succimer (Rx)

Frequency Not Defined

Nausea/vomiting

Diarrhea

Abd gas/pain

Transient LFTs incr (AST, AP)

Rash

Pruritus

Sore throat

Rhinorrhea

Drowsiness

Paresthesia

Thrombocytosis

Eosinophilia

Possible decr renal function

Fever

Contraindications

History of hypersensitivity to drug or excipients

Cautions

Clinical experience with product is limited; patients should be carefully observed during treatment

Keep out of reach of pediatric patients; product is not a substitute for effective abatement of lead exposure

Mild to moderate neutropenia reported; while causal relationship to drug not definitely established, neutropenia has been reported with other drugs in same chemical class; obtain complete blood count with white blood cell differential and direct platelet counts prior to and weekly during therapy; withhold therapy or discontinue if absolute neutrophil count (ANC) is below 1200/mcL and patient followed closely to document recovery of ANC to above 1500/mcL or to patient’s baseline neutrophil count; there is limited experience with reexposure in patients who have developed neutropenia; such patients should be rechallenged only if benefit of therapy clearly outweighs potential risk of another episode of neutropenia and then only with careful patient monitoring; patients treated with product should be instructed to promptly report any signs of infection; if infection suspected, the above laboratory tests should be conducted immediately

Elevated blood lead levels and associated symptoms may return rapidly after discontinuation of therapy because of redistribution of lead from bone stores to soft tissues and blood; after therapy, monitor patients for rebound of blood lead levels, by measuring blood lead levels at least once weekly until stable; however, severity of lead intoxication (as measured by initial blood lead level and rate and degree of rebound of blood lead) should be used as guide for more frequent blood lead monitoring

All patients undergoing treatment should be adequately hydrated; use caution in patients with compromised renal function; limited data suggests that product is dialyzable, but that the lead chelates are not

Transient mild elevations of serum transaminases observed in 6-10% of patients during course of therapy; monitor serum transaminases before start of therapy and at least weekly during therapy; monitor closely patients with a history of liver disease; no data are available regarding metabolism of drugs in patients with liver disease

Clinical experience with repeated courses limited; safety of uninterrupted dosing longer than three weeks not established and not recommended

Possibility of allergic or other mucocutaneous reactions to drug must be borne in mind on readministration (as well as during initial courses); patients requiring repeated courses of therapy should be monitored during each treatment course; one patient experienced recurrent mucocutaneous vesicular eruptions of increasing severity affecting the oral mucosa, external urethral meatus and perianal area on the third, fourth and fifth courses of therapy; the reaction resolved between courses and upon discontinuation of therapy

Pregnancy

Succimer has been shown to be teratogenic and fetotoxic in pregnant mice when given subcutaneously in a dose range of 410 to 1640 mg/kg/day during period of organogenesis; in a developmental study in rats, succimer produced maternal toxicity and deaths at the dose of 720 mg/kg/day or more during organogenesis

The dose of 510 mg/kg/day was the highest tolerable dose in pregnant rats; impaired development of reflexes was noted in pups of 720 mg/kg/day group dam; there are no adequate and well controlled studies in pregnant women; therapy should be administered during pregnancy only if potential benefit justifies potential risk to fetus

Lactation

Not known whether this drug is excreted in human milk; because many drugs and heavy metals are excreted in human milk, nursing mothers requiring therapy should be discouraged from nursing their infants

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

2 sulfhydryl groups capable of complexing to lead making it water soluble

Pharmacokinetics

Rapid but incomplete

Protein binding: Highly bound to albumin

Excretion: Feces (39%), urine (9%)

Time to peak: 1-2 hr (serum)

Half-life elimination: 2 days

Metabolism: Metabolized extensively to succimer cysteine sulfides