Dimercaptosuccinic acid, often abbreviated as DMSA, is a chelating agent used in medicine to treat heavy metal poisoning. It is also employed in imaging studies to assess renal (kidney) function. The chemical structure of dimercaptosuccinic acid includes two thiol (sulfhydryl) groups, which are responsible for its chelating properties.

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):

To treat lead poisoning with dimercaptosuccinic acid (DMSA), the recommended dose depends on the blood lead levels and symptoms:

• High Blood Lead Levels in Adults:
  • Chelation therapy is recommended if blood lead levels are greater than 50 mcg/dL and there are significant symptoms.
  • Chelation therapy may also be considered if blood lead levels are equal to or greater than 100 mcg/dL and/or there are symptoms.
• Consultation Recommendation:
  • It's highly recommended to consult with a clinical or medical toxicologist or a poison control center before starting chelation therapy.
• Oral Dosing for Children:
  • Use the labeled dose for children: 10 mg/kg/dose (or 350 mg/m²/dose) every 8 hours for 5 days.
  • After the initial 5 days, administer 10 mg/kg/dose (or 350 mg/m²/dose) every 12 hours for the next 14 days.
  • The maximum dose per administration is 500 mg.
• Note on Treatment Courses:
  • Treatment courses can be repeated if necessary.
  • However, it is generally recommended to wait at least 2 weeks between courses.
  • This interval is advised because lead redistributes between storage sites (like bone) and the bloodstream.

In summary, the treatment involves an initial 5-day period followed by a 14-day period for children, with doses based on their weight or body surface area.

Succimer (Dimercaptosuccinic acid) Dose in Childrens

Succimer Dose in the treatment of Lead poisoning:

For the treatment of lead poisoning in children, the recommended dose of dimercaptosuccinic acid (DMSA) is as follows:

• Criteria for Treatment:
  • Chelation treatment is recommended for high blood lead levels in children (>45 mcg/dL), according to the CDC (Centers for Disease Control and Prevention).
  • The AAP (American Academy of Pediatrics) recommends using succimer as the initial drug for asymptomatic children with blood lead levels >45 mcg/dL and <70 mcg/dL. For children with blood lead levels >70 mcg/dL or those with symptomatic lead poisoning, parenteral agents are recommended.
• Treatment Courses:
  • Treatment courses may be repeated, but it's generally advised to wait at least 2 weeks between courses.
  • Children who have previously received calcium disodium EDTA with or without BAL (British Anti-Lewisite) may be treated with succimer after at least 4 weeks have passed since the last treatment.
• Oral Dosing for Children and Adolescents:
  • Administer 10 mg/kg/dose (or 350 mg/m²/dose) every 8 hours for the first 5 days.
  • Follow the initial phase with 10 mg/kg/dose (or 350 mg/m²/dose) every 12 hours for the next 14 days.
  • The maximum dose per administration is 500 mg.
• Dosing Adjustment for Toxicity:
  • If the absolute neutrophil count (ANC) is less than 1,200/mm³, the manufacturer recommends withholding treatment.
  • Treatment may be cautiously resumed when the ANC returns to baseline or is greater than 1,500/mm³.
  • Consultation with a medical toxicologist is recommended to assess the risk versus benefit of withholding treatment in these cases.

Note: Dosing for children under 5 years of age should be based on body surface area, and doses should be rounded to the nearest 100 mg according to expert recommendations.

Pregnancy Risk Category: C

• Adverse effects were noticed in studies with animals during reproduction.
• When it comes to lead poisoning, lead can pass from the mother to the baby in the womb.
• This prenatal exposure to lead may lead to problems like miscarriage, having the baby too early, lower birth weight, and difficulties with brain development.
• Even if the mother's blood lead levels are below 10 mcg/dL, there could still be negative outcomes.
• Pregnant women exposed to lead might also have a higher chance of experiencing high blood pressure during pregnancy.
• If a pregnant woman has confirmed blood lead levels of 45 mcg/dL or higher, it's advisable to think about chelation therapy (a treatment to remove heavy metals from the body).
• If the blood lead levels are 70 mcg/dL or higher, chelation should be considered, no matter the trimester.
• It's essential to consult with experts in lead poisoning and high-risk pregnancy, and if a pregnant woman is encephalopathic (having brain-related symptoms), chelation is recommended regardless of the trimester, according to the CDC in 2010.

Use during breastfeeding:

• It's uncertain whether succimer, a medication used for treating lead poisoning, is passed into breast milk.
• When succimer is used to treat lead poisoning, the lead concentration in breast milk can vary, ranging from 0.6% to 3% of the amount found in the mother's blood.
• If a woman has confirmed blood lead levels of 40 mcg/dL or higher, it's advised that she should not start breastfeeding.
• Instead, pumping and discarding breast milk is recommended until blood lead levels drop below 40 mcg/dL.
• Once the levels are below this threshold, breastfeeding can be resumed, according to the CDC in 2010.
• Additionally, taking calcium supplements might help reduce the amount of lead in breast milk.

Dose in Kidney Disease:

• The medication succimer doesn't come with specific dosage adjustments in the manufacturer's instructions, so it should be used carefully.
• Succimer can be removed through a process called dialysis, but it's important to note that the chelates that bind to lead, the main reason for using succimer, are not removed by dialysis.
• This means that even though succimer itself can be filtered out by dialysis, the parts of it that grab onto and help get rid of lead stay in the body.

Dose in Liver disease:

• The manufacturer's instructions for this medication do not include any recommended changes to the dosage, and there hasn't been specific research on this topic.
• However, it's important to note that in individuals with a history of liver disease, there might be a need for more frequent monitoring of serum transaminases.
• This monitoring is essential because there is a potential risk of temporary increases in these liver enzymes.

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):

• If you are sensitive or allergic to succimer or any part of the medicine, you should avoid using it.
• This condition is called hypersensitivity, and it means that your body might react negatively to the medication or its ingredients.
• If you experience any signs of an allergic reaction, like rash, swelling, or difficulty breathing, it's crucial to seek medical help immediately.

Warnings and Precautions

Hematologic effects:

• The use of this medication can sometimes affect the blood, leading to mild-to-moderate neutropenia (a decrease in a type of white blood cells called neutrophils).
• To monitor this, it's advised to check a complete blood count (CBC) with differential at the beginning of treatment, weekly during the treatment, and right away if any signs of infection appear.
• If the absolute neutrophil count (ANC) drops below 1200/mm³, the manufacturer recommends stopping the treatment.
• It can be cautiously resumed once the ANC returns to the normal baseline or goes above 1500/mm³.
• It's crucial to talk to a medical toxicologist to carefully weigh the risks and benefits before deciding to stop or continue the treatment, especially in cases where the ANC is low.

Hepatic effects:

• This medication can temporarily increase the levels of certain enzymes in the liver, known as serum transaminases.
• To keep an eye on this, it's recommended to check these liver enzymes before starting the treatment and then every week while undergoing the treatment.

Hypersensitivity reactions:

• While using this medication, it's important to watch out for any signs of hypersensitivity reactions, which are allergic or other skin-related reactions.
• Keep an eye out for any unusual skin reactions or changes in mucous membranes.
• In rare cases, there have been reports of a reversible skin eruption with small blisters in areas like the mouth, external urethral meatus (urinary opening), or the skin around the anus.

Encephalopathy:

• Succimer, the medication used for lead toxicity, doesn't go into the brain because it can't cross the blood-brain barrier.
• This means it should not be used to treat encephalopathy, which is a condition involving the brain, associated with lead toxicity.
• If someone has symptoms of encephalopathy due to lead exposure, other treatments or interventions may be necessary.

Lead poisoning:

• When dealing with lead poisoning, it's crucial to first investigate, identify, and eliminate sources of lead exposure before starting treatment.
• Patients should not return to a contaminated environment until lead removal measures are finished.
• Before using chelation drug therapy, primary care providers should consult with experts who specialize in treating heavy metal toxicity.
• It's important to note that succimer, a chelation drug, is not used to prevent lead poisoning but rather to treat it.
• After treatment, there may be a temporary increase in blood lead levels as lead is released from storage sites.
• The seriousness of this rebound can influence how often future monitoring is needed and whether additional chelation therapy is necessary.

Renal impairment:

• If you have kidney problems, it's important to be cautious when using succimer.
• This medication can be eliminated through dialysis, a process that helps the kidneys filter waste from the blood.
• However, it's essential to note that while succimer itself can be removed by dialysis, the lead chelates, which are the substances that bind to lead and help remove it from the body, are not eliminated through dialysis.
• Therefore, even if the medication is removed, the part that works to get rid of lead stays in the body.

Monitoring parameters:

• Blood Lead Levels:
  • Check levels before starting treatment.
  • Monitor 7 to 21 days after completing chelation therapy.
• Liver Function (Serum Aminotransferase):
  • Assess baseline levels.
  • Weekly monitoring during treatment.
  • Consider more frequent checks for individuals with a history of liver disease.
• Complete Blood Count (CBC) with Differential and Platelets:
  • Evaluate baseline levels.
  • Weekly monitoring during treatment.
• Hemoglobin, Hematocrit, Iron Status, Free Erythrocyte Protoporphyrin or Zinc Protoporphyrin:
  • Assess these factors before starting treatment.
• Neurodevelopmental Changes:
  • Regularly evaluate for any changes in neurodevelopmental status.

Regular monitoring of these factors helps ensure the effectiveness and safety of the treatment for lead poisoning.

How to administer Dimercaptosuccinic acid (Succimer)?

If you find it difficult to swallow the whole capsule, here's an alternative way to take it:

• Separate and Sprinkle:
  • Open the capsule.
  • Sprinkle the contents on a small amount of soft food.
• Direct Spoon Administration:
  • Alternatively, you can place the contents directly on a spoon.
• Take with Fruit Drink:
  • Administer the contents followed by a fruit drink.

This method allows for easier ingestion, especially for those who may have difficulty swallowing pills.

Mechanism of action of Dimercaptosuccinic acid (Succimer):

• Succimer is similar to another substance called dimercaprol.
• It works by creating water-soluble combinations with heavy metals, and then the body gets rid of them through the kidneys.
• Succimer attaches to heavy metals, but we're not exactly sure about the specific chemical makeup of these combinations.
• Essentially, it helps the body remove heavy metals, but the exact way it does this is still a bit of a mystery.

Absorption:

• Succimer is absorbed quickly, but the absorption process is not entirely complete.

Distribution:

• The substance is mainly found outside cells, primarily in the extracellular space (Aposhian 1992).

Protein Binding:

• More than 95% of succimer binds mainly to a protein called albumin (Aposhian 1992).

Metabolism:

• Succimer is rapidly and extensively transformed into mixed succimer cysteine disulfides.

Half-life Elimination:

• The time it takes for half of the succimer to leave the body is approximately 3 hours (Aposhian 1992).

Time to Peak, Serum:

• It takes about 1 to 2 hours for succimer to reach its highest concentration in the bloodstream.

Excretion:

• The body eliminates succimer mainly through urine (about 25%), with the highest urinary excretion between 2 to 4 hours.
• This elimination includes 90% as mixed succimer-cysteine disulfide conjugates and 10% as unchanged drug. Some of it is also excreted in the feces as unabsorbed drug.

International Brand Names of Dimercaptosuccinic acid:

• Chemet
• Succicaptal

Dimercaptosuccinic acid Brand Names in Pakistan:

Not Available.