to drug-induced lupus associated with other drugs. The lupus erythematosus-like syndrome is not associated with hypocomplementemia and may be present without nephropathy. The development of a positive ANA test does not mandate discontinuance of the drug; however, the physician should be alerted to the possibility that a lupus erythematosus-like syndrome may develop in the future.
Some patients may develop oral ulcerations which in some cases have the appearance of aphthous stomatitis. The stomatitis usually recurs on rechallenge but often clears on a lower dosage. Although rare, cheilosis, glossitis, and gingivostomatitis have also been reported. These oral lesions are frequently dose-related and may preclude further increase in penicillamine dosage or require discontinuation of the drug.
Hypogeusia (a blunting or diminution in taste perception) has occurred in some patients. This may last two to three months or more and may develop into a total loss of taste; however, it is usually self-limited, despite continued penicillamine treatment. Such taste impairment is rare in patients with Wilson’s disease.
* Scheinberg, I.H., Sternlieb, I.: N Engl J Med 293: 1300-1302, December 18, 1975.
Penicillamine should not be used in patients who are receiving concurrently gold therapy, antimalarial or cytotoxic drugs, oxyphenbutazone, or phenylbutazone because these drugs are also associated with similar serious hematologic and renal adverse reactions. Patients who have had gold salt therapy discontinued due to a major toxic reaction may be at greater risk of serious adverse reactions with penicillamine, but not necessarily of the same type.
Patients who are allergic to penicillin may theoretically have cross-sensitivity to penicillamine. The possibility of reactions from contamination of penicillamine by trace amounts of penicillin has been eliminated now that penicillamine is being produced synthetically rather than as a degradation product of penicillin.
Because of their dietary restrictions, patients with Wilson’s disease and cystinuria should be given 25 mg/day of pyridoxine during therapy, since penicillamine increases the requirement for this vitamin. Patients also may receive benefit from a multivitamin preparation, although there is no evidence that deficiency of any vitamin other than pyridoxine is associated with penicillamine. In Wilson’s disease, multivitamin preparations must be copper-free.
Rheumatoid arthritis patients whose nutrition is impaired should also be given a daily supplement of pyridoxine. Mineral supplements should not be given, since they may block the response to penicillamine.
Iron deficiency may develop, especially in children and in menstruating women. In Wilson’s disease, this may be a result of adding the effects of the low copper diet, which is probably also low in iron, and the penicillamine to the effects of blood loss or growth. In cystinuria, a low methionine diet may contribute to iron deficiency, since it is necessarily low in protein. If necessary, iron may be given in short courses, but a period of two hours should elapse between administration of penicillamine and iron, since orally administered iron has been shown to reduce the effects of penicillamine.
