Pancuronium Bromide

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

Warning(s)

  • Should be administered only by individuals experienced in the use of neuromuscular blocking agents.a

Introduction

Nondepolarizing neuromuscular blocking agent.a

Uses for Pancuronium Bromide

Skeletal Muscle Relaxation

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

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Facilitation of endotracheal intubation.a

Treatment to increase pulmonary compliance during assisted or controlled respiration.a

Pancuronium Bromide Dosage and Administration

General

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

  • Assess neuromuscular blockade and recovery in patients undergoing anesthesia; a peripheral nerve stimulator is recommended to accurately monitor the degree of muscle relaxation and to minimize the possibility of overdosage.a

  • To avoid patient distress, administer only after unconsciousness has been induced.a b c

Facilitation of Endotracheal Intubation

  • Endotracheal intubation generally can be performed within 2–3 minutes following administration of 0.06-mg/kg dose.a (See Onset and also Duration under Pharmacokinetics.)

Maintenance of Neuromuscular Blockade

  • Supplemental doses to maintain muscle relaxation increase magnitude and duration of neuromuscular blockade.a

Reversal of Neuromuscular Blockade

  • To reverse neuromuscular blockade, administer a cholinesterase inhibitor (e.g., neostigmine, pyridostigmine, edrophonium), usually in conjunction with an antimuscarinic (e.g., atropine, glycopyrrolate) to block adverse muscarinic effects of the cholinesterase inhibitor.a c

Administration

IV Administration

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

Administer IV only; administer initial (intubating) dose by rapid IV injection.a

Consult specialized references for specific procedures and techniques of administration.b

Dosage

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

Pediatric Patients

Skeletal Muscle Relaxation
Initial Dosage
IV

Children >1 month of age: 0.04–0.1 mg/kg as adjunct to balanced anesthesia.a 0.06–0.1 mg/kg is recommended for endotracheal intubation.a (See Onset and also Duration under Pharmacokinetics.)

If administering following succinylcholine and/or maintenances doses of inhalation anesthetics (e.g., enflurane, halothane, isoflurane), use dosage at lower end of recommended initial range.a Administer after effects of succinylcholine subside.a

Neonates ≤1 month of age: Administer test dose of 0.02 mg/kg to determine responsiveness.a

Maintenance Dosage
IV

Children 3 months to 12 years of age: 0.01 mg/kg administered at 25- to 60-minute intervals to maintain skeletal muscle relaxation during prolonged surgery or assisted respiration;a b 0.015 mg/kg may be used to maintain relaxation for controlled respiration.b

Adults

Skeletal Muscle Relaxation
Initial Dosage
IV

0.04–0.1 mg/kg as adjunct to balanced anesthesia.a 0.06–0.1 mg/kg is recommended for endotracheal intubation.a (See Onset and also Duration under Pharmacokinetics.)

If administering following succinylcholine and/or maintenances doses of inhalation anesthetics (e.g., enflurane, halothane, isoflurane), use dosage at lower end of recommended initial range.a Administer after effects of succinylcholine subside.a

Maintenance Dosage
IV

0.01 mg/kg administered at 25- to 60-minute intervals to maintain skeletal muscle relaxation during prolonged surgery or assisted respiration.a b 0.015 mg/kg may be used to maintain relaxation for controlled respiration.b

Prescribing Limits

Pediatric Patients

Skeletal Muscle Relaxation
Initial Dosage
IV

Up to 0.16 mg/kg has been used; however, large doses may increase frequency and severity of tachycardia.b

Adults

Skeletal Muscle Relaxation
Initial Dosage
IV

Up to 0.16 mg/kg has been used; however, large doses may increase frequency and severity of tachycardia.b

Special Populations

Hepatic Impairment

Increased initial dosage may be required to achieve effective neuromuscular blockade; once blockade is established, duration of blockade may be prolonged.a (See Hepatic Impairment under Cautions.)

Renal Impairment

Careful and individualized dosing recommended.a (See Renal Impairment under Cautions.)

Patients with Biliary Disease

Increased initial dosage may be required to achieve effective neuromuscular blockade; once blockade is established, duration of blockade may be prolonged.a (See Biliary Disease under Cautions.)

Burn Patients

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

Patients with Neuromuscular Disease

Administer small test dose and monitor response.a (See Neuromuscular Disease under Cautions.)

Cautions for Pancuronium Bromide

Contraindications

  • Known hypersensitivity to pancuronium bromide or any ingredient in the formulation.a

Warnings/Precautions

Warnings

Respiratory Effects

Potential for severely compromised respiratory function and respiratory paralysis.c

Should be used only by individuals experienced in the use of neuromuscular blocking agents and in the maintenance of an adequate airway and respiratory support.a Facilities and personnel necessary for intubation, administration of oxygen, and assisted or controlled respiration should be immediately available.a

IV cholinesterase inhibitor (e.g., neostigmine, pyridostigmine, edrophonium) should be readily available.a (See Reversal of Neuromuscular Blockade under Dosage and Administration.)

Use with caution in patients with pulmonary impairment or respiratory depression.c

Neuromuscular Disease

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

Reduce initial dosage; monitor response carefully with a peripheral nerve stimulator.a

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions (bronchospasm, flushing, redness, hypotension, tachycardia) reported rarely.a

General Precautions

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.a

Use not recommended in patients with preexisting tachycardia or in patients in whom minor elevation in heart rate is undesirable.b

Intensive Care Setting

Possible prolonged paralysis and/or muscle weakness and atrophy.a

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

Impaired Circulation

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

Electrolyte Disturbances

Possible increased or decreased neuromuscular blockade in patients with electrolyte distrubances (e.g., adrenocortical insufficiency) or acid/base imbalances.a

Malignant Hyperthermia

Malignant hyperthermia is rarely associated with use of neuromuscular blocking agents and/or potent inhalation anesthetics.c Be vigilant for its possible development and prepared for its management in any patient undergoing general anesthesia.c

Obesity

Possible airway or ventilatory problems in patients with severe obesity.a Use with caution.a

Biliary Disease

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

Specific Populations

Pregnancy

Category C.a

Lactation

Not known whether pancuronium is distributed into milk.j

Pediatric Use

Excessive salivation may occur during very light anesthesia.b

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.a

Large amounts of benzyl alcohol (i.e., 100–400 mg/kg daily) have been associated with toxicity in neonates;a d e f g h i each mL of pancucronium bromide injection contains 10 mg of benzyl alcohol.a

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

Geriatric Use

Use with caution in geriatric or debilitated patients.a c

Hepatic Impairment

Possible slower onset and prolonged duration of neuromuscular blockade; use with caution.a (See Elimination: Special Populations, under Pharmacokinetics and also see Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Possible prolonged neuromuscular blockade; use with caution in patients with poor renal perfusion or severe renal disease.a b (See Elimination: Special Populations, under Pharmacokinetics.)

Common Adverse Effects

Skeletal muscle weakness, slight elevation in pulse rate and excessive salivation.a c

Interactions for Pancuronium Bromide

Specific Drugs

Drug

Interaction

Comments

Anesthetics, general (enflurane, halothane, isoflurane)

Increased potency of neuromuscular blockadea

Select pancuronium dosage at lower end of recommended initial range a

Antidepressants, tricyclic

Possible ventricular arrhythmias in patients receiving tricyclic antiderpessants concomitantly with pancuronium and halothanea

Use with cautiona

Anti-infective agents (aminoglycosides, bacitracin, polymyxins, tetracyclines)

Possible prolonged duration of neuromuscular blockadea

Magnesium salts

Possible increased neuromuscular blockadea

Reduce pancuronium dosage if necessary a

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

Increased potency of neuromuscular blockadea

Concomitant use not recommendeda

Quinidine

Possible recurrence of paralysisa

Succinylcholine

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

Allow effects of succinylcholine to subside before administering pancuroniuma

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

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.a

Elimination

Metabolism

Undergoes limited biotransformation.b

Elimination Route

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

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.a

Stability

Storage

Parenteral

Injection

2–8°C.a

Compatibility

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

Parenteral

Solution Compatibilitya

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

Cimetidine 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.a 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.a

  • 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).a

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

Preparations

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

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

Pancuronium Bromide

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Injection, for IV use only

1 mg/mL*

Pancuronium Bromide Injection (with benzyl alcohol 1%)

Abbott, Baxter, Sicor

2 mg/mL*

Pancuronium Bromide Injection (with benzyl alcohol 1%)

Abbott, Baxter, Sicor

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions August 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

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

100. Pavulon prescribing information. In: Huff BB, ed. Physicians’ desk reference. 42nd ed. Oradell, NJ: Medical Economics Company Inc; 1988:1491-3.

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. [IDIS 165379] [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. [IDIS 164399] [PubMed 6849508]

a. Baxter. Pancuronium bromide injection prescribing information. Deerfield, IL: 2003 Jun.

b. AHFS Drug Information 2004. McEvoy GK, ed. Pancuronium bromide. Bethesda, MD: American Society of Health-System Pharmacists; 2004:1313-4.

c. AHFS Drug Information 2004. McEvoy GK, ed. Neuromuscular blocking agents general statement. Bethesda, MD: American Society of Health-System Pharmacists; 2004:1303-6.

d. Anon. Benzyl alcohol may be toxic to newborns. FDA Drug Bull. 1982; 12:10-11. [PubMed 7188569]

e. Anon. Neonatal deaths associated with use of benzyl alcohol—United States. MMWR Morb Mortal Wkly Rep. 1982; 31:290-91. [IDIS 150868] [PubMed 6810084]

f. Gershanik J. Boecler B, Ensley H et al. The gasping syndrome and benzyl alcohol poisoning. N Engl J Med. 1982; 307:1384-8. [IDIS 160823] [PubMed 7133084]

g. 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. [PubMed 6440575]

h. Anderson CW, Ng KJ, Andresen B et al. Benzyl alcohol poisoning in a premature newborn infant. Am J Obstet Gynecol. 1984; 148:344-6. [IDIS 181207] [PubMed 6695984]

i. 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. [IDIS 175725] [PubMed 6889041]

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

HID. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2007:1281-3.

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