Dimercaprol (Monograph)

Brand name: BAL in Oil
Drug class: Heavy Metal Antagonists
- Sulfhydryl Donors
- Antidotes
ATC class: V03AB09
VA class: AD300
CAS number: 59-52-9

Introduction

Dithiol heavy metal antagonist; chelates arsenic, lead, mercury, gold, and other heavy metals.^{a b}

Uses for Dimercaprol

Arsenic, Mercury, and Gold Poisoning

Antidote of choice in treatment of acute arsenic (except arsine), mercury, or gold poisoning following ingestion of salts of these metals or overdosage of therapeutic agents containing these metals.^{a b}

Most effective when administered early in the course of poisoning; administration should be accompanied by appropriate supportive measures.^{a b}

For treatment of acute poisoning by mercury salts, most effective if administered within 1–2 hours following ingestion.^{a b} Does not reverse extensive mercury-induced renal damage.^a Minimally effective in chronic mercury poisoning.^{a b}

Usually of no value in the treatment of hypersensitivity reactions to mercury compounds; however, has been used to treat mercury-induced acrodynia (pink disease) in infants and children.^a

Usually effective in treatment of chronic poisoning from inorganic or organic arsenicals.^a

Consult most recent AAP and CDC recommendations for information regarding chelation therapy.^{a i}

Ineffective in the treatment of poisoning resulting from arsine gas (AsH₃).^a

May be effective in the treatment of gold-induced dermatitis and gold-induced thrombocytopenia.^a

Dermatologic or ocular manifestations of arsenic poisoning have been effectively treated with topical^{† [off-label]} dimercaprol ointment or oil solution, respectively.^a

Lead Poisoning

Used as an adjunct to edetate calcium disodium for chelation of lead in the management of acute lead encephalopathy or symptoms suggestive of encephalopathy and symptomatic lead poisoning in patients with severe lead poisoning (blood lead concentration >100 mcg/dL in adults or >70 mcg/dL in pediatric patients).^{f g h}

Has been used for managing moderate lead poisoning; however, other agents (e.g., edetate calcium disodium, succimer) preferred for managing most cases of moderate lead poisoning.^{102 103 g h}

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}

Not useful in acute poisonings resulting from alkyl lead compounds (e.g., tetraethyl lead).^a

Chemical Warfare Agent Poisoning

Has been used to treat lewisite or mustard-lewisite mixture poisoning^{† [off-label]} in chemical warfare or terrorism;¹⁰⁵ reserve for patients with signs of shock or substantial pulmonary injury.¹⁰⁵

Initial management 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

Other Heavy Metal Poisonings

No conclusive evidence regarding efficacy in the treatment of poisonings with other heavy metals^{† [off-label]} (e.g., antimony, bismuth).^{a b}

Ineffective in treatment of argyria or acute toxicity from thallium, tellurium, or vanadium.^a

Should not be used in iron, cadmium, selenium, or uranium poisoning; resulting dimercaprol-metal complexes more toxic than metals alone.^{a b}

Dimercaprol Dosage and Administration

General

• Administer at earliest possible time and at adequate doses at frequent intervals for greatest efficacy;^{a b} should always be accompanied by appropriate supportive measures.^{a b}

• Consult published protocols and specialized references for dosages of chelating agents, the method and sequence of administration, and specific information on precautions associated with chelation therapy.^{a i}

• Maintain alkaline urine during therapy to prevent dissociation of dimercaprol-metal complex and protect the kidneys.^{105 b f h} (See Renal Effects under Cautions.)

Lead Poisoning

• Various dosage regimens have been recommended in lead poisoning management;ⁱ total dose of chelator depends on patient’s response to, and tolerance of, the select agent,ⁱ as well as severity of lead toxicity.ⁱ

• When source for lead poisoning has been identified, remove patient from that source.^{102 103 104 g}

• Chelation therapy can increase absorption of lead from the GI tract; therefore, administer only to patients who reside in environments free of lead both during and after therapy.^{102 104}

• Administer in hospital setting; monitor cardiovascular and mental status closely.^{103 g}

• Subsequent course(s) of therapy may be required based on clinical symptoms and blood lead concentrations.^g In patients with severe lead poisoning, allow ≥2 days without treatment to elapse before a second 5-day course of therapy is considered.¹⁰³ Assess blood lead concentrations 10–14 days after completion of chelation therapy to allow reequilibration.^{103 g}

Administration

Administer by deep IM injection.^{a b}

Has also been administered topically^{† [off-label]} as a 5% ointment for dermatologic manifestations of arsenic poisoning or as a 5–10% oil solution for ocular manifestations of arsenic poisoning.^a

IM Administration

Administer by deep IM injection.^{a b}

Consider prophylactic or therapeutic administration of antihistamines to prevent or relieve mild adverse effects.^{103 a b}

Dosage

Pediatric Patients

Arsenic or Gold Poisoning

Mild Arsenicor Gold Poisoning

IM

2.5 mg/kg 4 times daily for 2 days; then 2.5 mg/kg twice daily on the third day; then 2.5 mg/kg once daily thereafter for 10 days.^{a b}

Severe Arsenicor Gold Poisoning

IM

3 mg/kg every 4 hours for 2 days; then 3 mg/kg 4 times daily on the third day; then 3 mg/kg twice daily thereafter for 10 days^{a b} or until recovery is complete.^a

Severe Gold Dermatitis

IM

2.5 mg/kg every 4 hours for 2 days, then 2.5 mg/kg twice daily for about 1 week.^a

Mercury Poisoning

IM

Initially, 5 mg/kg.^{a b} Then 2.5 mg/kg once or twice daily for 10 days.^{a b}

Mercury-induced Acrodynia

IM

Infants and children: 3 mg/kg every 4 hours for 2 days, then 3 mg/kg every 6 hours for 1 day, then 3 mg/kg every 12 hours for 7–8 days.^a

Lead Poisoning

Consult most recent published protocols, including those from AAP and CDC, and specialized references for combination therapy dosage recommendations.ⁱ

Lead Encephalopathy

IM

Initially, 4 mg/kg^{a b g} or 75 mg/m².^{f g} Then, at least 4 hours later^a (and when adequate urine flow established) begin 4 mg/kg^{a b} or 75 mg/m^{2f g} every 4 hours (i.e., 450 mg/m² daily),^g in conjunction with edetate calcium disodium (administered at separate injection sites), ^{a b} for at least 3 days (usual duration is 5 days).^{a f g}

Decision to repeat dual therapy should be based on clinical symptoms and blood lead concentrations.^g

Symptoms Suggestive of Encephalopathy or Blood Lead Concentration >70 mcg/dL

IM

Initially, 3–4 mg/kg^g or 50–75 mg/m².^a Then, at least 4 hours later^a (and when adequate urine flow established) begin 3–4 mg/kg^{b g} or 50–75 mg/m^2g every 4 hours (i.e., 300–450 mg/m² daily),^g in conjunction with edetate calcium disodium (administered at separate injection sites),^{a b} for 3–5 days.^{a f g}

Decision to repeat dual therapy should be based on clinical symptoms and blood lead concentrations.^g

Chemical Warfare Agent Poisoning

Lewisite or Mustard-lewisite Mixture Poisoning† [off-label]

IM

3–5 mg/kg every 4 hours for 4 doses.¹⁰⁵ Adjust dosage regimen based on extent of exposure and severity of symptoms.¹⁰⁵

Adults

Consult most recent published protocols, including those from AAP and CDC, and specialized references for combination therapy dosage recommendations.^{a i}

Arsenic or Gold Poisoning

Mild Arsenic or Gold Poisoning

IM

2.5 mg/kg 4 times daily for 2 days; then 2.5 mg/kg twice daily on the third day; then 2.5 mg/kg once daily thereafter for 10 days.^{a b}

Severe Arsenic or Gold Poisoning

IM

3 mg/kg every 4 hours for 2 days; then 3 mg/kg 4 times daily on the third day; then 3 mg/kg twice daily thereafter for 10 days^{a b} or until recovery is complete.^a

Alternatively, for severe arsenic poisoning, 3 mg/kg every 4 hours for 2 days and then 3 mg/kg twice daily thereafter for 7–10 days^f or 3–5 mg/kg every 4–6 hours for 1 day and then taper dose and frequency, depending on patient’s symptoms.^f

Severe Gold Dermatitis

IM

2.5 mg/kg every 4 hours for 2 days, then 2.5 mg/kg twice daily for about 1 week.^a

Gold-induced Thrombocytopenia

IM

100 mg twice daily for 15 days.^a

Mercury Poisoning

IM

Initially, 5 mg/kg.^{a b} Then 2.5 mg/kg once or twice daily for 10 days.^{a b}

Alternatively, 5 mg/kg initially and then 2.5 mg/kg every 8–12 hours for 1 day, followed by 2.5 mg/kg every 12–24 hours until patient improves, up to a total of 10 days;^f or 5 mg/kg every 4 hours for 48 hours, then 2.5 mg/kg every 6 hours for 48 hours, then 2.5 mg/kg every 12 hours for 7 days (total of 10 days).^j

Lead Poisoning

Consult most recent published protocols, including those from AAP and CDC, and specialized references for combination therapy dosage recommendations.^a

Lead Encephalopathy

IM

Initially, 4 mg/kg^{a b g} or 75 mg/m².^g Then, at least 4 hours later (and when adequate urine flow established) begin 4 mg/kg^{a b} or 75 mg/m^2g every 4 hours (i.e., 450 mg/m² daily),^g in conjunction with edetate calcium disodium (administered at separate injection sites), ^{a b} for at least 3 days (usual duration is 5 days).^a

Decision to repeat dual therapy should be based on clinical symptoms and blood lead concentrations.^g

Symptoms Suggestive of Encephalopathy or Blood Lead Concentration >100 mcg/dL

IM

Initially, 3–4 mg/kg^g or 50–75 mg/m².^a Then, at least 4 hours later (and when adequate urine flow established) begin 3–4 mg/kg^{b g} or 50–75 mg/m^2g every 4 hours (i.e., 300–450 mg/m² daily),^g in conjunction with edetate calcium disodium (administered at separate injection sites),^{a b} for at least 3–5 days.^{a f g}

Decision to repeat dual therapy should be based on clinical symptoms and blood lead concentrations.^g

Chemical Warfare Agent Poisoning

Lewisite or Mustard-lewisite Mixture Poisoning†

IM

3–5 mg/kg every 4 hours for 4 doses.¹⁰⁵ Adjust dosage regimen based on extent of exposure and severity of symptoms.¹⁰⁵

Special Populations

No special population dosage recommendations at this time.^b

Cautions for Dimercaprol

Contraindications

• Hepatic insufficiency (except for cases of postarsenical jaundice).^{a b}

• Known hypersensitivity to peanuts.¹⁰³ (See Peanut Sensitivity under Sensitivity Reactions.)

Warnings/Precautions

Warnings

Local Effects

Possible injection site pain or sterile abscesses at injection site.^{a b}

Fever

Children may experience fever usually starting after second or third dose;^{a b} may persist throughout therapy^b until drug discontinued.^a

Hematologic Effects

Possible transient reduction of the percentage of polymorphonuclear leukocytes.^{a b}

Sensitivity Reactions

Peanut Sensitivity

Dimercaprol injection contains 700 mg of peanut oil per 1 mL of injection solution, which may cause allergic-type reactions in susceptible individuals.^b Use with caution in patients with peanut sensitivities; drugs and equipment necessary to treat allergic reactions should be readily available.^b

General Precautions

Renal Effects

Potentially nephrotoxic.^a Chelate rapidly dissociates in acid medium; alkalinization of urine during therapy may prevent dissociation and protect the kidneys.^{a b}

Use with caution and/or reduce dosage in patients with oliguria.^a

If acute renal failure develops during therapy, discontinue drug or use very cautiously as serum concentrations of dimercaprol may reach toxic levels.^{a b}

Rheumatoid Arthritis

When used in the treatment of severe reactions to gold therapy, may terminate the gold-induced remission of rheumatoid arthritis.^a

Cardiovascular Effects

Potential dose-related rise in SBP and DBP; may be accompanied by tachycardia.^a May appear 15–30 minutes following the injection; BP usually returns to normal within 2 hours.^a Use with caution in patients with hypertension.^a

Repeated high doses may cause capillary damage and loss of protein from the circulation leading to vascular collapse.^a Extremely high doses may produce coma and/or seizures.^a

Oral Effects

Drug has a strong odor and may impart an unpleasant mercaptan-like odor to patient’s breath.^a

Possible burning sensation of lips or mouth.^a

Dermatologic Effects

Erythema and edema usually occur when applied topically.^a

Glucose-6-Phosphate Dehydrogenase Deficiency

May induce hemolysis, including severe forms, in patients with glucose-6-phosphate dehydrogenase deficiency.^a Screen high-risk individuals for this deficiency and monitor susceptible patients for hemolysis during therapy.^a

Specific Populations

Pregnancy

Category C.^{b e}

Lactation

Not known whether dimercaprol is distributed into human milk;^b however, breast-feeding is contraindicated in women receiving dimercaprol for treatment of maternal arsenic, gold, mercury, or lead poisoning because of the risk of exposing nursing infant to the toxic heavy metals.^e

Pediatric Use

Fever may occur in 30% of children; usually starts after second or third dose and may persist throughout therapy.^{a b}

Possible transient reduction of the percentage of polymorphonuclear leukocytes.^{a b}

Hepatic Impairment

Contraindicated in patients with impaired hepatic function, except postarsenical jaundice.^{a b} (See Contraindications under Cautions.)

Renal Impairment

Use with extreme caution or discontinue therapy if renal impairment develops during therapy.^{a b} (See Renal Effects under Cautions.)

Common Adverse Effects

Dose-related nausea/vomiting, ^{a b} BP elevation, tachycardia,^{a b} injection site pain, fever (in children).^a

Drug Interactions

Specific Drugs

Dimercaprol Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentrations attained 30–60 minutes following IM injection.^a

Slowly absorbed through the skin following topical application.^a

Distribution

Extent

Distributed into all tissues (mainly in the intracellular space) including the brain, with the highest concentrations in the liver and kidneys.^a

Elimination

Metabolism

Dimercaprol (not excreted as the dimercaprol-metal complex) is rapidly metabolized to inactive products.^a

Some drug may be excreted as a glucuronide conjugate.^a In humans, metabolism and excretion is probably complete within 4 hours.^a

Elimination Route

Excreted in urine and feces via bile.^a

Stability

Storage

Parenteral

Solution for IM Injection

20–25°C.^b

Actions

• Contains sulfhydryl groups that form heterocyclic ring complexes with heavy metals (particularly arsenic, mercury, and gold).^{a b}

• These complexes prevent or reverse the binding of metallic cations to body ligands such as essential sulfhydryl-dependent enzymes.^{a b} Does not protect sulfhydryl enzymes from metals, such as selenium, that inhibit such enzymes by an oxidation process.^a

• If the affinity of the metal for dimercaprol is greater than that for enzymes, a mercaptide is formed, which can be excreted from the body.

• 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.^a

• Has little affinity for the essential trace metals of the body (except copper); does not usually produce trace metal depletion syndromes.^a However, may interfere with normal accumulation of iodine by the thyroid.^a

Advice to Patients

• When used for lead poisoning, importance of identifying source of lead poisoning and then removing patient from that source. ^{102 103 104} Importance of patient residing in an environment free of lead both during and after therapy.^{102 104}

• Importance of informing clinician of allergy to peanuts.^a

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^b

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.^b

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

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.

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