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Pronunciation
(SUKS si mer)
U.S. Brand Names
Index Terms
Generic Available
No
Canadian Brand Names
Pharmacologic Category
Use: Labeled Indications
Treatment of lead poisoning in children with serum lead levels >45 mcg/dL
Use: Unlabeled/Investigational
Treatment of lead poisoning in symptomatic adults
Pregnancy Risk Factor
C
Pregnancy Considerations
Adverse events were observed in animal reproduction studies. Following maternal occupational exposure, lead crosses the placenta in amounts related to maternal plasma levels. Possible outcomes of maternal lead exposure >10 mcg/dL includes spontaneous abortion, postnatal developmental delay, and reduced birth weight. Chelation therapy during pregnancy is for maternal benefit only and should be limited to the treatment of severe, symptomatic lead poisoning.
Lactation
Excretion in breast milk unknown/not recommended
Breast-Feeding Considerations
It is not known if succimer is found in breast milk. The amount of lead in breast milk may range from 0.6% to 3% of the maternal serum concentration. Calcium supplementation may reduce the amount of lead in breast milk.
Contraindications
Hypersensitivity to succimer or any component of the formulation
Warnings/Precautions
Disease-related concerns:
• Lead poisoning: Investigate, identify, and remove sources of lead exposure prior to treatment. Succimer is not used to prevent lead poisoning. Primary care providers should consult experts in chemotherapy of lead toxicity before using chelation drug therapy.
• Encephalopathy: Succimer does not cross blood brain barrier and should not be used to treat encephalopathy associated with lead toxicity.
• Hepatic impairment: Use with caution in patients with hepatic impairment; monitor serum transaminase levels closely.
• Renal impairment: Use with caution in patients with renal impairment. Succimer is dialyzable, however, the lead chelates are not.
Other warnings/precautions:
• Hydration: Adequate hydration should be maintained during therapy.
• Rebounding serum lead levels: May occur after treatment as lead is released from storage sites into blood. Severity of rebound may guide intensity of future monitoring.
Adverse Reactions
Note: Percentages as reported in pediatric patients unless otherwise noted.
>10%: Gastrointestinal: Appetite decreased, diarrhea, hemorrhoid symptoms, metallic taste, loose stools, nausea, vomiting
1% to 10%:
Cardiovascular: Arrhythmia (adults 2%)
Central nervous system: Chills, dizziness, drowsiness, fatigue, fever, headache, sleepiness
Dermatologic: Rash (including papular rash, herpetic rash and mucocutaneous eruptions); pruritus
Endocrine & metabolic: Cholesterol increased
Gastrointestinal: Abdominal cramps, mucosal irritation, sore throat
Genitourinary: Proteinuria (adults), urine output decreased (adults), voiding difficulty (adults)
Hepatic: ALT/AST and alkaline phosphatase increased
Neuromuscular & skeletal: Back pain, flank pain, leg pain (adults), neuropathy, paresthesia, rib pain
Ocular: Cloudy film in eye, watery eyes
Otic: Otitis media, plugged ears
Respiratory: Cough, nasal congestion, rhinorrhea
Miscellaneous: Flu-like syndrome, moniliasis
<1%, postmarketing, and/or case reports: Allergic reactions (especially with retreatment), eosinophilia, neutropenia (causal relationship not established)
Drug Interactions
There are no known significant interactions.
Storage
Store between 15°C to 25?C (59?F to 77?F); avoid excessive heat.
Mechanism of Action
Succimer is an analog of dimercaprol. It forms water soluble chelates with heavy metals which are subsequently excreted renally. Succimer binds heavy metals; however, the chemical form of these chelates is not known.
Pharmacodynamics/Kinetics
Absorption: Rapid but incomplete
Protein binding: Highly bound to albumin
Metabolism: Rapidly and extensively to mixed succimer cysteine disulfides
Half-life elimination: 2 days
Time to peak, serum: ~1-2 hours
Excretion: Urine (~25%) with peak urinary excretion between 2-4 hours (90% as mixed succimer-cysteine disulfide conjugates, 10% as unchanged drug); feces (as unabsorbed drug)
Dosage
Note: For the treatment of high blood lead levels in children, the CDC recommends chelation treatment when blood lead levels are >45 mcg/dL (CDC, 2002). Children with blood lead levels >70 mcg/dL or symptomatic lead poisoning should be treated with parenteral agents (AAP, 2005). In adults, available guidelines recommend chelation therapy with blood lead levels >50 mcg/dL and significant symptoms; chelation therapy may also be indicated with blood lead levels ?100 mcg/dL and/or symptoms. (Kosnett, 2007).
Children: Oral: 10 mg/kg/dose (or 350 mg/m2/dose) every 8 hours for 5 days followed by 10 mg/kg/dose (or 350 mg/m2/dose) every 12 hours for 14 days. Maximum: 500 mg/dose. For children <5 years of age, dose should be based on mg/m2; dosing by mg/kg may be suboptimal.
Adults (mild symptoms or blood lead levels 70-100 mg/dL; unlabeled use): 10 mg/kg/dose (or 350 mg/m2/dose) every 8 hours for 5 days, followed by 10 mg/kg/dose (or 350 mg/m2/dose) every 12 hours for 14 days; Maximum: 500 mg/dose
Note: Treatment courses may be repeated, but 2-week intervals between courses is generally recommended.
Dosing adjustment in renal/hepatic impairment: Administer with caution and monitor closely
Administration: Oral
Capsule can be separated and contents sprinkled on a small amount of soft food, or the contents placed on a spoon and administered followed by fruit drink.
Monitoring Parameters
Blood lead levels (baseline and 7-21 days after completing chelation therapy); serum aminotransferase, CBC with differential, platelets (baseline, and weekly during treatment); hemoglobin or hematocrit, iron status, free erythrocyte protoporphyrin or zinc protoporphyrin; neurodevelopmental changes
Test Interactions
False-positive ketones (U) using nitroprusside methods, falsely decreased serum CPK; falsely decreased uric acid measurement
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause drowsiness or dizziness
Mental Health: Effects on Psychiatric Treatment
None reported
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule:
Chemet®:100 mg
References
Centers for Disease Control and Prevention (CDC), Managing Elevated Blood Lead Levels Among Young Children: Recommendations from the Advisory Committee on Childhood Lead Poisoning Prevention, Atlanta: CDC; 2002.
Centers for Disease Control and Prevention (CDC), “Interpreting and Managing Blood Lead Levels <10 microg/dL in Children and Reducing Childhood Exposures to Lead: Recommendations of CDC's Advisory Committee on Childhood Lead Poisoning Prevention,” MMWR Recomm Rep, 2007, 56(RR-8):1-16.
Dart RC, Hurlburt KM, Maiorino RM, et al, “Pharmacokinetics of Meso-2,3-Dimercaptosuccinic Acid in Patients With Lead Poisoning and in Healthy Adults,” J Pediatr, 1994, 125(2):309-16.
Fournier L, Thomas G, Garnier R, et al, “2,3-Dimercaptosuccinic Acid Treatment of Heavy Metal Poisoning in Humans,” Med Toxicol Adverse Drug Exp, 1988, 3(6):499-504.
Gardella C, “Lead Exposure in Pregnancy: A Review of the Literature and Argument for Routine Prenatal Screening,” Obstet Gynecol Surv, 2001, 56(4):231-8.
Glotzer DE, “The Current Role of 2,3 Dimercaptosuccinic Acid (DMSA) in Management of Childhood Lead Poisoning,” Drug Saf, 1993, 9(2):85-92.
Gracia RC and Snodgrass WR, “Lead Toxicity and Chelation Therapy,” Am J Health Syst Pharm, 2007, 64(1):45-53.
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(1):133-9.
Kosnett MJ, Wedeen RP, Rothenberg SJ, et al, “Recommendations for Medical Management of Adult Lead Exposure,” Environ Health Perspect, 2007, 115(3):463-71.
“Lead Exposure in Children: Prevention, Detection, and Management. American Academy of Pediatrics Committee on Environmental Health,” Pediatrics, 2005, 116(4):1036-46.
Mann KV and Travers JD, “Succimer, An Oral Lead Chelator,” Clin Pharm, 1991, 10(12):914-22.
Marcus S, Okose P, Jennis T, et al, “Untoward Effects of Oral Dimercaptosuccinic Acid in the Treatment for Lead Poisoning,” Vet Hum Toxicol, 1991, 33:376.
Shannon M, “Severe Lead Poisoning in Pregnancy,” Ambul Pediatr, 2003, 3(1):37-9.
Staudinger KC and Roth VS, “Occupational Lead Poisoning,” Am Fam Physician, 1998, 57(4):719-26.
International Brand Names
Lexi-Comp.com
Last full review/revision August 2008
Content last modified August 2008
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