PRALIDOXIME CHLORIDE INJECTION (AUTO-INJECTOR)

FOR USE IN NERVE AGENT POISONING ONLY

A Sterile Solution For Intramuscular Use Only

Rx Only

Pralidoxime Chloride Injection (auto-injector) provides pralidoxime chloride in a sterile solution for intramuscular injection.

Each prefilled auto-injector provides a dose of the antidote, pralidoxime chloride in a self-contained unit, specially designed for automatic self- or buddy-administration by military personnel. Pralidoxime in the auto-injector may also be administered by qualified civilian emergency responders who have had adequate training in the on-site recognition and treatment of nerve agent intoxication in the event of an accidental release of nerve agent. The recommended procedure (see DOSAGE AND ADMINISTRATION) is to inject the contents of the auto-injector into the muscles of an outer thigh.

After an auto-injector has been activated, the empty container should be disposed of properly (see DOSAGE AND ADMINISTRATION), it cannot be refilled nor can the protruding needle be retracted.

When activated, each auto-injector dispenses 600 mg of pralidoxime chloride in 2 mL of a sterile solution containing 20 mg/mL benzyl alcohol, 11.26 mg/mL glycine in Water for Injection, USP. The pH is adjusted with hydrochloric acid. The pH range is 2.0-3.0. The product is pyrogen free.

Pralidoxime chloride is a cholinesterase reactivator.

Chemical Name: 2-formyl-1 methylpyridinium chloride oxime (pyridine-2-aldoxime methochloride). Also referred to as 2-PAM Chloride.

Structural Formula:

Pralidoxime chloride occurs as an odorless, white, nonhygroscopic, crystalline powder which is soluble in water to the extent of 1 g in less than 1 mL.  Stable in air, it melts between 215°C and 225°C, with decomposition.

The specific activity of the drug resides in the 2-formyl-1 methylpyridinium ion and is independent of the particular salt employed. The chloride is preferred because of physiologic compatibility, excellent water solubility at all temperatures, and high potency per gram, due to its low (173) molecular weight.

Pralidoxime chloride is a cholinesterase reactivator.

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. 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 acetylcholine 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.

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.

The minimum therapeutic concentration of pralidoxime in plasma is 4 μg/mL, this level is reached in about 16 minutes after a single injection of 600 mg pralidoxime chloride. The apparent half-life of pralidoxime chloride is 74-77 minutes.

It has been reported that the supplemental use of oxime cholinesterase reactivators (such as pralidoxime) reduces the incidence and severity of developmental defects in chick embryos exposed to such known teratogens as parathion, bidrin, carbachol and neostigmine. This protective effect of the oximes was shown to be dose related.

This auto-injector for pralidoxime chloride is specifically indicated for intramuscular use as an adjunct to atropine in the treatment of poisoning by nerve agents having anticholinesterase activity.

The pralidoxime chloride auto-injector is contraindicated in patients who are hypersensitive to any component of the product.

Pralidoxime is not effective in the treatment of poisoning due to phosphorus, inorganic phosphates or organophosphates not having anticholinesterase activity.

Forty to 60 minutes after intramuscular injection, mild to moderate pain may be experienced at the site of injection.

Pralidoxime may cause blurred vision, diplopia and impaired accommodation, dizziness, headache, drowsiness, nausea, tachycardia, increased systolic and diastolic blood pressure, hyperventilation, and muscular weakness when given parenterally to normal volunteers who have not been exposed to anticholinesterase poisons. In patients it is very difficult to differentiate the toxic effects produced by atropine or the organophosphate compounds from those of the drug.

Elevations in SGOT and/or SGPT enzyme levels were observed in 1 of 6 normal volunteers given 1200 mg of pralidoxime chloride intramuscularly, and in 4 of 6 volunteers given 1800 mg intramuscularly. Levels returned to normal in about 2 weeks. Transient elevations in creatine phosphokinase were observed in all normal volunteers given the drug. A single intramuscular injection of 330 mg in 1 mL in rabbits caused myonecrosis, inflammation and hemorrhage.

When atropine and pralidoxime are used together, the signs of atropinization may occur earlier than might be expected when atropine is used alone. This is especially true if the total dose of atropine has been large and the administration of pralidoxime has been delayed.^{2, 3, 4} Excitement and manic behavior immediately following recovery of consciousness have been reported in several cases. However, similar behavior has occurred in cases of organophosphate poisoning that were not treated with pralidoxime.^{3, 5, 6}

Pralidoxime chloride is not subject to abuse and possesses no known potential for dependence.

Exposure to nerve agents possessing anticholinesterase activity (organophosphate type)

MILD CASE—headache, blurred vision, mild muscarinic signs

MODERATELY SEVERE CASE—excessive sweating, lacrimation, salivation, diarrhea, tightness in the chest

For optimal reactivation of organophosphate-inhibited cholinesterase, atropine and pralidoxime should be administered as soon as possible after exposure. Depending on the severity of symptoms, immediately administer one atropine-containing auto-injector, followed by one pralidoxime-containing auto-injector. Atropine must be given first until its effects become apparent and only then should pralidoxime be administered. If nerve agent symptoms are still present after 15 minutes, repeat injections. If symptoms still exist after an additional 15 minutes, repeat injections for a third time. If after the third set of injections, symptoms remain, do not give any more antidotes but seek medical help.

Pralidoxime chloride is supplied in aqueous solution prefilled in the auto-injector (600 mg, 2 mL) for military use and for use by qualified civilian emergency responders. Auto-injectors are supplied through the Directorate of Medical Materiel, Defense Supply Center Philadelphia or other analogous local, state or federal agency.

When activated, each auto-injector dispenses 600 mg of pralidoxime chloride in 2 mL of a sterile solution containing 20 mg/mL benzyl alcohol, 11.26 mg/mL glycine in Water for Injection, USP. The pH is adjusted with hydrochloric acid. The pH is 2.0-3.0 The product is pyrogen free.

Store at 25°C (77°F); Excursions permitted to 15-30°C (59-86°F).
[See USP Controlled Room Temperature] Keep from freezing.

Meridian Medical Technologies, Inc.
Columbia, MD 21046
A Pfizer Company

00001976
08/16

Printed in U.S.A.

1. Landauer, W.: Cholinomimetic tetrogens. V. The effect of oximes and related cholinesterase reactivators, Teratology 15:33 (Feb.) 1977.
2. Moller, K. O., Jenson-Holm, J., and Lausen, H. H.: Ugeskr. Laeg.123:501, 1961.
3. Namba, T., Nolte, C.T., Jackrel, Jr., and Grob, D.: Poisoning due to organophosphate insecticides. Acute and chronic manifestations, Amer. J. Med. 50:475 (Apr.) 1971.
4. Arena, J. M.: Poisoning. Toxicology. Symptoms. Treatments, ed. 4, Springfield, Ill., Charles C.Thomas, 1979, p. 133.
5. Brachfeld, J., and Zavon, M. R.: Organic phosphate (Phosdrin®) intoxication. Report of case and the results of treatment with 2-PAM, Arch. Environ. Health 11:859,1965.
6. Hayes, W. J., Jr.: Toxicology of Pesticides, Baltimore, The Williams & Wilkins Company, 1975, p. 416.
7. AMA Department of Drugs: AMA Drug Evaluations, ed. 4, Chicago, American Medical Association, 1980, p. 1455.

NDC 11704-107-01

PRALIDOXIME CHLORIDE INJECTION

FOR USE IN NERVE AGENT POISONING ONLY

Sterile solution for intramuscular use only

300 mg/mL (2 mL)

1 REMOVE GRAY SAFETY CAP

2 PLACE BLACK END ON OUTER THIGH AND PUSH HARD UNTIL INJECTOR FUNCTIONS

3 HOLD FIRMLY IN PLACE FOR TEN SECONDS

Each container dispenses 600mg of pralidoxime chloride when activated.

Also contains 20mg/mL benzyl alcohol, and 11.26 mg/mL glycine in

Water for Injection, USP. The pH is adjusted with hydrochloric acid.

Rx Only

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F).

[See USP Controlled Room Temperature]

Keep from freezing.

MERIDIAN MEDICAL TECHNOLIGIES^TM

Columbia, MD 21046, USA

A subsidiary of King Pharmaceuticals^®, Inc

NDC 11704-251-01

0001282

NSN 6505-01-125-3248