Note: IV doses <0.5 mg have been associated with paradoxical bradycardia (Boudet 1991; Lonnerholm 1975). Restrict total dose to 0.03 to 0.04 mg/kg in patients with ischemic heart disease.
Bradycardia during neuromuscular blockade reversal: IV: 5 to 7 mcg/kg when administered with edrophonium or 15 to 20 mcg/kg when administered with neostigmine (Cronnelly 1982; Gropper 2019; Mirakhur 1981; Naguib 1989).
Bradycardia, symptomatic:
Note: Atropine is ineffective in heart transplant recipients due to lack of vagal innervation and likely not effective for type II second-degree or third-degree atrioventricular node block (AHA [Hazinski 2015]).
IV, IM: 0.5 to 1 mg every 3 to 5 minutes; 1 mg is preferred for severe bradyarrhythmias (eg, hypotension/shock, altered mental status, acute heart failure); maximum total dose: 3 mg (AHA [Kusumoto 2018]; AHA [Panchal 2020]; AHA/CPR 2020).
Endotracheal: 1 to 2 mg every 3 to 5 minutes.
Inhibition of salivation and secretions (preanesthesia): IM, IV, SUBQ: 0.5 to 1 mg 30 to 60 minutes before procedure; repeat every 4 to 6 hours as needed; maximum total dose: 3 mg.
Muscarine-containing mushroom poisoning (off-label dose): IV: 1 to 2 mg; titrate and repeat as needed to reverse symptoms (ie, titrate to achieve decreased bronchial secretions) (Goldfrank 2019).
Organophosphate or carbamate insecticide or nerve agent poisoning:
Note: The dose of atropine required varies considerably with the severity of poisoning. The total amount of atropine used for carbamate poisoning is usually less than with organophosphate insecticide or nerve agent poisoning. Severely poisoned patients may exhibit significant tolerance to atropine; ≥2 times the suggested doses may be needed. Titrate to pulmonary status (decreased bronchial secretions); consider administration of atropine via continuous IV infusion in patients requiring large doses of atropine (King 2015). Once patient is stable for a period of time, the dose/dosing frequency may be decreased. Pralidoxime is an essential component of the management of organophosphate insecticide and nerve agent toxicity; refer to Pralidoxime monograph for the specific route and dose.
IV:
Mild to moderate symptoms: Initial: 1 to 2 mg bolus (Howland 2018); repeat by doubling the dose every 3 to 5 minutes if previous dose did not induce a response (Eddleston 2004b; Roberts 2007; Thiermann 2013). Maintain atropinization by administering repeat doses as needed for ≥2 to 12 hours based on recurrence of symptoms (Reigart 1999). After the desired response is achieved with bolus dosing, consider starting an IV continuous infusion for improved clinical outcomes (Abedin 2012; Eddleston 2004b; Roberts 2007).
Severe symptoms: Initial: 3 to 5 mg bolus (Howland 2018); repeat by doubling the dose every 3 to 5 minutes if previous dose did not induce a response (Eddleston 2004b; Roberts 2007; Thiermann 2013). Maintain atropinization by administering repeat doses as needed for ≥2 to 12 hours based on recurrence of symptoms (Reigart 1999). After the desired response is achieved with bolus dosing, consider starting an IV continuous infusion for improved clinical outcomes (Abedin 2012; Eddleston 2004b; Roberts 2007).
IV continuous infusion: After desired response is achieved with IV boluses, administer 10% to 20% of the total cumulative IV bolus dose as an IV continuous infusion per hour (eg, if 18 mg given by IV bolus is required to achieve the desired response, start an IV continuous infusion of 1.8 mg per hour); adjust infusion rate as needed to maintain adequate response without causing atropine toxicity (Abedin 2012; Eddleston 2004b; Roberts 2007).
IM (AtroPen):
Mild symptoms (≥2 mild symptoms): Administer 2 mg as soon as an exposure is known or strongly suspected. If severe symptoms develop after the first dose, 2 additional doses should be repeated in rapid succession 10 minutes after the first dose; do not administer more than 3 doses. If profound anticholinergic effects occur in the absence of excessive bronchial secretions, further doses of atropine should be withheld.
Severe symptoms (≥1 severe symptoms): Immediately administer three 2 mg doses in rapid succession.
Symptoms of insecticide or nerve agent poisoning, as provided by manufacturer in the AtroPen product labeling, to guide therapy:
Mild symptoms: Blurred vision, bradycardia, breathing difficulties, chest tightness, coughing, drooling, miosis, muscular twitching, nausea, runny nose, salivation increased, stomach cramps, tachycardia, teary eyes, tremor, vomiting, or wheezing.
Severe symptoms: Breathing difficulties (severe), confused/strange behavior, defecation (involuntary), muscular twitching/generalized weakness (severe), respiratory secretions (severe), seizure, unconsciousness, urination (involuntary).
Endotracheal: Usual dose: 2 to 2.5 times IV dose diluted in 5 to 10 mL of 0.9% sodium chloride or sterile water (Howland 2018).
Stress echocardiography (adjunctive agent) (diagnostic agent) (off-label use): IV: 0.25 to 0.5 mg every 1 minute as needed until 85% of age-predicted maximum heart rate is achieved; maximum total dose: 1 to 2 mg (ASE [Pellikka 2020]; ASNC [Henzlova 2016]).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
(For additional information see "Atropine (systemic): Pediatric drug information")
Bradycardia:
Infants, Children, and Adolescents:
IV, Intraosseous: 0.02 mg/kg/dose; minimum dose: 0.1 mg/dose, maximum dose: 0.5 mg/dose; may repeat once in 5 minutes; reserve use for those patients unresponsive to improved oxygenation and epinephrine (PALS [de Caen 2015]; PALS [Kleinman 2010]; PALS [Topijan 2020]); some have suggested the minimum dose should not be used in patients <5 kg (Barrington 2011; Prakash 2017).
Endotracheal: 0.04 to 0.06 mg/kg/dose; may repeat once if needed (PALS [de Caen 2015]; PALS [Kleinman 2010]).
Inhibit salivation and secretions (preoperative/intraoperative):
Infants and Children <12 years: IM, IV, SUBQ: 0.02 mg/kg/dose; maximum dose: 0.5 mg/dose; administer first dose 30 to 60 minutes preoperatively and then repeat every 4 to 6 hours as needed; maximum total dose: 1 mg/procedure.
Children ≥12 years and Adolescents: IM, IV, SUBQ: 0.02 mg/kg/dose; maximum dose: 1 mg/dose; administer first dose 30 to 60 minutes preoperatively and then repeat every 4 to 6 hours as needed; maximum total dose: 2 mg/procedure.
Intubation; emergent (premedication): Note: Routine use not recommended for preintubation in infants and children; atropine may be considered in situations with a high-risk of bradycardia (eg, succinylcholine use) (PALS [de Caen 2015]) or septic shock (Brierley 2009).
Infants and Children: IV: 0.02 mg/kg/dose with no minimum dose; maximum dose: 0.5 mg/dose (PALS [de Caen 2015]; PALS [Topjian 2020]).
Muscarine-containing mushroom poisoning: Limited data available: Infants, Children, and Adolescents: IV: 0.02 mg/kg/dose; minimum dose: 0.1 mg. Titrate and repeat as needed to reverse symptoms (ie, titrate to achieve decreased bronchial secretions) (Goldfrank 2018).
Organophosphate or carbamate insecticide or nerve agent poisoning:
Note: If exposure is known or suspected, antidotal therapy should be given as soon as symptoms appear; do not wait for confirmation. The dose of atropine required varies considerably with the severity of poisoning. The total amount of atropine used for carbamate poisoning is usually less than with organophosphate insecticide or nerve agent poisoning. Severely poisoned patients may exhibit significant tolerance to atropine; ≥2 times the suggested doses may be needed. Titrate to pulmonary status (decreased bronchial secretions); consider administration of atropine via continuous IV infusion in patients requiring large doses of atropine (King 2015). Once patient is stable for a period of time, the dose/dosing frequency may be decreased. Pralidoxime is a component of the management of organophosphate insecticide and nerve agent toxicity; refer to pralidoxime for the specific route and dose.
IV, IM, Intraosseous (Howland 2018):
Infants and Children: Initial: 0.05 to 0.1 mg/kg; repeat every 3 to 5 minutes as needed, double the dose if previous dose does not induce atropinization (AAP [Roberts 2012]; AAP [Shenoi 2020]; Roberts 2013; Rotenberg 2003). Maintain atropinization by administering repeat doses as needed for ≥2 to 12 hours based on recurrence of symptoms (Roberts 2013).
Adolescents: Initial: 1 to 3 mg; repeat every 3 to 5 minutes as needed, doubling the dose if previous dose does not induce atropinization. Maintain atropinization by administering repeat doses as needed for ≥2 to 12 hours based on recurrence of symptoms (Roberts 2013).
Continuous IV infusion: Infants, Children, and Adolescents: Following atropinization, administer 10% to 20% of the total loading dose required to induce atropinization as a continuous IV infusion per hour; adjust as needed to maintain adequate atropinization without atropine toxicity (Eddleston 2004; Roberts 2007; Roberts 2013).
IM (AtroPen): Infants, Children, and Adolescents: Number of doses dependent upon symptom severity:
Weight-directed dosing:
<7 kg (<15 lb): 0.25 mg/dose (yellow pen).
7 to 18 kg (15 to 40 lb): 0.5 mg/dose (blue pen).
>18 to 41 kg (>40 to 90 lb): 1 mg/dose (dark red pen).
>41 kg (>90 lb): 2 mg/dose (green pen).
Mild symptoms (≥2 mild symptoms): Administer the weight-directed dose listed above as soon as an exposure is known or strongly suspected. If severe symptoms develop after the first dose, 2 additional doses should be repeated in rapid succession 10 minutes after the first dose; do not administer more than 3 doses. If profound anticholinergic effects occur in the absence of excessive bronchial secretions, further doses of atropine should be withheld. Mild symptoms of insecticide or nerve agent poisoning, as provided by manufacturer in the AtroPen product labeling to guide therapy, include: Blurred vision, bradycardia, breathing difficulties, chest tightness, coughing, drooling, miosis, muscular twitching, nausea, runny nose, salivation increased, stomach cramps, tachycardia, teary eyes, tremor, vomiting, or wheezing.
Severe symptoms (≥1 severe symptom): Immediately administer three weight-directed doses in rapid succession (AAP [Shenoi 2020]). Severe symptoms of insecticide or nerve agent poisoning, as provided by manufacturer in the AtroPen product labeling to guide therapy, include: Breathing difficulties (severe), confused/strange behavior, defecation (involuntary), muscular twitching/generalized weakness (severe), respiratory secretions (severe), seizure, unconsciousness, urination (involuntary); Note: Infants may become drowsy or unconscious with muscle floppiness as opposed to muscle twitching.
Endotracheal: Infants, Children, and Adolescents: Increase the dose by 2 to 3 times the usual IV dose. Mix with 3 to 5 mL of normal saline and administer. Flush with 3 to 5 mL of NS and follow with 5 assisted manual ventilations (Rotenberg 2003).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection, as sulfate:
Generic: 8 mg/20 mL (20 mL)
Solution, Injection, as sulfate [preservative free]:
Generic: 0.4 mg/mL (1 mL); 1 mg/mL (1 mL)
Solution, Intravenous, as sulfate [preservative free]:
Generic: 0.4 mg/mL (1 mL); 1 mg/mL (1 mL)
Solution Auto-injector, Intramuscular, as sulfate:
AtroPen: 0.5 mg/0.7 mL (0.7 mL); 1 mg/0.7 mL (0.7 mL); 2 mg/0.7 mL (0.7 mL) [pyrogen free; contains phenol]
Solution Auto-injector, Intramuscular, as sulfate [preservative free]:
AtroPen: 0.25 mg/0.3 mL (0.3 mL) [pyrogen free]
Solution Prefilled Syringe, Injection, as sulfate:
Generic: 1 mg/10 mL (10 mL)
Solution Prefilled Syringe, Injection, as sulfate [preservative free]:
Generic: 0.25 mg/5 mL (5 mL); 0.5 mg/5 mL (5 mL); 1 mg/10 mL (10 mL)
May be product dependent
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection:
Generic: 0.6 mg/mL (1 mL)
Solution, Injection, as sulfate:
Generic: 0.1 mg/mL (10 mL); 0.4 mg/mL (1 mL, 10 mL)
Solution Prefilled Syringe, Injection:
Generic: 1 mg/5 mL (5 mL)
Solution Prefilled Syringe, Injection, as sulfate:
Generic: 0.5 mg/5 mL (5 mL)
The AtroPen formulation is available for use primarily by the Department of Defense.
IM: AtroPen: Administer to the outer thigh. Firmly grasp the autoinjector with the green tip (0.5 mg, 1 mg, and 2 mg autoinjector) or black tip (0.25 mg autoinjector) pointed down; remove the yellow safety release (0.5 mg, 1 mg, and 2 mg autoinjector) or gray safety release (0.25 autoinjector). Jab the green tip at a 90° angle against the outer thigh; may be administered through clothing as long as pockets at the injection site are empty. In thin patients, bunch up the thigh prior to injection. Hold the autoinjector in place for 10 seconds following the injection; remove the autoinjector and massage the injection site. 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.
IV: Administer undiluted by rapid IV injection; slow injection may result in paradoxical bradycardia. In bradycardia, atropine administration should not delay treatment with external pacing.
Intraosseous (IO): May administer intraosseous if needed.
Endotracheal: Dilute in ≤10 mL NS or sterile water. Absorption may be greater with sterile water. Stop compressions (if using for cardiac arrest), spray the drug quickly down the tube. Follow immediately with several quick insufflations and continue chest compressions.
SUBQ: May administer subcutaneous if needed.
Endotracheal: May administer dose undiluted, followed by flush with 1 to 5 mL of NS after endotracheal administration or may further dilute in NS or sterile water prior to administration (ie, 1 to 2 mg in ≤10 mL of NS or sterile water); follow with 5 assisted manual ventilations (Hegenbarth 2008; PALS [Kleinman 2010]; manufacturer's labeling). If using for cardiac arrest, stop compressions during drug administration and resume chest compressions following manual ventilation.
Flush volume based on indication:
Bradycardia:
Neonates: Flush with ≥1 mL NS (Eichenwald 2017).
Infants, Children, and Adolescents: Flush with 5 mL NS (PALS [Kleinman 2010]).
Organophosphate or carbamate insecticide or nerve agent poisoning: Flush with 3 to 5 mL NS (Rotenberg 2003).
Parenteral:
IV: Administer undiluted by rapid IV injection; slow injection may result in paradoxical bradycardia.
IM: AtroPen: Administer to the outer thigh. Firmly grasp the autoinjector with the green tip (0.5 mg, 1 mg, and 2 mg autoinjector) or black tip (0.25 mg autoinjector) pointed down; remove the yellow safety release (0.5 mg, 1 mg, and 2 mg autoinjector) or gray safety release (0.25 autoinjector). Firmly jab the green tip at a 90° angle against the outer thigh; may be administered through clothing as long as pockets at the injection site are empty. In thin patients or patients <6.8 kg (15 lb), bunch up the thigh prior to injection. Hold the autoinjector in place for 10 seconds following the injection; remove the autoinjector and massage the injection site. After administration, the needle will be visible; if the needle is not visible, repeat the above steps with more pressure. After use, bend the needle against a hard surface (needle does not retract) to avoid accidental injury.
Bradycardia during neuromuscular blockade reversal: Adjuvant use during neuromuscular blockade reversal with anticholinesterases (eg, edrophonium, neostigmine) to manage bradycardia.
Bradycardia, symptomatic: Treatment of symptomatic sinus bradycardia.
Inhibition of salivation and secretions (preanesthesia): Preoperative/preanesthetic medication to inhibit salivation and secretions.
Muscarine-containing mushroom poisoning: Treatment of symptoms from muscarine-containing mushroom poisoning.
Organophosphate or carbamate insecticide or nerve agent poisoning: Antidote for anticholinesterase poisoning (carbamate insecticides, nerve agents, organophosphate insecticides).
Stress echocardiography (adjunctive agent) (diagnostic agent)
Beers Criteria: Atropine is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older (independent of diagnosis or condition) due to its highly anticholinergic properties and uncertain effectiveness as an antispasmodic (Beers Criteria [AGS 2019]).
Pharmacy Quality Alliance (PQA): Atropine (excludes ophthalmic) is identified as a high-risk medication in patients 65 years and older on the for PQA’s, Use of High-Risk Medications in the Elderly performance measure, a safety measure used by the Centers for Medicare and Medicaid Services (CMS) for Medicare plans (PQA 2017).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not always defined. Severity and frequency of adverse reactions are dose related.
Cardiovascular: Asystole, atrial arrhythmia, atrial fibrillation, atrioventricular dissociation (transient), bigeminy, bradycardia, chest pain, decreased blood pressure, ECG changes (prolonged P wave, shortened PR segment, R on T phenomenon, shortened RT duration, prolonged QT interval, widening of QRS Complex, flattened T wave, repolarization abnormalities, ST segment elevation, retrograde conduction), ectopic beats (atrial), extrasystoles (nodal, ventricular, supraventricular), flushing, increased blood pressure, left heart failure, myocardial infarction, nodal arrhythmia (no P wave on ECG), palpitations, sinus tachycardia, supraventricular tachycardia (including junctional tachycardia), tachycardia, trigeminy, ventricular arrhythmia (including flutter), ventricular fibrillation, ventricular flutter, ventricular premature contractions, ventricular tachycardia, weak pulse (or impalpable peripheral pulses)
Central nervous system: Abnormal electroencephalogram (runs of alpha waves, increase in photic stimulation, and signs of drowsiness), agitation (children), amnesia, anxiety, ataxia, behavioral changes, coma, confusion, decreased deep tendon reflex, delirium, dizziness, drowsiness, dysarthria, dysmetria, emotional disturbance, excitement, feeling hot, hallucination (visual or aural), headache, hyperpyrexia, hyperreflexia, hypertonia, insomnia, intoxicated feeling, irritability (children), lack of concentration, lethargy (children), mania, myoclonus, neurologic abnormality, nocturnal enuresis, opisthotonus, paranoia, positive Babinski sign, restlessness, seizure (generally tonic-clonic), stupor, vertigo
Dermatologic: Anhidrosis, cold skin, dermatitis, dry and hot skin, erythematous rash, hyperhidrosis, macular eruption, maculopapular rash, papular rash, scarlatiniform rash, skin rash
Endocrine & metabolic: Dehydration, hyperglycemia, hypoglycemia, hypokalemia, hyponatremia, increased thirst, loss of libido
Gastrointestinal: Abdominal and bladder distension, abdominal pain, constipation, delayed gastric emptying, diminished bowel sounds, dry mucous membranes, dysphagia, malabsorption, nausea, oral lesion, paralytic ileus, salivation, vomiting, xerostomia
Genitourinary: Difficulty in micturition, impotence, urinary hesitancy, urinary retention, urinary urgency
Hematologic & oncologic: Abnormal erythrocytes (increased), decreased hemoglobin, increased hemoglobin, leukocytosis, petechiae
Hypersensitivity: Hypersensitivity reaction
Local: Injection site reaction
Neuromuscular & skeletal: Laryngospasm, muscle twitching, weakness
Ophthalmic: Abnormal eye movements (cyclophoria and heterophoria), angle-closure glaucoma (acute), blepharitis, blindness, blurred vision, conjunctivitis, crusted of eyelid, cycloplegia, decreased accommodation, decreased visual acuity, dry eye syndrome, eye irritation, lacrimation, mydriasis, photophobia, strabismus
Renal: Increased blood urea nitrogen
Respiratory: Bradypnea, changes in respiration (labored respiration), cyanosis, dyspnea, laryngitis, pulmonary edema, respiratory failure, stridor (inspiratory), tachypnea
Miscellaneous: Failure to thrive, fever (secondary to decreased sweat gland activity), swelling (children)
There are no contraindications listed in the manufacturer’s labeling.
Concerns related to adverse effects:
• Hypersensitivity: Hypersensitivity reactions, including anaphylactic reactions, may occur.
• Hyperthermia: Atropine may inhibit sweating and possibly lead to heat-related injury or hyperthermia in patients exposed to warm environments or exercise.
• Psychosis: Can occur in sensitive individuals or following use of excessive doses.
Disease-related concerns:
• Arrhythmias: Avoid relying on atropine for effective treatment of type II second-degree or third-degree AV block (with or without a new wide QRS complex). Asystole or bradycardic PEA: Although no evidence exists for significant detrimental effects, routine use is unlikely to have a therapeutic benefit and is no longer recommended (ACLS 2010).
• Cardiovascular disease: Use with caution in patients with myocardial ischemia, heart failure, tachyarrhythmias (including sinus tachycardia), and/or hypertension; 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 thickening of bronchial secretions and formation of dangerous viscid plugs.
• Glaucoma: Use with caution in patients with severe narrow-angle glaucoma; may precipitate acute glaucoma.
• Hepatic impairment: Use with caution in patients with hepatic impairment; effects of atropine may be prolonged in severe hepatic impairment.
• Hiatal hernia: Use with caution in patients with hiatal hernia associated with reflux esophagitis.
• Hyperthyroidism: Use with caution in patients with hyperthyroidism.
• Myasthenia gravis: Use with extreme caution when used to treat side effects of acetylcholinesterase inhibition or avoid; may precipitate a myasthenic crisis.
• Neuropathy: Use with caution in patients with autonomic neuropathy.
• Pyloric stenosis: Use with caution in patients with partial pyloric stenosis; may cause complete pyloric obstruction.
• Renal impairment: Use with caution in patients with renal impairment; effects of atropine may be prolonged in severe renal impairment.
• Urinary retention: Use with caution in patients with urinary obstruction; may cause urinary retention.
Special populations:
• Heart transplant recipients: Atropine will likely be ineffective in treatment of bradycardia due to lack of vagal innervation of the transplanted heart. Cholinergic reinnervation may occur over time (years), so atropine may be used cautiously; however, some may experience paradoxical slowing of the heart rate and high-degree AV block upon administration (ACLS 2010; Bernheim 2004).
• Pediatric: Children may be more sensitive to the anticholinergic effects of atropine. Use with caution in children with spastic paralysis.
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol and/or 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 suggest that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol and/or benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.
Other warnings/precautions:
• Appropriate use: Anticholinesterase poisoning: Atropine reverses the muscarinic but not the nicotinic effects associated with anticholinesterase toxicity. Clinical symptoms consistent with highly-suspected organophosphate or carbamate insecticides or nerve agent poisoning should be treated with antidote immediately; administration should not be delayed for confirmatory laboratory tests. Signs of atropinization include flushing, mydriasis, tachycardia, and dryness of the mouth or nose. Monitor effects closely when administering subsequent injections as necessary. The presence of these effects is not indicative of the success of therapy; inappropriate use of mydriasis as an indicator of successful treatment has resulted in atropine toxicity. Reversal of bronchial secretions is the preferred indicator of success. Adjunct treatment with a cholinesterase reactivator (eg, pralidoxime) may be required in patients with toxicity secondary to organophosphorus insecticides or nerve agents. 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.
Several reports in the literature have described neonates developing central anticholinergic syndrome after receiving atropine for bradycardia at doses of 0.1 mg, the minimum dose that has been described for preventing paradoxical bradycardia. When evaluated based on weight, this dose exceeded 0.02 mg/kg in all cases (Gillick 1974; Prakash 2017; Rizzi 2004); some literature has recommended against using a minimum dose in patients <5 kg to prevent overdose (Barrington 2011; Prakash 2017).
None known.
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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy
Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Amantadine: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy
Amezinium: Atropine (Systemic) may enhance the stimulatory effect of Amezinium. Risk C: Monitor therapy
Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Risk C: Monitor therapy
Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy
Cannabinoid-Containing Products: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Chloral Betaine: May enhance the adverse/toxic effect of Anticholinergic Agents. Risk C: Monitor therapy
Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Risk X: Avoid combination
CloZAPine: Anticholinergic Agents may enhance the constipating effect 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
Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Risk X: Avoid combination
EPHEDrine (Systemic): Atropine (Systemic) may enhance the therapeutic effect of EPHEDrine (Systemic). Risk C: Monitor therapy
Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy
Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor therapy
Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Risk X: Avoid combination
Glycopyrronium (Topical): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Risk C: Monitor therapy
Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Risk X: Avoid combination
Macimorelin: Atropine (Systemic) may diminish the diagnostic effect of Macimorelin. Risk X: Avoid combination
Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy
Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Risk C: Monitor therapy
Nitroglycerin: Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Risk C: Monitor therapy
Opioid Agonists: Anticholinergic Agents may enhance the adverse/toxic effect of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination. Risk C: Monitor therapy
Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: 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. Risk X: Avoid combination
Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. Risk X: Avoid combination
Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Risk X: Avoid combination
Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy
Revefenacin: Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin. Risk X: Avoid combination
Ritodrine: Atropine (Systemic) may enhance the adverse/toxic effect of Ritodrine. Risk C: Monitor therapy
Secretin: Anticholinergic Agents may diminish the therapeutic effect 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 diminish the therapeutic effect 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
Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy
Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Risk X: Avoid combination
Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Risk C: Monitor therapy
Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Atropine crosses the placenta.
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). Medications used for the treatment of cardiac arrest in pregnancy are the same as in the non-pregnant woman. Doses and indications should follow current Advanced Cardiovascular Life Support guidelines. Appropriate medications should not be withheld due to concerns of fetal teratogenicity (Jeejeebhoy [AHA] 2015).
Atropine is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Heart rate, blood pressure, pulse, mental status; intravenous administration requires a cardiac monitor
Organophosphate or carbamate insecticide or nerve agent poisoning: Heart rate, blood pressure, respiratory status, oxygenation secretions. Maintain atropinization with repeated dosing as indicated by clinical status. Crackles in lung bases, or continuation of cholinergic signs, may be signs of inadequate dosing. Pulmonary improvement may not parallel other signs of atropinization. Monitor for signs and symptoms of atropine toxicity (eg, fever, muscle fasciculations, delirium); if toxicity occurs, discontinue atropine and monitor closely.
Consult individual institutional policies and procedures.
Blocks the action of acetylcholine at parasympathetic sites in smooth muscle, secretory glands, and the CNS; increases cardiac output, dries secretions. Atropine reverses the muscarinic effects of cholinergic poisoning due to agents with acetylcholinesterase inhibitor activity by acting as a competitive antagonist of acetylcholine at muscarinic receptors. The primary goal in cholinergic poisonings is reversal of bronchorrhea and bronchoconstriction. Atropine has no effect on the nicotinic receptors responsible for muscle weakness, fasciculations, and paralysis; concurrent administration of pralidoxime is necessary to reverse the nicotinic effects associated with organophosphate insecticide or nerve agent toxicity.
Onset of action:
Inhibition of salivation: IM: Within 30 minutes; maximum effect: 30 to 60 minutes (Mirakhur 1980; Volz-Zang 1995)
Increased heart rate:
IM: Within 15 to 30 minutes (Kentala 1990; Volz-Zang 1995); maximum effect: 45 to 60 minutes (Mirakhur 1980; Volz-Zang 1995)
IV: Immediate; maximum effect: 0.7 to 4 minutes (Lonnerholm 1975; Santini 1999)
Duration: Inhibition of salivation: IM: ≤4 hours (Mirakhur 1980; Volz-Zang 1995)
Absorption: Rapid and well absorbed from all dosage forms
Distribution: Widely throughout the body; crosses blood-brain barrier
Protein binding: 14% to 44%
Metabolism: Hepatic via enzymatic hydrolysis
Half-life elimination: Children <2 years: 6.9 ± 3 hours; Children >2 years: 2.5 ± 1.2 hours; Adults: 3 ± 0.9 hours; Elderly 65 to 75 years of age: 10 ± 7.3 hours
Time to peak: IM: 30 minutes; IM autoinjector: 3 minutes
Excretion: Urine (13% to 50% as unchanged drug and metabolites)
Older adult: Elimination half-life is more than doubled.
Sex: AUC and Cmax are 15% higher in females than males; Elimination half-life is ~20 minutes shorter in females than males.
Solution (Atropine Sulfate Injection)
0.4 mg/mL (per mL): $9.60
1 mg/mL (per mL): $15.07
8 mg/20 mL (per mL): $2.11 - $4.20
Solution (Atropine Sulfate Intravenous)
0.4 mg/mL (per mL): $12.96 - $14.40
1 mg/mL (per mL): $20.35 - $22.61
Solution Auto-injector (AtroPen Intramuscular)
0.25 mg/0.3 mL (per 0.3 mL): $36.28
0.5 mg/0.7 mL (per 0.7 mL): $30.36
1 mg/0.7 mL (per 0.7 mL): $30.36
2 mg/0.7 mL (per 0.7 mL): $30.36
Solution Prefilled Syringe (Atropine Sulfate Injection)
0.25 mg/5 mL (per mL): $3.34 - $4.04
0.5 mg/5 mL (per mL): $2.18 - $2.64
1 mg/10 mL (per mL): $0.84 - $1.51
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