Pralidoxime chloride

The same label also covers control of overdosage by anticholinesterase drugs used in myasthenia gravis. Treatment should include general supportive care, atropinization and decontamination in addition to pralidoxime; 'After the effects of atropine become apparent, PROTOPAM Chloride may be administered.' Treatment is most effective if initiated immediately after poisoning; 'Generally, little is accomplished if PROTOPAM Chloride is given more than 36 hours after termination of exposure to the poison.' Keep the patient under observation for at least 48 to 72 hours. ADULT INTRAVENOUS (label): 'Inject an initial dose of 1000 to 2000 mg of PROTOPAM Chloride, preferably as an infusion in 100 mL of normal saline, over a 15- to 30-minute period. If this is not practical or if pulmonary edema is present, the dose should be given slowly (over not less than five minutes) by intravenous injection, as a 50 mg/mL solution in water (e.g., 1000 mg in 20 mL). A second dose of 1000 to 2000 mg may be indicated after about one hour if muscle weakness has not been relieved. Additional doses may be given every 10-12 hours if muscle weakness persists.' Where the poison has been ingested, continuing absorption can cause fatal relapses: additional doses may be needed every three to eight hours, titrated 'as long as signs of poisoning recur'. RATE: the intermittent infusion rate should not exceed 200 mg/minute; infusing too rapidly may cause temporary worsening of cholinergic manifestations (tachycardia, cardiac arrest, laryngospasm, muscle rigidity or paralysis). If intravenous administration is not feasible, intramuscular or subcutaneous injection should be used. ADULT INTRAMUSCULAR (label, approx. 300 mg/mL solution): mild symptoms - 600 mg (2 mL), wait 15 minutes, a second 600 mg if mild symptoms persist, and after a further 15 minutes a third 600 mg, total cumulative dose 1800 mg; if severe symptoms develop at any time, give two additional 600 mg doses in rapid succession (total 1800 mg); severe symptoms - three 600 mg intramuscular doses in rapid succession (total 1800 mg); if symptoms persist after the complete 1800 mg regimen, the series may be repeated beginning approximately 1 hour after the last injection. ANTICHOLINESTERASE OVERDOSAGE (myasthenia gravis drugs - neostigmine, pyridostigmine, ambenonium): 'may be given in a dosage of 1000 to 2000 mg intravenously followed by increments of 250 mg every five minutes.' PREPARATION (label): reconstitute a 1000 mg vial with 20 mL Sterile Water for Injection (50 mg/mL), then dilute with Normal Saline to 10 to 20 mg/mL (e.g. 1000 mg in 100 mL or 2000 mg in 100 mL) for infusion; for fluid-restricted patients or rapid administration (over at least 5 min) a maximum concentration of 50 mg/mL may be used. Not effective for poisoning due to phosphorus, inorganic phosphates, or organophosphates without anticholinesterase activity; not indicated for carbamate pesticide poisoning (may increase toxicity of carbaryl). The label prints no daily maximum dose, so maxDose is left empty (the 200 mg/minute figure is a maximum infusion RATE, not a dose ceiling). No UK SPC for pralidoxime chloride is listed on eMC — this dose is from US prescribing information (Protopam Chloride) and must be verified against UK practice.

US label 'Pediatric Dosing (for patients 16 years and under)'. If intravenous infusion is not practical or pulmonary edema is present, the 20-50 mg/kg dose should be given slowly (over not less than five minutes) by intravenous injection as a 50 mg/mL solution in water; additional doses every 10-12 hours if muscle weakness persists. The label states there are no adequate and well-controlled clinical trials establishing effectiveness in paediatric patients; efficacy has been extrapolated from adults and the IM regimen was derived by pharmacokinetic modelling. Infants and young children may become drowsy or unconscious with muscle floppiness rather than twitching. Clinician to verify against a children's formulary before use.