Dimercaprol is a dithiol heavy metal antagonist that chelates arsenic, lead, mercury, and other heavy metals.
Arsenic, Mercury, and Gold Poisoning
Dimercaprol is the antidote of choice in the treatment of acute arsenic (except arsine), mercury, or gold poisoning resulting from ingestion of salts of these metals or following overdosage of therapeutic agents containing these metals. Dimercaprol administration should be accompanied by appropriate supportive measures and is most effective when administered early in the course of the poisoning. In the treatment of acute poisoning by mercury salts, dimercaprol is most effective if administered within 1-2 hours following ingestion, since extensive mercury-induced renal damage cannot be reversed. Dimercaprol is not effective in the treatment of poisonings resulting from monoalkyl mercury compounds, and the drug is only minimally effective in chronic mercury poisoning. Although dimercaprol is usually of no value in the treatment of hypersensitivity reactions to mercury compounds, mercury-induced acrodynia (pink disease) in infants and children responds to treatment with dimercaprol. Dimercaprol is usually effective in the treatment of chronic poisoning from inorganic or organic arsenicals, but may be of little value if aplastic anemia, hemorrhagic encephalitis, or jaundice has developed. In one patient who experienced protein-loss enteropathy in association with arsenic poisoning, hypoproteinemia and edema improved following dimercaprol therapy. The drug is ineffective in the treatment of poisoning resulting from arsine gas (AsH3). Gold-induced dermatitis and gold-induced thrombocytopenia may improve following dimercaprol therapy.
Dermatologic or ocular manifestations of arsenic poisoning have been effectively treated with topical† dimercaprol ointment or oil solution, respectively.
Although dimercaprol chelates lead, other agents (e.g., edetate calcium disodium [calcium EDTA], succimer) generally are preferred for the management of most cases of moderate lead poisoning.102, 103 However, dimercaprol is useful as an adjunct to edetate calcium disodium and concomitant administration of the drugs is preferred, at least initially, in the management of patients with severe lead poisoning (blood lead concentrations exceeding 70 mcg/dL) and/or in those with acute lead encephalopathy (which occurs most often in children).102, 103, 104 Concomitant administration of dimercaprol and edetate calcium disodium increases the rate of excretion of lead, lowers mortality, and may lower the incidence of brain damage as compared with the use of edetate calcium disodium alone; however, such concomitant therapy does not completely eliminate the risk of permanent severe residual brain damage. Since lead encephalopathy occurs only rarely in adults, experience with the use of the combination in these patients is limited; however, use of dimercaprol and edetate calcium disodium has resulted in prompt relief of symptoms in a few adults with lead encephalopathy. Although concomitant therapy with dimercaprol and edetate calcium disodium also has been recommended in symptomatic patients with blood lead concentrations less than 70 mcg/dL,102 the American Academy of Pediatrics currently states that the toxicity of dimercaprol and the current availability of alternative drugs mandate its use only in the most serious cases of lead poisoning (i.e., blood lead concentrations exceeding 70 mcg/dL or when symptoms suggestive of encephalopathy are present).103 Edetate calcium disodium generally is used alone (i.e., without dimercaprol) in asymptomatic patients with blood lead concentrations of 45-70 mcg/dL.100, 101, 102, 103 Clinicians should consult specialized references for detailed information on the diagnosis and management of suspected or known lead intoxication and on the decision to employ chelation therapy.100, 101, 102 For further discussion of lead intoxication and its management, see Uses: Lead Poisoning, in Edetate Calcium Disodium 64:00.
Dimercaprol is not useful in acute poisonings resulting from alkyl lead compounds (e.g., tetraethyl lead).
Chemical Warfare Agent Poisoning
Dimercaprol also is used for the treatment of lewisite or mustard-derivative mixture poisoning† in the context of chemical warfare or terrorism.105 Lewisite is an organic arsenical vesicant; mustard-lewisite mixture is a mixture of mustard and lewisite. Lewisite and mustard-lewisite mixture are blister agents that are highly (and immediately) irritating to the skin, eyes, and airways; contact with liquid or vapor forms may result in skin erythema and blistering, corneal damage and iritis, damage to the airway mucosa, pulmonary edema, and death.105 In addition, the mustard component of the mustard-lewisite mixture may cause bone marrow suppression.105 Although the exact mechanism by which lewisite damages cells remains to be determined, the agent inhibits many enzymes, especially those with thiol groups.105 Mustard-lewisite mixture shares the vesicant properties of lewisite and the DNA alkylation and cross-linking properties of mustard.105
Initial management of lewisite or mustard-lewisite mixture poisoning includes respiratory support and immediate decontamination to prevent further absorption by the victim and to prevent contamination of others (e.g., emergency personnel, health-care workers) by direct contact or off-gassing of vapors from contaminated clothing.105 Chelation therapy with dimercaprol reduces the systemic effects from lewisite exposure. Because of potential adverse effects associated with dimercaprol therapy, the drug should be reserved for use in patients with signs of shock or substantial pulmonary injury.105 Alkalization of the urine stabilizes the dimercaprol-metal complex and may protect the kidneys during chelation therapy.105 If acute renal impairment develops, hemodialysis should be considered to remove the dimercaprol-metal complex.105
There is no conclusive evidence that dimercaprol is effective in the treatment of poisonings with other heavy metals†; however, the drug has been used successfully in the management of some cases of antimony, bismuth, chromium, copper, nickel, tungsten, or zinc poisoning. Although penicillamine is the drug of choice, dimercaprol may be of some value in the treatment of Wilson's disease† (hepatolenticular degeneration).
Dimercaprol is ineffective in the treatment of argyria or acute toxicity from thallium, tellurium, or vanadium. Dimercaprol should not be used in iron, cadmium, selenium, or uranium poisoning because the resulting dimercaprol-metal complexes are more toxic than the metals alone.
Chromium dermatitis† has been effectively treated with topical† dimercaprol ointment.
Dimercaprol is administered only by deep IM injection.
Arsenic, Mercury, and Gold Poisoning
In the treatment of severe arsenic or gold poisoning, dimercaprol 3 mg/kg is given IM every 4 hours for the first 2 days, 4 times daily on the third day, then twice daily for 10 days or until recovery is complete. In mild cases, 2.5 mg/kg may be given 4 times daily on the first 2 days, twice daily on the third day, and once daily for 10 days. When dimercaprol is used in the treatment of severe gold dermatitis, an IM dosage of 2.5 mg/kg every 4 hours for 2 days, then twice daily for about 1 week may be given. In the treatment of gold-induced thrombocytopenia, 100 mg of dimercaprol has been administered twice daily for 15 days. Dimercaprol has been used topically† as a 5% ointment in the treatment of dermatologic manifestations of arsenic poisoning. Dimercaprol has also been applied topically to the eye† as a 5-10% oil solution in the management of ocular symptoms of arsenic toxicity.
In acute mercury poisoning, an initial dimercaprol dose of 5 mg/kg is given IM followed by 2.5 mg/kg once or twice daily for 10 days.
Acrodynia in infants and children has been treated with dimercaprol 3 mg/kg IM every 4 hours for 2 days, then every 6 hours for 1 day, then every 12 hours for 7-8 days.
When a source for lead poisoning has been identified, the patient should be removed from that source.102, 103, 104 Because chelation therapy can increase absorption of lead from the GI tract, such therapy should be administered only to children who reside in environments that are free of lead both during and after therapy.102, 104
When dimercaprol is used in conjunction with edetate calcium disodium (calcium EDTA) in the treatment of severe lead poisoning, adults and children with symptoms of lead encephalopathy and/or blood lead concentrations greater than 70 mcg/dL (with or without symptoms) may be given dimercaprol 4 mg/kg or 75-83 mg/m2 IM initially. At least four hours later (but not until adequate urine flow is established) and at 4-hour intervals thereafter for a minimum of 3 days but usually for 5 days, dimercaprol 4 mg/kg or 75-83 mg/m2 (i.e., 450-500 mg/m2 daily) and edetate calcium disodium 250 mg/m2 (i.e., 1.5 g/m2 daily) both may be given by deep IM injection simultaneously at separate injection sites, although the American Academy of Pediatrics (AAP) and some experts recommend that edetate calcium disodium preferably be administered IV over several hours or by continuous IV infusion (e.g., at a dosage of 50 mg/kg daily) whenever possible because of the pain associated with IM injection of the drug. The AAP states that after a minimum of 3 days of concomitant therapy with edetate calcium disodium and dimercaprol, therapy with both drugs or with edetate calcium disodium alone may be continued for a total of 5 days.103 In patients with lead encephalopathy, parenteral chelation therapy with both dimercaprol and edetate calcium disodium should be continued until the patient is clinically stable before therapy is changed.103 The US Centers for Disease Control and Prevention (CDC) state that a second course of chelation therapy may be required if blood lead concentration rebounds to 45 mcg/dL or higher within 5-7 days after the initial course, but edetate calcium disodium generally is given alone (i.e., without dimercaprol) for such repeat courses of chelation therapy.102 Alternatively, the CDC states that a second course of edetate calcium disodium alone may be administered if the blood lead concentration rebounds to greater than 35 mcg/dL beyond 3 days after the initial course.102
The AAP states that in patients receiving concomitant dimercaprol-edetate calcium disodium, a minimum of 2 days without treatment should elapse before a second 5-day course of therapy with either combined dimercaprol and edetate calcium disodium or edetate calcium disodium alone is considered in patients with severe lead poisoning.103 Blood lead concentrations should be assessed 10-14 days after completion of 1-2 courses of chelation therapy; retreatment based on blood lead concentrations using regimens recommended for initial treatment is required in patients with residual blood lead concentrations greater than 45 mcg/dL.103 (See Uses: Lead Poisoning, in Edetate Calcium Disodium 64:00)
Chemical Warfare Agent Poisoning
The usual dosage of dimercaprol for the treatment of lewisite or mustard-lewisite mixture poisoning† in the context of chemical warfare or terrorism is 3-5 mg/kg administered IM every 4 hours for 4 doses.105 The dosage regimen can be adjusted depending on the extent of exposure and severity of symptoms.105
Dimercaprol has been used topically† as a 5% ointment in the treatment of chromium dermatitis†.
Adverse effects of dimercaprol are usually mild and transitory and occur in about one-half of patients who receive an IM dose of 5 mg/kg. If the dose of dimercaprol exceeds 5 mg/kg, most patients will experience vomiting, seizures, and stupor or coma which may begin within 30 minutes after injection and usually subside in 1-6 hours. Prophylactic or therapeutic administration of ephedrine or an antihistamine may prevent or relieve many of the mild adverse effects of dimercaprol. The most frequent adverse effect, a rise in systolic and diastolic blood pressure which is dose related and may be accompanied by tachycardia, may appear 15-30 minutes following the injection and blood pressure usually returns to normal within 2 hours. Frequently pain and occasionally sterile abscesses occur at the injection site, particularly if the drug is not administered deep IM.
Other adverse effects that may occur include nausea, vomiting, headache, sweating, and a feeling of constriction (or pain) in the throat, chest, or hands which may be accompanied by anxiety, nervousness or restlessness, and weakness. Muscular aches and pains, muscle spasms, tingling of extremities, and abdominal pain have also been reported.
Dimercaprol has a strong odor and imparts an unpleasant mercaptan-like odor to the patient's breath. The drug may also produce a burning sensation of the lips, mouth, throat, eyes, and penis, and pain in the teeth. Blepharal spasm, conjunctivitis, lacrimation, rhinorrhea, and salivation may also occur. When the drug is applied topically, it produces erythema and edema.
Fever occurs frequently in children receiving dimercaprol, usually after the second or third dose and often persisting until the drug is discontinued. Children may also show a transient reduction in polymorphonuclear leukocytes.
Dimercaprol has been reported to induce hemolysis (which may be severe) in individuals with glucose-6-phosphate dehydrogenase deficiency. Therefore, high-risk individuals should be screened for this deficiency, and susceptible patients should be monitored for hemolysis during therapy with dimercaprol.
Animal studies indicate that the drug may induce metabolic acidosis associated with elevated serum lactate concentrations. Repeated high doses of dimercaprol may cause capillary damage and loss of protein from the circulation leading to vascular collapse, and extremely high doses have produced coma and/or seizures in animals.
Precautions and Contraindications
Dimercaprol is potentially nephrotoxic. Since the chelate dissociates in acid medium, the urine should be kept alkaline during dimercaprol therapy to protect the kidneys. Dimercaprol should be used with caution and/or the dosage reduced in patients with oliguria. If acute renal failure develops during therapy, the drug should be discontinued or used very cautiously because serum concentrations of dimercaprol may reach toxic levels.
In patients with hypertension, dimercaprol should be used with caution. If dimercaprol is used to treat severe reactions to gold therapy, the fact that the drug may terminate the gold-induced remission of rheumatoid arthritis should be kept in mind.
Because chelation therapy can increase absorption of lead from the GI tract, such therapy should only be administered to children who reside in environments that are free of lead both during and after therapy.102, 104
Dimercaprol is contraindicated in patients with impaired hepatic function, except those with postarsenical jaundice. Dimercaprol also is contraindicated in individuals with known hypersensitivity to peanuts, since the injection is only available as a solution in peanut oil.103
Safe use of dimercaprol during pregnancy has not been established. In teratogenicity studies in mice, dimercaprol produced malformations in the skeletal system, growth retardation, and an increase in embryo mortality. However, 2 normal infants were born to one woman who received dimercaprol for the treatment of Wilson's disease throughout 2 pregnancies. Dimercaprol should not be used during pregnancy unless use of the drug is considered necessary in the treatment of life-threatening acute poisoning.
Dimercaprol forms a toxic complex with iron, cadmium, selenium, or uranium. Iron therapy should not be given concurrently with dimercaprol, and it has been suggested that iron therapy be deferred until at least 24 hours after the last dose of dimercaprol.
Dimercaprol interferes with the normal accumulation of iodine by the thyroid, and iodine I 131 thyroidal uptake values may be decreased if this test is performed during or immediately following dimercaprol therapy.
The sulfhydryl groups of dimercaprol form heterocyclic ring complexes with heavy metals (particularly arsenic, mercury, and gold), and these complexes prevent or reverse the binding of metallic cations to body ligands such as essential sulfhydryl-dependent enzymes. However, dimercaprol does not protect sulfhydryl enzymes from metals, such as selenium, which inhibit such enzymes by an oxidation process. If the affinity of the metal for dimercaprol is greater than that for enzymes, a mercaptide is formed and can be excreted from the body. However, the dimercaprol-metal complex can dissociate (particularly in an acid medium or as the level of dimercaprol declines) or be oxidized, thus releasing the metal to exert its toxic effects again. For this reason, the dosage of dimercaprol must be sufficient to assure an excess of free dimercaprol in body fluids until the excretion of the metal is complete. Obviously, no metal antagonist will be completely effective in the presence of overwhelming amounts of metal. Although dimercaprol has little affinity for the essential trace metals of the body (except copper) and does not usually produce trace metal depletion syndromes, the drug may interfere with the normal accumulation of iodine by the thyroid. (See Laboratory Test Interferences.)
Following IM injection of therapeutic doses of dimercaprol, peak blood concentrations are attained in 30-60 minutes. Dimercaprol is slowly absorbed through the skin following topical application.
Following absorption, dimercaprol is distributed to all tissues (mainly in the intracellular space) including the brain, with highest concentrations in the liver and kidneys.
The dimercaprol that is not excreted as the dimercaprol-metal complex is rapidly metabolized to inactive products and excreted in urine, and in feces via bile. Animal evidence suggests that some of the drug may be excreted as a glucuronide conjugate. In humans, the metabolism and excretion of dimercaprol is probably complete within 4 hours. Because the dimercaprol-metal complex rapidly dissociates in an acid medium and most metals and dimercaprol are nephrotoxic, alkalinization of the urine during dimercaprol therapy may prevent dissociation and protect the kidneys. (See Cautions: Precautions and Contraindications.)
Dimercaprol is a dithiol chelating agent originally developed as an antidote to an arsenic-containing chemical warfare agent known as Lewisite. Dimercaprol occurs as a colorless or almost colorless, viscous liquid with a disagreeable, mercaptan-like odor and is soluble in water, in alcohol, and in vegetable oils. The commercially available injection is a peanut oil solution containing benzyl benzoate to increase the solubility and stability of the drug in the oil.
The drug is unstable in aqueous solution.
The injection, a yellow, viscous solution with a pungent, disagreeable odor, may be turbid or contain small amounts of flocculent material. This sediment, which develops during sterilization, does not indicate that the solution is deteriorating.
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection, for IM use only | 100 mg/mL | BAL in Oil® (with benzyl benzoate 200 mg/mL and peanut oil 700 mg/mL) |
Only references cited for selected revisions after 1984 are available electronically.
100. Piomelli S, Rosen JF, Chisolm JJ Jr et al. Management of childhood lead poisoning. J Pediatr . 1984; 105:523-32. [PubMed 6481529]
101. Pincus D, Saccar CV. Lead poisoning. Am Fam Physician . 1979; 19:120-4. [PubMed 110123]
102. US Department of Health and Human Services. Preventing lead poisoning in young children: a statement by the Centers for Disease Control October 1991. Atlanta, GA: Centers for Disease Control, National Center for Environmental Health and Injury Control 1991-537-304.
103. Committee on Drugs, American Academy of Pediatrics. Treatment guidelines for lead exposure in children. Pediatrics . 1995; 96:155-60. [PubMed 7596706]
104. Committee on Environmental Health, American Academy of Pediatrics. Lead poisoning: from screening to primary prevention. Pediatrics . 1993; 92:176-83. [PubMed 8516071]
105. Agency for Toxic Substances and Disease Registry. Blister agents: lewisite (L), mustard-lewisite mixture (HL). From the CDC website. Accessed Nov 12, 2001. [Web]