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تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
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Dimercaptosuccinic acid (succimer): Drug information

Dimercaptosuccinic acid (succimer): Drug information
(For additional information see "Dimercaptosuccinic acid (succimer): Patient drug information" and see "Dimercaptosuccinic acid (succimer): Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Chemet
Pharmacologic Category
  • Antidote
Dosing: Adult

Note: Consultation with a clinical toxicologist or an expert in the treatment of heavy metal poisoning is highly recommended.

Arsenic poisoning

Arsenic poisoning (off-label use): Dosing is based on the use of succimer for the treatment of lead poisoning (Howland 2018; Kosnett 2013). Consultation with a clinical toxicologist or poison control center is highly recommended in patients who are being considered for chelation therapy.

Oral: 10 mg/kg 3 times daily for 5 days followed by 10 mg/kg twice daily for 14 days (Howland 2018).

Lead poisoning

Lead poisoning (off-label use): Available guidelines recommend chelation therapy with blood lead levels (BLL) >50 mcg/dL and significant symptoms; chelation therapy may also be indicated for most patients with BLL ≥80 mcg/dL and all patients with BLL ≥100 mcg/dL and/or symptoms (CSTE 2013; Kosnett 2007). Selection of chelating regimen should be made in consultation with a clinical toxicologist or expert in the treatment of heavy metal poisoning.

Oral: 10 mg/kg 3 times daily for 5 days followed by 10 mg/kg twice daily for 14 days (Howland 2018).

Note: Treatment courses may be repeated, but 2-week intervals between courses is generally recommended because lead re-equilibrates between the extravascular storage sites (eg, bone) and the vascular compartment. High initial blood lead levels (eg, >100 mcg/dL) or presence of lead encephalopathy may indicate the need for more prompt retreatment (Howland 2018); consultation with a clinical toxicologist or poison control center is highly recommended.

Mercury poisoning

Mercury poisoning (off-label use): Dosing is based on the use of succimer for the treatment of lead poisoning (Howland 2018; Kosnett 2013). Consultation with a clinical toxicologist or poison control center is highly recommended in patients who are being considered for chelation therapy.

Oral: 10 mg/kg 3 times daily for 5 days followed by 10 mg/kg twice daily for 14 days (Howland 2018).

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; use with caution. Succimer is dialyzable; however, the lead chelates are not.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; has not been studied. More frequent monitoring of serum transaminases may be required in patients with a history of liver disease due to the risk of transient increases.

Dosing: Adjustment for Toxicity: Adult

ANC <1200 mm3: The manufacturer recommends withholding treatment; treatment may be cautiously resumed when ANC returns to baseline or >1500/mm3. Consultation with a medical toxicologist to determine the risk versus benefit of withholding treatment is recommended.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Dimercaptosuccinic acid (succimer): Pediatric drug information")

Note: Consultation with a clinical toxicologist, poison control center, or an expert in the treatment of heavy metal poisoning is highly recommended. Dosing is presented in both mg/kg and mg/m2; use caution.

Arsenic poisoning

Arsenic poisoning: Limited data available: Note: Dosing is based on the use of succimer for the treatment of lead poisoning (Howland 2018; Kosnett 2013). Experts recommend dosing for children <5 years of age should be based on body surface area (AAP 2005; Howland 2018).

Children <5 years: Oral: 350 mg/m2/dose every 8 hours for 5 days followed by 350 mg/m2/dose every 12 hours for 14 days; maximum dose: 500 mg/dose; round dose to the nearest 100 mg (Howland 2018).

Children ≥5 years and Adolescents: 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; round dose to the nearest 100 mg; maximum dose: 500 mg/dose (Howland 2018).

Lead poisoning, mild and asymptomatic

Lead poisoning, mild and asymptomatic:

Note: For the treatment of high blood lead levels (BLL) in children, the CDC recommends chelation treatment when BLL >45 mcg/dL (ACCLPP 2012; CDC 2002). The AAP recommends succimer as the drug used for initial management in asymptomatic children when BLL >45 mcg/dL and <70 mcg/dL; children with BLL ≥70 mcg/dL or symptomatic lead poisoning should be treated with parenteral agents (AAP [Shenoi 2020]; Calello 2018). Selection of chelating regimen should be made in consultation with a clinical toxicologist or expert in the treatment of heavy metal poisoning.

Children and Adolescents: 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 dose: 500 mg/dose; maximum daily dose: 1,500 mg/day. Note: Some experts recommend dosing for children <5 years of age should be based on body surface area (AAP 2005; Howland 2018); round doses to the nearest 100 mg.

Note: Treatment courses may be repeated, but 2-week intervals between courses is generally recommended because lead re-equilibrates between the extravascular storage sites (eg, bone) and the vascular compartment (Calello 2018).

Mercury poisoning

Mercury poisoning: Limited data available: Note: Dosing is based on the use of succimer for the treatment of lead poisoning (Howland 2018; Kosnett 2013). Experts recommend dosing for children <5 years of age should be based on body surface area (AAP 2005; Howland 2018); round doses to the nearest 100 mg.

Children <5 years: Oral: 350 mg/m2/dose every 8 hours for 5 days followed by 350 mg/m2/dose every 12 hours for 14 days; maximum dose: 500 mg/dose; round dose to the nearest 100 mg (Howland 2018).

Children ≥5 years and Adolescents: 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 dose: 500 mg/dose.

Dosing adjustment for toxicity: Children and Adolescents: ANC <1,200/mm3: The manufacturer recommends withholding treatment; treatment may be cautiously resumed when ANC returns to baseline or >1,500/mm3. Consultation with a clinical toxicologist to determine the risk versus benefit of withholding treatment is recommended.

Dosing: Kidney Impairment: Pediatric

Children and Adolescents: There are no dosage adjustments in the manufacturer's labeling; use with caution and monitor closely. Succimer is dialyzable; however, the lead chelates are not.

Dosing: Hepatic Impairment: Pediatric

Children and Adolescents: There are no dosage adjustments in the manufacturer's labeling; has not been studied. More frequent monitoring of serum transaminases may be required in patients with a history of liver disease due to the risk of transient increases.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

1% to 10%:

Cardiovascular: Cardiac arrhythmia (adults: 2%)

Hepatic: Increased serum transaminases (6% to 10%)

Frequency not defined:

Central nervous system: Chills, dizziness, drowsiness, fatigue, flank pain, headache, heavy headedness, metallic taste, paresthesia, sensorimotor neuropathy

Dermatologic: Mucocutaneous eruptions, papular rash, pruritus, skin rash, vesicular eruption (mucocutaneous)

Endocrine & metabolic: Increased serum cholesterol

Gastrointestinal: Abdominal cramps, decreased appetite, diarrhea, hemorrhoids, loose stools, nausea, sore throat, stomach pain, vomiting

Genitourinary: Decreased urine output, difficulty in micturition, proteinuria

Hematologic & oncologic: Eosinophilia, neutropenia, quantitative disorders of platelets (increase)

Hepatic: Increased serum alkaline phosphatase

Infection: Candidiasis, common cold, herpetic lesion

Neuromuscular & skeletal: Back pain, knee pain, lower extremity pain, rib pain

Ophthalmic: Cloudy vision (cloudy film in eye), watery eyes

Otic: Blockage of external ear, otitis media

Respiratory: Cough, flu-like symptoms, nasal congestion, rhinorrhea

Miscellaneous: Fever

<1%, postmarketing, and/or case reports: Angioedema, hypersensitivity reaction (especially with retreatment), urticaria

Contraindications

Hypersensitivity to succimer or any component of the formulation

Warnings/Precautions

Concerns related to adverse effects:

• Hematologic effects: Mild to moderate neutropenia has been reported; evaluate CBC with differential at baseline, weekly during treatment, and immediately upon the development of any sign of infection. The manufacturer recommends withholding treatment for ANC <1,200/mm3; treatment may be cautiously resumed when ANC returns to baseline or >1,500/mm3. Consultation with a clinical toxicologist to determine the risk versus benefit of withholding treatment is recommended.

• Hepatic effects: Transient elevations in serum transaminases have been reported. Evaluate serum transaminases at baseline and weekly during treatment; more frequent monitoring may be required in patients with a history of liver disease.

• Hypersensitivity reactions: Monitor for the development of allergic or other mucocutaneous reactions. A reversible mucocutaneous vesicular eruption of the oral mucosa, external urethral meatus, or perianal area has been reported (rarely).

Disease-related concerns:

• Encephalopathy: Succimer does not cross blood-brain barrier and should not be used to treat encephalopathy associated with lead toxicity.

• Lead poisoning: Investigate, identify, and remove sources of lead exposure prior to treatment; do not permit patients to reenter the contaminated environment until lead abatement has been completed. Consultation with a clinical toxicologist or an expert in the treatment of heavy metal poisoning is highly recommended before initiating chelation therapy. Succimer is not used to prevent lead poisoning. A rebound rise in serum lead levels may occur after treatment as lead is released from storage sites into blood. The severity of rebound may guide the frequency of future monitoring and the need for additional chelation therapy. In a small prospective, randomized, open-label trial, succimer was shown to improve clinical signs and symptoms of lead poisoning and to reduce blood lead levels more effectively than edetate calcium disodium (Sakthithasan 2018).

• 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.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Chemet: 100 mg

Generic Equivalent Available: US

No

Pricing: US

Capsules (Chemet Oral)

100 mg (per each): $26.44

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Administration: Adult

If unable to swallow whole, capsule may 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.

Administration: Pediatric

Oral: Ensure adequate patient hydration; for patients who cannot swallow the capsule whole, immediately prior to administration open the capsule and sprinkle the medicated beads into a small amount of juice or on a small amount of apple sauce, ice cream, or soft food or placed on a spoon and followed with fruit drink to mask the odor (Howland 2018).

Use: Labeled Indications

Lead poisoning: Treatment of lead poisoning in children with blood lead levels >45 mcg/dL.

Use: Off-Label: Adult

Lead poisoning; Mercury poisoning; Arsenic poisoning

Metabolism/Transport Effects

None known.

Drug Interactions

There are no known significant interactions.

Pregnancy Considerations

Adverse events were observed in animal reproduction studies.

Lead poisoning: Lead is known to cross the placenta in amounts related to maternal plasma levels. Prenatal lead exposure may be associated with adverse events such as spontaneous abortion, preterm delivery, decreased birth weight, and impaired neurodevelopment. Some adverse outcomes may occur with maternal blood lead levels <10 mcg/dL. In addition, pregnant women exposed to lead may have an increased risk of gestational hypertension. Consider chelation therapy in pregnant women with confirmed blood lead levels ≥45 mcg/dL (pregnant women with blood lead levels ≥70 mcg/dL should be considered for chelation regardless of trimester); consultation with experts in lead poisoning and high-risk pregnancy is recommended. Encephalopathic pregnant women should be chelated regardless of trimester (CDC 2010).

Breastfeeding Considerations

It is not known if succimer is excreted in breast milk. When used for the treatment of lead poisoning, the amount of lead in breast milk may range from 0.6% to 3% of the maternal serum concentration. Women with confirmed blood lead levels ≥40 mcg/dL should not initiate breastfeeding; pumping and discarding breast milk is recommended until blood lead levels are <40 mcg/dL, at which point breastfeeding may resume (CDC 2010). Calcium supplementation may reduce the amount of lead in breast milk.

Monitoring Parameters

Blood lead levels (baseline and 7 to 21 days after completing chelation therapy); serum transaminases (baseline and weekly during treatment; may require more frequent monitoring in patients with a history of liver disease), CBC with differential and platelets (baseline, and weekly during treatment); hemoglobin or hematocrit, iron status, free erythrocyte protoporphyrin or zinc protoporphyrin; neurodevelopmental changes.

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.

Pharmacokinetics (Adult Data Unless Noted)

Absorption: Rapid but incomplete

Distribution: Primarily extracellular (Aposhian 1992)

Protein binding: >95% primarily to albumin (Aposhian 1992)

Metabolism: Rapidly and extensively to mixed succimer cysteine disulfides

Half-life elimination: ~3 hours (Aposhian 1992)

Time to peak, serum: ~1 to 2 hours

Excretion: Urine (~25%) with peak urinary excretion between 2 to 4 hours (90% as mixed succimer-cysteine disulfide conjugates, 10% as unchanged drug); feces (as unabsorbed drug)

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (CH) Switzerland: Succicaptal;
  • (CO) Colombia: Chemet;
  • (CZ) Czech Republic: Succicaptal;
  • (FR) France: Succicaptal;
  • (GR) Greece: Succicaptal;
  • (NO) Norway: Succicaptal;
  • (PL) Poland: Succicaptal;
  • (PR) Puerto Rico: Chemet;
  • (PT) Portugal: Chemet
  1. Advisory Committee on Childhood Lead Poisoning Prevention (ACCLPP). Low-level lead exposure harms children: A renewed call for primary intervention. January 4, 2012. Available at http://www.cdc.gov/nceh/lead/acclpp/final_document_030712.pdf . Last accessed on March 17, 2017)
  2. Agency for Toxic Substances & Disease Registry (ATSDR). Medical management guidelines for arsenic (As) and inorganic arsenic compounds. 2014a. Available at: https://www.atsdr.cdc.gov/MHMI/mmg2.pdf
  3. Agency for Toxic Substances & Disease Registry (ATSDR). Medical management guidelines for mercury (Hg). 2014b. Available at: https://www.atsdr.cdc.gov/MHMI/mmg46.pdf
  4. American Academy of Pediatrics Committee on Environmental Health. Lead exposure in children: prevention, detection, and management. Pediatrics. 2005;116(4):1036-1046. doi:10.1542/peds.2005-1947 [PubMed 16199720]
  5. Andersen O. Principles and recent developments in chelation treatment of metal intoxication. Chem Rev. 1999;99(9):2683-2710. [PubMed 11749497]
  6. Aposhian HV, Maiorino RM, Rivera M, et al, “Human Studies With the Chelating Agents, DMPS and DMSA,” Clin Toxicol, 1992, 30(4):505-28. [PubMed 1331491]
  7. Bradberry S and Vale A, "Dimercaptosuccinic Acid (Succimer; DMSA) in Inorganic Lead Poisoning," Clin Toxicol (Phila), 2009, 47(7):617-31. [PubMed 19663612]
  8. Calello DP, Henretig FM. Lead. In: Nelson LS, Howland MA, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS, eds. Goldfrank's Toxicologic Emergencies. 11th ed. McGraw-Hill; 2018: 1292-1308.
  9. Centers for Disease Control and Prevention (CDC), Guidelines for the Identification and Management of Lead Exposure in Pregnant and Lactating Women, Atlanta: CDC; 2010.
  10. 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.
  11. Chemet (succimer) [prescribing information]. Lebanon, NJ: Recordati Rare Diseases Inc; October 2018.
  12. Crinnion WJ, "EDTA Redistribution of Lead and Cadmium into Soft Tissues in a Human With a High Lead Burden: Should DMSA Always be used to Follow EDTA in Such Cases?" Alt Med Rev, 2011, 16(2):109-112. [PubMed 21649453]
  13. Council of State and Territorial Epidemiologists (CSTE). Management guidelines for blood lead levels in adults. https://dhhs.ne.gov/Lead%20Documents/Adult-Lead-Management-Guidelines.pdf. Published June 12, 2013. Accessed February 14, 2022.
  14. Dart RC, Goldfrank LR, Erstad BL, et al. Expert consensus guidelines for stocking of antidotes in hospitals that provide emergency care. Ann Emerg Med. 2018;71(3):314-325.e1. doi:10.1016/j.annemergmed.2017.05.021 [PubMed 28669553]
  15. 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. [PubMed 8040783]
  16. Drasch G, Boese-O'Reilly S, Illig S. Increase of renal excretion of organo-mercury compounds like methylmercury by DMPS (2,3-dimercapto-1-propanesulfonic acid, dimaval). Clin Toxicol (Phila). 2007;45(3):266-269. [PubMed 17453878]
  17. 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. [PubMed 11285436]
  18. Gracia RC and Snodgrass WR, “Lead Toxicity and Chelation Therapy,” Am J Health Syst Pharm, 2007, 64(1):45-53. [PubMed 17189579]
  19. Howland MA. Antidotes in depth: succimer (2,3-dimercaptosuccinic acid) and DMPS (2,3-dimercapto-1-propanesulfonic acid). In: Nelson LS, Howland MA, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS, eds. Goldfrank's Toxicologic Emergencies. 11th ed. McGraw-Hill; 2018.
  20. Kosnett MJ. The role of chelation in the treatment of arsenic and mercury poisoning. J Med Toxicol. 2013;9(4):347-354. doi:10.1007/s13181-013-0344-5 [PubMed 24178900]
  21. Kosnett MJ, Wedeen RP, Rothenberg SJ, et al. Recommendations for medical management of adult lead exposure. Environ Health Perspect. 2007;115(3):463-471. doi:10.1289/ehp.9784 [PubMed 17431500]
  22. Mann KV and Travers JD, “Succimer, An Oral Lead Chelator,” Clin Pharm, 1991, 10(12):914-22. [PubMed 1663439]
  23. Sakthithasan K, Lévy P, Poupon J, Garnier R. A comparative study of edetate calcium disodium and dimercaptosuccinic acid in the treatment of lead poisoning in adults. Clin Toxicol (Phila). 2018;56(11):1143-1149. doi:10.1080/15563650.2018.1478424 [PubMed 29889577]
  24. Shenoi RP, Timm N; Committee on Drugs; Committee on Pediatric Emergency Medicine. Drugs Used to Treat Pediatric Emergencies. Pediatrics. 2020;145(1):e20193450. [PubMed 31871244]
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