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Pancuronium Bromide

Class: Neuromuscular Blocking Agents
VA Class: MS300
CAS Number: 15500-66-0

Warning(s)

  • Should be administered only by adequately trained clinicians experienced in the use and complications of neuromuscular blocking agents.100

Introduction

Nondepolarizing neuromuscular blocking agent; aminosteroid.100

Uses for Pancuronium Bromide

Skeletal Muscle Relaxation

Production of skeletal muscle relaxation during surgery after general anesthesia has been induced.100 420

Facilitation of endotracheal intubation;100 however, a neuromuscular blocking agent with a rapid onset of action (e.g., succinylcholine, rocuronium) generally preferred in emergency situations when rapid intubation is required.421 424

Also used to facilitate mechanical ventilation in the ICU;341 420 421 however, manufacturer states insufficient data available to support dosage recommendations for such use.100 Whenever neuromuscular blocking agents are used in the ICU, consider benefits versus risks of such therapy and assess patients frequently to determine need for continued paralysis.100 421 (See Intensive Care Setting under Cautions.)

Compared with other neuromuscular blocking agents, pancuronium has a slow onset and long duration of action; therefore, not appropriate for emergency intubation but may be used for other indications (e.g., mechanical ventilation in the ICU) in which rapid onset and short duration of action are not as important.100 420 421 424

Because of prominent vagolytic effects, generally should not be used in patients with preexisting tachycardia or in patients who cannot tolerate an increase in heart rate (e.g., those with cardiovascular disease).341 420 421 424

Pancuronium Bromide Dosage and Administration

General

  • Facilities and personnel necessary for intubation, administration of oxygen, and respiratory support should be immediately available.100 359 424 (See Boxed Warning.)

  • Adjust dosage carefully according to individual requirements and response.100

  • Assess neuromuscular blockade and recovery with a peripheral nerve stimulator to accurately monitor the degree of muscle relaxation, determine need for additional doses, and minimize possibility of overdosage.100 421 (See Administration Precautions under Cautions.)

  • To avoid patient distress, administer in conjunction with adequate analgesia and sedation, and only after unconsciousness has been induced.100 359 421 423

  • A reversal agent should be readily available in the event of a failed intubation or to accelerate neuromuscular recovery after surgery.100 359 421 (See Reversal of Neuromuscular Blockade under Dosage and Administration.)

Reversal of Neuromuscular Blockade

  • To reverse neuromuscular blockade, administer a cholinesterase inhibitor (e.g., neostigmine, pyridostigmine, edrophonium) in conjunction with an anticholinergic agent such as atropine or glycopyrrolate to block adverse muscarinic effects of the cholinesterase inhibitor.100

  • To minimize risk of residual neuromuscular blockade, attempt reversal only after some degree of spontaneous recovery has occurred; monitor patients closely until adequate recovery of normal neuromuscular function is assured (i.e., ability to maintain satisfactory ventilation and a patent airway).100 355 356 357 358 421

Administration

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer IV only.100 Usually administered by direct IV injection, but also has been given as a continuous IV infusion.100 341

Use of a controlled-infusion device recommended during continuous IV infusion.359

Consult specialized references for specific procedures and techniques of administration.

Dilution

For continuous IV infusion, may dilute with 5% dextrose, 5% dextrose and 0.9% sodium chloride, 0.9% sodium chloride, or lactated Ringer's injection.100 Infusion solutions are stable for 48 hours.100

Dosage

Available as pancuronium bromide; dosage expressed in terms of the salt.100

Pediatric Patients

Skeletal Muscle Relaxation
Initial Dose
IV

Children >1 month of age: 0.04–0.1 mg/kg as adjunct to balanced anesthesia.100 For endotracheal intubation, dose of 0.06–0.1 mg/kg recommended; conditions satisfactory for intubation generally occur within 2–3 minutes following this dose.100 (See Onset and also Duration under Pharmacokinetics.)

If administering following succinylcholine and/or maintenance doses of inhalation anesthetics (e.g., enflurane, isoflurane), select initial dose at lower end of recommended range.100 Administer pancuronium after effects of succinylcholine subside.100

Neonates ≤1 month of age: Manufacturer recommends administering a test dose of 0.02 mg/kg to determine responsiveness.100 (See Intensive Care Setting under Cautions.)

Maintenance Dosage
IV

May administer additional incremental doses starting at 0.01 mg/kg to maintain skeletal muscle relaxation during prolonged surgery.100

Manufacturer states that continuous IV infusions or intermittent IV injections to support mechanical ventilation in the ICU not adequately studied to establish dosage recommendations.100

Adults

Skeletal Muscle Relaxation
Initial Dose
IV

0.04–0.1 mg/kg as adjunct to balanced anesthesia.100 For endotracheal intubation, dose of 0.06–0.1 mg/kg recommended; conditions satisfactory for intubation generally occur within 2–3 minutes following this dose.100 (See Onset and also Duration under Pharmacokinetics.)

If administering following succinylcholine and/or maintenance doses of inhalation anesthetics (e.g., enflurane, isoflurane), select initial dose at lower end of recommended range.100 Administer pancuronium after effects of succinylcholine subside.100

Maintenance Dosage
IV

May administer additional incremental doses starting at 0.01 mg/kg to maintain skeletal muscle relaxation during prolonged surgery.100

Manufacturer states that continuous IV infusions or intermittent IV injections to support mechanical ventilation in the ICU not adequately studied to establish dosage recommendations.100

Special Populations

Patients with Hepatic or Biliary Disease

Increased initial dose may be required to achieve effective neuromuscular blockade; once blockade is established, duration of blockade may be prolonged.100 (See Biliary Disease and also see Hepatic Impairment under Cautions.)

Burn Patients

Substantially increased doses may be required due to development of resistance.c (See Burn Patients under Cautions.)

Patients with Altered Circulation Time

Patients with slower circulations (e.g., those with cardiovascular disease, edema, or advanced age) may have delayed onset; however, do not increase dosage.100

Patients with Neuromuscular Diseases

Small test dose is recommended to monitor response.100 (See Neuromuscular Diseases under Cautions.)

Cautions for Pancuronium Bromide

Contraindications

  • Known hypersensitivity to pancuronium.100

Warnings/Precautions

Warnings

Administration Precautions

Because of the potential for severely compromised respiratory function and other complications, take special precautions during administration.100 c (See Boxed Warning and also see General under Dosage and Administration.)

Sensitivity Reactions

Hypersensitivity Reactions

Serious hypersensitivity reactions, including anaphylaxis, reported rarely.100 422 Potential for cross-sensitivity with other neuromuscular blocking agents (both depolarizing and nondepolarizing).100 422

Take appropriate precautions; emergency treatment for anaphylaxis should be immediately available.100

General Precautions

Neuromuscular Diseases

Possible profound neuromuscular blockade in patients with neuromuscular diseases (e.g., myasthenia gravis, Eaton-Lambert syndrome).100

Monitor degree of neuromuscular blockade with a peripheral nerve stimulator.100 Particular care may be required to maintain adequate airway and ventilation support prior to, during, and following administration of pancuronium.100

Burn Patients

Resistance to therapy with neuromuscular blocking agents can develop in burn patients,c particularly those with burns over 25–30% or more of body surface area.c

Resistance generally becomes apparent ≥1 week after the burn, peaks ≥2 weeks after the burn, persists for several months or longer, and decreases gradually with healing.c

Consider possible need for substantially increased doses.c

Cardiovascular Effects

Possible increased heart rate, arterial pressure, and cardiac output.100

Use not recommended in patients with preexisting tachycardia or in patients in whom minor elevation in heart rate is undesirable.341 420 421 424

Possible delayed onset of action in patients with impaired circulation (e.g., cardiovascular disease, edema); however, larger than usual doses are not recommended.100

Intensive Care Setting

Prolonged paralysis and severe muscle weakness reported rarely with long-term use in neonates undergoing mechanical ventilation in the ICU.100 Although definitive causal relationship not established, consider risks versus benefits of such use.100

Continuous monitoring of neuromuscular transmission recommended during neuromuscular blocking agent therapy in intensive care setting.c Do not administer additional doses before there is a definite response to nerve stimulation tests.c If no response is elicited, discontinue administration until a response returns.c

Obesity

Possible airway or ventilatory problems in patients with severe obesity.100 Particular care may be required to maintain adequate airway and ventilation support prior to, during, and following administration of pancuronium.100

Biliary Disease

Possible slower onset and prolonged duration of neuromuscular blockade.100 (See Elimination: Special Populations, under Pharmacokinetics and also see Patients with Hepatic or Biliary Disease under Dosage and Administration.)

Specific Populations

Pregnancy

Category C.100

Lactation

Not known whether pancuronium is distributed into milk.106

Pediatric Use

Clinically important methemoglobinemia reported rarely in premature neonates receiving pancuronium in combination with fentanyl and atropine for emergency anesthesia and surgery; however, direct causal relationship not established.100

Large amounts of benzyl alcohol (i.e., 100–400 mg/kg daily) have been associated with toxicity in neonates;100 114 115 116 117 118 each mL of pancuronium bromide injection contains 10 mg of benzyl alcohol.100

Neonates (<1 month of age) are particularly sensitive to neuromuscular blocking agents; administer test dose to determine responsiveness.100 (See Pediatric Patients under Dosage and Administration.) Carefully consider risks and benefits of long-term therapy in neonates.100 (See Intensive Care Setting under Cautions.)

Hepatic Impairment

Possible slower onset and prolonged duration of neuromuscular blockade.100 (See Elimination: Special Populations, under Pharmacokinetics and also see Patients with Hepatic or Biliary Disease under Dosage and Administration.)

Renal Impairment

Possible prolonged neuromuscular blockade; use with caution in patients with renal failure.100 (See Elimination: Special Populations, under Pharmacokinetics.)

Common Adverse Effects

Various degrees of skeletal muscle weakness.100

Interactions for Pancuronium Bromide

Specific Drugs

Drug

Interaction

Comments

Anesthetics, general (principally enflurane and isoflurane)

Increased potency of neuromuscular blockade100

Select dose of pancuronium at lower end of recommended initial range 100

Antidepressants, tricyclic

Possible ventricular arrhythmias in patients receiving tricyclic antidepressants concomitantly with pancuronium and halothane100

Use concomitantly with caution100

Anti-infective agents (e.g., aminoglycosides, bacitracin, polymyxins, tetracyclines)

Possible prolonged duration of neuromuscular blockade100

Magnesium salts

Possible increased neuromuscular blockade and incomplete reversal in patients receiving magnesium sulfate for toxemias of pregnancy 100

Reduce pancuronium dosage if necessary 100

Neuromuscular blocking agents, nondepolarizing (e.g., atracurium, vecuronium)

Insufficient data to support concomitant use of other nondepolarizing neuromuscular blocking agents100

Quinidine

Possible recurrence of paralysis100

Succinylcholine

Prior administration of succinylcholine may increase potency and prolong duration of neuromuscular blockade100

Allow effects of succinylcholine to subside before administering pancuronium; pancuronium dose at lower end of recommended range may be sufficient100

Pancuronium Bromide Pharmacokinetics

Absorption

Bioavailability

Poorly absorbed from the GI tract.c

Onset

Onset of paralysis is dose related.b

Following IV administration of 0.06 mg/kg, clinically sufficient neuromuscular blockade occurs within 2–3 minutes.b

Duration

Duration of paralysis is dose related.b

Duration of clinically sufficient neuromuscular blockade induced by 0.06 mg/kg is about 35–45 minutes.b

Duration of clinically sufficient neuromuscular blockade induced by 0.1 mg/kg approximately 100 minutes.100

Supplemental doses may increase magnitude and duration of neuromuscular blockade.b

Distribution

Extent

Crosses the placenta in small amounts.b

Plasma Protein Binding

Approximately 87% (mainly γ-globulin; albumin to a lesser extent).100 101 102 104 May be concentration dependent.101 103 104

Special Populations

Hepatic103 or renal105 impairment does not affect protein binding. Impaired hepatic or biliary function may increase volume of distribution.100

Elimination

Metabolism

Undergoes limited biotransformation.b

Elimination Route

Excreted principally in urine as unchanged drug and to a lesser extent in bile.100

Half-life

Triphasic; terminal half-life is approximately 2 hours.b

Special Populations

Impaired renal or hepatic function or biliary disease may decrease clearance and prolong half-life.100

Stability

Storage

Parenteral

Injection

2–8°C.100 May store for ≤6 months at room temperature.100

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility100

Compatible

Dextrose 5% in sodium chloride 0.45 or 0.9%

Dextrose 5% in water

Ringer's injection, lactated

Sodium chloride 0.9%

Drug Compatibility
Admixture CompatibilityHID

Compatible

Ciprofloxacin

Verapamil HCl

Y-site CompatibilityHID

Compatible

Aminophylline

Cefazolin sodium

Cefuroxime sodium

Dexmedetomidine HCl

Co-trimoxazole

Dobutamine HCl

Dopamine HCl

Epinephrine HCl

Esmolol HCl

Etomidate

Fenoldopam mesylate

Fentanyl citrate

Fluconazole

Gentamicin sulfate

Heparin sodium

Hetastarch in lactated electrolyte injection (Hextend)

Hydrocortisone sodium succinate

Isoproterenol HCl

Levofloxacin

Lorazepam

Midazolam HCl

Milrinone lactate

Morphine sulfate

Nitroglycerin

Ranitidine HCl

Sodium nitroprusside

Vancomycin HCl

Incompatible

Diazepam

Thiopental sodium

Variable

Propofol

Actions

  • Produces skeletal muscle relaxation by causing a decreased response to acetylcholine (ACh) at the myoneural (neuromuscular) junction of skeletal muscle.c

  • Exhibits high affinity for ACh receptor sites and competitively blocks access of ACh to motor end-plate of myoneural junction; may affect ACh release.100 c

  • Blocks the effects of both the small quantities of ACh that maintain muscle tone and the large quantities of ACh that produce voluntary skeletal muscle contraction; does not alter the resting electrical potential of the motor end-plate or cause muscular contractions.c

  • Produces little or no histamine release.b c

Advice to Patients

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.100

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., cardiovascular disease, neuromuscular disease).100

  • Importance of informing patients of other important precautionary information.100 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Pancuronium Bromide

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IV use only

1 mg/mL*

Pancuronium Bromide Injection

AHFS DI Essentials. © Copyright 2017, Selected Revisions October 23, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

Only references cited for selected revisions after 1984 are available electronically.

100. Hospira. Pancuronium bromide injection prescribing information. Lake Forest, IL; 2016 Dec.

101. Thompson JM. Pancuronium binding by serum proteins. Anaesthesia. 1976; 31:219-27. [PubMed 59554]

102. Foldes FF, Derby A. Protein binding of atracurium and other short-acting neuromuscular blocking agents and their interaction with human cholinesterases. Br J Anaesth. 1983; 55:31-4S.

103. Duvaldestin P, Henzel D. Binding of tubocurarine, fazadinium, pancuronium and Org NC45 to serum proteins in normal man and in patients with cirrhosis. Br J Anaesth. 1982; 54:513-6. [PubMed 6122460]

104. Ramzan MI, Somogyi AA, Walker JS et al. Clinical pharmacokinetics of the non-depolarising muscle relaxants. Clin Pharmacokinet. 1981; 6:25-60. [PubMed 7018787]

105. Wood M, Stone WJ, Wood AJJ. Plasma binding of pancuronium: effects of age, sex, and disease. Anesth Analg. 1983; 62:29-32. [PubMed 6849508]

106. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 6th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2002:1058-62.

114. American Academy of Pediatrics Committee on Fetus and Newborn and Committee on Drugs. Benzyl alcohol: toxic agent in neonatal units. Pediatrics. 1983; 72:356 8.

115. Anon. Benzyl alcohol may be toxic to newborns. FDA Drug Bull. 1982; 12(2):10 11.

116. Gershanik J, Boecler B, Ensley H et al. The gasping syndrome and benzyl alcohol poisoning. N Engl J Med. 1982; 307:1384 8.

117. Menon PA, Thach BT, Smith CH et al. Benzyl alcohol toxicity in a neonatal intensive care unit: incidence, symptomatology, and mortality. Am J Perinatol. 1984; 1:288 92.

118. Anderson CW, Ng KJ, Andresen B et al. Benzyl alcohol poisoning in a premature newborn infant. Am J Obstet Gynecol. 1984; 148:344 6

341. Society of Critical Care Medicine and American Society of Health-System Pharmacists. Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient. Am J Health-Syst Pharm. 2002; 59:179-95. [PubMed 11826571]

355. Bevan DR, Donati F, Kopman AF. Reversal of neuromuscular blockade. Anesthesiology. 1992; 77:785-805. [PubMed 1416176]

356. Srivastava A, Hunter JM. Reversal of neuromuscular block. Br J Anaesth. 2009; 103:115-29. [PubMed 19468024]

357. Brull SJ, Murphy GS. Residual neuromuscular block: lessons unlearned. Part II: methods to reduce the risk of residual weakness. Anesth Analg. 2010; 111:129-40. [PubMed 20442261]

358. Murphy GS, Brull SJ. Residual neuromuscular block: lessons unlearned. Part I: definitions, incidence, and adverse physiologic effects of residual neuromuscular block. Anesth Analg. 2010; 111:120-8. [PubMed 20442260]

359. Institute for Safe Medication Practices. Paralyzed by mistakes: reassess the safety of neuromuscular blockers in your facility. ISMP Medication Safety Alert! Acute Care edition. Horsham, PA; 2016 June. From ISMP website

420. McManus MC. Neuromuscular blockers in surgery and intensive care, part 1. Am J Health-Syst Pharm. 2001; 58:2287-99. [PubMed 11763807]

421. McManus MC. Neuromuscular blockers in surgery and intensive care, part 2. Am J Health-Syst Pharm. 2001; 58: 2381-99. [PubMed 11794954]

422. Claudius C, Garvey LH, Viby-Mogensen J. The undesirable effects of neuromuscular blocking drugs. Anaesthesia. 2009; 64 Suppl 1:10-21. [PubMed 19222427]

423. Murray MJ, DeBlock H, Erstad B et al. Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient. Crit Care Med. 2016; 44:2079-2103. [PubMed 27755068]

424. Hampton JP. Rapid-sequence intubation and the role of the emergency department pharmacist. Am J Health Syst Pharm. 2011; 68:1320-30. [PubMed 21719592]

b. AHFS Drug Information 2018. McEvoy GK, ed. Pancuronium bromide. Bethesda, MD: American Society of Health-System Pharmacists; 2018.

c. AHFS Drug Information 2018. McEvoy GK, ed. Neuromuscular blocking agents general statement. Bethesda, MD: American Society of Health-System Pharmacists; 2018.

HID. Trissel LA. Handbook on injectable drugs. 18th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2015:918-20.

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