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Protopam

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Protopam

Protopam

INDICATIONS

PROTOPAM (pralidoxime chloride) is indicated as an antidote:

  1. In the treatment of poisoning due to those pesticides and chemicals (e.g., nerve agents) of the organophosphate class which have anticholinesterase activity and
  2. In the control of overdosage by anticholinesterase drugs used in the treatment of myasthenia gravis.

The principal indications for the use of PROTOPAM (pralidoxime chloride) are muscle weakness and respiratory depression. In severe poisoning, respiratory depression may be due to muscle weakness.

DOSAGE AND ADMINISTRATION

Organophosphate Poisoning

Treatment should include general supportive care, atropinization, and decontamination, in addition to the use of PROTOPAM (pralidoxime chloride) . Treatment is most effective if initiated immediately after poisoning. Administration of PROTOPAM (pralidoxime chloride) should be carried out slowly and, preferably, by infusion. If intravenous administration is not feasible, intramuscular or subcutaneous injection should be used. Generally, little is accomplished if PROTOPAM (pralidoxime chloride) is given more than 36 hours after termination of exposure to the poison. When the poison has been ingested, it is particularly important to take into account the likelihood of continuing absorption from the lower bowel since this constitutes new exposure and fatal relapses have been reported after initial improvement. In such cases, additional doses of PROTOPAM (pralidoxime chloride) may be needed every three to eight hours. In effect, the patient should be “titrated” with PROTOPAM (pralidoxime chloride) as long as signs of poisoning recur. As in all cases of organophosphate poisoning, care should be taken to keep the patient under observation for at least 48 to 72 hours.

If dermal exposure has occurred, clothing should be removed and the hair and skin washed thoroughly with sodium bicarbonate or alcohol as soon as possible.

Supportive care, including airway management, respiratory and cardiovascular support, correction of metabolic abnormalities, and seizure control, may be necessary in cases of severe organophosphate poisoning.

Atropine should be given as soon as possible after hypoxemia is improved. Atropine should not be given in the presence of significant hypoxia due to the risk of atropine-induced ventricular fibrillation. In adults, atropine may be given intravenously in doses of 2 to 4 mg. This should be repeated at 5- to 10-minute intervals until full atropinization (secretions are inhibited) or signs of atropine toxicity appear (delirium, hyperthermia, muscle twitching).

Some degree of atropinization should be maintained for at least 48 hours, and until any depressed blood cholinesterase activity is reversed.

Use of morphine, theophylline, aminophylline, reserpine, and phenothiazine-type tranquilizers should be avoided in patients with organophosphate poisoning (see PRECAUTIONS: DRUG INTERACTIONS). Prolonged paralysis has been reported in patients when succinylcholine is given with drugs having anticholinesterase activity; therefore, it should be used with caution.

After the effects of atropine become apparent, PROTOPAM (pralidoxime chloride) may be administered.

Symptoms Of Nerve Agent And Insecticide Poisoning

PROTOPAM (pralidoxime chloride) dosing is based, in part, on the severity of symptoms of nerve agent intoxication. These symptoms include the following:

MILD symptoms

  • Blurred vision and sore eyes
  • Teary eyes*
  • Runny nose*
  • Increased salivation such as sudden drooling*
  • Chest tightness or difficulty breathing
  • Tremors throughout the body or muscular twitching
  • Nausea and vomiting
  • Involuntary respiratory secretions

SEVERE symptoms

  • Strange or confused behavior
  • Severe difficulty breathing or respiratory secretions
  • Severe muscular twitching and general weakness**
  • Involuntary urination and defecation*
  • Convulsions
  • Unconsciousness

Symptoms in INFANTS AND YOUNG CHILDREN

* These symptoms are sometimes observed in healthy infants and young children. In this age group, these symptoms are less reliable than other symptoms listed. Symptoms must be considered collectively when nerve agent or pesticide exposure is known or suspected.

** Infants may become drowsy or unconscious, with muscle floppiness rather than muscle twitching, soon after exposure to nerve agents or pesticides.

ADULT DOSING

ADULT INTRAVENOUS DOSING

Refer to the Preparation for Administration section for instructions on reconstitution and dilution of PROTOPAM (pralidoxime chloride) that result in a 10-20 mg/mL solution for intravenous infusion.

Inject an initial dose of 1000 to 2000 mg of PROTOPAM (pralidoxime 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.

Intravenous administration of PROTOPAM (pralidoxime chloride) should be carried out slowly and, preferably, by continuous or intermittent infusion, since temporary worsening of cholinergic manifestations (i.e. tachycardia, cardiac arrest, laryngospasm, and muscle rigidity or paralysis) may occur if PROTOPAM (pralidoxime chloride) is infused too rapidly. The intermittent infusion rate should not exceed 200 mg/minute. If intravenous administration is not feasible, intramuscular or subcutaneous injection should be used.

Evidence suggests that a loading dose followed by continuous intravenous infusion of PROTOPAM (pralidoxime chloride) may maintain therapeutic levels longer than traditional short intermittent infusion therapy (see Pharmacokinetics).

ADULT INTRAMUSCULAR DOSING

Refer to the Preparation for Administration section for instructions on reconstitution of PROTOPAM (pralidoxime chloride) that result in an approximate 300 mg/mL solution for intramuscular administration.

Intramuscular dosing in adults should be based on the severity of clinical symptoms.

MILD SYMPTOMS

  • For treatment of mild symptoms, administer a 600 mg (2 mL) intramuscular dose of PROTOPAM (pralidoxime chloride) . Wait 15 minutes for PROTOPAM (pralidoxime chloride) to take effect.
  • If, after 15 minutes, mild symptoms persist, then administer a second 600 mg (2 mL) intramuscular dose of PROTOPAM (pralidoxime chloride) .
  • If, after an additional 15 minutes, mild symptoms continue to persist, a third 600 mg (2 mL) intramuscular dose of PROTOPAM (pralidoxime chloride) may be administered for a total cumulative dose of 1800 mg.
  • If at any time after the first dose, the patient develops severe symptoms, administer two additional 600 mg intramuscular doses in rapid succession for a total cumulative dose of 1800 mg of PROTOPAM (pralidoxime chloride) .

SEVERE SYMPTOMS

  • For treatment of severe symptoms, administer three 600 mg intramuscular doses (3 doses of 2 mL each) in rapid succession for a total dose of 1800 mg of PROTOPAM (pralidoxime chloride) .

PERSISTENT SYMPTOMS

  • If symptoms persist after administering the complete 1800 mg regimen (3 injections of 600 mg each), the series may be repeated beginning approximately 1 hour after administration of the last injection.

PEDIATRIC DOSING (FOR PATIENTS 16 YEARS AND UNDER)

PEDIATRIC INTRAVENOUS DOSING

Refer to the Preparation for Administration section for instructions on reconstitution and dilution of PROTOPAM (pralidoxime chloride) that result in a 10-20 mg/mL solution for intravenous infusion.

PROTOPAM (pralidoxime chloride) can be given as intermittent intravenous infusions or as a loading dose followed by continuous intravenous infusion, depending upon the patient's clinical condition. The specific dose given should depend upon the severity of the symptoms.

Loading Dose Followed By Continuous Infusion

Administer a loading dose of 20-50 mg/kg (not to exceed 2000 mg/dose) over 15-30 minutes followed by a continuous infusion of 10-20 mg/kg/hour.

Intermittent Infusion Dosing

Administer an initial intermittent infusion of 20-50 mg/kg (not to exceed 2000 mg/dose) over 15-30 minutes. A second dose of 20-50 mg/kg may be indicated after about one hour if muscle weakness has not been relieved. Repeat dosing is permissible every 10-12 hours as needed.

If it is not practical to administer intermittent or continuous intravenous infusions, or if 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 (see Preparation for Administration section). Additional doses may be given every 10-12 hours if muscle weakness persists.

PEDIATRIC INTRAMUSCULAR DOSING

Refer to the Preparation for Administration section for instructions on reconstitution of PROTOPAM (pralidoxime chloride) that result in an approximate 300 mg/mL solution for intramuscular administration.

Intramuscular injections in children should be administered in the anterolateral aspect of the thigh to avoid the nerve, artery and vein, as well as the femur.

Pharmacokinetic modeling using published data from the scientific literature was conducted to derive intramuscular dosing recommendations in the pediatric population. The specific intramuscular dose of PROTOPAM (pralidoxime chloride) should depend upon the severity of the symptoms.

MILD SYMPTOMS

  • For treatment of mild symptoms, administer a weight-appropriate intramuscular dose (see Table 1 below) of PROTOPAM (pralidoxime chloride) . Wait 15 minutes for PROTOPAM (pralidoxime chloride) to take effect.
  • If, after 15 minutes, mild symptoms persist, then administer a second weight-appropriate intramuscular dose of PROTOPAM (pralidoxime chloride) .
  • If after an additional 15 minutes, mild symptoms continue to persist, a third weight-appropriate intramuscular dose of PROTOPAM (pralidoxime chloride) may be administered.
  • The three PROTOPAM (pralidoxime chloride) injections together are considered a single course of treatment, and the total amount of PROTOPAM (pralidoxime chloride) administered per course of treatment (i.e., 3 weight-appropriate injections) should not exceed the total amounts listed in Table 1 below.
  • If at any time after the first dose, the patient develops severe symptoms, administer two additional weight-appropriate intramuscular doses of PROTOPAM (pralidoxime chloride) in rapid succession.

SEVERE SYMPTOMS

  • For treatment of severe symptoms, administer the weight-appropriate intramuscular dose (see Table 1 below) of PROTOPAM (pralidoxime chloride) as three injections, in rapid succession, into the patient's anterolateral thigh (see Table 1 below).

PERSISTENT SYMPTOMS

If symptoms persist after administering a complete course (3 injections of the weight-appropriate dose each), the series may be repeated beginning approximately 1 hour after administration of the last injection.

Table 1: Pediatric Intramuscular Dosing Recommendations1

Weight in kg Dose Per Injection2 Total Dose per Three- Injection Course3
< 40 kg 15 mg/kg 45 mg/kg
≥ 40 kg4 Use Adult Dosing Recommendations5 Use Adult Dosing Recommendations
1 Dosing is based on an approximate 300 mg/mL solution.
2 During the treatment for mild symptoms, if at any time after the first dose, the patient develops severe symptoms, administer two additional weight- appropriate intramuscular doses of PROTOPAM (pralidoxime chloride) in rapid succession.
3 Additional courses of PROTOPAM (pralidoxime chloride) may be administered beginning one hour after the last injection. A single course consists of three separate, weight-appropriate injections, administered either with 15 minute inter-injection observation periods for patients with mild symptoms, or all in rapid succession for patients with severe symptoms.
4 Weight of 40 kg corresponds to approximately the 50th percentile for a 12 year old child per the weight-for-age percentile growth charts published by the Centers for Disease Control and Prevention in 2000.
5 Adult Dose Per Injection is 600 mg; Total Adult Dose per Three-Injection Course is 1800 mg.

Anticholinesterase Overdosage

As an antagonist to such anticholinesterases as neostigmine, pyridostigmine, and ambenonium, which are used in the treatment of myasthenia gravis, PROTOPAM (pralidoxime chloride) may be given in a dosage of 1000 to 2000 mg intravenously followed by increments of 250 mg every five minutes.

Preparation for Administration

PROTOPAM (pralidoxime chloride) is supplied as 1000 mg single-dose vials for injection.

For INTRAVENOUS infusion: Reconstitute a single PROTOPAM (pralidoxime chloride) 1000 mg vial by adding 20 mL of Sterile Water for Injection, USP, which results in a 50 mg/mL concentration.

The solution should be further diluted with Normal Saline for Injection, USP to achieve a concentration of 10 to 20 mg/mL (e.g. 1000 mg in 100 mL or 2000 mg in 100 mL).

For fluid restricted patients or for rapid administration (over at least 5 min), a maximum concentration of 50 mg/mL may be used.

For INTRAMUSCULAR injection: Reconstitute a single PROTOPAM (pralidoxime chloride) 1000 mg vial by adding 3.3 mL of Sterile Water for Injection, USP for an approximate concentration of 300 mg/mL.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Discard unused solution after a dose has been withdrawn.

HOW SUPPLIED

NDC 60977-141-01—Hospital Package: This contains six 20 mL vials of 1 g each of sterile PROTOPAM Chloride (pralidoxime chloride) for Injection white to off-white porous cake*, without diluent or syringe.

Storage

Store at 20°-25°C (68°-77°F), excursions permitted to 15°-30°C (59°-86°F) [see USP Controlled Room Temperature].

REFERENCES

*When necessary, sodium hydroxide is added during processing to adjust the pH.

Manufactured for : Baxter Healthcare Corporation, Deerfield, IL 60015 USA By: Baxter Pharmaceutical Solutions LLC Bloomington, IN 47403. For Product Inquiry 1 800 ANA DRUG (1-800-262-3784).

Last reviewed on RxList: 10/13/2010
This monograph has been modified to include the generic and brand name in many instances.

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