ATROPINE SULFATE (Generic for ISOPTO ATROPINE)

General Administration Information
For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
IV Push
-Infuse via IV push. If administered into a peripheral vein during CPR, follow dose with a flush to facilitate drug delivery.


Intramuscular Administration
Intramuscular (IM) Autoinjector

-If possible, only persons with adequate training in the recognition and treatment of nerve agent or insecticide intoxication should administer the atropine autoinjector. If a trained provider is not available during an emergency, patient or caregiver administration is acceptable.
-Remove the autoinjector from the plastic sleeve.
-Firmly grasp the autoinjector with the green tip pointed downward. Pull off the yellow safety cap with the other hand.
-Inject in the mid-lateral thigh area at a 90-degree angle. Inject through clothing if necessary, but make sure pockets at the injection site are empty. In smaller individuals, bunch up the thigh to provide a thicker area for injection.
-Hold the autoinjector firmly in place for at least 10 seconds, then remove and massage the injection site in a circular motion for several seconds. If the needle is not visible after removing the autoinjector from the outer thigh, the injection is not complete. In this circumstance, check to make sure the yellow safety cap has been removed and repeat the steps for injection, pressing more firmly on the thigh. If the needle is still not visible, discard, and use a new autoinjector.
-Each autoinjector has a single dose; if you need more than 1 injection, repeat the steps for injection using a new autoinjector.
-After injection, bend the needle back against the autoinjector using a hard surface. Use the bent needle as a hook to pin the used autoinjector to the exposed person's clothing, or use an alternative method to notify medical professionals of the dose and number of autoinjectors given.
-Move yourself and the victim away from the contaminated area immediately and locate additional medical care.
-Closely observe treated patients for at least 48 to 72 hours.

Intramuscular (IM) Injection
-Inject deeply into a large muscle mass (e.g., anterolateral thigh or deltoid [children and adolescents only]).

Subcutaneous Administration
-Inject subcutaneously taking care not to inject intradermally.

Other Injectable Administration
Intraosseous (IO) Infusion
NOTE: Atropine is not approved by the FDA for IO administration.
-During cardiopulmonary resuscitation, the same dosage may be given via the IO route when IV access is not available.



Ophthalmic Administration
-For ophthalmic use only.
-Instruct patient on proper instillation of eye ointment or solution (see Patient Information).
-Do not to touch the tip of the dropper or tube to the eye, fingertips, or other surface.


Other Administration Route(s)
Endotracheal (ET) Administration
NOTE: Atropine is not approved by the FDA for ET administration. According to ACLS and PALS guidelines, the parenteral atropine product may be administered via the ET route.
-ET administration is associated with lower blood drug concentrations compared to IV administration and may be unreliable. Tracheal drug absorption may be unreliable; higher ET doses may be required.
-ET administration should only be used if access to IV or intraosseous routes cannot be achieved or is delayed.
-The optimal dosage for ET administration has not been established.
-After dose administration, flush the ET tube with saline and follow with 5 ventilations.

Dry mouth and nasal dryness are common and, in some cases, desired reactions to atropine. Xerostomia (dry mouth) is caused by inhibition of acetylcholine activity in the salivary glands. Saliva substitutes may be useful in patients who suffer this adverse effect. Rarely hypersalivation and oral ulceration have also been reported.

Blurred vision and photophobia are common adverse reactions to atropine, regardless of administration route. After ophthalmic administration, atropine-induced cycloplegia and mydriasis are pronounced. Photophobia can occur while pupils are dilated. Prolonged use of ophthalmic formulations may result in local irritation characterized by follicular conjunctivitis, vascular congestion, edema, exudate, and exfoliative dermatitis (reported as eczematoid dermatitis). Mydriasis, pupils not properly responding to light, decreased contrast sensitivity, visual impairment (decreased visual acuity), decreased accommodation, strabismus, heterophoria, cycloplegia, cyclophoria, acute angle closure glaucoma, conjunctivitis, keratoconjunctivitis sicca, blindness, lacrimation, xerophthalmia (dry eyes), irritated eyes, crusting of the eyelid, and blepharitis have also been reported with atropine use.

Atropine antagonizes the actions of acetylcholine on gastrointestinal smooth muscle, thus causing constipation. Abdominal pain, dysphagia, nausea, vomiting, failure to feed, decreased bowel sounds, distended abdomen, delayed gastric emptying, decreased food absorption, and paralytic ileus have also been reported. Of these, constipation, abdominal distention, nausea, and vomiting are the most common.

Atropine has been reported to lead to a wide array of cardiac conduction abnormalities. In doses of 0.4 to 0.6 mg, atropine causes slight sinus bradycardia due to vagal stimulation. In larger doses (1 to 2 mg), it causes sinus tachycardia secondary to inhibition of vagal control of the SA node in the heart. Other cardiovascular adverse reactions reported include hypertension, hypotension, labile blood pressure, weak pulses, asystole, atrial fibrillation, atrial ectopic beats, palpitations, premature ventricular contractions (PVCs), bigeminal beats, trigeminal beats, nodal extrasystole, ventricular extrasystole, supraventricular extrasystole, cardiac syncope, prolongation of sinus node recovery time, chest pain (unspecified), cardiac dilation, myocardial infarction, QT prolongation, no P wave, prolonged P wave, shortened PR segment, R on T phenomenon, shortened RT duration, widening and flattening of QRS complex, flattening of T wave, repolarization abnormalities, ST-T wave changes, retrograde conduction, transient AV dissociation, junctional tachycardia, supraventricular tachycardia (SVT), left ventricular failure, atrial arrhythmia, ventricular arrhythmia, ventricular flutter, ventricular fibrillation, and ventricular tachycardia.

Tachypnea, slow respirations, shallow respirations, labored respirations, breathing difficulty, respiratory failure (respiratory arrest), laryngitis, laryngospasm, pulmonary edema, subcostal recession, and inspiratory stridor have been reported with atropine use.

Atopic dermatitis, macular rash, papular rash, maculopapular rash, anhidrosis, rash (sometimes progressing to exfoliation), scarlatiniform rash, erythematous rash, petechiae, dry warm skin, dry mucous membranes, flushed skin, cold skin, cyanosed skin (cyanosis), and sweating/moist skin have been reported with atropine use.

Atropine can cause urinary retention, a common adverse reaction, secondary to decreased tone and amplitude of contractions of the ureters and bladder. Urinary incontinence, urinary urgency, urinary hesitancy, bladder distension, bed-wetting, and difficult micturation have also been reported.

Dehydration, lethargy, flushing, excessive thirst (polydipsia), weakness, tongue chewing, feeling hot, and fever have been reported with atropine use. The administration of therapeutic doses of parenteral atropine may result in intense flushing of the face (blush area) and may cause "fever" in infants and small children due to suppression of sweat gland. This is called the 'atropine flush' and is not harmful when it occurs.

Anaphylactoid reactions have been reported with atropine use.

Confusion, headache, and dizziness are the most commonly reported CNS adverse reactions associated with atropine. Anxiety, amnesia, abnormal movements, dysarthria, hyperreflexia, hypertonia, muscle twitching, muscle clonus, opisthotonos, diminished tendon reflexes, Babinski's reflex/Chaddock reflex, dysmetria, restlessness, ataxia, stupor, disorientation, impaired cognition, sensation of intoxication, coma, mania, withdrawn behavior, difficulty concentrating, myoclonia, insomnia, drowsiness, paranoia, hallucinations (visual or aural), seizures (generally tonic-clonic), vertigo, excitement, agitation, changes in behavior, and mental disorders have also been reported. Larger doses of atropine may produce restlessness, tremor, locomotor difficulties, fatigue, delirium, hallucinations, depression, and ultimately muscle paralysis and coma. A 30-day-old infant, weighing 2.2 kg, experienced toxic side effects including lethargy, opisthotonus, seizures, periodic breathing with apnea, dilated unresponsive pupils, dry mucous membranes and skin, and urinary retention after 2 doses of atropine 0.1 mg (0.045 mg/kg/dose) over 5 hours. Death in pediatric patients from atropine poisoning has been reported with doses of 0.05 mg/kg and 0.2 mg/kg. Coma and seizures have been reported in children receiving doses of 0.5 mg/kg. Manufacturers of ophthalmic atropine preparations state that coma and death have occurred in the very young.

An injection site reaction, including muscle tightness and mild to moderate pain at the site of injection, may occur with injectable atropine use.

Leukocytosis, erythrocytosis, hyponatremia, hypoglycemia, hyperglycemia, hypokalemia, elevated hemoglobin, anemia (reported as low hemoglobin), and elevated BUN have been reported with atropine use. EEG changes including increase in photic stimulation on EEG, signs of drowsiness of EEG, runs of alpha waves on EEG, and alpha waves blocked upon opening eyes have also been reported.

Atropine should not be used in patients with known atropine or other belladonna alkaloids hypersensitivity because they may develop an allergic or other adverse reaction, including anaphylaxis. NOTE: Intense flushing of the face (blush area) and trunk may occur after parenteral injection of atropine. This is called the 'atropine flush' and is not harmful when it occurs.

Parenteral atropine products may contain sodium metabisulfite. Use these formulations with caution in patients with known sulfite hypersensitivity in which sulfites may precipitate an allergic reaction.

Atropine autoinjectors are indicated only for treatment of organophosphate or carbamate poisoning and are intended as an initial treatment of muscarinic symptoms. Do not rely upon atropine to provide complete protection. Seek definitive medical care immediately. Preferably, persons with adequate training in the recognition and treatment of nerve agent or insecticide intoxication should administer the autoinjector; however, caregiver or self-administration is acceptable in an emergency situation when a trained provider is not available. Use protective masks and clothing when available, evacuate from the contaminated environment immediately, and undertake decontamination as soon as possible. Provide symptomatic support as needed (e.g., respiration, bronchial secretion suction).

Due to the potential for toxicity, atropine should not be taken in amounts above prescription limits. Because atropine may cause blurred vision, drowsiness, or dizziness, advise any patient (or their caregiver) to use caution when performing activities requiring coordination and concentration. Use of ophthalmic atropine to neonates may result in feeding intolerance, so it is recommended to withhold feeding for 4 hours after administration.

Use atropine with caution in patients with known cardiac disease including cardiac arrhythmias, congestive heart failure, coronary artery disease, angina, recent myocardial infarction, or other cardiac instabilities where an increase in heart rate could be detrimental. Atropine-induced tachycardia may cause ischemia, extend or initiate myocardial infarcts, and stimulate ventricular ectopy and fibrillation. Increased heart rate is also undesirable in patients with hyperthyroidism (thyrotoxicosis) or cardiovascular instability in acute hemorrhage (bleeding). To minimize tachycardia, restrict the total dose of atropine to 2 to 3 mg (maximum 0.03 to 0.04 mg/kg). Use antimuscarinics with caution in patients with mitral stenosis since tachycardia could exacerbate the clinical symptoms of this condition and in patients with hypertension since they have some actions on the heart that can exacerbate this condition.

Atropine may be used with caution to treat bradycardia after heart transplant. Atropine is likely to be ineffective after cardiac transplantation because the transplanted heart lacks vagal innervation. One small uncontrolled study of 25 adult, cardiac transplant patients has documented paradoxical slowing of the heart rate and high-degree AV block following atropine administration.

Atropine reduces respiratory secretions, relieves bronchoconstriction and bronchospasm, and may reduce the paralysis of respiration during toxic exposure. However, atropine should be used cautiously in those with chronic lung disease (CLD). Because the use of atropine may dry and thicken bronchial secretions in the respiratory tract and result in the formation of dangerous viscid plugs in patients with chronic lung disease, it should be used with caution in patients with asthma, CLD, pulmonary disease, or respiratory infection.

Atropine is extensively metabolized in the liver. Patients with hepatic disease may be at increased risk for developing increased drug concentrations, with resultant side effects.

Antimuscarinics, including atropine, should be used with caution in patients with renal impairment or renal failure. Metabolites and unchanged drug are excreted in the kidneys. Additionally, the antimuscarinic actions of atropine may cause urinary retention. Atropine should be avoided in patients whose conditions may be worsened by urinary retention such as bladder obstruction or urinary tract obstruction.

Except in doses usually used as part of a preanesthesia regimen, parenteral atropine is contraindicated in patients with pyloric stenosis as use may convert partial pyloric stenosis into complete pyloric obstruction. Administer atropine with caution to patients with GI disease. Use atropine with caution in patients with GI obstruction (e.g., achalasia, etc.) because atropine can further decrease GI motility and cause paralytic ileus. Likewise, antimuscarinics should be used cautiously in patients with ulcerative colitis, ileus, and intestinal atony because decreases in GI motilitycan exacerbate these conditions. Toxic megacolon may also be precipitated or aggravated. Use extreme caution in persons with suspected or known GI infection such as infectious diarrhea (e.g., pseudomembranous colitis) because atropine may decrease elimination of the bacteria or toxin from the body and thus prolong the infection. Also, atropine should be used with caution in patients with diarrhea that may be an early sign of incomplete GI obstruction, especially in patients with ileostomy or colostomy. This drug should be used cautiously in patients with gastroesophageal reflux disease (GERD) or hiatal hernia associated with reflux esophagitis. Atropine may decrease gastric motility and relax the lower esophageal sphincter, promoting gastric retention and reflux. Although antimuscarinics have been used as adjunct treatment of peptic ulcer disease, there are no conclusive data that the drug aids in healing, decreases rate of recurrence, or prevents the complications of peptic ulcer. In patients with gastric ulcer, antimuscarinics may delay gastric emptying and promote antral stasis.

Atropine ophthalmic ointment is contraindicated in people with primary glaucoma or a predisposition to narrow-angle glaucoma. To avoid inducing closed-angle glaucoma, an estimation of the depth of the anterior chamber angle should be made. Use systemic and ophthalmic atropine with caution in those at risk for acute glaucoma and in those who have severe narrow angle glaucoma. Monitor for signs and symptoms of intraocular pressure as appropriate.

Atropine may suppress sweat gland activity which, in a warm environment or with strenuous exercise, can lead to hyperthermia and heat injury. Avoid conditions that elevate core body temperature (e.g., strenuous exercise, ambient temperature increase, fever, dehydration) and excessive heat exposure.

Pediatric patients are sometimes more sensitive than adults to the anticholinergic effects of atropine; neonates, infants, and young children are at particular risk for adverse effects. Monitor heart rate after administration. Serious adverse effects appear to be uncommon. In a survey of children accidentally exposed to higher doses of atropine (up to 0.175 mg/kg), few serious adverse events were reported (primarily consisting of tachycardia). Systemic adverse effects have been observed even after conjunctival instillation in some circumstances. Secondary to the potential association between cycloplegia caused by administration of ophthalmic atropine and development of amblyopia, the manufacturer recommends to avoid use within the first 3 months of life.

Description: Atropine is a naturally occurring tertiary amine extracted from belladonna alkaloid that consists of a racemic mixture of both d- and l-hyoscyamine, which differ in their antimuscarinic potencies. Atropine is the prototype antimuscarinic from which other antimuscarinic agents were developed. Atropine counteracts cholinergic-mediated reductions in heart rate, vascular resistance, and blood pressure. Atropine has many applications in clinical medicine but most commonly is used systemically to treat symptomatic bradycardia and as a preoperative agent to reduce secretions prior to surgery. Available evidence does not support routine use of atropine as a premedicant for emergency intubation in critically ill children; however, it may be considered when there is a high risk of bradycardia. In pediatric patients, the recommended minimum single dose for the treatment of bradycardia is 0.1 mg; however, this dose is controversial for very small neonates when the dose would be more than 0.02 mg/kg. There are currently no minimum dosage recommendations in neonates. Atropine also is used to produce mydriasis during ophthalmic examination. Atropine decreases the muscarinic cholinergic adverse reactions associated with organophosphate toxicity (e.g., lacrimation, sweating, breathing problems, bradycardia) and is well known as an useful as an adjunct in nerve agent and insecticide poisoning. Atropine is FDA-approved for pediatric patients, although no minimum age is specified.

General Dosing Information
-Patients with known coronary artery disease dosing: limit the total dose of parenteral atropine to 0.03 to 0.04 mg/kg.

For the treatment of symptomatic bradycardia* (e.g., vasovagal response, AV block, or bradyarrhythmias):
NOTE: Atropine may be administered in higher initial doses for bradycardia resulting from acetylcholinesterase-inhibiting agents; large total doses may be required.
Intravenous or Intraosseous* dosage:
Neonates: 0.02 mg/kg/dose IV; may repeat dose 1 time. Per PALS, the minimum single dose is 0.1 mg, however, some argue that this may be an excessive dose in very small neonates since the total dosage would be greater than 0.02 mg/kg. The same dosage may be given via the intraosseous route when IV access is not available.
Infants, Children, and Adolescents: 0.02 mg/kg/dose IV (minimum dose: 0.1 mg IV) is recommended by PALS; the dose may be repeated 1 time. Max: 0.5 mg/dose IV. The same dosage may be given via the intraosseous route when IV access is not available.
Endotracheal dosage:
NOTE: Drug effects after endotracheal (ET) administration may not be uniform; use only if access to IV or IO routes is not available.
Neonates: 0.01 to 0.03 mg/kg/dose ET; may repeat dose 1 time. Flush the ET tube with a minimum of 1 to 5 mL (dependent on body weight with smaller patients getting smaller volumes) 0.9% Sodium Chloride Injection and follow with 5 ventilations.
Infants, Children, and Adolescents: 0.04 to 0.06 mg/kg/dose ET (minimum dose: 0.1 mg ET); may repeat dose 1 time. Max: 0.5 mg/dose ET. Flush the ET tube with a minimum of 5 mL 0.9% Sodium Chloride Injection and follow with 5 ventilations. The optimal dosage has not been established.
Intramuscular dosage:
Neonates, Infants, Children, and Adolescents: 0.02 to 0.04 mg/kg/dose IM.

For the treatment of bradyasystolic cardiac arrest:
Intravenous or Intraosseous* dosage:
Neonates: 0.01 to 0.03 mg/kg/dose IV. Atropine is not included in the PALS algorithm for cardiac arrest and is no longer routinely recommended due to unlikely therapeutic benefit in PEA or asystole. The previous PALS dosage recommendation was 0.02 mg/kg/dose IV with a second dose administered if indicated. When using atropine, PALS recommends a minimum single dose of 0.1 mg, however, some feel this dose may be excessive in very small neonates since the total dosage would be greater than 0.02 mg/kg. The same dosage may be given via the intraosseous route when IV access is not available. Do not interrupt CPR to administer drug therapy.
Infants, Children, and Adolescents: 0.01 to 0.03 mg/kg/dose IV. Atropine is not included in the PALS algorithm for cardiac arrest and is no longer routinely recommended due to unlikely therapeutic benefit in PEA or asystole. The previous PALS dosage recommendation was 0.02 mg/kg/dose IV (minimum dose of 0.1 mg; Max: 0.5 mg) with a second dose administered if indicated. The same dosage may be given via the intraosseous route when IV access is not available. Do not interrupt CPR to administer drug therapy. Do not interrupt CPR to administer drug therapy. Cardiac arrest in children is uncommon and usually results from progressive respiratory failure or shock (e.g., asphyxial arrest) rather than from cardiac etiology.
Endotracheal dosage:
NOTE: Drug effects after endotracheal (ET) administration may not be uniform; use only if access to IV or IO routes is not available.
Neonates, Infants, Children, and Adolescents: Atropine is not included in the PALS algorithm for cardiac arrest and is no longer routinely recommended due to unlikely therapeutic benefit in PEA or asystole. The previous PALS dosage recommendation was 0.04 to 0.06 mg/kg/dose for ET administration with a second dose administered if indicated. Flush the ET tube with 0.9% Sodium Chloride Injection (1 to 5 mL for neonates and 5 mL or more for infants, children, and adolescents) and follow with 5 ventilations. Do not interrupt CPR to administer drug therapy.

For preoperative use to decrease secretions (i.e., aspiration prophylaxis) and block cardiovagal reflexes and/or succinylcholine-induced arrhythmias during surgery:
Intravenous, Intramuscular, or Subcutaneous dosage:
Neonates : 0.02 mg/kg/dose IV, IM, or subcutaneous before administration of sedative/anesthetic and paralytic agents. Use of 0.1 mg in neonates will result in dosages greater than 0.02 mg/kg; there is no documented minimum dosage in this age group.
Infants, Children, and Adolescents: 0.01 to 0.02 mg/kg/dose IV or IM (minimum dose: 0.1 mg; Max: 1 mg) before administration of sedative/anesthetic and paralytic agents. According to FDA-approved product labeling, dose may also be given subcutaneously 30 minutes before surgery. Various fixed dosing schedules are also available. The following is one example: 0.1 mg for patient weight 3.2 to 7 kg; 0.15 mg for weight 8 to 11 kg; 0.2 mg for weight 11 to 18 kg; 0.3 mg for weight 18 to 29 kg; and 0.4 mg for weight 30 to 41 kg.

For the treatment of cholinergic crisis (e.g., chemical nerve agent or carbamate or organophosphate insecticide toxicity):
NOTE: Give atropine as soon as symptoms of toxicity occur. In general, do not use atropine until cyanosis has been overcome; atropine may produce ventricular fibrillation and possible seizures in the presence of hypoxia.
Intravenous, Intramuscular, or Intraosseous* dosage (using parenteral solution; NOT autoinjector):
Neonates: 0.05 to 0.1 mg/kg/dose IV, IM, or IO every 5 to 15 minutes as needed until symptoms dissipate. IV route is preferred. Repeat doses based on recurrence of symptoms for 2 to 12 hours or longer depending on severity of poisoning. When symptoms are stable for 6 hours or more, the dosing may be decreased. In severely poisoned patients, the dose may need to be more than 2 times suggested dose. The dosing interval may be decreased, or continuous IV infusion may be necessary with high atropine requirements. If continuous infusion is required to maintain atropinization, begin with 10% to 20% of the total loading dose administered hourly.
Infants, Children, and Adolescents: 0.05 to 0.1 mg/kg/dose IV, IM, or IO every 5 to 15 minutes as needed until symptoms dissipate. IV route is preferred. Repeat doses based on recurrence of symptoms for 2 to 12 hours or longer depending on severity of poisoning. When symptoms are stable for 6 hours or more, the dosing may be decreased. In severely poisoned patients, the dose may need to be more than 2 times suggested dose. The dosing interval may be decreased, or continuous IV infusion may be necessary with high atropine requirements. If continuous infusion is required to maintain atropinization, begin with 10% to 20% of the total loading dose administered hourly.
Intramuscular dosage (autoinjector only):
Neonates and Infants weighing less than 7 kg: 0.25 mg/dose IM as soon as symptoms of poisoning appear (usually tearing, excess saliva, wheezing, drowsiness, muscle floppiness). Give 1 dose for known or suspected poisoning with 2 or more mild symptoms (e.g., blurred vision, miosis, watery eyes, runny nose, increased salivation, chest tightness or difficulty breathing, tremors, muscle twitching, nausea or vomiting, unexplained wheezing or coughing, acute stomach cramping, tachycardia, or bradycardia). Give 2 additional doses in rapid succession 10 minutes after giving the first injection if any severe symptom appears (e.g., confusion, severe breathing difficulties, severe lung secretions, severe muscle twitching and general weakness, involuntary urination and defecation, seizures, unconsciousness). Give 3 doses in rapid succession to any victim found unconscious or presenting with severe symptoms. Anticonvulsants and pralidoxime may be administered concurrently.
Infants and Children weighing 7 to 18 kg: 0.5 mg/dose IM as soon as symptoms of poisoning appear (usually tearing, excess saliva, wheezing, drowsiness, muscle floppiness). Give 1 dose for known or suspected poisoning with 2 or more mild symptoms (e.g., blurred vision, miosis, watery eyes, runny nose, increased salivation, chest tightness or difficulty breathing, tremors, muscle twitching, nausea or vomiting, unexplained wheezing or coughing, acute stomach cramping, tachycardia, or bradycardia). Give 2 additional doses in rapid succession 10 minutes after giving the first injection if any severe symptom appears (e.g., confusion, severe breathing difficulties, severe lung secretions, severe muscle twitching and general weakness, involuntary urination and defecation, seizures, unconsciousness). Give 3 doses in rapid succession to any victim found unconscious or presenting with severe symptoms. Anticonvulsants and pralidoxime may be administered concurrently.
Children weighing 18 to 41 kg: 1 mg/dose IM as soon as symptoms of poisoning appear (usually tearing, excess saliva, wheezing, drowsiness, muscle twitching). Give 1 dose for known or suspected poisoning with 2 or more mild symptoms (e.g., blurred vision, miosis, watery eyes, runny nose, increased salivation, chest tightness or difficulty breathing, tremors, muscle twitching, nausea or vomiting, unexplained wheezing or coughing, acute stomach cramping, tachycardia, or bradycardia). Give 2 additional doses in rapid succession 10 minutes after giving the first injection if any severe symptom appears (e.g., confusion, severe breathing difficulties, severe lung secretions, severe muscle twitching and general weakness, involuntary urination and defecation, seizures, unconsciousness). Give 3 doses in rapid succession to any victim found unconscious or presenting with severe symptoms. Anticonvulsants and pralidoxime may be administered concurrently.
Children and Adolescents weighing more than 41 kg: 2 mg/dose IM as soon as symptoms of poisoning appear (usually tearing, excess saliva, wheezing, drowsiness, muscle twitching). Give 1 dose for known or suspected poisoning with 2 or more mild symptoms (e.g., blurred vision, miosis, watery eyes, runny nose, increased salivation, chest tightness or difficulty breathing, tremors, muscle twitching, nausea or vomiting, unexplained wheezing or coughing, acute stomach cramping, tachycardia, or bradycardia). Give 2 additional doses in rapid succession 10 to 15 minutes after giving the first injection if any severe symptom appears (e.g., confusion, severe breathing difficulties, severe lung secretions, severe muscle twitching and general weakness, involuntary urination and defecation, seizures, unconsciousness). Give 3 doses in rapid succession to any victim found unconscious or presenting with severe symptoms. Anticonvulsants and pralidoxime may be administered concurrently.

For cholinesterase inhibitor-induced muscarinic effects prophylaxis when anticholinesterase agents (i.e., neostigmine, physostigmine, pyridostigmine) are used to reverse the neuromuscular blockade produced by curariform agents:
Intravenous dosage:
Children: 0.05 mg/kg IV (up to initial adult dose: 2 to 5 mg). Repeat/adjust dose every 10 to 20 minutes as needed; double the dose if inadequate response/atropinization to initial dose.

For mydriasis induction or cycloplegia induction:
Ophthalmic Dosage (Ophthalmic solution only):
Infants and Children 3 months up to 3 years: 1 drop of 1% solution topically to the cul-de-sac of the conjunctiva in 1 or both eyes as indicated, 40 minutes before the intended maximal dilation time. In one study for cycloplegic refraction in strabismic children, 1 drop 3-times daily for 3 days administered prior to the procedure was compared to 2 drops given 5 minutes apart; children younger than 2.5 years received a 0.5% concentration and children 2.5 years or older received 1% concentration. The differences in cycloplegic refraction were not significant between the 2 groups.
Children and Adolescents 3 years and older: 1 drop of 1% solution topically to the cul-de-sac of the conjunctiva in 1 or both eyes as indicated, 40 minutes before the intended maximal dilation time. Dose may be repeated up to twice daily as needed. In one study for cycloplegic refraction in strabismic children, 1 drop 3-times daily for 3 days administered prior to the procedure was compared to 2 drops given 5 minutes apart; children younger than 2.5 years received a 0.5% concentration and children 2.5 years or older received 1% concentration. The differences in cycloplegic refraction were not significant between the 2 groups.
Ophthalmic Dosage (Ophthalmic ointment only):
Infants 3 months and older, Children, and Adolescents: Apply a small amount of the ointment in the conjunctival sac 1- to 2-times per day; take care to avoid overdosage.

For the treatment of iritis or uveitis:
Ophthalmic dosage (1% solution or ointment):
Children and Adolescents: 1 drop to the affected eye(s) 2 to 3 times daily; 1 to 2 drops once daily has also been used. For the ointment, apply a small amount in the conjunctival sac of the affected eye(s) 1 or 2 times daily.

For penalization of the healthy eye in the treatment of amblyopia:
Ophthalmic dosage:
Children and Adolescents 3 years and older: 1 drop of 1% solution topically to the cul-de-sac of the conjunctiva, 40 minutes before the intended maximal dilation time. Dose may be repeated up to twice daily as needed. 1 drop of 1% solution instilled in the unaffected eye once daily results comparable improvement in visual acuity to patching. In a clinical trial, 419 children ages 3 to 7 years with moderate amblyopia (i.e., visual acuity 20/40 to 20/100) were randomly assigned to receive patching for a minimum of 6 hours daily or 1 drop of atropine 1% ophthalmic solution in the unaffected eye every day. Although more rapid improvement was noted initially in the patching group, the difference was clinically insignificant after 6 months (about one-third of a line). After the initial 6 months of treatment, investigators were permitted to prescribe any type of amblyopia therapy. In 363 patients, visual acuity continued to be improved when evaluated 2 years after initial randomization; the authors concluded that use of atropine or patching for 6 months followed by regular care did not lend to differences in visual acuity 2 years later. Additionally, in a subgroup analysis of 176 children who were evaluated at age 10 years, improvement of amblyopia was maintained in both groups, although approximately half experienced mild residual amblyopia (i.e., visual acuity less than 20/25).

For the prevention of bradycardia and reduction of oral secretions during rapid-sequence intubation*:
Intravenous dosage:
Neonates: 0.02 mg/kg/dose IV.
Infants, Children, and Adolescents: 0.02 mg/kg/dose IV (with no minimum dose) given 1 to 2 minutes prior to intubation. Max: 0.5 mg/dose. Available evidence does not support routine use of atropine as a premedicant for emergency intubation in critically ill children; however, it may be considered when there is a high risk of bradycardia.

For the treatment of symptomatic bradycardia associated with beta-blocker toxicity* or calcium-channel blocker toxicity*:
Intravenous dosage:
Infants, Children, and Adolescents: 0.02 mg/kg/dose IV (minimum dose: 0.1 mg); may repeat once. Max: 0.5 mg/dose. Atropine is unlikely to have a significant or persisting effect on heart rate; anticipate quickly moving on to other resuscitation measures.

Maximum Dosage Limits:
The maximum dosage of atropine is variable depending on the indication for use, route of administration, and the individual patient response. In patients with known coronary artery disease, limit the total dose of parenteral atropine to 0.03 to 0.04 mg/kg.

Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available.

Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Atropine is a competitive inhibitor at autonomic postganglionic cholinergic receptors. These include receptors found in GI and pulmonary smooth muscle, exocrine glands, the heart, and the eye. Atropine does not block the actions of acetylcholine at the neuromuscular junction. The activity of atropine is due primarily to l-hyoscyamine, which possesses all of the antimuscarinic activity, and not d-hyoscyamine, which essentially has no peripheral antimuscarinic activity. The degree of sensitivity of various muscarinic receptors to antimuscarinic agents is dose-dependent. The most sensitive receptors are those of the salivary, bronchial, and sweat glands. Next are the receptors in the eye and heart, followed by the receptors in the GI tract.

The principal clinical effects of atropine are a reduction in salivary, bronchial, and sweat gland secretions; mydriasis; cycloplegia; changes in heart rate; contraction of the bladder detrusor muscle and of the GI smooth muscle; decreased gastric secretion; and decreased GI motility. At lower doses, a paradoxical decrease in heart rate occurs, and at higher doses, effects are seen at nicotinic receptors in autonomic ganglia, causing restlessness, hallucinations, disorientation, and/or delirium. Unlike scopolamine, atropine does not produce CNS depression (drowsiness, euphoria, amnesia, fatigue, decreased REM sleep) at usual therapeutic doses. Also, atropine's antimuscarinic potency is greater in the heart, bronchial, and GI smooth muscle, and is lesser in the iris; ciliary body; and salivary, sweat, and bronchial glands.

The respiratory effects of atropine include reducing the volume of secretions from the nose, mouth, pharynx, and bronchi and relaxing smooth muscles of the bronchi and bronchioles, which decrease airway resistance. Since atropine is a potent bronchodilator, it is especially effective in blocking the acetylcholine-induced stimulation of guanyl cyclase, which is responsible for producing cyclic guanosine monophosphate (cGMP), a mediator of bronchoconstriction released from mast cells. These actions of atropine are useful, but controversial, in the treatment of antigen-, methacholine-, and exercise-induced bronchospasm in asthmatic patients.

Pharmacokinetics: Atropine is administered via oral, parenteral, endotracheal, oral inhalation, or ophthalmic routes. After absorption, the drug is widely distributed throughout the body and crosses the blood-brain barrier. Protein binding is 14% to 22%. The primary route of metabolism is via enzymatic hydrolysis in the liver to metabolites, including tropic acid. The half-life of atropine is approximately 2 to 4 hours in adults. Atropine and metabolites are primarily excreted renally and, to a lesser extent, by the pulmonary and fecal routes. Approximately 13% to 57% of administered atropine is excreted unchanged in the urine.

Affected cytochrome P450 isoenzymes and drug transporters: none


-Route-Specific Pharmacokinetics
Oral Route
Atropine is well absorbed after oral administration. Peak plasma concentrations are seen within 1 hour after oral administration in adult patients.

Intramuscular Route
Maximum concentrations (9.6 ng/mL) are attained in a mean of 3 minutes after administration of a 2 mg autoinjector in adult patients.

Inhalation Route
Atropine is well absorbed after oral inhalation. After oral inhalation, peak plasma concentrations are reached in about 0.5 to 1.5 hours.

Other Route(s)
Endotracheal Route
Atropine is well absorbed after endotracheal administration.


-Special Populations
Pediatrics
Infants, Children, and Adolescents
The half-life of atropine is prolonged in pediatric patients. In a small pharmacokinetic study (n = 13), the half-life of atropine after IV administration was longer in children younger than 2 years of age (about 7 hours) compared to children older than 2 years (2.5 hours). In this same study, the reported mean half-life for patients 0.8 to 10 years was 4.8 +/- 3.5 hours and for patients 16 to 58 years was 3 +/- 0.9 hours. Another pharmacokinetic study of 23 pediatric patients (age range 4 to 15 years) reported a mean half-life of 6.5 hours (range 2.2 to 12.8 hours) after atropine 0.02 mg/kg IV. In 10 pediatric patients (mean age 4.8 years +/- 2.3 years), after administration of 0.03 mg/kg PO of atropine, the time to peak concentration was 2 hours. In another 10 pediatric patients (mean age 5.5 years +/- 2.9 years) after administration of 0.02 mg/kg IM of atropine, the time to peak concentration and half-life was 30 minutes and 4.4 hours, respectively.

Gender Differences
AUC and Cmax are 15% higher in females compared to males. Half-life is slightly shorter (approximately 20 minutes) in females than males.