Penicillamine

Approximately 33% of patients will experience an allergic reaction. Rash may occur early (more commonly) or late in therapy; early-onset rash typically resolves within days of discontinuation of therapy and does not recur upon rechallenge with reduced dose; discontinue therapy for late-onset rash (eg, after >6 months) and do not rechallenge; rash typically recurs with rechallenge. Discontinue therapy for skin reactions accompanied by lymphadenopathy, fever, arthralgia, or other allergic reactions.

Has been reported rarely with use; instruct patients to report pulmonary symptoms (eg, unexplained wheezing or cough, exertional dyspnea) and consider pulmonary function testing in such patients.

Penicillamine increases the amount of soluble collagen; may increase skin friability, particularly at sites subject to pressure or trauma (eg, knees, elbows shoulders). Purpuric areas with localized bleeding (if skin is broken) or vesicles with dark blood may be observed. Effects are considered localized and do not necessitate discontinuation of therapy; may not recur with dose reduction. Macular cutaneous eruptions are sometimes observed in conjunction with drug fever, usually 2 -3 weeks after therapy initiation. Dose reduction may be considered prior to surgical procedures. May resume normal recommended dosing postoperatively once wound healing is complete.

Drug fever may be observed, usually 2-3 weeks after therapy initiation. Discontinue use in patients with rheumatoid arthritis, Wilson’s disease, or cystinuria who develop a marked febrile response. Consider alternative therapy for patients with rheumatoid arthritis due to high incidence of fever reoccurrence with penicillamine rechallenge. May resume therapy at a reduced dose in Wilson’s disease or cystinuria upon resolution of fever; dose should then be gradually titrated to effective dose.

Taste alteration may occur (rare in Wilson’s disease); usually self-limited with continued therapy, however may last ≥2 months and result in total loss of taste. Oral ulceration (eg, stomatitis) may occur; typically recurs on rechallenge but often resolves with dose reduction. Other dose-related lesions (eg, glossitis, gingivostomatitis) have been observed with use and may require therapy discontinuation.

Penicillamine has been associated with fatalities due to Goodpasture's syndrome. Discontinue therapy immediately in patients with abnormal urinary findings in association with hemoptysis and pulmonary infiltrates on chest x-ray.

Penicillamine has been associated with fatalities due to agranulocytosis, aplastic anemia, and thrombocytopenia. Discontinue therapy for WBC 3. Withhold therapy at least temporarily for platelet counts 3 or a progressive fall in WBC or platelets in 3 successive determinations, even though values may remain within the normal range. Monitor for signs/symptoms of leukopenia and thrombocytopenia.

Monitor liver function tests periodically due to rare reports of intrahepatic cholestasis or toxic hepatitis. More frequent monitoring is required during the first year of therapy in patients with Wilson’s disease.

May be observed in some patients; positive antinuclear antibody (ANA) test does not necessitate therapy discontinuation but should alert clinicians of possible future development of lupus erythematosus-like syndrome.

May occur early or late in therapy; discontinue use with suspicion of pemphigus. May treat with high-dose corticosteroids alone, or in conjunction with an immunosuppressant; treatment duration can range from weeks to >1 year.

Patients with a penicillin allergy may theoretically have cross-sensitivity to penicillamine; however, the possibility has been eliminated now that penicillamine is produced synthetically and no longer contains trace amounts of penicillin.

Proteinuria or hematuria may develop; monitor for membranous glomerulopathy which can lead to nephrotic syndrome. In rheumatoid arthritis patients, discontinue if gross hematuria or persistent microscopic hematuria develop and discontinue therapy or reduce dose for proteinuria that is either >1 g/day or progressively increasing. Dose reduction may lead to resolution of proteinuria.

Penicillamine has been associated with myasthenic syndrome, and in some cases, progression to myasthenia gravis. Resolution of symptoms has been observed in most cases following discontinuation of therapy.

Patients should be warned to report promptly any symptoms suggesting toxicity (fever, sore throat, chills, bruising, or bleeding); toxicity may be dose related. Disease-related concerns:

Continue treatment on a daily basis; interruptions of even a few days have been followed by hypersensitivity with reinstitution of therapy. Patients should receive pyridoxine supplementation (25 mg/day).

Investigate, identify, and remove sources of lead exposure and confirm lead-containing substances are absent from the GI tract prior to initiating therapy. Do not permit patients to re-enter the contaminated environment until lead abatement has been completed. Penicillamine is considered to be a third-line agent for the treatment of lead poisoning in children due to the overall toxicity associated with its use (AAP, 2005; Chandran, 2010); penicillamine should only be used when unacceptable reactions have occurred with edetate CALCIUM disodium and succimer. Primary care providers should consult experts in the chemotherapy of lead toxicity before using chelation drug therapy.

Patients with rheumatoid arthritis and impaired nutrition should receive pyridoxine supplementation (25 mg/day).

Continue treatment on a daily basis; interruptions of even a few days have been followed by hypersensitivity with reinstitution of therapy. Worsening of neurologic symptoms may occur during initiation of therapy however discontinuation of therapy is not recommended; may consider concomitant use of short term dimercaprol in patients whose symptoms continue to worsen 1 month following therapy initiation. Patients should receive pyridoxine supplementation (25-50 mg/day; Roberts, 2008). Concurrent drug therapy issues:

Use with caution in patients on other hematopoietic-depressant drugs (eg, gold, immunosuppressants, antimalarials, phenylbutazone; Canadian labeling contraindicates concomitant use with these agents); hematologic and renal adverse reactions are similar. Special populations:

Use with caution in the elderly; may be more susceptible to skin rash and/or taste alterations. Other warnings/precautions:

Should be administered under the close supervision of a physician familiar with the toxicity and dosage considerations.