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UNITHIOL

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Unithiol is a water-soluble chelating agent structurally related to dimercaprol, but reportedly less toxic.

Specific Substances

    1) 2,3-Dimercaptopropane sulfonic acid sodium salt
    2) Dimaval(R)
    3) DMPS
    4) Sodium 2,3-dimercapto-1-propanesulfonate
    5) Unithiolum
    6) Unitiol
    7) Unitioli
    8) CAS 4076-02-2
    1.2.1) MOLECULAR FORMULA
    1) C(3)H(7)NaO(3)S(3)

Available Forms Sources

    A) FORMS
    1) Unithiol is available as ampoules containing 250 mg unithiol in 5 mL for injection (Prod Info Dimaval(R) intravenous intramuscular injection solution, 2013), and as 100 mg hard capsules available in packages of 3, 9 and 20 capsules (Prod Info DIMAVAL(R) oral capsules, 2004).
    B) SOURCES
    1) Unithiol is available outside the US from Heyl Chem-pharm Fabrik (Germany) (www.heyl-berlin.de) (Prod Info Dimaval(R) intravenous intramuscular injection solution, 2013). It is not approved for human use by the US FDA. In the US, unithiol has been obtained from compounding pharmacies for use in heavy metal intoxication.
    C) USES
    1) MERCURY
    a) Unithiol has been used to treat patients with acute or chronic poisoning with organic and inorganic forms of mercury (Prod Info Dimaval(R) intravenous intramuscular injection solution, 2013; Toet et al, 1994; Campbell et al, 1986; Dargan et al, 2003).
    b) Unithiol has been shown to increase urinary mercury excretion after excessive exposure to organic mercury (Drasch et al, 2007), inorganic mercury (Garza-Ocanas et al, 1997), and in patients with elemental mercury exposure (Torres-Alanis et al, 1995; Vamnes et al, 2003; Torres-Alanis et al, 2000).
    c) In a study of patients with methylmercury poisoning, unithiol decreased mercury half life to 10 days, compared with a half life of 65 days in patients receiving no treatment and 60 days in patients receiving placebo (Clarkson et al, 1981).
    d) In an open label study of patients with mercury poisoning secondary to gold mining, use of unithiol was associated with an increase in urinary excretion of mercury and a reduction in neurologic symptoms of poisoning (Bose-O'Reilly et al, 2003).
    2) ARSENIC
    a) Unithiol has been used in the treatment of acute and chronic arsenic poisoning (Kruszewska et al, 1996; Moore et al, 1994).
    b) Unithiol has been shown to increase urinary arsenic excretion and has been associated with clinical improvement in patients with acute and chronic arsenic poisoning (Mazumder et al, 2001; Wax & Thornton, 2000; Heinrich-Ramm et al, 2003).
    3) LEAD
    a) Oral unithiol increased urinary excretion of lead in 6 children with chronic lead poisoning (Chisolm & Thomas, 1985).
    4) BISMUTH
    a) Unithiol has been used to treat patients with acute bismuth intoxication; it induces a small increase in renal elimination, but allows removal of bismuth by hemodialysis (Hruz et al, 2002).
    b) In a patient with bismuth intoxication, unithiol increased urinary bismuth clearance (from a baseline of 2.2 L/min to 8.2 to 9.7 mL/min) and increased the amount of bismuth removed by hemodialysis (from none without unithiol to 10 to 52 mL/min with unithiol) (Stevens et al, 1995).
    5) OTHER
    a) In a study of 11 subjects, treatment with unithiol increased urinary excretion of copper (2 to 119 fold), selenium (3 to 43.8 fold), zinc (1.6 to 44 fold) and magnesium (1.75 to 42.7 fold) (Torres-Alanis et al, 2000).
    b) Unithiol increased urinary copper excretion in patients with Wilson's disease (Wang et al, 2003).
    c) In China, unithiol has been used to treat human poisoning with non-metallic pesticides, such as tetramine, nereistoxin, chloridmieform, and bactercide 402 (Chen & Lu, 2004; Chan & Chan, 2006). It is unclear what data supports this use.
    d) The manufacturer states that unithiol may also be suitable to increase elimination of antimony, chromium and cobalt, but provides no data to support this (Prod Info DIMAVAL(R) oral capsules, 2004).

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: Unithiol, a chelator, is used as an antidote to treat mercury poisoning. Unithiol is available in Russia and Germany. It is not approved for human use by the US FDA. In the US, unithiol has been obtained from compounding pharmacies for use in heavy metal intoxication.
    B) PHARMACOLOGY: Unithiol is a chelating agent. It has two neighboring SH groups, which form stable complexes with heavy metals such as mercury. This allows complexation of the heavy metal in serum, and the resulting metal-unithiol complex is then excreted into the urine via the kidneys.
    C) EPIDEMIOLOGY: Exposure is uncommon.
    D) WITH THERAPEUTIC USE
    1) ADVERSE EFFECTS: Chills, fever and rashes are the most common adverse effects. Prolonged use may cause mineral imbalance (especially zinc and copper). Hypotension, nausea, vertigo and weakness may develop after rapid injection. Elevated aminotransferase concentrations, reduced white blood cell count, angina pectoris, loss of appetite, pain at the injection site, unpleasant hydrogen sulfide smell, and taste disturbance occurs rarely. An asthma attack can occur in patients with asthma following rapid administration.
    E) WITH POISONING/EXPOSURE
    1) OVERDOSE: No human overdose data available. Overdose may cause hypotension, nausea, weakness and vertigo. Mineral imbalance, particularly low levels of zinc and copper, may also develop after overdose.
    0.2.20) REPRODUCTIVE
    A) Animal studies have not revealed any evidence of toxicity or teratogenic effects from unithiol. If unithiol is used in a pregnant patient, mineral balance (particularly zinc and copper) should be monitored closely.
    0.2.21) CARCINOGENICITY
    A) At unithiol concentrations of 0.004 to 2.5 micromolar, the Ames test did not reveal evidence of mutagenicity.

Laboratory Monitoring

    A) Monitor vital signs. Monitor CBC. Monitor serum concentration of electrolytes and trace elements (especially magnesium, zinc and copper) and transaminase levels after a large overdose.
    B) Monitor renal function as indicated once mercury is mobilized by unithiol therapy; mercury may trigger renal failure.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF TOXICITY
    1) Treatment is symptomatic and supportive. Significant hypersensitivity has been rarely reported. Severe toxicity is not expected.
    B) DECONTAMINATION
    1) PREHOSPITAL: GI decontamination is generally not necessary.
    2) HOSPITAL: GI decontamination is generally not necessary unless the ingestion is extremely large or there are coingestants with potential toxicity.
    C) HYPOTENSION
    1) Avoid rapid IV administration of unithiol. Monitor blood pressure. Initially treat with IV 0.9% saline 10 to 20 mL/kg, if hypotension persists consider dopamine, norepinephrine.
    D) HYPERSENSITIVITY REACTION
    1) Skin rash and itch may develop with IV administration; stop unithiol therapy. Significant hypersensitivity has been rarely reported. MILD/MODERATE: Antihistamines with or without inhaled beta agonists, corticosteroids or epinephrine. SEVERE: Administer oxygen, aggressive airway management, antihistamines, epinephrine, corticosteroids, ECG monitoring, and IV fluids.
    E) ENHANCED ELIMINATION
    1) Unithiol can be removed by dialysis.
    F) PATIENT DISPOSITION
    1) HOME CRITERIA: Unithiol is typically used only in a hospital setting; home care is not indicated.
    2) OBSERVATION CRITERIA: Patients with a deliberate overdose, and those who are symptomatic should be observed with frequent monitoring of vital signs. Patients that remain asymptomatic can be discharged.
    3) ADMISSION CRITERIA: Patients that develop significant hypotension or a hypersensitivity reaction may need to be admitted to the hospital until symptoms resolve.
    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.
    0.4.6) PARENTERAL EXPOSURE
    A) Unithiol is also available orally; see ORAL Overview for further information.

Range Of Toxicity

    A) TOXICITY: A toxic dose has not been established. There are no overdose cases reported.
    B) THERAPEUTIC DOSE: INTRAVENOUS: DAY 1: The usual dose is 250 mg IV every 3 to 4 hours; DAY 2: 250 mg IV every 4 to 6 hours; DAY 3: 250 mg every 6 to 8 hours; DAY 4: 250 mg IV every 8 to 12 hours; subsequent days: depends on the severity of poisoning. ORAL: The oral dose ranges from 200 mg every 2 hours to 100 mg every 6 to 8 hours depending on the severity of poisoning.

Clinical Effects

Summary Of Exposure

    A) USES: Unithiol, a chelator, is used as an antidote to treat mercury poisoning. Unithiol is available in Russia and Germany. It is not approved for human use by the US FDA. In the US, unithiol has been obtained from compounding pharmacies for use in heavy metal intoxication.
    B) PHARMACOLOGY: Unithiol is a chelating agent. It has two neighboring SH groups, which form stable complexes with heavy metals such as mercury. This allows complexation of the heavy metal in serum, and the resulting metal-unithiol complex is then excreted into the urine via the kidneys.
    C) EPIDEMIOLOGY: Exposure is uncommon.
    D) WITH THERAPEUTIC USE
    1) ADVERSE EFFECTS: Chills, fever and rashes are the most common adverse effects. Prolonged use may cause mineral imbalance (especially zinc and copper). Hypotension, nausea, vertigo and weakness may develop after rapid injection. Elevated aminotransferase concentrations, reduced white blood cell count, angina pectoris, loss of appetite, pain at the injection site, unpleasant hydrogen sulfide smell, and taste disturbance occurs rarely. An asthma attack can occur in patients with asthma following rapid administration.
    E) WITH POISONING/EXPOSURE
    1) OVERDOSE: No human overdose data available. Overdose may cause hypotension, nausea, weakness and vertigo. Mineral imbalance, particularly low levels of zinc and copper, may also develop after overdose.

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) ANGINA
    1) WITH THERAPEUTIC USE
    a) Angina is rarely reported with therapeutic use (Prod Info DIMAVAL(R) IV, IM injection, 2004).
    B) HYPOTENSIVE EPISODE
    1) WITH THERAPEUTIC USE
    a) Hypotension, nausea, vertigo and weakness may develop after rapid intravenous administration (Prod Info Dimaval(R) intravenous intramuscular injection solution, 2013).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) ASTHMA
    1) WITH THERAPEUTIC USE
    a) Unithiol should be used with caution in patients with asthma. In rare cases, an asthma attack can occur in patients with a history of asthma during or immediately after injection of unithiol (Prod Info Dimaval(R) intravenous intramuscular injection solution, 2013).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) LOSS OF APPETITE
    1) WITH THERAPEUTIC USE
    a) Loss of appetite, dysgeusia and abdominal complaints may develop with therapeutic doses (Prod Info Dimaval(R) intravenous intramuscular injection solution, 2013).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) LEUKOPENIA
    1) WITH THERAPEUTIC USE
    a) A 50% reduction in white blood cell count has been reported rarely with therapeutic use (Prod Info Dimaval(R) intravenous intramuscular injection solution, 2013).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) ERUPTION
    1) WITH THERAPEUTIC USE
    a) Rashes and pruritus are among the more common adverse effects; they usually subside with the cessation of therapy. More severe rashes such as erythema exsudativum multiforme and Stevens-Johnson syndrome have been rarely reported (Prod Info Dimaval(R) intravenous intramuscular injection solution, 2013).

Reproductive

    3.20.1) SUMMARY
    A) Animal studies have not revealed any evidence of toxicity or teratogenic effects from unithiol. If unithiol is used in a pregnant patient, mineral balance (particularly zinc and copper) should be monitored closely.
    3.20.3) EFFECTS IN PREGNANCY
    A) LACK OF INFORMATION
    1) There are no reported cases of use of unithiol by pregnant women. If unithiol is used in a pregnant patient, mineral balance (particularly zinc and copper) should be monitored closely, to avoid deficiency of essential trace elements in the fetus (Prod Info Dimaval(R) intravenous intramuscular injection solution, 2013).
    B) ANIMAL STUDIES
    1) Animal studies have not revealed any evidence of toxicity or teratogenic effects from unithiol (Prod Info Dimaval(R) intravenous intramuscular injection solution, 2013).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) LACK OF INFORMATION
    1) It is not know if unithiol is excreted in human milk; however breast feeding should generally be avoided in patients with heavy metal poisoning (Prod Info Dimaval(R) intravenous intramuscular injection solution, 2013).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS4076-02-2 (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
    3.21.2) SUMMARY/HUMAN
    A) At unithiol concentrations of 0.004 to 2.5 micromolar, the Ames test did not reveal evidence of mutagenicity.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor vital signs. Monitor CBC. Monitor serum concentration of electrolytes and trace elements (especially magnesium, zinc and copper) and transaminase levels after a large overdose.
    B) Monitor renal function as indicated once mercury is mobilized by unithiol therapy; mercury may trigger renal failure.
    4.1.2) SERUM/BLOOD
    A) Monitor CBC. Monitor serum concentration of electrolytes and trace elements (especially magnesium, zinc and copper) and transaminase levels after a large overdose (Prod Info Dimaval(R) intravenous intramuscular injection solution, 2013).
    4.1.3) URINE
    A) In patients being treated for heavy metal poisoning, urinary concentrations of the heavy metal are generally monitored with and without chelation to determine the efficacy of and need for further chelation. A 24 hour collection is preferred if possible.
    4.1.4) OTHER
    A) OTHER
    1) Monitor vital signs. Rapid administration of IV unithiol may produce a decrease in blood pressure (Prod Info Dimaval(R) intravenous intramuscular injection solution, 2013).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients that develop significant hypotension or a hypersensitivity reaction may need to be admitted to the hospital until symptoms resolve.
    6.3.1.2) HOME CRITERIA/ORAL
    A) Unithiol is typically used only in a hospital setting; home care is not indicated.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with a deliberate overdose, and those who are symptomatic should be observed with frequent monitoring of vital signs. Patients that remain asymptomatic can be discharged.

Monitoring

    A) Monitor vital signs. Monitor CBC. Monitor serum concentration of electrolytes and trace elements (especially magnesium, zinc and copper) and transaminase levels after a large overdose.
    B) Monitor renal function as indicated once mercury is mobilized by unithiol therapy; mercury may trigger renal failure.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Prehospital GI decontamination is generally not necessary.
    6.5.3) TREATMENT
    A) SUPPORT
    1) Treatment is symptomatic and supportive. Limited data. Significant hypersensitivity has been rarely reported. Severe toxicity is not expected.
    B) MONITORING OF PATIENT
    1) Monitor vital signs. Monitor CBC. Monitor serum concentration of electrolytes and trace elements (especially magnesium, zinc and copper) and transaminase levels after a large overdose. Monitor renal function as indicated once mercury is mobilized by unithiol therapy; mercury may trigger renal failure.
    C) HYPOTENSIVE EPISODE
    1) Avoid rapid administration of unithiol. Monitor blood pressure. Initially treat with IV 0.9% saline at 10 to 20 mL/kg, if hypotension persists consider dopamine, norepinephrine.
    2) SUMMARY
    a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.
    3) DOPAMINE
    a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    4) NOREPINEPHRINE
    a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
    b) DOSE
    1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
    2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
    3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).
    D) HYPERSENSITIVITY REACTION
    1) SUMMARY
    a) Skin rash and itch may develop with IV administration; stop unithiol therapy. Significant hypersensitivity has been rarely reported (Prod Info Dimaval(R) intravenous intramuscular injection solution, 2013).
    2) SUMMARY
    a) Mild to moderate allergic reactions may be treated with antihistamines with or without inhaled beta adrenergic agonists, corticosteroids or epinephrine. Treatment of severe anaphylaxis also includes oxygen supplementation, aggressive airway management, epinephrine, ECG monitoring, and IV fluids.
    3) BRONCHOSPASM
    a) ALBUTEROL
    1) ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007). CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 mg/kg (up to 10 mg) every 1 to 4 hours as needed, or 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).
    4) CORTICOSTEROIDS
    a) Consider systemic corticosteroids in patients with significant bronchospasm.
    b) PREDNISONE: ADULT: 40 to 80 milligrams/day. CHILD: 1 to 2 milligrams/kilogram/day (maximum 60 mg) in 1 to 2 divided doses divided twice daily (National Heart,Lung,and Blood Institute, 2007).
    5) MILD CASES
    a) DIPHENHYDRAMINE
    1) SUMMARY: Oral diphenhydramine, as well as other H1 antihistamines can be used as indicated (Lieberman et al, 2010).
    2) ADULT: 50 milligrams orally, or 10 to 50 mg intravenously at a rate not to exceed 25 mg/min or may be given by deep intramuscular injection. A total of 100 mg may be administered if needed. Maximum daily dosage is 400 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
    3) CHILD: 5 mg/kg/24 hours or 150 mg/m(2)/24 hours. Divided into 4 doses, administered intravenously at a rate not exceeding 25 mg/min or by deep intramuscular injection. Maximum daily dosage is 300 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
    6) MODERATE CASES
    a) EPINEPHRINE: INJECTABLE SOLUTION: It should be administered early in patients by IM injection. Using a 1:1000 (1 mg/mL) solution of epinephrine. Initial Dose: 0.01 mg/kg intramuscularly with a maximum dose of 0.5 mg in adults and 0.3 mg in children. The dose may be repeated every 5 to 15 minutes, if no clinical improvement. Most patients respond to 1 or 2 doses (Nowak & Macias, 2014).
    7) SEVERE CASES
    a) EPINEPHRINE
    1) INTRAVENOUS BOLUS: ADULT: 1 mg intravenously as a 1:10,000 (0.1 mg/mL) solution; CHILD: 0.01 mL/kg intravenously to a maximum single dose of 1 mg given as a 1:10,000 (0.1 mg/mL) solution. It can be repeated every 3 to 5 minutes as needed. The dose can also be given by the intraosseous route if IV access cannot be established (Lieberman et al, 2015). ALTERNATIVE ROUTE: ENDOTRACHEAL ADMINISTRATION: If IV/IO access is unavailable. DOSE: ADULT: Administer 2 to 2.5 mg of 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube. CHILD: DOSE: 0.1 mg/kg to a maximum of 2.5 mg administered as a 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube (Lieberman et al, 2015).
    2) INTRAVENOUS INFUSION: Intravenous administration may be considered in patients poorly responsive to IM or SubQ epinephrine. An epinephrine infusion may be prepared by adding 1 mg (1 mL of 1:1000 (1 mg/mL) solution) to 250 mL D5W, yielding a concentration of 4 mcg/mL, and infuse this solution IV at a rate of 1 mcg/min to 10 mcg/min (maximum rate). CHILD: A dosage of 0.01 mg/kg (0.1 mL/kg of a 1:10,000 (0.1 mg/mL) solution up to 10 mcg/min (maximum dose 0.3 mg) is recommended for children (Lieberman et al, 2010). Careful titration of a continuous infusion of IV epinephrine, based on the severity of the reaction, along with a crystalloid infusion can be considered in the treatment of anaphylactic shock. It appears to be a reasonable alternative to IV boluses, if the patient is not in cardiac arrest (Vanden Hoek,TLet al,null).
    8) AIRWAY MANAGEMENT
    a) OXYGEN: 5 to 10 liters/minute via high flow mask.
    b) INTUBATION: Perform early if any stridor or signs of airway obstruction.
    c) CRICOTHYROTOMY: Use if unable to intubate with complete airway obstruction (Vanden Hoek,TLet al,null).
    d) BRONCHODILATORS are recommended for mild to severe bronchospasm.
    e) ALBUTEROL: ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007).
    f) ALBUTEROL: CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 milligram/kilogram (maximum 10 milligrams) every 1 to 4 hours as needed OR administer 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).
    9) MONITORING
    a) CARDIAC MONITOR: All complicated cases.
    b) IV ACCESS: Routine in all complicated cases.
    10) HYPOTENSION
    a) If hypotensive give 500 to 2000 milliliters crystalloid initially (20 milliliters/kilogram in children) and titrate to desired effect (stabilization of vital signs, mentation, urine output); adults may require up to 6 to 10 L/24 hours. Central venous or pulmonary artery pressure monitoring is recommended in patients with persistent hypotension.
    1) VASOPRESSORS: Should be used in refractory cases unresponsive to repeated doses of epinephrine and after vigorous intravenous crystalloid rehydration (Lieberman et al, 2010).
    2) DOPAMINE: Initial Dose: 2 to 20 micrograms/kilogram/minute intravenously; titrate to maintain systolic blood pressure greater than 90 mm Hg (Lieberman et al, 2010).
    11) H1 and H2 ANTIHISTAMINES
    a) SUMMARY: Antihistamines are second-line therapy and are used as supportive therapy and should not be used in place of epinephrine (Lieberman et al, 2010).
    1) DIPHENHYDRAMINE: ADULT: 25 to 50 milligrams via a slow intravenous infusion or IM. PEDIATRIC: 1 milligram/kilogram via slow intravenous infusion or IM up to 50 mg in children (Lieberman et al, 2010).
    b) RANITIDINE: ADULT: 1 mg/kg parenterally; CHILD: 12.5 to 50 mg parenterally. If the intravenous route is used, ranitidine should be infused over 10 to 15 minutes or diluted in 5% dextrose to a volume of 20 mL and injected over 5 minutes (Lieberman et al, 2010).
    c) Oral diphenhydramine, as well as other H1 antihistamines, can also be used as indicated (Lieberman et al, 2010).
    12) DYSRHYTHMIAS
    a) Dysrhythmias and cardiac dysfunction may occur primarily or iatrogenically as a result of pharmacologic treatment (epinephrine) (Vanden Hoek,TLet al,null). Monitor and correct serum electrolytes, oxygenation and tissue perfusion. Treat with antiarrhythmic agents as indicated.
    13) OTHER THERAPIES
    a) There have been a few reports of patients with anaphylaxis, with or without cardiac arrest, that have responded to vasopressin therapy that did not respond to standard therapy. Although there are no randomized controlled trials, other alternative vasoactive therapies (ie, vasopressin, norepinephrine, methoxamine, and metaraminol) may be considered in patients in cardiac arrest secondary to anaphylaxis that do not respond to epinephrine (Vanden Hoek,TLet al,null).

Enhanced Elimination

    A) HEMODIALYSIS
    1) Unithiol and be removed by dialysis (Prod Info Dimaval(R) intravenous intramuscular injection solution, 2013).

Range Of Toxicity

Summary

    A) TOXICITY: A toxic dose has not been established. There are no overdose cases reported.
    B) THERAPEUTIC DOSE: INTRAVENOUS: DAY 1: The usual dose is 250 mg IV every 3 to 4 hours; DAY 2: 250 mg IV every 4 to 6 hours; DAY 3: 250 mg every 6 to 8 hours; DAY 4: 250 mg IV every 8 to 12 hours; subsequent days: depends on the severity of poisoning. ORAL: The oral dose ranges from 200 mg every 2 hours to 100 mg every 6 to 8 hours depending on the severity of poisoning.

Therapeutic Dose

    7.2.1) ADULT
    A) MERCURY POISONING
    1) IV: The dosing regimen depends on the severity of poisoning. Unithiol should be injected slowly over 3 to 5 minutes . Do not mix with other solutions (Prod Info Dimaval(R) intravenous intramuscular injection solution, 2013):
    1) FIRST DAY: 5 mL (one ampule) every 3 to 4 hours.
    2) SECOND DAY: 5 mL (one ampule) every 4 to 6 hours.
    3) THIRD DAY: 5 mL (one ampule) every 6 to 8 hours.
    4) FOURTH DAY: 5 mL (one ampule) every 8 to 12 hours.
    5) SUBSEQUENT DAYS: Depending on the patient's clinical condition, administer 5 mL (one ampule) 1 to 3 times daily.
    2) IM INJECTION: The dosing regimen depends on the severity of poisoning. Do not mix with other solutions (Prod Info Dimaval(R) intravenous intramuscular injection solution, 2013):
    1) FIRST DAY: 5 mL (one ampule) by every 3 to 4 hours.
    2) SECOND DAY: 5 mL (one ampule) every 4 to 6 hours.
    3) THIRD DAY: 5 mL (one ampule) every 6 to 8 hours.
    4) FOURTH DAY: 5 mL (one ampule) every 8 to 12 hours.
    5) SUBSEQUENT DAYS: Depending on the patient's clinical condition, administer 5 mL (one ampule) 1 to 3 times daily.
    3) ORAL: The patient may be switched to the oral dose after the fourth day of treatment via IV or IM injection (Prod Info Dimaval(R) intravenous intramuscular injection solution, 2013).
    7.2.2) PEDIATRIC
    A) MERCURY POISONING
    1) IV and IM INJECTION: Safety and efficacy have not been established in pediatric patients (Prod Info Dimaval(R) intravenous intramuscular injection solution, 2013).
    2) ORAL: Oral unithiol should be used only if medically necessary. The recommended initial dose: 20 to 30 mg/kg/day in many equally divided doses. The recommended maintenance dose: 1.5 to 15 mg/kg/day (Arbeitsgruppe BGVV, 1996).

Workplace Standards

    A) ACGIH TLV Values for CAS4076-02-2 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS4076-02-2 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS4076-02-2 :
    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 CAS4076-02-2 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) LD50- (SUBCUTANEOUS)MOUSE:
    1) 2000 mg/kg (Prod Info DIMAVAL(R) IV, IM injection, 2004)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Unithiol is a chelating agent. It has two neighboring SH groups, which form stable complexes with heavy metals such as mercury. This allows complexation of the heavy metal in serum, and the resulting metal-unithiol complex is then excreted into the urine via the kidneys (Prod Info DIMAVAL(R) IV, IM injection, 2004).

Physicochemical

Molecular Weight

    A) 210.3

References

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