Enlon

Careful observation should be made for severe cholinergic reactions in the hyperreactive individual. The myasthenic patient in crisis who is being tested with Enlon (edrophonium injection) ® should be observed for bradycardia or cardiac standstill and cholinergic reactions if an overdose is given.

The following reactions common to anticholinesterase agents may occur, although not all of these reactions have been reported with the administration of Enlon (edrophonium injection) ®, probably because of its short duration of action and limited indications:

Enlon (edrophonium injection) ® is an anticholinesterase drug. Its pharmacologic action is due primarily to the inhibition or inactivation of acetylcholinesterase at sites of cholinergic transmission. Its effect is manifest within 30 to 60 seconds after injection and lasts an average of 10 minutes.

See WARNINGS, PRECAUTIONS and CONTRAINDICATIONS.

Edrophonium is injected into a muscle, or into a vein through an IV. A healthcare provider will give you this injection.

When used in testing for myasthenia gravis, edrophonium is given in small doses over 15 to 45 seconds. After each dose you will be observed for certain reactions to this medicine (muscle twitching, vision changes, increased muscle weakness, sweating, stomach cramps, nausea, and other symptoms). You may receive other medications to treat the reaction to edrophonium.

The test you are receiving may be repeated a second time.

Your specific edrophonium test may be performed in a different manner than described above.

Edrophonium injection is used to help diagnose myasthenia gravis (severe muscle weakness) and may be used to help select the proper treatment for the disease. It is also used to reverse the effects of certain muscle relaxants (eg, gallamine, tubocurarine) during surgery or after an overdose of the muscle relaxant. Edrophonium is an anticholinesterase agent.

This medicine is to be given only by or under the direct supervision of a doctor.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of edrophonium injection in children.

Geriatric

No information is available on the relationship of age to the effects of edrophonium injection in geriatric patients.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are receiving this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Bupropion
• Donepezil

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Allergy to sulfites, history of—May cause severe allergic reactions.

• Asthma or other breathing problems, history of or
• Bradycardia (slow heart beat) or
• Heart rhythm problems—Use with caution. May make these conditions worse.

• Bladder blockage (unable to urinate) or
• Bowel blockage (unable to have a stool) or
• Kidney blockage (unable to urinate)—Should not be used in patients with these conditions.

Enlon is an anticholinesterase drug. Its pharmacologic action is due primarily to the inhibition or inactivation of acetylcholinesterase at sites of cholinergic transmission. Its effect is manifest within 30 to 60 seconds after injection and lasts an average of 10 minutes.

Pediatric Pharmacology

The pharmacology of edrophonium chloride was studied in 14 infants (between 3 weeks and 11 months old) and 12 children (between 1 year and 6 years old) during a steady-state infusion of d-tubocurarine during N2O-halothane anesthesia and controlled ventilation for elective surgery.1 The ED50 dose (dose producing 50% antagonism of 90% neuromuscular depression) for edrophonium chloride was 145 mcg/kg in infants and 233 mcg/kg in children not significantly different from that observed in adult patients; however, there was greater variability among infants and children than adults. Time to peak antagonism and duration of antagonism were similar between the two pediatric age groups and adult patients. Edrophonium chloride pharmacokinetics were studied in four infants (3 months through 7 months of age) and four children (1 through 4 years of age). Total clearance was 17.8 mL/kg•min in infants and 14.2 mL/kg•min in children. Total clearance was significantly greater in infants than in adults (8.3 + 2.9 mL/kg•min) p<0.05. Elimination half-life was 73 ± 30 minutes in infants and 99 ± 31 minutes in children compared with 126 ± 59 minutes in adult patients. Volume of distribution in infants and children was 1.18 ± 0.20 L/kg and 1.22 ± 0.74 L/kg, respectively, compared with 0.90 ± 0.13 L/kg in adults.

Enlon is recommended for the differential diagnosis of myasthenia gravis and as an adjunct in the evaluation of treatment requirements in this disease. It may also be used for evaluating emergency treatment in myasthenic crises. Because of its brief duration of action, it is not recommended for maintenance therapy in myasthenia gravis.

Enlon is also useful whenever a curare antagonist is needed to reverse the neuromuscular block produced by curare, tubocurarine, gallamine triethiodide or dimethyl-tubocurarine. It is not effective against decamethonium bromide and succinylcholine chloride. It may be used adjunctively in the treatment of respiratory depression caused by curare overdosage.

Careful observation should be made for severe cholinergic reactions in the hyperreactive individual. The myasthenic patient in crisis who is being tested with Enlon should be observed for bradycardia or cardiac standstill and cholinergic reactions if an overdose is given.

The following reactions common to anticholinesterase agents may occur, although not all of these reactions have been reported with the administration of Enlon, probably because of its short duration of action and limited indications:

Enlon Test in the Differential Diagnosis of Myasthenia Gravis7-14

Intravenous Dosage (Adults)

A tuberculin syringe containing 1 mL (10 mg) of Enlon is prepared with an intravenous needle, and 0.2 mL (2 mg) is injected intravenously within 15 to 30 seconds. The needle is left in situ. Only if no reaction occurs after 45 seconds is the remaining 0.8 mL (8 mg) injected. If a cholinergic reaction (muscarinic side effects, skeletal muscle fasciculations and increased muscle weakness) occurs after injection of 0.2 mL (2 mg), the test is discontinued and atropine sulfate, 0.4 mg to 0.5 mg, is administered intravenously. After one-half hour the test may be repeated.

Intramuscular Dosage (Adults)

In adults with inaccessible veins, dosage for intramuscular injection is 1 mL (10 mg) of Enlon. Subjects who demonstrate hyperreactivity to this injection (cholinergic reaction), should be retested after one-half hour with 0.2 mL (2 mg) of Enlon intramuscularly to rule out false-negative reactions.

The intravenous testing dose of Enlon in pediatric patients weighing up to 75 lbs is 0.1 mL (1 mg); above this weight, the dose is 0.2 mL (2 mg). If there is no response after 45 seconds, it may be titrated up to 0.5 mL (5 mg) in pediatric patients under 75 lbs, given in increments of 0.1 mL (1 mg) every 30 to 45 seconds and up to 1 mL (10 mg) in heavier patients. In infants, the recommended dose is 0.05 mL (0.5 mg). Because of technical difficulty with intravenous injection in pediatric patients, the intramuscular route may be used. In pediatric patients weighing up to 75 lbs, 0.2 mL (2 mg) is injected intramuscularly. In pediatric patients weighing more than 75 lbs, 0.5 mL (5 mg) is injected intramuscularly. All signs which would appear with the intravenous test appear with the intramuscular test except that there is a delay of 2 to 10 minutes before a reaction is noted.

Enlon Test for Evaluation of Treatment Requirements in Myasthenia Gravis

The recommended dose is 0.1 mL to 0.2 mL (1 mg to 2 mg) of Enlon, administered intravenously 1 hour after oral intake of the drug being used in treatment.7-11 Response will be myasthenic in the undertreated patient, adequate in the controlled patient, and cholinergic in the overtreated patient. Responses to Enlon in myasthenic and nonmyasthenic individuals are summarized in the following chart.8

Enlon Test in Crisis

The term crisis is applied to the myasthenic whenever severe respiratory distress with objective ventilatory inadequacy occurs and the response to medication is not predictable. This state may be secondary to a sudden increase in severity of myasthenia gravis (myasthenic crisis), or to overtreatment with anticholinesterase drugs (cholinergic crisis).

When a patient is apneic, controlled ventilation must be secured immediately in order to avoid cardiac arrest and irreversible central nervous system damage. No attempt is made to test with Enlon until respiratory exchange is adequate.

Dosage used at this time is most important

If the patient is cholinergic, Enlon will cause increased oropharyngeal secretions and further weakness in the muscles of respiration. If the crisis is myasthenic, the test clearly improves respiration and the patient can be treated with longer-acting intravenous anticholinesterase medication. When the test is performed, there should not be more than 0.2 mL (2 mg) Enlon in the syringe. An intravenous dose of 0.1 mL (1 mg) is given initially. The patient’s heart action is carefully observed. If, after an interval of 1 minute, this dose does not further impair the patient, the remaining 0.1 mL (1 mg) can be injected. If no clear improvement of respiration occurs after 0.2 mL (2 mg) dose, it is usually wisest to discontinue all anticholinesterase drug therapy and secure controlled ventilation by tracheostomy with assisted respiration.5

For Use as a Curare Antagonist

Enlon should be administered by intravenous injection in 1 mL (10 mg) doses given slowly over a period of 30 to 45 seconds so that the onset of cholinergic reaction can be detected. This dosage may be repeated whenever necessary. The maximal dose for any one patient should be 4 mL (40 mg). Because of its brief effect, Enlon should not be given prior to the administration of curare, tubocurarine, gallamine triethiodide or dimethyl-tubocurarine: it should be used at the time when its effect is needed. When given to counteract curare overdosage, the effect of each dose on the respiration should be carefully observed before it is repeated, and assisted ventilation should always be employed.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.