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DIMERCAPROL

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Dimercaprol is a chelator used in the treatment of acute poisoning by arsenic, gold, and mercury (inorganic, elemental). It is also used in combination with edetate calcium disodium in severe lead poisoning. It is of questionable value for other heavy metals poisoning (eg; antimony, bismuth).

Specific Substances

    1) 2,3-dimercaptopropan-1-ol
    2) 2,3-dimercaptopropanol
    3) 2,3-dimercapto-1-propanol
    4) BAL
    5) British Anti-Lewisite
    6) Dimercaprolum
    7) CAS 59-52-9
    1.2.1) MOLECULAR FORMULA
    1) C3-H8-O-S2

Available Forms Sources

    A) FORMS
    1) Dimercaprol is available as 3-mL ampules containing 100 mg/mL (10%) of BAL for deep intramuscular injection. Each 1 mL of this product also contains 700 mg of peanut oil and 200 mg of benzyl benzoate (Prod Info BAL In Oil intramuscular injection, 2008).
    B) USES
    1) Dimercaprol is used for the treatment of mercury (inorganic and elemental), arsenic, and gold poisoning. It is also used in combination with Edetate Calcium Disodium injection to treat patients with severe lead poisoning (Prod Info BAL In Oil intramuscular injection, 2008). Dimercaprol is contraindicated in methyl mercury poisoning (Howland, 2002; Clarkson, 1990).
    2) Dimercaprol is not indicated for iron, cadmium, or selenium poisoning because the dimercaprol-metal complexes are more toxic than the metal alone, especially to the kidneys. It is of questionable value for other heavy metals poisoning (eg; antimony, bismuth) (Edge & Somers, 1948; Prod Info BAL in Oil Ampoules, 1998).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Dimercaprol is used for the treatment of mercury (inorganic and elemental), arsenic, and gold poisoning. It is also used in combination with Edetate Calcium Disodium injection to treat patients with severe lead poisoning. Dimercaprol is contraindicated in methyl mercury poisoning.
    B) PHARMACOLOGY: Dimercaprol contains two sulfhydryl groups that form a stable relatively nontoxic chelate 5-membered heterocyclic ring with heavy metals. The most stable complexes are formed with Class B metals, including arsenic, mercury, and gold. Lead and tin, Class A metals, form stable complexes with nitrogen, oxygen, sulfur, and phosphorus-containing chelates, and thus will combine with both dimercaprol and EDTA. The resulting complex contains a 1:1 or 2:1 ratio of dimercaprol to metal. The combination of dimercaprol with the metal prevents the metal from combining with sulfhydryl groups on physiologic proteins, such as enzymes, and keeps them inert until they can be excreted.
    C) EPIDEMIOLOGY: Overdose is rare.
    D) WITH THERAPEUTIC USE
    1) The majority of patients receiving therapeutic doses of dimercaprol intramuscularly will experience a transient increase in pulse and blood pressure. The onset is between 5 and 40 minutes, usually peaking at 30 minutes, and subsiding gradually within 3 hours. Transient erythema and whealing, contact dermatitis, pain at the injection site, nausea, vomiting, abdominal pain, lacrimation, conjunctivitis, blepharospasm, pain in the limbs, muscle stiffness, paresthesias, headache, tremors, weakness, fatigue, rhinorrhea, a burning sensation of the lips, mouth, and throat, and fever have also been reported. Fever is more common in children, occurring in about 30%; this subsides rapidly when the drug is discontinued.
    E) WITH POISONING/EXPOSURE
    1) Anorexia, restlessness, vomiting, pain at injection site, salivation, hypertension, fever, tachycardia, seizures, and "leukotoxic" effect have been reported in patients after receiving 5 to 40.5 mg/kg of dimercaprol.
    2) A syndrome similar to hypertensive encephalopathy (eg, vasomotor changes, severe hypertension, seizures, coma, and stupor) has been reported after excessive doses. Vomiting, seizures, and/or stupor have been reported following dimercaprol doses greater than 5 mg/kg beginning within 30 minutes and subsiding within 6 hours of injection.
    0.2.20) REPRODUCTIVE
    A) Dimercaprol is classified as FDA pregnancy category C. The number of pregnant women exposed to dimercaprol and reported in the literature is so limited that no pattern or estimate of risk can be determined at this time. Apparently normal infants have been born to women treated with dimercaprol for Wilson disease during pregnancy and a case report describes the complete recovery of a woman and her 20-week old fetus after she experienced an acute ingestion of inorganic arsenic.

Laboratory Monitoring

    A) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    B) Monitor vital signs.
    C) Monitor serum electrolytes in patients with significant vomiting.
    D) Institute continuous cardiac monitoring and obtain an ECG in symptomatic patients.
    E) For more information regarding laboratory evaluation after heavy metal poisoning, refer to "LEAD", "GOLD DRUGS", "ARSENIC", "MERCURY, ELEMENTAL", "MERCURY, INORGANIC" documents.

Treatment Overview

    0.4.6) PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is symptomatic and supportive. Correct any significant fluid and/or electrolyte abnormalities in patients with severe vomiting. The majority of patients receiving therapeutic doses of dimercaprol intramuscularly will experience a transient increase in pulse and blood pressure. Monitor vital signs. For mild/moderate asymptomatic hypertension (no end organ damage), pharmacologic treatment is generally not necessary.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is symptomatic and supportive. For severe hypertension, nitroprusside is preferred. Labetalol, nitroglycerin, and phentolamine are alternatives. Treat seizures with IV benzodiazepines; barbiturates or propofol may be needed if seizures persist or recur.
    C) DECONTAMINATION
    1) Gastrointestinal decontamination is not recommended; administered via the parenteral route.
    D) AIRWAY MANAGEMENT
    1) Ensure adequate ventilation and perform endotracheal intubation early in patients with severe allergic reactions (peanut allergy).
    E) ANTIDOTE
    1) None.
    F) ENHANCED ELIMINATION
    1) In patients with renal insufficiency or oliguric renal failure, hemodialysis may be used to remove the metal-dimercaprol complex.
    G) PATIENT DISPOSITION
    1) HOME CRITERIA: There is no data to support home management, and dimercaprol is generally only used in the hospital setting.
    2) OBSERVATION CRITERIA: Any patient with symptoms should be observed with frequent monitoring of vital signs. Patients that remain asymptomatic can be discharged.
    3) ADMISSION CRITERIA: Patients with severe hypertension, tachycardia, and persistent seizures should be admitted to an intensive care setting.
    4) CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    H) PITFALLS
    1) Patients may already be experiencing symptoms of metal toxicity. Adverse effects are common even at therapeutic doses. In most patients, therapy should be switched to a less toxic chelator as soon as the clinical condition permits.
    I) PHARMACOKINETICS
    1) Tmax: IM: 30 to 60 min. Dimercaprol is lipid-soluble and can enter cells. The oxidized form of dimercaprol (an active metabolite) is found in the urine. Excretion: Renal: 40% to 60% excreted in the urine rapidly, within 6 to 24 hours. Bile: approximately 50% of an injected dose is excreted in the bile. Elimination half-life: very short, with complete excretion within 4 hours.
    J) DIFFERENTIAL DIAGNOSIS
    1) Includes other agents that cause hypertension, tachycardia, or seizures.

Range Of Toxicity

    A) TOXICITY: About 20% of children develop mild adverse effects at doses less than 3 mg/kg. About two-thirds of children develop adverse effects at doses between 3 and 4.9 mg/kg. At doses of 5 mg/kg or more virtually all children develop adverse effects. Anorexia, restlessness, vomiting, pain at injection site, salivation, hypertension, fever, tachycardia, seizures, and leukotoxic effect have been reported in patients after receiving 5 to 40.5 mg/kg of dimercaprol. Hypertensive encephalopathy (eg, vasomotor changes, hypertension, seizures, coma, and stupor) has been reported after doses greater than 5 mg/kg.
    B) THERAPEUTIC DOSE: Varies by indication; range, 2.5 to 5 mg/kg IM every 4 to 6 hours daily.

Clinical Effects

Summary Of Exposure

    A) USES: Dimercaprol is used for the treatment of mercury (inorganic and elemental), arsenic, and gold poisoning. It is also used in combination with Edetate Calcium Disodium injection to treat patients with severe lead poisoning. Dimercaprol is contraindicated in methyl mercury poisoning.
    B) PHARMACOLOGY: Dimercaprol contains two sulfhydryl groups that form a stable relatively nontoxic chelate 5-membered heterocyclic ring with heavy metals. The most stable complexes are formed with Class B metals, including arsenic, mercury, and gold. Lead and tin, Class A metals, form stable complexes with nitrogen, oxygen, sulfur, and phosphorus-containing chelates, and thus will combine with both dimercaprol and EDTA. The resulting complex contains a 1:1 or 2:1 ratio of dimercaprol to metal. The combination of dimercaprol with the metal prevents the metal from combining with sulfhydryl groups on physiologic proteins, such as enzymes, and keeps them inert until they can be excreted.
    C) EPIDEMIOLOGY: Overdose is rare.
    D) WITH THERAPEUTIC USE
    1) The majority of patients receiving therapeutic doses of dimercaprol intramuscularly will experience a transient increase in pulse and blood pressure. The onset is between 5 and 40 minutes, usually peaking at 30 minutes, and subsiding gradually within 3 hours. Transient erythema and whealing, contact dermatitis, pain at the injection site, nausea, vomiting, abdominal pain, lacrimation, conjunctivitis, blepharospasm, pain in the limbs, muscle stiffness, paresthesias, headache, tremors, weakness, fatigue, rhinorrhea, a burning sensation of the lips, mouth, and throat, and fever have also been reported. Fever is more common in children, occurring in about 30%; this subsides rapidly when the drug is discontinued.
    E) WITH POISONING/EXPOSURE
    1) Anorexia, restlessness, vomiting, pain at injection site, salivation, hypertension, fever, tachycardia, seizures, and "leukotoxic" effect have been reported in patients after receiving 5 to 40.5 mg/kg of dimercaprol.
    2) A syndrome similar to hypertensive encephalopathy (eg, vasomotor changes, severe hypertension, seizures, coma, and stupor) has been reported after excessive doses. Vomiting, seizures, and/or stupor have been reported following dimercaprol doses greater than 5 mg/kg beginning within 30 minutes and subsiding within 6 hours of injection.

Vital Signs

    3.3.3) TEMPERATURE
    A) WITH THERAPEUTIC USE
    1) FEVER: Fever is more common in children, occurring in about 30%; this subsides rapidly when the drug is discontinued (Prod Info BAL in Oil(R), 1999; Prod Info BAL In Oil intramuscular injection, 2008; Gilman et al, 1990).
    2) Fever occurred in 8 of 27 children following the second or third injection of BAL (doses more than 3 mg/kg); fever persisted until BAL was stopped (Woody & Kometani, 1948).

Heent

    3.4.3) EYES
    A) WITH THERAPEUTIC USE
    1) Lacrimation, conjunctivitis, and blepharospasm are frequently occurring side effects. A burning or tingling of the eyes may also occur (Prod Info BAL In Oil intramuscular injection, 2008; Chisolm, 1968a; Sulzberger et al, 1946a; Eagle & Magnuson, 1946; Modell et al, 1946).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) HYPERTENSIVE EPISODE
    1) WITH THERAPEUTIC USE
    a) The majority of patients receiving therapeutic doses of dimercaprol intramuscularly will experience a transient increase in pulse and blood pressure. The onset is between 5 and 40 minutes, usually peaking at 30 minutes, and subsiding gradually within 3 hours (Prod Info BAL In Oil intramuscular injection, 2008; Chisolm, 1968a; Woody & Kometani, 1948; Sulzberger et al, 1946a; Modell et al, 1946).
    b) A rise in blood pressure was observed in 7 of 9 patients with secondary or tertiary syphilis following administration of dimercaprol, usually occurring after the second dose of 5 mg/kg. The blood pressure increase ranged from 14 to 52 mmHg systolic, and 10 to 40 mmHg diastolic. In one patient with pre-existing essential hypertension, the blood pressure fell after treatment with dimercaprol (Sulzberger et al, 1946a).
    2) WITH POISONING/EXPOSURE
    a) After receiving 5 to 40.5 mg/kg of BAL, hypertension occurred in 5 of 12 children (Woody & Kometani, 1948).
    b) A constellation of effects clinically resembling hypertensive encephalopathy (severe hypertension, seizures, coma, and stupor) has been described in patients receiving very large doses (greater than 5 mg/kg)(Woody & Kometani, 1948).
    B) SINUS TACHYCARDIA
    1) WITH THERAPEUTIC USE
    a) The majority of patients receiving therapeutic doses of dimercaprol intramuscularly will experience a transient increase in pulse and blood pressure. The onset is between 5 and 40 minutes, peaking at 30 minutes, and subsiding gradually within 3 hours (Prod Info BAL In Oil intramuscular injection, 2008; Chisolm, 1968a).
    b) A moderate acceleration of heart rate is common during the peak effect of dimercaprol (Modell et al, 1946).
    2) WITH POISONING/EXPOSURE
    a) After receiving 5 to 40.5 mg/kg of BAL, tachycardia occurred in 5 of 12 children (Woody & Kometani, 1948).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) NASAL DISCHARGE
    1) WITH THERAPEUTIC USE
    a) Rhinorrhea is a frequently occurring side effect (Prod Info BAL In Oil intramuscular injection, 2008; Sulzberger et al, 1946a; Eagle & Magnuson, 1946).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM FINDING
    1) WITH THERAPEUTIC USE
    a) Central nervous system effects are common, and include paresthesias, apprehension, headache, tremors, anxiety, followed by weakness and fatigue in severe cases (Prod Info BAL In Oil intramuscular injection, 2008; Sulzberger et al, 1946a; Modell et al, 1946; Eagle & Magnuson, 1946).
    b) Animal studies suggest that BAL can mobilize arsenic and mercury, causing an increase of the concentration of metal in the brain (Aposhian et al, 1995).
    2) WITH POISONING/EXPOSURE
    a) A constellation of effects clinically resembling hypertensive encephalopathy (severe hypertension, convulsions, coma, and stupor) has been described in patients receiving very large doses (>5 mg/kg)(Woody & Kometani, 1948).
    b) Vomiting, convulsions, and/or stupor have been reported following dimercaprol doses greater than 5 mg/kg beginning within 30 minutes and subsiding within 6 hours of injection (Prod Info BAL in Oil(R), 1999; Prod Info BAL In Oil intramuscular injection, 2008).
    c) In 12 children who received 5 to 40.5 mg/kg of BAL, restlessness (7 patients) and convulsions (3 patients), were reported (Woody & Kometani, 1948).
    B) HEADACHE
    1) WITH THERAPEUTIC USE
    a) Headache is a frequently occurring side effect; the severity is dose-related (Prod Info BAL In Oil intramuscular injection, 2008; Sulzberger et al, 1946a; Eagle & Magnuson, 1946); the incidence was 3 of 5 subjects given 350 mg intramuscularly (5 mg/kg) every 2 to 4 hours (Sulzberger et al, 1946a).
    C) PARESTHESIA
    1) WITH THERAPEUTIC USE
    a) Burning or tingling of the nose, eyes, mouth, and skin is a common adverse reaction to dimercaprol. These symptoms may be accompanied by perspiration, a sense of warmth, and a feeling of extreme unrest and apprehension (Prod Info BAL In Oil intramuscular injection, 2008; Chisolm, 1968a; Modell et al, 1946; Eagle & Magnuson, 1946).
    D) TREMOR
    1) WITH THERAPEUTIC USE
    a) Shakiness and tremor were reported in 2 of 5 volunteers given 350 mg intramuscularly every 2 to 4 hours (Sulzberger et al, 1946a).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) GASTROINTESTINAL TRACT FINDING
    1) WITH THERAPEUTIC USE
    a) Moderate to severe abdominal pain was described in 4 of 5 healthy subjects given 350 mg intramuscularly at 0, 2, 6, and 10 hours. The greatest intensity occurred with the second dose (given two hours after the initial dose); a cumulative effect was suspected (Sulzberger et al, 1946a).
    b) Nausea and vomiting are among the most frequently occurring adverse reactions. Vomiting is usually associated with most severe reactions. Salivation and a sense of warmth or pain in the abdomen are also common (Prod Info BAL In Oil intramuscular injection, 2008; Chisolm, 1968a; Sulzberger et al, 1946a; Eagle & Magnuson, 1946; Modell et al, 1946; Longcope et al, 1946).
    c) Nausea and vomiting were the most frequently occurring adverse reactions following intramuscular injection of dimercaprol in a study of 34 healthy male volunteers. Vomiting occurred in 11 subjects. Nausea was noted even at the lowest dosage (150 mg) and was unequivocal at doses of 250 mg (3.6 mg/kg). The onset was within a few minutes, peaked at 10 to 30 minutes, and subsided rapidly after injection (Sulzberger et al, 1946a).
    d) A burning sensation of the lips, mouth, and throat, sometimes accompanied by a constricted feeling, and throat, chest, or hand pain, were described in all 5 volunteers given 350 mg every 2 to 4 hours (Prod Info BAL In Oil intramuscular injection, 2008; Sulzberger et al, 1946a; Eagle & Magnuson, 1946; Longcope et al, 1946).
    2) WITH POISONING/EXPOSURE
    a) Vomiting, convulsions, and/or stupor have been reported following dimercaprol doses greater than 5 mg/kg beginning within 30 minutes and subsiding within 6 hours of injection (Prod Info BAL in Oil(R), 1999; Prod Info BAL in Oil Ampoules, 1998).
    b) In 12 patients who received 5 to 40.5 mg/kg of BAL, anorexia (6 patients), vomiting (4 patients), and salivation (2 patients) were reported (Woody & Kometani, 1948).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) HEMOLYTIC ANEMIA
    1) WITH THERAPEUTIC USE
    a) Two 3-year-old, black male G6PD-deficient children developed hemolytic anemia following therapy with dimercaprol 4 mg/kg every 4 hours for 30 doses for treatment of lead poisoning. The onset was during the third or fourth day of therapy, with a return to normal on the tenth day following discontinuation of therapy (Janakiraman et al, 1978).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) DERMATOLOGICAL FINDING
    1) WITH THERAPEUTIC USE
    a) Topical application of dimercaprol induces an immediate transient erythema and whealing, with an onset of 15 minutes to 2 hours. Following resolution of this effect, sensitized individuals may then experience a delayed contact dermatitis, occurring 24 to 48 hours after application. This type of reaction occurs in about 19% of normal individuals receiving prolonged therapy (Sulzberger et al, 1946; Sulzberger et al, 1946a).
    b) The vigorous application of one ounce of 5% dimercaprol (total dose 1.5 g) over the back, shoulders, chest, abdomen, and upper arms in 5 healthy volunteers resulted in severe generalized whealing in one subject, which gradually resolved over 36 hours. Two other subjects developed moderate evanescent urticaria (Sulzberger et al, 1946a).
    B) CONTACT DERMATITIS
    1) WITH THERAPEUTIC USE
    a) Topical application of 5% dimercaprol in three different vehicles, applied to the flexor aspect of the left forearm daily for 14 days, induced a delayed contact dermatitis in 19% of 88 volunteers. The reactions were similar to Type IV reactions, with an onset of 24 to 48 hours; but dissimilar in the type of lesion produced, with erythema, edema, and papules, but no vesiculation. The reactions were typically confined to the site of the initial application; subsequent application to distant sites in sensitized individuals produced a lower frequency and severity of reaction. Damaged skin was more sensitive, with an incidence of dermatitis in 36% of subjects. Intramuscular injection also induced sensitization to subsequent topical administration; however, readministration of an intramuscular dose did not produce cutaneous reactions (Sulzberger et al, 1946; Eagle & Magnuson, 1946).
    C) INJECTION SITE PAIN
    1) WITH THERAPEUTIC USE
    a) Intramuscular administration of dimercaprol frequently results in pain at the injection site, followed by residual tenderness over the next several hours (Aposhian et al, 1995; Eagle & Magnuson, 1946; Modell et al, 1946; Sulzberger et al, 1946a).
    b) Varying degrees of pain around the injection site, with some radiating pain and limb stiffness, were noted in a study of 34 healthy male volunteers given intramuscular injections of BAL in Oil(R) in the upper outer gluteal regions. Doses ranged from 1.5 to 3 mL. Most injection sites displayed slight tenderness at 24 hours postinjection; no severe reactions were noted (Sulzberger et al, 1946a). Sterile abscesses have been described (Prod Info BAL In Oil intramuscular injection, 2008; Harth et al, 1978). Administration of procaine into the injection site prior to injection of dimercaprol may decrease the pain associated with injection (Stafford & Crosby, 1978).
    c) An abscess at the site of an injection has been reported in one patient (Longcope et al, 1946).
    2) WITH POISONING/EXPOSURE
    a) In one study, pain at injection site occurred in 2 of 12 children after receiving 5 to 40.5 mg/kg of BAL (Woody & Kometani, 1948)

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) MUSCULOSKELETAL FINDING
    1) WITH THERAPEUTIC USE
    a) Pain in the limbs and muscle stiffness may occur following injection (Modell et al, 1946; Eagle & Magnuson, 1946; Longcope et al, 1946).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) ACUTE ALLERGIC REACTION
    1) WITH THERAPEUTIC USE
    a) PEANUT ALLERGY: Patients with peanut allergy may experience acute allergic reactions (Prod Info BAL In Oil intramuscular injection, 2008).

Reproductive

    3.20.1) SUMMARY
    A) Dimercaprol is classified as FDA pregnancy category C. The number of pregnant women exposed to dimercaprol and reported in the literature is so limited that no pattern or estimate of risk can be determined at this time. Apparently normal infants have been born to women treated with dimercaprol for Wilson disease during pregnancy and a case report describes the complete recovery of a woman and her 20-week old fetus after she experienced an acute ingestion of inorganic arsenic.
    3.20.2) TERATOGENICITY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the teratogenic potential of this agent (Prod Info BAL in Oil injection, 2006).
    B) LACK OF EFFECT
    1) Dimercaprol has been used to treat Wilson disease in pregnancy with delivery of apparently normal infants (Dreifuss & McKinney, 1966).
    C) ANIMAL STUDIES
    1) No reproductive animal studies have been conducted for dimercaprol (Prod Info BAL in Oil injection, 2006).
    3.20.3) EFFECTS IN PREGNANCY
    A) LACK OF INFORMATION
    1) The number of pregnant women exposed to dimercaprol and reported in the literature is so limited that no pattern or estimate of risk can be determined at this time (Prod Info BAL in Oil injection, 2006).
    B) PREGNANCY CATEGORY
    1) Dimercaprol is classified as FDA pregnancy category C (Prod Info BAL in Oil injection, 2006).
    C) LACK OF EFFECT
    1) CASE REPORT: One case report describes the complete recovery of a woman and her 20-week old fetus after she experienced an acute ingestion of inorganic arsenic (Daya et al, 1989).
    2) CASE REPORT: Dimercaprol has been used to treat Wilson disease in pregnancy with delivery of apparently normal infants (Dreifuss & McKinney, 1966).
    D) ANIMAL STUDIES
    1) No reproductive animal studies have been conducted for dimercaprol (Prod Info BAL in Oil injection, 2006).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) LACK OF INFORMATION
    1) It is unknown whether dimercaprol is excreted in human milk (Prod Info BAL in Oil injection, 2006). According to The World Health Organization, the use of dimercaprol should be avoided in general, particularly in premature infants, those less than one month of age, and individuals with glucose-6-phosphate dehydrogenase deficiency (Anon, 2002). Because data are lacking, the manufacturer recommends exercising caution when administering dimercaprol to a nursing mother (Prod Info BAL in Oil injection, 2006). If used during lactation, monitor infants for side effects such as hemolysis and jaundice (Anon, 2002).
    3.20.5) FERTILITY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects on fertility from exposure to dimercaprol.

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS59-52-9 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) Not Listed

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    B) Monitor vital signs.
    C) Monitor serum electrolytes in patients with significant vomiting.
    D) Institute continuous cardiac monitoring and obtain an ECG in symptomatic patients.
    E) For more information regarding laboratory evaluation after heavy metal poisoning, refer to "LEAD", "GOLD DRUGS", "ARSENIC", "MERCURY, ELEMENTAL", "MERCURY, INORGANIC" documents.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.2) DISPOSITION/PARENTERAL EXPOSURE
    6.3.2.1) ADMISSION CRITERIA/PARENTERAL
    A) Patients with severe hypertension, tachycardia, and persistent seizures should be admitted to an intensive care setting.
    6.3.2.2) HOME CRITERIA/PARENTERAL
    A) There is no data to support home management, and dimercaprol is generally only used in the hospital setting.
    6.3.2.3) CONSULT CRITERIA/PARENTERAL
    A) Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    6.3.2.5) OBSERVATION CRITERIA/PARENTERAL
    A) Any patient with symptoms should be observed with frequent monitoring of vital signs. Patients that remain asymptomatic can be discharged.

Monitoring

    A) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    B) Monitor vital signs.
    C) Monitor serum electrolytes in patients with significant vomiting.
    D) Institute continuous cardiac monitoring and obtain an ECG in symptomatic patients.
    E) For more information regarding laboratory evaluation after heavy metal poisoning, refer to "LEAD", "GOLD DRUGS", "ARSENIC", "MERCURY, ELEMENTAL", "MERCURY, INORGANIC" documents.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Gastrointestinal decontamination is not recommended; administered via the parenteral route.

Range Of Toxicity

Summary

    A) TOXICITY: About 20% of children develop mild adverse effects at doses less than 3 mg/kg. About two-thirds of children develop adverse effects at doses between 3 and 4.9 mg/kg. At doses of 5 mg/kg or more virtually all children develop adverse effects. Anorexia, restlessness, vomiting, pain at injection site, salivation, hypertension, fever, tachycardia, seizures, and leukotoxic effect have been reported in patients after receiving 5 to 40.5 mg/kg of dimercaprol. Hypertensive encephalopathy (eg, vasomotor changes, hypertension, seizures, coma, and stupor) has been reported after doses greater than 5 mg/kg.
    B) THERAPEUTIC DOSE: Varies by indication; range, 2.5 to 5 mg/kg IM every 4 to 6 hours daily.

Therapeutic Dose

    7.2.1) ADULT
    A) FOR MILD ARSENIC OR GOLD POISONING: 2.5 mg/kg 4 times daily for 2 days, 2 times on the third day, and once daily thereafter for 10 days. Administered by deep intramuscular injection only. Continue the treatment for 2 to 7 days depending on clinical response (Prod Info BAL In Oil intramuscular injection, 2008).
    B) FOR SEVERE ARSENIC OR GOLD POISONING: 3 mg/kg every 4 hours for 2 days, 4 times on the third day, then twice daily thereafter for 10 days. Administered by deep intramuscular injection only. Continue the treatment for 2 to 7 days depending on clinical response (Prod Info BAL In Oil intramuscular injection, 2008).
    C) FOR MERCURY (ELEMENTAL, INORGANIC) POISONING: 5 mg/kg initially, then 2.5 mg/kg 1 or 2 times daily for 10 days. Administered by deep intramuscular injection only. Continue the treatment for 2 to 7 days depending on clinical response (Prod Info BAL In Oil intramuscular injection, 2008).
    D) FOR ACUTE LEAD ENCEPHALOPATHY: 4 mg/kg is given alone in the first dose and thereafter at 4-hour intervals with Edetate Calcium Disodium injection administered at a separate site. For less severe poisoning, dimercaprol dose can be decreased to 3 mg/kg after the first dose. Administered by deep intramuscular injection only. Continue the treatment for 2 to 7 days depending on clinical response (Prod Info BAL In Oil intramuscular injection, 2008).
    E) ORGANIC MERCURY: Dimercaprol therapy has been shown to increase brain mercury levels in experimental animal models of methyl mercury (Berlin et al, 1965; Zimmer & Carter, 1979) and phenylmercuric acetate (Berlin & Rylander, 1964) poisoning. It is CONTRAINDICATED in methyl mercury poisoning (Clarkson, 1990).

Maximum Tolerated Exposure

    A) In children, doses less than 3 mg/kg are associated with mild adverse reactions (irritability, anorexia, restlessness) in about 20% of patients. Similar effects as well as fever developed in about 66% of children treated with 3 to 4.9 mg/kg. At doses of 5 mg/kg or greater, all children had adverse reactions, including irritability, restlessness, increased heart rate and blood pressure, and fever(Woody & Kometani, 1948).
    B) A constellation of effects clinically resembling hypertensive encephalopathy (severe hypertension, convulsions, coma, and stupor) has been described in patients receiving very large doses (greater than 5 mg/kg) (Woody & Kometani, 1948). Vomiting, seizures, and/or stupor have been reported following dimercaprol doses greater than 5 mg/kg beginning within 30 minutes and subsiding within 6 hours of injection (Prod Info BAL In Oil intramuscular injection, 2008).
    C) Anorexia, restlessness, vomiting, pain at injection site, salivation, hypertension, fever, tachycardia, convulsions, and leukotoxic effect have been reported in patients after receiving 5 to 40.5 mg/kg of dimercaprol (Woody & Kometani, 1948).

Workplace Standards

    A) ACGIH TLV Values for CAS59-52-9 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS59-52-9 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS59-52-9 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS59-52-9 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) LD50- (INTRAMUSCULAR)RAT:
    1) 105 mg/kg (Prod Info BAL In Oil intramuscular injection, 2008)
    B) LD50- (INTRAPERITONEAL)RAT:
    1) 140 mg/kg (Prod Info BAL In Oil intramuscular injection, 2008)
    C) LD50- (INTRAPERITONEAL)MOUSE:
    1) 125 mg/kg (Prod Info BAL In Oil intramuscular injection, 2008)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Dimercaprol contains two sulfhydryl groups that form a stable relatively nontoxic chelate 5-membered heterocyclic ring with heavy metals. The most stable complexes are formed with Class B metals, including arsenic, mercury, and gold. Lead and tin, Class A metals, form stable complexes with nitrogen, oxygen, sulfur, and phosphorus-containing chelates, and thus will combine with both dimercaprol and EDTA. The resulting complex contains a 1:1 or 2:1 ratio of BAL to metal (Prod Info BAL in Oil Ampoules, 1998; Gilman, 1990; Chisolm, 1968). The combination of dimercaprol with the metal prevents the metal from combining with sulfhydryl groups on physiologic proteins, such as enzymes, and keeps them inert until they can be excreted (Prod Info BAL in Oil Ampoules, 1998; Deane et al, 1953).

Physicochemical

Physical Characteristics

    A) Dimercaprol injection is an oil soluble (Aposhian et al, 1995; Prod Info BAL in Oil Ampoules, 1998), colorless or almost colorless liquid with a disagreeable, mercaptan-like odor (Prod Info BAL in Oil injection, 2006).

Molecular Weight

    A) 124.22 (Prod Info BAL in Oil injection, 2006)

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