DESCRIPTION

British anti-Lewisite (dimercaprol, BAL) is a heavy metal chelating agent used in the treatment of arsenic, mercury, lead, or gold toxicity.

FORMS AND USES

• Each milliliter of BAL in oil contains 100 mg dimercaprol, 200 mg benzyl benzoate, and 700 mg peanut oil.
• The chemical structure of dimercaprol, the active ingredient in BAL, is CH₂(SH)CH(SH)CH₂OH (dithiol).
• BAL is highly lipid soluble but has limited water solubility.
• It is a colorless liquid with a sulfur odor, similar to rotten eggs.

MECHANISM OF ACTION

Sulfhydryl groups bind heavy metals, thereby preventing or possibly removing metal from binding sites on enzymes or other physiologic proteins.

DRUG AND DISEASE INTERACTIONS

• Iron supplementation should not be given to patients receiving BAL due to the potential for increased toxicity of the BAL-iron complex.
• BAL administration to patients on gold therapy for rheumatoid arthritis may lead to an exacerbation of the arthritis.

PREGNANCY AND LACTATION

• The safety of BAL in human pregnancy has not been established.
• BAL is teratogenic in animal models; therefore, it should be used during pregnancy only to treat life-threatening toxicity.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• MECHANISM OF ACTION
• DRUG AND DISEASE INTERACTIONS
• PREGNANCY AND LACTATION

ACUTE INORGANIC ARSENIC TOXICITY

• BAL use is indicated if oral agents, such as succimer, cannot be used.
• BAL therapy has not been proven effective for chronic arsenic or arsine toxicity.

MERCURY TOXICITY (ACUTE INORGANIC, ELEMENTAL, OR NON-SHORT/CHAIN ORGANIC MERCURY)

• BAL should be used if oral agents, such as succimer, cannot be used.
• BAL therapy has not been proven effective for chronic organic mercury toxicity or short-chain organic mercury (methylmercury) toxicity.
• BAL is not routinely recommended for chelation of short-chain organic mercury compounds such as methylmercury due to a theoretical concern that chelation may facilitate the redistribution of mercury into the CNS.

LEAD TOXICITY

• BAL is recommended for acute poisoning associated with encephalopathy. It is commonly used in combination with calcium disodium EDTA (CaNa₂EDTA).
• BAL therapy is not recommended for symptomatic lead toxicity without encephalopathy or in asymptomatic children or adults with elevated blood lead levels.
• Potential benefits of BAL chelation prior to chelation with CaNa₂EDTA include limiting the redistribution of lead into the CNS, mobilizing lead from the CNS, and making it more accessible to the water-soluble CaNa₂EDTA.

GOLD TOXICITY

• BAL has been used for hematologic effects resulting from gold toxicity.

OTHER PROPOSED USES

• Toxicity resulting from antimony, bismuth, chromium, copper, nickel, tungsten, or zinc.

Section Outline:

• ACUTE INORGANIC ARSENIC TOXICITY
  • MERCURY TOXICITY (ACUTE INORGANIC, ELEMENTAL, OR NON-SHORT/CHAIN ORGANIC MERCURY)
• LEAD TOXICITY
• GOLD TOXICITY
• OTHER PROPOSED USES

CONTRAINDICATIONS

• Patients with peanut allergy should not receive BAL because of its peanut oil base.
• Patients with glucose-6-phosphate deficiency should not receive BAL due to its potential for hemolysis.
• In the case of iron toxicity, the BAL-metal complex may be more toxic than the iron itself.
• BAL should not be given to patients with hepatic insufficiency unless the insufficiency is related to postarsenical jaundice.

ADVERSE EFFECTS

• Allergic reactions may occur in patients with peanut or other nut allergies.
• Pain at the injection site is common; it may be reduced by using a local anesthetic prior to or with the injection.
• Abscess formation at the injection site is possible.
• Other adverse reactions are dose related; administration of more than 5 mg/kg frequently produces serious adverse events.
  • Viral syndrome-like symptoms are common: fever, headache, chest pain, nausea, vomiting, diaphoresis, rhinorrhea, lacrimation, salivation, sore throat, myalgia, abdominal pain, dental pain, and urticaria; the effect peaks soon after administration and resolves in an hour.
  • Paresthesia, anxiety, and apprehension are common; the effect peaks soon after administration and resolves in an hour.
  • Tachycardia and hypertension occur, more commonly in patients with underlying hypertension.
  • Increased excretion of essential metals such as copper and zinc may occur.
  • Nephrotoxicity related to the metal chelate may occur.

Section Outline:

• CONTRAINDICATIONS
• ADVERSE EFFECTS

ACUTE ARSENIC POISONING

• BAL should be administered if vomiting or other conditions preclude the administration of an oral antidote.
• In potentially serious poisoning, BAL should be administered as soon as poisoning is suspected.
• The adult and pediatric dose is 2.5 to 5.0 mg/kg intramuscularly every 4 hours for 24 hours, tapering over 1 to 2 days at intervals of every 6 to 12 hours until an oral antidote can be tolerated. An alternative pediatric dose is 300 to 450 mg/m²/day divided four times per day.
• BAL dosing may be discontinued when signs and symptoms of arsenic toxicity resolve, when the 24-hour urinary arsenic concentration is less than 50 to 100 µg/ml, or when chelation with an oral agent such as succimer or 2,3-dimercapto-1-propanesulfonate (DMPS) is instituted.

MERCURY TOXICITY

Acute Inorganic Mercury

• BAL should be administered if vomiting or other conditions preclude the administration of an oral chelating agent.
• The dose for adult or pediatric patients is 2.5 to 5.0 mg/kg intramuscularly every 4 hours, tapering over 1 to 2 days at intervals of every 6 to 12 hours until an oral antidote can be tolerated. An alternative pediatric dose is 300 to 450 mg/m²/day in four divided doses.
• BAL dosing may be discontinued when signs and symptoms of mercury toxicity resolve or chelation with an oral agent such as D-penicillamine, succimer, or DMPS is instituted.

Elemental Mercury

• This exposure rarely requires chelation unless mercury vapor is inhaled.
• A parenteral agent is rarely required, because oral administration is feasible.
• The same dosing regimen should be followed as for acute inorganic mercury poisoning.

Acute Organic Mercury (Excluding Methylmercury)

• A parenteral agent is rarely required, because oral administration is feasible.
• The same dosing regimen should be followed as for acute inorganic mercury poisoning.

LEAD TOXICITY

• The dose for adult or pediatric patients is 2.5 to 5.0 mg/kg intramuscularly every 4 hours prior to the first dose of CaNa₂EDTA; BAL should be administered at least 4 hours prior to the administration of CaNa₂EDTA. An alternative pediatric dose is 300 to 450 mg/m²/day in four divided doses.
• Administration of BAL should rarely be continued for more than 24 hours.
• BAL dosing may be discontinued when signs and symptoms of lead encephalopathy resolve or chelation with another chelating agent such as succimer is instituted.

GOLD TOXICITY

• The dose for pediatric or adult patients is 2.5 to 5.0 mg/kg intramuscularly every 4 hours, tapering over 1 to 2 days at intervals of every 6 to 12 hours until an oral antidote can be tolerated. An alternative pediatric dose is 300 to 450 mg/m²/day in four divided doses.
• BAL dosing may be discontinued when signs and symptoms of gold toxicity resolve.

Section Outline:

• ACUTE ARSENIC POISONING
• MERCURY TOXICITY
  • Acute Inorganic Mercury
  • Elemental Mercury
  • Acute Organic Mercury (Excluding Methylmercury)
• LEAD TOXICITY
• GOLD TOXICITY

• BAL is often continued unnecessarily after the patient has regained the ability to tolerate an oral agent.
• Dosage of BAL should be reduced or treatment discontinued if renal insufficiency develops during therapy.
• Hemodialysis may be indicated in order to remove the metal-BAL complex in patients with renal insufficiency or oliguric renal failure.

Poisoning by other specified systemic agents.

See Also: SECTION IV, Arsenic, Gold, Lead, and Mercury chapters.

RECOMMENDED READING

Howland MA. Dimercaprol (BAL). In: Goldfrank LR, Flomenbaum NE, Lewin NS, et al., eds. Goldfrank's toxicologic emergencies, 6th ed. East Norwalk, CT: Appleton & Lange, 1998.

Woody NC, Kometani JT. BAL in the treatment of arsenic ingestion of children. Pediatrics 1948;1:372-378.

Author: Edwin K. Kuffner

Reviewer: Richard C. Dart