Succimer (Dimercaptosuccinic acid) is a chelating agent. It binds to heavy metals (lead, mercury, and arsenic) in the blood and makes them water-soluble which are then excreted from the body. It is primarily used to treat lead poisoning.

Succimer (Dimercaptosuccinic acid) Uses:

• Used to treat lead poisoning in children with serum lead levels >45 mcg/dL

• Off Label Use of Dimercaptosuccinic acid in Adults:

  • Lead poisoning
  • Mercury poisoning
  • Arsenic poisoning

Succimer (Dimercaptosuccinic acid) Dose in Adults 

Succimer Dose in the treatment of Lead poisoning (off-label use), arsenic poisoning (off-label use), mercury poisoning (off-label use):

Recommended as a chelating agent with blood lead levels >50 mcg/dL and significant symptoms; may also give chelation therapy with blood lead levels ≥100 mcg/dL and/or symptoms. It's highly recommended to consult a clinical or medical toxicologist or poison control center for patients who are being considered for chelation therapy.

• Oral: Using labeled dose should be cosnidered for children:
  • 10 mg/kg/dose (or 350 mg/m² /dose) every 8 hourly for 5 days, followed by 10 mg/kg/dose (or 350 mg/m² /dose) every 12 hourly for 14 days;
• The Maximum dose is 500 mg/dose.

Note:  May repeat treatment course, but it is recommended to put a gap of two weeks between courses for the lead to reequilibrate between the extravascular storage sites (eg, bone) and the vascular compartment.

Succimer (Dimercaptosuccinic acid) Dose in Childrens

Succimer Dose in the treatment of Lead poisoning:

Note:

• For the treatment of high blood lead levels in children, the CDC has recommended chelation treatment when blood lead levels are more than 45 mcg/dL.
• The AAP has recommended using succimer as the drug for initial treatment in children with no symptoms blood lead levels between >45 mcg/dL and <70 mcg/dL; parenteral therapy should be used in children with blood lead levels >70 mcg/dL or symptomatic lead poisoning.
• May repeat treatment course, but it is recommended to put a gap of two weeks between courses for the lead to reequilibrate between the extravascular storage sites (eg, bone) and the vascular compartment.
• May use succimer in patients who have received calcium disodium EDTA with or without BAL, after at least 4 weeks have passed since treatment.

• Children and Adolescents:

  • Oral: 10 mg/kg/dose (or 350 mg/m²/dose) thrice daily for 5 days followed by 10 mg/kg/dose (or 350 mg/m²/dose) twice daily for 14 days;
  • The maximum dose: 500 mg/dose.
  • Note: Body surface area should determine the dosing in children <5 years as per experts recommendation; doses should be rounded to the nearest 100 mg

Succimer Dosing adjustment for toxicity:

• Children and Adolescents:

  • ANC <1,200/mm³: As per the manufacturer treatment should be withheld; May resume treatment cautiously when ANC returns to baseline or >1,500/mm³. Must consult a medical toxicologist to determine the risk versus benefit of withholding treatment.

Pregnancy Risk Category: C

• Animal reproduction studies have shown adverse events.
• Lead poisoning: Lead crosses the placenta in amounts proportional to maternal plasma levels. Lead exposure prenatally may be linked to adverse events such as spontaneous abortion, preterm delivery, decreased birth weight, and impaired neurodevelopment. Maternal blood lead levels <10 mcg/dL may also result in some of the adverse outcomes.
• In addition, lead exposure during pregnancy may impose an increased risk of gestational hypertension.
• Chelation therapy should be considered in pregnant women with confirmed blood lead levels ≥45 mcg/dL (consider chelation therapy in pregnant women with blood lead levels ≥70 mcg/dL irrespective of trimester); must consult experts in lead poisoning and high-risk pregnancy. Treat encephalopathic pregnant women with chelation irrespective of the trimester.

Use during breastfeeding:

• Its presence in breast milk is not known.
• The amount of lead in breast milk may range from 0.6% to 3% of the maternal serum concentration during treatment for lead poisoning.
• Breastfeeding should not be started in women with confirmed blood lead levels ≥40 mcg/dL; it is recommended to pump and discard breast milk until blood lead levels are <40 mcg/dL, breastfeeding may be resumed at this point.
• The amount of lead in breast milk may be reduced with calcium supplementation.

Dose in Kidney Disease:

No dosage adjustments provided in the manufacturer's labeling; use cautiously. Succimer is dialyzable; however, the lead chelates are not.

Dose in Liver disease:

• No dosage adjustments provided in the manufacturer's labeling; no studies have been done.
• History of liver disease requires frequent monitoring of serum transaminases due to the risk of transient increases.

Side Effects of Dimercaptosuccinic acid (Succimer):

• Cardiovascular:

  • Cardiac arrhythmia

• Hepatic:

  • Increased serum transaminases

Less common side effects of Succimer:

• 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

Contraindications to Dimercaptosuccinic acid (Succimer):

• Hypersensitivity (to succimer or any component of the formulation)

Warnings and Precautions

• Hematologic effects:

  • Mild-to-moderate neutropenia may occur
  • CBC with differential should be done at baseline, weekly during treatment, and immediately upon the development of any sign of infection.
  • Withhold treatment for ANC <1200/mm
  • May resume treatment cautiously when ANC returns to baseline or >1500/mm.
  • Consult a medical toxicologist to determine the risk versus benefit of withholding treatment.

• Hepatic effects:

  • May cause transient elevations in serum transaminases.
  • Serum transaminases should be checked at baseline and weekly during treatment; history of liver disease requires more frequent monitoring.

• Hypersensitivity reactions:

  • Allergic or other mucocutaneous reactions may occur, monitor accordingly.
  • Rarely a reversible mucocutaneous vesicular eruption of the oral mucosa, external urethral meatus, or perianal area may occur.

• Encephalopathy:

  • The blood-brain barrier cannot be crossed by succimer, therefore, do not use for encephalopathy associated with lead toxicity.

• Lead poisoning:

  • Sources of lead exposure should be identified and removed before starting treatment; patients should not be allowed to re-enter the contaminated environment until lead abatement has been completed.
  • Consultation from the experts in chemotherapy of heavy metal toxicity should be sought by the primary care providers before using chelation drug therapy.
  • Succimer cannot prevent lead poisoning.
  • May cause a rebound rise in serum lead levels after treatment as lead is released from storage sites into the blood.
  • The frequency of future monitoring and the need for additional chelation therapy is determined by the severity of rebound.

• Renal impairment:

  • Use cautiously.
  • Succimer is dialyzable; however, the lead chelates are not.

Monitoring parameters:

• Blood lead levels (baseline and 7 to 21 days after completing chelation therapy)
• Serum aminotransferase (baseline and weekly during treatment; a history of liver disease demands more frequent monitoring)
• CBC with differential and platelets (baseline, and weekly during treatment);
• Hemoglobin or hematocrit, iron status, free erythrocyte protoporphyrin or zinc protoporphyrin
• Neurodevelopmental changes

How to administer Dimercaptosuccinic acid (Succimer)?

If cannot be swallowed as a whole, may separate the capsule and sprinkle the contents on a small amount of soft food, or place the contents on a spoon and take with a fruit drink.

Mechanism of action of Dimercaptosuccinic acid (Succimer):

• Succimer is a dimercaprol analog.
• It chelates with heavy metals to form water-soluble complexes which are subsequently excreted by kidneys.
• Succimer can bind to heavy metals; however, the chemical form of these chelates is unknown.

Absorption:

• Rapid but incomplete absorption

Distribution:

• Primarily extracellular

Protein binding:

• >95% primarily to albumin

Metabolism:

• Metabolized rapidly and extensively to mixed succimer cysteine disulfides

Half-life elimination:

• Almost 3 hours

Time to peak, serum:

• Almost 1 to 2 hours

Excretion:

• Almost 25% excreted via urine with peak urinary excretion between 2 to 4 hours (90% as mixed succimer-cysteine disulfide conjugates, 10% as unchanged drug)
• feces (as unabsorbed drug)

International Brand Names of Dimercaptosuccinic acid:

• Chemet
• Succicaptal

Dimercaptosuccinic acid Brand Names in Pakistan:

No Brands Available in Pakistan.