Medication Guide App

Edrophonium (Systemic)


VA CLASSIFICATION
Primary: AU300
Secondary: DX900; AD900

Commonly used brand name(s): Enlon; Reversol; Tensilon.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Cholinergic (cholinesterase inhibitor)—

diagnostic aid (myasthenia gravis)—

antidote (to nondepolarizing neuromuscular block)—
Note: Cholinergic (cholinesterase inhibitor) is the basic category; the other categories are specific categories of use.



Indications

Accepted

Myasthenia gravis (diagnosis)—Edrophonium is indicated in the differential diagnosis of myasthenia gravis and as an adjunct in the evaluation of treatment requirements in the disease {07} {08} {10} {11} {22}. It is also indicated for evaluating emergency treatment in myasthenic crisis {04} {07} {08} {10} {11} {22}. Edrophonium is not recommended for maintenance therapy in myasthenia gravis {04} because of its short duration of action {07} {08} {10} {11} {22}.

Neuromuscular blockade, nondepolarizing (treatment){28} and
Toxicity, curare (treatment)—Edrophonium is indicated to reverse the neuromuscular blockade produced by many nondepolarizing agents, including atracurium, gallamine, metocurine, mivacurium {25} {32} {33} {35}, pancuronium {36}, rocuronium, tubocurarine {36}, and vecuronium {07} {08} {09} {10} {11} {21} {22} {23}. Although edrophonium is frequently used {18} to reverse moderate degrees of residual neuromuscular blockade, other cholinesterase inhibitors (such as neostigmine) may better antagonize profound levels of neuromuscular blockade {15} {16} {19} {20} and neuromuscular blockade induced by doxacurium and pipecuronium {28}.
—Edrophonium is not effective against depolarizing agents such as decamethonium {04} {21} {22} and succinylcholine {04} {07} {08} {09} {10} {11} {21} {22}.
—Also, edrophonium is indicated as an adjunct in the treatment of respiratory depression caused by overdosage of nondepolarizing neuromuscular blocking agents {04} {07} {08} {09} {10} {11} {21} {22}.

Unaccepted
Edrophonium has been used to terminate supraventricular tachycardia (SVT; paroxysmal atrial tachycardia) but has generally been replaced by other antiarrhythmic agents.


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    201.7 {29}


Other characteristics
    Edrophonium injection: pH between 5 and 5.8 {38}.

Mechanism of action/Effect:


Cholinergic (cholinesterase inhibitor):

Inhibits destruction of acetylcholine by acetylcholinesterase {04} {07} {09} {10} {21} {22}, thereby facilitating transmission of impulses across the myoneural junction {04} {08} {11} {21}.

Diagnostic aid (myasthenia gravis): By prolonging the duration of action of acetylcholine at the motor end plate, edrophonium transiently increases muscle strength in patients with myasthenia gravis, whereas patients with other disorders develop either no increase in strength or even a slight weakness and possibly fasciculations.

Antidote (to nondepolarizing neuromuscular block): Since nondepolarizing neuromuscular blocking agents combine reversibly with the receptors, preventing access of acetylcholine, antagonism can be overcome by increasing the amount of agonist at the receptors; therefore, muscle paralysis induced by nondepolarizing neuromuscular blocking agents is reversed by edrophonium, which increases the concentration of acetylcholine at the receptors. {09}


Distribution:

The volume of distribution (Vol D) of edrophonium is 1.1 ± 0.2 L per kg {02} {12}.

Half-life:

Distribution—7 to 12 minutes {12}.

Elimination—33 to 110 minutes {12} {22}.

Onset of action:

Intramuscular—2 to 10 minutes {03} {07} {08} {10}.

Intravenous—Within 30 to 60 seconds {03} {07} {08} {10} {11} {22}. Onset of reversal of muscle relaxant–induced depression in twitch tension occurs within 3 minutes {39}.

Time to peak effect:

Following a 0.5 to 1 mg per kg of body weight (mg/kg) intravenous dose—Within 1.2 minutes {39}.

Duration of action:


In the diagnosis of myasthenia gravis:

Intramuscular: 5 to 30 minutes {03}.

Intravenous: 5 to 10 minutes {27}.



For reversal of neuromuscular blockade:

Following a 0.5 to 1 mg per kg of body weight (mg/kg) intravenous dose: 70 minutes {39}.


Elimination:
    Renal {09} {21}. The clearance of edrophonium is about 0.5 L per kg per hour {12}.


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to sulfites may be sensitive to edrophonium because of the sulfite preservatives present.

Pregnancy/Reproduction

Pregnancy—
Studies have not been done in humans {21} {22}.

Studies have not been done in animals {04} {21}.

FDA Pregnancy Category C {04} {08} {10}.

Breast-feeding

It is not known whether edrophonium is distributed into breast milk {04} {21}. However, problems in humans have not been documented.

Pediatrics

A study performed in 4 infants and 12 children did not show any pediatrics-specific problems that would limit the usefulness of edrophonium for neuromuscular blockade in children {37} {41}. Caution and careful monitoring are recommended {40}.


Geriatrics


Extensive studies on the relationship of age to the effects of edrophonium have not been performed in the geriatric population. However, in two studies comparing small numbers of patients 76 to 87 years of age with younger adults, the onset of action and the duration of antagonism of neuromuscular blockade by edrophonium in the older group were no different from those in younger patients. {05} {06} {13} {25}

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

Cholinesterase inhibitors, other,{07}{08}{09}{10}{11} including antimyasthenics, demecarium, echothiophate, and isoflurophate and possibly topical malathion in excessive quantities    (caution is recommended when administering edrophonium to patients with symptoms of myasthenic weakness who are also receiving these medications, since symptoms of cholinergic crisis [overdosage] may be similar to those occurring with myasthenic crisis [underdosage], and the patient's condition may be worsened by use of edrophonium {04} {07} {08} {09} {10} {21})


Digitalis glycosides{09}    (when used concurrently with edrophonium, the additive vagomimetic effects may cause excessive bradycardia)


Neuromuscular blocking agents    (phase I block of depolarizing neuromuscular blocking agents such as succinylcholine may be prolonged when these medications are used concurrently with edrophonium; however, if these blocking agents have been used over a prolonged period of time and the depolarization block has changed to a nondepolarization block, edrophonium may reverse the nondepolarization block)

    (effects of many nondepolarizing neuromuscular blocking agents are antagonized by edrophonium, especially moderate degrees of residual neuromuscular blockade; profound levels of neuromuscular blockade may be better antagonized by other agents such as neostigmine {15} {16} {19} {20})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problem exists:
» Intestinal{07}{09}{10}{11}{21}{22} or urinary tract{04}{07}{08}{09}{10}{11}{21}{22} obstruction, mechanical
Risk-benefit should be considered when the following medical problems exist
» Asthma, bronchial{04}{07}{08} {09}{10}{11}{21}{22}    (increase in bronchial secretions and other respiratory effects of edrophonium may aggravate condition)


Cardiac dysrhythmias{04}{07}{08}{09}{10}{11}{21}{22} such as bradycardia and atrioventricular (AV) block    (increased risk of cardiac arrhythmias)


Sensitivity to edrophonium{04}{07}{08}{09}{10}{11}{21}{22}


Side/Adverse Effects

Note: Severe side/adverse effects occur rarely with usual doses of edrophonium. Any side effects that may occur with edrophonium are usually short-lived because of its short duration of action {07} {10} {11} and are usually less severe than those that occur with neostigmine, pyridostigmine, or ambenonium.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence rare {04} {07} {08} {09} {10} {11} {21} {22}
    
Muscarinic effects (shortness of breath, troubled breathing, wheezing or tightness in chest; slow heartbeat; unusual tiredness or weakness)
    
nicotinic effects (muscle weakness, cramps, or twitching)

Note: Cholinergic reaction includes severe muscarinic side effects in addition to nicotinic effects.




Those indicating need for medical attention only if they continue or are bothersome
Incidence less frequent or rare {04} {07} {08} {09} {10} {11} {21} {22}
    
Muscarinic effects (blurred vision; diarrhea; frequent urge to urinate; increased sweating; increased watering of eyes or mouth; increase in bronchial secretions; nausea or vomiting; stomach cramps or pain)





Overdose
For specific information on the agents used in the management of edrophonium overdose, see:    • Atropine in Anticholinergics/Antispasmodics (Systemic) monograph; and/or
   • Pralidoxime (Systemic) monograph.


For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Acute and/or chronic
    
Muscarinic effects ( diarrhea; bradycardia; increased bronchial and salivary secretions; nausea and/or vomiting; sweating)


Treatment of overdose
Discontinuation of edrophonium {01} {04} {07} {08} {09} {10} {11} {21}.

Specific treatment—Use of intravenous atropine or pralidoxime to control muscarinic effects {26}. See package insert or Atropine in Anticholinergics/Antispasmodics (Systemic) or Pralidoxime (Systemic) monographs for specific dosing guidelines. However, use may be limited due to the short half-life of edrophonium {42}.

May include treatment of seizures or shock as appropriate {26}.

Monitoring—May include monitoring of cardiac function {26}.

Supportive care—May include maintaining an open airway and possible suctioning of bronchial secretions; and use of assisted respiration {26}.


General Dosing Information
When edrophonium is used for testing, atropine injection should always be readily available to counteract severe cholinergic reactions, which may occur in hypersensitive individuals {04} {07} {08} {09} {10} {11} {21} {22}.

Atropine will prevent or relieve the muscarinic side effects {18}, but is usually not required, except in patients older than 50 years of age, who should be given atropine before myasthenic testing to prevent bradycardia and hypotension.

Atropine may be administered to relieve the transient bradycardia that may occur with the use of edrophonium {04} {07} {08} {09} {10} {11}.

When used to reverse the effects of nondepolarizing neuromuscular blockade, edrophonium should not be administered prior to the nondepolarizing neuromuscular blocking agent but at the time the effect is needed {07} {08} {09} {10}.

When used as a test for the evaluation of treatment requirements in myasthenia gravis:    • In patients who require additional anticholinesterase medication, a transient increase in muscle strength without fasciculation or muscarinic side effects will occur (myasthenic response) {07} {08} {10}.
   • In patients who have been overtreated with anticholinesterase agents, muscle strength is decreased, muscle fasciculations may occur, and severe muscarinic effects usually occur (cholinergic response) {07} {08} {10}.
   • In patients being adequately treated with anticholinesterase agents, there is no change in muscle strength, muscle fasciculations may occur, and side effects, if any occur, are mild {07} {08} {10}.


When used to differentiate myasthenic crisis from cholinergic crisis, edrophonium may temporarily increase muscle strength if treatment has been inadequate (myasthenic crisis), whereas in overtreatment (cholinergic crisis) the condition may worsen {07} {08} {10}.


Parenteral Dosage Forms

EDROPHONIUM CHLORIDE INJECTION USP

Usual adult and adolescent dose
For evaluation of treatment requirements in myasthenia gravis
Intravenous, 1 to 2 mg one hour after administration of anticholinesterase agent {04} {07} {08} {10}.

To differentiate cholinergic crisis from myasthenic crisis
Intravenous, initially 1 mg, followed after one minute by an additional 1 mg if the initial dose does not further impair patient {04} {07} {08} {10} {11} {14} {22}.

Diagnostic aid (myasthenia gravis)
Intramuscular, 10 mg {04} {07} {08} {10}.

Note: If cholinergic reaction occurs, test should be repeated after thirty minutes using a dose of 2 mg, to rule out a false-negative reaction {04} {07} {08} {10}.


Intravenous, initially 2 mg administered within fifteen to thirty seconds, followed by 8 mg if no response after forty-five seconds {04} {07} {08} {10} {11} {14} {22}.

Note: If cholinergic reaction occurs after initial dose of 2 mg, test should be discontinued and 400 mcg (0.4 mg) of atropine given intravenously. Test may be repeated after thirty to sixty minutes {04} {07} {08} {10} {41}.


Reversal of nondepolarizing neuromuscular blockade
Intravenous, 10 mg administered over a period of thirty to forty-five seconds, repeated as needed, up to a maximum total dose of 40 mg {04} {07} {08} {10} {11} {22}. Alternatively, doses of 0.5 to 1 mg of edrophonium per kg of body weight are used {15} {16} {17} {18} {19}.


Usual pediatric dose
Diagnostic aid (myasthenia gravis)
Infants:

Intramuscular or subcutaneous, 500 mcg (0.5 mg) {14} to 1 mg.

Intravenous, 500 mcg (0.5 mg) {07} {08}.

Children up to 34 kg of body weight:

Intramuscular, 2 mg {04} {07} {08} {10} {14}.

Intravenous, 1 mg initially; if no response within forty-five seconds, then 1 mg every thirty to forty-five seconds up to a total dose of 5 mg {04} {07} {08} {10}.

Children 34 kg of body weight and over:

Intramuscular, 5 mg {04} {07} {08} {10}.

Intravenous, 2 mg initially; if no response within forty-five seconds, then 1 mg every thirty to forty-five seconds up to a total dose of 10 mg {04} {07} {08} {10}.


Usual geriatric dose
See Usual adult and adolescent dose.

Note: Patients older than 50 years of age should be given atropine before myasthenic testing to prevent bradycardia and hypotension.


Strength(s) usually available
U.S.—


10 mg per mL (Rx) [Enlon (phenol 0.45%) (sodium sulfite 0.2%) (sodium citrate) (citric acid)] [Reversol (phenol 0.45%) (sodium sulfite 0.2%) (sodium citrate) (citric acid)] [Tensilon (sodium sulfite 0.2%) (sodium citrate) (citric acid—in 1-mL ampuls) (or phenol 0.45%) (sodium sulfite 0.2%) (sodium citrate) (citric acid—in 10-mL vials)]

Canada—


10 mg per mL (Rx) [Enlon (phenol 0.45%) (sodium sulfite 0.2%) (sodium citrate) (citric acid)] [Tensilon (phenol 0.45%) (sodium sulfite 0.2%) (sodium citrate) (citric acid) (sodium < 1 mmol per mL)]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), {04} {22} unless otherwise specified by manufacturer. Protect from freezing.

Additional information:
A combination of edrophonium and atropine ( Enlon-Plus) is available in the U.S.



Developed:
Revised: 01/21/1998



References
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  1. HOLD
  1. HOLD
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  1. HOLD
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