Vecuronium

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous, as bromide:

Generic: 10 mg (1 ea); 20 mg (1 ea)

Solution Reconstituted, Intravenous, as bromide [preservative free]:

Generic: 10 mg (1 ea); 20 mg (1 ea)

Pharmacology

Mechanism of Action

Blocks acetylcholine from binding to receptors on motor endplate inhibiting depolarization

Pharmacokinetics/Pharmacodynamics

Distribution

V_d: 0.3 to 0.4 L/kg

Metabolism

Active metabolite: 3-desacetyl vecuronium (¹/₂ the activity of parent drug)

Excretion

Primarily feces (40% to 75%); urine (30% as unchanged drug and metabolites); the rate of elimination is appreciably reduced with hepatic dysfunction but not with renal dysfunction

Onset of Action

Good intubation conditions: Within 2.5 to 3 minutes; Maximum neuromuscular blockade: Within 3 to 5 minutes

Duration of Action

Under balanced anesthesia (time to recovery to 25% of control): 25 to 40 minutes; recovery 95% complete ~45 to 65 minutes after injection of intubating dose; hypothermia may prolong the duration of action

Half-Life Elimination

Infants: 65 minutes

Children: 41 minutes

Healthy adult surgical patients and renal failure patients undergoing transplant surgery: 65 to 75 minutes; Late pregnancy: 35 to 40 minutes

Half-life, distribution: Adults: 4 minutes

Protein Binding

60% to 80%

Use: Labeled Indications

Neuromuscular blockade for endotracheal intubation, surgery, or mechanical ventilation: As adjunct to general anesthesia to facilitate endotracheal intubation and to relax skeletal muscles during surgery or mechanical ventilation in adequately sedated ICU patients

Note: Neuromuscular blockade does not provide pain control, sedation, or amnestic effects. Appropriate analgesic and sedative mediations should be used before and during administration of neuromuscular blockade to achieve deep sedation.

Use: Off Label

Acute respiratory distress syndromeyes

Based on the Society for Critical Care Medicine Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient, a neuromuscular blocker may be considered for short-term use (up to 48 hours) during the early course of acute respiratory distress syndrome (ARDS) in adults with PaO₂/FiO₂ <150 mmHg SCCM [Murray 2016]. Some experts recommend that neuromuscular blockers be considered for short-term use (up to 48 hours) only in patients with ARDS and severe gas exchange abnormalities (PaO₂/FiO₂ ≤120 mmHg) Siegel 2018. Note: Only cisatracurium has been studied in patients with ARDS. Whether or not other neuromuscular blockers will yield similar results is unknown.

Shivering due to therapeutic hypothermia following cardiac arrestyes

Based on the Society for Critical Care Medicine Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient, a neuromuscular blocker may be used to manage overt shivering in therapeutic hypothermia following cardiac arrest.

Contraindications

Hypersensitivity to vecuronium or any component of the formulation

Documentation of allergenic cross-reactivity for neuromuscular blockers is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosage and Administration

Dosing: Adult

Note: Dose to effect; doses will vary due to interpatient variability. Ensure adequate pain control and sedation prior to and during administration neuromuscular blockade to achieve deep sedation (SCCM [Murray 2016]).

Neuromuscular blockade for endotracheal intubation, surgery, or mechanical ventilation (as adjunct to general anesthesia): IV:

Tracheal intubation: IV: Initial: 0.08 to 0.1 mg/kg. Note: If intubation is performed using succinylcholine, the initial dose of vecuronium may be reduced to 0.04 to 0.06 mg/kg with inhalation anesthesia and 0.05 to 0.06 mg/kg with balanced anesthesia.

Obesity: For obese (≥130% of IBW) adult patients, may use ideal body weight (IBW) (Erstad 2004; Schwartz 1992; Weinstein 1988); onset time may be slightly delayed using IBW.

Pretreatment/priming: 10% of intubating dose given 3 to 5 minutes before intubating dose

Maintenance for continued surgical relaxation (only after return of neuromuscular function): Intermittent dosing: 0.01 to 0.015 mg/kg or continuous infusion of 0.8 to 1.2 mcg/kg/minute (0.048 to 0.072 mg/kg/hour).

Note: Use lower end of the dosing range when anesthesia is maintained with an inhaled anesthetic agent, with the redosing interval guided by monitoring with a peripheral nerve stimulator.

Intensive care unit paralysis (eg, use for up to 48 hours in patients with early ARDS with PaO₂/FiO₂ <150, to facilitate mechanical ventilation, shivering from therapeutic hypothermia) (off-label dosing): IV: Initial bolus dose: 0.08 to 0.1 mg/kg, then a continuous IV infusion of 0.8 to 1.7 mcg/kg/minute (0.048 to 0.102 mg/kg/hour); monitor depth of blockade every 1 to 2 hours initially until stable dose, then every 8 to 12 hours. Usual maintenance infusion dose range: 0.8 to 1.2 mcg/kg/minute (0.048 to 0.072 mg/kg/hour) (ACCM/SCCM/ASHP [Murray 2002]; Darrah 1989; Greenberg 2013; Rudis 1997)

Dosage adjustment: Adjust rate of administration in increments of 0.3 mcg/kg/minute (or 0.018 mg/kg/hour) or by 50% reductions of previous dose according to desired clinical response and possibly using peripheral nerve stimulation response. Discontinue infusion if neuromuscular function does not return (Rudis 1996; Rudis 1997).

Note: When possible, minimize depth and duration of paralysis. Stopping the infusion daily for some time until forced to restart based on patient condition is recommended to reduce post-paralytic complications (eg, acute quadriplegic myopathy syndrome [AQMS]) (ACCM/SCCM/ASHP [Murray 2002]; SCCM [Murray 2016]; Segredo 1992)

Intermittent bolus dosing: 0.1 to 0.2 mg/kg/dose; may be repeated when neuromuscular function returns (Hunter 1985); for shivering from therapeutic hypothermia may use 8 to 12 mg, repeated as needed to maintain adequate control (Bernard 2002; Nolan 2003; Polderman 2009)

Dosing: Geriatric

Refer to adult dosing. Dose selection should be cautious, at low end of dosage range, and titration should be slower to evaluate response.

Dosing: Pediatric

Note: Dose to effect; doses will vary due to interpatient variability. Dosing in obese patients should be calculated using ideal body weight (Playfor 2007).

Paralysis/skeletal muscle relaxation:

Manufacturer's labeling: Surgical relaxation, tracheal intubation: Infants >7 weeks, Children, and Adolescents: IV: 0.08 to 0.1 mg/kg; Note: If intubation is performed using succinylcholine, the initial dose of vecuronium may be reduced to 0.04 to 0.06 mg/kg with inhalation anesthesia and 0.05 to 0.06 mg/kg with balanced anesthesia. Children 1 to 10 years may require slightly higher initial doses and more frequent supplementation.

Alternate dosing (Martin 1999; Playfor 2007):

Infants:

IV: 0.08 to 0.1 mg/kg/dose; repeat as needed

Continuous IV infusion: 0.8 to 1.7 mcg/kg/minute (0.05 to 0.1 mg/kg/hour)

Children and Adolescents:

IV: 0.08 to 0.1 mg/kg/dose; repeat as needed

Continuous IV infusion: 0.8 to 2.5 mcg/kg/minute (0.05 to 0.15 mg/kg/hour)

Dosing: Obesity

Refer to indication-specific dosing for obesity-related information (may not be available for all indications). Ideal body weight or adjusted body weight is generally recommended when calculating dose for obese patients (SCCM [Murray 2016]).

Reconstitution

Reconstitute with compatible solution (eg, D5W, NS) for injection to final concentration of 1 mg/mL. May further dilute reconstituted vial to 0.1 to 0.2 mg/mL in a compatible solution for IV infusion.

Administration

IV: For IV administration only; do not administer IM. Concentration of 1 mg/mL may be administered by rapid IV injection; may also be used for IV infusion in fluid-restricted patients.

Storage

Store intact vials at 20°C to 25°C (68°F to 77°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 (including D5W, D5NS, LR, NS) should be stored under refrigeration and used within 24 hours.

Drug Interactions

Acetylcholinesterase Inhibitors: May diminish the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Aminoglycosides: May enhance the respiratory depressant effect of Neuromuscular-Blocking Agents. Monitor therapy

Bacitracin (Systemic): May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Botulinum Toxin-Containing Products: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Bromperidol: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Calcium Channel Blockers: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Capreomycin: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

CarBAMazepine: May decrease the serum concentration of Vecuronium. Monitor therapy

Cardiac Glycosides: Neuromuscular-Blocking Agents may enhance the arrhythmogenic effect of Cardiac Glycosides. Monitor therapy

Clindamycin (Topical): May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Colistimethate: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Consider therapy modification

Corticosteroids (Systemic): Neuromuscular-Blocking Agents (Nondepolarizing) may enhance the adverse neuromuscular effect of Corticosteroids (Systemic). Increased muscle weakness, possibly progressing to polyneuropathies and myopathies, may occur. Consider therapy modification

CycloSPORINE (Systemic): May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Dantrolene: May enhance the neuromuscular-blocking effect of Vecuronium. Monitor therapy

Fosphenytoin-Phenytoin: May diminish the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Fosphenytoin-Phenytoin may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Fosphenytoin-Phenytoin may decrease the serum concentration of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Inhalational Anesthetics: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Ketorolac (Nasal): May enhance the adverse/toxic effect of Neuromuscular-Blocking Agents (Nondepolarizing). Specifically, episodes of apnea have been reported in patients using this combination. Monitor therapy

Ketorolac (Systemic): May enhance the adverse/toxic effect of Neuromuscular-Blocking Agents (Nondepolarizing). Specifically, episodes of apnea have been reported in patients using this combination. Monitor therapy

Lincosamide Antibiotics: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Lithium: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Local Anesthetics: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Exceptions: Benzocaine; Benzydamine; Cocaine (Topical); Dibucaine; Dyclonine; Ethyl Chloride; Hexylresorcinol; Lidocaine (Ophthalmic); Lidocaine (Topical); Pramoxine; Proparacaine; Tetracaine (Ophthalmic); Tetracaine (Topical). Monitor therapy

Loop Diuretics: May diminish the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Loop Diuretics may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Magnesium Salts: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

MetroNIDAZOLE (Systemic): May enhance the neuromuscular-blocking effect of Vecuronium. Monitor therapy

Minocycline (Systemic): May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Pholcodine: May enhance the adverse/toxic effect of Neuromuscular-Blocking Agents. Specifically, anaphylaxis has been reported. Monitor therapy

Piperacillin: May enhance the neuromuscular-blocking effect of Vecuronium. Monitor therapy

Polymyxin B: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Consider therapy modification

Procainamide: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

QuiNIDine: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

QuiNINE: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Avoid combination

Spironolactone: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Tetracyclines: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Thiazide and Thiazide-Like Diuretics: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Trimebutine: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Vancomycin: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Adverse Reactions

<1%, postmarketing, and/or case reports: Bradycardia, circulatory shock, edema, flushing, hypersensitivity reaction (including erythema, hypotension, tachycardia, urticaria), pruritus, skin rash

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylaxis: Severe anaphylactic reactions have been reported with vecuronium use; some life-threatening and fatal. Appropriate emergency treatment (including epinephrine 1 mg/mL) should be immediately available during use. Use caution in patients with previous anaphylactic reactions to other neuromuscular-blocking agents.
• Prolonged paralysis: Some patients may experience delayed recovery of neuromuscular function after administration (especially after prolonged use). Other factors associated with delayed recovery should be considered (eg, corticosteroid use, disease-related conditions).

Disease-related concerns:

• Burn injury: Resistance may occur in burn patients (≥20% of total body surface area), usually several days after the injury, and may persist for several months after wound healing (Han 2009).
• Conditions that may antagonize neuromuscular blockade (decreased paralysis): Respiratory alkalosis, hypercalcemia, demyelinating lesions, peripheral neuropathies, denervation, and muscle trauma may result in antagonism of neuromuscular blockade (ACCM/SCCM/ASHP [Murray 2002]; Greenberg 2013; Miller 2010; Naguib 2002).
• Conditions that may potentiate neuromuscular blockade (increased paralysis): Electrolyte abnormalities (eg, severe hypocalcemia, severe hypokalemia, hypermagnesemia), neuromuscular diseases, metabolic acidosis, respiratory acidosis, Eaton-Lambert syndrome, and myasthenia gravis may result in potentiation of neuromuscular blockade (Greenberg 2013; Miller 2010; Naguib 2002).
• Hepatic impairment: Use with caution in patients with hepatic impairment; clinical duration may be prolonged.
• Renal impairment: In general, patients with renal impairment do not experience clinically significant prolongation of neuromuscular blockade with vecuronium; however, in patients who are anephric, the clinical duration may be prolonged.
• Respiratory disease: Use with caution in patients with underlying respiratory disease.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Use with caution in the elderly, effects and duration are more variable; dosage reduction may be considered.
• Immobilized patients: Resistance may occur in patients who are immobilized.
• Pediatric: Children 1-10 years of age may require slightly higher initial doses and slightly more frequent supplementation.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Diluent may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer’s labeling.

Other warnings/precautions:

• Appropriate use: Maintenance of an adequate airway and respiratory support is critical. All patients should receive eye care including liberal use of lubricating drops, gel, or ointment and eyelids should remain closed during continuous neuromuscular blockade to protect against damage to the cornea (ulceration and drying).
• Experienced personnel: [US Boxed Warning]: Should be administered by adequately trained individuals familiar with its use.
• Risk of medication errors: Accidental administration may be fatal. Confirm proper selection of intended product, store vial so the cap and ferrule are intact and the possibility of selecting the wrong product is minimized, and ensure that the intended dose is clearly labeled and communicated, when applicable.

Monitoring Parameters

Vital signs (heart rate, blood pressure, respiratory rate); degree of muscle paralysis (eg, presence of spontaneous movement, ventilator asynchrony, shivering, and consider use of a peripheral nerve stimulator with train of four monitoring along with clinical assessments)

In the ICU setting, prolonged paralysis and generalized myopathy, following discontinuation of agent, may be minimized by appropriately monitoring degree of blockade.

Pregnancy

Pregnancy Risk Factor

C

Pregnancy Considerations

Animal reproduction studies have not been conducted. The pharmacokinetics of vecuronium are altered during pregnancy. Use in cesarean section has been reported; umbilical venous concentrations were 11% of maternal values at delivery.

Patient Education

What is this drug used for?

• It is used to calm muscles during surgery.
• It is used to calm muscles while on a breathing machine.

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.