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DRUG RECORD

 

SUCCIMER

OVERVIEW
Succimer

 

Introduction

Succimer is an oral heavy metal chelating agent used to treat lead and heavy metal poisoning.  Succimer has been linked to a low rate of transient serum aminotransferase elevations during therapy, but its use has not been linked to cases of clinically apparent liver injury with jaundice.

 

Background

Succimer (sux’ i mer) or dimercaptosuccinic acid (DMSA) is an orally available heavy metal chelating agent that is used to treat lead poisoning in children.  Succimer is an organo-sulfur compound with two sulfhydryl groups that bind divalent metal ions such as lead, cadmium, mercury, and arsenic.  Succimer does not significantly chelate essential metals such as zinc, copper or iron, and its specificity, safety and oral availability make it preferable to other chelating agents for treating lead poisoning such as Ca-EDTA which must be given intravenously and dimercaprol (British anti-Lewisite [BAL]) which requires intramuscular administration.  Succimer has been shown to lower blood lead levels and improve symptoms of chronic lead poisoning.  Succimer was approved for use in the United States in 1991, and current indications are for treatment of lead poisoning in pediatric patients with plasma lead levels above 45 µg/dL.  It is used off label to treat adults with lead poisoning and for therapy of arsenic and mercury intoxication.  Succimer is also used in naturopathic medicine as a part of chelation therapy for various conditions.  Succimer is available in capsules of 100 mg generically and under the brand name Chemet.  The recommended dose is 10 mg/kg (or 30 mg/m2) every 8 hours for 5 days, with 2 week rest periods between repeated courses if lead levels remain high.  Side effects are generally mild and may include headache, nausea, anorexia, diarrhea, rash and renal dysfunction. Uncommon, but potentially severe adverse events include hypersensitivity reactions.

 

Hepatotoxicity

In clinical trials conducted in children with lead poisoning, serum aminotransferase levels elevations occurred in 7% of succimer- vs 4% of placebo-treated subjects.  However, ALT levels above 5 times the upper limit of normal were rare (<1% of treated patients) and no child had to stop therapy early because of liver test abnormalities.  There have been no clinical reports of liver injury with jaundice attributed to succimer.

 

Mechanism of Injury

The mechanism of injury accounting for serum enzyme elevations during succimer therapy is not known.  Succimer-metal chelates are eliminated in the urine.

 

Outcome and Management

Serum aminotransferase elevations above 5 times the upper limit of normal (if confirmed) should lead to dose reduction or temporary cessation.  Succimer has not been implicated in cases of acute liver failure, chronic hepatitis or vanishing bile duct syndrome.  There does not appear to be cross reactivity in risk for hepatic injury between succimer and other chelating agents including deferoxamine or deferiprone.

 

Drug Class:  Chelating Agents, Lead Chelators

 

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REPRESENTATIVE TRADE NAMES
Succimer – Generic, Chemet®

 

DRUG CLASS
Chelating Agents

 

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

 

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DRUG CAS REGISTRY NO. MOLECULAR FORMULA STRUCTURE
Succimer 304-55-2 C4-H6-O4-S2 Succimer structure

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REFERENCES
Succimer

 

References updated:  18 August 2014

  1. Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999.  (Review of hepatotoxicity published in 1999; succimer is not discussed).

  2. Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013.  (Textbook on hepatotoxicity; chelating agents are not discussed).

  3. Byrns MC, Penning TM. Treatment of metal exposure. Environmental toxicology: carcinogens and heavy metals. In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp. 1872-6.  (Textbook of pharmacology and therapeutics).

  4. Graziano JH, Lolacono NJ, Moulton T, Mitchell ME, Slavkovich V, Zarate C. Controlled study of meso-2,3-dimercaptosuccinic acid for the management of childhood lead intoxication. J Pediatr 1992; 120: 133-9. PubMed Citation  (Among 19 children with high blood lead levels [50-69 µg/dL], succimer lowered levels by 61% which was more than achieved with intravenous Ca-EDTA [45%], and repeated courses of succimer prevented the rebound that typically occurs after a single course of therapy; one child had a transient minor increase in ALT levels [26 to 62 U/L]).

  5. Glotzer DE. The current role of 2,3-dimercaptosuccinic acid (DMSA) in the management of childhood lead poisoning. Drug Saf 1993; 9: 85-92. PubMed Citation  (Review of the mechanism of action, efficacy and safety of succimer as a chelating agent for lead poisoning mentions that its safety profile is encouraging, but its use has been limited and its efficacy in preventing neurotoxicity from lead poisoning remains unproven).

  6. Miller AL. Dimercaptosuccinic acid (DMSA), a non-toxic, water-soluble treatment for heavy metal toxicity. Altern Med Rev 1998; 3: 199-207. PubMed Citation  (Review of heavy metal poisoning from lead, mercury, arsenic and cadmium and the role of succimer therapy).

  7. Guha Mazumder DN, Ghoshal UC, Saha J, Santra A, De BK, Chatterjee A, Dutta S, et al. Randomized placebo-controlled trial of 2,3-dimercaptosuccinic acid in therapy of chronic arsenicosis due to drinking arsenic-contaminated subsoil water. J Toxicol Clin Toxicol 1998; 36: 683-90. PubMed Citation  (Among 21 patients with chronic arsenic toxicity due to drinking water contamination in West Bengal, there were no differences between succimer and placebo therapy in changes in symptoms or arsenic levels after two 2-week courses).

  8. Safety and efficacy of succimer in toddlers with blood lead levels of 20-44 microg/dL. Treatment of Lead-Exposed Children (TLC) Trial Group. Pediatr Res 2000; 48: 593-9. PubMed Citation  (Among 780 children, ages 1-3 years, with moderately elevated blood lead levels [20-44 µg/dL] treated with up to 3 courses of succimer or placebo, there was no excess of any adverse event in either group, Alk P elevations occurred in 39% of both groups, ALT elevations greater than 2 times ULN occurred in 0.8% of succimer- and 1.1% in placebo-recipients, but were transient and confirmed on repeat testing in only 1 child).

  9. Chisolm JJ Jr. Safety and efficacy of meso-2,3-dimercaptosuccinic acid (DMSA) in children with elevated blood lead concentrations. J Toxicol Clin Toxicol 2000; 38: 365-75. PubMed Citation  (Among 59 children given 116 four-week courses of succimer for lead toxicity, lead levels fell rapidly on treatment, but rebounded to 58% of pretreatment values thereafter; there were no adverse reactions).

  10. Centers for Disease Control and Prevention (CDC). Deaths associated with hypocalcemia from chelation therapy--Texas, Pennsylvania, and Oregon, 2003-2005. MMWR Morb Mortal Wkly Rep 2006; 55: 204-7. PubMed Citation  (Description of 3 cases of sudden death from hypocalcemia caused by intravenous administration of Na2-EDTA as chelation for lead poisoning or as naturopathic chelation therapy to remove heavy metals; the patient with lead poisoning was also receiving oral succimer, and Na2-EDTA was mistakenly given instead of Ca-EDTA).

  11. Adams JB, Baral M, Geis E, Mitchell J, Ingram J, Hensley A, Zappia I, et al. Safety and efficacy of oral DMSA therapy for children with autism spectrum disorders: Part A.medical results. BMC Clin Pharmacol 2009; 9: 16. PubMed Citation  (Among 65 children with autism spectrum disorder, ages 3 to 8 years, treated with up to nine 3-day cycles of succimer therapy, urinary excretion of lead, tin, copper, manganese and bismuth increased significantly, and there was no significant change in any blood chemistry result).

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OTHER REFERENCE LINKS
Succimer
  1. PubMed logoRecent References on Succimer

  2. Clinical Trials logoTrials on Succimer

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