What are the primary uses of edrophonium. How does edrophonium work in the body. What are the potential side effects of edrophonium administration. Why is edrophonium no longer used for myasthenia gravis diagnosis. How is edrophonium administered for different purposes.

Understanding Edrophonium: A Rapid-Acting Acetylcholinesterase Inhibitor

Edrophonium is a synthetic compound that has played a significant role in neuromuscular medicine for decades. As a reversible acetylcholinesterase inhibitor, it has been utilized for various medical purposes, primarily in the diagnosis and management of neuromuscular disorders. Its rapid onset and short duration of action make it a unique tool in the medical arsenal, though its use has evolved over time due to advancements in diagnostic techniques and the development of alternative treatments.

Key Characteristics of Edrophonium

• Rapid onset of action (within 1 minute)
• Short duration of effect (approximately 10 minutes)
• Reversible inhibition of acetylcholinesterase
• Increases acetylcholine levels in the neuromuscular junction

Historical and Current Indications for Edrophonium Use

Edrophonium has been employed in various medical scenarios, with its primary applications changing over time due to advancements in medical knowledge and diagnostic techniques.

Diagnosis of Myasthenia Gravis

Historically, edrophonium was widely used in the diagnosis of myasthenia gravis (MG), a neuromuscular disorder characterized by muscle weakness. The drug was marketed as the Tensilon test and was FDA-approved for this purpose. However, why is edrophonium no longer used for MG diagnosis? The FDA discontinued its approval in 2018 due to high rates of false-positive results and the development of more accurate serological antibody testing, which has become the gold standard for diagnosing MG.

Differential Diagnosis: Myasthenic Crisis vs. Cholinergic Crisis

Edrophonium was also employed to differentiate between myasthenic crisis and cholinergic crisis in MG patients. This application relied on the drug’s ability to temporarily improve symptoms in myasthenic crisis while potentially worsening symptoms in cholinergic crisis.

Reversal of Neuromuscular Blocking Agents

Currently, edrophonium remains FDA-approved for reversing the effects of non-depolarizing neuromuscular blocking agents (NMBAs) after surgical procedures. However, it is worth noting that neostigmine is generally preferred for this purpose due to its longer duration of action and higher potency.

Potential Novel Applications

Research is ongoing into new potential uses for edrophonium. One area of investigation is its possible application in diagnosing blepharospasm, though further studies are needed before this can be incorporated into clinical practice.

Mechanism of Action: How Edrophonium Works in the Body

To understand how edrophonium exerts its effects, it’s crucial to examine its interaction with the neuromuscular system.

The Role of Acetylcholine in Neuromuscular Function

Acetylcholine is a neurotransmitter synthesized and stored in presynaptic neurons of the neuromuscular junction (NMJ). When released, it binds to postsynaptic nicotinic acetylcholine receptors, facilitating muscle contraction. Under normal circumstances, acetylcholinesterase enzymes rapidly break down acetylcholine, terminating its effects.

Edrophonium’s Inhibitory Action

How does edrophonium work in the body? Edrophonium functions as a competitive inhibitor of acetylcholinesterase. It forms non-covalent bonds at the serine-103 allosteric site of these enzymes, preventing them from breaking down acetylcholine. This inhibition results in increased levels of acetylcholine in the neuromuscular junction.

Effects on Myasthenia Gravis Symptoms

In patients with myasthenia gravis, the increased acetylcholine levels temporarily overcome the antibody-mediated blockade of nicotinic receptors. This leads to a brief improvement in muscle strength, which was the basis for its use in diagnosing the condition.

Administration of Edrophonium: Methods and Considerations

The administration of edrophonium varies depending on its intended use. While some applications are now obsolete, understanding these methods provides insight into the drug’s properties and potential effects.

Myasthenia Gravis Diagnosis (Historical Method)

How was edrophonium administered for MG diagnosis? The test was performed incrementally:

1. An initial dose of 2 mg was administered intravenously (IV)
2. Additional 2 mg doses were given at 60-second intervals
3. The process continued until symptoms improved or a total dose of 10 mg was reached
4. Atropine (0.4 to 0.6 mg) was kept ready to counteract potential severe side effects

Differentiating Myasthenic and Cholinergic Crisis

For this purpose, administration involved:

• Preparing a tuberculin syringe with 1 mL (10 mg) of edrophonium
• Administering 0.2 mL (2 mg) intravenously
• Observing for cholinergic reactions (e.g., muscle fasciculations, increased weakness)
• Discontinuing administration and providing atropine if cholinergic crisis was suspected

Reversal of Neuromuscular Blockade

When used to reverse non-depolarizing NMBAs, edrophonium is typically administered with atropine to minimize muscarinic side effects. If glycopyrronium is used instead of atropine, it should be given a few minutes before edrophonium due to its slower onset of action.

Side Effects and Safety Considerations of Edrophonium

What are the potential side effects of edrophonium administration? As with any medication, edrophonium can cause various adverse effects, ranging from mild to severe. Understanding these potential reactions is crucial for safe use and appropriate patient monitoring.

Common Side Effects

• Nausea and vomiting
• Increased salivation
• Sweating
• Dizziness
• Muscle cramps or twitching

Serious Adverse Reactions

More severe side effects can occur, particularly in susceptible individuals or with higher doses:

• Bradycardia (slow heart rate)
• Bronchospasm
• Syncope (fainting)
• Seizures
• Severe allergic reactions

Precautions and Contraindications

Edrophonium should be used with caution in patients with:

• Cardiovascular disease
• Asthma or other respiratory conditions
• History of seizures
• Urinary tract obstruction
• Hyperthyroidism

It is contraindicated in patients with known hypersensitivity to the drug or mechanical obstruction of the intestinal or urinary tract.

Alternatives to Edrophonium in Modern Medicine

As medical science has advanced, several alternatives to edrophonium have emerged for its various applications.

Diagnosis of Myasthenia Gravis

Serological antibody testing has largely replaced the edrophonium test for diagnosing MG. This method offers higher accuracy and fewer risks. Other diagnostic tools include:

• Electromyography (EMG)
• Repetitive nerve stimulation tests
• Single-fiber EMG
• Imaging studies (e.g., CT or MRI of the chest to check for thymoma)

Reversal of Neuromuscular Blockade

Neostigmine is now preferred over edrophonium for reversing non-depolarizing NMBAs due to its longer duration of action and higher potency. Other options include:

• Sugammadex: A selective relaxant binding agent specifically designed to reverse certain NMBAs
• Pyridostigmine: Another acetylcholinesterase inhibitor with a longer duration of action than edrophonium

Future Perspectives: Potential New Applications for Edrophonium

While edrophonium’s use has declined in some areas, researchers continue to explore its potential in other medical fields.

Diagnosis of Blepharospasm

Preliminary studies suggest that edrophonium may have a role in diagnosing blepharospasm, a condition characterized by involuntary eye muscle contractions. The edrophonium challenge test has shown promise in augmenting the clinical features of this disorder, potentially aiding in its diagnosis. However, further research is needed to validate this approach and establish standardized protocols.

Neurodegenerative Disorders

Some researchers are investigating the potential of acetylcholinesterase inhibitors, including edrophonium, in managing certain neurodegenerative disorders. While most of this research focuses on longer-acting drugs like donepezil, edrophonium’s rapid action could potentially offer insights into disease mechanisms or serve as a model for developing new therapeutic agents.

Anesthesiology Research

In the field of anesthesiology, edrophonium continues to be a valuable tool for studying neuromuscular physiology and pharmacology. Its well-characterized effects and short duration make it useful for investigating neuromuscular junction function and the effects of various anesthetic agents.

As medical knowledge continues to evolve, it’s possible that new applications for edrophonium may emerge. While its role has diminished in some areas, its unique pharmacological profile ensures that it remains a subject of interest in neuromuscular medicine and related fields.

Edrophonium – StatPearls – NCBI Bookshelf

Abdullah Naji; Michael L. Owens.

Author Information and Affiliations

Last Update: September 3, 2022.

Indications

Edrophonium is a reversible acetylcholinesterase inhibitor with rapid onset and short duration of action resulting in an increase of acetylcholine in the neuromuscular junction (NMJ).[1] Since the early 1930s, it has been a diagnostic tool for myasthenia gravis (MG). MG is a neuromuscular disorder characterized by muscular weakness due to antibody production that inhibits or destroys post-synaptic nicotinic acetylcholine receptors in the NMJ. Muscle weakness in MG presents as ptosis, diplopia, dysarthria, and dysphagia and can progress to fatal respiratory depression in critically ill patients. For many years, edrophonium, marketed as the Tensilon test, was FDA-approved to be utilized to diagnose MG.

Edrophonium was classically used for differentiation of cholinergic crisis from the myasthenic crisis. [2] Edrophonium briefly ameliorated the symptoms of MG by increasing the amount of acetylcholine in the NMJ synapses. The increased levels of acetylcholine in the NMJ resulted in brief improvements in skeletal and muscular strength in MG patients. Edrophonium’s historical use was in MG patients with ptosis or extraocular muscle weaknesses with immediate improvement upon drug administration. As of 2018, the FDA discontinued edrophonium, which is no longer available in the United States due to its high rate of false-positive results and the development of serological antibody testing as the gold standard for diagnosing MG.[3]

Edrophonium is FDA-approved for use in the reversal of non-depolarizing neuromuscular blocking agents (NMBA) after a surgical procedure. Nonetheless, neostigmine is preferably utilized instead of edrophonium to reverse non-depolarizing NMBA.[4] Neostigmine has a longer duration of action, and it is 12 to 16 times more potent than edrophonium making it more effective in reversing long-acting non-depolarizing NMBA. In rare cases, when using edrophonium as a reversing agent, it is administered simultaneously with atropine to minimize the muscarinic side effects. If administering glycopyrronium with edrophonium, its administration must be a few minutes before edrophonium since it has a slower onset of action.[5][6]

Novel use of edrophonium challenge test for diagnosis of blepharospasm has been suggested. The clinical features of blepharospasm are augmented by edrophonium. However, further research is needed before instituting this test into clinical practice.[7]

Mechanism of Action

Acetylcholine synthesis and storage occur in the presynaptic neurons of the NMJ. Acetylcholine binds to postsynaptic nicotinic acetylcholine receptors upon its release from the presynaptic neurons. In the NMJ, acetylcholine is metabolized by acetylcholinesterases via hydrolysis, attenuating its physiological effects. Edrophonium is a synthetic short-acting acetylcholinesterase competitive inhibitor that functions by forming non-covalent bonds at the serine-103 allosteric site of acetylcholinesterase enzymes. Thus, edrophonium increases the amount of acetylcholine in the NMJ synapses. The higher amounts of acetylcholine in the NMJ synapses overcome the antibodies on the nicotinic receptors in MG, resulting in a brief improvement of muscular strength. Edrophonium has a rapid onset of action occurring within 1 minute of administration and a short duration of action lasting 10 minutes.[8][9]

Administration

Diagnosis of Myasthenia Gravis: The edrophonium test for MG diagnosis is performed in an incremental approach. Initially, the patient receives 2 mg intravenously (IV) of edrophonium. After each 60-second interval, the patient will receive another 2 mg IV dose until the symptoms improve. MG symptoms usually improve after 4 to 6 mg for most patients. Therefore, this incremental approach of administering 2 mg doses every 60 seconds prevents unnecessary muscarinic side effects. 0.4 to 0.6 mg of atropine must be readily available when performing the Tensilon test. Atropine is reserved for situations where serious side effects of bradycardia or bronchospasm manifest in patients receiving edrophonium. [1][10]

Differential Diagnosis of Myasthenia Gravis vs. Cholinergic Crisis: A tuberculin syringe containing 1 mL (10 mg) of edrophonium is prepared with an intravenous needle of 0.2 mL (2 mg) and is administered intravenously. The needle is left in situ. If there is a cholinergic reaction (skeletal muscle fasciculations and increased muscle weakness)  after administering the edrophonium, the drug is immediately discontinued, and atropine is administered intravenously.

Reversal of Neuromuscular Block: Edrophonium is rarely used to reverse non-depolarizing NMBA after a surgical procedure. Nonetheless, for the rare cases where it is used, an IV dose of 0.5 to 1.0 mg/kg of edrophonium is either simultaneously administered with atropine or a few minutes after glycopyrrolate to prevent bradycardia and other cholinergic adverse effects.[11]

Use in the Specific Patient Population

Patients with Hepatic Impairment: No information has been provided in the manufacturer’s product labeling regarding the use of edrophonium in patients with hepatic impairment.

Patients with Renal Impairment: No information has been provided in the manufacturer’s product labeling regarding the use of edrophonium in patients with renal impairment.

Pregnancy Considerations: The safety of edrophonium use during pregnancy has not been established according to the manufacturer’s product labeling.

Breastfeeding Considerations: Edrophonium has a short half-life and quaternary ammonium structure; hence it is unlikely to be excreted into breastmilk or orally absorbed by the infant. Administering the edrophonium just after breastfeeding and waiting 2 to 3 hours before breastfeeding should avoid any adverse drug reactions in the infant. There is no information regarding the use of edrophonium during breastfeeding. Therefore, using edrophonium in nursing mothers requires risk-benefit analysis considering possible hazards to mother and child.[12]

Adverse Effects

The adverse effects of edrophonium occur due to the increased levels of acetylcholine binding to muscarinic acetylcholine receptors. The more serious adverse effects are cardiac arrhythmias, especially bradycardia, atrioventricular block, and cardiac arrest. The muscarinic cholinergic adverse effects also include bronchoconstriction due to airway smooth muscle contraction secondary to increased stimulation of muscarinic receptors. Other adverse effects include bronchial secretions, diarrhea, salivation, lacrimation, increased urinary frequency and urgency, and miosis. Clinicians can attenuate most of the adverse effects with the simultaneous administration of atropine, which functions as a muscarinic receptor antagonist to prevent developing these cholinergic adverse effects.[13]

Contraindications

Absolute contraindications to edrophonium include hypersensitivity to edrophonium patients with gastrointestinal and urinary obstruction. Edrophonium administration requires extreme vigilance and monitoring in patients with cardiac arrhythmias and asthma. Physicians are cautious with the use of edrophonium in asthmatic patients due to possible oxygen desaturation from bronchoconstriction and increased bronchial secretions. In the setting of non-depolarizing NMBA reversal, edrophonium administration is contraindicated and cannot be administered when the peripheral nerve stimulation does not elicit at least one twitch.

According to the manufacturer’s product labeling information, the excipient contains sodium sulfite, which may cause allergic reactions, including anaphylaxis. The clinical presentation of sulfite allergy includes hives, rhinorrhea, bronchoconstriction, flushing, and cardiovascular collapse. Hence use with extreme caution in patients with sulfite allergy.[14]

Monitoring

Heart, respiratory, and blood pressure require monitoring when administering edrophonium. In using edrophonium for MG diagnosis, a cumulative dose of 10 mg is the recommended maximum to prevent excessive cholinergic muscarinic side effects.[15] According to the manufacturer’s labeling, whenever edrophonium is used for testing, a syringe containing 1 mg of atropine sulfate should be immediately available to be given intravenously to counteract severe cholinergic reactions.

Toxicity

Overdose of edrophonium will result in muscarinic symptoms due to the cholinergic crisis manifested by excessive acetylcholine binding to muscarinic receptors. The cholinergic crisis includes diarrhea, increased urination, miosis, muscle weakness, bronchospasm, bradycardia, emesis, and lacrimation. The more serious outcomes of edrophonium overdose involve respiratory muscle weakness and cardiac arrhythmias that can progress to a fatal outcome. Hence, clinicians must ensure patent airway and circulation. The treatment of an edrophonium overdose is atropine. Atropine is an ideal antidote for edrophonium since it has a similar onset of action as edrophonium. Atropine functions by competitively inhibiting the muscarinic receptors on structures innervated by postganglionic cholinergic nerves and inhibiting muscarinic receptors on smooth muscle. Atropine can be administered up to 1.2 mg intravenously initially and repeated every 20 minutes until secretions are controlled. If convulsions are present, clinicians should institute appropriate supportive measures. For convulsions, supportive treatment is required.[16]

Enhancing Healthcare Team Outcomes

Neurologists and other healthcare providers historically utilized edrophonium to aid in diagnosing MG. In rare situations, it can be a reversal agent for non-depolarizing NMBA after a surgical procedure. Edrophonium’s adverse effects manifest due to its cholinergic profile. The adverse effects of edrophonium can progress to fatal outcomes secondary to respiratory muscle weakness or cardiac arrhythmias. Therefore, it is imperative that healthcare workers utilizing edrophonium monitor vital signs closely and have atropine readily available; this requires working as an interprofessional healthcare team that includes clinicians, specialists, nurses, and pharmacists. Myasthenia gravis (MG) is a chronic medical condition requiring high coordination among professionals and disciplines. The care pathway model has been described. A study examined the comprehensive and multidisciplinary care for diagnosing and treating patients with myasthenia gravis. The study concluded that the interprofessional care pathway model for myasthenia gravis could help achieve better patient outcomes.[17]

The administration of edrophonium and the management of its adverse effects is enhanced when using an interprofessional healthcare team approach. Pharmacists should be consulted for information regarding dosing, drug-drug interactions, and contraindications for patients with extensive comorbidities. Nursing staff must be educated on the adverse effect profile of edrophonium and recognize when the patient is decompensating since, in many situations, they are the sole healthcare worker caring for the patient. Ultimately, an interprofessional approach to using and monitoring edrophonium will ensure appropriate administration, adequate management of adverse effects, and prevention of fatal outcomes. [Level 5]

Review Questions

• Access free multiple choice questions on this topic.

• Comment on this article.

References

1.

Pascuzzi RM. The edrophonium test. Semin Neurol. 2003 Mar;23(1):83-8. [PubMed: 12870109]

2.

Gilhus NE. Myasthenia Gravis. N Engl J Med. 2016 Dec 29;375(26):2570-2581. [PubMed: 28029925]

3.

Motomura M, Fukuda T. [Lambert-Eaton myasthenic syndrome]. Brain Nerve. 2011 Jul;63(7):745-54. [PubMed: 21747145]

4.

Pani N, Dongare PA, Mishra RK. Reversal agents in anaesthesia and critical care. Indian J Anaesth. 2015 Oct;59(10):664-9. [PMC free article: PMC4645356] [PubMed: 26644615]

5.

Zafirova Z, Dalton A. Neuromuscular blockers and reversal agents and their impact on anesthesia practice. Best Pract Res Clin Anaesthesiol. 2018 Jun;32(2):203-211. [PubMed: 30322460]

6.

Katz RL. Neuromuscular effects of d-tubocurarine, edrophonium and neostigmine in man. Anesthesiology. 1967 Mar-Apr;28(2):327-36. [PubMed: 6026052]

7.

Matsumoto S, Murakami N, Koizumi H, Takahashi M, Izumi Y, Kaji R. Edrophonium Challenge Test for Blepharospasm. Front Neurosci. 2016;10:226. [PMC free article: PMC4894005] [PubMed: 27375406]

8.

ROBERTS DV. THE ANATOMY AND PHYSIOLOGY OF THE NEUROMUSCULAR JUNCTION. Br J Anaesth. 1963 Sep;35:510-20. [PubMed: 14066100]

9.

Thapa S, Lv M, Xu H. Acetylcholinesterase: A Primary Target for Drugs and Insecticides. Mini Rev Med Chem. 2017;17(17):1665-1676. [PubMed: 28117022]

10.

Ing EB, Ing SY, Ing T, Ramocki JA. The complication rate of edrophonium testing for suspected myasthenia gravis. Can J Ophthalmol. 2000 Apr;35(3):141-4; discussion 145. [PubMed: 10812483]

11.

Engbaek J, Ording H, Ostergaard D, Viby-Mogensen J. Edrophonium and neostigmine for reversal of the neuromuscular blocking effect of vecuronium. Acta Anaesthesiol Scand. 1985 Jul;29(5):544-6. [PubMed: 2863917]

12.

Drugs and Lactation Database (LactMed®) [Internet]. National Institute of Child Health and Human Development; Bethesda (MD): Dec 3, 2018. Edrophonium. [PubMed: 29999829]

13.

Ohbe H, Jo T, Matsui H, Fushimi K, Yasunaga H. Cholinergic Crisis Caused by Cholinesterase Inhibitors: a Retrospective Nationwide Database Study. J Med Toxicol. 2018 Sep;14(3):237-241. [PMC free article: PMC6097965] [PubMed: 29907949]

14.

Burbridge MA, Jaffe RA. Excipients in Anesthesia Medications. Anesth Analg. 2019 May;128(5):891-900. [PubMed: 29505449]

15.

Seybold ME. The office Tensilon test for ocular myasthenia gravis. Arch Neurol. 1986 Aug;43(8):842-3. [PubMed: 3729766]

16.

Drugs and Lactation Database (LactMed®) [Internet]. National Institute of Child Health and Human Development; Bethesda (MD): May 17, 2021. Belladonna. [PubMed: 30000920]

17.

Payedimarri AB, Ratti M, Rescinito R, Vasile A, Seys D, Dumas H, Vanhaecht K, Panella M. Development of a Model Care Pathway for Myasthenia Gravis. Int J Environ Res Public Health. 2021 Nov 04;18(21) [PMC free article: PMC8582978] [PubMed: 34770107]

Disclosure: Abdullah Naji declares no relevant financial relationships with ineligible companies.

Disclosure: Michael Owens declares no relevant financial relationships with ineligible companies.

Edrophonium – StatPearls – NCBI Bookshelf

Abdullah Naji; Michael L. Owens.

Author Information and Affiliations

Last Update: September 3, 2022.

Indications

Edrophonium is a reversible acetylcholinesterase inhibitor with rapid onset and short duration of action resulting in an increase of acetylcholine in the neuromuscular junction (NMJ).[1] Since the early 1930s, it has been a diagnostic tool for myasthenia gravis (MG). MG is a neuromuscular disorder characterized by muscular weakness due to antibody production that inhibits or destroys post-synaptic nicotinic acetylcholine receptors in the NMJ. Muscle weakness in MG presents as ptosis, diplopia, dysarthria, and dysphagia and can progress to fatal respiratory depression in critically ill patients. For many years, edrophonium, marketed as the Tensilon test, was FDA-approved to be utilized to diagnose MG.

Edrophonium was classically used for differentiation of cholinergic crisis from the myasthenic crisis.[2] Edrophonium briefly ameliorated the symptoms of MG by increasing the amount of acetylcholine in the NMJ synapses. The increased levels of acetylcholine in the NMJ resulted in brief improvements in skeletal and muscular strength in MG patients. Edrophonium’s historical use was in MG patients with ptosis or extraocular muscle weaknesses with immediate improvement upon drug administration. As of 2018, the FDA discontinued edrophonium, which is no longer available in the United States due to its high rate of false-positive results and the development of serological antibody testing as the gold standard for diagnosing MG.[3]

Edrophonium is FDA-approved for use in the reversal of non-depolarizing neuromuscular blocking agents (NMBA) after a surgical procedure. Nonetheless, neostigmine is preferably utilized instead of edrophonium to reverse non-depolarizing NMBA.[4] Neostigmine has a longer duration of action, and it is 12 to 16 times more potent than edrophonium making it more effective in reversing long-acting non-depolarizing NMBA. In rare cases, when using edrophonium as a reversing agent, it is administered simultaneously with atropine to minimize the muscarinic side effects. If administering glycopyrronium with edrophonium, its administration must be a few minutes before edrophonium since it has a slower onset of action.[5][6]

Novel use of edrophonium challenge test for diagnosis of blepharospasm has been suggested. The clinical features of blepharospasm are augmented by edrophonium. However, further research is needed before instituting this test into clinical practice.[7]

Mechanism of Action

Acetylcholine synthesis and storage occur in the presynaptic neurons of the NMJ. Acetylcholine binds to postsynaptic nicotinic acetylcholine receptors upon its release from the presynaptic neurons. In the NMJ, acetylcholine is metabolized by acetylcholinesterases via hydrolysis, attenuating its physiological effects. Edrophonium is a synthetic short-acting acetylcholinesterase competitive inhibitor that functions by forming non-covalent bonds at the serine-103 allosteric site of acetylcholinesterase enzymes. Thus, edrophonium increases the amount of acetylcholine in the NMJ synapses. The higher amounts of acetylcholine in the NMJ synapses overcome the antibodies on the nicotinic receptors in MG, resulting in a brief improvement of muscular strength. Edrophonium has a rapid onset of action occurring within 1 minute of administration and a short duration of action lasting 10 minutes.[8][9]

Administration

Diagnosis of Myasthenia Gravis: The edrophonium test for MG diagnosis is performed in an incremental approach. Initially, the patient receives 2 mg intravenously (IV) of edrophonium. After each 60-second interval, the patient will receive another 2 mg IV dose until the symptoms improve. MG symptoms usually improve after 4 to 6 mg for most patients. Therefore, this incremental approach of administering 2 mg doses every 60 seconds prevents unnecessary muscarinic side effects. 0.4 to 0.6 mg of atropine must be readily available when performing the Tensilon test. Atropine is reserved for situations where serious side effects of bradycardia or bronchospasm manifest in patients receiving edrophonium.[1][10]

Differential Diagnosis of Myasthenia Gravis vs. Cholinergic Crisis: A tuberculin syringe containing 1 mL (10 mg) of edrophonium is prepared with an intravenous needle of 0.2 mL (2 mg) and is administered intravenously. The needle is left in situ. If there is a cholinergic reaction (skeletal muscle fasciculations and increased muscle weakness)  after administering the edrophonium, the drug is immediately discontinued, and atropine is administered intravenously.

Reversal of Neuromuscular Block: Edrophonium is rarely used to reverse non-depolarizing NMBA after a surgical procedure. Nonetheless, for the rare cases where it is used, an IV dose of 0.5 to 1.0 mg/kg of edrophonium is either simultaneously administered with atropine or a few minutes after glycopyrrolate to prevent bradycardia and other cholinergic adverse effects.[11]

Use in the Specific Patient Population

Patients with Hepatic Impairment: No information has been provided in the manufacturer’s product labeling regarding the use of edrophonium in patients with hepatic impairment.

Patients with Renal Impairment: No information has been provided in the manufacturer’s product labeling regarding the use of edrophonium in patients with renal impairment.

Pregnancy Considerations: The safety of edrophonium use during pregnancy has not been established according to the manufacturer’s product labeling.

Breastfeeding Considerations: Edrophonium has a short half-life and quaternary ammonium structure; hence it is unlikely to be excreted into breastmilk or orally absorbed by the infant. Administering the edrophonium just after breastfeeding and waiting 2 to 3 hours before breastfeeding should avoid any adverse drug reactions in the infant. There is no information regarding the use of edrophonium during breastfeeding. Therefore, using edrophonium in nursing mothers requires risk-benefit analysis considering possible hazards to mother and child.[12]

Adverse Effects

The adverse effects of edrophonium occur due to the increased levels of acetylcholine binding to muscarinic acetylcholine receptors. The more serious adverse effects are cardiac arrhythmias, especially bradycardia, atrioventricular block, and cardiac arrest. The muscarinic cholinergic adverse effects also include bronchoconstriction due to airway smooth muscle contraction secondary to increased stimulation of muscarinic receptors. Other adverse effects include bronchial secretions, diarrhea, salivation, lacrimation, increased urinary frequency and urgency, and miosis. Clinicians can attenuate most of the adverse effects with the simultaneous administration of atropine, which functions as a muscarinic receptor antagonist to prevent developing these cholinergic adverse effects. [13]

Contraindications

Absolute contraindications to edrophonium include hypersensitivity to edrophonium patients with gastrointestinal and urinary obstruction. Edrophonium administration requires extreme vigilance and monitoring in patients with cardiac arrhythmias and asthma. Physicians are cautious with the use of edrophonium in asthmatic patients due to possible oxygen desaturation from bronchoconstriction and increased bronchial secretions. In the setting of non-depolarizing NMBA reversal, edrophonium administration is contraindicated and cannot be administered when the peripheral nerve stimulation does not elicit at least one twitch.

According to the manufacturer’s product labeling information, the excipient contains sodium sulfite, which may cause allergic reactions, including anaphylaxis. The clinical presentation of sulfite allergy includes hives, rhinorrhea, bronchoconstriction, flushing, and cardiovascular collapse. Hence use with extreme caution in patients with sulfite allergy. [14]

Monitoring

Heart, respiratory, and blood pressure require monitoring when administering edrophonium. In using edrophonium for MG diagnosis, a cumulative dose of 10 mg is the recommended maximum to prevent excessive cholinergic muscarinic side effects.[15] According to the manufacturer’s labeling, whenever edrophonium is used for testing, a syringe containing 1 mg of atropine sulfate should be immediately available to be given intravenously to counteract severe cholinergic reactions.

Toxicity

Overdose of edrophonium will result in muscarinic symptoms due to the cholinergic crisis manifested by excessive acetylcholine binding to muscarinic receptors. The cholinergic crisis includes diarrhea, increased urination, miosis, muscle weakness, bronchospasm, bradycardia, emesis, and lacrimation. The more serious outcomes of edrophonium overdose involve respiratory muscle weakness and cardiac arrhythmias that can progress to a fatal outcome. Hence, clinicians must ensure patent airway and circulation.  The treatment of an edrophonium overdose is atropine. Atropine is an ideal antidote for edrophonium since it has a similar onset of action as edrophonium. Atropine functions by competitively inhibiting the muscarinic receptors on structures innervated by postganglionic cholinergic nerves and inhibiting muscarinic receptors on smooth muscle. Atropine can be administered up to 1.2 mg intravenously initially and repeated every 20 minutes until secretions are controlled. If convulsions are present, clinicians should institute appropriate supportive measures. For convulsions, supportive treatment is required.[16]

Enhancing Healthcare Team Outcomes

Neurologists and other healthcare providers historically utilized edrophonium to aid in diagnosing MG. In rare situations, it can be a reversal agent for non-depolarizing NMBA after a surgical procedure. Edrophonium’s adverse effects manifest due to its cholinergic profile. The adverse effects of edrophonium can progress to fatal outcomes secondary to respiratory muscle weakness or cardiac arrhythmias. Therefore, it is imperative that healthcare workers utilizing edrophonium monitor vital signs closely and have atropine readily available; this requires working as an interprofessional healthcare team that includes clinicians, specialists, nurses, and pharmacists. Myasthenia gravis (MG) is a chronic medical condition requiring high coordination among professionals and disciplines. The care pathway model has been described. A study examined the comprehensive and multidisciplinary care for diagnosing and treating patients with myasthenia gravis. The study concluded that the interprofessional care pathway model for myasthenia gravis could help achieve better patient outcomes.[17]

The administration of edrophonium and the management of its adverse effects is enhanced when using an interprofessional healthcare team approach. Pharmacists should be consulted for information regarding dosing, drug-drug interactions, and contraindications for patients with extensive comorbidities. Nursing staff must be educated on the adverse effect profile of edrophonium and recognize when the patient is decompensating since, in many situations, they are the sole healthcare worker caring for the patient. Ultimately, an interprofessional approach to using and monitoring edrophonium will ensure appropriate administration, adequate management of adverse effects, and prevention of fatal outcomes. [Level 5]

Review Questions

• Access free multiple choice questions on this topic.

• Comment on this article.

References

1.

Pascuzzi RM. The edrophonium test. Semin Neurol. 2003 Mar;23(1):83-8. [PubMed: 12870109]

2.

Gilhus NE. Myasthenia Gravis. N Engl J Med. 2016 Dec 29;375(26):2570-2581. [PubMed: 28029925]

3.

Motomura M, Fukuda T. [Lambert-Eaton myasthenic syndrome]. Brain Nerve. 2011 Jul;63(7):745-54. [PubMed: 21747145]

4.

Pani N, Dongare PA, Mishra RK. Reversal agents in anaesthesia and critical care. Indian J Anaesth. 2015 Oct;59(10):664-9. [PMC free article: PMC4645356] [PubMed: 26644615]

5.

Zafirova Z, Dalton A. Neuromuscular blockers and reversal agents and their impact on anesthesia practice. Best Pract Res Clin Anaesthesiol. 2018 Jun;32(2):203-211. [PubMed: 30322460]

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Disclosure: Abdullah Naji declares no relevant financial relationships with ineligible companies.

Disclosure: Michael Owens declares no relevant financial relationships with ineligible companies.

Xilen :: Instructions :: Price :: Description of the drug

Xilen (Xilen)

1 ml nasal drops Xylen 0.05% contains:
Xylometazoline hydrochloride – 0.5 mg;
Additional ingredients.

1 ml Xylen nasal spray 0.05% contains:
Xylometazoline hydrochloride 0.5 mg;
Additional ingredients.

Xylene nasal drops 0.1% 1 ml contains:
Xylometazoline hydrochloride – 1 mg;
Additional ingredients.

1 ml Xylen nasal spray 0.1% contains:
Xylometazoline hydrochloride 1 mg;
Additional ingredients.

Xilen is a local drug with a pronounced vasoconstrictive (decongestant) effect. Xylene contains the active ingredient xylometazoline, a substance of the alpha-adrenergic agonist group. Xylometazoline with intranasal use leads to a narrowing of the vessels of the nasopharyngeal mucosa, a decrease in edema and hyperemia of the mucosa. When using Xylen, the severity of rhinorrhea decreases and nasal breathing is facilitated.

The therapeutic effect of Xylen develops within 3-5 minutes after application and lasts for 8-10 hours.
With intranasal use of xylometazoline at therapeutic doses, systemic absorption is negligible. However, when using high doses of Xilen in patients, an increase in systemic absorption and the development of systemic effects of xylometazoline are possible.

Xylene is used for the symptomatic treatment of acute rhinitis of various etiologies (including allergic rhinitis and acute respiratory rhinitis).
Xilen is prescribed as a symptomatic treatment for sinusitis.
To reduce swelling of the nasopharynx, Xylen may be given to patients with otitis media.
Nasal drops and nasal spray Xylen may be recommended in preparation for diagnostic procedures, in particular in preparation for rhinoscopy.

Xylen Nasal Drops 0.05% and 0.1%:
The preparation is intended for intranasal use. Before each use of nasal drops, it is recommended to clear the nasal passages of mucus. After making the drops, clean the dropper nozzle and tightly close the vial with a cap. The duration of therapy and the dose of xylometazoline are determined by the doctor.
Adults and children over 6 years of age are usually prescribed 1-2 drops of Xylen 0.1% in each nasal passage twice or thrice a day.
Children from birth to 6 years of age are usually prescribed 1-2 drops of Xilen 0. 05% in each nasal passage once or twice a day.
The minimum recommended interval between applications of Xylen is 8 hours.
The maximum recommended duration of Xylen therapy is 5 days.
If a dose of Xilen is missed, the next dose should not be doubled.

Xylen Nasal Spray 0.1% and 0.05%:
The preparation is intended for intranasal use. Before using the Xylen spray, clear the nasal passages of mucus. After using the drug, clean the spray nozzle and close the bottle tightly with a cap. The duration of the course of therapy and the dose of xylometazoline is determined by the doctor.
Adults and children over 6 years of age are usually given 1 spray of Xylen 0.1% in each nasal passage twice or thrice daily.
Children 2 to 6 years of age are usually given 1 spray of Xilen 0.05% in each nasal passage once or twice a day.
The minimum recommended interval between applications of Xylen is 8 hours.
The maximum recommended duration of therapy is 5 days.
If a dose of Xilen is missed, do not double the next dose.

Xylene is generally well tolerated by patients. The development of undesirable effects has usually been noted with frequent use or the use of high doses of xylometazoline. In particular, during therapy with Xilen, patients may develop sneezing, paresthesia, irritation and dryness of the nasopharyngeal mucosa, hypersecretion, as well as tachycardia, palpitations and arterial hypertension. In isolated cases, the development of insomnia, swelling of the nasal mucosa, headache, decreased visual acuity, depressive states and arrhythmia was noted.

With prolonged (more than 5 days) use of Xilen, patients may develop swelling of the nasal mucosa and atrophic rhinitis.

Xylene is not indicated in patients with individual hypersensitivity to xylometazoline or any of the other ingredients of the formulation.
Xylene is not used for the treatment of patients suffering from severe arterial hypertension, tachycardia, severe atherosclerosis, glaucoma, and atrophic rhinitis.
Xylen should not be administered to patients with a history of meningeal surgery.
In pediatric practice, Xylen 0.05% spray is used only for the treatment of children older than 2 years.
In pediatric practice, Xylen 0.1% is used only for the treatment of children over 6 years of age.

Caution should be exercised when prescribing Xylen to patients suffering from ischemic heart disease, benign prostatic hyperplasia, diabetes mellitus and hyperthyroidism.
Xylen is not used for the treatment of patients with chronic rhinitis (since xylometazoline is used only for short-term treatment).
During the period of use of the drug Xylen, activities that require a high concentration of attention and speed of psychomotor reactions should be avoided.

Xylometazoline should be used with caution during pregnancy. If it is impossible to avoid the use of xylometazoline, the drug should be used in minimal doses and not more than 3 days in a row.
During lactation, before starting therapy with xylometazoline, the question of a possible interruption of breastfeeding should be considered.

The combined use of xylometazoline with monoamine oxidase inhibitors is prohibited. Xylen can be used no earlier than 2 weeks after the end of therapy with drugs that inhibit monoamine oxidase.
Xylen should not be administered to patients receiving tricyclic antidepressants.

When using high doses of Xilen, patients may develop severe systemic adverse effects of xylometazoline. In particular, with the intranasal use of high doses of xylometazoline, patients develop depression, tachycardia, arterial pressure lability, as well as paresthesia and seizures.
No specific antidote. In case of an overdose, the abolition of Xilen is indicated, as well as symptomatic therapy and measures aimed at maintaining the function of the cardiovascular system.

Nasal drops Xylen 0.1% and Xylen 0.05% 10 ml each in dropper bottles made of polymeric materials or dark glass bottles with a dropper nozzle, 1 bottle is enclosed in a cardboard box.
Nasal spray Xylen 0.1% and Xylen 0. 05% 10 ml each in dropper bottles made of polymeric materials or dark glass bottles with a dropper nozzle, 1 bottle is enclosed in a cardboard box.

Xylen should be stored and transported in its original packaging at temperatures between 15 and 25 degrees Celsius.
The shelf life of the drug, subject to the recommendations for storage, is 3 years.

Galazolin, Dlyanos, Grippostad Rino, Farmazolin, Rinostop, Snoop, Xylometazoline.
See also the list of Xilen analogues.

The instruction was compiled by a team of authors and editors of the Piluli website. The list of authors of the drug reference book is presented on the site editorial page: Site editors.

References to used sources of information.

Attention!
The description of the drug “ Xilen ” on this page is a simplified and supplemented version of the official instructions for use. Before purchasing or using the drug, you should consult your doctor and read the annotation approved by the manufacturer.