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Dimercaptosuccinic acid (succimer): Pediatric drug information

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

For abbreviations, symbols, and age group definitions show table
Brand Names: US
  • Chemet
Therapeutic Category
  • Antidote, Lead Toxicity;
  • Chelating Agent, Oral
Dosing: Pediatric

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.

Dosing: Adult

(For additional information see "Dimercaptosuccinic acid (succimer): Drug information")

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.

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: 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).

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.

Storage/Stability

Store between 15°C to 25°C (59°F to 77°F); avoid excessive heat.

Pharmacy supply of emergency antidotes: Guidelines suggest that at least 1 to 3 g of succimer be stocked, especially in locations with a historical rate of pediatric lead poisonings. Suggested amount is stated to be a sufficient quantity to treat 1 patient weighing 100 kg for an initial 8- to 24-hour period (Dart 2018); actual amount to be stocked should take into account site-specific and population-specific needs.

Use

Treatment of lead poisoning in patients with blood levels >45 mcg/dL (FDA approved in pediatric patients ≥1 year of age); has also been used for arsenic and mercury poisoning.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program

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).

Monitoring Parameters

Blood lead concentrations (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;
  • (QA) Qatar: Chemet
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