IV Dilution &
Medication Reference

Vecuronium (Norcuron ®)

Usual Diluents

Standard Dilutions [Amount of drug] [Infusion volume] [Infusion rate]

Alternative (less support):
50 mg/ 50 ml (Undiluted-viaflex)
Concentration: 1 mg/ml

(Dilute each 10mg vial with
10 ml sterile water)

Stability / Miscellaneous

Stability
Store intact vials of powder for injection at room temperature 15°C to 30°C (59°F to 86°F). Vials reconstituted with bacteriostatic water for injection (BWFI) may be stored for 5 days under refrigeration or at room temperature. Vials reconstituted with other compatible diluents (nonbacteriostatic) should be stored under refrigeration and used within 24 hours. Reconstitute with compatible solution for injection to final concentration of 1 mg/mL. Stable in D5W, D5NS, LR, NS, SWI, BWFI.

Intermittent dosing: initially 0.08 to 0.1 mg/kg ideal body weight IV bolus. (Higher initial doses-up to 0.3 mg/kg-may be used for rapid onset.

Maintenance: 0.01 to 0.015 mg/kg q25 to 45min prn.

Continuous infusion: Start IV bolus (0.08 to 0.3 mg/kg), followed by (after 20-40min),1 mcg/kg/min infusion (usual range: 0.8 to 1.2 mcg/kg/min). Dosage reductions are not req'd in renal failure.

Overview: Neuromuscular blocking agents are used in the ICU setting for 3 reasons: (1) to eliminate spontaneous breathing and promote mechanical ventilation (eg eliminate urge to fight the vent.) (2) Cause a pharmacologic restraint so patients do not harm themselves. (3) To decrease oxygen consumption.

CLINICAL PHARMACOLOGY
Vecuronium for injection is a nondepolarizing neuromuscular blocking agent possessing all of the characteristic pharmacological actions of this class of drugs (curariform). It acts by competing for cholinergic receptors at the motor end-plate. The antagonism to acetylcholine is inhibited and neuromuscular block is reversed by acetylcholinesterase inhibitors such as neostigmine, edrophonium, and pyridostigmine. Vecuronium is about 1/3 more potent than pancuronium; the duration of neuromuscular blockade produced by vecuronium bromide is shorter than that of pancuronium at initially equipotent doses. The time to onset of paralysis decreases and the duration of maximum effect increases with increasing vecuronium bromide doses. The use of a peripheral nerve stimulator is recommended in assessing the degree of muscular relaxation with all neuromuscular blocking drugs. The ED90 (dose required to produce 90% suppression of the muscle twitch response with balanced anesthesia) has averaged 0.057 mg/kg (0.049 to 0.062 mg/kg in various studies). An initial vecuronium bromide dose of 0.08 to 0.10 mg/kg generally produces first depression of twitch in approximately 1 minute, good or excellent intubation conditions within 2.5 to 3 minutes, and maximum neuromuscular blockade within 3 to 5 minutes of injection in most patients.

Under balanced anesthesia, the time to recovery to 25% of control (clinical duration) is approximately 25 to 40 minutes after injection and recovery is usually 95% complete approximately 45-65 minutes after injection of intubating dose. The neuromuscular blocking action of vecuronium is slightly enhanced in the presence of potent inhalation anesthetics. If vecuronium is first administered more than 5 minutes after the start of the inhalation of enflurane, isoflurane, or halothane, or when steady state has been achieved, the intubating dose of vecuronium bromide may be decreased by approximately 15% (see DOSAGE AND ADMINISTRATION section). Prior administration of succinylcholine may enhance the neuromuscular blocking effect of vecuronium and its duration of action. With succinylcholine as the intubating agent, initial doses of 0.04-0.06 mg/kg of vecuronium will produce complete neuromuscular block with clinical duration of action of 25-30 minutes. If succinylcholine is used prior to vecuronium, the administration of vecuronium should be delayed until the patient starts recovering from succinylcholine-induced neuromuscular blockade. The effect of prior use of other nondepolarizing neuromuscular blocking agents on the activity of vecuronium has not been studied (see PRECAUTIONS. See package insert for Drug Interactions ).

Repeated administration of maintenance doses of vecuronium has little or no cumulative effect on the duration of neuromuscular blockade. Therefore, repeat doses can be administered at relatively regular intervals with predictable results. After an initial dose of 0.08 to 0.10 mg/kg under balanced anesthesia, the first maintenance dose (suggested maintenance dose is 0.010 to 0.015 mg/kg) is generally required within 25 to 40 minutes; subsequent maintenance doses, if required, may be administered at approximately 12 to 15 minute intervals. Halothane anesthesia increases the clinical duration of the maintenance dose only slightly. Under enflurane a maintenance dose of 0.010 mg/kg is approximately equal to 0.015 mg/kg dose under balanced anesthesia.

The recovery index (time from 25% to 75% recovery) is approximately 15-25 minutes under balanced or halothane anesthesia. When recovery from vecuronium neuromuscular blocking effect begins, it proceeds more rapidly than recovery from pancuronium. Once spontaneous recovery has started, the neuromuscular block produced by vecuronium is readily reversed with various anticholinesterase agents, e.g., pyridostigmine, neostigmine, or edrophonium in conjunction with an anticholinergic agent such as atropine or glycopyrrolate. Rapid recovery is a finding consistent with vecuronium short elimination half-life, although there have been occasional reports of prolonged neuromuscular blockade in patients in the intensive care unit (see PRECAUTIONS ).

The administration of clinical doses of vecuronium bromide is not characterized by laboratory or clinical signs of chemically mediated histamine release. This does not preclude the possibility of rare hypersensitivity reactions (see See package insert for ADVERSE REACTIONS).

INDICATIONS AND USAGE
Vecuronium bromide is indicated as an adjunct to general anesthesia, to facilitate endotracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation.

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

WARNINGS
VECURONIUM BROMIDE SHOULD BE ADMINISTERED IN CAREFULLY ADJUSTED DOSAGE BY OR UNDER THE SUPERVISION OF EXPERIENCED CLINICIANS WHO ARE FAMILIAR WITH ITS ACTIONS AND THE POSSIBLE COMPLICATIONS THAT MIGHT OCCUR FOLLOWING ITS USE. THE DRUG SHOULD NOT BE ADMINISTERED UNLESS FACILITIES FOR INTUBATION, ARTIFICIAL RESPIRATION, OXYGEN THERAPY, AND REVERSAL AGENTS ARE IMMEDIATELY AVAILABLE. THE CLINICIAN MUST BE PREPARED TO ASSIST OR CONTROL RESPIRATION. TO REDUCE THE POSSIBILITY OF PROLONGED NEUROMUSCULAR BLOCKADE AND OTHER POSSIBLE COMPLICATIONS THAT MIGHT OCCUR FOLLOWING LONG-TERM USE IN THE ICU, VECURONIUM BROMIDE OR ANY OTHER NEUROMUSCULAR BLOCKING AGENT SHOULD BE ADMINISTERED IN CAREFULLY ADJUSTED DOSES BY OR UNDER THE SUPERVISION OF EXPERIENCED CLINICIANS WHO ARE FAMILIAR WITH ITS ACTIONS AND WHO ARE FAMILIAR WITH APPROPRIATE PERIPHERAL NERVE STIMULATOR MUSCLE MONITORING TECHNIQUES (see PRECAUTIONS). In patients who are known to have myasthenia gravis or the myasthenic (Eaton-Lambert) syndrome, small doses of vecuronium bromide 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.

PRECAUTIONS
Renal Failure: Vecuronium is well tolerated without clinically significant prolongation of neuromuscular blocking effect in patients with renal failure who have been optimally prepared for surgery by dialysis. Under emergency conditions in anephric patients some prolongation of neuromuscular blockade may occur; therefore, if anephric patients cannot be prepared for non-elective surgery, a lower initial dose of vecuronium should be considered.

Altered Circulation Time: Conditions associated with slower circulation time in cardiovascular disease, old age, and edematous states resulting in increased volume of distribution may contribute to delay in onset time; therefore, dosage should not be increased.

Hepatic Disease: Experience in patients with cirrhosis or cholestasis has revealed prolonged recovery time in keeping with the role the liver plays in vecuronium metabolism and excretion (see See package insert for CLINICAL PHARMACOLOGY, Pharmacokinetics). Data currently available do not permit dosage recommendations in patients with impaired liver function.

Long-term Use in I.C.U.: In the intensive care unit, long-term use of neuromuscular blocking drugs to facilitate mechanical ventilation may be associated with prolonged paralysis and/or skeletal muscle weakness that may be first noted during attempts to wean such patients from the ventilator. Typically, such patients receive other drugs such as broad spectrum antibiotics, narcotics and/or steroids and may have electrolyte imbalance and diseases which lead to electrolyte imbalance, hypoxic episodes of varying duration, acid-base imbalance and extreme debilitation, any of which may enhance the actions of a neuromuscular blocking agent. Additionally, patients immobilized for extended periods frequently develop symptoms consistent with disuse muscle atrophy. The recovery picture may vary from regaining movement and strength in all muscles to initial recovery of movement of the facial and small muscles of the extremities then to the remaining muscles. In rare cases recovery may be over an extended period of time and may even, on occasion, involve rehabilitation. Therefore, when there is a need for long-term mechanical ventilation, the benefits-to-risk ratio of neuromuscular blockade must be considered.

Continuous infusion or intermittent bolus dosing to support mechanical ventilation has not been studied sufficiently to support dosage recommendations. IN THE INTENSIVE CARE UNIT, APPROPRIATE MONITORING, WITH THE USE OF A PERIPHERAL NERVE STIMULATOR TO ASSESS THE DEGREE OF NEUROMUSCULAR BLOCKADE IS RECOMMENDED TO HELP PRECLUDE POSSIBLE PROLONGATION OF THE BLOCKADE. WHENEVER THE USE OF VECURONIUM OR ANYNEUROMUSCULAR BLOCKING AGENT IS CONTEMPLATED IN THE ICU, IT IS RECOMMENDED THAT NEUROMUSCULAR TRANSMISSION BE MONITORED CONTINUOUSLY DURING ADMINISTRATION AND RECOVERY WITH THE HELP OF A NERVE STIMULATOR. ADDITIONAL DOSES OF VECURONIUM BROMIDE OR ANY OTHER NEUROMUSCULAR BLOCKING AGENT SHOULD NOT BE GIVEN BEFORE THERE IS A DEFINITE RESPONSE TO T1 OR TO THE FIRST TWITCH. IF NO RESPONSE IS ELICITED, INFUSION ADMINISTRATION SHOULD BE DISCONTINUED UNTIL A RESPONSE RETURNS.

Severe Obesity or Neuromuscular Disease: Patients with severe obesity or neuromuscular disease may pose airway and/or ventilatory problems requiring special care before, during and after the use of neuromuscular blocking agents such as vecuronium.

Malignant Hyperthermia: Many drugs used in anesthetic practice are suspected of being capable of triggering a potentially fatal hypermetabolism of skeletal muscle known as malignant hyperthermia. There are insufficient data derived from screening in susceptible animals (swine) to establish whether or not vecuronium is capable of triggering malignant hyperthermia.

C.N.S.: Vecuronium has no known effect on consciousness, the pain threshold or cerebration. Administration must be accompanied by adequate anesthesia or sedation

DOSAGE AND ADMINISTRATION
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 by volatile anesthetics and by prior use of succinylcholine (see PRECAUTIONS/ See package insert for Drug Interactions). Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

To obtain maximum clinical benefits of vecuronium 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 0.10 mg/kg (1.4 to 1.75 times the ED90) 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 25-30 minutes, with recovery to 25% of control achieved approximately 25 to 40 minutes after injection and recovery to 95% of control achieved approximately 45-65 minutes after injection. In the presence of potent inhalation anesthetics, the neuromuscular blocking effect of vecuronium is enhanced. If vecuronium 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., 0.060 to 0.085 mg/kg.

Prior administration of succinylcholine may enhance the neuromuscular blocking effect and duration of action of vecuronium. If intubation is performed using succinylcholine, a reduction of initial dose of vecuronium bromide to 0.04-0.06 mg/kg with inhalation anesthesia and 0.05-0.06 mg/kg with balanced anesthesia may be required.

During prolonged surgical procedures, maintenance doses of 0.010 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 25 to 40 minutes. However, clinical criteria should be used to determine the need for maintenance doses.

Since vecuronium lacks clinically important cumulative effects, subsequent maintenance doses, if required, may be administered at relatively regular intervals for each patient, ranging approximately from 12 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 (See package insert for CLINICAL PHARMACOLOGY).

Use by Continuous Infusion: After an intubating dose of 80-100 mcg/kg, a continuous infusion of 1 mcg/kg/min can be initiated approximately 20-40 min later. Infusion of vecuronium 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. (see PRECAUTIONS ).

The infusion of vecuronium 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 25-60 percent, 45-60 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 infusion may be expected to proceed at rates comparable to that following a single bolus dose (See package insert for CLINICAL PHARMACOLOGY).

Infusion solutions of vecuronium can be prepared by mixing vecuronium with an appropriate infusion solution such as Dextrose Injection 5%, Sodium Chloride Injection 0.9%, Dextrose (5%) and Sodium Chloride 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

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.

NOTE: If a concentration of 0.2 mg/mL is used (20 mg in 100 mL), the rate should be decreased by one-half.

Dosage in Pediatric Patients: Older pediatric patients (10 to 17 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 one year of age but older than 7 weeks are moderately more sensitive to vecuronium 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 neonates (see PRECAUTIONS ). 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 Injection 0.9%
Dextrose Injection 5%
Sterile Water for Injection
Dextrose (5%) and Sodium Chloride Injection
Lactated Ringer's Injection
Use within 24 hours of mixing with the above solutions.

After Reconstitution:
When reconstituted with supplied bacteriostatic water for injection: CONTAINS BENZYL ALCOHOL, WHICH IS NOT INTENDED FOR USE IN NEWBORNS. Use within 5 days. May be stored at room temperature or refrigerated.

When reconstituted with sterile water for injection or other compatible I.V. solutions: Refrigerate vial. Use within 24 hours. Single use only. Discard unused portion.

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

HOW SUPPLIED

Store dry powder at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.] Protect from light.

December, 2004
©Hospira 2004 EN-0775 Printed in USA
HOSPIRA, INC., LAKE FOREST, IL 60045 USA

Source: [package insert]