5 FDA-Indicated Antidotes for Poisonings - #MEDSHED

Antidotes are needed for toxic environmental and industrial exposures. Let's get you familiar with five FDA-antidotes for poisonings -

Antidotes are needed for toxic environmental and industrial exposures. There are several antidotes available for a variety of poisonings. For those interested in emergency medicine and critical care, you should be familiar with these agents (dependent on location). Here are five FDA-approved agents for non-prescribed environmental and industrial poisonings.

#1 - Cyanokit (hydroxycobalamin)

Indication

• Treatment of known or suspected cyanide poisoning

Mechanism

• Inhibition of nitric oxide synthase

• Binds to cyanide by substituting it for the hydroxo-ligand linked to the trivalent cobalt ion, to form cyanocobalamin

Cyanide Poisoning

• Exposures from inhalation, ingestion, or dermal exposure to cyanide-containing compounds, including smoke from closed-space fires

Signs and Symptoms of Cyanide Poisoning

Dosing

• 5 gm (2.5 gm vial x 2) over 15 minutes

• Depending clinical severity and response

  • May repeat x 1 (max 10 gm) over 15 minutes to 2 hours

ADE (>10%)

• Chromaturia (red-colored urine)

• Erythema

• Rash

• Elevated blood pressure

Caution

• Hypersensitivity reactions

• Interference with clinical laboratory assays

#2 - Antizol (fomepizole)

Indication

• Toxic alcohol poisonings

Mechanism

• Competitive inhibitor of alcohol dehydrogenase

Toxic Alcohol Poisonings

• Ethylene glycol and methanol are metabolized by alcohol dehydrogenase into toxic byproducts

• Fomepizole inhibits the metabolism of parent alcohols into toxic metabolites

  • EG - glycolic and oxalic acid

  • MET - formic acid

Clinical Presentation of Toxic Alcohol Poisonings

Dosing

• FMP 15 mg IV every 12 hours x 4 doses, and then 10 mg IV every 12 hours thereafter

• Treat with high clinical suspicion OR serum EG/MET level > 20 mg/dL

• Discontinue treatment when asymptomatic with normal pH, and undetectable level or serum level < 20 mg/dL

ADE

• Mild side effects reported in package insert; rash

Caution

• Renally metabolized (dose adjust in renal impairment and hemodialysis)

• Potent CYP2E1 inhibitor

• Do not give undiluted - phlebosclerosis

#3 - PROVAYBLUE (methylene Blue)

Indication

• Acquired methemeglobinemia

Mechanism

• Promotes a non-enyzmatic redox conversion of metHb to hemoglobin.

Metheglobinemia

• Dimished oxygen-carrying capacity of hemoglobin secondary to conversion of reduced ferrous (Fe2+) to oxidized ferric (Fe3+)

Clinical Presentation of Metheglobinemia

• Cyanosis

• Pallor

• Metabolic acidosis

• AMS

• Seizures

• Cardiovascular collapse

Dosing

• Administer 1 gm/ IV over 5 to 30 minutes.

• If methemoglobin remains > 30% or if clinical symptoms persist, may give repeat dose of up to 1 mg/kg one hour after the first dose

• Consider alternative treatments after 2 doses

• Different off-label dosing regimens have been investigated

ADE (> 10%)

• Pain in extremity

• Chromaturia

• Hyperhidrosis

• Dysgeusia

• Headache/dizziness

Caution

• Serotonin syndrome

Contraindications

• Severe hypersensitivity to methylene blue

• Glucose-6-phosphate dehydrogenase deficiency (G6PD) due to the risk of hemolytic anemia

#4 - CroFab [crotalidae polyvalent immune fab (ovine)] and Anavip [crotalidae immune F(ab’)2 (equine)]

Indication

• North American crotalid envenomation

Mechanism

• Venom-specific antivenom that binds and neutralizes toxins.

• Assists with redistribution away from tissues and processed for elimination

Clinical Presentation of Snake Envenomations

• Venom burden varies greatly from patient to patient

• Administer antivenom with any signs

  • Local injury

  • Coagulapathies

  • System signs of envenomation

Dosing (Product Dependent on Availability/Formulary)

CroFab ADE (> 5%)

• Urticaria, rash, nausea, pruritus and back pain

Anavip ADE (> 2%)

• Pruritus, nausea, rash, arthralgia, peripheral edema, erythema, headache, myalgia, pain in extremity, and vomiting.

Caution

• Hypersensitivities, including related-products;

  • CroFab: papayapapain, chymopapain, papaya extracts, bromelain

  • Anavip: equine

• Delayed serum sickness

#5 - Anascorp

Indication

• Scorpion sting envenomation

Mechanism

• Binds and neutralizes venom toxins

• Facilitates redistribution away from target tissues and elimination from the body

Clinical Presentation of Scorpion Envenomation

• Autonomic excitation, dysregulation between sympathetic and parasympathetic nervous system

• Loss of muscle control, roving or abnormal eye movements, slurred speech, respiratory distress, excessive salivation, frothing at the mouth and vomiting

Dosing

• Initiate treatment with Anascorp for patients who develop clinically important signs of scorpion envenomation

• Initial: 3 vials over 10 minutes

• May repeat 1 vial every 30 to 60 minutes PRN envenomation arrest

• Consider alternative treatments after 2 doses

• Different off-label dosing regimens have been investigated

ADE (> 2%)

• Pyrexia

• Rash

• Pruritis

Caution

• Hypersensitivities, including equine products

• Delayed serum sickness

Know What to Give, How to Get

By being familiar with antidotes, you can anticipate procurement and triage inventory issues (vials can go very fast with the snake envenomations). Cyanokit for cyanide toxicity. Fomepizole for toxic alcohols. Methylene blue for methemeglobinemia. CroFab and Snavip for snake envenomations. Anascorp for scorpion stings. Delays in care can potentially be life-threatening; stay on top of communication and stock.

Mark Nguyen, PharmD, BCEMP

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