Pralidoxime, a quaternary ammonium oxime also known as 2-PAM, is an antidote used to reverse muscle paralysis resulting from organophosphate anticholinesterase poisoning. Organophosphorus compounds are used as pesticides and developed as warfare nerve agents such as tabun, soman, sarin, VX, and others. Respiratory failure is often considered to be the major fatal factor affecting organophosphate poisoning victims. Respiratory failure in these patients typically consists of three components: increased airway resistance, weakness and paralysis of muscles of respiration, and depression of the central respiratory center. Pralidoxime is a cholinesterase reactivator that exerts its effects primarily on skeletal neuromuscular junctions, which can relieve paralysis of skeletal muscle, including muscles of respiration. Pralidoxime does not significantly relieve depression of the central respiratory center or decrease the muscarinic effects of anticholinesterase poisoning; therefore, atropine must be administered concomitantly to relieve muscarinic effects such as bronchoconstriction, bronchorrhea, bradycardia, and central nervous system effects. Supportive measures, including maintenance of an adequate airway and ventilation and the prompt management of seizures, must be implemented simultaneously with pralidoxime administration. Pralidoxime is also used to reverse the effects of overdosage of anticholinesterase agents used in the treatment of myasthenia gravis (i.e., neostigmine, pyridostigmine, and ambenonium). Pralidoxime also has been used off-label prophylactically in workers before exposure to organophosphates, subconjunctivally in the treatment of organophosphate anticholinesterase poisoning, and in the treatment of echothiophate ophthalmic solution overdose. Pralidoxime was approved for use in adults by the FDA in 1964 and for use in pediatric patients in September 2010.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
NOTE: Treatment should commence as soon as possible after poisoning. Atropine should be administered concomitantly. If treatment is not commenced within 36-48 hours after poisoning, it may be ineffective.
Route-Specific Administration
Injectable Administration
-Pralidoxime is preferably administered by IV infusion or IV injection. If IV administration is not feasible, IM or SC injection should be used.
-If skin exposure occurs, thoroughly wash hair and skin in sodium bicarbonate or alcohol as soon as possible.
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
Reconstitution for intravenous administration :
-Reconstitute each 1000 mg vial with 20 ml Sterile Water for Injection, USP to yield a 50 mg/ml solution.
Intermittent or Continuous IV infusion :
-Further dilute the reconstituted solution to a final concentration of 10 to 20 mg/ml with Normal Saline for injection.
-Infuse IV intermittent doses over 15-30 minutes. Administration rate should not exceed 200 mg/min.
-Administration via continuous infusion is only recommended for pediatric patients depending on severity of symptoms (see Dosage).
Intravenous injection :
-When IV infusion is not practical, the appropriate dose may be diluted to a 50 mg/ml solution and administered by slow IV injection over at least 5 minutes.
Intramuscular Administration
Reconstitution for intramuscular administration :
-Reconstitute each 1000 mg vial with 3.3 ml Sterile Water for Injection, USP to yield approximately a 300 mg/ml solution.
Intramuscular injection:
-Inject deeply into a large muscle. Aspirate prior to injection to avoid injection into a blood vessel.
-In infants and children, administer the injection in the anterolateral aspect of the thigh to avoid the nerve, artery, vein, and femur.
Subcutaneous Administration
-Inject subcutaneously taking care not to inject intradermally.
Differentiating the adverse effects associated with pralidoxime, those related to anticholinesterase poisoning, and those caused by concomitant administration of atropine is difficult. Adverse events that may be associated with any one or any combination of the three factors include dizziness, blurred vision, diplopia, headache, nausea, vomiting, drowsiness, hyperventilation, hypertension, sinus tachycardia, rash (unspecified), and myasthenia.
Differentiating the adverse effects associated with pralidoxime, those related to anticholinesterase poisoning, and those caused by concomitant administration of atropine is difficult. Anticholinergic effects associated with atropine administration, such as tachycardia, xerostomia, and flushing, can occur earlier than anticipated when administering pralidoxime with atropine.
Intravenous doses of pralidoxime should be administered slowly, by infusion if possible, because some of the reported adverse effects of the drug (i.e., neuromuscular blockade (muscle paralysis), muscle spasm (hypertonia), laryngospasm, hypertension, and tachycardia) may be related to excessively rapid administration. For intramuscular administration, an injection site reaction may be experienced 40-60 minutes after injection.
Differentiating the adverse effects associated with pralidoxime, those related to anticholinesterase poisoning, and those caused by concomitant administration of atropine is difficult. Mania, myoclonia, and agitation have been reported during pralidoxime administration, but these effects have also occurred in cases of organophosphate poisoning that were not treated with pralidoxime.
The possibility of precipitating a myasthenic crisis should be considered if pralidoxime is administered to patients receiving anticholinesterase agents for the treatment of myasthenia gravis.
Excretion of pralidoxime is mainly renal. Renal dysfunction can increase blood concentrations of pralidoxime through decreased excretion. Patients with renal disease should be treated with caution, and dosage should be reduced in patients with renal impairment.
Pralidoxime is classified as pregnancy category C. Because pralidoxime is used only in emergency situations, no adequate human studies have examined the effects of this drug on the fetus. Therefore, in making the decision to administer this drug during pregnancy, the potential risks to the fetus must be weighed against the potential benefits to the mother.
It is unknown if pralidoxime is excreted in breast milk; therefore, the manufacturer recommends to administer it with caution to breast-feeding mothers. The molecular weight suggests that it may be excreted into breast milk; however, its rapid elimination should limit transfer into breast milk. Due to the emergency nature the use of pralidoxime, nursing is likely not to occur when used. It would be prudent to hold breast-feeding for at least 6-7 hours (about 5 half-lives) after the dose is administered. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Clinical studies of pralidoxime did not include sufficient numbers of geriatric patients (>= 65 years of age) to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger adults. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
For use as an antidote to organophosphate insecticide toxicity:
Intravenous dosage:
Adults and Adolescents >= 17 years: Initially, 1 to 2 g IV, given as a 15- to 30-minute infusion in 100 mL of normal saline. If pulmonary edema is present or an IV infusion is not practical, may administer dosage by slow IV injection of a 5% solution in water over more than 5 minutes. Too-rapid administration may result in temporary worsening of cholinergic manifestations. Repeat dosage in 1 hour if muscle weakness persists. Dosage may be repeated every 10 to 12 hours if muscle weakness is not alleviated.
Neonates, Infants, Children, and Adolescents <= 16 years: Initially, 20 to 50 mg/kg IV, not to exceed 2 g, infused over 15 to 30 minutes. Then, depending on the severity of symptoms, either begin a continuous infusion of 10 to 20 mg/kg/hour IV OR repeat a dose of 20 to 50 mg/kg IV, not to exceed 2 grams/dose, after approximately 1 hour if muscle weakness has not been relieved. If intermittent dosing is used, repeat the dose every 10 to 12 hours if needed. If administration by continuous or intermittent infusions is not practical or if pulmonary edema is present, then the 20 to 50 mg/kg dose may be given as a 50 mg/mL solution by slow IV injection (over no less than 5 minutes) and repeated every 10 to 12 hours.
Intramuscular dosage:
NOTE: Intravenous infusion is the preferred method of administration. Only if intravenous administration is not feasible should intramuscular administration be employed.
Adults and Children and Adolescents weighing >= 40 kg with mild symptoms: 600 mg IM. After 15 minutes, if mild symptoms persist, then give another 600 mg IM. After another 15 minutes, if mild symptoms persist, then give another 600 mg IM. If mild symptoms persist 1 hour after the last dose, then the series may be repeated. If the patient develops severe symptoms any time after the first dose, then give two 600-mg doses IM in rapid succession for a total cumulative dose of 1,800 mg.
Adults and Children and Adolescents weighing >= 40 kg with severe symptoms: Three 600-mg IM doses in rapid succession for a total dose of 1,800 mg. If symptoms persist after 1 hour, then the series may be repeated.
Neonates, Infants, and Children and Adolescents weighing < 40 kg with mild symptoms: 15 mg/kg IM. After 15 minutes, if mild symptoms persist, then give another 15 mg/kg IM. After another 15 minutes, if mild symptoms persist, then give another 15 mg/kg IM. If mild symptoms persist 1 hour after the last dose, then the series may be repeated. If the patient develops severe symptoms any time after the first dose, then give two 15-mg/kg doses IM in rapid succession for a total cumulative dose of 45 mg/kg.
Neonates, Infants, and Children and Adolescents weighing < 40 kg with severe symptoms: Three 15-mg/kg IM doses in rapid succession for a total dose of 45 mg/kg. If symptoms persist after 1 hour, the series may be repeated.
For the treatment of cholinesterase inhibitor toxicity secondary to agents used in the treatment of myasthenia gravis (e.g., neostigmine, pyridostigmine):
Intravenous dosage:
Adults: Initially, 1 to 2 g IV, followed by increments of 250 mg every 5 minutes.
Maximum Dosage Limits:
-Adults
2 g/dose IV/IM/SC.
-Elderly
2 g/dose IV/IM/SC.
-Adolescents
Safe and effective use has not been established; doses up to 50 mg/kg/dose IV/IM/SC (not to exceed 2g/dose) have been recommended for the management of organophosphate insecticide toxicity.
-Children
Safe and effective use has not been established; doses up to 50 mg/kg/dose IV/IM/SC (not to exceed 2g/dose) have been recommended for the management of organophosphate insecticide toxicity.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Dosage should be modified depending on clinical response and degree of renal impairment, but no quantitative recommendations are available.
*non-FDA-approved indication
Amitriptyline: (Moderate) Tricyclic antidepressants (TCAs) may antagonize some of the effects of parasympathomimetics (e.g., cholinesterase inhibitors) due to their anticholinergic activity. However, parasympathomimetics like bethanechol have occasionally been used historically to offset some of the adverse peripheral antimuscarinic (anticholinergic) effects of TCAs, such as dry mouth, constipation, or urinary retention. For years, physostigmine was used as an adjunct to the treatment of TCA overdose; however, its efficacy was limited to addressing anticholinergic effects. Additionally, case reports suggest that harmful effects such as seizures and bradyarrhythmias progressing to asystole, especially in patients with cardiac conduction abnormalities at baseline, are possible. For these reasons, physostigmine is no longer considered a standard of care in the treatment of TCA overdose.
Amobarbital: (Major) The action of barbiturates is potentiated by the acetylcholinesterase inhibitors, which should be considered when using pralidoxime. Barbiturates should be used with caution to treat convulsions produced by acetylcholinesterase inhibitors.
Amoxapine: (Major) Amoxapine may antagonize some of the effects of parasympathomimetics. However, bethanechol has occasionally been used therapeutically to offset some of the adverse antimuscarinic effects of cyclic antidepressants. Due to their anticholinergic actions, some cyclic antidepressants, such as amoxapine, may potentially antagonize the therapeutic actions of cholinergic agonists.
Anticholinergics: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Aspirin, ASA; Butalbital; Caffeine: (Major) The action of barbiturates is potentiated by the acetylcholinesterase inhibitors, which should be considered when using pralidoxime. Barbiturates should be used with caution to treat convulsions produced by acetylcholinesterase inhibitors.
Atropine: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Atropine; Difenoxin: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Barbiturates: (Major) The action of barbiturates is potentiated by the acetylcholinesterase inhibitors, which should be considered when using pralidoxime. Barbiturates should be used with caution to treat convulsions produced by acetylcholinesterase inhibitors.
Belladonna; Opium: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Benztropine: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Bethanechol: (Moderate) Pralidoxime and bethanechol are both cholinergic agonists. Coadministration is expected to result in additive parasympathomimetic effects.
Budesonide; Glycopyrrolate; Formoterol: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Butalbital; Acetaminophen: (Major) The action of barbiturates is potentiated by the acetylcholinesterase inhibitors, which should be considered when using pralidoxime. Barbiturates should be used with caution to treat convulsions produced by acetylcholinesterase inhibitors.
Butalbital; Acetaminophen; Caffeine: (Major) The action of barbiturates is potentiated by the acetylcholinesterase inhibitors, which should be considered when using pralidoxime. Barbiturates should be used with caution to treat convulsions produced by acetylcholinesterase inhibitors.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) The action of barbiturates is potentiated by the acetylcholinesterase inhibitors, which should be considered when using pralidoxime. Barbiturates should be used with caution to treat convulsions produced by acetylcholinesterase inhibitors.
Butalbital; Aspirin; Caffeine; Codeine: (Major) The action of barbiturates is potentiated by the acetylcholinesterase inhibitors, which should be considered when using pralidoxime. Barbiturates should be used with caution to treat convulsions produced by acetylcholinesterase inhibitors.
Cevimeline: (Moderate) Cevimeline and pralidoxime are both cholinergic agonists. Coadministration is expected to result in additive parasympathomimetic effects.
Chlordiazepoxide; Amitriptyline: (Moderate) Tricyclic antidepressants (TCAs) may antagonize some of the effects of parasympathomimetics (e.g., cholinesterase inhibitors) due to their anticholinergic activity. However, parasympathomimetics like bethanechol have occasionally been used historically to offset some of the adverse peripheral antimuscarinic (anticholinergic) effects of TCAs, such as dry mouth, constipation, or urinary retention. For years, physostigmine was used as an adjunct to the treatment of TCA overdose; however, its efficacy was limited to addressing anticholinergic effects. Additionally, case reports suggest that harmful effects such as seizures and bradyarrhythmias progressing to asystole, especially in patients with cardiac conduction abnormalities at baseline, are possible. For these reasons, physostigmine is no longer considered a standard of care in the treatment of TCA overdose.
Chlordiazepoxide; Clidinium: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Cholinesterase inhibitors: (Major) Cholinergic agonists can cause additive pharmacodynamic effects if used concomitantly with cholinesterase inhibitors. Concurrent use is unlikely to be tolerated by the patient and should be avoided.
Clomipramine: (Moderate) Tricyclic antidepressants (TCAs) may antagonize some of the effects of parasympathomimetics (e.g., cholinesterase inhibitors) due to their anticholinergic activity. However, parasympathomimetics like bethanechol have occasionally been used historically to offset some of the adverse peripheral antimuscarinic (anticholinergic) effects of TCAs, such as dry mouth, constipation, or urinary retention. For years, physostigmine was used as an adjunct to the treatment of TCA overdose; however, its efficacy was limited to addressing anticholinergic effects. Additionally, case reports suggest that harmful effects such as seizures and bradyarrhythmias progressing to asystole, especially in patients with cardiac conduction abnormalities at baseline, are possible. For these reasons, physostigmine is no longer considered a standard of care in the treatment of TCA overdose.
Desipramine: (Moderate) Tricyclic antidepressants (TCAs) may antagonize some of the effects of parasympathomimetics (e.g., cholinesterase inhibitors) due to their anticholinergic activity. However, parasympathomimetics like bethanechol have occasionally been used historically to offset some of the adverse peripheral antimuscarinic (anticholinergic) effects of TCAs, such as dry mouth, constipation, or urinary retention. For years, physostigmine was used as an adjunct to the treatment of TCA overdose; however, its efficacy was limited to addressing anticholinergic effects. Additionally, case reports suggest that harmful effects such as seizures and bradyarrhythmias progressing to asystole, especially in patients with cardiac conduction abnormalities at baseline, are possible. For these reasons, physostigmine is no longer considered a standard of care in the treatment of TCA overdose.
Dicyclomine: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Diphenoxylate; Atropine: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Disopyramide: (Moderate) Disopyramide possesses clinically significant antimuscarinic properties and these appear to be dose-related. It is possible that disopyramide could antagonize the muscarinic actions of cholinergic agonists. Clinicians should be alert to this possibility.
Donepezil: (Major) Cholinergic agonists can cause additive pharmacodynamic effects if used concomitantly with cholinesterase inhibitors. Concurrent use is unlikely to be tolerated by the patient and should be avoided.
Donepezil; Memantine: (Major) Cholinergic agonists can cause additive pharmacodynamic effects if used concomitantly with cholinesterase inhibitors. Concurrent use is unlikely to be tolerated by the patient and should be avoided.
Doxepin: (Moderate) Tricyclic antidepressants (TCAs) may antagonize some of the effects of parasympathomimetics (e.g., cholinesterase inhibitors) due to their anticholinergic activity. However, parasympathomimetics like bethanechol have occasionally been used historically to offset some of the adverse peripheral antimuscarinic (anticholinergic) effects of TCAs, such as dry mouth, constipation, or urinary retention. For years, physostigmine was used as an adjunct to the treatment of TCA overdose; however, its efficacy was limited to addressing anticholinergic effects. Additionally, case reports suggest that harmful effects such as seizures and bradyarrhythmias progressing to asystole, especially in patients with cardiac conduction abnormalities at baseline, are possible. For these reasons, physostigmine is no longer considered a standard of care in the treatment of TCA overdose.
Flavoxate: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Galantamine: (Major) Cholinergic agonists can cause additive pharmacodynamic effects if used concomitantly with cholinesterase inhibitors. Concurrent use is unlikely to be tolerated by the patient and should be avoided.
Glycopyrrolate: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Glycopyrrolate; Formoterol: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Guanidine: (Moderate) Guanidine and pralidoxime are both cholinergic agonists. Coadministration is expected to result in additive parasympathomimetic effects.
Homatropine; Hydrocodone: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Hyoscyamine: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Imipramine: (Moderate) Tricyclic antidepressants (TCAs) may antagonize some of the effects of parasympathomimetics (e.g., cholinesterase inhibitors) due to their anticholinergic activity. However, parasympathomimetics like bethanechol have occasionally been used historically to offset some of the adverse peripheral antimuscarinic (anticholinergic) effects of TCAs, such as dry mouth, constipation, or urinary retention. For years, physostigmine was used as an adjunct to the treatment of TCA overdose; however, its efficacy was limited to addressing anticholinergic effects. Additionally, case reports suggest that harmful effects such as seizures and bradyarrhythmias progressing to asystole, especially in patients with cardiac conduction abnormalities at baseline, are possible. For these reasons, physostigmine is no longer considered a standard of care in the treatment of TCA overdose.
Indacaterol; Glycopyrrolate: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Maprotiline: (Major) Maprotiline may antagonize some of the effects of parasympathomimetics. However, bethanechol has occasionally been used therapeutically to offset some of the adverse antimuscarinic effects of cyclic antidepressants. Due to their anticholinergic actions, some cyclic antidepressants like maprotiline may potentially antagonize the therapeutic actions of the cholinesterase-inhibitors used for the treatment of dementia.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Methohexital: (Major) The action of barbiturates is potentiated by the acetylcholinesterase inhibitors, which should be considered when using pralidoxime. Barbiturates should be used with caution to treat convulsions produced by acetylcholinesterase inhibitors.
Methscopolamine: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Neostigmine: (Major) Cholinergic agonists can cause additive pharmacodynamic effects if used concomitantly with cholinesterase inhibitors. Concurrent use is unlikely to be tolerated by the patient and should be avoided.
Neostigmine; Glycopyrrolate: (Major) Cholinergic agonists can cause additive pharmacodynamic effects if used concomitantly with cholinesterase inhibitors. Concurrent use is unlikely to be tolerated by the patient and should be avoided. (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Nortriptyline: (Moderate) Tricyclic antidepressants (TCAs) may antagonize some of the effects of parasympathomimetics (e.g., cholinesterase inhibitors) due to their anticholinergic activity. However, parasympathomimetics like bethanechol have occasionally been used historically to offset some of the adverse peripheral antimuscarinic (anticholinergic) effects of TCAs, such as dry mouth, constipation, or urinary retention. For years, physostigmine was used as an adjunct to the treatment of TCA overdose; however, its efficacy was limited to addressing anticholinergic effects. Additionally, case reports suggest that harmful effects such as seizures and bradyarrhythmias progressing to asystole, especially in patients with cardiac conduction abnormalities at baseline, are possible. For these reasons, physostigmine is no longer considered a standard of care in the treatment of TCA overdose.
Oxybutynin: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Pentobarbital: (Major) The action of barbiturates is potentiated by the acetylcholinesterase inhibitors, which should be considered when using pralidoxime. Barbiturates should be used with caution to treat convulsions produced by acetylcholinesterase inhibitors.
Perphenazine; Amitriptyline: (Moderate) Tricyclic antidepressants (TCAs) may antagonize some of the effects of parasympathomimetics (e.g., cholinesterase inhibitors) due to their anticholinergic activity. However, parasympathomimetics like bethanechol have occasionally been used historically to offset some of the adverse peripheral antimuscarinic (anticholinergic) effects of TCAs, such as dry mouth, constipation, or urinary retention. For years, physostigmine was used as an adjunct to the treatment of TCA overdose; however, its efficacy was limited to addressing anticholinergic effects. Additionally, case reports suggest that harmful effects such as seizures and bradyarrhythmias progressing to asystole, especially in patients with cardiac conduction abnormalities at baseline, are possible. For these reasons, physostigmine is no longer considered a standard of care in the treatment of TCA overdose.
Phenobarbital: (Major) The action of barbiturates is potentiated by the acetylcholinesterase inhibitors, which should be considered when using pralidoxime. Barbiturates should be used with caution to treat convulsions produced by acetylcholinesterase inhibitors.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) The action of barbiturates is potentiated by the acetylcholinesterase inhibitors, which should be considered when using pralidoxime. Barbiturates should be used with caution to treat convulsions produced by acetylcholinesterase inhibitors. (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Physostigmine: (Major) Cholinergic agonists can cause additive pharmacodynamic effects if used concomitantly with cholinesterase inhibitors. Concurrent use is unlikely to be tolerated by the patient and should be avoided.
Pilocarpine: (Moderate) Pilocarpine and pralidoxime are both cholinergic agonists. Coadministration is expected to result in additive parasympathomimetic effects.
Primidone: (Major) The action of barbiturates is potentiated by the acetylcholinesterase inhibitors, which should be considered when using pralidoxime. Barbiturates should be used with caution to treat convulsions produced by acetylcholinesterase inhibitors.
Propantheline: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Protriptyline: (Moderate) Tricyclic antidepressants (TCAs) may antagonize some of the effects of parasympathomimetics (e.g., cholinesterase inhibitors) due to their anticholinergic activity. However, parasympathomimetics like bethanechol have occasionally been used historically to offset some of the adverse peripheral antimuscarinic (anticholinergic) effects of TCAs, such as dry mouth, constipation, or urinary retention. For years, physostigmine was used as an adjunct to the treatment of TCA overdose; however, its efficacy was limited to addressing anticholinergic effects. Additionally, case reports suggest that harmful effects such as seizures and bradyarrhythmias progressing to asystole, especially in patients with cardiac conduction abnormalities at baseline, are possible. For these reasons, physostigmine is no longer considered a standard of care in the treatment of TCA overdose.
Pyridostigmine: (Major) Cholinergic agonists can cause additive pharmacodynamic effects if used concomitantly with cholinesterase inhibitors. Concurrent use is unlikely to be tolerated by the patient and should be avoided.
Rivastigmine: (Major) Cholinergic agonists can cause additive pharmacodynamic effects if used concomitantly with cholinesterase inhibitors. Concurrent use is unlikely to be tolerated by the patient and should be avoided.
Scopolamine: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Secobarbital: (Major) The action of barbiturates is potentiated by the acetylcholinesterase inhibitors, which should be considered when using pralidoxime. Barbiturates should be used with caution to treat convulsions produced by acetylcholinesterase inhibitors.
Tricyclic antidepressants: (Moderate) Tricyclic antidepressants (TCAs) may antagonize some of the effects of parasympathomimetics (e.g., cholinesterase inhibitors) due to their anticholinergic activity. However, parasympathomimetics like bethanechol have occasionally been used historically to offset some of the adverse peripheral antimuscarinic (anticholinergic) effects of TCAs, such as dry mouth, constipation, or urinary retention. For years, physostigmine was used as an adjunct to the treatment of TCA overdose; however, its efficacy was limited to addressing anticholinergic effects. Additionally, case reports suggest that harmful effects such as seizures and bradyarrhythmias progressing to asystole, especially in patients with cardiac conduction abnormalities at baseline, are possible. For these reasons, physostigmine is no longer considered a standard of care in the treatment of TCA overdose.
Trihexyphenidyl: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Trimipramine: (Moderate) Tricyclic antidepressants (TCAs) may antagonize some of the effects of parasympathomimetics (e.g., cholinesterase inhibitors) due to their anticholinergic activity. However, parasympathomimetics like bethanechol have occasionally been used historically to offset some of the adverse peripheral antimuscarinic (anticholinergic) effects of TCAs, such as dry mouth, constipation, or urinary retention. For years, physostigmine was used as an adjunct to the treatment of TCA overdose; however, its efficacy was limited to addressing anticholinergic effects. Additionally, case reports suggest that harmful effects such as seizures and bradyarrhythmias progressing to asystole, especially in patients with cardiac conduction abnormalities at baseline, are possible. For these reasons, physostigmine is no longer considered a standard of care in the treatment of TCA overdose.
Trospium: (Moderate) Pharmacologically, parasympathomimetic drugs enhance muscarinic/cholinergic function. Because trospium is an antimuscarinic, the muscarinic actions of drugs known as parasympathomimetics, including direct cholinergic agonists, could be antagonized when used concomitantly with trospium.
Pralidoxime is a cholinesterase reactivator that reverses muscle paralysis after organophosphate poisoning. Organophosphate compounds inhibit cholinesterase via phosphorylation of the enzyme. The inhibited cholinesterase is unable to metabolize acetylcholine resulting in an accumulation of the neurotransmitter. Acetylcholine is present in the central nervious system, parts of the autonomic nervous system, and at the skeletal muscle end plates; therefore, accumulation of this neurotransmitter after organophosphate poisoning adversely affects each of these systems. In the somatic nervous system, acetylcholine accumulation leads to paralysis. The clinical effects of pralidoxime are most evident at skeletal neuromuscular junctions. Pralidoxime reverses the paralysis by removing the phosphoryl group from the inhibited cholinesterase molecule, reactivating the enzyme and restoring the body's ability to metabolize acetylcholine. Because pralidoxime's effects are not effective in reversing the effects of the toxin In addition, the drug may have a direct protective effect on cholinesterase and may combine with certain organophosphates, detoxifying them before they can inhibit cholinesterase. Pralidoxime is most effective when given as soon as possible after organophosphate exposure, and as a general rule, little clinical effect is accomplished if the drug is administered more than 36 hours after exposure.
Pralidoxime acts primarily to reverse cholinesterase inhibition at the neuromuscular junction of skeletal and respiratory muscles. Pralidoxime-induced cholinesterase reactivation also occurs at autonomic (nicotinic) receptors, thereby decreasing blood pressure and reducing salivation, muscle twitching, cramps, weakness, tachycardia, and facial pallor. The clinical importance of pralidoxime-induced relief of nicotinic-related effects is questionable because the concomitant administration of atropine will also alleviate these symptoms.
Pralidoxime is administered by intravenous infusion, or by intravenous, intramuscular, or subcutaneous injection. Therapeutic plasma concentrations are estimated to be approximately 4 mcg/mL. Peak plasma levels of pralidoxime are achieved 2-3 hours, 5-15 minutes, and 10-20 minutes following oral, intravenous, and intramuscular administration, respectively. The drug distributes throughout the extracellular water and is not plasma protein-bound. It is not clear whether the drug crosses the blood-brain barrier or distributes into breast milk. Pralidoxime is metabolized by the liver, with a half-life of approximately 74-77 minutes. This rapid excretion may necessitate repeat doses in cases of continued poison absorption. Both unchanged drug and metabolite are excreted by the kidneys.
-Route-Specific Pharmacokinetics
Oral Route
If administered orally, pralidoxime is variably and erratically absorbed across the GI tract with peak plasma levels achieved at 2-3 hours post-administration.
Intravenous Route
Peak plasma levels of pralidoxime are achieved 5-15 minutes following intravenous administration.
Intramuscular Route
Peak plasma levels of pralidoxime are achieved 10-20 minutes following intramuscular administration.