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Pancuronium Bromide

Pronunciation: pan-kure-OH-nee-um
Class: Nondepolarizing neuromuscular blocker

Trade Names

Pancuronium Bromide
- Injection, solution 1 mg/mL
- Injection, solution 2 mg/mL

Pharmacology

Binds competitively to cholinergic receptors on motor end-plate to antagonize action of acetylcholine, resulting in block of neuromuscular transmission.

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Pharmacokinetics

Distribution

Rapidly distributed into body tissues and crosses the placenta in small amounts. Vd ranges from 241 to 280 mL/kg. Pancuronium exhibits strong binding to gamma globulin and moderate binding to albumin. Approximately 80% is bound to plasma proteins; 13% is unbound to plasma protein.

Metabolism

Hepatic to active 3-hydroxy metabolite, which is half as potent a blocking agent as pancuronium. Other less potent metabolites include 17-hydroxy metabolite and 3,17-dihydroxy metabolite.

Elimination

Urine (40% as unchanged), bile (11% as metabolites). The half-life is 89 to 161 min. Plasma Cl is approximately 1.1 to 1.9 mL/min/kg.

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.

Hepatic Function Impairment

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

Biliary obstruction

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

Indications and Usage

As an adjunct to general anesthesia to facilitate tracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation.

Contraindications

Known hypersensitivity to the drug.

Dosage and Administration

Adjunct to General Anesthesia
Adults and pediatric patients older than 1 mo

IV 0.04 to 0.1 mg/kg initially. For maintenance therapy, use incremental doses beginning with 0.01 mg/kg.

Newborns younger than 1 mo

IV 0.02 mg/kg as a test dose should be given first to measure responsiveness.

Endotracheal Intubation
Adults and pediatric patients older than 1 mo

IV bolus 0.06 to 0.1 mg/kg.

Newborns younger than 1 mo

IV 0.02 mg/kg as a test dose should be given first to measure responsiveness.

General Advice

  • For IV administration only.
  • Individualize dose to each case.
  • May be diluted with sodium chloride 0.9% injection, dextrose 5% injection, dextrose 5% and sodium chloride injection, or lactated Ringer's injection.
  • Do not administer if solution is cloudy or discolored, or contains particulate matter.
  • Ensure that resuscitative and tracheal intubation equipment, oxygen, and an antagonist (eg, neostigmine) are available at all times.
  • Ensure that a peripheral nerve stimulator is used to monitor neuromuscular function during administration in order to monitor effectiveness of dosing and the need for additional doses, and to confirm recovery from neuromuscular blockade.
  • Ensure that patient has adequate anesthesia or sedation before administering pancuronium because the drug has no known effect on consciousness, pain threshold, or cerebration.
  • Because potent inhalational anesthetics or prior use of succinylcholine may enhance the intensity and duration of pancuronium, the lower end of the recommended initial dosage range may suffice when pancuronium is first used after intubation with succinylcholine and/or after maintenance doses of volatile liquid inhalational anesthetics are started. If succinylcholine is used before pancuronium, the administration of pancuronium should be delayed until the patient starts recovering from succinylcholine neuromuscular blockade.

Storage/Stability

Store in refrigerator between 36° and 46°F. The 10 mL vial will maintain potency for up to 6 mo at room temperature. When mixed with the approved solutions in glass or plastic containers, pancuronium will remain stable in solution for 48 h with no alteration in potency or pH, no decomposition, and no adsorption to either the glass or plastic container.

Drug Interactions

Antibiotics (eg, aminoglycosides [eg, gentamicin, kanamycin, neomycin, streptomycin], bacitracin, clindamycin, lincomycin, polymyxin B, tetracyclines, vancomycin)

May augment action of pancuronium. If coadministration cannot be avoided, carefully titrate the pancuronium dose and closely monitor neuromuscular function.

Azathioprine, mercaptopurine

Possible resistance to or reversal of neuromuscular blocking effects of pancuronium. Dosage requirements for pancuronium may be increased.

Carbamazepine

May cause resistance to or reversal of the neuromuscular blocking effects of pancuronium. Pancuronium dosage requirements may be increased. Closely monitor patients for a more rapid recovery from neuromuscular blockade than expected.

Cyclosporine

The neuromuscular blocking effects of pancuronium may be increased. Closely monitor patients for the extent and duration of neuromuscular blockade. Decrease the dosage of pancuronium and provide mechanical respiratory support as needed.

Hydantoins (eg, phenytoin)

Resistance to the neuromuscular blocking effects of pancuronium may occur. In patients receiving hydantoins for at least 7 days prior to pancuronium administration, closely monitor neuromuscular blockade. Higher dosages of pancuronium may be required.

Inhalational anesthetics (eg, enflurane, isoflurane)

Neuromuscular blockade of pancuronium may be increased. Potentiation is most prominent with use of enflurane and isoflurane. With volatile inhalational anesthetics, the intubating dose of pancuronium may be the same as with balanced anesthesia unless the inhalational anesthetic has been administered for a sufficient time at a sufficient dose to have reached clinical equilibrium. The relatively long duration of action of pancuronium should be considered when the drug is selected for intubation in these circumstances.

Ketamine

Because of additive positive inotropic effects, heart rate may increase, resulting in decreased myocardial perfusion. Coadminister with caution. Carefully monitor cardiac function and hemodynamic status.

Magnesium salts

Magnesium salts may enhance the neuromuscular blockade of pancuronium. If coadministration cannot be avoided, carefully titrate the dose of pancuronium and closely monitor neuromuscular function.

Nondepolarizing neuromuscular blocking agents (eg, atracurium, vecuronium)

Other nondepolarizing neuromuscular blocking agents behave clinically similar to pancuronium. There are insufficient data to support concomitant use of pancuronium and other nondepolarizing neuromuscular blocking agents.

Quinidine

Experience with injection of quinidine during recovery from use of other muscle relaxants suggests that recurrent paralysis may occur. This possibility must also be considered for pancuronium. Avoid coadministration.

Succinylcholine

Prior administration of succinylcholine may enhance the neuromuscular blocking effect of pancuronium and increase its duration of action. If succinylcholine is used before pancuronium, the administration of pancuronium should be delayed until the patient starts recovering from succinylcholine-induced neuromuscular blockade.

Theophyllines

Neuromuscular blocking effects of pancuronium may be decreased; cardiac arrhythmias may occur. Pancuronium dosing requirements may be increased. Avoid coadministration.

Verapamil

The neuromuscular blocking effects of pancuronium may be increased. Excessive respiratory depression with periods of prolonged apnea may occur. Coadminister with caution. Carefully titrate the dose of pancuronium and closely monitor neuromuscular function. Provide mechanical respiratory support if necessary.

Adverse Reactions

Cardiovascular

Rise in arterial pressure, cardiac output, and heart rate; decrease in central venous pressure.

Hypersensitivity

Hypersensitivity reactions (eg, bronchospasm, flushing, redness, hypotension, tachycardia); anaphylactic and anaphylactoid reactions (postmarketing).

Miscellaneous

Rash; salivation; skeletal muscle weakness to profound and prolonged skeletal muscle paralysis resulting in respiratory insufficiency or apnea.

Precautions

Warnings

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


Monitor

Use of a peripheral nerve stimulator will usually be of value for monitoring neuromuscular blocking effects, avoiding overdosage, and assisting in evaluation of recovery.


Pregnancy

Category C . It is recommended that the interval between use of pancuronium and delivery be reasonably short to avoid clinically significant placental transfer.

Lactation

Undetermined.

Children

Prolonged use in newborns undergoing mechanical ventilation has been associated with severe skeletal muscle weakness and methemoglobinemia. Contains benzyl alcohol, which is related to a fatal gasping syndrome in premature infants.

Hypersensitivity

Severe anaphylactic reactions, in some cases life-threatening and fatal, have been reported.

Renal Function

Use with caution.

Hepatic Function

Use with caution.

Special Risk Patients

Patients with severe obesity may pose airway and ventilatory problems requiring special care before, during, and after the use. Use with caution in patients with preexisting pulmonary disease. Conditions associated with slower circulation time (CV disease, old age, edematous states resulting in increased volume of distribution) may contribute to a delay in onset time. Electrolyte imbalance and diseases that lead to electrolyte imbalance, such as adrenal cortical insufficiency, have been shown to alter neuromuscular blockade.

Long-term use

In the intensive care unit, in rare cases, long-term use may be associated with prolonged paralysis and/or skeletal muscle weakness that may be first noted during attempts to wean such patients from the ventilator.

Neuromuscular disease

In patients who are known to have myasthenia gravis or the myasthenic (Eaton-Lambert) syndrome, small doses may have profound effects. Patients with neuromuscular disease may pose airway and ventilatory problems requiring special care before, during, and after the use of pancuronium.

Overdosage

Symptoms

Apnea, decreased respiratory reserve, low tidal volume, prolonged neuromuscular blockade, skeletal muscle relaxation.

Patient Information

  • Inform patients that severe anaphylactic reactions to neuromuscular blocking agents have been reported.

Copyright © 2009 Wolters Kluwer Health.

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