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List of 8 Selected Essential Antidotes and How They Are Used

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List of 8 Selected Essential Antidotes and How They Are Used 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 <<DRAFT>> unintentional and intentional poisoning. The aim of this information note is to give an overview of the 8 essential antidotes that are available to the WHO South-East Asia Region for coordinated joint annual procurement (2018-2019) with assistance from Thailand. Please note in the future this list may be revised. For more information: icaps.strikingly.com 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). 1 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. 2 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. 4 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. 5 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 6 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);
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