Succimer

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Related FACEM curriculum (2022) learning objectives:

• ME 3.8.1.6(e) Principles of management of toxicological presentations including: Indications for antidotes
• ME 3.8.2.4 Identify the appropriate antidote or antivenom.

Presentations

• aka (2,3-Dimercaptosuccinic Acid, DMSA)
• 100 mg oral tablets (100), available under the Special Access Scheme in Australia.

Toxicological Indications

• Adult lead poisoning:
  • Symptomatic cases.
  • Asymptomatic with blood lead >60 µg/dL (>2.9 µmol/L).
• Paediatric lead poisoning:
  • Symptomatic cases.
  • Asymptomatic with blood lead >45 µg/dL (2.17 µmol/L).
• Other heavy metal poisoning:
  • Mercury, arsenic, bismuth, antimony, copper (limited clinical experience).

Contraindications

• Known hypersensitivity to succimer.
• Ongoing heavy metal exposure.

Mechanism of Action

• Succimer is a water-soluble analogue of dimercaprol, which chelates heavy metal ions through its sulfhydryl groups.
• The resulting succimer-metal complexes are excreted in the urine.

Pharmacokinetics

• Rapidly absorbed orally and metabolised quickly.
• Excreted in the urine as metabolites and some unchanged drug.

Administration

• Lead poisoning:
  • Outpatient treatment possible.
  • Initial dose: 10 mg/kg orally, 3 times daily for 5 days.
  • Follow-up: 10 mg/kg orally, 2 times daily for 14 days.
  • Monitor blood lead levels after the initial course; additional courses may be required if blood levels rebound without further exposure.
  • Severe cases may require parenteral treatment with sodium calcium edetate before starting succimer.
• Other heavy metal poisoning:
  • Administer similarly to lead poisoning in the absence of specific guidelines.

Adverse Drug Reactions and Management

• Hypersensitivity reactions.
• Gastrointestinal upset: Common due to the foul-smelling nature of succimer.
  • Symptomatic treatment may be needed; parenteral therapy could be considered.
• Transient liver function test abnormalities (up to 60% of cases).
• Reversible neutropenia (rare).

Specific Considerations

• Pregnancy: Safety not established. Consider chelation at lower blood lead levels due to potential fetal central nervous system vulnerability.
• Paediatrics: Doses are the same as for adults. The threshold for treatment may be lower in children due to neurodevelopmental risks.

Handy Tips

• Oral succimer is preferred for asymptomatic or minimally symptomatic patients who can tolerate it, rather than sodium calcium edetate.
• Outpatient administration is suitable for compliant patients.

Pitfall

• Succimer may be difficult to obtain as it is only available in Australia under the Special Access Scheme.

Controversy

• The blood lead level threshold for succimer chelation in children remains highly debated. While low lead levels can negatively impact neurodevelopment, evidence does not clearly show that chelation improves outcomes.