Succimer (Monograph)

Brand name: Chemet
Drug class: Heavy Metal Antagonists
- Sulfhydryl Donors
- Antidotes
ATC class: V03AB
VA class: AD300
Chemical name: Meso 2,3-dimercaptosuccnic acid
Molecular formula: C₄H₆O₄S₂
CAS number: 304-55-2

Introduction

Heavy metal antagonist; chelates lead.

Uses for Succimer

Lead Poisoning

Alternative for treatment of lead poisoning in children with blood lead concentrations >45 mcg/dL (designated an orphan drug by FDA for this use).

The AAP recommends succimer in the treatment of lead poisoning in children with blood lead concentrations of 45–70 mcg/dL who do not have symptoms of lead encephalopathy. Alternatively, parenteral therapy with edetate calcium disodium (calcium EDTA) alone is recommended.

CDC and AAP do not recommend routine chelation therapy in pediatric patients with blood lead concentrations 25–45 mcg/dL. However, oral chelation therapy with succimer may be recommended in certain patients (e.g., blood lead concentrations of 35–44 mcg/dL, children <2 years of age, evidence of toxicity or symptoms).

The AAP currently states that patients with blood lead concentrations >70mcg/dL or with symptoms of lead encephalopathy require inpatient combined therapy with parenteral calcium EDTA and dimercaprol.

Children may need to be hospitalized during initiation of therapy to monitor for adverse effects, ensure patient compliance, and allow time for implementation of environmental lead abatement procedures.

Used in conjunction with a lead abatement program.

Notto be used prophylactically for the prevention of lead poisoning in a lead-containing environment.

Management of lead poisoning^{† [off-label]} in adults with blood lead concentrations 70–100 mcg/dL or mild symptoms.

Other Heavy Metal Poisoning

Has been used in the treatment of mercury poisoning^{† [off-label]} (designated an orphan drug by FDA for this use).

Has been used in the treatment of arsenic poisoning^{† [off-label]}.

Succimer Dosage and Administration

General

When source for lead poisoning has been identified, remove patient from that source.
Maintain adequate hydration to ensure renal excretion of chelating agents.

Administration

Oral Administration

Administer orally.

In patients who cannot swallow capsules, administer by opening capsule and sprinkling beads on a small amount of soft food or by putting beads in a spoon and following with fruit drink.

Dosage

Pediatric Patients

Lead Poisoning

Blood Lead Concentration 45–70 mcg/dL

Oral

Children >12 months of age: 10 mg/kg or 350 mg/m² every 8 hours for 5 days followed by 10 mg/kg or 350 mg/m² every 12 hours for 14 days. Full course of treatment is 19 days.

Intervals ≥2 weeks are recommended between courses of succimer therapy unless blood lead concentrations require more prompt drug therapy.

≥4 week interval is recommended when succimer is given subsequent to calcium EDTA therapy, with or without dimercaprol.

Adults

Lead Poisoning

Mild Symptoms or Blood Lead Concentration 70–100 mcg/dL

Oral

10 mg/kg or 350 mg/m² every 8 hours for 5 days followed by 10 mg/kg or 350 mg/m² every 12 hours for 14 days. Full course of treatment is 19 days.

Intervals ≥2 weeks are recommended between courses of succimer therapy unless blood lead concentrations require more prompt drug therapy.

≥4 week interval is recommended when succimer is given subsequent to calcium EDTA therapy, with or without dimercaprol.

Prescribing Limits

Pediatric Patients

Lead Poisoning

Oral

Children >12 months of age: Initially, maximum 10 mg/kg or 350 mg/m² every 8 hours.

Safety of uninterrupted dosing >3 weeks not established and not recommended.

Adults

Lead Poisoning

Oral

Safety of uninterrupted dosing >3 weeks not established and not recommended.

Special Populations

No special population dosage recommendations at this time.

Cautions for Succimer

Contraindications

Known hypersensitivity to succimer or any ingredient in the formulation.

Warnings/Precautions

Warnings

Lead Exposure

Not a substitute for the abatement of lead exposure.

Neutropenia

Risk of mild to moderate neutropenia, possibly resulting in infection.

Perform CBCs, including differential and platelet counts, prior to and weekly during therapy. Withhold therapy if ANC <1200/mm³; continue monitoring until ANC >1500/mm³ or recovery to patient’s baseline neutrophil count. Rechallenge only if the benefit of therapy outweighs the risk of neutropenia and only with careful monitoring.

Assess blood counts if infection is suspected.

Sensitivity Reactions

Hypersensitivity

Possible allergic or mucocutaneous reactions; may occur with readministration as well as during initial course.

Recurrent mucocutaneous vesicular eruptions affecting oral mucosa, external urethral meatus, and perianal area reported in one patient; reactions increased in severity with administration of each subsequent course and resolved between courses and upon discontinuance of therapy.

General Precautions

Monitoring

Clinical experience is limited; careful observation recommended during therapy.

Rebound Lead Toxicity

Risk of elevated blood lead concentrations and associated symptoms after discontinuance of drug due to redistribution of lead from bone stores to soft tissues and blood.

After completion of therapy, monitor blood lead concentrations at least once weekly until stable. Use the severity of lead intoxication (as measured by the initial blood lead concentration and the rate and degree of rebound of blood lead) as a guide for more frequent monitoring.

Elevated Serum Transaminases

Transient mild elevations of serum transaminases observed in 6–10% of patients. Obtain baseline and weekly serum transaminase levels during therapy.

Specific Populations

Pregnancy

Category C.

Lactation

Not known whether succimer is distributed into milk; however, breastfeeding is contraindicated in women receiving succimer due to maternal lead poisoning and risk of exposing nursing infant to the toxic heavy metal.

Pediatric Use

Safety and efficacy not established in children <12 months of age.

Hepatic Impairment

Use with caution; assess hepatic function prior to and periodically during therapy.

Closely monitor patients with a history of liver disease.

Renal Impairment

Use with caution; assess renal function prior to and periodically during prolonged therapy. Adequately hydrate patients during therapy. Limited data suggests that succimer is dialyzable, but the lead chelates are not.

Common Adverse Effects

GI symptoms (nausea, vomiting, diarrhea, appetite loss, loose stools, metallic taste), elevated serum transaminases, rash, neutropenia.

Drug Interactions

Chelating Agents

Concomitant administration with other chelating agents (i.e., edetate sodium dicalcium) is not recommended.

Laboratory Tests

May interfere with serum and urinary laboratory tests. May cause false positive results for ketones in urine using nitroprusside reagents (e.g., Ketostix) and falsely decreased measurements of serum uric acid and CPK.

Succimer Pharmacokinetics

Absorption

Bioavailability

Absorption is rapid and variable, with peak plasma concentrations obtained at 1–2 hours.

Elimination

Metabolism

Approximately 90% of absorbed dose is metabolized to mixed succimer-cysteine disulfides.

Elimination Route

Unabsorbed drug excreted principally in feces; absorbed drug excreted principally in the urine as metabolites.

Half-life

Approximately 2 days.

Stability

Storage

Oral

Capsules

15–25°C. Avoid excessive heat.

Actions

Chelates heavy metals with a high specificity for lead.
Forms water soluble chelates with lead and increases urinary excretion of lead.
At recommended oral doses, decreases average blood lead concentrations by 72.5%. An average of 19 mg of lead was excreted in urine following administration of 30 mg/kg of succimer daily for 5 days.
Improves clinical symptoms (e.g., headache, colic) and biochemical indices of lead poisoning.
Does not affect urinary elimination of iron, calcium, or magnesium; however, may double zinc excretion.

Advice to Patients

Importance of identifying source of lead poisoning and then removing patient from that source. Importance of patient residing in an environment free of lead both during and after therapy.
For patients unable to swallow capsules, contents of capsules may be sprinkled on soft food just before administration or placed on a spoon for administration and taken with fruit juice.
Importance of maintaining adequate fluid intake.
Importance of informing clinicians if rash or infection occurs.
Importance of completing full course of therapy.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
Importance of keeping succimer out of reach of children.
Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.