VECURONIUM BROMIDE

General Administration Information
For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
-Accidental administration of neuromuscular blocking agents can be fatal. Store vecuronium with the cap and ferrule intact, in a manner that minimizes the possibility of selecting the wrong product.
Intravenous Administration
-Only experienced clinicians, familiar with the use of neuromuscular blocking drugs, should administer or supervise the use of vecuronium. Adequacy of respiration must be assured through assisted or controlled ventilation.
-To avoid distress to the patient, administer vecuronium only after unconsciousness has been induced. Adequate amnesia, sedation, and analgesia should accompany neuromuscular blockade.
-Do not mix vecuronium with alkaline solutions (e.g., barbiturate solutions such as thiopental) in the same syringe or administer simultaneously during IV infusion through the same needle or through the same IV line; vecuronium has an acidic pH.

Reconstitution
-Reconstitute by adding 10 or 20 mL of Bacteriostatic Water for Injection to 10 or 20 mg, respectively, to give a parenteral solution containing 1 mg/mL. For neonates, use Sterile Water for Injection to avoid the administration of benzyl alcohol.
-Storage: When reconstituted with Bacteriostatic Water for Injection, store at room temperature or refrigerated for up to 5 days. When reconstituted with Sterile Water for Injection, the vial is single-use; store in the refrigerator for up to 24 hours. Discard any unused solution.

Intermittent IV Injection
-No further dilution necessary.
-Administer by direct IV injection.

Continuous IV Infusion
-Dilute the reconstituted solution with 0.9% Sodium Chloride Injection, 5% Dextrose Injection, 5% Dextrose and 0.9% Sodium Chloride Injection, Lactated Ringer's Injection, or Sterile Water for Injection to a concentration of 0.1 to 0.2 mg/mL. Concentrations up to 1 mg/mL are commonly used in pediatric patients.
-Infuse at a rate based on patient response and requirements.
-A peripheral nerve stimulator is recommended to monitor vecuronium's effects. Target response is typically 1 to 2 twitches. Incorrect electrode placement, direct stimulation of muscle due to large electrode size, acute illness, capillary leak, and edema may affect an appropriate assessment. Monitor visual and tactile stimulation on muscle movement as well as heart rate, blood pressure, and mechanical ventilator status during administration.

Although rare, severe anaphylactic or anaphylactoid reactions to neuromuscular blocking agents (NMBAs), including vecuronium, have been reported; some cases have been fatal. Immediate availability of appropriate emergency treatment for anaphylaxis is advised because of the potential life-threatening severity of a reaction. Vecuronium has minimal histamine-release at therapeutic doses and is less likely to cause bronchospasm or cardiac adverse effects than NMBAs with significant histamine-releasing properties such as atracurium, mivacurium, or succinylcholine. However, rare hypersensitivity reactions (e.g., angioedema, bronchospasm, wheezing, flushing, rash, erythema, urticaria, pruritus, hypotension, sinus tachycardia) related to histamine release have been reported after vecuronium administration.

Malignant hyperthermia can be precipitated by many drugs used in anesthetic practice, including halogenated anesthetics and depolarizing neuromuscular blocking agents (e.g., succinylcholine). It is unknown whether vecuronium is capable of triggering hyperthermia; however, because of the potentially fatal outcome, consider all patients undergoing anesthesia with neuromuscular blocking agents, such as vecuronium, at risk.

Vecuronium is used for the purpose of inducing temporary paralysis; however, some of its most serious adverse effects are extensions of its therapeutic use. Careful monitoring of physiologic parameters and response to a peripheral nerve stimulator is recommended during continuous infusions or repeated dosing. Though paralysis may be used to facilitate mechanical ventilation, hypoxia may result from inadequate ventilation and/or a deterioration in pulmonary mechanics associated with prolonged paralysis. Excessive doses or prolonged exposure to neuromuscular blocking agents (NMBAs) can cause skeletal muscle weakness, and patients may consequentially experience prolonged apnea, dyspnea, respiratory depression, and/or profound muscular weakness (muscle paralysis). Muscle weakness in critically ill patients is multifactorial; however, prolonged recovery is most often related to excessive dosing of neuromuscular blockers or use of these agents in patients with hepatic or renal dysfunction. These patients may take hours to days to recover due to long-term accumulation of the drug and its metabolites. Perhaps the most devastating complication of neuromuscular blockade, acute quadriplegic myopathy syndrome (AQMS), presents as acute paresis, myonecrosis with increased creatine phosphokinase (CPK), and abnormal electromyography (EMG). After drug discontinuation, patients present with flaccid paralysis, decreased deep tendon reflexes, and respiratory insufficiency. Sensory function and extraocular movement are preserved, and there are no abnormal cerebrospinal fluid findings. Prolonged rehabilitation as well as chronic ventilatory support are often needed in patients with AQMS. Recovery may take weeks to months. To reduce the risk of prolonged recovery and AQMS, periodic screening of CPK during ongoing neuromuscular blockage may be helpful. Though periodic interruption of therapy is often not feasible and there is no direct evidence showing that it reduces the incidence of AQMS, daily 'drug holidays' may be considered for patients who will tolerate an interruption in therapy.

Patients receiving vecuronium are at risk for developing xerophthalmia, leading to keratitis, conjunctivitis, and corneal abrasion because muscle paralysis inhibits eyelid movement and complete closure. Prophylactic eye care is essential; use artificial tears or ophthalmic ointment at regular intervals during neuromuscular blockade. Additionally, paralyzed patients with prolonged immobility are at risk for skin erosion, skin ulcer (pressure sore), and deep vein thrombosis (DVT). Frequent repositioning, physical therapy, and DVT prophylaxis are indicated. The use of special mattresses may be considered.

Awake, paralyzed patient-anxiety and panic may be the most bothersome adverse effect associated with neuromuscular blockade. Neuromuscular blockers, such as vecuronium, do not provide sedation or analgesia and should be administered only after unconsciousness has been induced. It is essential that amnesia, sedation, and analgesia are adequately maintained throughout paralyzation. Depth of sedation is difficult to monitor due to lack of movement with paralyzation. Physiologic parameters such as heart rate or blood pressure may be of use; however, there are many confounding influences on these parameters in critically ill patients.

Patients who receive neuromuscular blocking agents for a prolonged period may develop tachyphylaxis (i.e., tolerance). Prolonged blockade leads to proliferation of acetylcholine receptors at the neuromuscular junction resulting in increased drug requirements. Switch patients who develop tachyphylaxis to vecuronium and still require neuromuscular blockade to another agent. Continuous monitoring of neuromuscular transmission with a peripheral nerve stimulator is strongly recommended during continuous infusion or repeated dosing. Target response is typically 1 to 2 twitches. Incorrect electrode placement, direct stimulation of muscle due to large electrode size, acute illness, capillary leak, and edema may affect an appropriate assessment. Monitor visual and tactile stimulation on muscle movement as well as heart rate, blood pressure, and mechanical ventilator status during administration.

Administer vecuronium only after unconsciousness has been induced; maintain adequate amnesia and analgesia throughout paralyzation. Neuromuscular blocking agents do not cause sedation or analgesia. Individualize vecuronium doses. Use of a peripheral nerve stimulator will permit the most advantageous use of vecuronium, minimize the possibility of overdosage or underdosage, and assist in the evaluation of recovery.

Vecuronium administration requires an experienced clinician who is familiar with its actions and the possible complications that may occur after its use as well as requires a specialized care setting where facilities for intubation, artificial respiration, oxygen therapy, and reversal agents are immediately available. Accidental exposure to a neuromuscular blocking agent may be fatal in a patient for whom it is not intended. Store vecuronium with cap and ferrule intact and in a manner that minimizes the possibility of selecting the wrong product. Confirm proper medication selection and clearly communicate the intended dose.

Vecuronium is contraindicated in patients known to have a vecuronium bromide hypersensitivity. Use vecuronium with caution in patients with neuromuscular blocking agent hypersensitivity since cross-reactivity between neuromuscular blocking agents, both depolarizing and non-depolarizing, has been reported. Severe anaphylactic reactions to neuromuscular blocking agents, including vecuronium, have been reported. These reactions have been life-threatening and fatal in some cases. Due to the potential severity of these reactions, ensure the necessary precautions, such as the immediate availability of appropriate emergency treatment.

Patients with burns have a decreased sensitivity to vecuronium's ability to produce neuromuscular blockade. Resistance to blockade usually develops in patients with burns more than 10% total body surface area approximately 1 week after thermal injury. Increased doses may be required in burn patients; alteration in drug effect may be seen for up to 1 year. In patients with more than 40% total body surface area burns, significant increases in dosage requirements (i.e., 2.5 to 5 times the usual dose) have been reported.

Various physiologic states can alter the expected effects of vecuronium; carefully consider each patient's clinical condition when dosing vecuronium and monitoring the patient. Cachectic and debilitated patients are more sensitive to neuromuscular blocking agents (NMBAs). Electrolyte imbalance can alter a patient's sensitivity to NMBAs. Hypercalcemia can decrease sensitivity to NMBAs, while most other electrolyte disturbances increase sensitivity (e.g., hypokalemia, hypocalcemia, hypermagnesemia). Use vecuronium cautiously in patients with conditions that may lead to electrolyte imbalances, such as adrenal insufficiency. Severe acid/base imbalance may alter a patient's sensitivity to NMBAs: metabolic alkalosis, metabolic acidosis, and respiratory acidosis may enhance neuromuscular blockade and/or prolong recovery time, while respiratory alkalosis reduces the potency of the drug. Dehydration and hypothermia can also increase a patient's sensitivity to NMBAs.

Use neuromuscular blocking agents (NMBAs), including vecuronium, with caution in patients with asthma or other pulmonary conditions. NMBAs stimulate histamine release, which could exacerbate asthma. Compared with other NMBAs, vecuronium produces little or no histamine release. While some experts consider vecuronium to be an NMBA of choice in asthmatic patients, it should be used with caution in those with any condition in which a significant release of histamine may be contraindicated. Also, NMBAs cause respiratory muscle paralysis; residual muscle weakness and decreased respiratory function (respiratory depression) can persist even after drug discontinuation. Use NMBAs with caution in patients with pulmonary disease and conditions associated with low pulmonary function reserve, such as neonatal chronic lung disease (CLD). Carefully monitor respiratory status and adequacy of ventilation after drug recovery until the patient is clearly stabilized.

Use vecuronium with caution in patients with neuromuscular disease (e.g., myasthenia gravis, myasthenic syndrome [Eaton Lambert syndrome]); prolonged or exaggerated neuromuscular blockade may occur after nondepolarizing agent use. Additionally, patients with weak muscle tone or severe obesity are at an increased risk for airway and ventilation complications. Consider the use of a small test dose and a peripheral nerve stimulator to monitor response in these patients. Monitor patients carefully until recovery is fully complete. Guidelines for sustained neuromuscular blockade in critically ill children recommend calculating the dose according to IBW.

Use vecuronium with caution in patients with cardiac disease or other conditions that may be associated with a slower circulation time. Changes in the volume of distribution related to poor circulation or edema can delay the onset of neuromuscular blockade. Particular care is required in administering subsequent doses when it is uncertain whether maximum effect has been attained.

Experience with vecuronium in patients with hepatic disease (i.e., cirrhosis, cholestasis) has revealed prolonged recovery time.

Prolonged recovery due to accumulation of the active metabolite and parent compound may occur in patients with uremia. Although vecuronium is primarily dependent on hepatic clearance, hepatic elimination is decreased in patients with uremia. Prolonged recovery may also occur in anephric patients when preoperative dialysis is not possible. Consider a lower dosage in such situations. Vecuronium is well tolerated in patients with renal failure who have been optimally prepared for surgery by dialysis.

Treat patients with a personal or familial history of malignant hyperthermia with extreme caution. Malignant hyperthermia can be precipitated by many drugs used in anesthetic practice, including halogenated anesthetics and depolarizing neuromuscular blocking agents (e.g., succinylcholine). It is unknown whether vecuronium is capable of triggering hyperthermia.

Younger children (1 to 10 years) may require a slightly higher initial vecuronium dose and may also require supplementation slightly more often than adults. Neonates and infants are more sensitive to the effects of vecuronium compared to older patients; they may take up to 1.5 times as long to recover from neuromuscular blockade. Monitor young patients carefully during and after administration.

Description: Vecuronium is a parenteral, intermediate-acting, nondepolarizing, neuromuscular blocking agent indicated as an adjunct to general anesthesia to facilitate endotracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation. Vecuronium is approximately one-third more potent than pancuronium, with a shorter duration of action at initially equipotent doses. It is one of the most common neuromuscular blockers used in critically ill children. While continuous infusions of neuromuscular blocking agents are often used in critically ill adults, the use of sustained neuromuscular blockade is less common in pediatric intensive care units. Consensus guidelines from the United Kingdom recommend vecuronium or atracurium as the preferred agents for critically ill children requiring sustained neuromuscular blockade, although strong data comparing neuromuscular blocking agents in pediatric patients are not available. Vecuronium causes minimal catecholamine and histamine release and is not likely to cause clinically significant bronchospasm or cardiac adverse effects compared to agents with histamine-releasing properties such as atracurium and succinylcholine. For this reason, vecuronium is often considered to be a preferred agent in patients with cardiac conditions, hemodynamic instability, asthma, or severe allergic reactions. Vecuronium is FDA-approved in pediatric patients as young as 7 weeks.

General dosing information:
-Based on physiologic differences, neonates and infants tend to be more sensitive to paralysis with neuromuscular blocking agents (resulting in a recovery time approximately 1.5 times that of adults), while children tend to require larger doses than those of infants or adults.
-Guidelines for sustained neuromuscular blockade in critically ill children recommend calculating the dose according to IBW.
-Use a peripheral nerve stimulator during continuous infusion or repeated dosing to monitor vecuronium's effects. Target response is typically 1 to 2 twitches. Incorrect electrode placement, direct stimulation of muscle due to large electrode size, acute illness, capillary leak, and edema may affect an appropriate assessment. Monitor visual and tactile stimulation on muscle movement as well as heart rate, blood pressure, and mechanical ventilator status during administration.
-Switch patients who develop tachyphylaxis to vecuronium and still require paralysis to another agent.

For muscular relaxation during non-emergent endotracheal intubation or rapid-sequence intubation (RSI)*:
Intravenous dosage:
Neonates*: 0.1 mg/kg/dose IV. Onset of intubating conditions is 2.5 to 3 minutes. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
Infants younger than 7 weeks*: 0.1 mg/kg/dose IV. Onset of intubating conditions is 2.5 to 3 minutes. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
Infants, Children, and Adolescents 7 weeks to 17 years: 0.15 to 0.2 mg/kg/dose IV. Onset of intubating conditions is 2.5 to 3 minutes. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
-for defasciculation before succinylcholine administration*:
Intravenous dosage:
Children and Adolescents 6 to 17 years: 0.01 mg/kg/dose IV given 1 to 3 minutes prior to succinylcholine. Defasciculation is not commonly used in pediatric patients. Defasciculation delays paralysis and may increase the succinylcholine dose requirement. In patients with significant hemodynamic and/or respiratory compromise, the defasciculation dose may be enough to result in respiratory compromise.

For neuromuscular blockade during mechanical ventilation:
Intermittent Intravenous dosage:
Neonates*: 0.03 to 0.15 mg/kg/dose IV every 30 to 40 minutes as needed; adjust dose and interval to patient's twitch response. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
Infants younger than 7 weeks*: 0.03 to 0.15 mg/kg/dose IV every 30 to 40 minutes as needed; adjust dose and interval to patient's twitch response. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
Infants, Children, and Adolescents 7 weeks to 17 years: 0.08 to 0.1 mg/kg IV once, followed by 0.01 to 0.015 mg/kg/dose IV every 12 to 15 minutes as needed; adjust dose and interval to patient's twitch response. Generally, the first maintenance dose is required within 25 to 40 minutes after the initial dose. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
Continuous Intravenous Infusion dosage*:
Neonates: Limited data; 0.1 mg/kg/dose IV bolus, followed by 0.3 to 1 mcg/kg/minute continuous IV infusion; titrate by 10% to patient's twitch response. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
Infants: 0.08 to 0.1 mg/kg IV bolus, followed by 0.3 to 1.6 mcg/kg/minute continuous IV infusion; titrate by 10% to patient's twitch response. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
Children and Adolescents: 0.08 to 0.1 mg/kg IV bolus, followed by 0.8 to 2.5 mcg/kg/minute continuous IV infusion; titrate by 10% to patient's twitch response. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

For neuromuscular blockade during surgery:
Intermittent Intravenous dosage:
Infants, Children, and Adolescents 7 weeks to 17 years: 0.08 to 0.1 mg/kg IV once, followed by 0.01 to 0.015 mg/kg/dose IV every 12 to 15 minutes as needed; adjust dose and interval to patient's twitch response. Generally, the first maintenance dose is required within 25 to 40 minutes after the initial dose. Higher doses up to 0.28 mg/kg/dose have been used. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Maximum Dosage Limits:
Specific maximum dosage information is not available. Dosage must be individualized based on clinical response.

Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available. Experience with vecuronium in patients with hepatic disease has revealed prolonged recovery time.

Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available. Prolonged recovery due to accumulation of the active metabolite and parent compound may occur in patients with uremia. Prolonged recovery may also occur in anephric patients when preoperative dialysis is not possible. Consider a lower dosage in such situations. Vecuronium is well tolerated in patients with renal failure who have been optimally prepared for surgery by dialysis.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Muscle contraction is initiated by an action potential traveling from the central nervous system to the nerve terminal. At the nerve terminal, the action potential causes an influx of calcium, initiating release of acetylcholine (ACh) into the synaptic cleft. ACh binds to ACh receptors on the muscle fiber's motor end-plate causing a conformational change that briefly opens sodium ion channels. When an adequate number of ACh receptors are activated, membrane potential decreases and voltage-dependent sodium ion channels of adjacent muscle membranes activate, transmitting the action potential throughout the muscle fiber and resulting in muscle contraction. Nondepolarizing agents such as vecuronium produce skeletal muscle paralysis by competing with ACh for cholinergic receptor sites at the motor end-plate. Neuromuscular blockade progresses in a predictable order, beginning with muscles associated with fine movements (e.g., eyes, face, and neck), followed by muscles of the limbs, chest, and abdomen and, finally, the diaphragm. Larger doses increase the chance of respiratory depression associated with relaxation of the intercostal muscles and the diaphragm. Muscle tone returns in the reverse order. Vecuronium produces minimal to no histamine release and no ganglion blockade; therefore, hypotension and bronchospasm are not associated with its use.

Pharmacokinetics: Vecuronium is administered intravenously. At usual therapeutic doses, vecuronium is approximately 60% to 80% protein bound. After administration, the drug is rapidly distributed to the extracellular space. Distribution half-life is approximately 4 minutes in adults. Vd varies with age and is larger in infants compared to children. The metabolic fate of vecuronium is unclear, but spontaneous hydrolysis of the ester groups is known to occur. The 3-desacetyl metabolite is 50% to 70% as potent as the parent compound. The 3-deacetyl derivative accounts for up to 10% of a dose excreted in the urine and up to 25% of the drug excreted in the bile. Approximately 3% to 35% of an intravenous dose is excreted in the urine within 24 hours and 25% to 50% in the feces via the bile within 42 hours. Due to developmental changes, clearance of vecuronium varies depending on age and is highest during childhood. In general, the elimination half-life is 65 minutes in infants, 41 minutes in children, and 65 to 75 minutes in adults.

Affected cytochrome P450 isoenzymes and drug transporters: none


-Route-Specific Pharmacokinetics
Intravenous Route
In pediatric patients, neuromuscular blockade begins within 1 to 3 minutes and lasts 30 to 40 minutes. Intensity and duration of action are affected by the dose, age of the patient, and the use of concurrent anesthetics and other neuromuscular blocking agents.


-Special Populations
Pediatrics
Neonates and Infants
Infants have a larger extracellular fluid compartment resulting in a large Vd compared to other populations. The Vd of vecuronium in infants is 0.36 L/kg, compared to 0.2 L/kg in children and 0.27 L/kg in adults. Although a large Vd could suggest larger dosage requirements, infants have fewer acetylcholine receptors; therefore, plasma concentrations of vecuronium needed to maintain paralysis are lower. Additionally, hepatic enzyme immaturity may play a role in slower clearance compared to other populations. In a pharmacokinetic study of pediatric patients (n = 81), vecuronium 0.1 mg/kg and 0.15 mg/kg maintained neuromuscular blockade at 90% or greater of baseline for 59 and 110 minutes, respectively, in neonates and infants, 18 and 38 minutes in children, and 37 and 68 minutes in adolescents. In another study, the vecuronium dose required to produce 95% suppression of the muscle twitch response (ED95) was identical in neonates and infants (47 mcg/kg) and was significantly less than that required in children. Elimination half-life in infants is 65 minutes, which is similar to that of adults.

Children
The Vd of vecuronium in children is 0.2 L/kg, compared to 0.36 L/kg in infants and 0.27 L/kg in adults. Although a smaller Vd suggests a smaller dosage requirement, acetylcholine receptor availability must also be considered. Children have a larger number of acetylcholine receptors compared to infants, adolescents, and adults due to their larger muscle mass to fat ratio. The plasma concentration of a drug needed to maintain paralysis increases as receptor numbers increase. Therefore, dosage requirements on a mg/kg basis are higher in children than in other populations. The dose required to produce 95% suppression of the muscle twitch response (ED95) of vecuronium is significantly greater in children (81 mcg/kg) than in neonates and infants. In a pharmacokinetic study of pediatric patients (n = 81), vecuronium 0.1 mg/kg and 0.15 mg/kg maintained neuromuscular blockade at 90% or greater of baseline for a shorter duration in children (18 and 38 minutes, respectively) compared to neonates/infants (59 and 110 minutes) and adolescents (37 and 68 minutes). Elimination half-life in children is 41 minutes, compared to 65 minutes in infants and 71 minutes in adults.

Hepatic Impairment
A significant amount of a vecuronium dose is hepatically eliminated. In patients with hepatic dysfunction, duration of action is prolonged. Data from patients with cirrhosis or cholestasis suggests recovery time may be doubled with vecuronium use.

Renal Impairment
Approximately 3% to 35% of a vecuronium dose is renally eliminated. In patients with renal failure, duration of action may be prolonged due to accumulation of 3-desacetyl vecuronium (active metabolite).