Dimercaptosuccinic acid

Table of contents

• What is dimercaptosuccinic acid?
• How does dimercaptosuccinic acid work?
• Which conditions is it used or studied for?
• How is dimercaptosuccinic acid given?
• What do the clinical trials show?
• What side effects are known?

What is dimercaptosuccinic acid?

Dimercaptosuccinic acid (DMSA) is a chelating agent, a substance that binds to metals in the body. It is classified as technetium (99mTc) succimer (ATC code V09CA02) when used as a radiopharmaceutical.^[1] The registry lists it as a mixture of chemical origin, supplied as a kit for radiopharmaceutical preparation under the product name RENOCIS 1 mg kit for radiopharmaceutical preparation.^[1] DMSA is authorised as a medicine, with the authorisation held by CIS BIO INTERNATIONAL.^[1] The same substance is also available as an oral capsule called CHEMET, approved in the United States since 1982 for treating lead poisoning.^[3]

How does dimercaptosuccinic acid work?

DMSA works by chelation, meaning it binds to metals and helps remove them from the body. As an oral medicine, succimer binds to lead in the blood so that the lead can be excreted.^[3] As a radiopharmaceutical, DMSA is labelled with the radioactive isotope technetium-99m (99mTc). When injected intravenously, it is taken up by the renal proximal tubules, allowing doctors to measure how well the kidneys reabsorb low-molecular-weight proteins (LMWPs).^[1] In the trial, improvement in renal uptake of 99mTc-DMSA is used as a measure of the reabsorption capacity of renal proximal tubules.^[1]

Which conditions is it used or studied for?

• Lead poisoning — CHEMET capsules are indicated for treating lead poisoning in children aged 1 year and older with blood lead levels above 45 mcg/dL.^[3]
• Dent 2 disease — 99mTc-DMSA is used in a phase 2 trial to measure kidney reabsorption capacity in patients with this rare kidney disorder.^[1]
• Kidney imaging — as a radiopharmaceutical, 99mTc-DMSA is used to assess renal function through imaging.^[1]

How is dimercaptosuccinic acid given?

DMSA is available in two different forms. As a radiopharmaceutical, it is supplied as a kit for radiopharmaceutical preparation and given by intravenous injection or intravenous infusion.^[1] As an oral medicine, succimer is available as 100 mg capsules (CHEMET) for oral use. The prescribing information describes a dosage of 10 mg/kg or 350 mg/m² orally every 8 hours for five days, followed by every 12 hours for an additional 14 days.^[3]

What do the clinical trials show?

One authorised phase 2 pilot study (2024-514196-17-00) is listed in the EU Clinical Trials Information System. The ALPEDENT study is a no-profit, open-label trial testing the efficacy and safety of alpelisib in patients with Dent 2 disease.^[1] In this trial, DMSA serves as an auxiliary substance: the radiopharmaceutical 99mTc-DMSA is used to measure the primary outcome, which is improvement in renal uptake after 4 weeks of treatment, with a p-value of ≤ 0.05 considered statistically significant.^[1]

The trial plans to enrol 4 participants. Patients are treated for 4 weeks at a starting oral dose of alpelisib 50 mg/day for 1 week, followed by 150 mg/day for 3 weeks.^[1] The study is currently authorised, meaning it has received regulatory approval to proceed.^[1]

What side effects are known?

The oral form of succimer (CHEMET) is associated with hypersensitivity and dermatologic reactions, including rash and mucocutaneous vesicular eruptions, which may require interrupting treatment.^[3] Neutropenia, a low count of a type of white blood cell, has also been reported; monitoring of complete blood counts is recommended.^[3] In an animal study of DMSA-coated iron oxide nanoparticles, changes in liver enzymes were observed in mice, particularly at concentrations above 100 mg per kg of body weight, though no irreversible effects were seen below 200 mg/kg.^[2]