Drug Detail:Protopam chloride (Pralidoxime [ pral-i-dox-eem ])
Generic Name: PRALIDOXIME CHLORIDE 1g in 20mL
Dosage Form: injection, powder, lyophilized, for solution
Drug Class: Antidotes
Organophosphate Poisoning
Treatment should include general supportive care, atropinization, and decontamination, in addition to the use of PROTOPAM Chloride. Treatment is most effective if initiated immediately after poisoning. Administration of PROTOPAM 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 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 Chloride may be needed every three to eight hours. In effect, the patient should be “titrated” with PROTOPAM 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 Chloride may be administered.
Symptoms Of Nerve Agent And Insecticide Poisoning
PROTOPAM Chloride dosing is based, in part, on the severity of symptoms of nerve agent intoxication. These symptoms include the following:
MILD symptoms:
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- Blurred vision and sore eyes
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- Teary eyes*
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- Runny nose*
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- Increased salivation such as sudden drooling*
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- Chest tightness or difficulty breathing
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- Tremors throughout the body or muscular twitching
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- Nausea and vomiting
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- Involuntary respiratory secretions
SEVERE symptoms:
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- Strange or confused behavior
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- Severe difficulty breathing or respiratory secretions
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- Severe muscular twitching and general weakness**
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- Involuntary urination and defecation*
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- Convulsions
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- 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 Chloride that result in a 10-20 mg/mL solution for intravenous infusion.
Inject an initial dose of 1000 to 2000 mg of PROTOPAM 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 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 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 Chloride may maintain therapeutic levels longer than traditional short intermittent infusions therapy (see Pharmacokinetics).
ADULT INTRAMUSCULAR DOSING:
Refer to the Preparation for Administration section for instructions on reconstitution of PROTOPAM 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
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- For treatment of mild symptoms, administer a 600 mg (2 mL) intramuscular dose of PROTOPAM Chloride. Wait 15 minutes for PROTOPAM Chloride to take effect.
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- If, after 15 minutes, mild symptoms persist, then administer a second 600 mg (2 mL) intramuscular dose of PROTOPAM Chloride.
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- If, after an additional 15 minutes, mild symptoms continue to persist, a third 600 mg (2 mL) dose of PROTOPAM Chloride may be administered for a total cumulative dose of 1800 mg.
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- 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 Chloride.
SEVERE SYMPTOMS
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- 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 Chloride.
PERSISTENT SYMPTOMS
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- 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 Chloride that result in 10-20 mg/mL solution for intravenous infusion.
PROTOPAM 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 Following 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 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 Chloride should depend upon the severity of the symptoms.
MILD SYMPTOMS
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- For the treatment of mild symptoms, administer a weight-appropriate intramuscular dose (see Table 1 below) of PROTOPAM Chloride. Wait 15 minutes for PROTOPAM Chloride to take effect.
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- If, after 15 minutes, mild symptoms persist, then administer a second weight-appropriate intramuscular dose of PROTOPAM Chloride.
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- If after an additional 15 minutes, mild symptoms continue to persist, a third weight-appropriate intramuscular dose of PROTOPAM Chloride may be administered.
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- The three PROTOPAM Chloride injections together are considered a single course of treatment, and the total amount of PROTOPAM Chloride administered per course of treatment (i.e., 3 weight-appropriate injections) should not exceed the total amounts listed in Table 1 below.
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- If at any time after the first dose, the patient develops severe symptoms, administer two additional weight-appropriate intramuscular doses of PROTOPAM Chloride in rapid succession.
SEVERE SYMPTOMS
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- For treatment of severe symptoms, administer the weight-appropriate intramuscular dose (see Table 1 below) of PROTOPAM Chloride Injection as three injections, in rapid succession, into the patient’s anterolateral thigh (see Table 1 below).
PERSISTENT SYMPTOMS
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- 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.
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Weight in kg |
Dose Per Injection† |
Total Dose per Three-Injection Course‡ |
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< 40kg |
15 mg/kg |
45 mg/kg |
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≥ 40 kg§ |
Use Adult Dosing Recommendations¶ |
Use Adult Dosing Recommendations |
Anticholinesterase Overdosage
As an antagonist to such anticholinesterases as neostigmine, pyridostigmine, and ambenonium, which are used in the treatment of myasthenia gravis, PROTOPAM 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 Chloride is supplied as 1000 mg single-dose vials for injection.
For INTRAVENOUS infusion: Reconstitute a single PROTOPAM 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 further be 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 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.
