DESCRIPTION

Succimer (dimercaptosuccinic acid, DMSA, Chemet) is a metal-chelating agent with a strong sulfur odor similar to rotten eggs.

FORMS AND USES

• Succimer is primarily used for lead poisoning, occasionally for mercury or arsenic poisoning.
• Succimer is formulated in 100-mg capsules for oral use; capsules contain microspheres that may be mixed into food or drink for children.
• The sodium salt of succimer has been used parenterally but is not available in the United States.

MECHANISM OF ACTION

• Succimer binds lead, mercury, or arsenic, probably via sulfhydryl groups, thereby preventing toxic metal effect or possibly removing the metal from binding sites on enzymes or other physiologic proteins.
• The succimer-heavy metal complex is then excreted renally; succimer increases urinary excretion of lead, mercury, and arsenic and lowers blood lead levels in humans.
• Succimer use does not result in the elimination of clinically significant amounts of trace essential minerals such as zinc, copper, iron, magnesium, and calcium; it differs from other chelators such as British anti-Lewisite and ethylenediaminetetraacetic acid (EDTA) in this respect.
• In animal models, succimer does not appear to redistribute lead from the blood to the brain.

DRUG AND DISEASE INTERACTIONS

Unlike British anti-Lewisite, succimer can be administered concurrently with iron without detrimental effect.

PREGNANCY AND LACTATION

US FDA Pregnancy Category C. The drug exerts animal teratogenic or embryocidal effects, but there are no controlled studies in women, or no studies are available in either animals or women.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• MECHANISM OF ACTION
• DRUG AND DISEASE INTERACTIONS
• PREGNANCY AND LACTATION

• Oral treatment of lead poisoning
  • FDA-approved use is for children with blood lead levels at or above 45 µg/dl.
  • Succimer is also often used to treat children with blood lead level between 20 and 45 µg/dl when removing the child from the lead-contaminated environment does not decrease the blood lead level.
  • Succimer is also used for adults with symptoms of lead poisoning or elevated blood lead level, but the exact level at which to chelate is controversial.
• Chelation of other heavy metals such as mercury and arsenic. Succimer is used for confirmed symptomatic mercury or arsenic poisoning or to prevent severe anticipated poisoning (e.g., ingestion of large amount and presentation to health care before toxic effects develop). However, precise criteria for treatment have not been established.

History of allergy to succimer precludes its use.

ADVERSE EFFECTS

• Elevations of alanine aminotransferase and aspartate aminotransferase have occurred during succimer use but have resolved despite continued therapy.
• The drug imparts a sulfur-like odor to the patient's body fluids, which may decrease compliance, especially in adolescents.
• Other side effects of oral administration of succimer are rare and mild; they include gastrointestinal discomfort and mild pain, rashes, and eosinophilia, which have not required treatment.
• One case of hemolysis in a glucose-6-phosphate dehydrogenase-deficient patient has been reported.

LEAD POISONING (ADULTS AND CHILDREN)

• Patient should be removed from lead exposure.
• Patient should receive 10 mg/kg (or 350 mg/m²) orally three times a day for 5 days followed by 10 mg/kg twice a day for 14 days (capsules contain microspheres that may be poured into food or drink for consumption by small children).
• The blood lead level should be checked several days after completion of therapy and every 2 to 4 weeks thereafter until the level stabilizes.
  • If the blood lead level rebounds to 45 µg/dl or above, interim repeat exposure to lead should be investigated; if repeat exposure has not occurred, the course of chelation should be repeated. If repeat exposure has occurred, the patient should be moved to lead-free housing and the course of chelation repeated.
  • If the blood level rebounds to 20 to 45 µg/dl, treatment recommendations are uncertain; many treatment centers would perform at least one more course of chelation.

ARSENIC OR MERCURY POISONING (ADULTS AND CHILDREN)

• A baseline 24-hour urine collection should be performed for the metal of interest.
• Succimer should be administered; because the proper dose is unknown, most practitioners use the same dose as recommended for lead poisoning.
• It may be necessary to begin therapy with a parenteral chelator such as British anti-Lewisite or EDTA due to vomiting; the patient can often be switched to succimer after a day of parenteral therapy.
• Because arsenic and mercury are renally excreted, 24-hour urine collection should be repeated during the first day of therapy.
  • If this collection does not demonstrate marked increase in metal excretion, succimer will probably not be clinically helpful.
• Repeated courses of chelation have been used in patients with persistent symptoms of arsenic or mercury toxicity and persistent elevation of urine metal excretion; however, the exact indications for repeat courses of therapy have not been established.

Section Outline:

• LEAD POISONING (ADULTS AND CHILDREN)
• ARSENIC OR MERCURY POISONING (ADULTS AND CHILDREN)

• Succimer primarily chelates lead in blood and soft tissues; following discontinuation of therapy, blood lead levels often rebound to approximately two thirds of the original value.
  • This phenomenon is affected by the duration of lead poisoning and repeated courses of chelation.
  • Blood lead levels should be repeated every 2 to 4 weeks until stable; repeat chelation may be needed.
• Some patients find the sulfur odor objectionable and are noncompliant with therapy; the patient should be informed that a sulfur-like odor of the body and urine may occur (presence of this odor can be used to confirm compliance with therapy).

Toxic effect of lead and its compounds.

See Also: SECTION IV, Arsenic, Lead, and Mercury chapters.

RECOMMENDED READING

Fournier L, Thomas G, Garnier R, et al. 2,3-Dimercaptosuccinic acid treatment of heavy metal poisoning in humans. Med Toxicol 1988;3:499-504.

Graziano JH, Lolacono NJ, Moulton T, et al. Controlled study of meso-2,3-dimercaptosuccinic acid for the management of childhood lead intoxication. J Pediatr 1992;120:133-139.

Liebelt EL, Shannon M, Graef JW. Efficacy of oral meso-2,3-dimercaptosuccinic acid therapy for low-level childhood plumbism. J Pediatr 1994;124:313-317.

Author: Lada Kokan

Reviewer: Katherine M. Hurlbut