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Edrophonium and Atropine

Pronunciation

(ed roe FOE nee um & A troe peen)

Index Terms

  • Atropine Sulfate and Edrophonium Chloride
  • Edrophonium Chloride and Atropine Sulfate
  • Edrophonium Chloride/Atropine

Dosage Forms

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

Solution, Intravenous:

Enlon-Plus: Edrophonium chloride 10 mg/mL and atropine sulfate 0.14 mg/mL (15 mL [DSC]) [contains phenol, sodium sulfite]

Enlon-Plus: Edrophonium chloride 10 mg/mL and atropine sulfate 0.14 mg/mL (5 mL [DSC]) [contains sodium sulfite]

Brand Names: U.S.

  • Enlon-Plus [DSC]

Pharmacologic Category

  • Acetylcholinesterase Inhibitor
  • Anticholinergic Agent
  • Antidote

Pharmacology

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).

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.

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.

Dosing: Renal Impairment

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

Dosing: Hepatic Impairment

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

Administration

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

AbobotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of AbobotulinumtoxinA. Monitor therapy

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

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

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

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

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

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. Avoid combination

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

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. Avoid combination

OnabotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of OnabotulinumtoxinA. 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

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

RimabotulinumtoxinB: Anticholinergic Agents may enhance the anticholinergic effect of RimabotulinumtoxinB. Monitor therapy

Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid using drugs with substantial anticholinergic effects in patients receiving secretin whenever possible. If such agents must be used in combination, monitor closely for a diminished response to secretin. 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 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 polyuria. Have patient report immediately to prescriber abnormal heartbeat, difficulty breathing, slow breathing, shallow breathing, severe dizziness, passing out, seizures, difficulty speaking, difficulty swallowing, bradycardia, tachycardia, 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.

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