In patients with Wilson’s disease or cystinuria the risks of continued penicillamine therapy in patients manifesting potentially serious urinary abnormalities must be weighed against the expected therapeutic benefits.

When penicillamine is used in cystinuria, an annual x-ray for renal stones is advised. Cystine stones form rapidly, sometimes in six months.

Up to one year or more may be required for any urinary abnormalities to disappear after penicillamine has been discontinued.

Because of rare reports of intrahepatic cholestasis and toxic hepatitis, liver function tests are recommended every six months for the duration of therapy.

Goodpasture’s syndrome has occurred rarely. The development of abnormal urinary findings associated with hemoptysis and pulmonary infiltrates on x-ray requires immediate cessation of penicillamine.

Obliterative bronchiolitis has been reported rarely. The patient should be cautioned to report immediately pulmonary symptoms such as exertional dyspnea, unexplained cough, or wheezing. Pulmonary function studies should be considered at that time.

Myasthenic syndrome sometimes progressing to myasthenia gravis has been reported. Ptosis and diplopia, with weakness of the extraocular muscles, are often early signs of myasthenia. In the majority of cases, symptoms of myasthenia have receded after withdrawal of penicillamine.

Most of the various forms of pemphigus have occurred during treatment with penicillamine. Pemphigus vulgaris and pemphigus foliaceus are reported most frequently, usually as a late complication of therapy. The seborrhea-like characteristics of pemphigus foliaceus may obscure an early diagnosis. When pemphigus is suspected, Depen should be discontinued. Treatment has consisted of high doses of corticosteroids alone or, in some cases, concomitantly with an immunosuppressant. Treatment may be required for only a few weeks or months, but may need to be continued for more than a year.

Once instituted for Wilson’s disease or cystinuria, treatment with penicillamine should, as a rule, be continued on a daily basis. Interruptions for even a few days have been followed by sensitivity reactions after reinstitution of therapy.

Use In Pregnancy - Penicillamine has been shown to be teratogenic in rats when given in doses 6 times higher than the highest dose recommended for human use (based on a standard weight of 50 kg). Skeletal defects, cleft palates, and fetal toxicity (resorptions) have been reported.

There are no controlled studies on the use of penicillamine in pregnant women. Although normal outcomes have been reported, characteristic congenital cutis laxa and associated birth defects have been reported in infants born of mothers who received therapy with penicillamine during pregnancy. Penicillamine should be used in women of childbearing potential only when the expected benefits outweigh the possible hazards. Women on therapy with penicillamine who are of childbearing potential should be apprised of this risk, advised to report promptly any missed menstrual periods or other indications of possible pregnancy, and followed closely for early recognition of pregnancy.

Wilson’s Disease - Reported experience* shows that continued treatment with penicillamine throughout pregnancy protects the mother against r