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.^{1 2 3 4}

Uses for Succimer

Lead Poisoning

Alternative for treatment of lead poisoning in children with blood lead concentrations >45 mcg/dL^{1 2} (designated an orphan drug by FDA for this use).⁹

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.⁵ Alternatively, parenteral therapy with edetate calcium disodium (calcium EDTA) alone is recommended.⁵

CDC and AAP do not recommend routine chelation therapy in pediatric patients with blood lead concentrations 25–45 mcg/dL.^{5 b} 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).^{5 b}

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.^{4 5 8}

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.^{5 6}

Used in conjunction with a lead abatement program.^a

Notto be used prophylactically for the prevention of lead poisoning in a lead-containing environment.^{1 2}

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

Other Heavy Metal Poisoning

Has been used in the treatment of mercury poisoning^{† [off-label]} (designated an orphan drug by FDA for this use).^{1 2 9}

Has been used in the treatment of arsenic poisoning^{† [off-label]}.^{1 2 9}

Related/similar drugs

glucagon, mannitol, Lexiscan, Ceretec, arginine, metyrapone, Chemet

Succimer Dosage and Administration

General

• When source for lead poisoning has been identified, remove patient from that source.^a

• Maintain adequate hydration to ensure renal excretion of chelating agents.^a

Administration

Oral Administration

Administer orally.^{1 2}

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.^a

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.^{1 2 a b d} Full course of treatment is 19 days.^{1 2 a}

Intervals ≥2 weeks are recommended between courses of succimer therapy unless blood lead concentrations require more prompt drug therapy.^{1 2 a}

≥4 week interval is recommended when succimer is given subsequent to calcium EDTA therapy, with or without dimercaprol.^{1 2 a}

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.^b Full course of treatment is 19 days.^b

Intervals ≥2 weeks are recommended between courses of succimer therapy unless blood lead concentrations require more prompt drug therapy.^{1 2}

≥4 week interval is recommended when succimer is given subsequent to calcium EDTA therapy, with or without dimercaprol.^{1 2}

Prescribing Limits

Pediatric Patients

Lead Poisoning

Oral

Children >12 months of age: Initially, maximum 10 mg/kg or 350 mg/m² every 8 hours.^{1 2}

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

Adults

Lead Poisoning

Oral

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

Special Populations

No special population dosage recommendations at this time.^a

Cautions for Succimer

Contraindications

• Known hypersensitivity to succimer or any ingredient in the formulation.^a

Warnings/Precautions

Warnings

Lead Exposure

Not a substitute for the abatement of lead exposure.^a

Neutropenia

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

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

Assess blood counts if infection is suspected.^a

Sensitivity Reactions

Hypersensitivity

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

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.^a

General Precautions

Monitoring

Clinical experience is limited; careful observation recommended during therapy.^a

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.^a

After completion of therapy, monitor blood lead concentrations at least once weekly until stable.^a 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.^a

Elevated Serum Transaminases

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

Specific Populations

Pregnancy

Category C.^a

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.^{a e}

Pediatric Use

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

Hepatic Impairment

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

Closely monitor patients with a history of liver disease.^a

Renal Impairment

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

Common Adverse Effects

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

Drug Interactions

Chelating Agents

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

Laboratory Tests

May interfere with serum and urinary laboratory tests.^a 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.^a

Succimer Pharmacokinetics

Absorption

Bioavailability

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

Elimination

Metabolism

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

Elimination Route

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

Half-life

Approximately 2 days.^a

Stability

Storage

Oral

Capsules

15–25°C.^a Avoid excessive heat.^a

Actions

• Chelates heavy metals with a high specificity for lead.^{4 a}

• Forms water soluble chelates with lead and increases urinary excretion of lead.^a

• At recommended oral doses, decreases average blood lead concentrations by 72.5%.^a An average of 19 mg of lead was excreted in urine following administration of 30 mg/kg of succimer daily for 5 days.^a

• Improves clinical symptoms (e.g., headache, colic) and biochemical indices of lead poisoning.^a

• Does not affect urinary elimination of iron, calcium, or magnesium; however, may double zinc excretion.^a

Advice to Patients

• Importance of identifying source of lead poisoning and then removing patient from that source.^{1 2} Importance of patient residing in an environment free of lead both during and after therapy.^{1 2}

• 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.^a

• Importance of maintaining adequate fluid intake.^a

• Importance of informing clinicians if rash or infection occurs.^a

• Importance of completing full course of therapy.^a

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^a

• Importance of keeping succimer out of reach of children.^a

• Importance of informing patients of other important precautionary information.^a (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.

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