VECURON

Monoquaternary homolog of pancuronium.

A non-depolarizing neuromuscular blocking agent with shorter duration of action than pancuronium.

Its lack of significant cardiovascular effects and lack of dependence on good kidney function for elimination as well as its short duration of action and easy reversibility provide advantages over, or alternatives to, other established neuromuscular blocking agents.

Vecuronium is a muscle relaxing agent and is used as an adjunct in general anesthesia.

The principal pharmacologic effects demonstrated by vecuronium revolve around its competitive binding of cholinergic receptors located at motor end plates.

This competitive binding results in muscle relaxant effects that are typically employed as an adjunct to general anesthesia.

Fecal (40-75%) and renal (30% as unchanged drug and metabolites).

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The possibility of iatrogenic overdosage can be minimized by carefully monitoring muscle twitch response to peripheral nerve stimulation.

Excessive doses of vecuronium produce enhanced pharmacological effects.

Residual neuromuscular blockade beyond the time period needed may occur with vecuronium as with other neuromuscular blockers.

This may be manifested by skeletal muscle weakness, decreased respiratory reserve, low tidal volume, or apnea.

A peripheral nerve stimulator may be used to assess the degree of residual neuromuscular blockade from other causes of decreased respiratory reserve.

Respiratory depression may be due either wholly or in part to other drugs used during the conduct of general anesthesia such as narcotics, thiobarbiturates and other central nervous system depressants.

Under such circumstances the primary treatment is maintenance of a patent airway and manual or mechanical ventilation until complete recovery of normal respiration is assured.

Pyridostigmine, neostigmine, or edrophonium, in conjunction with atropine or glycopyrrolate will usually antagonize the skeletal muscle relaxant action of vecuronium.

Satisfactory reversal can be judged by adequacy of skeletal muscle tone and by adequacy of respiration.

A peripheral nerve stimulator may also be used to monitor restoration of twitch height.

Failure of prompt reversal (within 30 minutes) may occur in the presence of extreme debilitation, carcinomatosis, and with concomitant use of certain broad spectrum antibiotics, or anesthetic agents and other drugs which enhance neuromuscular blockade or cause respiratory depression of their own.

Under such circumstances the management is the same as that of prolonged neuromuscular blockade.

Ventilation must be supported by artificial means until the patient has resumed control of his respiration.

Prior to the use of reversal agents, reference should be made to the specific package insert of the reversal agent.

The effects of hemodialysis and peritoneal dialysis on plasma levels of vecuronium and its metabolite are unknown.

Severe anaphylactic reactions to neuromuscular blocking agents, including VECURONIUM BROMIDE, have been reported.

These reactions have in some cases been life-threatening and fatal.

Due to the potential severity of these reactions, the necessary precautions, such as the immediate availability of appropriate emergency treatment, should be taken.

Precautions should also be taken in those individuals who have had previous anaphylactic reactions to other neuromuscular blocking agents since cross-reactivity between neuromuscular blocking agents, both depolarizing and non-depolarizing, has been reported.

In patients who are known to have myasthenia gravis or the myasthenic (Eaton-Lambert) syndrome, small doses of vecuronium may have profound effects.

In such patients, a peripheral nerve stimulator and use of a small test dose may be of value in monitoring the response to administration of muscle relaxants.

Risk of Death due to Medication Errors Administration of vecuronium bromide results in paralysis, which may lead to respiratory arrest and death; this progression may be more likely to occur in a patient for whom it is not intended.

Confirm proper selection of intended product and avoid confusion with other injectable solutions that are present in critical care and other clinical settings.

If another healthcare provider is administering the product, ensure that the intended dose is clearly labeled and communicated.

Vecuronium bromide is contraindicated in patients known to have a hypersensitivity to it.

Vecuronium bromide for injection is for intravenous use only.

This drug should be administered by or under the supervision of experienced clinicians familiar with the use of neuromuscular blocking agents.

Dosage must be individualized in each case.

The dosage information which follows is derived from studies based upon units of drug per unit of body weight and is intended to serve as a guide only, especially regarding enhancement of neuromuscular blockade of vecuronium bromide by volatile anesthetics and by prior use of succinylcholine.

To obtain maximum clinical benefits of vecuronium bromide and to minimize the possibility of overdosage, the monitoring of muscle twitch response to peripheral nerve stimulation is advised.

The recommended initial dose of vecuronium bromide is 0.08 to 0.1 mg/kg (1.4 to 1.75 times the ED 90 ) given as an intravenous bolus injection.

This dose can be expected to produce good or excellent non-emergency intubation conditions in 2.5 to 3 minutes after injection.

Under balanced anesthesia, clinically required neuromuscular blockade lasts approximately to 30 minutes, with recovery to 25% of control achieved approximately to 40 minutes after injection and recovery to 95% of control achieved approximately to 65 minutes after injection.

In the presence of potent inhalation anesthetics, the neuromuscular blocking effect of vecuronium bromide is enhanced.

If vecuronium bromide is first administered more than 5 minutes after the start of inhalation agent or when steady-state has been achieved, the initial vecuronium bromide dose may be reduced by approximately 15%, i.e., 0.06 to 0.085 mg/kg. Prior administration of succinylcholine may enhance the neuromuscular blocking effect and duration of action of vecuronium bromide.

If intubation is performed using succinylcholine, a reduction of initial dose of vecuronium bromide to 0.04 to 0.06 mg/kg with inhalation anesthesia and 0.05 to 0.06 mg/kg with balanced anesthesia may be required.

During prolonged surgical procedures, maintenance doses of 0.01 to 0.015 mg/kg of vecuronium bromide are recommended; after the initial vecuronium bromide injection, the first maintenance dose will generally be required within to 40 minutes.

However, clinical criteria should be used to determine the need for maintenance doses.

Since vecuronium bromide lacks clinically important cumulative effects, subsequent maintenance doses, if required, may be administered at relatively regular intervals for each patient, ranging approximately from to 15 minutes under balanced anesthesia, slightly longer under inhalation agents. (If less frequent administration is desired, higher maintenance doses may be administered). Should there be reason for the selection of larger doses in individual patients, initial doses ranging from 0.15 mg/kg up to 0.28 mg/kg have been administered during surgery under halothane anesthesia without ill effects to the cardiovascular system being noted as long as ventilation is properly maintained.

After an intubating dose of to 100 mcg/kg, a continuous infusion of 1 mcg/kg/min can be initiated approximately to 40 minutes later.

Infusion of vecuronium bromide should be initiated only after early evidence of spontaneous recovery from the bolus dose.

Long-term intravenous infusion to support mechanical ventilation in the intensive care unit has not been studied sufficiently to support dosage recommendations. .

The infusion of vecuronium bromide should be individualized for each patient.

The rate of administration should be adjusted according to the patient’s twitch response as determined by peripheral nerve stimulation.

An initial rate of 1 mcg/kg/min is recommended, with the rate of the infusion adjusted thereafter to maintain a 90% suppression of twitch response.

Average infusion rates may range from 0.8 to 1.2 mcg/kg/min. Inhalation anesthetics, particularly enflurane and isoflurane may enhance the neuromuscular blocking action of nondepolarizing muscle relaxants.

In the presence of steady-state concentrations of enflurane or isoflurane, it may be necessary to reduce the rate of infusion to 60 percent, 45 to 60 min after the intubating dose.

Under halothane anesthesia it may not be necessary to reduce the rate of infusion.

Spontaneous recovery and reversal of neuromuscular blockade following discontinuation of vecuronium bromide infusion may be expected to proceed at rates comparable to that following a single bolus dose.

Infusion solutions of vecuronium bromide can be prepared by adding vecuronium bromide with an appropriate infusion solution such as Dextrose 5% Injection, Sodium Chloride 0.9% Injection, Dextrose 5% and Sodium Chloride 0.9% Injection, or Lactated Ringer’s Injection.

Unused portions of infusion solutions should be discarded.

Infusion rates of vecuronium bromide can be individualized for each patient using the following table: 10 mg of Vecuronium bromide in 100 mL solution ‡ 20 mg of Vecuronium bromide in 100 mL solution Drug Delivery Rate Infusion Delivery Rate (mcg/kg/min) (mL/kg/min) 0.1 mg/mL 0.2 mg/mL ‡ 0.7 0.007 0.0035 0.8 0.008 0.004 0.9 0.009 0.0045 1 0.01 0.005 1.1 0.011 0.0055 1.2 0.012 0.006 1.3 0.013 0.0065 The following table is guideline for mL/min delivery for a solution of 0.1 mg/mL (10 mg in 100 mL) with an infusion pump.

• mL/min Amount of Drug mcg/kg/min Patient Weight.

• kg 40 50 60 70 80 90 100 0.7 0.28 0.35 0.42 0.49 0.56 0.63 0.7 0.8 0.32 0.4 0.48 0.56 0.64 0.72 0.8 0.9 0.36 0.45 0.54 0.63 0.72 0.81 0.9 1 0.4 0.5 0.6 0.7 0.8 0.9 1 1.1 0.44 0.55 0.66 0.77 0.88 0.99 1.1 1.2 0.48 0.6 0.72 0.84 0.96 1.08 1.2 1.3 0.52 0.65 0.78 0.91 1.04 1.17 1.3 NOTE: If a concentration of 0.2 mg/mL is used (20 mg in 100 mL), the rate should be decreased by one-half.

Pediatric patients (10 to 16 years of age) have approximately the same dosage requirements (mg/kg) as adults and may be managed the same way.

Younger pediatric patients (1 to 10 years of age) may require a slightly higher initial dose and may also require supplementation slightly more often than adults.

Infants under 1 year of age but older than 7 weeks are moderately more sensitive to vecuronium bromide on a mg/kg basis than adults and take about 1½ times as long to recover.

See also subsection of PRECAUTIONS titled Pediatric Use.

Information presently available does not permit recommendation on usage in pediatric patients less than 7 weeks of age.

There are insufficient data concerning continuous infusion of vecuronium in pediatric patients, therefore, no dosing recommendations can be made.

COMPATIBILITY Vecuronium bromide is compatible in solution with: Sodium Chloride 0.9% Injection Dextrose 5% Injection Sterile Water for Injection Dextrose 5% in Sodium Chloride 0.9% Injection Lactated Ringer’s Injection Use within 24 hours of mixing with the above solutions.

Vecuronium bromide is also compatible in solution with: bacteriostatic water for injection ( NOT FOR USE IN NEWBORNS ).

Use within 5 days of mixing with the above solution.

Reconstituted vecuronium bromide, which has an acid pH, should not be mixed with alkaline solutions (e.g., barbiturate solutions such as thiopental) in the same syringe or administered simultaneously during intravenous infusion through the same needle or through the same intravenous line.

See DOSAGE AND ADMINISTRATION-COMPATIBILITY for diluents compatible with Vecuronium Bromide for Injection.

When reconstituted with compatible I.V. solutions not containing an antimicrobial preservative (e.g., sterile water for injection), refrigerate and use within 24 hours.

Discard unused portion.

Use: ( NOT FOR USE IN NEWBORNS). When reconstituted with bacteriostatic water for injection, use within 5 days.

The reconstituted solution may be stored at room temperature or refrigerated.

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

Accidental administration of neuromuscular blocking agents may be fatal.

Store vecuronium bromide for injection with the cap and ferrule intact and in a manner that minimizes the possibility of selecting the wrong product.

Vecuronium Bromide for

Injection is a sterile, nonpyrogenic, white to off-white lyophilized cake or powder and is supplied as follows: 10 mg per vial 10 Vials in a Carton NDC 55150-235-11 20 mg per vial 10 Vials in a Carton NDC 55150-236-21 Store dry powder at 20° to 25°C (68° to 77°F) .

Protect from light.

Retain in carton until time of use.

The vial stoppers are not made with natural rubber latex.

Distributed by

Eugia US LLC 279 Princeton-Hightstown Rd.

E. Windsor, NJ 08520.

Animal reproduction studies have not been conducted with vecuronium.

It is also not known whether vecuronium can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.

Vecuronium should be given to a pregnant woman only if clearly needed.

It is not known whether this drug is excreted in human milk.

Because many drugs are excreted in human milk, caution should be exercised when vecuronium is administered to a nursing woman.

Infants under 1 year of age but older than 7 weeks also tested under halothane anesthesia, are moderately more sensitive to vecuronium on a mg/kg basis than adults and take about 1½ times as long to recover.

Use in Pediatrics subsection for recommendations for use in pediatric patients 7 weeks to 16 years of age.

The safety and effectiveness of vecuronium in pediatric patients less than 7 weeks of age have not been established.

Clinical studies of vecuronium did not include sufficient numbers of subjects aged and over to determine whether they respond differently from younger subjects.

There are some reports in the peer reviewed literature of increased effect and longer duration of action of vecuronium in the elderly compared to younger patients.

However, other reports have found no significant differences between healthy elderly and younger adults.

Advanced age or other conditions associated with slower circulation time, may be associated with a delay in onset time.

Nevertheless, recommended doses of vecuronium should not be increased in these patients to reduce onset time, as higher doses produce a longer duration of action.

Dose selections for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Close monitoring of neuromuscular function is recommended.