Pralidoxime

Serious side effects have been reported with pralidoxime.  See the "Drug Precautions" section.

Common side effects of pralidoxime include the following:

• headache
• blurred vision
• nausea
• increased heart rate
• increased blood pressure
• muscle weakness
• injection site pain
• dizziness

This is not a complete list of pralidoxime side effects.  Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects.  You may report side effects to the FDA at 1-800-FDA-1088.

Pralidoxime is usually given as soon as possible after the onset of poisoning or overdose symptoms. You may need to receive pralidoxime for several days.

Pralidoxime is injected into a muscle, under the skin, or into a vein through an IV. A healthcare provider will give you this injection. Pralidoxime must be given slowly. The IV infusion can take up to 30 minutes to complete.

Your breathing, blood pressure, oxygen levels, kidney function, and other vital signs will be watched closely while you are receiving this medication.

After treatment with pralidoxime, you may be watched for up to 72 hours to make sure the medicine has been effective and you no longer have any effects of the poison or drug overdose.

Since this medication is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

Overdose symptoms may include some of the side effects listed in this medication guide.

Some of the side effects of pralidoxime may be similar to the symptoms of poisoning. Your caregivers will watch you closely to determine whether your body is responding well to the medication, or if you are having any serious side effects.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Tell your caregivers at once if you have a serious side effect such as:

• fast heart rate;

• rapid breathing;

• increased muscle stiffness;

• a choking feeling;

Less serious side effects may include:

• pain where the medicine was injected;

• blurred vision;

• feeling dizzy or drowsy;

• headache; or

• nausea.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

• Antidote

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

Distribution

Vdss: 0.6 to 2.7 L/kg; Severely poisoned pediatric patients (n=11; age: 0.8 to 18 years): ~9 L/kg (range: 1.7 to 13.8 L/kg) (Schexnayder 1998); may increase with increasing severity of organophosphate intoxication

Metabolism

Hepatic

Excretion

Urine (80% as metabolites and unchanged drug)

Time to Peak

Serum: IV: 5 to 15 minutes; IM: ~35 minutes

Half-Life Elimination

Apparent: 74 to 77 minutes; Poisoned patients (IM, IV): 3 to 4 hours; Pediatric patients (n=11; age: 0.8 to 18 years): 2.4 to 5 hours

Protein Binding

None

Anticholinesterase overdose (eg, neostigmine, pyridostigmine): IV: 1000-2000 mg; followed by increments of 250 mg every 5 minutes as needed

Organophosphate poisoning: Note: Use in conjunction with atropine; a response to atropine should be established before pralidoxime is administered. IM or SubQ administration should be considered when IV administration is not feasible:

IV: Loading dose: 1000-2000 mg; Maintenance: Repeat bolus of 1000-2000 mg after 1 hour and repeated every 10-12 hours thereafter, as needed. Alternatively, administer a loading dose of 30 mg/kg followed by a maintenance infusion of 8 mg/kg/hour (off-label dose; Roberts, 2007).

IM:

Mild symptoms: 600 mg; repeat as needed for persistent mild symptoms every 15 minutes to a maximum total dose of 1800 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 1800 mg

Persistent symptoms: May repeat the entire series (1800 mg) beginning ~1 hour after administration of the last injection

Disease-related concerns:

• Carbamate poisoning: Pralidoxime is not indicated for the treatment of carbamate poisoning; 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.

Applies to pralidoxime: intravenous powder for injection

General

Pralidoxime has been well tolerated in most cases; however, it should be considered that the desperate condition of the organophosphate-poisoned patient generally masks the minor signs and symptoms noted in normal subjects who have not been exposed to anticholinesterase poisons. Many of the signs and symptoms of organophosphate poisoning are similar to the side effects of pralidoxime. It may be difficult to ascertain which effects are due to the drug and which are toxic symptoms produced by atropine or the organophosphate compounds.[Ref]

Cardiovascular

Cardiovascular side effects have included tachycardia and increased systolic and diastolic blood pressure in normal subjects. Tachycardia has also occurred after excessively rapid infusions. Asystole and cardiac arrest have been reported; however, causality is unclear due to the presence of atropine and an organophosphate insecticide.[Ref]

Musculoskeletal

Musculoskeletal side effects have included muscle weakness in normal subjects. Laryngospasm and muscle rigidity have occurred after excessively rapid infusions.[Ref]

Nervous system

Nervous system side effects have included dizziness, headache, and drowsiness in normal subjects.[Ref]

Respiratory

Respiratory side effects have included hyperventilation in normal subjects.[Ref]

Ocular

Ocular side effects have included blurred vision, diplopia, and impaired accommodation in normal subjects.[Ref]

Gastrointestinal

Gastrointestinal side effects have included nausea in normal subjects.[Ref]

Metabolic

Metabolic side effects have included transient elevations of creatine phosphokinase in all normal subjects.

Hepatic

Hepatic side effects have included elevations of AST and/or ALT in normal subjects.[Ref]

Elevated AST and/or ALT were reported in 1 of 6 normal subjects given 1200 mg intramuscularly and 4 of 6 normal subjects given 1800 mg intramuscularly. Levels returned to normal in about 2 weeks.[Ref]

Local

Local side effects have included mild to moderate injection site pain, 40 to 60 minutes after intramuscular injection.[Ref]

Some side effects of pralidoxime may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

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.

16 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.

Data not available