Adverse Effects of Reduced-Dose d-Penicillamine in Children with Mild-to-Moderate Lead Poisoning

Abstract

BACKGROUND: Oral chelation therapy with d-penicillamine (d-PCN) has been proven to be effective in the treatment of mild-to-moderate lead poisoning. However, d-PCN is associated with a relatively high incidence of adverse effects when given in the standard dose of 25–30 mg/kg/d. Lower doses of d-PCN may reduce the rate of adverse effects without a significant reduction in the drug's efficacy. OBJECTIVE: To examine the incidence of rash, white blood cell and platelet count depression, and abnormal urinalysis with d-PCN when given in a dose of 15 mg/kg/d to children with blood lead concentrations <40 μg/dL. METHODS: Retrospective analysis of a clinical treatment course of children who received d-PCN during 1996 in the Lead and Toxicology Clinic of Children's Hospital, Boston. All children were treated under a reduced-dose d-PCN chelation protocol. RESULTS: During the study period, 55 children (mean age 37.4 mo) received 66 courses of d-PCN. Mean blood lead concentration before chelation was 24 μg/dL (range 15–37), with a corresponding erythrocyte protoporphyrin concentration of 42 μg/dL. After 77 days of treatment with d-PCN, blood lead concentration was reduced to mean 16 μg/dL (mean fall 35%; p = 0.005) and erythrocyte protoporphyrin was reduced to 28 μg/dL (p = 0.009). During chelation therapy, the white blood cell count fell below 5000/mm3 in seven cases (9.7%); there were no episodes of platelet counts falling below 150 000/mm3. No cases of abnormal urinalysis were reported; three episodes of rash (4.5%) were recorded. The only patients prematurely terminated from therapy were those who developed rash; in all three cases, drug eruption was an isolated occurrence, which resolved within 48 hours of diphenhydramine therapy. All adverse effects were transient and resolved during or immediately after chelation therapy. CONCLUSIONS: Reduced-dose d-PCN appears to maintain efficacy at reducing blood lead concentrations. Reduced-dose d-PCN also appears to be associated with a rate of adverse effects lower than previously reported; observed adverse effects appear to be benign and transient.