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Pancuronium


General


Pronunciation

(pan kyoo ROE nee um)


Indications


Use: Labeled Indications

Facilitation of endotracheal intubation and relaxation of skeletal muscles during surgery; facilitation of mechanical ventilation in ICU patients; does not relieve pain or produce sedation


Contraindications


Hypersensitivity to pancuronium, bromide, or any component of the formulation


ALERT: U.S. Boxed Warning

Experienced personnel:

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


Dosing and Administration


Dosing: Adult

Administer IV; dose to effect; doses will vary due to interpatient variability

Surgery: Initial: 0.06-0.1 mg/kg or 0.05 mg/kg after initial dose of succinylcholine for intubation; maintenance dose: 0.01 mg/kg administered 60-100 minutes after initial dose and then 0.01 mg/kg every 25-60 minutes

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

ICU paralysis (eg, facilitate mechanical ventilation) in select adequately sedated patients: 0.06-0.1 mg/kg bolus followed by either:

Continuous infusion: 1-2 mcg/kg/minute (0.06-0.12 mg/kg/hour) (Murray, 2002) or 0.8-1.7 mcg/kg/minute (0.048-0.102 mg/kg/hour) (Greenberg, 2013)

or

Intermittent bolus: 0.1-0.2 mg/kg every 1-3 hours


Dosing: Geriatric

Refer to adult dosing.


Dosing: Pediatric

Infants >1 month and Children: Refer to adult dosing.


Dosing: Renal Impairment

Elimination half-life is doubled, plasma clearance is reduced and rate of recovery is sometimes much slower. No dosage adjustment provided in manufacturer 's labeling; however, the following adjustments have been recommended (Aronoff 2007):

CrCl >50 mL/minute: No dosage adjustment necessary.

CrCl 10-50 mL/minute: Administer 50% of normal dose

CrCl <10 mL/minute: Avoid use.

Hemodialysis/peritoneal dialysis: Avoid use.

CRRT: Administer 50% of normal dose.


Dosing: Hepatic Impairment

Elimination half-life is doubled, plasma clearance is doubled, recovery time is prolonged, volume of distribution is increased (50%) and results in a slower onset, higher total dosage, and prolongation of neuromuscular blockade. Patients with liver disease may develop slow resistance to nondepolarizing muscle relaxant. Large doses may be required and problems may arise in antagonism.


Administration

May be administered undiluted by rapid IV injection


Storage

Refrigerate; however, stable for up to 6 months at room temperature.


Dosage Forms/Strengths


Dosage Forms

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

Solution, Intravenous, as bromide:

Generic: 1 mg/mL (10 mL); 2 mg/mL (2 mL, 5 mL)


Compatibility

Stable in D5NS, D5W, LR, NS.

Y-site administration: Incompatible with diazepam, pantoprazole, thiopental.

Compatibility in syringe: Incompatible with pantoprazole.


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

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

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

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

Theophylline Derivatives: May enhance the adverse/toxic effect of Pancuronium. Theophylline Derivatives may diminish the neuromuscular-blocking effect of Pancuronium. Management: Pancuronium dosage adjustment may be necessary to induce paralysis in patients receiving concomitant theophylline derivatives. Monitor closely for adverse effects (e.g., cardiac effects) with concomitant use of these agents. Consider therapy modification

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


Monitoring Parameters

Heart rate, blood pressure, assisted ventilation status; cardiac monitor, blood pressure monitor, and ventilator required


Adverse Reactions


Frequency not defined.

Cardiovascular: Elevation in pulse rate, elevated blood pressure and cardiac output, tachycardia, edema, skin flushing, circulatory collapse

Dermatologic: Rash, itching, erythema, burning sensation along the vein

Gastrointestinal: Excessive salivation

Neuromuscular & skeletal: Profound muscle weakness

Respiratory: Wheezing, bronchospasm

Miscellaneous: Hypersensitivity reaction

Postmarketing and/or case reports: Acute quadriplegic myopathy syndrome (prolonged use), anaphylactoid reactions, anaphylaxis, myositis ossificans (prolonged use)


Warnings/Precautions


Special Populations: Renal Function Impairment

In patients with renal failure, elimination half-life doubles, plasma Cl is reduced 60%, and Vd may be elevated and variable.


Special Populations: Hepatic Function Impairment

In patients with cirrhosis, the Vd increases approximately 50%, plasma Cl decreases 22%, and elimination half-life doubles.


Special Populations Note

Biliary obstruction: Plasma Cl decreases 50%, Vd increases approximately 50%, and elimination half-life doubles.


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.

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: Elimination half-life is doubled due to reduced clearance of pancuronium and recovery is prolonged; use with caution in patients with hepatic impairment and adjust dose appropriately.

- Renal impairment: Elimination half-life is doubled due to reduced clearance of pancuronium and recovery is prolonged; use with caution in patients with renal impairment and adjust dose appropriately.

Special populations:

- Elderly: Use with caution in the elderly, effects and duration are more variable.

- Immobilized patients: Resistance may occur in patients who are immobilized.

Dosage form specific issues:

- Benzyl alcohol and derivatives: Some dosage forms 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.

- Experienced personnel: [U.S. Boxed Warning]: Should be administered by adequately trained individuals familiar with its use.


Pregnancy Risk Factor

C


Pregnancy Considerations

Animal reproduction studies have not been conducted. Small amounts of pancuronium cross the placenta (Daily, 1984). May be used short-term in cesarean section; reduced doses recommended in patients also receiving magnesium sulfate due to enhanced effects.


Actions


Pharmacology

Blocks neural transmission at the myoneural junction by binding with cholinergic receptor sites


Distribution

Vd: 0.24 to 0.28 L/kg


Metabolism

Hepatic (30% to 45%); active metabolite 3-hydroxypancuronium (1/3 to 1/2 the activity of parent drug)


Excretion

Urine (40%); bile (11%)

Clearance: ~1 to 2 mL/kg/minute


Onset of Action

Infants: 2 to 5 minutes; Children: 2 to 4 minutes; Adults: 3 to 5 minutes (Martin 1999)


Duration of Action

Dose dependent: Children: 24 minutes; Adults: 22 minutes (Martin 1999)


Half-Life Elimination

89 to 161 minutes


Protein Binding

87%


Patient and Family Education


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?)

- Patient may experience drooling. Have patient report immediately to prescriber flushing, redness, tachycardia, severe dizziness, or syncope (HCAHPS).

- 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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