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Edrophonium and Atropine

Generic name: atropine/edrophonium systemic

Brand names: Enlon-Plus

Pharmacology

Mechanism of Action

Edrophonium: Inhibits destruction of acetylcholine by acetylcholinesterase. This facilitates transmission of impulses across myoneural junction and results in increased cholinergic response.

Atropine: Minimizes or prevents the muscarinic cholinergic effects caused by edrophonium (eg, bradycardia, bronchoconstriction, increased secretions).

Pharmacokinetics/Pharmacodynamics

Excretion

Edrophonium: Primarily urine (67%)

Onset of Action

Edrophonium: Antagonism of nondepolarizing muscle relaxants: 3 minutes; Atropine: Heart rate: Immediate

Time to Peak

Edrophonium: Antagonism of nondepolarizing muscle relaxants: 1.2 minutes; Atropine: Heart rate: 2 to 16 minutes

Duration of Action

Edrophonium: Antagonism of nondepolarizing muscle relaxants: 70 minutes; Atropine: Heart rate: 170 minutes

Half-Life Elimination

Edrophonium: Adults: 1.2 to 2.4 hours; Anephric patients: 2.4 to 4.4 hours

Protein Binding

Atropine: ~14%

Use: Labeled Indications

Respiratory depression caused by curare overdosage: Adjunctive treatment of respiratory depression caused by curare overdosage.

Reversal of nondepolarizing neuromuscular blocking agents: Reversal of nondepolarizing neuromuscular-blocking agents.

Contraindications

Hypersensitivity to edrophonium, atropine, or any component of the formulation; intestinal or urinary obstruction of the mechanical type. Atropine is contraindicated in acute glaucoma, adhesions (synechiae) between the iris and lens of the eye, and pyloric stenosis.

Documentation of allergenic cross-reactivity for anticholinesterase muscle stimulants is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosage and Administration

Dosing: Adult

Note: Enlon-Plus is no longer available in the U.S.

Reversal of neuromuscular blockade: IV: 0.05 to 0.1 mL/kg given over 45 to 60 seconds. The dose delivered is 0.5 to 1 mg/kg of edrophonium and 0.007 to 0.014 mg/kg of atropine. An edrophonium dose of 1 mg/kg should rarely be exceeded. Note: Monitor closely for bradyarrhythmias.

Dosing: Geriatric

Refer to adult dosing.

Administration

IV: Administer IV slowly over 45 seconds to 1 minute at a point of at least 5% recovery of twitch response to neuromuscular stimulation (95% block).

Storage

Store at 20°C to 25°C (68°F to 77°F).

Drug Interactions

Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Monitor therapy

Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Amantadine: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy

Amezinium: Atropine (Systemic) may enhance the stimulatory effect of Amezinium. Monitor therapy

Amifampridine: Acetylcholinesterase Inhibitors may enhance the therapeutic effect of Amifampridine. Amifampridine side effects may also be increased. Amifampridine may enhance the therapeutic effect of Acetylcholinesterase Inhibitors. Acetylcholinesterase inhibitor side effects may also be increased. Monitor therapy

Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Monitor therapy

Anticholinergic Agents: Acetylcholinesterase Inhibitors may diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Monitor therapy

Benoxinate: Acetylcholinesterase Inhibitors may enhance the therapeutic effect of Benoxinate. Specifically, the effects of benoxinate may be prolonged. Monitor therapy

Beta-Blockers: Acetylcholinesterase Inhibitors may enhance the bradycardic effect of Beta-Blockers. Exceptions: Levobunolol; Metipranolol. Monitor therapy

Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy

Cannabinoid-Containing Products: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Exceptions: Cannabidiol. Monitor therapy

Cardiac Glycosides: Edrophonium may enhance the AV-blocking effect of Cardiac Glycosides. Monitor therapy

Chloral Betaine: May enhance the adverse/toxic effect of Anticholinergic Agents. Monitor therapy

Cholinergic Agonists: Acetylcholinesterase Inhibitors may enhance the adverse/toxic effect of Cholinergic Agonists. Monitor therapy

Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Avoid combination

Corticosteroids (Systemic): May enhance the adverse/toxic effect of Acetylcholinesterase Inhibitors. Increased muscular weakness may occur. Monitor therapy

Dipyridamole: May diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Monitor therapy

Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Avoid combination

EPHEDrine (Systemic): Atropine (Systemic) may enhance the therapeutic effect of EPHEDrine (Systemic). Monitor therapy

Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Monitor therapy

Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Monitor therapy

Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Avoid combination

Glycopyrronium (Topical): May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Monitor therapy

Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Avoid combination

Macimorelin: Atropine (Systemic) may diminish the diagnostic effect of Macimorelin. Avoid combination

Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy

Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Monitor therapy

Neuromuscular-Blocking Agents (Nondepolarizing): Acetylcholinesterase Inhibitors may diminish the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Nitroglycerin: Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Monitor therapy

Opioid Agonists: Anticholinergic Agents may enhance the adverse/toxic effect of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination. Monitor therapy

Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Avoid combination

Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. Avoid combination

Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Consider therapy modification

Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Monitor therapy

Revefenacin: Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin. Avoid combination

Ritodrine: Atropine (Systemic) may enhance the adverse/toxic effect of Ritodrine. Monitor therapy

Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Consider therapy modification

Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Consider therapy modification

Succinylcholine: Acetylcholinesterase Inhibitors may increase the serum concentration of Succinylcholine. Management: Consider alternatives to this combination due to a risk of prolonged neuromuscular blockade. Consider therapy modification

Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Avoid combination

Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Monitor therapy

Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Adverse Reactions

See individual agents.

Warnings/Precautions

Concerns related to adverse effects:

  • Anticholinesterase insensitivity: If patient becomes insensitive to the drug, reduce dose or discontinue edrophonium until patient sensitive again.
  • Respiratory arrest: Rare reports of respiratory arrest have occurred with edrophonium.
  • Tissue irritation: May cause tissue irritation if extravasated.

Disease-related concerns:

  • Arrhythmias: Use with caution in patients with cardiac arrhythmias (eg, bradyarrhythmias).
  • Asthma: Use with caution in patients with bronchial asthma.
  • Chronic lung disease: Use with caution in patients with chronic lung disease.
  • Prostatic hyperplasia: Use with caution in patients with prostatic hyperplasia.
  • Myasthenia gravis: Avoid use in myasthenia gravis; may exacerbate muscular weakness.

Concurrent drug therapy issues:

  • Anticholinergics: Consider additive adverse effects with concurrent use of atropine and other anticholinergics (eg, tricyclic antidepressants, antipsychotics, some antihistamines, anti-Parkinson drugs).
  • Atropine: Patients who are bradycardic or at risk of being bradycardic (eg, those on a beta-blocker or cardiovascular patients who received anesthesia with an opioid and nitrous oxide only) should first receive atropine prior to edrophonium-atropine combination. Most arrhythmias occur within 2 minutes of administration and reverse shortly thereafter. Atropine should be available for immediate use in case of severe cholinergic reaction. Bradyarrhythmias respond to small doses of atropine.
  • Nondepolarizing muscle relaxants: Should not be administered before any nondepolarizing muscle relaxant.

Dosage form specific issues:

  • Sodium sulfite: Products may contain sodium sulfite.

Monitoring Parameters

Vital signs, ECG, and ventilatory support; neuromuscular function

Pregnancy

Pregnancy Risk Factor

C

Pregnancy Considerations

Animal reproduction studies have not been conducted with this combination. Refer to individual agents.

Patient Education

  • Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
  • Patient may experience dry mouth, nausea, vomiting, diarrhea, abdominal cramps, loss of strength and energy, sweating a lot, or passing a lot of urine. Have patient report immediately to prescriber abnormal heartbeat, difficulty breathing, slow breathing, shallow breathing, severe dizziness, passing out, seizures, difficulty speaking, difficulty swallowing, slow heartbeat, fast heartbeat, or severe injection site redness, burning, or pain (HCAHPS).
  • Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Source: Wolters Kluwer Health. Last updated January 15, 2020.