Information note: List of 8 selected essential antidotes and how they are used
Antidotes are life-saving medicines that are used in the treatment of <
This note only provides basic information. It is strongly recommended you consult a medical professional and/or poisons information centers for detailed information on local treatment guidelines.
Table 1. List of 8 Selected Essential Antidotes* Included in WHO Essential Medicines List (2017) –Please note, more detail on next pages. 1. Activated charcoal *For emergency cases 2. Dimercaprol (BAL) additional antidotes may be 3. Methylene blue available through iCAPS (with 4. Penicillamine support from Thailand), such as diphtheria antitoxin and 5. Sodium calcium edetate (EDTA) botulism antitoxin. Please 6. Sodium nitrite enquire. 7. Sodium thiosulfate 8. Succimer (DMSA)
Table 2. How are the 8 selected antidotes used to treat acute poisoning? Non-specific poisoning Activated charcoal (most effective within one hour of ingestion)
Heavy-metal poisoning Dimercaprol (antimony, arsenic, bismuth, gold, mercury, possibly thallium) Penicillamine (heavy metals, particularly lead and copper) Sodium calcium edetate (EDTA) (with dimercaprol in lead poisoning) Cyanide poisoning Sodium nitrite followed by sodium thiosulfate
Lead poisoning Succimer (treatment of children with blood lead concentrations between 45 mcg/dL and 69 mcg/dL)# Dimercaprol# and Sodium calcium edetate (EDTA) (treatment of children with blood lead concentrations 69 mcg/dL or signs of encephalopathy)# Penicillamine (When blood lead is consistently = 25-45 mcg/dL) # Methaemoglobinaemia* Methylene blue (Methylthioninium chloride) *blood hemoglobin unable to release oxygen to body Source: WHO Model Formulary (2008. #Review of Succimer for treatment of lead poisoning (2010).
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Table 3. Eight Selected essential antidotes and how they are used Source: WHO Model Formulary (2008) 1. Charcoal, activated. Powder. Activated Charcoal Uses: treatment of acute poisoning.
(non- Contraindications: poisoning by hydrocarbons with high potential for harm if specific) aspirated; poisoning by corrosive substances (may prevent visualization of lesions caused by the poison).
Precautions: drowsy or unconscious patients (risk of aspiration; intubate before administration via nasogastric or gastric tube); not effective for poisoning with alcohols, clofenotane (dicophane, DDT), cyanides, malathion, and metal salts including those of iron and lithium.
Dose: Poisoning (reduction of absorption), by mouth, as soon as possible after ingestion of poison, ADULT, 50–100 g as a single dose; CHILD 1 g/kg as a single dose Poisoning (active elimination), by mouth, ADULT, 50 g then 25-50 g every 4-6 hours; CHILD, 1 g/kg then 0.5 g/kg every 4–6 hours.
Adverse effects: black stools; vomiting, constipation or diarrhoea; pneumonitis (due to aspiration). Reference:
• WHO. "Antidotes and other substances used in poisonings ". Retrieved 24 Jan, 2020, from http://archives.who.int/eml/wmf/2004/English/ Antidotes%20and%20other%20substances%20used%20in%20poisonings.pdf.
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Continued…Table 3. Eight Selected essential antidotes and how they are used Source: WHO Model Formulary (2008) 2. Dimercaprol. Injection in oil: 50 mg/ml in 2-ml ampoule. Dimercaprol (BAL) Uses: acute poisoning by antimony, arsenic, bismuth, gold, mercury, possibly thallium; adjunct (with sodium calcium edetate) in lead poisoning.
Contraindications: iron, selenium, and cadmium poisoning, organic mercury; severe hepatic impairment (unless due to arsenic poisoning; see also Appendix 5).
Precautions: hypertension; renal impairment (discontinue or use with extreme caution if impairment develops during treatment; see also Appendix 4); any abnormal reaction such as hyperpyrexia should be assessed; the elderly; pregnancy (Appendix 2) and breastfeeding (Appendix 3); interactions: Appendix 1. Administration: Deep intramuscular injection Dose: Poisoning by heavy metals, by intramuscular injection,
Arsenic and Gold toxicity: ADULT and CHILD, Mild to moderate 2.5 mg/kg 4 times daily for 2 days then 2 times on 3rd day, then OD for 10 day Severe: 3 mg/kg every 4 hours for 2 days then 4 times on 3rd day and twice daily for 10 days or until recovery
Lead toxicity: Mild to moderate: ADULT, 300-450 mg/m2/day or 50–75 mg/m2 IM q4h or 4 mg/kg followed by 3 mg/kg every 4 hours for 3-5 days; CHILD, 300 - 450 mg/m2/day or 50-75 mg/m2 IM every 4 hours for 3 - 5 days Lead encephalopathy: ADULT, 450 mg/m2/day or 75 mg/m2 IM every 4 hours or 4 st mg/kg q4h for 5 days after the 1 dose combined therapy with CaNa2 EDTA; CHILD, 450 mg/m2/day or 75 mg/m2 IM every 4 hours for 5 days
Mercury (inorganic) toxicity: ADULT and CHILD, 5 mg/kg IM followed by 2.5 mg/kg IM every 12-24 hours for 10 days
Adverse effects: hypertension, tachycardia; malaise, nausea, vomiting, abdominal pain, salivation, lacrimation, sweating, burning sensation in the mouth, throat, and eyes; feeling of constriction in the throat and chest; headache, muscle spasms, tingling of the extremities; fever in children; local pain and abscess at injection site.
Reference: 3
• IBM Micromedex® DRUGDEX® [Database on the internet]. Colorado: IBM Corporation; [update Nov 2018] IBM Micromedex®, Dimercaprol; [cite 2018 Dec 1]. Available at: https://www.micromedexsolutions.com. Subscription required to view. • Olson KR. Poisoning & Drug overdose. 7th ed. New York, USA: McGrawHill. • Goldfrank’s Toxicologic Emergencies. 11th ed. New York, USA: McGrawHill; 2019.
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Continued…Table 3. Eight Selected essential antidotes and how they are used Source: WHO Model Formulary (2008) 3. Methylthioninium chloride (methylene blue) Methylene blue Injection: 10 mg/ml in 5-ml ampoule.
Uses: acute methaemoglobinaemia. Contraindications: severe renal impairment; methaemoglobinaemia due to chlorate or induced by sodium nitrite in treatment of cyanide poisoning.
Precautions: G6PD deficiency (may cause haemolytic anaemia); monitor blood methaemoglobin throughout treatment; pregnancy (Appendix 2) and breastfeeding (Appendix 3).
Dose: Acute methemoglobinemia, by slow intravenous injection over 5minutes ADULT and CHILD, 1–2 mg/kg as a single dose; may be repeated after 1 hour if required. INFANT (≤ 3-month old), 0.3 –0.5 mg/kg
Administration. According to manufacturer’s directions. Adverse effects: nausea, vomiting, abdominal pain, chest pain, headache, dizziness, confusion, profuse sweating; hypertension or hypotension reported; haemolytic anaemia (in G6PD deficiency); methaemoglobinaemia (with high dosage); bluish skin discoloration; blue saliva, urine and faeces. Reference:
• WHO. "Antidotes and other substances used in poisonings ". Retrieved 24 Jan, 2020, from http://archives.who.int/eml/wmf/2004/English/ Antidotes%20and%20other%20substances%20used%20in%20poisonings.pdf.
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Continued…Table 3. Eight Selected essential antidotes and how they are used Source: WHO Model Formulary (2008) 4. Penicillamine Capsule or tablet: 250 mg. Penicillamine Uses: poisoning by heavy metals, particularly lead and copper; Wilson disease; severe rheumatoid arthritis (section 2.4).
Contraindications: hypersensitivity; lupus erythematosus.
Precautions: monitor throughout treatment (including blood counts and urine tests); renal impairment (Appendix 4); pregnancy (Appendix 2) and breastfeeding (Appendix 3); avoid concurrent gold, chloroquine or immunosuppressive treatment; avoid oral iron within 2 hours of a dose; penicillin hypersensitivity (risk of cross-reactivity); interactions: Appendix 1. BLOOD COUNTS. In Wilson disease, consider withdrawal if platelet count falls
below 120 000/mm3 or white blood cells fall below 2500/mm3 or if 3 successive falls are recorded (can restart at reduced dose when counts return to within a reference range but permanent withdrawal is necessary if neutropenia or thrombocytopenia recur). PATIENT ADVICE. In Wilson disease, warn patient to tell doctor immediately if sore throat, fever, infection, non-specific illness, unexplained bleeding and bruising, purpura, mouth ulcers, or rash develop.
Administration: oral route with empty stomach, 1 hour before or 2-3 hours after meal or at least 1 hour apart from any other drug, food or milk
Dose: Lead poisoning, by mouth, ADULT, 1–1.5 g daily in divided doses before food; CHILD (lead level <45 mcg/dL), 15-30 mg/kg daily in 2-4 divided doses. Elderly: 20 mg/kg divided dose. Initiating treatment at 25% of this dose and gradually increasing to the full dose over 2-3 week for minimized ADRs.
Wilson disease, by mouth, ADULT, 1.5–2 g daily in divided doses before food (maximum, 2 g daily for 1 year), thereafter 0.75–1 g daily; ELDERLY,20 mg/kg daily in divided doses adjusted according to response; CHILD, up to 20 mg/kg daily in divided doses (minimum, 500 mg daily).
Consider pyridoxine (B6) 25 mg/day in the patient with long period treatment
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especially restricted diet.
Adverse effects: initially nausea (less of a problem if taken with food and on retiring), anorexia, fever and skin reactions; taste loss (mineral supplements not recommended); blood disorders including thrombocytopenia, leukopenia, agranulocytosis, and aplastic anaemia; proteinuria, rarely haematuria (withdraw immediately); haemolytic anaemia, nephrotic syndrome, lupus erythematosus-like syndrome, myasthenia gravis-like syndrome, polymyositis (rarely with cardiac involvement), dermatomyositis, mouth ulcers, stomatitis, alopecia, bronchiolitis and pneumonitis, pemphigus, Goodpasture syndrome, and Stevens-Johnson syndrome also reported; male and female breast enlargement reported; in non- rheumatic conditions rheumatoid arthritis-like syndrome also reported; rash early in treatment (usually allergic – may need temporary withdrawal), late rash (reduce dose or withdraw treatment). Reference:
• Olson KR. Poisoning & Drug overdose. 7th ed. New York, USA: McGrawHill. • Goldfrank’s Toxicologic Emergencies. 11th ed. New York, USA: McGrawHill; 2019.
Continued…Table 3. Eight Selected essential antidotes and how they are used 7
Source: WHO Model Formulary (2008) 5. Sodium calcium edetate. Injection: 200 mg/ml in 5-ml ampoule. Sodium calcium edetate Uses: lead poisoning.
Contraindication: drug, hypersensitivity, anuria, hepatitis, active renal disease
Precautions: renal impairment (Appendix 4). Infused over 24 hours, rapid IV infusions in patients with lead encephalopathy may increase intracranial pressure and cerebral edema.
Dose: Lead poisoning: Mild symptomatic or lead level (LL) 45-69 mcg/dL (child): CHILD, 1000 mg/m2/day IV infusion over 8-12 hours or 2-4 divided doses daily, for 5 days. Moderate symptomatic or LL over 100 mcg/dL (adult), over 69 mcg/dL (child): ADULT, 1500 mg/m2/day IV infusion over 8 to 12 hours or 2-4 divided doses daily for 5 days; CHILD, 1000-1500 mg/m2/day IV infusion over 8-12 hours or 2-4 divided doses daily, for 5 days (starting 4 hours after dimercaprol). Lead encephalopathy: (for lead encephalopathy and cerebral edema IM route is preferred, combined therapy with dimercaprol); ADULT and CHILD, 1500 mg/m2/day continuous over 8-12 hours IV infusion or IV/IM 2-4 divided dose, starting 4 hours after dimercaprol, for 5 days, repeated if necessary after interval of 48 hours, and followed by an additional 5-day course if indicated. Lead nephropathy: ADULT; 500 mg/m2 every 24 hours for 5 days for Scr 2-3 mg/dL 500 mg/m2 every 48 hours for 5 days for Scr 3-4 mg/dL 500 mg/m2 once weekly for Scr over 4 mg/dL
Dilution and administration: IM or IV infusion over 8-12 hours diluted in normal saline or 5% dextrose
Adverse effects: renal tubular necrosis; nausea, diarrhoea, abdominal cramps; pain at injection site, thrombophlebitis (if given too rapidly or as too concentrated a solution), fever, malaise, headache, myalgia, thirst, chills, histamine-like responses (sneezing, nasal congestion, lacrimation) and transient hypotension.
Reference:
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• IBM Micromedex® DRUGDEX® [Database on the internet]. Colorado: IBM Corporation; [update Nov 2018] IBM Micromedex®, Edetate Calcium Disodium; [cite 2018 Dec 1]. Available at: https://www.microme dexsolutions.com. Subscription required to view. • Olson KR. Poisoning & Drug overdose. 7th ed. New York, USA: McGrawHill. • Goldfrank’s Toxicologic Emergencies. 11th ed. New York, USA: McGrawHill; 2019.
Continued…Table 3. Eight Selected essential antidotes and how they are used Source: WHO Model Formulary (2008) 9
6. Sodium nitrite. Injection: 30 mg/ml in 10-ml ampoule. Sodium nitrite Uses: cyanide poisoning (together with sodium thiosulfate). Precautions: anemia (monitor plasma methemoglobin levels); severe cardiovascular or cerebrovascular disease.
Dose: Cyanide poisoning, by slow intravenous injection over 3-5 minutes (2.5-5 ml/min), ADULT, 300 mg (followed by sodium thiosulfate); further dose of 150 mg after 30 minutes if symptoms recur; CHILD, 6 mg/kg or 0.2 ml/kg (initially lower dose) not exceed 10 ml (300 mg) followed by sodium thiosulfate.
Pediatric Sodium Nitrite Guidelines
Hb (g) NaNO2 (mg/kg) 3% NaNO2 sol. (mL/kg)
7.0 5.8 0.19
8.0 6.6 0.22 9.0 7.5 0.25
10.0 8.3 0.27 11.0 9.1 0.30
12.0 10.0 0.33
13.0 10.8 0.36 14.0 11.6 0.39
Adapted from Berlin CM: The treatment of cyanide poisoning in children. Pediatrics. 1970;46:793–796.
Reference:
• Olson KR. Poisoning & Drug overdose. 7th ed. New York, USA: McGrawHill. • Goldfrank’s Toxicologic Emergencies. 11th ed. New York, USA: McGrawHill; 2019.
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7. Sodium thiosulfate. Injection: 250 mg/ml in 50-ml ampoule. Sodium thiosulfate Uses: cyanide poisoning (together with sodium nitrite); pityriasis versicolor. Dose: Cyanide poisoning, after administration of sodium nitrite, by slow intravenous injection over about 10 minutes (rate 2.5-5 ml/min), ADULT, 12.5 g; further dose of 6.25 g after 30 minutes if symptoms recur; CHILD, 400 mg/kg (1.65 ml/kg) (maximum dose 12.5 gm).
Reference:
• Olson KR. Poisoning & Drug overdose. 7th ed. New York, USA: McGrawHill. • Goldfrank’s Toxicologic Emergencies. 11th ed. New York, USA: McGrawHill; 2019.
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Continued…Table 3. Eight Selected essential antidotes and how they are used Source: Review of Succimer for treatment of lead poisoning (2010). http://www.who.int/selection_medicines/committees/expert/18/applications/succimer.pdf 8. Succimer, also called Dimercaptosuccinic acid (DMSA) Succimer Uses: lead poisoning.
Contraindication: drug, hypersensitivity
Precautions: renal impairment
Dose: Lead poisoning (Mild symptomatic or lead level (LL) 70-100 mcg/dL (adult), 45-69 mcg/dL (child)), mercury and arsenic poisoning: ADULT and CHILD: 10 mg/kg (or pediatric 350mg/m2) every 8 hours a day for 5 days followed by 10mg/kg (or pediatric 350mg/m2) twice daily for 14 days
Reference:
• Olson KR. Poisoning & Drug overdose. 7th ed. New York, USA: McGrawHill. • Goldfrank’s Toxicologic Emergencies. 11th ed. New York, USA: McGrawHill; 2019.
Additional Resources: WHO. Brief guide to analytical methods for measuring lead in blood. 2011. http://bit.ly/2LUR9fJ
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