Reactivates cholinesterase that had been inactivated by phosphorylation due to exposure to organophosphate pesticides and cholinesterase-inhibiting nerve agents (eg, terrorism and chemical warfare agents such as sarin) by displacing the enzyme from its receptor sites; removes the phosphoryl group from the active site of the inactivated enzyme

Anticholinesterase overdose: Treatment of overdose of anticholinesterase medications used to treat myasthenia gravis (ambenonium, neostigmine, pyridostigmine).

There are no absolute contraindications listed within the manufacturer’s labeling. Note: According to the manufacturer, relative contraindications include hypersensitivity to pralidoxime or any component of the formulation and other situations where the risk of administration clearly outweighs possible benefit.

Dosing: Adult Anticholinesterase overdose Anticholinesterase overdose (eg, neostigmine, pyridostigmine): IV: 1,000 to 2,000 mg; followed by increments of 250 mg every 5 minutes as needed. Organophosphate poisoning Organophosphate poisoning (eg, pesticides and nerve agents): Note: Must be used in conjunction with atropine; a response to atropine should be established before pralidoxime is administered. A combination product containing both pralidoxime and atropine is available as an auto-injector kit (eg, Duodote) which is used most often by civilian first responders or by military personnel for self-injected or buddy administration. The response to pralidoxime is highly variable and is dependent on the organophosphate, the length of time since the exposure, and the toxic dose (Lee 2014; Moon 2015); the optimal dosing regimen for pralidoxime has not been established (WHO 2006). IM or SUBQ administration should be considered when IV administration is not feasible: IV: Note: In patients with severe intoxication, maintenance treatment should be administered as a continuous infusion when possible (WHO 2006). Loading dose: 30 mg/kg (maximum: 2,000 mg) (Howland 2018; Roberts 2007) or 2,000 mg (WHO 2006). Maintenance: Continuous infusion (preferred): 8 to 10 mg/kg/hour (maximum: 650 mg/hour) (Howland 2018; Roberts 2007) or 500 mg/hour (WHO 2006); severe intoxication may result in prolonged redistribution of the organophosphate; the duration of therapy should reflect the clinical status of the patient. Intermittent infusion: May repeat loading dose after 1 to 2 hours if muscle weakness has not been relieved, followed by repeated dosing every 4 to 6 hours as needed (WHO 2006). IM (preferred), SUBQ: Mild symptoms: 600 mg; repeat as needed for persistent mild symptoms every 15 minutes to a maximum total dose of 1,800 mg; may administer doses in rapid succession if severe symptoms develop. Severe symptoms: 600 mg; repeat twice in rapid succession to deliver a total dose of 1,800 mg. Persistent symptoms: May repeat the entire series (1,800 mg) beginning ~1 hour after administration of the last injection.

IV:

Uterine contractions

Sublingual powder

IM: 2 to 3 hours; IV: 1 hour

Adverse Reactions The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not defined. Cardiovascular: Cardiac arrest, hypertension, tachycardia Central nervous system: Dizziness, drowsiness, headache, paralysis, seizure Dermatologic: Maculopapular rash Gastrointestinal: Nausea, vomiting Hepatic: Increased serum ALT (transient), increased serum AST (transient) Local: Pain at injection site (IM) Neuromuscular & skeletal: Fasciculations, increased creatine phosphokinase, laryngospasm, muscle rigidity, weakness Ophthalmic: Abnormal accommodation, blurred vision, diplopia Renal: Renal insufficiency Respiratory: Apnea, hyperventilation

Warnings/Precautions Disease-related concerns: • Carbamate poisoning: Pralidoxime is not indicated for the treatment of carbamate poisoning (WHO 2006); acetylcholinesterase is weakly, but not permanently, affected by carbamates. • Myasthenia gravis: Use with caution in patients with myasthenia gravis; administration may precipitate a myasthenic crisis. • Nonanticholinesterase poisoning: Pralidoxime is not indicated for the treatment of poisoning due to phosphorus, inorganic phosphates, or organophosphates without anticholinesterase activity. • Renal impairment: Use with caution in patients with renal impairment; dosage modification required. Other warnings/precautions: • Appropriate use: Clinical symptoms that are consistent with suspected organophosphate poisoning (eg, organophosphate anticholinesterase pesticides and nerve agents) should be treated with the antidote immediately; administration should not be delayed for confirmatory laboratory tests. Treatment should include proper evacuation and decontamination procedures as indicated; medical personnel should protect themselves from inadvertent contamination. Antidote administration is intended only for initial management; definitive and more intensive medical care is required following administration. Individuals should not rely solely on antidote for treatment; the concomitant use of atropine will be necessary and other supportive measures (eg, artificial respiration) may still be required.