Pancuronium

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous, as bromide:

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

Pharmacology

Mechanism of Action

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

Pharmacokinetics/Pharmacodynamics

Distribution

V_d: 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); hypothermia may prolong the duration of action

Half-Life Elimination

89 to 161 minutes

Protein Binding

87%

Use in Specific Populations

Special Populations: Renal Function Impairment

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

Special Populations: Hepatic Function Impairment

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

Special Populations Note

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

Use: Labeled Indications

Neuromuscular blockade for endotracheal intubation, surgery, or mechanical ventilation: As an 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 pancuronium, bromide, 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 of neuromuscular blockade to achieve deep sedation (SCCM [Murray 2016]).

Neuromuscular blockade for endotracheal intubation, surgery, or mechanical ventilation (as adjunct to general anesthesia): IV: Initial: 0.04 to 0.1 mg/kg or 0.05 mg/kg after initial dose of succinylcholine for intubation; maintenance dose: 0.01 mg/kg administered 60 to 100 minutes after initial dose and then 0.01 mg/kg every 25 to 60 minutes

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

Intensive care unit paralysis (eg, use for up to 48 hours in patients with early ARDS with PaO₂/FiO₂ <150, to facilitate mechanical ventilation, or for shivering from therapeutic hypothermia) (off-label dosing): IV: 0.06 to 0.1 mg/kg bolus followed by 1 to 2 mcg/kg/minute (0.06 to 0.12 mg/kg/hour) (SCCM [Murray 2002]) or 0.8 to 1.7 mcg/kg/minute (0.048 to 0.102 mg/kg/hour) (Greenberg 2013)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Dosing in obese patients should be calculated using ideal body weight (Playfor 2007):

Paralysis/skeletal muscle relaxation: IV:

Infants:

Intermittent IV: 0.05 to 0.1 mg/kg/dose as needed (usually every 4 to 6 hours) (Martin 1999; Playfor 2007)

Continuous IV infusion: 0.4 to 0.6 mcg/kg/minute (0.02 to 0.04 mg/kg/hour) (Martin 1999)

Children:

Intermittent IV: 0.05 to 0.15 mg/kg/dose as needed (usually every 4 to 6 hours) (Martin 1999; Playfor 2007)

Continuous IV infusion: 0.5 to 1 mcg/kg/minute (0.03 to 0.06 mg/kg/hour) (Martin 1999)

Adolescents:

Intermittent IV: 0.05 to 0.15 mg/kg/dose as needed (usually every 4 to 6 hours) (Martin 1999; Playfor 2007)

Continuous IV infusion: 0.4 to 0.6 mcg/kg/minute (0.02 to 0.04 mg/kg/hour) (Martin 1999)

Dosing: Obesity

Ideal body weight or adjusted body weight is recommended when calculating dose for obese patients (SCCM [Murray 2016]).

Reconstitution

Parenteral: Continuous IV infusion: Dilute in D5NS, D5W, LR, or NS; final concentrations of 0.01 to 1 mg/mL have been used by some centers (Murray 2014; Sinclair-Pingel 2006). Product formulations may contain benzyl alcohol; in neonates, consider using the 2 mg/mL product for preparation to decrease amount of benzyl alcohol delivered.

Administration

IV: May be administered undiluted by rapid IV injection.

Storage

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

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 Neuromuscular-Blocking Agents (Nondepolarizing). 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

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

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

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

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

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

Frequency not defined.

Cardiovascular: Flushing, increased blood pressure, increased cardiac work, increased pulse, severe myasthenia (long-term use)

Central nervous system: Paralysis (long-term use)

Dermatologic: Skin rash (transient)

Gastrointestinal: Sialorrhea

<1%, postmarketing, and/or case reports: Anaphylactoid reaction, anaphylaxis, bronchospasm, erythema, hypersensitivity reaction, hypotension, tachycardia

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylaxis: Severe anaphylactic reactions have been reported (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.

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 (increase 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: 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. 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. 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.

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 severe headache, flushing, redness, fast heartbeat, vision changes, severe dizziness, or passing out (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 health care 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.