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Atropine

Pronunciation

Class: Antimuscarinics/Antispasmodics
VA Class: AU350
CAS Number: 51-55-8
Brands: AtroPen

Warning(s)

  • Pesticide and Chemical Warfare Agent Poisoning
  • Primary protection against exposure to chemical nerve agents and insecticide poisoning is the wearing of protective garments (e.g., specialized masks).105

  • Do not rely solely on antidotes such as atropine and pralidoxime to provide complete protection from chemical nerve agents and insecticide poisoning.105

  • Seek immediate medical attention after injection with an atropine auto-injector.105

Introduction

Antimuscarinic; a naturally occurring tertiary amine.

Uses for Atropine

Surgery

Used as a preoperative medication to inhibit salivation and excessive secretions of the respiratory tract (antisialagogue).196 198 200 However, current surgical practice (e.g., using general anesthetics that do not stimulate salivary and tracheobronchial secretions) has reduced the need to control excessive respiratory secretions during surgery.b

Used to prevent other cholinergic effects during surgery (e.g., cardiac arrhythmias, hypotension, bradycardia) secondary to excessive vagal stimulation, carotid sinus stimulation, or pharmacologic effect of drugs (e.g., succinylcholine).196 200 402

Used to block adverse muscarinic effects of anticholinesterase agents (e.g., neostigmine, pyridostigmine) that are used after surgery to reverse the effects of neuromuscular blocking agents.120 121 196

Used as a premedication for bradycardia during emergency pediatric intubation.402 Not routinely recommended because of lack of supporting evidence, but may be considered in situations where there is an increased risk of bradycardia (e.g., when succinylcholine is used to facilitate intubation).402

Ineffective for preventing acid-aspiration pneumonitis during surgery.b

ACLS and Bradyarrhythmias

Used in ACLS for management of symptomatic bradycardia.400 401 403 Reverses cholinergically mediated decreases in heart rate, systemic vascular resistance, and BP.106 401

Considered initial drug of choice in adults with unstable bradycardia (e.g., that accompanied by altered mental status, cardiac ischemia, acute heart failure, hypotension, or other signs of shock).400 401

In pediatric advanced life support (PALS), used for treatment of bradycardia secondary to increased vagal activity or primary AV block when bradycardia persists despite adequate oxygenation, ventilation, and CPR (if indicated).403

Previously included in ACLS guidelines for treatment of asystole or pulseless electrical activity (PEA) during CPR;106 however, routine use during cardiac arrest no longer recommended because of lack of evidence demonstrating benefit.400 401 402 403

May be beneficial for treatment of AV nodal block.401 403 However, not likely to be effective in patients with type II second-degree or third-degree AV block, including third-degree AV block accompanied by a new wide QRS complex where location of block is at or below the His-Purkinje level; transcutaneous pacing or rate-accelerating β-adrenergic drugs (e.g., dopamine or epinephrine) preferred in these patients until transvenous pacing can be performed.401

Used in patients with MI who develop symptomatic or hemodynamically unstable sinus bradycardia.201 202 Other uses in MI setting include treatment of sustained bradycardia and hypotension associated with nitroglycerin use, and treatment of nausea and vomiting associated with morphine use.202

Use cautiously in the presence of acute myocardial ischemia or MI because heart rate is a major determinant of myocardial oxygen requirements.b

May be ineffective in patients who have undergone cardiac transplantation due to lack of vagal innervation in transplanted heart.401 Risk of paradoxical slowing of the heart rate and high-degree AV block in patients receiving atropine after cardiac transplantation.401

Pesticide Poisoning

Used concomitantly with a cholinesterase reactivator (pralidoxime chloride) to reverse muscarinic effects associated with toxic exposure to organophosphate anticholinesterase pesticides.103 105 200

Used to reverse muscarinic effects associated with toxic exposure to carbamate anticholinesterase pesticides.105 197 Concomitant cholinesterase reactivator (pralidoxime chloride) therapy may not be necessary.197

A challenge (test) dose of atropine may be useful in diagnosing cholinergic poisoning.197 Failure of the challenge dose to elicit typical antimuscarinic effects (e.g., mydriasis, tachycardia, dry mucous membranes) strongly suggests the presence of organophosphate or carbamate poisoning.197

Use atropine in conjunction with other protective measures (e.g., decontamination, immediate evacuation, specialized masks and clothing) and treatments (e.g., anticonvulsant for seizures).105

Chemical Warfare Agent Poisoning

Used concomitantly with a cholinesterase reactivator (pralidoxime chloride) to reverse muscarinic effects associated with toxic exposure to organophosphate anticholinesterase nerve agents (e.g., sarin, soman, tabun, VX [methylphosphonothioic acid]) in the context of chemical warfare or terrorism.101 102 103 104 105

Initial management of nerve agent poisoning includes aggressive airway control and ventilation (administration of nebulized β-adrenergic agonist [e.g., albuterol] and antimuscarinics [e.g., ipratropium bromide] may be necessary), and administration of atropine and pralidoxime chloride;101 102 103 diazepam may be needed for seizure control.101

Mushroom Poisoning

Treatment of muscarinic effects associated with toxic ingestion of mushrooms containing muscarine (e.g., certain members of the Clitocybe and Inocybe genera).197 200 However, substantial toxicity is uncommon, and supportive symptomatic care (e.g., atropine) rarely is necessary.197

Radiographic Uses

Has been used to facilitate hypotonic duodenography or contrast examination of the colon; however, glucagon appears to be more effective and generally is preferred in these examinations.b

Has been used to increase visualization of the urinary tract in excretion urography.b

Bronchospasm

Has been used by oral inhalation as a bronchodilator for short-term treatment of bronchospasm associated with bronchial asthma, bronchitis, and COPD; however, a solution for oral inhalation no longer commercially available in the US.b

GI Disorders

Has been used as an adjunct in the treatment of peptic ulcer disease;b c however, no conclusive data that the drug promotes healing, decreases rate of recurrence, or prevents complications of peptic ulcers.b

With the advent of more effective therapies for the treatment of peptic ulcer disease, antimuscarinics have only limited usefulness in this condition.b

Has been used in the treatment of functional disturbances of GI motility such as irritable bowel syndrome;b however, efficacy is limited.b Use only if other measures (e.g., diet, sedation, counseling, amelioration of environmental factors) have been of little or no benefit.b

GU Disorders

Has been used as adjunctive therapy in the management of hypermotility disorders of the lower urinary tract.b May provide symptomatic relief, but the underlying cause should be determined and specifically treated.b

With the exception of uninhibited or reflex neurogenic bladder, there is generally little evidence to support the use of antimuscarinics in the treatment of various GU disorders.c

Biliary Disorders

Has been used in conjunction with morphine or other opiates for symptomatic relief of biliary or renal colic; however, only exerts weak biliary antispasmodic action.b

Pancreatitis

Has been used to reduce pain and hypersecretions in acute pancreatitis, but little evidence of benefit.b

Atropine Dosage and Administration

Administration

Administer by sub-Q, IM, or direct IV injection.105 198 200 IV administration preferred for treatment of severe or life-threatening muscarinic effects.200

Also has been administered by intraosseous (IO) injection† in the ACLS setting, generally when IV access not readily available; onset of action and systemic concentrations are comparable to those achieved with venous administration.401 403 May be administered endotracheally; however, vascular (IV or IO) administration preferred because of more predictable drug delivery and pharmacologic effect.200 403

Has been administered orally;199 however, oral dosage form no longer commercially available in US.

Has been administered via oral inhalation for bronchodilation; however, solution for inhalation no longer commercially available in US.b

IV Administration

Administer by direct IV injection.198 200 b

Occasionally has been administered by IV infusion for management of muscarinic poisoning (e.g., organophosphate pesticides).197

For solution and drug compatibility information, see Compatibility under Stability.

Rate of Administration

Preferably give IV injections rapidly because slow injection may cause a paradoxical slowing of the heart rate.b

IM Administration

Commercially available in a prefilled auto-injector (e.g., AtroPen) for treatment of pesticide or nerve agent poisoning.105

The AtroPen auto-injector may be self-administered by the patient or caregiver in an out-of-hospital setting to facilitate the initial treatment of muscarinic poisoning (usually breathing difficulty secondary to increased secretions); however, definitive medical care should be sought immediately.105

For self-medication, instruct patients and caregivers carefully in proper administration techniques using auto-injector.197 105

Inject weight-appropriate IM dose into anterolateral aspect of the thigh.105

In very thin patients and small children, bunch up the thigh prior to injection to provide a thicker injection area.105

AtroPen 0.5, 1, or 2 mg: Grasp prefilled auto-injector with green tip pointed downward; the yellow activation (safety) cap should be removed.105 Point green tip toward outer thigh and jab it firmly into outer thigh so that the auto-injector is perpendicular (90° angle) to the thigh, and hold firmly for at least 10 seconds until dose is delivered.105

AtroPen 0.25 mg: Grasp prefilled auto-injector with black tip pointed downward; the grey activation (safety) cap should be removed.105 Point black tip toward outer thigh and jab it firmly into outer thigh so that the auto-injector is perpendicular (90° angle) to the thigh, and hold firmly for at least 10 seconds until dose is delivered.105

Administer through clothing if necessary.105

Massage injection area for several seconds.105

Consult manufacturer's prescribing information for additional instructions on use of the auto-injectors.105

Endotracheal Administration

When IV or IO access cannot be established, may administer by the endotracheal route.200 403

For endotracheal administration in adults, dilute dose in 5–10 mL of 0.9% sodium chloride injection or sterile water.200 401

In pediatric patients, flush with 5 mL of 0.9% sodium chloride injection after dose is administered.403

Dosage

Individualize dosage based on indication, patient characteristics, and response (e.g., heart rate, BP); pediatric patients are more susceptible than adults to toxic effects of atropine overdosage.198 200

Pediatric Patients

Surgery
Preoperatively for Antisialagogue or Antivagal Effects
IV, IM, or Sub-Q

Dosing in pediatric patients not well studied.200

Usual initial dose is 0.01–0.03 mg/kg, administered 30–60 minutes prior to surgery.195 198 200 May repeat every 4–6 hours.195

Premedication for Bradycardia in Emergency Intubation
IV

Infants and children: AHA recommends a preintubation dose of 0.02 mg/kg (with no minimum).402 Although minimum dose of 0.1 mg was previously recommended because of concerns about paradoxical bradycardia, current evidence suggests that minimum dose not necessary.402

Muscarinic Blockade during Anticholinesterase Reversal of Neuromuscular Blocking Agents

Administer concurrently with (but in a separate syringe) or a few minutes before the anticholinesterase agent.b

If bradycardia is present, administer before the anticholinesterase agent to increase pulse to about 80 bpm.b

IV

Neonates and infants: 0.02-mg/kg dose of atropine sulfate has been given concomitantly with each 0.04-mg/kg dose of neostigmine methylsulfate.b

Children: 0.01- to 0.04-mg/kg dose of atropine sulfate has been given concomitantly with each 0.025- to 0.08-mg/kg dose of neostigmine methylsulfate.194

PALS and Bradyarrhythmias
IV or IO

Infants and children with symptomatic bradycardia secondary to increased vagal activity or primary AV block: 0.02 mg/kg; repeat once if needed.403

PALS guideline recommends minimum dose of 0.1 mg and maximum single dose of 0.5 mg.403

Larger doses may be required in special resuscitation situations (e.g., organophosphate toxicity or exposure to nerve gas agents) and smaller doses (i.e., <0.1 mg) may cause paradoxical bradycardia.195 403

Endotracheal

Infants and children: 0.04–0.06 mg/kg; repeat once if needed.403

PALS guideline recommends minimum dose of 0.1 mg and maximum single dose of 0.5 mg.403

Larger doses may be required in special resuscitation situations (e.g., organophosphate toxicity or exposure to nerve gas agents).195 403

If CPR is in progress, stop chest compressions briefly to administer atropine; follow with a flush of at least 5 mL of 0.9% sodium chloride injection and 5 consecutive positive-pressure ventilations.403

Pesticide Poisoning

Various doses and dosing intervals have been recommended; dosage requirements are based on severity of poisoning and individual patient response.105 195 198 200

Organophosphate Anticholinesterase Pesticides

Preferably should be administered IV, especially the initial dose.b

A cholinesterase reactivator (pralidoxime) is administered concomitantly.197 b

Some degree of atropinism should be maintained for at least 48 hours; prolonged therapy (e.g., for several weeks) may be necessary in severe cases.197

IV or IM

Children: 0.05–0.1 mg/kg every 5–10 minutes until muscarinic signs and symptoms disappear.195

Alternatively, infuse IV at a rate of 0.025 mg/kg per hour; continuous infusions have been maintained for up to several weeks in severe cases.197

IM Self-administration

For self-administration using a prefilled auto-injector (e.g., AtroPen), dose is based on body weight and symptom severity.105

Mild symptoms include miosis, blurred vision, tearing, runny nose, hypersalivation, drooling, wheezing, muscle fasciculations, nausea/vomiting.105

Severe symptoms include behavioral changes, severe breathing difficulty, severe respiratory secretions, severe muscle twitching, involuntary defecation or urination, seizures, unconsciousness.105

Children <7 kg: Inject 0.25 mg IM initially for mild symptoms.105 If severe symptoms develop, inject 2 additional 0.25-mg IM doses in rapid succession 10 minutes after the initial dose.105

Children <7 kg who present with severe symptoms or are unconscious: Inject three 0.25-mg IM doses in rapid succession.105

Children <7 kg: Additional doses (i.e., >3) should only be administered under the supervision of trained medical personnel.105

Children 7–18 kg: Inject 0.5 mg IM initially for mild symptoms.105 If severe symptoms develop, inject 2 additional 0.5-mg IM doses in rapid succession 10 minutes after the initial dose.105

Children 7–18 kg who present with severe symptoms or are unconscious: Inject three 0.5-mg IM doses in rapid succession.105

Children 7–18 kg: Additional doses (i.e., >3) should only be administered under the supervision of trained medical personnel.105

Children 18–41 kg: Inject 1 mg IM initially for mild symptoms.105 If severe symptoms develop, inject 2 additional 1-mg IM doses in rapid succession 10 minutes after the initial dose.105

Children 18–41 kg who present with severe symptoms or are unconscious: Inject three 1-mg IM doses in rapid succession.105

Children 18–41 kg: Additional doses (i.e., >3) should only be administered under the supervision of trained medical personnel.105

Children >41 kg: Inject 2 mg IM initially for mild symptoms.105 If severe symptoms develop, inject 2 additional 2-mg IM doses in rapid succession 10 minutes after the initial dose.105

Children >41 kg who present with severe symptoms or are unconscious: Inject three 2-mg IM doses in rapid succession.105

Children >41 kg: Additional doses (i.e., >3) should only be administered under the supervision of trained medical personnel.105

Endotracheal

Children: 0.05–0.1 mg/kg every 5–10 minutes until muscarinic signs and symptoms disappear.195

Dilute in 1–2 mL of 0.9% sodium chloride injection for endotracheal administration.195

Carbamate Anticholinesterase Pesticides

Carbamate poisoning is treated with the same doses of atropine sulfate as for organophosphate poisoning and IM self-administration can be employed when necessary.105 197 (See Organophosphate Anticholinesterase Pesticides under Dosage.)

Concomitant cholinesterase reactivator (pralidoxime chloride) therapy may not be necessary and atropine therapy generally is less prolonged (e.g., only 1 or 2 days) and symptoms usually do not recur once asymptomatic.197

Chemical Warfare Agent Poisoning

Various doses and dosing intervals have been recommended; dosage requirements are based on severity of poisoning and individual patient response.101 105 195 198 200

Organophosphate Anticholinesterase Nerve Agents

Administer IM in out-of-hospital setting or emergency department.101 105 b

A cholinesterase reactivator (pralidoxime chloride) is administered concomitantly.b 197

Give diazepam for seizure control.101

Total atropine sulfate doses usually are much less than those required for organophosphate anticholinesterase pesticide poisoning.197

IM

Minimum dose in children is 0.1 mg.197

Children 0–2 years of age with mild to moderate symptoms: Usual initial IM dose is 0.05 mg/kg.101

Children 0–2 years of age with severe symptoms: Usual initial IM dose is 0.1 mg/kg.101

Children 2–10 years of age with mild to moderate symptoms: Usual initial IM dose is 1 mg.101

Children 2–10 years of age with severe symptoms: Usual initial IM dose is 2 mg.101

Children older than 10 years of age with mild to moderate symptoms: Usual initial IM dose is 2 mg.101

Children older than 10 years of age with severe symptoms: Usual initial IM dose is 4 mg.101

Repeat doses every 2–10 minutes as needed until muscarinic toxicity resolves (e.g., secretions have diminished and breathing is comfortable or airway resistance has returned to near normal).101 197

IM Self-administration

For self-administration using a prefilled auto-injector (e.g., AtroPen), dose is based on body weight and symptom severity.105

Mild symptoms include miosis, blurred vision, tearing, runny nose, hypersalivation, drooling, wheezing, muscle fasciculations, nausea/vomiting.105

Severe symptoms include behavioral changes, severe breathing difficulty, severe respiratory secretions, severe muscle twitching, involuntary defecation or urination, seizures, unconsciousness.105

Children <7 kg: Inject 0.25 mg IM initially for mild symptoms.105 If severe symptoms develop, inject 2 additional 0.25-mg IM doses in rapid succession 10 minutes after the initial dose.105

Children <7 kg who present with severe symptoms or are unconscious: Inject three 0.25-mg IM doses in rapid succession.105

Children <7 kg: Additional doses (i.e., >3) should only be administered under the supervision of trained medical personnel.105

Children 7–18 kg: Inject 0.5 mg IM initially for mild symptoms.105 If severe symptoms develop, inject 2 additional 0.5-mg IM doses in rapid succession 10 minutes after the initial dose.105

Children 7–18 kg who present with severe symptoms or are unconscious: Inject three 0.5-mg IM doses in rapid succession.105

Children 7–18 kg: Additional doses (i.e., >3) should only be administered under the supervision of trained medical personnel.105

Children 18–41 kg: Inject 1 mg IM initially for mild symptoms.105 If severe symptoms develop, inject 2 additional 1-mg IM doses in rapid succession 10 minutes after the initial dose.105

Children 18–41 kg who present with severe symptoms or are unconscious: Inject three 1-mg IM doses in rapid succession.105

Children 18–41 kg: Additional doses (i.e., >3) may be given every 5–10 minutes197 but only under the supervision of trained medical personnel.105

Children >41 kg: Inject 2 mg IM initially for mild symptoms.105 If severe symptoms develop, inject 2 additional 2-mg IM doses in rapid succession 10 minutes after the initial dose.105

Children >41 kg who present with severe symptoms or are unconscious: Inject three 2-mg IM doses in rapid succession.105

Children >41 kg: Additional doses (i.e., >3) may be given every 5–10 minutes197 but only under the supervision of trained medical personnel.105

IV

Children 0–2 years of age with mild, moderate, or severe symptoms: May receive 0.02 mg/kg IV, if treated in an emergency department.101

Mushroom Poisoning
Muscarine-containing Clitocybes and Inocybes
IV

If needed for severe symptoms, 0.02 mg/kg IV (minimum of 0.1 mg), repeated and titrated as needed according to response.197

Adults

Surgery
Preoperatively for Antisialagogue or Antivagal Effects
IV, IM, or Sub-Q

0.5–1 mg administered 30–60 minutes prior to surgery.195 200 May repeat in 1–2 hours.200

Muscarinic Blockade during Anticholinesterase Reversal of Neuromuscular Blocking Agents
IV

0.6–1.2 mg for each 0.5–2.5 mg of neostigmine methylsulfate or 10–20 mg of pyridostigmine bromide given.b

Administer concurrently with (but in a separate syringe) or a few minutes before the anticholinesterase agent.b

If bradycardia is present, administer before the anticholinesterase agent to increase pulse to 80 bpm.b

ACLS and Bradyarrhythmias
Bradycardia
IV

For symptomatic bradycardia, AHA recommends initial dose of 0.5 mg; may repeat every 3–5 minutes up to 3 mg.401 Doses <0.5 mg may cause paradoxical slowing of heart rate.401

Asystole or PEA
IV or IO

In previous ACLS guidelines, 1 mg every 3–5 minutes up to 3 doses recommended.106

Endotracheal

Optimum dose not established; typical doses 2–2.5 times usual IV doses.401

One manufacturer recommends a dose of 1–2 mg (diluted in no more than 10 mL with sterile water or 0.9% sodium chloride injection).200

Pesticide Poisoning

Various doses and dosing intervals have been recommended; dosage requirements are based on severity of poisoning and individual patient response.105 195 198 200

Organophosphate Anticholinesterase Pesticides

Preferably should be administered IV, especially the initial dose.b

A cholinesterase reactivator (pralidoxime chloride) is administered concomitantly.b 197

Some degree of atropinism should be maintained for at least 48 hours; prolonged therapy (e.g., for several weeks) may be necessary in severe cases.197

IV or IM

Usual initial dose 1–2 mg IV (preferable) or IM; some clinicians recommend that additional 2-mg doses may be administered every 5–60 minutes until muscarinic symptoms disappear.b For severe cases, 2–6 mg may be given initially, repeating doses every 5–60 minutes.195 200 b

Alternatively, infuse IV at an initial rate of 0.5–1 mg/hour, adjusting rate according to response.197

Mildly symptomatic poisoning may respond to 1–2 mg for reversal of muscarinic toxicity whereas moderate poisoning commonly requires total doses up to 40 mg.197

For severe poisoning, 5-mg doses may be repeated every 2–3 minutes for stabilization.197

Cumulative doses up to 1 g in 24 hours or 11 g over a course of treatment have been used.197

IM Self-administration

For self-administration using a prefilled auto-injector (e.g., AtroPen), dose is based on body weight and symptom severity.105

Mild symptoms include miosis, blurred vision, tearing, runny nose, hypersalivation, drooling, wheezing, muscle fasciculations, nausea/vomiting.105

Severe symptoms include behavioral changes, severe breathing difficulty, severe respiratory secretions, severe muscle twitching, involuntary defecation or urination, seizures, unconsciousness.105

Adults >41 kg: Inject 2 mg IM initially for mild symptoms.105 If severe symptoms develop, inject 2 additional 2-mg IM doses in rapid succession 10 minutes after the initial dose.105

Adults >41 kg who present with severe symptoms or are unconscious: Inject three 2-mg IM doses in rapid succession.105

Additional doses (i.e., >3) should only be administered under the supervision of trained medical personnel.105

Adults <41 kg: Pediatric doses can be used.105 (See Pediatric Patients: Pesticide Poisoning, under Dosage.)

Carbamate Anticholinesterase Pesticides

Carbamate poisoning is treated with the same doses of atropine sulfate as for organophosphate poisoning and IM self-administration can be employed when necessary.105 197 (See Organophosphate Anticholinesterase Pesticides under Dosage.)

Concomitant cholinesterase reactivator (pralidoxime chloride) therapy may not be necessary and atropine therapy generally is less prolonged (e.g., only 1 or 2 days) and symptoms usually do not recur once asymptomatic.197

Chemical Warfare Agent Poisoning

Various doses and dosing intervals have been recommended; dosage requirements are based on severity of poisoning and individual patient response.105 195 198 200

Organophosphate Anticholinesterase Nerve Agents

Administered IM in out-of-hospital setting or emergency department.101 105 b

A cholinesterase reactivator (pralidoxime chloride) is administered concomitantly.197 b

Give diazepam for seizure control.101

Total atropine sulfate doses usually are much less than those required for organophosphate anticholinesterase pesticide poisoning.197

IM

Mild to moderate symptoms: Usual initial IM dose is 2–4 mg.101 197

Severe symptoms: 5–6 mg.101 197

Frail geriatric patients with mild to moderate symptoms: 1 mg.101

Frail geriatric patients with severe symptoms: 2–4 mg.101

Repeat doses every 2–10 minutes as needed until muscarinic toxicity resolves (e.g., secretions have diminished and breathing is comfortable or airway resistance has returned to near normal).101 197

Up to 15–20 mg may be required within the first 3 hours,104 but most patients respond to <20 mg usually during the initial 24 hours.197 In a report of sarin poisoning, <20% of moderately symptomatic patients required more than 2 mg.197 Pralidoxime chloride is administered concomitantly with atropine.101

IM Self-administration

For self-administration using a prefilled auto-injector (e.g., AtroPen), dose is based on body weight and symptom severity.105

Mild symptoms include miosis, blurred vision, tearing, runny nose, hypersalivation, drooling, wheezing, muscle fasciculations, nausea/vomiting.105

Severe symptoms include behavioral changes, severe breathing difficulty, severe respiratory secretions, severe muscle twitching, involuntary defecation or urination, seizures, unconsciousness.105

Adults >41 kg: Inject 2 mg IM initially for mild symptoms.105 If severe symptoms develop, inject 2 additional 2-mg IM doses in rapid succession 10 minutes after the initial dose.105

Adults >41 kg who present with severe symptoms or are unconscious: Inject three 2-mg IM doses in rapid succession.105

Additional doses (i.e., >3) may be given every 5–10 minutes197 but only under the supervision of trained medical personnel.105

Adults <41 kg: Pediatric doses can be used.105 (See Pediatric Patients: Pesticide Poisoning, under Dosage.)

Mushroom Poisoning
Muscarine-containing Clitocybes and Inocybes
IV

If needed for severe symptoms, 1–2 mg IV (minimum of 0.1 mg), repeated and titrated as needed according to response.197

Radiographic Uses
Hypotonic Radiograph of the GI Tract
IM

Usual dose is 1 mg.b

Prescribing Limits

Pediatric Patients

PALS and Bradyarrhythmias
Bradycardia
IV, IO, or Endotracheal

Infants and children: AHA recommends maximum single dose of 0.5 mg.403

Adults

ACLS and Bradyarrhythmias
Asystole, PEA, and Bradycardia
IV

Maximum total dose of 3 mg recommended.106 401

Special Populations

Hepatic Impairment

No specific hepatic dosage recommendations.105 198 200

Renal Impairment

No specific renal dosage recommendations.105 198 200

Geriatric Patients

Similar response between geriatric and younger patients.200 In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.101 200

Cautions for Atropine

Contraindications

  • No absolute contraindications to use in life-threatening conditions (e.g., poisoning by organophosphate nerve agents and pesticides).105 200

  • Relative contraindications include:

    • known hypersensitivity to atropine or any ingredient in the formulation105 b

    • angle-closure glaucoma105 b c

    • obstructive uropathy (e.g., bladder neck obstruction secondary to prostatic hypertrophy)c

    • obstructive GI disease (e.g., pyloroduodenal stenosis, achalasia)c

    • paralytic ileusc

    • intestinal atony (especially in geriatric and debilitated patients)c

    • severe ulcerative colitisc

    • toxic megacolonc

    • tachycardia secondary to cardiac insufficiency or thyrotoxicosis

    • acute hemorrhage when cardiovascular status is unstablec

    • myasthenia gravis (unless used to reduce adverse muscarinic effects of an anticholinesterase agent such as neostigmine)c

Warnings/Precautions

Warnings

Overdosage

Avoid overdosage, especially with IV administration.198

Pediatric patients are particularly susceptible to overdosage.198

Pesticide and Chemical Warfare Agent Poisoning

Use in patients with a history of anaphylactic reaction to atropine and mildly symptomatic organophosphate pesticide or nerve agent poisoning only when there is adequate medical supervision.105

Severe breathing difficulty requires artificial respiration because atropine alone is not dependable in reversing respiratory muscle weakness or paralysis.105

Administer with extreme caution when the symptoms of nerve agent poisoning are less severe in patients with disorders of heart rhythm (e.g., atrial flutter), substantial renal insufficiency, or a recent MI.105

No more than 3 doses should be self-administered IM; additional doses require medical supervision.105

Sensitivity Reactions

Parabens present in multiple-dose preparations may cause hypersensitivity reactions.c

Hypersensitivity reactions may occasionally occur; usually skin rashes that may progress to exfoliation.105 200

Major Toxicities

Cardiovascular Effects

Caution in patients with cardiac disease.105 200 Because heart rate is a major determinant of myocardial oxygen requirements, excessive rate acceleration in patients with acute myocardial ischemia or infarction may worsen ischemia or increase extent of infarction.b

CNS Disturbances

Large or toxic doses or usual doses in patients with excess susceptibility may produce marked CNS disturbances (e.g., ranging from marked excitement, ataxia, hallucination, depression, and/or disorientation to active delirium to coma to death [secondary to respiratory failure]).105 200

Marked somnolence in susceptible patients.c

Mental confusion and/or excitement, especially in geriatric patients.c

GI Disturbances

Extreme caution in known or suspected GI infections because of decreased GI motility and retention of causative organism and/or toxins.c

Extreme caution in mild to moderate ulcerative colitis because of suppressed intestinal motility and resultant paralytic ileus and toxic megacolon.c

Extreme caution in diarrhea (especially in patients with ileostomy or colostomy) because it may be an early sign of intestinal obstruction.c

Caution in gastric ulcer because of delayed gastric emptying and possible antral stasis.c

Caution in esophageal reflux and hiatal hernia because of decreased gastric motility and lower esophageal sphincter pressure leading to gastric retention and reflux aggravation.c

GU Disturbances

Extreme caution in patients with partial obstructive uropathy because of decreased tone and amplitude of contractions of ureters and bladder and resultant urinary retention.c (See Contraindications under Cautions)

Respiratory Effects

Caution with systemically administered atropine in debilitated patients with chronic pulmonary disease because a reduction in bronchial secretions may lead to inspissation and formation of bronchial plugs; however, has been used effectively as bronchodilator when administered via oral inhalation.

Thermoregulatory Effects

Exposure to high environmental temperatures may result in heat prostration due to decreased sweating.c Increased risk of hyperthermia in patients who are febrile.c

General Precautions

Neuropathy

Extreme caution in patients with autonomic neuropathy.c

Down’s Syndrome, Spastic Paralysis, and Brain Damage

Increased sensitivity to antimuscarinic effects (e.g., mydriasis, positive chronotropic effect).c

Hypertension

Caution in hypertensive patients.c

Hyperthyroidism

Caution in hyperthyroid patients.c

Seizure Management in Anticholinesterase Poisoning

Use barbiturates cautiously to manage seizures because the drugs are potentiated by anticholinesterases.105 Diazepam is preferred for seizure control.101

Specific Populations

Pregnancy

Category C.105 c

Lactation

Atropine is found in human milk in trace amounts; use caution when administered to a nursing woman.105

Pediatric Use

Safety and efficacy in the setting of organophosphate pesticide poisoning established in children of all ages.105

Increased susceptibility to the effects of atropine.105 c More susceptible than adults to toxic effects; deaths at doses as low as 10 mg.c

Infants, patients with Down’s syndrome (mongolism), and children with spastic paralysis or brain damage may be hypersensitive to antimuscarinic effects (e.g., mydriasis, positive chronotropic effect).c

Geriatric Use

Increased susceptibility to the effects of atropine.105 c Mental confusion and/or excitement are especially likely in geriatric patients.c

Hepatic Impairment

Use with caution in hepatic disease.c

Renal Impairment

Use with caution in renal disease.c

Common Adverse Effects

Most adverse effects are manifestations of pharmacologic effects at muscarinic-cholinergic receptors and usually are reversible when therapy is discontinued.c

Severity and frequency of adverse effects are dose related and individual intolerance varies greatly; adverse effects occasionally may be obviated by a reduction in dosage but this also may eliminate potential therapeutic effects.c

Frequent effects include xerostomia (dry mouth), dry skin, blurred vision, cycloplegia, mydriasis, photophobia, anhidrosis, urinary hesitancy and retention, tachycardia, palpitation, xerophthalmia, and constipation,105 200 c which may appear at therapeutic or subtherapeutic doses.c In many patients, xerostomia is the dose-limiting effect.c

Other common effects include increased ocular tension (especially in patients with angle-closure glaucoma), loss of taste, headache, nervousness, restlessness, drowsiness, weakness, dizziness, flushing, insomnia, nausea, vomiting, bloated feeling, anhidrosis (especially in hot environments),105 200 mild to moderate pain at the injection site,105 c loss of libido, and erectile dysfunction (via block of cholinergically mediated vasodilation).105 c

Interactions for Atropine

Drugs with Anticholinergic Effects

Additive adverse effects resulting from cholinergic blockade (e.g., xerostomia, blurred vision, constipation).c Advise of possibility of increased anticholinergic effects and monitor carefully.c

Effects on GI Absorption of Drugs

By inhibiting the motility of the GI tract and prolonging GI transit time, antimuscarinics have the potential to alter GI absorption of various drugs.c

Specific Drugs

Drug

Interaction

Comments

Amantadine

Increased anticholinergic effectsc

Inform patient and monitor carefullyc

Antacids

Decreased GI absorption of atropinec

Administer oral atropine at least 1 hour before antacidsc

Anticholinergic drugs

Increased anticholinergic effectsc

Inform patient and monitor carefullyc

Antihistamines (anticholinergic)

Increased anticholinergic effectsc

Inform patient and monitor carefullyc

Antiparkinsonian (antimuscarinic) agents

Increased anticholinergic effectsc

Inform patient and monitor carefullyc

Corticosteroids

Increased IOPc

Caution; monitor IOPc

Digoxin (slow dissolving)

Increased serum digoxinc

Use digoxin oral solution (elixir) or rapidly dissolving tablets (e.g., Lanoxin)c

Disopyramide

Increased anticholinergic effectsc

Inform patient and monitor carefullyc

Ketoconazole

Increased gastric pH decreases ketoconazole absorptionc

Administer atropine at least 2 hours after ketoconazolec

Levodopa

Increased GI metabolism of levodopa & decreased systemic concentrationsc

Adjust levodopa dosage if atropine is started or discontinuedc

Meperidine

Increased anticholinergic effectsc

Inform patient and monitor carefullyc

Mexiletine

Decreased GI absorption rate of mexiletine; no effect on bioavailability200

Muscle (anticholinergic) relaxants

Increased anticholinergic effectsc

Inform patient and monitor carefullyc

Phenothiazines

Increased anticholinergic effectsc

Inform patient and monitor carefullyc

Potassium chloride

Slowed GI transit potentiates adverse GI effects of oral potassium chloride (especially wax-matrix tablets)c

Caution if used concomitantly; monitor for possible GI mucosal lesionsc

Procainamide

Increased anticholinergic effectsc

Inform patient and monitor carefullyc

Pralidoxime

Increased rate of atropinizationc

Tricyclic antidepressants

Increased anticholinergic effectsc

Inform patient and monitor carefullyc

Atropine Pharmacokinetics

Absorption

Bioavailability

Well absorbed (90%) from the GI tract, principally from upper small intestine.b

Rapidly and well absorbed after IM injection.b Physical exercise, either prior to or immediately following IM injection, increases absorption due to muscle perfusion and decreases clearance.200

Well absorbed following endotracheal administration.b Dilution with sterile water versus 0.9% sodium chloride injection may increase endotracheal absorption.401

Onset

Inhibition of salivation occurs within 30 minutes and peaks within 1–1.6 hours after IM administration.b

Increase in heart rate occurs within 2–4 minutes after IV injection.b

Increase in heart rate occurs within 5–40 minutes and peaks within 20–60 minutes after IM administration.b

Duration

Inhibition of salivation persists for up to 4 hours.b

Plasma Concentrations

Following IM administration, peak plasma concentrations are reached within 30 minutes.b

Distribution

Extent

Rapidly and well distributed throughout the body, including the CNS.105 b

Traces are found in various secretions, including milk.200

Crosses the placental barrier and enters fetal circulation but is not found in amniotic fluid.200

Plasma Protein Binding

Low binding (about 18%) to serum albumin.b

Elimination

Metabolism

Via the liver to several metabolites including tropic acid, atropine (or a chromatographically similar compound), and, possibly, esters of tropic acid and glucuronide conjugates.b

Elimination Route

About 30–50% of a dose is excreted in urine unchanged.b

Excreted mainly through the kidneys;b however, small amounts may be excreted in the feces and expired air.b

Half-life

2–3 hours.b

Biphasic following IM injection; 2–3-hours initially followed by a terminal half-life of 12.5 hours or longer.b

Special Populations

Elimination half-life is more than doubled in children <2 years and the elderly (>65 years of age) compared with other age groups.200

No gender effect on pharmacokinetics and pharmacodynamics.200

Stability

Storage

Parenteral

Injection

25°C (may be exposed to 15–30°C).105

Protect from freezing and light.105

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution CompatibilityHID

Compatible

Sodium chloride 0.9%

Drug Compatibility
Admixture CompatibilityHID

Compatible

Dobutamine HCl

Furosemide

Meropenem

Sodium bicarbonate

Verapamil HCl

Y-Site CompatibilityHID

Compatible

Abciximab

Amiodarone HCl

Argatroban

Bivalirudin

Dexmedetomidine HCl

Doripenem

Etomidate

Famotidine

Fenoldopam mesylate

Fentanyl citrate

Heparin sodium

Hydrocortisone sodium succinate

Hydromorphone HCl

Meropenem

Methadone HCl

Morphine sulfate

Nafcillin sodium

Palonosetron HCI

Potassium chloride

Tirofiban HCl

Variable

Propofol

Compatibility in SyringeHID

Compatible

Buprenorphine HCl

Butorphanol tartrate

Chlorpromazine HCl

Dimenhydrinate

Diphenhydramine HCl

Droperidol

Fentanyl citrate

Glycopyrrolate

Heparin sodium

Hydromorphone HCl

Hydroxyzine HCl

Meperidine HCl

Metoclopramide HCl

Midazolam HCl

Milrinone lactate

Morphine sulfate

Nalbuphine HCl

Ondansetron HCl

Pentazocine lactate

Prochlorperazine edisylate

Promethazine HCl

Ranitidine HCl

Scopolamine HBr

Incompatible

Pantoprazole sodium

Variable

Pentobarbital sodium

Actions

  • Competitively inhibits acetylcholine or other cholinergic stimuli at autonomic effectors innervated by postganglionic cholinergic nerves and, to a lesser extent, on smooth muscles that lack cholinergic innervation.c At usual doses, principally antagonizes cholinergic stimuli at muscarinic receptors and has little or no effect on cholinergic stimuli at nicotinic receptors.c

  • Antimuscarinics also have been referred to as anticholinergics (cholinergic blocking agents), but this term is appropriate only when it describes the antagonism of cholinergic stimuli at any cholinergic receptor, whether muscarinic or nicotinic.c

  • Also have been referred to as parasympatholytics because the antagonized functions principally are under the parasympathetic division of the nervous system.c

  • Receptors at various sites are not equally sensitive to inhibition of muscarinic effects.c Relative sensitivity of physiologic functions (proceeding from the most sensitive) is as follows: secretions of the salivary, bronchial, and sweat glands; pupillary dilation, ocular accommodation, and heart rate; contraction of the detrusor muscle of the bladder and smooth muscle of the GI tract; and gastric secretion and motility.c Doses used to decrease gastric secretions are likely to cause dryness of the mouth (xerostomia) and interfere with visual accommodation, and possibly cause difficulty in urinating.c

  • Various antisecretory effects in the GI tract, including reduction of salivation (producing xerostomia) and gastric secretions (only partial reduction in gastric acid secretion).c Prolonged inhibitory effects on the motility of the esophagus, stomach, duodenum, jejunum, ileum, and colon.c

  • Relaxes lower esophageal sphincter with a resultant decrease in lower esophageal sphincter pressure.c

  • Decreases the tone and amplitude of contractions of the ureters and bladder.c May cause urinary retention (e.g., in patients with urinary obstruction).c In patients with uninhibited or reflex neurogenic bladder, the amplitude and frequency of uninhibited contractions are reduced and bladder capacity is increased.c

  • Positive chronotropic effect (increased SA node automaticity), accelerating sinus rate by direct parasympathetic blockade.c Stimulates the AV functional pacemaker.c Facilitates AV nodal conduction in a normal AV node.c

  • Can reverse reflex vagal cardiac slowing or asystole such as that induced by inhalation of irritant vapors or by vagal stimulation (e.g., carotid sinus stimulation, pressure on the eyeball).c

  • May cause cutaneous vasodilation, especially at toxic doses (atropine flush).c

  • Reduces secretions from the nose, mouth, pharynx, and bronchi.c Relaxes smooth muscles of the bronchi and bronchioles with a resultant decrease in airway resistance.c Potent bronchodilation, particularly in large bronchial airways; especially effective in reversing bronchoconstriction induced by parasympathetic stimulation.c

  • Stimulates the medulla and higher cerebral centers and exhibits CNS effects similar to those produced by antimuscarinics used in the treatment of parkinsonian syndrome (e.g., trihexyphenidyl).c

  • Blocks the responses of the sphincter muscle of the iris and the ciliary muscle of the lens to cholinergic stimulation, producing mydriasis and cycloplegia and a resultant decrease in ocular accommodation.c Little effect on IOP except with angle-closure glaucoma where IOP may increase.c

  • Reduces the volume of perspiration by inhibiting sweat-gland secretions.c May suppress sweating sufficiently to increase body temperature.c

Advice to Patients

  • Seek immediate medical attention after injection with an atropine injection auto-injector.105

  • Advise that dry mouth may occur.105 b

  • Advise of risk of hyperthermia and heat prostration; avoid exposure to high environmental temperatures and avoid use when febrile.c

  • Advise patients receiving chronic therapy of possible blurred vision with the drug; activities that require good, clear vision should be avoided.105 b

  • Risk of dizziness or drowsiness; avoid driving or operating machinery until effects on individual are known.c

  • For IM self-administration in nerve gas and pesticide poisoning, proper techniques for storage, attention to expiration dating (replacing before expiration), use, and disposal of the prefilled auto-injector (e.g., AtroPen) and for administration of the drug.105

  • For IM self-administration in nerve gas and pesticide poisoning, importance of understanding the indications for use and the symptoms of poisoning.105

  • For IM self-administration in nerve gas and pesticide poisoning, importance of ensuring adequate understanding of the recognition and treatment of such poisoning and when concomitant cholinesterase reactivator (pralidoxime chloride) therapy may be necessary.105

  • For IM self-administration in nerve gas and pesticide poisoning, importance of not exceeding 3 doses unless under medical supervision.105

  • For IM self-administration in nerve gas and pesticide poisoning, importance of seeking immediate medical attention once the initial dose(s) is administered because respiratory and other supportive care and prolonged atropinization may be needed.105

  • For IM self-administration in nerve gas and pesticide poisoning, importance of recognizing that inadvertent administration when such poisoning is not present could result in atropine toxicity and temporary incapacitation (inability to walk properly, see clearly, or think clearly for several hours or longer).105

  • For self-administration in nerve gas and pesticide poisoning, importance of not contaminating other individuals (e.g., medical and emergency personnel) by clothing exposure; aggressive and safe decontamination by trained personnel is strongly suggested.105

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.105 b

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.105

  • Importance of informing patients of other important precautionary information.105 b (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Atropine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Bulk

Powder

Parenteral

Injection

equivalent to Atropine Sulfate 0.25 mg/0.3 mL

AtroPen Auto-Injector (“yellow label”)

Meridian

equivalent to Atropine Sulfate 0.5 mg/0.7 mL

AtroPenAuto-Injector (“blue label”)

Meridian

equivalent to Atropine Sulfate 1 mg/0.7 mL

AtroPenAuto-Injector (“dark red label”)

Meridian

equivalent to Atropine Sulfate 2 mg/0.7 mL

AtroPenAuto-Injector (“green label”)

Meridian

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Atropine Sulfate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Bulk

Powder*

Parenteral

Injection

0.05 mg/mL*

Atropine Sulfate Injection

0.1 mg/mL*

Atropine Sulfate Injection

0.4 mg/mL*

Atropine Sulfate Injection

1 mg/mL*

Atropine Sulfate Injection

AHFS DI Essentials. © Copyright 2017, Selected Revisions April 24, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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102. DeLorenzo RA. Exposed: signs, symptoms & EMS management of nerve-agent poisoning. J Emerg Med Serv JEMS. 2001; 26:48-57. [PubMed 11409202]

103. In Ellenhorn MJ, Schonwald S, Ordog G, Wasserberger J, eds. Ellenhorn’s medical toxicology: diagnosis and treatment of human poisoning. 2nd ed. Baltimore: Williams & Wilkins; 1997:1267-90.

104. Anon. Prevention and treatment of nerve gas poisoning. Med Lett Drugs Ther. 1990; 32:103-5. [PubMed 2233511]

105. Meridian Medical Technologies. AtroPen (atropine injection) prescribing information. Columbia, MD; 2004 Aug.

106. The American Heart Association. Guidelines 2005 for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2005; 112(Suppl I): IV1-IV211.

107. Brown AFT. Anaphylaxis gets adrenaline going. Emerg Med J. 2004; 21:128-9. [PubMed 14988331]

109. Eigel B. (American Heart Association, Dallas, TX): Personal communication; 2006 Aug 17.

120. Bevan DR, Donati F, Kopman AF. Reversal of neuromuscular blockade. Anesthesiology. 1992; 77:785-805. [PubMed 1416176]

121. Srivastava A, Hunter JM. Reversal of neuromuscular block. Br J Anaesth. 2009; 103:115-29. [PubMed 19468024]

194. The Harriet Lane handbook: a manual for pediatric house officers. 16th ed. Gunn VL, Nechyba C, eds. Baltimore, MD: Mosby; 2002:600-1,772.

195. The Harriet Lane handbook: a manual for pediatric house officers. 20th ed. Tschudy MM, Arcara KM, eds. Baltimore, MD: Mosby; 2012:706-7.

196. World Health Organization. WHO model prescribing information: Drugs used in anesthesia. From WHO website. Accessed 2017 Jan 6.

197. Goldfrank’s toxicologic emergencies. 7th ed. Goldfrank LR, Howland MA, Flomenbaum NE et al, eds. New York: McGraw-Hill; 2002:1353-6.

198. West-ward Pharmaceuticals. Atropine sulfate injection prescribing information. Eatontown, NJ; 2011 June .

199. Hope Pharmaceuticals. Atropine sulfate, USP prescribing information. Scottsdale, AZ; 1998 Nov.

200. Hospira. Atropine sulfate injection prescribing information. Lake Forest, IL; 2015 Nov.

201. American College of Emergency Physicians, Society for Cardiovascular Angiography and Interventions, O'Gara PT et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013; 61:e78-140. [PubMed 23256914]

202. Ryan TJ, Anderson JL, Antman EM et al. ACC/AHA guidelines for the management of patients with acute myocardial infarction: executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction). Circulation. 1996; 94:2341-50. [PubMed 8901709]

400. Link MS, Berkow LC, Kudenchuk PJ et al. Part 7: Adult Advanced Cardiovascular Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2015; 132(18 Suppl 2):S444-64. [PubMed 26472995]

401. Neumar RW, Otto CW, Link MS et al. Part 8: adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010; 122(18 Suppl 3):S729-67. [PubMed 20956224]

402. de Caen AR, Berg MD, Chameides L et al. Part 12: Pediatric Advanced Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2015; 132(18 Suppl 2):S526-42. [PubMed 26473000]

403. Kleinman ME, Chameides L, Schexnayder SM et al. Part 14: pediatric advanced life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010; 122(18 Suppl 3):S876-908. [PubMed 20956230]

b. AHFS Drug Information 2018. McEvoy, GK, ed. Atropine. Bethesda, MD: American Society of Health-System Pharmacists; 2018.

c. AHFS Drug Information 2018. McEvoy, GK, ed. Antimuscarinics/Antispasmodics General Statement. Bethesda, MD: American Society of Health-System Pharmacists; 2018.

HID. Trissel LA. Handbook on injectable drugs. 18th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2015:141-5.

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