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Atropine and Pralidoxime

Pronunciation

(A troe peen & pra li DOKS eem)

Index Terms

  • Atropine and Pralidoxime Chloride
  • Mark 1
  • NAAK
  • Nerve Agent Antidote Kit
  • Pralidoxime and Atropine

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, solution:

ATNAA, Duodote™: Atropine 2.1 mg/0.7 mL and pralidoxime chloride 600 mg/2 mL [contains benzyl alcohol; prefilled autoinjector]

Brand Names: U.S.

  • ATNAA
  • Duodote

Pharmacologic Category

  • Anticholinergic Agent
  • Antidote

Pharmacology

Atropine: Functions as a competitive antagonist of acetylcholine at muscarinic receptors in the peripheral and central nervous system, thus reducing the symptoms of parasympathetic overstimulation resulting from excess acetylcholine caused by organophosphate insecticide or nerve agent poisoning. The parasympatholytic action of atropine decreases oral and respiratory secretions, relieves airway constriction, and attenuates the bradycardia induced by organophosphate insecticides and nerve agents. Antagonizes acetylcholine accumulation at respiratory center and may reduce centrally-mediated respiratory paralysis.

Pralidoxime: An oxime which functions by way of nucleophilic attack on the ester site of the acetylcholinesterase enzyme which has been deactivated by phosphorylation. Displacement of the phosphoryl group allows reactivation of acetylcholinesterase’s hydrolytic activity, thus permitting renewed catalysis of accumulated acetylcholine. Destruction of accumulated acetylcholine allows for restoration of normal functioning at neuromuscular junctions and relief from respiratory muscle paralysis.

Use: Labeled Indications

ATNAA: Treatment of poisoning in patients who have been exposed to organophosphate nerve agents (eg, tabun, sarin, soman) that have acetylcholinesterase-inhibiting activity for self- or buddy-administration by military personnel

Duodote™: Treatment of poisoning by organophosphate nerve agents (eg, tabun, sarin, soman) or organophosphate insecticides for use by trained emergency medical services personnel

Contraindications

No contraindications exist in the treatment of life-threatening organophosphate insecticide or nerve agent poisoning

Dosing: Adult

Organophosphate insecticide or nerve agent: IM: Note: If exposure is suspected, antidotal therapy should be given immediately as soon as symptoms appear (critical to administer immediately in case of soman exposure). Definitive medical care should be sought after any injection given. One injection only may be given as self-aid. If repeat injections needed, administration must be done by another trained individual. Emergency medical personnel who have self-administered a dose must determine capacity to continue to provide care.

ATNAA:

Mild symptoms (some or all mild symptoms): Self-Aid or Buddy-Aid: 1 injection (wait 10-15 minutes for effect); if the patient is able to ambulate, and knows who and where they are, then no further injections are needed. If symptoms still present: Buddy-Aid: May repeat 1-2 more injections

Severe symptoms (if most or all): Buddy-Aid: If no self-aid given, 3 injections in rapid succession; if 1 self-aid injection given, 2 injections in rapid succession

Maximum cumulative dose: 3 injections

Symptoms of organophosphate insecticide or nerve agent poisoning, as provided by manufacturer in the ATNAA product labeling to guide therapy:

Mild symptoms: Breathing difficulties, chest tightness, coughing, difficulty in seeing, drooling, headache, localized sweating and muscular twitching, miosis, nausea (with or without vomiting), runny nose, stomach cramps, tachycardia (followed by bradycardia), wheezing

Severe symptoms: Bradycardia, confused/strange behavior, convulsions, increased wheezing and breathing difficulties, involuntary urination/defecation, miosis (severe), muscular twitching/generalized weakness (severe), red/teary eyes, respiratory failure, unconsciousness, vomiting

Duodote™:

Mild symptoms (≥2 mild symptoms): 1 injection (wait 10-15 minutes for effect); if after 10-15 minutes no severe symptoms emerge, no further injections are indicated; if any severe symptoms emerge at any point following initial injection, repeat dose by giving 2 additional injections in rapid succession. Transport to medical care facility.

Severe symptoms (≥1 severe symptom): 3 injections in rapid succession. Transport to medical care facility.

Maximum cumulative dose: 3 injections unless medical care support (eg, hospital, respiratory support) is available

Symptoms of organophosphate insecticide or nerve agent poisoning, as provided by manufacturer in the Duodote™ product labeling to guide therapy:

Mild symptoms: Airway secretions increased, blurred vision, bradycardia, breathing difficulties, chest tightness, drooling miosis, nausea, vomiting, runny nose, salivation, stomach cramps (acute onset), tachycardia, teary eyes, tremors/muscular twitching, wheezing/coughing

Severe symptoms: Breathing difficulties (severe), confused/strange behavior, convulsions, copious secretions from lung or airway, involuntary urination/defecation, muscular twitching/generalized weakness (severe)

Dosing: Geriatric

Refer to adult dosing. No dosing adjustment recommended.

Dosing: Renal Impairment

Use caution in renal impairment; pralidoxime is renally eliminated.

Dosing: Hepatic Impairment

No dosage adjustment provided in manufacturer’s labeling.

Administration

ATNAA: May be administered in the lateral thigh muscle or buttocks. The first dose may be self-administered; subsequent doses must be administered by a buddy. Remove the gray safety cap from the back end; place the front end on the outer thigh or buttocks and push hard to activate the injector. Hold firmly in place for 10 seconds. After use, bend the needle into a hook shape against a hard surface.

Duodote™: Self-administration: Hold the device firmly at the center with the green tip (needle end) pointing down; remove the gray safety release with the other hand; do not touch the green tip at any time. The device is ready for administration into the mid-outer thigh; removal of clothing is not necessary, but pockets should be empty. Swing at a 90° angle to allow the green tip to push against the mid-outer thigh. Hold firmly in place until auto-injector triggers and an additional 10 seconds after device has triggered. After administration, the needle will be visible; if the needle is not visible, repeat the above steps. After use, bend the needle against a hard surface (needle does not retract) to avoid accidental injury.

Storage

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F); avoid freezing. Protect from light.

Note: As of May 2014, for certain lots of DuoDote, the U.S. Food and Drug Administration (FDA) has granted extended expiration dating for up to 2 years beyond the manufacturer’s labeled expiration dating. Further information may be found at http: / / www.fda.gov / drugs / drugsafety / ucm376367.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.

Drug Interactions

AbobotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of AbobotulinumtoxinA. Monitor therapy

Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Monitor therapy

Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Analgesics (Opioid): Anticholinergic Agents may enhance the adverse/toxic effect of Analgesics (Opioid). Specifically, the risk for constipation and urinary retention may be increased with this combination. Monitor therapy

Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Monitor therapy

Cannabinoid-Containing Products: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Exceptions: Cannabidiol. Monitor therapy

Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Avoid combination

Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Avoid combination

EPHEDrine (Systemic): Atropine (Systemic) may enhance the therapeutic effect of EPHEDrine (Systemic). Monitor therapy

Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Monitor therapy

Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Avoid combination

Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Avoid combination

Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Monitor therapy

Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Avoid combination

Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy

Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Monitor therapy

OnabotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of OnabotulinumtoxinA. Monitor therapy

Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Avoid combination

Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Consider therapy modification

Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Monitor therapy

RimabotulinumtoxinB: Anticholinergic Agents may enhance the anticholinergic effect of RimabotulinumtoxinB. Monitor therapy

Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid using drugs with substantial anticholinergic effects in patients receiving secretin whenever possible. If such agents must be used in combination, monitor closely for a diminished response to secretin. Consider therapy modification

Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Avoid combination

Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Monitor therapy

Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Adverse Reactions

Frequency not defined. Reactions reported with Duodote. Also see individual agents.

Cardiovascular: Transient increase of blood pressure (usually occurring 15 minutes after administration and returning to baseline 4 hours post-dose)

Central nervous system: Hypertonia (at injection site; mild-to-moderate)

Local: Pain at injection site (mild-to-moderate)

Warnings/Precautions

Concerns related to adverse effects:

• Atropinization: Signs of atropinization (eg, flushing, mydriasis, tachycardia, dryness of mouth or nose) may occur earlier than expected with the use of a combination product as compared to atropine alone. Monitor effects closely when administering subsequent injections as necessary. The presence of these effects is not indicative of the success of therapy. Reversal of bronchial secretions is the preferred indicator of success.

• Hyperthermia: Atropine may inhibit sweating and possibly lead to heat-related injury or hyperthermia in patients exposed to warm environments or exercise.

Disease-related concerns: The following diseases are relative precautions only when symptoms of poisoning are not severe:

• Cardiovascular disease: Use with caution in patients with heart disease, arrhythmias (eg, atrial flutter), severe CAD, or history of recent MI; treatment-related blood pressure increases and tachycardia may lead to ischemia, precipitate an MI, or increase arrhythmogenic potential.

• Chronic lung disease: Use with caution in patients with chronic lung disease patients; may cause inspiration of bronchial secretions and formation of dangerous viscid plugs.

• Hepatic impairment: Use with caution in patients with hepatic impairment; effects of atropine may be prolonged in severe hepatic impairment.

• Myasthenia gravis: Use with caution in patients with myasthenia gravis; may precipitate myasthenic crisis.

• Narrow-angle glaucoma: Use with caution in patients with severe narrow-angle glaucoma; may precipitate acute glaucoma.

• Prostatic hyperplasia: Use with caution in patients with prostatic hyperplasia; may cause urinary retention.

• Pyloric stenosis: Use with caution in patients with pyloric stenosis; may cause complete pyloric obstruction.

• Renal impairment: Use with caution in renal impairment; pralidoxime is excreted renally and the effects of atropine may be prolonged in severe renal impairment.

Special populations:

• Elderly: Elderly patients may be more sensitive to the anticholinergic effects of atropine.

• Pediatric: Children may be more sensitive to the anticholinergic effects of atropine.

Other warnings/precautions:

• Appropriate use: Clinical symptoms consistent with highly-suspected organophosphate insecticide or nerve agent poisoning should be treated with antidote immediately; administration should not be delayed for confirmatory laboratory tests. Treatment should always include proper evacuation and decontamination procedures; medical personnel should protect themselves from inadvertent contamination. Antidotal administration is intended only for initial management; definitive and more extensive medical care is required following administration. Individuals should not rely solely on antidote for treatment, as other supportive measures (eg, artificial respiration) may still be required.

Monitoring Parameters

Respiratory status, ABGs, pulse oximeter; body temperature (especially in warm climates); blood pressure (peak effect occurs ~15 minutes after administration); symptoms of poisoning

Pregnancy Risk Factor

C

Pregnancy Considerations

Reproduction studies have not been conducted with this combination. Also refer to individual agents. The risk:benefit ratio must be considered in pregnant patients who have been exposed to a nerve agent such as sarin. While adequate studies have not been conducted, survival of the mother may be dependent upon administering atropine and pralidoxime.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience muscle rigidity, injection site pain, nasal dryness, vision changes, dry eyes, sensitivity to light, enlarged pupils, dizziness, flushing, constipation, abdominal pain, stomach edema, nausea, vomiting, lack of sweating, fatigue, muscle weakness, dry skin, or dry mouth. Have patient report immediately to prescriber fast breathing, severe dizziness, severe headache, confusion, difficult urination, decreased libido, passing out, sexual dysfunction, urinary retention, change in amount of urine passed, abnormal heartbeat, angina, or tachycardia (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating, and advising patients.

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