Lead Toxicity Medication

Updated: Apr 23, 2018
  • Author: Pranay Kathuria, MD, FACP, FASN, FNKF; Chief Editor: Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS  more...
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Medication

Medication Summary

The mainstay of treatment is chelation therapy. Chelation agents contain sulfhydryl groups that bind or chelate lead, and the resulting complex is excreted either renally or hepatically. The chelation agents succimer and penicillamine are given orally, whereas dimercaprol and edetate (EDTA) calcium disodium (CaNa2 EDTA) are administered parenterally.

These agents reduce body stores of lead. Reducing blood lead levels also may mobilize skeletal stores of lead. Therefore, caution must be exercised in using chelation agents, both because of their adverse effects and because of their ability to mobilize lead.

Dimercaptopropanesulfonic acid (DPMS) has received much attention worldwide, but it is not yet available in the United States, except under special FDA Investigational New Drug (IND) permits. In Europe and Asia, DPMS has become the drug of choice for most heavy metal intoxications. It is available both in an oral form and in a water-based parenteral form.

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Antidotes

Class Summary

Antidotes are used to prevent intoxication resulting from lead poisoning. These agents bind lead in the vascular compartment and prevent it from reaching the end organs of toxicity. Chelators promote the excretion of lead.

Succimer (Chemet)

Succimer, or meso 2,3-dimercaptosuccinic acid (DMSA), is an analogue of dimercaprol used in lead poisoning. It has high sensitivity for lead, but its ability to chelate essential trace metals is low. It is available as capsules of 100 mg. Succimer is generally well tolerated after oral (PO) administration and produces a linear dose-dependent reduction in serum lead concentration. It forms a water-soluble chelate with heavy metals and is excreted in urine. It produces plumburesis approaching that achieved with the combination of CaNa2EDTA and dimercaprol.

In January 1991, succimer became the only drug approved by the US Food and Drug Administration (FDA) specifically for lead chelation in children and the only drug approved to treat a specific laboratory test—namely, a blood lead level (BLL) higher than 45 µg/dL (2.17 mmol/L). It has been shown to be an effective oral chelator.

Although never a substitute for careful environmental controls, succimer produces a rapid decline in lead level and reverses many of the biochemical indicators of toxicity. It is not currently licensed for use in adults. Although experience suggests that this agent is safe and effective, its use must be considered carefully. Adults exposed from an occupational source must be carefully excluded from further exposure.

Patients with extremely high lead levels may experience abnormalities in gastrointestinal (GI) motility; thus, the absorption of succimer may be unpredictable or erratic. Use of this agent in patients with lead levels higher than 60 µg/dL has not been carefully studied. Therefore, consideration should be given to the use of parenteral therapy until lead levels drop below this value.

Edetate calcium disodium

CaNa2EDTA is nearly the perfect chelator. It is water-soluble, can be administered either intravenously (IV) or intramuscularly (IM), allows lead to be renally eliminated, is not metabolized, and has few toxic effects. Its main limitation is that it removes lead from extracellular spaces only.

CaNa2EDTA should generally be given IV, diluted to a concentration of less than 0.5% in 5% dextrose in water (D5W) or isotonic saline. In patient with acute lead encephalopathy and increased intracranial pressure, dilution to concentration of less than 3.0% may be necessary, or the IM route may be preferred to limit fluids. Ideally, the first dose of dimercaprol should be given at least 4 hours before CaNa2EDTA. Note that CaNa2EDTA initially may aggravate symptoms of lead toxicity because of its mobilization of stored lead.

CaNa2EDTA may induce central nervous system (CNS) toxicity if BAL therapy is not initiated first when blood lead levels are higher than 70 µg/dL in children or 100 µg/dL in adults and in encephalopathy. To prevent hypocalcemia, only CaNa2EDTA should be used for chelation in heavy metal toxicity.

When CaNa2EDTA is given IM, the same daily dose is used, divided into 2-6 doses. IM preparations of CaNa2EDTA are extremely irritating to muscle and intensely painful. Lidocaine or procaine with the IM preparation lessens the pain.

Dimercaprol (BAL in Oil)

Dimercaprol (British antilewisite [BAL], or 2,3-dimercapto-1-propanol) was the first chelator used in encephalopathic individuals and is the drug of choice for treatment of lead toxicity. It is a chelating agent for intracellular and extracellular lead that and diffuses into red blood cells (RBCs) and rapidly crosses the blood-brain barrier. Sulfhydryl groups combine with ions of heavy metals to form soluble, nontoxic complexes that are excreted renally. Dimercaprol is excreted primarily in bile, making it an agent that can be used in patients with renal failure.

Combination therapy with dimercaprol and CaNa2EDTA is recommended in all cases of severe, acute intoxication (eg, BLL > 100 µg/dL), particularly when encephalopathy is present. Dimercaprol is administered IM every 4 hours, mixed in a peanut oil base; therefore, it should not be used in patients allergic to peanuts. In very severely poisoned patients, the dose is increased to 7 mg/kg, with great caution.

Adverse effects are fever, pain at the injection site, nausea, vomiting, headache, and sterile abscess formation.

D-penicillamine (Cuprimine, Depen Titratabs)

D-penicillamine (3-mercapto-D-valine), a second-line oral chelating agent, is a hydrolysis product of penicillin that is FDA-approved for the treatment of Wilson disease and cystinosis. It has been used as an oral chelator of lead for 30 years but has never been licensed for this indication by the FDA.

Penicillamine is effective orally and has few adverse effects. It can be administered over an extended period (weeks to months) for children with lead levels below 45 µg/dL. Penicillamine is available as capsules of 125 mg and 250 mg. Pyridoxine supplementation is required. Adjust the dose for patients with compromised renal function.

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