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Atropine and pralidoxime: Pediatric drug information

Atropine and pralidoxime: Pediatric drug information
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For additional information see "Atropine and pralidoxime: Drug information" and "Atropine and pralidoxime: Patient drug information"

For abbreviations, symbols, and age group definitions show table
Brand Names: US
  • ATNAA;
  • Duodote [DSC]
Therapeutic Category
  • Anticholinergic Agent;
  • Antidote
Dosing: Pediatric
Organophosphate insecticide or nerve agent poisoning

Organophosphate insecticide or nerve agent poisoning: Note: If exposure is known or suspected, antidotal therapy should be given immediately as soon as symptoms appear (critical to administer immediately in case of soman exposure since its adverse effects develop within minutes). Only health care providers who have had adequate training in the recognition and treatment of nerve agent or insecticide intoxication should administer.

Children and Adolescents weighing >41 kg: DuoDote (atropine 2.1 mg/pralidoxime 600 mg per autoinjector):

Mild symptoms (≥2 mild symptoms): IM: 1 injection (wait 10 to 15 minutes for effect); if after 10 to 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): IM: 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), unconsciousness

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling. Use with caution; pralidoxime can cause kidney impairment.

Dosing: Liver Impairment: Pediatric

There are no dosage adjustments provided in manufacturer's labeling. Use with caution in severe impairment.

Dosing: Adult

(For additional information see "Atropine and pralidoxime: Drug information")

Organophosphate insecticide or nerve agent poisoning

Organophosphate insecticide or nerve agent poisoning: 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 since its adverse effects develop within minutes). Definitive medical care should be sought after any injection given. One injection only may be given as self-aid. If repeat injections are needed, administration must be done by another trained individual. Emergency medical personnel who have self-administered a dose must determine their capacity to continue to provide care.

ATNAA:

Mild symptoms (some or all mild symptoms): Self-Aid or Buddy-Aid: 1 injection (wait 10 to 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 are still present: Buddy-Aid: May repeat 1 to 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 to 15 minutes for effect); if after 10 to 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), unconsciousness

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

There are no specific dosage adjustments provided in the manufacturer's labeling. Use with caution; pralidoxime may cause decreased renal function.

Dosing: Liver Impairment: Adult

There are no specific dosage adjustments provided in the manufacturer's labeling; use with caution in patients with severe impairment.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

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)

Contraindications

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

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; 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.

• 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.

• Urinary obstruction: Use with caution in patients with urinary obstruction; may cause urinary retention.

Special populations:

• Older adult: May be more sensitive to the anticholinergic effects of atropine.

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

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.

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. Continued administration of additional doses in asymptomatic patients may result in atropine toxicity.

Warnings: Additional Pediatric Considerations

CNS effects (eg, restlessness, tremor, fatigue, locomotor difficulties, delirium, hallucinations) of atropine are often seen earlier and at lower doses in pediatric patients compared to adults.

Dosage Forms: US

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

Injection, solution:

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

Generic Equivalent Available: US

No

Pricing: US

Solution Auto-injector (DuoDote Intramuscular)

2.1-600 mg (per mL): $22.58

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Additional Information

Evacuation and decontamination procedures should be undertaken as soon as possible. Medical personnel need to protect themselves from accidental exposure. Primary prophylaxis against organophosphate nerve agents should always consist of appropriate protective garments and masks. Organophosphate agents are well absorbed through skin, lungs, and GI tract. They are usually described as having a petroleum or garlic like odor. Once absorbed, organophosphate agents bind to acetylcholinesterase (also known as RBC acetylcholinesterases) and inactivate the enzyme. Acetylcholinesterases catalyze the hydrolysis of acetylcholine to choline and acetic acid; therefore, once inactivated excess acetylcholine accumulates.

Clinical symptoms of toxicity are associated with cholinergic excess and involve the autonomic nervous system, CNS, and neuromuscular junction. Clinical features of acute cholinergic toxicity include bradycardia, miosis, lacrimation, salivation, bronchorrhea, bronchospasm, emesis and diarrhea. At times, mydriasis and tachycardia may be observed. 100% oxygen and fluid resuscitation are important initial steps in management. Onset and duration of clinical features consistent with poisoning vary depending on agent and route of exposure; therefore, every effort should be made to identify poisoning agent. In addition, time interval to “aging” process (irreversible binding between organophosphates and acetylcholinesterase) vary depending on nerve agent. Once “aging” has occurred, oxime therapy (eg, pralidoxime) is ineffective, thus making timing of antidote administration critical, particularly in the case of soman exposure where “aging” process occurs within minutes of exposure.

Prescribing and Access Restrictions

ATNAA (Antidote Treatment-Nerve Agent Auto-Injector) is only available for use by US Armed Forces military personnel. Information on distribution is available at Defense Services Supply Center-Philadelphia at 215-737-2341.

Duodote is only available for use by trained emergency medical services personnel to treat civilians. Distribution is limited to directly from manufacturer (Meridian Medical Technologies, Inc) to emergency medical service organizations or their suppliers.

Administration: Pediatric

IM:

DuoDote: Administer IM into the mid-lateral thigh. 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 now ready for administration into the mid-lateral thigh; removal of clothing is not necessary, but pockets should be empty. If patient does not have a lot of fat at the injection site, bunch up thigh tissue for a thicker injection area. Firmly push the green tip against the mid-lateral thigh. Hold firmly in place until auto-injector triggers and continue to hold for 10 seconds after the device has triggered. The needle does not retract; after administration, the needle should be visible; if the needle is not visible, repeat the above steps. After use, bend the needle against a hard surface to avoid accidental injury.

Administration: Adult

IM:

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. Removal of clothing is not necessary, but pockets should be empty. Firmly push green tip straight down (90° angle) against the mid-lateral thigh. Hold firmly in place until auto-injector triggers and for ~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/Stability

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F); avoid freezing. Protect from light.

Note: FDA has granted extended expiration dating for certain lots of Duodote 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.

Use

DuoDote: Treatment of poisoning by organophosphate nerve agents (eg, tabun, sarin, soman) or organophosphate insecticides for use by trained emergency medical services personnel (FDA approved in pediatric patients weighing >41 kg and adults).

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 (FDA approved in adults).

Metabolism/Transport Effects

Refer to individual components.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program

Acetylcholinesterase Inhibitors: May decrease therapeutic effects of Agents with Clinically Relevant Anticholinergic Effects. Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Acetylcholinesterase Inhibitors. Risk C: Monitor

Aclidinium: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid

Acrivastine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Alpha1-Agonists: Atropine (Systemic) may increase hypertensive effects of Alpha1-Agonists. Risk C: Monitor

Amantadine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Amezinium: Atropine (Systemic) may increase stimulatory effects of Amezinium. Risk C: Monitor

Benperidol: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Benperidol. Risk C: Monitor

Benztropine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Benztropine. Risk C: Monitor

Beta-Acetyldigoxin: Atropine (Systemic) may increase serum concentration of Beta-Acetyldigoxin. Risk C: Monitor

Biperiden: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Biperiden. Risk C: Monitor

Bornaprine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Bornaprine. Risk C: Monitor

Botulinum Toxin-Containing Products: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Bromperidol: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Bromperidol. Risk C: Monitor

Buclizine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Buclizine. Risk C: Monitor

Cannabinoid-Containing Products: Agents with Clinically Relevant Anticholinergic Effects may increase tachycardic effects of Cannabinoid-Containing Products. Risk C: Monitor

Chlorprothixene: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Chlorprothixene. Risk C: Monitor

Cimetropium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Cimetropium. Risk X: Avoid

CloZAPine: Agents with Clinically Relevant Anticholinergic Effects may increase constipating effects of CloZAPine. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for signs and symptoms of gastrointestinal hypomotility and consider prophylactic laxative treatment. Risk D: Consider Therapy Modification

Cyclizine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Darifenacin: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Darifenacin. Risk C: Monitor

Dicyclomine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Dicyclomine. Risk C: Monitor

Dimethindene (Systemic): Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Dimethindene (Systemic). Risk C: Monitor

DroNABinol: Agents with Clinically Relevant Anticholinergic Effects may increase tachycardic effects of DroNABinol. Risk X: Avoid

Eluxadoline: Agents with Clinically Relevant Anticholinergic Effects may increase constipating effects of Eluxadoline. Risk X: Avoid

EPHEDrine (Systemic): Atropine (Systemic) may increase therapeutic effects of EPHEDrine (Systemic). Risk C: Monitor

Fesoterodine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Fesoterodine. Risk C: Monitor

FluPHENAZine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Gastrointestinal Agents (Prokinetic): Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Gastrointestinal Agents (Prokinetic). Risk C: Monitor

Gepotidacin: May decrease anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Glucagon: Agents with Clinically Relevant Anticholinergic Effects may increase adverse/toxic effects of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor

Glycopyrrolate (Oral Inhalation): Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Glycopyrrolate (Oral Inhalation). Risk X: Avoid

Glycopyrrolate (Systemic): Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Glycopyrrolate (Systemic). Risk C: Monitor

Glycopyrronium (Topical): May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid

Ipratropium (Nasal): May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Ipratropium (Oral Inhalation): May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid

Itopride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Itopride. Risk C: Monitor

Levosulpiride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Levosulpiride. Risk X: Avoid

Macimorelin: Coadministration of Atropine (Systemic) and Macimorelin may alter diagnostic results. Risk X: Avoid

Maprotiline: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Maprotiline. Risk C: Monitor

Melperone: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Methotrimeprazine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Methotrimeprazine. Risk C: Monitor

Methscopolamine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Methscopolamine. Risk C: Monitor

Mirabegron: Agents with Clinically Relevant Anticholinergic Effects may increase adverse/toxic effects of Mirabegron. Risk C: Monitor

Nitroglycerin: Agents with Clinically Relevant Anticholinergic Effects may decrease absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Risk C: Monitor

OLANZapine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of OLANZapine. Risk C: Monitor

Opioid Agonists: Agents with Clinically Relevant Anticholinergic Effects may increase adverse/toxic effects of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination. Risk C: Monitor

Opipramol: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Oxatomide: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid

OxyBUTYnin: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of OxyBUTYnin. Risk C: Monitor

Perazine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Perphenazine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Perphenazine. Risk C: Monitor

Potassium Chloride: Agents with Clinically Relevant Anticholinergic Effects may increase ulcerogenic effects of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Risk X: Avoid

Potassium Citrate: Agents with Clinically Relevant Anticholinergic Effects may increase ulcerogenic effects of Potassium Citrate. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium citrate. Risk X: Avoid

Pramlintide: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. These effects are specific to the GI tract. Risk X: Avoid

Promethazine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Promethazine. Risk C: Monitor

Propantheline: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Propantheline. Risk C: Monitor

Propiverine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

QuiNIDine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Ramosetron: Agents with Clinically Relevant Anticholinergic Effects may increase constipating effects of Ramosetron. Risk C: Monitor

Revefenacin: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Revefenacin. Risk X: Avoid

Ritodrine: Atropine (Systemic) may increase adverse/toxic effects of Ritodrine. Risk C: Monitor

Rivastigmine: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Rivastigmine. Rivastigmine may decrease therapeutic effects of Agents with Clinically Relevant Anticholinergic Effects. Management: Use of rivastigmine with an anticholinergic agent is not recommended unless clinically necessary. If the combination is necessary, monitor for reduced anticholinergic effects. Risk D: Consider Therapy Modification

Scopolamine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Scopolamine. Risk C: Monitor

Secretin: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Risk D: Consider Therapy Modification

Sincalide: Drugs that Affect Gallbladder Function may decrease therapeutic effects of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider Therapy Modification

Sofpironium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Sofpironium. Risk X: Avoid

Thiazide and Thiazide-Like Diuretics: Agents with Clinically Relevant Anticholinergic Effects may increase serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor

Thiothixene: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Thiothixene. Risk C: Monitor

Tiapride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Tiapride. Risk C: Monitor

Tiotropium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Tiotropium. Risk X: Avoid

Tolterodine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Tolterodine. Risk C: Monitor

Topiramate: Agents with Clinically Relevant Anticholinergic Effects may increase adverse/toxic effects of Topiramate. Risk C: Monitor

Tricyclic Antidepressants: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Tricyclic Antidepressants. Risk C: Monitor

Trimethobenzamide: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Trimethobenzamide. Risk C: Monitor

Trospium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Trospium. Risk C: Monitor

Umeclidinium: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid

Zuclopenthixol: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Zuclopenthixol. Risk C: Monitor

Pregnancy Considerations

Atropine crosses the placenta.

Information related to the use of atropine/pralidoxime following organophosphate poisoning in pregnant patients is limited (Bailey 2003; Kamha 2005; Sun 2015). In general, medications used as antidotes should take into consideration the health and prognosis of the mother; antidotes should be administered to pregnant women if there is a clear indication for use and should not be withheld because of fears of teratogenicity (Bailey 2003).

Refer to individual monographs for additional information.

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.

Reference Range

Direct measurement of RBC acetylcholinesterase activity provides a measure of degree of toxicity, although symptoms may not correlate with degree of inactivation unless activity reduced to <50%. Sequential measurement (if rapidly available) may help to determine the effectiveness of oxime therapy. Plasma (or pseudo) cholinesterase activity is more easily performed, but does not correlate well with the severity and should not be used to guide therapy.

Mechanism of Action

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.

Pharmacokinetics (Adult Data Unless Noted)

See individual agents.

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