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Vecuronium

Pronunciation

Pronunciation

(vek ue ROE nee um)

Index Terms

  • Norcuron
  • ORG NC 45

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)

Pharmacologic Category

  • Neuromuscular Blocker Agent, Nondepolarizing

Pharmacology

Blocks acetylcholine from binding to receptors on motor endplate inhibiting depolarization

Distribution

Vd: 0.3-0.4 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 2.5-3 minutes; Maximum neuromuscular blockade: Within 3-5 minutes

Duration of Action

Under balanced anesthesia (time to recovery to 25% of control): 25-40 minutes; recovery 95% complete ~45-65 minutes after injection of intubating dose

Half-Life Elimination

Infants: 65 minutes

Children: 41 minutes

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

Half-life, distribution: Adults: 4 minutes

Protein Binding

60% to 80%

Use: Labeled Indications

To facilitate endotracheal intubation and to relax skeletal muscles during surgery; to facilitate mechanical ventilation in ICU patients; does not relieve pain or produce sedation

Contraindications

Hypersensitivity to vecuronium or any component of the formulation

Dosing: Adult

Dose to effect; doses will vary due to interpatient variability.

Surgical relaxation: IV (do not administer IM):

Tracheal intubation: IV: Initial: 0.08-0.1 mg/kg. Note: If intubation is performed using succinylcholine (not preferred agent in pediatric patients), the initial dose of vecuronium may be reduced to 0.04-0.06 mg/kg with inhalation anesthesia and 0.05-0.06 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: Adults: 10% of intubating dose given 3-5 minutes before intubating dose

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

ICU paralysis (eg, facilitate mechanical ventilation) in selected adequately sedated patients (Darrah, 1989; Greenberg, 2013; Murray, 2002; Rudis, 1997): IV: Initial bolus dose: 0.08-0.1 mg/kg, then a continuous IV infusion of 0.8-1.7 mcg/kg/minute (0.048-0.102 mg/kg/hour); monitor depth of blockade every 1-2 hours initially until stable dose, then every 8-12 hours. Usual maintenance infusion dose range: 0.8-1.2 mcg/kg/minute (0.048-0.072 mg/kg/hour).

Dosage adjustment (Rudis, 1996; Rudis, 1997): 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 peripheral nerve stimulation response or desired clinical response. Discontinue infusion if neuromuscular function does not return.

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]) (Murray, 2002; Segredo, 1992).

Intermittent bolus dosing (Hunter, 1985): 0.1-0.2 mg/kg/dose; may be repeated when neuromuscular function returns

Control of refractory shivering in adequately sedated patients during therapeutic hypothermia after cardiac arrest (off-label use; Bernard, 2002; Nolan, 2003; Polderman, 2009): IV: 8-12 mg; redose as needed to control shivering. Note: Duration of action prolonged in hypothermic patients. May mask seizure activity.

Dosing: Geriatric

No specific guidelines available; 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

Dose to effect; doses will vary due to interpatient variability.

Surgical relaxation: Tracheal intubation: IV (do not administer IM): Children ≥1 year: Refer to adult dosing. Note: Children 1-10 years may require slightly higher initial doses and more frequent supplementation.

ICU paralysis (eg, facilitate mechanical ventilation) in selected adequately sedated patients (off-label; Martin, 1999): IV: Initial bolus dose: 0.1-0.15 mg/kg, then a continuous IV infusion of 1-2.5 mcg/kg/minute (0.06-0.15 mg/kg/hour); monitor depth of blockade using peripheral nerve stimulator every 2-3 hours initially until stable dose, then every 8-12 hours

Intermittent bolus dosing (Eldadah, 1989): 0.1 mg/kg every 1 hour as needed

Dosing: Renal Impairment

No dosage adjustment provided in manufacturer’s labeling. However, patients with renal impairment do not experience clinically significant prolongation of neuromuscular blockade with vecuronium; however, in patients who are anephric, the clinical duration is prolonged.

Dosing: Hepatic Impairment

No dosage adjustment provided in manufacturer’s labeling. However, dosage reduction may be necessary in patients with liver disease.

Dosing: Obesity

Refer to indication-specific dosing for obesity-related information (may not be available for all indications).

Reconstitution

Reconstitute with compatible solution 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

Concentration of 1 mg/mL may be administered by rapid IV injection; may also be used for IV infusion in fluid-restricted patients.

Compatibility

Stable in D5W, D5NS, LR, NS, SWI, BWFI; incompatible with alkaline solutions/medications.

Y-site administration: Incompatible with amphotericin B cholesteryl sulfate complex, diazepam, etomidate, furosemide, micafungin, pantoprazole, thiopental.

Compatibility in syringe: Incompatible with pantoprazole.

Storage

Store intact vials of powder for injection at room temperature 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

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

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

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

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

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

OnabotulinumtoxinA: Neuromuscular-Blocking Agents may enhance the neuromuscular-blocking effect of OnabotulinumtoxinA. 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

RimabotulinumtoxinB: Neuromuscular-Blocking Agents may enhance the neuromuscular-blocking effect of RimabotulinumtoxinB. Monitor therapy

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

Tetracycline Derivatives: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. 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% (Limited to important or life-threatening): Bradycardia, circulatory shock, critical illness myopathy (prolonged use), edema, flushing, hypersensitivity reaction (including erythema, hypotension, tachycardia, urticaria), muscle calcification (prolonged use), pruritus, skin rash

ALERT: U.S. Boxed Warning

Experienced personnel:

This drug should be administered by adequately trained individuals familiar with its actions, characteristics, and hazards.

Warnings/Precautions

Concerns related to adverse effects:

• Neuromuscular cross-sensitivity: Cross-sensitivity with other neuromuscular-blocking agents may occur; use extreme caution in patients with previous anaphylactic reactions.

• 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 which may antagonize neuromuscular blockade: Respiratory alkalosis, hypercalcemia, demyelinating lesions, peripheral neuropathies, denervation, and muscle trauma may result in antagonism of neuromuscular blockade (Greenberg, 2013; Miller, 2010; Murray, 2002; Naguib, 2002).

• Conditions which may potentiate neuromuscular blockade: Electrolyte abnormalities (eg, severe hypocalcemia, severe hypokalemia, hypermagnesemia), neuromuscular diseases, metabolic acidosis, metabolic alkalosis, 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:

• Corticosteroids: In addition to prolonging recovery from neuromuscular blockade, concomitant use with corticosteroids has been associated with development of acute quadriplegic myopathy syndrome (AQMS). Current guidelines recommend neuromuscular blockers be discontinued as soon as possible in patients receiving corticosteroids or interrupted daily until necessary to restart them based on clinical condition (Murray, 2002).

• High potential for interactions: Numerous drugs either antagonize (eg, acetylcholinesterase inhibitors) or potentiate (eg, calcium channel blockers, certain antimicrobials, inhalation anesthetics) the effects of neuromuscular blockade; use with caution in patients receiving these agents.

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. Vecuronium does not relieve pain or produce sedation; use should include appropriate anesthesia, pain control, and sedation. In patients requiring long-term administration, use of a peripheral nerve stimulator to monitor drug effects is strongly recommended. Additional doses of vecuronium or any other neuromuscular-blocking agent should be avoided unless nerve stimulation response suggests inadequate neuromuscular blockade.

• Experienced personnel: [US Boxed Warning]: Should be administered by adequately trained individuals familiar with its use.

Monitoring Parameters

Blood pressure, heart rate; peripheral nerve stimulation (eg, train-of-four [TOF] count)

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

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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