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Medication Safety Issues
International issues:
Genatropine® [France] may be confused with Genotropin®
Pronunciation
(A troe peen)
U.S. Brand Names
Index Terms
Generic Available
Yes: Excludes tablet
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Injection: Preoperative medication to inhibit salivation and secretions; treatment of symptomatic sinus bradycardia; AV block (nodal level); ventricular asystole; antidote for anticholinesterase inhibitor poisoning (carbamate insecticides, nerve agents, organophosphate insecticides)
Ophthalmic: Produce mydriasis and cycloplegia for examination of the retina and optic disc and accurate measurement of refractive errors; uveitis
Oral: Inhibit salivation and secretions
Use: Dental
Reduction of salivation and bronchial secretions
Use: Unlabeled/Investigational
Pulseless electric activity, asystole, neuromuscular blockade reversal
Restrictions
The AtroPen® formulation is available for use primarily by the Department of Defense.
Pregnancy Risk Factor
C
Pregnancy Considerations
Animal reproduction studies have not been conducted. Atropine has been found to cross the human placenta.
Lactation
Enters breast milk (trace amounts)/use caution (AAP rates “compatible”)
Breast-Feeding Considerations
Anticholinergic agents may suppress lactation.
Contraindications
Hypersensitivity to atropine or any component of the formulation; narrow-angle glaucoma; adhesions between the iris and lens; tachycardia; obstructive GI disease; paralytic ileus; intestinal atony of the elderly or debilitated patient; severe ulcerative colitis; toxic megacolon complicating ulcerative colitis; hepatic disease; obstructive uropathy; renal disease; myasthenia gravis (unless used to treat side effects of acetylcholinesterase inhibitor); asthma; thyrotoxicosis; Mobitz type II block
Warnings/Precautions
Concerns related to adverse effects:
• Hyperthermia: In the presence of a high environmental temperature, heat prostration can occur.
• Psychosis: Can occur in sensitive individuals.
Disease-related concerns:
• Autonomic neuropathy: Use with caution in patients with autonomic neuropathy.
• Benign prostatic hyperplasia (BPH): Use with caution in patients with BPH.
• Cardiovascular disease: Use with caution in patients with myocardial ischemia, HF, tachyarrhythmias, and/or hypertension.
• Hiatal hernia: Use with caution in patients with hiatal hernia associated with reflux esophagitis.
• Hyperthyroidism: Use with caution in patients with hyperthyroidism.
Special populations:
• Elderly: Use with caution in the elderly; may be sensitive to side effects.
• Pediatrics: Use with caution in children with spastic paralysis.
Dosage form specific issues:
• AtroPen®: There are no absolute contraindications for the use of atropine in severe organophosphate poisonings, however in mild poisonings, use caution in those patients where the use of atropine would be otherwise contraindicated. Formulation for use by trained personnel only.
Adverse Reactions
Severity and frequency of adverse reactions are dose related and vary greatly; listed reactions are limited to significant and/or life-threatening.
Cardiovascular: Arrhythmia, flushing, hypotension, palpitation, tachycardia
Central nervous system: Ataxia, coma, delirium, disorientation, dizziness, drowsiness, excitement, fever, hallucinations, headache, insomnia, nervousness
Dermatologic: Anhidrosis, urticaria, rash, scarlatiniform rash
Gastrointestinal: Bloating, constipation, delayed gastric emptying, loss of taste, nausea, paralytic ileus, vomiting, xerostomia, dry throat, nasal dryness
Genitourinary: Urinary hesitancy, urinary retention
Neuromuscular & skeletal: Weakness
Ocular: Angle-closure glaucoma, blurred vision, cycloplegia, dry eyes, mydriasis, ocular tension increased
Respiratory: Dyspnea, laryngospasm, pulmonary edema
Miscellaneous: Anaphylaxis
Drug Interactions
Acetylcholinesterase Inhibitors (Central): Anticholinergics may diminish the therapeutic effect of Acetylcholinesterase Inhibitors (Central). Acetylcholinesterase Inhibitors (Central) may diminish the therapeutic effect of Anticholinergics. If the anticholinergic action is a side effect of the agent, the result may be beneficial. Risk C: Monitor therapy
Anticholinergics: May enhance the adverse/toxic effect of other Anticholinergics. Exceptions: Paliperidone. Risk C: Monitor therapy
Cannabinoids: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoids. Risk C: Monitor therapy
Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Risk D: Consider therapy modification
Pramlintide: May enhance the anticholinergic effect of Anticholinergics. These effects are specific to the GI tract. Risk D: Consider therapy modification
Secretin: Anticholinergic Agents may diminish the stimulatory effect of Secretin. Risk D: Consider therapy modification
Storage
Store injection at controlled room temperature of 15°C to 30°C (59°F to 86°F); avoid freezing. In addition, AtroPen® should be protected from light.
Compatibility
Y-site administration: Compatible: Etomidate, famotidine, heparin, hydrocortisone sodium succinate, inamrinone, meropenem, nafcillin, potassium chloride, propofol, sufentanil, vitamin B complex with C. Incompatible: Thiopental.
Compatibility in syringe: Compatible: Butorphanol, chlorpromazine, cimetidine, dimenhydrinate, diphenhydramine, droperidol, fentanyl, glycopyrrolate, heparin, hydromorphone, hydroxyzine, hydroxyzine with meperidine, meperidine, meperidine with promethazine, metoclopramide, midazolam, milrinone, morphine, nalbuphine, ondansetron, pentazocine, perphenazine, prochlorperazine, promazine, promethazine, propiomazine, ranitidine, scopolamine, sufentanil. Incompatible: Cimetidine with pentobarbital. Variable (consult detailed reference): Pentobarbital.
Compatibility when admixed: Compatible: Dobutamine, furosemide, meropenem, sodium bicarbonate, verapamil. Incompatible: Floxacillin, metaraminol, methohexital, norepinephrine.
Mechanism of Action
Blocks the action of acetylcholine at parasympathetic sites in smooth muscle, secretory glands, and the CNS; increases cardiac output, dries secretions. Atropine reverses the muscarinic effects of cholinergic poisoning. The primary goal in cholinergic poisonings is reversal of bronchorrhea and bronchoconstriction. Atropine has no effect on the nicotinic receptors responsible for muscle weakness, fasciculations, and paralysis.
Pharmacodynamics/Kinetics
Onset of action: I.V.: Rapid
Absorption: Complete
Distribution: Widely throughout the body; crosses placenta; trace amounts enter breast milk; crosses blood-brain barrier
Metabolism: Hepatic
Half-life elimination: 2-3 hours
Excretion: Urine (30% to 50% as unchanged drug and metabolites)
Dosage
Neonates, Infants, and Children: Doses <0.1 mg have been associated with paradoxical bradycardia.
Inhibit salivation and secretions (preanesthesia): Oral, I.M., I.V., SubQ:
<5 kg: 0.02 mg/kg/dose 30-60 minutes preop then every 4-6 hours as needed. Use of a minimum dosage of 0.1 mg in neonates <5 kg will result in dosages >0.02 mg/kg. There is no documented minimum dosage in this age group.
>5 kg: 0.01-0.02 mg/kg/dose to a maximum 0.4 mg/dose 30-60 minutes preop; minimum dose: 0.1 mg
Alternate dosing:
3-7 kg (7-16 lb): 0.1 mg
8-11 kg (17-24 lb): 0.15 mg
11-18 kg (24-40 lb): 0.2 mg
18-29 kg (40-65 lb): 0.3 mg
>30 kg (>65 lb): 0.4 mg
Bradycardia: I.V., intratracheal: 0.02 mg/kg, minimum dose 0.1 mg, maximum single dose: 0.5 mg in children and 1 mg in adolescents; may repeat in 5-minute intervals to a maximum total dose of 1 mg in children or 2 mg in adolescents. (Note: For intratracheal administration, the dosage must be diluted with normal saline to a total volume of 1-5 mL). When treating bradycardia in neonates, reserve use for those patients unresponsive to improved oxygenation and epinephrine.
Infants and Children: Nerve agent toxicity management: See Note under adult dosing.
Prehospital (“in the field”): I.M.:
Birth to <2 years: Mild-to-moderate symptoms: 0.05 mg/kg; severe symptoms: 0.1 mg/kg
2-10 years: Mild-to-moderate symptoms: 1 mg; severe symptoms: 2 mg
>10 years: Mild-to-moderate symptoms: 2 mg; severe symptoms: 4 mg
Hospital/emergency department: I.M.:
Birth to <2 years: Mild-to-moderate symptoms: 0.05 mg/kg I.M. or 0.02 mg/kg I.V.; severe symptoms: 0.1 mg/kg I.M. or 0.02 mg/kg I.V.
2-10 years: Mild-to-moderate symptoms: 1 mg; severe symptoms: 2 mg
>10 years: Mild-to-moderate symptoms: 2 mg; severe symptoms: 4 mg
Note: Pralidoxime is a component of the management of nerve agent toxicity; consult Pralidoxime for specific route and dose. For prehospital (“in the field”) management, repeat atropine I.M. (children: 0.05-0.1 mg/kg) at 5-10 minute intervals until secretions have diminished and breathing is comfortable or airway resistance has returned to near normal. For hospital management, repeat atropine I.M. (infants 1 mg; all others: 2 mg) at 5-10 minute intervals until secretions have diminished and breathing is comfortable or airway resistance has returned to near normal.
Children: Organophosphate or carbamate poisoning:
I.V.: 0.03-0.05 mg/kg every 10-20 minutes until atropine effect, then every 1-4 hours for at least 24 hours
I.M. (AtroPen®): Mild symptoms: Administer dose listed below as soon as exposure is known or suspected. If severe symptoms develop after first dose, 2 additional doses should be repeated in 10 minutes; do not administer more than 3 doses. Severe symptoms: Immediately administer 3 doses as follows:
<6.8 kg (15 lb): Use of AtroPen® formulation not recommended; administer atropine 0.05 mg/kg
6.8-18 kg (15-40 lb): 0.5 mg/dose
18-41 kg (40-90 lb): 1 mg/dose
>41 kg (>90 lb): 2 mg/dose
Adults (doses <0.5 mg have been associated with paradoxical bradycardia):
Asystole or pulseless electrical activity:
I.V.: 1 mg; repeat in 3-5 minutes if asystole persists; total dose of 0.04 mg/kg.
Intratracheal: Administer 2-2.5 times the recommended I.V. dose; dilute in 10 mL NS or distilled water. Note: Absorption is greater with distilled water, but causes more adverse effects on PaO2.
Inhibit salivation and secretions (preanesthesia):
I.M., I.V., SubQ: 0.4-0.6 mg 30-60 minutes preop and repeat every 4-6 hours as needed
Oral: 0.4 mg; may repeat in 4 hours if necessary; 0.4 mg initial dose may be exceeded in certain cases and may repeat in 4 hours if necessary
Bradycardia: I.V.: 0.5-1 mg every 5 minutes, not to exceed a total of 3 mg or 0.04 mg/kg; may give intratracheally in 10 mL NS (intratracheal dose should be 2-2.5 times the I.V. dose)
Neuromuscular blockade reversal: I.V.: 25-30 mcg/kg 30-60 seconds before neostigmine or 7-10 mcg/kg 30-60 seconds before edrophonium
Organophosphate or carbamate poisoning: Note: The dose of atropine required varies considerably with the severity of poisoning. Total amount of atropine used in carbamate poisoning is usually less. Severely poisoned patients may exhibit significant tolerance to atropine; ?2 times the suggested doses may be needed. Titrate to pulmonary status (decreased bronchial secretions). Once patient is stable for a period of time, the dose/dosing frequency may be decreased. If atropinization occurs after 1-2 mg of atropine then re-evaluate working diagnosis.
I.V.: Initial: 1-5 mg; doses should be doubled every 5 minutes until signs of muscarinic excess abate (clearing of bronchial secretions, bronchospasm, and adequate oxygenation). Overly aggressive dosing may cause anticholinergic toxicity (eg, delirium, hyperthermia, and muscle twitching).
I.V. Infusion: 0.5-1 mg/hour or 10% to 20% of loading dose/hour
I.M. (AtroPen®): Mild symptoms: Administer 2 mg as soon as exposure is known or suspected. If severe symptoms develop after first dose, 2 additional doses should be repeated in 10 minutes; do not administer more than 3 doses. Severe symptoms: Immediately administer three 2 mg doses.
Nerve agent toxicity management: I.M.: See Note. Prehospital (“in the field”) or hospital/emergency department: Mild-to-moderate symptoms: 2-4 mg; severe symptoms: 6 mg
Note: Pralidoxime is a component of the management of nerve agent toxicity; consult Pralidoxime for specific route and dose. For prehospital (“in the field”) management, repeat atropine I.M. (2 mg) at 5-10 minute intervals until secretions have diminished and breathing is comfortable or airway resistance has returned to near normal. For hospital management, repeat atropine I.M. (2 mg) at 5-10 minute intervals until secretions have diminished and breathing is comfortable or airway resistance has returned to near normal.
Mydriasis, cycloplegia (preprocedure): Ophthalmic (1% solution): Instill 1-2 drops 1 hour before procedure.
Uveitis: Ophthalmic:
1% solution: Instill 1-2 drops 4 times/day
Ointment: Apply a small amount in the conjunctival sac up to 3 times/day; compress the lacrimal sac by digital pressure for 1-3 minutes after instillation
Elderly, frail patients: Nerve agent toxicity management (unlabeled use): I.M.: See Note under adult dosing.
Prehospital (“in the field”): Mild-to-moderate symptoms: 1 mg; severe symptoms: 2-4 mg
Hospital/emergency department: Mild-to-moderate symptoms: 1 mg; severe symptoms: 2 mg
Dental Usual Dosing
Inhibit salivation and secretions (preanesthesia): Adults (doses <0.5 mg have been associated with paradoxical bradycardia):
I.M., I.V., SubQ: 0.4-0.6 mg 30-60 minutes preop and repeat every 4-6 hours as needed
Oral: 0.4 mg; may repeat in 4 hours if necessary; 0.4 mg initial dose may be exceeded in certain cases and may repeat in 4 hours if necessary (see Dental Comment)
Administration: I.M.
AtroPen®: Administer to outer thigh. May be given through clothing as long as pockets at the injection site are empty. Hold autoinjector in place for 10 seconds following injection; massage the injection site.
Administration: I.V.
Administer undiluted by rapid I.V. injection; slow injection may result in paradoxical bradycardia.
Administration: Other
Intratracheal: Dilute in NS or distilled water. Absorption is greater with distilled water, but causes more adverse effects on PaO2. Pass catheter beyond tip of tracheal tube, stop compressions, spray drug quickly down tube. Follow immediately with several quick insufflations and continue chest compressions.
Administration: I.V. Detail
pH: 3-6.5; AtroPen®: pH: 4-5
Monitoring Parameters
Heart rate, blood pressure, pulse, mental status; intravenous administration requires a cardiac monitor
Patient Education
Take oral forms exactly as directed, 30 minutes before meals. Maintain adequate hydration (2-3 L/day of fluids) unless instructed to restrict fluid intake. Void before taking medication. You may experience dizziness, blurred vision, sensitivity to light (use caution when driving or engaging in tasks requiring alertness until response to drug is known); dry mouth, nausea, or vomiting (small frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help); orthostatic hypotension (use caution when climbing stairs and when rising from lying or sitting position); constipation (increased exercise, fluids, fruit, or fiber may help; if not effective, consult prescriber); increased sensitivity to heat and decreased perspiration (avoid extremes of heat, reduce exercise in hot weather); or decreased milk if breast-feeding. Report hot, dry, flushed skin; blurred vision or vision changes; difficulty swallowing; chest pain, palpitations, or rapid heartbeat; painful or difficult urination; increased confusion, depression, or loss of memory; rapid or difficult respirations; muscle weakness or tremors; or eye pain.
Ophthalmic: Instill as often as recommended. Wash hands before using. Sit or lie down, open eye, look at ceiling, and instill prescribed amount of solution. Do not blink for 30 seconds, close eye and roll eye in all directions, and apply gentle pressure to inner corner of eye for 1-2 minutes. Do not let tip of applicator touch eye; do not contaminate tip of applicator (may cause eye infection, eye damage, or vision loss). Temporary stinging or blurred vision may occur.
Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.
Geriatric Considerations
Anticholinergic agents are generally not well tolerated in the elderly and their use should be avoided when possible. In elderly, anticholinergic agents should not be used as prophylaxis against extrapyramidal symptoms.
Anesthesia and Critical Care Concerns/Other Considerations
Atropine, at usual recommended cardiovascular doses, causes blockade of muscarinic receptors at the cardiac SA-node and is parasympatholytic (ie, blocks vagal activity increasing heart rate). A dose 0.5-1 mg is recommended for the treatment of bradyarrhythmias. In administering atropine, it is important to recognize that lower doses (<0.5 mg) may have vagalmimetic effects (ie, increase vagal tone causing paradoxical bradycardia). A total dose of 3 mg (0.04 mg/kg) results in full vagal blockade in humans. In the absence of vascular access, atropine can be administered intratracheally.
Cardiovascular Considerations
Atropine, at usual recommended cardiovascular doses, causes blockade of muscarinic receptors at the cardiac SA-node and is parasympatholytic (ie, blocks vagal activity increasing heart rate). A dose 0.5-1 mg is recommended for the treatment of bradyarrhythmias. In administering atropine, it is important to recognize that lower doses (<0.5 mg) may have vagalmimetic effects (ie, increase vagal tone causing paradoxical bradycardia). It is likely that the vagal tonic effects of atropine are mediated by blockade of muscarinic receptors at the level of the brain. Thus, it is important that the recommended dose of atropine be administered by rapid intravenous injection. Slow injection may result in paradoxical bradycardia. Atropine is also recommended as part of the ACLS protocol. In this situation, in the absence of vascular access, atropine can be administered intratracheally. For intratracheal administration, the dosage must be diluted with normal saline to a total volume of 10 mL.
Atropine causes mydriasis which makes the pupils unable to be evaluated in a neurologic examination.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia and changes in salivation (normal salivary flow resumes upon discontinuation), dry throat, and nasal dryness
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Dental Comment
The possibility of the need for an initial dose in excess of 0.4 mg has been confirmed by the American Dental Association in its recommendation on the use of this medication to reduce salivation during dental procedures.
Mental Health: Effects on Mental Status
Use of injectable dosage form may cause ataxia, hallucinations, dizziness, amnesia, difficulty concentrating, agitation, delirium, paranoia, anxiety, and mania
Mental Health: Effects on Psychiatric Treatment
May decrease the effects of phenothiazines; concurrent use with psychotropics may result in additive anticholinergic side effects (dry mouth, blurred vision, constipation)
Nursing: Physical Assessment/Monitoring
Assess other medications patient may be taking for effectiveness and interactions. Monitor for tachycardia, hypotension especially if cardiac problems are present. Be alert to the potential of heat prostration in the presence of high temperatures. Assess knowledge/teach patient appropriate use, interventions to reduce side effects, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution, as sulfate: 0.05 mg/mL (5 mL); 0.1 mg/mL (5 mL, 10 mL); 0.4 mg/0.5 mL (0.5 mL); 0.4 mg/mL (0.5 mL, 1 mL, 20 mL); 1 mg/mL (1 mL)
AtroPen®: 0.25 mg/0.3 mL (0.3 mL); 0.5 mg/0.7 mL (0.7 mL); 1 mg/0.7 mL (0.7 mL); 2 mg/0.7 mL (0.7 mL) [prefilled autoinjector]
Ointment, ophthalmic, as sulfate: 1% (3.5 g)
Solution, ophthalmic, as sulfate: 1% (2 mL, 5 mL, 15 mL)
Atropine-Care®: 1% (2 mL) [contains benzalkonium chloride]
Isopto® Atropine: 1% (5 mL, 15 mL) [contains benzalkonium chloride]
Tablet, as sulfate:
Sal-Tropine™: 0.4 mg
Pricing: U.S. (www.drugstore.com)
Ointment (Atropine Sulfate)
1% (3.5): $8.99
Solution (Atropine Sulfate)
0.4 mg/mL (200): $23.14
1% (5): $8.99
1% (15): $12.99
Solution (Atropine-Care)
1% (2): $7.99
Solution (Isopto Atropine)
1% (5): $24.13
1% (15): $31.45
Tablets (Sal-Tropine)
0.4 mg (30): $19.99
References
American Academy of Pediatrics Committee on Drugs, “The Transfer of Drugs and Other Chemicals Into Human Milk,” Pediatrics, 2001, 108(3):776-89.
Eddleston M, Buckley NA, Checketts H, et al, “Speed of Initial Atropinisation in Significant Organophosphorus Pesticide Poisoning - A Systematic Comparison of Recommended Regimens,” J Toxicol Clin Toxicol, 2004, 42(6):865-75.
Eisenberg MS and Mengert TJ, “Cardiac Resuscitation,” N Engl J Med, 2001, 344(17):1304-13.
Emergency Cardiac Care Committee and Subcommittees, “2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiac Care,” Circulation, 2005, 112(24 Suppl):V1-203.
“Medical Management Guidelines (MMGs) for Nerve Agents: Tabun (GA); Sarin (GB); Soman (GD); and VX.” Available at: www.atsdr.cdc.gov/MHMI/mmg166.html. Accessed January 8, 2003.
Mokhlesi B, Leikin JB, Murray P, et al, “Adult Toxicology in Critical Care: Part II: Specific Poisonings,” Chest, 2003, 123(3):897-922.
Reigart JR and Roberts JR, “Recognition And Management Of Pesticide Poisonings,” U.S. Environmental Protection Agency, Washington, D.C., 5th edition, 1999: 34-47, available at http://www.epa.gov/pesticides/safety/healthcare.
International Brand Names
Lexi-Comp.com
Last full review/revision August 2008
Content last modified August 2008
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