Drug information of Pralidoxime

Mechanism of effect

The principal action of pralidoxime is to reactivate cholinesterase (mainly outside of the central nervous system) which has been inactivated by phosphorylation due to an organophosphate pesticide or related compound.
The destruction of accumulated acetylcholine can then proceed and neuromuscular junctions will again function normally. Pralidoxime also slows the process of "aging" of phosphorylated cholinesterase to a non-reactivatable form, and detoxifies certain organophosphates by direct chemical reaction .

Pharmacodynamic

Pralidoxime Chloride is a cholinesterase reactivator. The drug has its most critical effect in relieving paralysis of the muscles of respiration. Because pralidoxime is less effective in relieving depression of the respiratory center, atropine is always required concomitantly to block the effect of accumulated at this site .
Pralidoxime relieves muscarinic signs and symptoms, salivation, bronchospasm, etc., but this action is relatively unimportant since atropine is adequate for this purpose.

Pharmacokinetics

Following IM administration, peak plasma concentrations achieved in about 28 minutes. Pralidoxime is distributed throughout the extracellular water, it is not bound to plasma protein. The drug is rapidly excreted in the urine partly unchanged, and partly as a metabolite produced by the liver.
Consequently, pralidoxime is relatively short acting and repeated doses may be needed, especially where there is any evidence of continuing absorption of the poison.pralidoxime is excreted in the urine.

Dosage

Usual Adult Dose for Organophosphate Poisoning
IV :
- Initial dose : 1 to 2 g, preferably as an IV infusion in 100 mL of normal saline, over 15 to 30 minutes; if an infusion is not practical or if pulmonary edema is present, the dose should be given slowly (over at least 5 minutes) by IV injection as a 50 mg/mL solution in Sterile Water for Injection (e.g., 1000 mg in 20 mL)
- Second dose : 1 to 2 g may be indicated after about 1 hour if muscle weakness has not been relieved
- Additional doses may be given every 10 to 12 hours if muscle weakness persists.
IM :
Mild symptoms :
- Initial dose : 600 mg IM; recommend waiting 15 minutes for pralidoxime to take effect
- Second dose : 600 mg IM if mild symptoms persist after 15 minutes
Third dose : 600 mg IM (cumulative dose of 1800 mg) if mild symptoms persist after an additional 15 minutes
If severe symptoms develop at any time after the first dose, 2 additional 600 mg IM doses in rapid succession should be administered for a total cumulative dose of 1800 mg.
- Severe symptoms : Three 600 mg IM doses in rapid succession should be administered for a total cumulative dose of 1800 mg.
- Persistent symptoms : If symptoms persist after administration of the complete 1800 mg regimen, the series may be repeated starting about 1 hour after the administration of the last injection.
Usual Adult Dose for Nerve Agent Poisoning
IV : - Initial dose: 1 to 2 g, preferably as an IV infusion in 100 mL of normal saline, over 15 to 30 minutes; if an infusion is not practical or if pulmonary edema is present, the dose should be given slowly (over at least 5 minutes) by IV injection as a 50 mg/mL solution in Sterile Water for Injection (e.g., 1000 mg in 20 mL)
- Second dose: 1 to 2 g may be indicated after about 1 hour if muscle weakness has not been relieved
Additional doses may be given every 10 to 12 hours if muscle weakness persists.
IM :
Mild symptoms :
- Initial dose : 600 mg IM; recommend waiting 15 minutes for pralidoxime to take effect
- Second dose : 600 mg IM if mild symptoms persist after 15 minutes
- Third dose : 600 mg IM (cumulative dose of 1800 mg) if mild symptoms persist after an additional 15 minutes
If severe symptoms develop at any time after the first dose, 2 additional 600 mg IM doses in rapid succession should be administered for a total cumulative dose of 1800 mg.
- Severe symptoms: Three 600 mg IM doses in rapid succession should be administered for a total cumulative dose of 1800 mg.
- Persistent symptoms: If symptoms persist after administration of the complete 1800 mg regimen, the series may be repeated starting about 1 hour after the administration of the last injection.
Usual Adult Dose for Anticholinesterase Overdose
- Initial dose : 1 to 2 g IV slowly
- Maintenance dose : Increments of 250 mg IV every 5 minutes as needed to control symptoms
Usual Pediatric Dose for Organophosphate Poisoning and Nerve Agent PoPoisoni16 years or younger :
IV :
- Pralidoxime can be given as a loading dose followed by continuous IV infusion or as intermittent IV infusions, depending upon patient's clinical condition. The specific dose given should depend upon the severity of symptoms.
- Loading dose : 20 to 50 mg/kg (not to exceed 2 g/dose) over 15 to 30 minutes followed by continuous infusion
- Continuous infusion : 10 to 20 mg/kg/hour following the loading dose
Intermittent infusion :
- Initial dose : 20 to 50 mg/kg (not to exceed 2 g/dose) over 15 to 30 minutes
- Second dose : 20 to 50 mg/kg may be indicated after about 1 hour if muscle weakness has not been relieved
- Repeat dosing : Permissible every 10 to 12 hours as needed.
If administration by continuous or intermittent IV infusion is not practical, or if pulmonary edema is present, the 20 to 50 mg/kg dose should be given slowly (over at least 5 minutes) by IV injection as a 50 mg/mL solution in Sterile Water for Injection .
Additional doses may be given every 10 to 12 hours if muscle weakness persists.
IM :
Less than 40 kg :
Mild symptoms :
- Initial dose: 15 mg/kg IM; recommend waiting 15 minutes for pralidoxime to take effect
- Second dose : 15 mg/kg IM if mild symptoms persist after 15 minutes
- Third dose: 15 mg/kg IM (total cumulative dose of 45 mg/kg) if mild symptoms persist after an additional 15 minutes
If severe symptoms develop at any time after the first dose, 2 additional 15 mg/kg IM doses in rapid succession should be administered for a total cumulative dose of 45 mg/kg.
- Severe symptoms : Three 15 mg/kg IM doses in rapid succession should be administered for a total cumulative dose of 45 mg/kg.
Persistent symptoms: If symptoms persist after administration of the complete 45 mg/kg regimen, the series may be repeated starting about 1 hour after the administration of the last injection.
40 kg or more :
Mild symptoms :
- Initial dose : 600 mg IM; recommend waiting 15 minutes for pralidoxime to take effect
- Second dose : 600 mg IM if mild symptoms persist after 15 minutes
- Third dose : 600 mg IM (total cumulative dose of 1800 mg) if mild symptoms persist after an additional 15 minutes
If severe symptoms develop at any time after the first dose, 2 additional 600 mg IM doses in rapid succession should be administered for a total cumulative dose of 1800 mg.
- Severe symptoms : Three 600 mg IM doses in rapid succession should be administered for a total cumulative dose of 1800 mg.
Persistent symptoms : If symptoms persist after administration of the complete 1800 mg regimen, the series may be repeated starting about 1 hour after the administration of the last injection.

Drug contraindications

Side effects

Interactions

Alerts

 Pralidoxime is not effective in the treatment of poisoning due to phosphorus, inorganic phosphates or organophosphates not having anti cholinesterase activity.
 Pralidoxime has been very well tolerated in most cases, but it must be remembered that the desperate condition of the organophosphate-poisoned patient will generally mask such minor signs and symptoms as have been noted in normal subjects.
 Because pralidoxime is excreted in the urine, a decrease in renal function will result in increased blood levels of the drug. Thus, the dosage of pralidoxime should be reduced in the presence of renal insufficiency.
 Use with caution in patients with myasthenia gravis receiving anticholinesterase agents. May precipitate a myasthenic crisis.
 Hypertension reported. If possible, monitor BP during treatment.

Points of recommendation

Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you :
• If you have an allergy to pralidoxime or any other part of pralidoxime.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
This medicine may interact with other drugs or health problems.

Pregnancy level

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