Atropine

Pharmacologic Category

Anticholinergic Agent; Antidote; Antispasmodic Agent, Gastrointestinal

Dosing: Adult

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.

Inhibit salivation and secretions (preanesthesia): IM, IV, SubQ: 0.4 to 1 mg 30 to 60 minutes preoperatively and repeat every 4 to 6 hours as needed; maximum total dose: 3 mg.

Bradycardia: Note: Atropine may be ineffective in heart transplant patients due to lack of vagal innervation.

IV, IM: 0.5 mg every 3 to 5 minutes; maximum total dose: 3 mg

Endotracheal: 1 to 2 mg every 3 to 5 minutes

Muscarine-containing mushroom poisoning (off-label dose): IV: 1 to 2 mg; titrate and repeat as needed (Goldfrank 2015).

Neuromuscular blockade reversal: IV: 15 to 30 mcg/kg administered with neostigmine or 7 to 10 mcg/kg administered with edrophonium (Cronnelly 1982; Miller 2010; Mirakhur 1981; Naguib 1989)

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 a component of the management of organophosphate insecticide and nerve agent toxicity; refer to Pralidoxime monograph for the specific route and dose.

IV, IM, endotracheal: Initial: 1 to 6 mg; repeat every 3 to 5 minutes as needed, doubling the dose if previous dose did not induce a response. Administer repeat doses as needed for ≥2 to 12 hours based on recurrence of symptoms (Reigart 1999).

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)

IV Infusion: Administer 10% to 20% of the total loading dose required to induce the desired response as a continuous IV infusion per hour; adjust as needed to maintain adequate response without atropine toxicity

Rapid sequence intubation (premedication) (off-label use): IV: 0.01 to 0.02 mg/kg (minimum dose: 0.1 mg; maximum single dose: 0.5 mg) (AHA [Hazinski 2015])

Stress echocardiography (adjunct chronotropic agent) (off-label use): IV: 0.25 to 0.5 mg up to a total dose of 1 to 2 mg until 85% of target heart rate is achieved (ASNC [Henzlova 2009])

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling.

Dosing: Pediatric

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]); 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]).

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 (Goldfrank 2015)

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. 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:

Infants and Children: Initial: 0.05 to 0.1 mg/kg; repeat every 5 to 10 minutes as needed, doubling the dose if previous dose does not induce atropinization (AAP [Roberts 2012]; Hegenbarth 2008; 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/dose; 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. 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).

Dosing: Renal Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Use: Labeled Indications

Antidote: Antidote for anticholinesterase poisoning (carbamate insecticides, nerve agents, organophosphate insecticides); antidote for muscarine-containing mushroom poisoning.

Adjuvant use with anticholinesterases (eg, edrophonium, neostigmine) to decrease their adverse effects during reversal of neuromuscular blockade.

Cardiovascular conditions: Treatment of symptomatic sinus bradycardia, atrioventricular (AV) nodal block.

Note: Likely not effective for type II second-degree or third-degree AV block (AHA [Hazinski 2015]). Use is no longer recommended in the management of asystole or pulseless electrical activity (PEA) (ACLS 2010).

Respiratory tract: Preoperative/preanesthetic medication to inhibit salivation and secretions.

Use: Off-Label: Adult

Rapid sequence intubation (premedication)Level of Evidence [C, G]

Clinical experience suggests the utility of atropine in adults who are at risk of developing bradycardia during rapid sequence intubation, such as those receiving conduction-altering drugs (eg, beta-blockers).

Based on the American Heart Association 2015 Handbook of Emergency Cardiovascular Care for Healthcare Providers, the use of atropine is effective and recommended as a premedication to prevent bradycardia in adults undergoing rapid sequence intubation Ref.

Stress echocardiography (adjunct chronotropic agent)Level of Evidence [A, G]

Data from a number of clinical studies evaluating the use of atropine to increase heart rate as an adjunctive agent during dobutamine stress echocardiography supports the use of atropine when at least 85% of the age-predicted maximal target heart rate is not achieved with dobutamine alone Ref.

Based on the American Society of Nuclear Cardiology, atropine may be administered as an adjunctive agent to increase heart rate in patients who do not achieve target heart rate with dobutamine alone.

Level of Evidence Definitions

Level of Evidence Scale

Use: Unsupported: Adult

Closed head injuries

Although included as a Food and Drug Administration (FDA)-approved use in the manufacturer's prescribing information to treat closed head injuries that cause acetylcholine to be released or to be present in cerebrospinal fluid, there is insufficient evidence to recommend the use of atropine for this indication.

Crying and laughing episodes in patients with brain lesions

Although included as an FDA-approved use in the manufacturer's prescribing information to control crying and laughing episodes in patients with brain lesions, there is insufficient evidence to recommend the use of atropine for this indication.

GI conditions

Although included as FDA-approved uses in the manufacturer's prescribing information to relieve pylorospasm, hypertonicity of small intestine, and hypermotility of colon, to relax upper GI tract and colon during hypertonic radiography, to relax the spasm of biliary and ureteral colic and bronchial spasm, and for the management of peptic ulcer, there is insufficient evidence to recommend the use of atropine for these indications.

GU conditions

Although included as FDA-approved uses in the manufacturer's prescribing information to diminish the tone of the detrusor muscle of the urinary bladder in the treatment of urinary tract disorders and to relieve hypertonicity of the uterine muscle, there is insufficient evidence to recommend the use of atropine for these indications.

Rhinorrhea of acute rhinitis or hay fever

Although included as an FDA-approved use in the manufacturer's prescribing information to control rhinorrhea of acute rhinitis or hay fever, there is insufficient evidence to recommend the use of injectable atropine for this indication.

Parkinsonism

Although included as an FDA-approved use in the manufacturer's prescribing information to treat parkinsonism, there is insufficient evidence to recommend the use of atropine for this indication.

Class and Related Monographs

Gastrointestinal Anticholinergics/Antispasmodics

Clinical Practice Guidelines

Advanced Cardiac Life Support (ACLS)/Emergency Cardiovascular Care (ECC):

AHA, “2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care,” October 2015.

AHA, "2010 Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care,” November 2010.

AHA, “Cardiac Arrest in Pregnancy,” October 2015

Bradycardia:

ACC/AHA/HRS, “Guideline on the evaluation and management of patients with bradycardia and cardiac conduction delay,” November 2018

Erectile dysfunction:

AUA, “Erectile Dysfunction,” 2018

Administration: 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.

Administration: 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.

Administration: Injectable Detail

pH: 3 to 6.5; AtroPen: pH: 4 to 5

Administration: Subcutaneous

May administer subcutaneous if needed.

Administration: 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.

Administration: Intraosseous

May administer intraosseous if needed.

Administration: Pediatric

Endotracheal: Administer and flush with 1 to 5 mL NS or SWFI based on patient size, followed by 5 manual ventilations. 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.

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.

Storage/Stability

Store injection at room temperature; avoid freezing. After initial use of multiple-dose vial, discard within 24 hours. In addition, AtroPen should be protected from light. Preparation of bulk atropine solution for mass chemical terrorism at a concentration of 1 mg/mL is stable for 72 hours at 4°C to 8°C (39°F to 46°F); 20°C to 25°C (68°F to 77°F); 32°C to 36°C (90°F to 97°F) (Dix 2003).

Preparation for Administration: Adult

Parenteral: Mass chemical terrorism: Preparation of bulk atropine solution: Add atropine sulfate powder to 100 mL of NS in polyvinyl chloride bags to yield a final concentration of 1 mg/mL (Dix 2003).

Preparation for Administration: Pediatric

Parenteral: Mass chemical terrorism: Preparation of bulk atropine solution: Add atropine sulfate powder to 100 mL NS in polyvinyl chloride bags to yield a final concentration of 1 mg/mL (Dix 2003).

Compatibility

See Trissel’s IV Compatibility Database

Open Trissel's IV Compatibility

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to treat some poisonings.

• In surgery, it is used to lower secretions such as saliva.

• It is used to treat muscle spasms of the GI (gastrointestinal) tract, gallbladder system, or urinary system.

• It is used when the heart is not beating.

Frequently reported side effects of this drug

• Blurred vision

• Sensitivity to light

• Constipation

• Dry mouth

• Nasal dryness

• Flushing

• Headache

• Enlarged pupils

• Injection site pain

• Nausea

• Vomiting

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Unable to pass urine

• Change in amount of urine passed

• Fast heartbeat

• Abnormal heartbeat

• Severe dizziness

• Passing out

• Difficulty breathing

• Slow breathing

• Shallow breathing

• Confusion

• Change in balance

• Sensing things that seem real but are not

• Severe loss of strength and energy

• Agitation

• Tremors

• Abdominal edema

• Sexual dysfunction

• Decreased sex drive

• Vision changes

• Eye pain

• Severe eye irritation

• Lack of sweating

• Depression

• Signs of a significant reaction like 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. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Medication Safety Issues

Geriatric Patients: High-Risk Medication:

Prescribing and Access Restrictions

The AtroPen formulation is available for use primarily by the Department of Defense.

Contraindications

There are no contraindications listed in the manufacturer’s labeling.

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylaxis: May occur.

• Hyperthermia: In the presence of a high environmental temperature, heat prostration can occur.

• 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).

• Autonomic neuropathy: Use with caution in patients with autonomic neuropathy.

• 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.

• Gastrointestinal disease: Use may convert partial organic pyloric stenosis into complete obstruction. Avoid use in patients with paralytic ileus, intestinal atony of the elderly or debilitated patient, severe ulcerative colitis, and toxic megacolon complicating ulcerative colitis.

• Glaucoma: Use 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.

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

• Respiratory impairment: Use may cause thickening of bronchial secretions and formation of viscid plugs in patients with chronic lung disease.

• Urinary retention: Use may lead to complete urinary retention in patients with prostatic hypertrophy. Avoid use if possible in patients with obstructive uropathy or in other conditions resulting in urinary retention

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

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.

Geriatric Considerations

Anticholinergic agents are generally not well tolerated in the elderly and their use should be avoided when possible.

Warnings: Additional Pediatric Considerations

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).

Pregnancy Considerations

Atropine has been found to cross the human placenta (Kanto 1981). 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).

Breast-Feeding Considerations

Trace amounts of atropine are present in breast milk. Atropine may suppress lactation or cause adverse events in the breastfeeding infant (data is conflicting). The manufacturer recommends that caution be exercised when administering atropine to breastfeeding women.

Briggs' Drugs in Pregnancy & Lactation

• Atropine

Adverse Reactions

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, keratoconjunctivitis sicca, 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)

Allergy and Idiosyncratic Reactions

• Belladonna Alkaloid Allergy

Metabolism/Transport Effects

None known.

Drug Interactions Open Interactions

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. Exceptions: Cannabidiol. 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

Monitoring Parameters

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.

Advanced Practitioners Physical Assessment/Monitoring

Monitor heart rate, blood pressure, pulse, and mental status. Use cardiac monitor in patients receiving intravenous. Assess for tachycardia and hypotension.

Nursing Physical Assessment/Monitoring

Monitor heart rate, blood pressure, pulse, and mental status. Use cardiac monitor in patients receiving intravenous. Monitor for tachycardia and hypotension.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Injection, as sulfate:

Generic: 1 mg/mL (1 mL [DSC]); 8 mg/20 mL (20 mL)

Solution, Injection, as sulfate [preservative free]:

Generic: 0.4 mg/0.5 mL (0.5 mL [DSC]); 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)

Dosage Forms: Canada

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)

Anatomic Therapeutic Chemical (ATC) Classification

• A03BA01

Generic Available (US)

May be product dependent

Pricing: US

Solution (Atropine Sulfate Injection)

0.4 mg/mL (per mL): $9.23

1 mg/mL (per mL): $14.50

8 mg/20 mL (per mL): $2.11 - $4.20

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): $3.33

0.5 mg/5 mL (per mL): $2.18

1 mg/10 mL (per mL): $0.66 - $1.21

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.

Mechanism of Action

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.

Pharmacodynamics/Kinetics

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)

Dental Use

Reduction of salivation and bronchial secretions

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Xerostomia and changes in salivation (normal salivary flow resumes upon discontinuation), dry throat, and nasal dryness

Effects on Bleeding

No information available to require special precautions

Dental Usual Dosing

Inhibit salivation and secretions (preanesthesia): Adults (doses <0.5 mg have been associated with paradoxical bradycardia):

IM, IV, SubQ: 0.4-0.6 mg 30-60 minutes preop and repeat every 4-6 hours as needed

Related Information

• Adult ACLS Algorithms
• Beers Criteria 2019: Potentially Inappropriate Medication Use in Older Adults ≥65 Years of Age
• Pediatric ALS (PALS) Algorithms
• Pralidoxime

Index Terms

Atropine Sulfate

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Brand Names: International

Anespin (PH); Atren (IN); Atro (IN); Atropa (LK); Atropan (PH); Atropin (SE); Atropin Biotika (CZ); Atropion (BR); Atrosol (PK); Bellafit (FR); Bellafit N (CH); Cholspas Atropin (DE); Ciratro (LK); Dysurgal (DE); Endotropina (AR, UY); Estropin (BD); Santropina (BR); Stellatropine (BE); Tropin (PH); Tropyn (MX)

Last Updated 4/21/20