Succimer, an oral lead chelator.Clin Pharm. 1991 Dec; 10(12):914-22.CP
The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of succimer when used for the treatment of lead poisoning are reviewed. Succimer is an orally active, heavy-metal chelating agent that forms stable, water-soluble complexes with lead; it also chelates other toxic heavy metals, such as arsenic and mercury. It is a designated orphan drug that is indicated for the treatment of lead poisoning, specifically in children with blood lead concentrations higher than 45 micrograms/dL. Succimer reverses the adverse metabolic effects of lead on heme synthesis while increasing urinary lead output without adversely affecting essential mineral excretion at the recommended dosage regimen. The rebound in lead concentrations that can occur after short courses of chelating therapies (caused by redistribution of lead from bone stores) may require frequent and multiple courses of chelation therapy. The most common adverse effects reported in clinical trials of succimer in children and adults were nausea, vomiting, diarrhea, appetite loss, and loose stools; these effects may be related to the drug's unpleasant mercaptan odor. There are no known drug interactions between succimer and other drugs, including iron supplements, although data are limited. The recommended initial dosage in children is 10 mg/kg or 350 mg/sq m every eight hours for five days. The dosage is then reduced to 10 mg/kg or 350 mg/sq m every 12 hours for an additional two weeks. Clinical studies indicate that succimer is relatively selective for lead and effectively lowers blood lead concentrations. Although clinical experience is limited, an oral lead chelator may offer advantages over currently available agents.