Pipecuronium (Systemic)


VA CLASSIFICATION
Primary: MS300



Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

*Not commercially available in the U.S.

Not commercially available in Canada.



Category:


Neuromuscular blocking (paralyzing) agent—

Indications

Accepted

Skeletal muscle paralysis—Pipecuronium is indicated as an adjunct to anesthesia to induce skeletal muscle relaxation and to facilitate the management of patients undergoing mechanical ventilation {01} {03} {04} {05} {06} {07} {08} {09} {10} {11} {12} {13} {14} {15}. Pipecuronium has a long duration of action and is recommended only for surgical procedures expected to last 90 minutes or longer {01}.

Acceptance not established
Pipecuronium has not been adequately studied for facilitating prolonged mechanical ventilation in intensive care patients {01}. In a study of intermittent dosing of pipecuronium to facilitate prolonged mechanical ventilation in intensive care patients, patients required an average of 3 mg of pipecuronium per hour {16}. None of the patients experienced prolonged paralysis after discontinuation of pipecuronium {16}. The patients included in this study required intensive care following trauma, and they did not receive corticosteroids concomitantly with pipecuronium {16}. More data are needed to assess the role of pipecuronium to facilitate prolonged mechanical ventilation in intensive care patients, including those patients requiring intensive care and mechanical ventilation because of medical illnesses instead of traumatic injury.

Unaccepted
Pipecuronium has not been adequately studied, and is not recommended, for administration prior to or following use of other nondepolarizing neuromuscular blocking agents, or for obstetrical use (cesarean section) {01}.


Pharmacology/Pharmacokinetics

Note: Pharmacokinetic studies on the volume of distribution, distribution and elimination half-lives, and clearance of pipecuronium have been done in a limited number of patients; data presented below must be considered preliminary and subject to interpatient variability {01}.


Physicochemical characteristics:
Molecular weight—
    Pipecuronium bromide: 762.71 {02}

Mechanism of action/Effect:

Pipecuronium is a nondepolarizing neuromuscular blocking agent. Neuromuscular blocking agents produce skeletal muscle paralysis by blocking neural transmission at the myoneural junction. The paralysis is selective initially and usually appears in the following muscles consecutively: levator muscles of eyelids, muscles of mastication, limb muscles, abdominal muscles, muscles of the glottis, and finally, the intercostal muscles and the diaphragm {31}. Neuromuscular blocking agents have no clinically significant {24} effect on consciousness or the pain threshold {01}.

Nondepolarizing neuromuscular blocking agents inhibit neuromuscular transmission by competing with acetylcholine for the cholinergic receptors of the motor end plate {01}, thereby reducing the response of the end plate to acetylcholine. This type of neuromuscular block is usually antagonized by anticholinesterase agents {01}.

Distribution:


Volume of distribution (steady-state):

Normal renal function: 0.25 (range, 0.12 to 0.37) L per kg of body weight {01} {04}.

Renal function impairment: 0.37 (range, 0.28 to 0.51) L per kg of body weight {01} {10}.


Half-life:


Distribution:

Normal renal function: 6.22 (range, 1.34 to 10.66) minutes {01} {04}.

Renal function impairment: 4.33 (range, 1.69 to 6.17) minutes {01}.



Elimination:

Normal renal function: 1.7 (range, 0.9 to 2.7) hours {01} {04}. The elimination half-life is not altered by hypothermia and bypass {08}.

Renal function impairment: 4 (range, 2 to 8.2) hours {01} {10}.


Onset of action:

Intubating conditions are achieved in 2.5 to 3 minutes {01} {06} with doses of 70 {01} {06} to 100 {06} mcg per kg of body weight (mcg/kg). The time to achieve intubating conditions may be somewhat longer when lower doses are administered {32}.

Time to peak effect:

In adults, maximum (95%) suppression of the twitch response to peripheral nerve stimulation is achieved in about 5.5 to 6 minutes following a dose of 50 mcg/kg {05} and in about 3 to 5 minutes after single doses of 70 to 85 mcg/kg {01} {33} {34}. The peak effect time is not significantly affected by the type of anesthesia administered {05} {13}.

Duration of action:


Initial dose:


Adults—

Long-acting; dependent on dose and on type of anesthesia {01} {06}. With neurolept (nitrous oxide–fentanyl–droperidol) anesthesia, the expected duration of clinical effect (time until the twitch response returns to 25% of the control value as determined using a peripheral nerve stimulator) is about 30 minutes following a dose of 50 mcg/kg {05}. With “balanced” anesthesia (in which a neuromuscular blocking agent may be used together with other medications, such as an induction agent [e.g., an ultrashort-acting barbiturate or propofol], an opioid analgesic, and an inhalation anesthetic [usually nitrous oxide]), doses of 70 to 85 mcg/kg usually provide about 1 to 2 hours of clinical relaxation {01}. Values ranging from 30 to 175 minutes have been reported with 70 mcg/kg and values ranging from 40 to 211 minutes have been reported with 80 to 85 mcg/kg {01}. After the twitch response has recovered to 25% of control, spontaneous recovery to 50% of the control value takes about 24 minutes (range, 8 to 131 minutes) {01} and spontaneous recovery to 75% of the control value takes about 33 minutes {13}.

When pipecuronium is administered following recovery from succinylcholine-assisted endotracheal intubation, a dose of 50 mcg/kg provides about 45 minutes of clinical relaxation, and a dose of 70 to 85 mcg/kg provides the same clinical duration as occurs without prior administration of succinylcholine {01}.



Infants and children—

Intermediate- to long-acting and age-dependent; the expected duration of clinical effect (time until the twitch response returns to 25% of the control value as determined using a peripheral nerve stimulator) provided by an effective dose is about 13 minutes in infants < 3 months of age {11}, 10 to 44 minutes in infants 3 months to 1 year of age {01} {11} {12}, and 18 to 52 minutes in children 1 to 14 years of age {01} {13}. After the twitch response has recovered to 25% of control, spontaneous recovery to 75% of the control value takes about 25 to 30 minutes {11} {12} {13}.




Maintenance doses:


Adults—

The expected clinical duration of additional doses of 10 to 15 mcg/kg, administered when the twitch response has returned to 25% of the control value, is about 50 (range, 17 to 175) minutes {01} {05}.



Note: The clinical duration of initial and maintenance doses is increased by use of enflurane {01} {15} or isoflurane {01} {05} {13}, and possibly by other potentiating medications {01}, but is not significantly prolonged by halothane {01} {05} {13}.
In patients with renal function impairment, the duration of action is more variable than in patients with normal renal function {10}; accumulation of pipecuronium may lead to a significant prolongation of neuromuscular blockade {01} {20}.
No significant correlation was found between the duration of pipecuronium-induced neuromuscular blockade and the pharmacokinetic variables studied (volume of distribution, distribution and elimination half-lives, and plasma clearance) in a study in patients with normal renal function {04}.


Elimination:
    Renal {01}. In one study in patients undergoing coronary artery bypass surgery who received 200 mcg/kg (double the currently recommended maximum adult dose), 56% of the administered dose was excreted in the urine within 24 hours, 41% of the dose as unchanged pipecuronium and 15% as the active 3-decacetyl metabolite {01} {08}. In animals, this metabolite has about 40 to 50% of the activity of the parent compound {01}.
    Clearance—0.12 to 0.15 L per kg of body weight (L/kg) per hour in patients with normal renal function and 0.08 L/kg per hour in patients with renal function impairment {01} {04}.


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to bromides may be sensitive to pipecuronium bromide also.

Mutagenicity

No evidence of mutagenicity was found in the Ames test or the sister chromatid exchange test {01}.

Pregnancy/Reproduction
Fertility—
Animal studies have not been done {01}.

Pregnancy—
Adequate and well-controlled studies have not been done in pregnant women {01}.

Pipecuronium did not cause teratogenicity in rats receiving up to 50 mcg per kg of body weight intravenously. However, the highest dose caused embryotoxicity (increase in early fetal resorptions) secondary to maternal toxicity {01}.

FDA Pregnancy Category C {01}.


Labor and delivery—

Pipecuronium is not recommended for use in obstetrics (cesarean section) because of insufficient information on placental transfer and possible consequent effects on the neonate. Also, pipecuronium's duration of action exceeds the expected duration of cesarean section {01}.

Breast-feeding

It is not known whether pipecuronium is distributed into breast milk. However, problems in nursing babies have not been reported.

Pediatrics

Pipecuronium has not been studied in neonates. Infants 3 months to 1 year of age receiving balanced or halothane anesthesia experience responses to pipecuronium similar to those of adults {01}. Children 1 to 14 years of age are less sensitive to the effects of pipecuronium than are adults {01} {11} or infants < 1 year of age {01} {11} {12} {13} {18}. The duration of clinical effect (time to recovery of the twitch response to 25% of the control value) is shorter in infants and children than in adults {01} {11} {12}.


Geriatrics


One study in patients 66 to 79 years of age has shown that response and dosage requirements for pipecuronium are not significantly different in geriatric patients than in younger adults {14}. However, whether the results reported in the relatively few elderly patients studied to date can be applied to the geriatric population in general has not been determined {26}. Also, elderly patients are more likely to have age-related renal function impairment, {22} which requires caution and possibly dosage reduction and/or longer intervals between doses {24} in patients receiving pipecuronium {01}.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.
Some of the following interactions have not been documented with pipecuronium. However, because they have been reported to occur with other nondepolarizing neuromuscular blocking agents, the possibility of a significant interaction with pipecuronium must be considered {01}.

» Aminoglycosides, possibly including oral neomycin (if significant quantities are absorbed in patients with renal function impairment) or
» Anesthetics, parenteral-local (large doses leading to significant plasma concentrations) or
Bacitracin or{01}{27}
» Capreomycin or
» Citrate-anticoagulated blood (massive transfusions) or
» Clindamycin or
Colistin or{01}{27}
Colistimethate sodium or{01}{27}
Lidocaine (intravenous doses > 5 mg/kg) or
» Lincomycin or
» Polymyxins or
Procaine (intravenous) or
Tetracyclines or{01}{27}
Trimethaphan (large doses)    (neuromuscular blocking activity of these medications may be additive to that of neuromuscular blocking agents; increased or prolonged respiratory depression or paralysis [apnea] may occur, but is of minor clinical significance while the patient is being mechanically ventilated; however, caution and careful monitoring of the patient are recommended during and following concurrent or sequential use, especially if there is a possibility of incomplete reversal of neuromuscular blockade postoperatively)


Analgesics, opioid (narcotic), especially those commonly used as adjuncts to anesthesia    (central respiratory depressant effects of opioid analgesics may be additive to the respiratory depressant effects of neuromuscular blocking agents; increased or prolonged respiratory depression or paralysis [apnea] may occur, but is of minor clinical significance while the patient is being mechanically ventilated; however, caution and careful monitoring of the patient are recommended during and following concurrent or sequential use, especially if there is a possibility of incomplete reversal of neuromuscular blockade postoperatively)

    (although specific information for pipecuronium is not available, high doses of sufentanil reduce initial dosage requirements for other nondepolarizing neuromuscular blocking agents {23}; it is recommended that a peripheral nerve stimulator be used to determine dosage)

    (concurrent use of a neuromuscular blocking agent prevents or reverses muscle rigidity induced by sufficiently high doses of most opioid analgesics, especially alfentanil, fentanyl, or sufentanil {23})

    (pipecuronium has no vagolytic activity {17} and will therefore not decrease the risk of opioid analgesic–induced bradycardia or hypotension {01}; in some patients [especially patients with compromised cardiac function and/or those receiving a beta-adrenergic blocking agent preoperatively], the incidence and/or severity of these effects may be increased)


Anesthetics, hydrocarbon inhalation     (neuromuscular blocking activity of inhalation hydrocarbon anesthetics, especially enflurane or isoflurane, may be additive to that of nondepolarizing neuromuscular blocking agents; enflurane {01} {09} {15} and isoflurane {01} {05} {12} {13} have been shown to increase pipecuronium's duration of action by about 50% {01} {15} and 12% {01}, respectively, but halothane has not been shown to prolong pipecuronium's effects significantly {01} {05} {13})


Antimyasthenics or
Edrophonium    (these agents antagonize the effects of nondepolarizing neuromuscular blocking agents; parenteral neostigmine or pyridostigmine are indicated to reverse neuromuscular blockade following surgery; edrophonium in a dose of 0.5 mg per kg of body weight [mg/kg] is not recommended for reversal of pipecuronium because it has been reported to be less effective than neostigmine [dose of 40 mcg (0.04 mg)/kg] {01} {05} {21}; use of higher doses of edrophonium or of pyridostigmine for reversal of pipecuronium has not been studied {01})

    (neuromuscular blocking agents may antagonize the effects of antimyasthenics on skeletal muscle; temporary dosage adjustment may be required to control symptoms of myasthenia gravis following surgery)


Calcium salts    (calcium salts may {28} reverse the effects of nondepolarizing neuromuscular blocking agents)


Doxapram    (the residual effects of neuromuscular blocking agents may be masked temporarily by doxapram when it is used post-anesthesia)


Magnesium salts, parenteral or
» Procainamide or
» Quinidine    (these medications may enhance the effects of the neuromuscular blocking agents; increased or prolonged respiratory depression or paralysis [apnea] may occur but is of minor clinical significance while the patient is being mechanically ventilated {01}; however, caution and careful monitoring of the patient are recommended during and following concurrent or sequential use, especially if there is a possibility of incomplete reversal of neuromuscular blockade postoperatively)


Neuromuscular blocking agents, other    (pipecuronium may be administered following recovery from succinylcholine when the latter has been administered to facilitate endotracheal intubation; administration of pipecuronium prior to succinylcholine, to prevent or attenuate succinylcholine-induced side effects, has not been studied {01})

    (administration of pipecuronium in conjunction with other nondepolarizing neuromuscular blocking agents has not been studied {01})


Potassium-depleting medications, such as:
Corticosteroids, glucocorticoid, especially with significant mineralocorticoid activity
Corticosteroids, mineralocorticoid
Amphotericin B
Bumetanide
Carbonic anhydrase inhibitors
Corticotropin, chronic therapeutic use of
Ethacrynic acid
Furosemide
Indapamide
Thiazide diuretics    (serum potassium determinations and correction of serum potassium concentration may be necessary prior to administration of pipecuronium because hypokalemia induced by these medications may enhance the effects of nondepolarizing neuromuscular blocking agents; increased or prolonged respiratory depression or paralysis [apnea] may occur but is of minor clinical significance while the patient is being mechanically ventilated; however, caution and careful monitoring of the patient are recommended during and following concurrent or sequential use, especially if there is a possibility of incomplete reversal of neuromuscular blockade postoperatively)



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Creatinine and
Potassium    (serum concentrations may be increased—incidence of each < 1% {01})


Glucose concentration, in blood    (may be decreased—incidence < 1% {01})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
Biliary obstruction or
Hepatic function impairment    (time to onset and maximum effect, pharmacokinetics, and dosage requirements of pipecuronium have not been studied in patients with moderate or severe hepatic function impairment or biliary obstruction {01})


Cardiovascular disease leading to slower circulation time or
Edema or
Other conditions associated with increased distribution volume    (time to onset of action and maximum effect of pipecuronium may be prolonged; a delay in readiness for intubation or surgery should be anticipated and allowed; administration of higher doses of pipecuronium to compensate for a delayed response is not recommended {01})


Dehydration or
Electrolyte or acid-base imbalance{01}    (action of neuromuscular blocking agents may be altered {01}; neuromuscular blockade usually is counteracted by alkalosis and enhanced by acidosis, but mixed imbalances may be present, leading to unpredictable responses {01})


Hypothermia    (intensity and duration of action of nondepolarizing neuromuscular blocking agents may be increased {35})


Myasthenia gravis{01} or
Myasthenic syndrome (Eaton-Lambert syndrome){01}    (risk of severe and prolonged muscle paralysis or weakness; a neuromuscular blocking agent with a shorter duration of action may be preferable {01} [although caution is required even with shorter-acting agents])


Pulmonary function impairment or
Respiratory depression    (risk of additive respiratory depression or impairment)


Renal function impairment, mild or moderate or
» Renal function impairment, severe    (duration of action of pipecuronium may be prolonged {01} or unpredictable {10}; a reduction in dosage may be necessary {01}, but use of a neuromuscular blocking agent with a more predictable duration of action in patients with renal function impairment [e.g., atracurium or vecuronium] may be preferable {01} {10})


Sensitivity to pipecuronium or to bromides


Side/Adverse Effects

Note: Unlike gallamine and pancuronium, pipecuronium has no vagolytic activity {01} {03} {06} {17}. Also, unlike several other neuromuscular blocking agents (especially tubocurarine, and, to a somewhat lesser extent, atracurium, metocurine, or succinylcholine), pipecuronium has not been reported to cause histamine release {11} {19}. It therefore causes minimal hemodynamic disturbance {01} {03} {06} {19}, although bradycardia and/or hypotension may occur because pipecuronium does not counteract the bradycardia and/or hypotension induced by other medications (e.g., anesthetics, opioid analgesics) or vagal stimulation {03}.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence less frequent (1% or higher)
    
Bradycardia{01} —incidence 1.4%
    
hypotension{01} —incidence 2.5%

Incidence rare (< 1%)
    
Anuria{01}
    
atelectasis{01}
    
atrial fibrillation{01}
    
central nervous system (CNS) depression{01}
    
cerebrovascular accident{01}
    
dyspnea{01}
    
hypertension{01}
    
hypesthesia{01}
    
laryngismus{01}
    
muscle atrophy{01}
    
myocardial ischemia{01}
    
respiratory depression{01}
    
skin rash{01}
    
thrombosis{01}
    
urticaria{01}
    
ventricular extrasystole{01}





Overdose
For specific information on the agents used in the management of pipecuronium overdose, see:
   • Atropine in Anticholinergics/Antispasmodics (Systemic) monograph; and/or
   • Neostigmine in Antimyasthenics (Systemic) monograph.
For more information on the management of overdose, contact a Poison Control Center (see Poison Control Center Listing ).

Treatment of overdose


Specific treatment {01}:
Anticholinesterase agents, such as neostigmine, can be administered to antagonize the action of pipecuronium. Edrophonium (0.5 mg/kg) does not sufficiently antagonize the effects of the medication {01}, i.e., it does not increase the twitch response to peripheral nerve stimulation to 70% of the control value or higher, especially when potent hydrocarbon inhalation anesthetics (enflurane or isoflurane) have been administered {05}. Use of higher doses of edrophonium or of pyridostigmine for antagonism of pipecuronium has not been studied {01}. It is recommended that atropine or another suitable anticholinergic agent be administered prior to or concurrently with the antagonist to counteract its muscarinic {28} side effects. However, use of an antagonist is merely an adjunct to, and not to be substituted for, the institution of measures to ensure adequate ventilation. Ventilatory assistance must be continued until the patient can maintain adequate ventilation unassisted {01}.



Monitoring:
A peripheral nerve stimulator can be used to determine the nature and degree of the neuromuscular blockade {01}.

The patient should be monitored following successful antagonism, because the duration of action of pipecuronium may exceed that of the antagonist {29} {38}.



Supportive care for apnea or prolonged paralysis:
Maintaining an adequate airway and assisting or controlling {24} ventilation. Artificial respiration should be continued until adequate spontaneous ventilation can be maintained {37}.



General Dosing Information
Neuromuscular blocking agents have no clinically significant {24} effect on consciousness or the pain threshold; therefore, when used as an adjunct to surgery, the neuromuscular blocking agent should always be used with adequate anesthesia {01}.

Since neuromuscular blocking agents may cause respiratory depression, they should be used only by those individuals experienced in the techniques of tracheal intubation, artificial respiration, and the administration of oxygen under positive pressure; facilities for these procedures should be immediately available {01}. The need to support ventilation for patients receiving pipecuronium should be anticipated {01}.

Pipecuronium is intended for intravenous administration only {01}.

The stated doses are intended as guidelines. Actual dosage must be individualized. It is recommended that a peripheral nerve stimulator be used to monitor response, need for additional doses, and reversal {01}.

Patients can be monitored for recovery from the effects of pipecuronium by evaluating the ability of the patient to lift his/her head (5-second head lift), adequate phonation, and ability to ventilate and maintain an adequate airway. Ventilatory support must be provided until the patient can ventilate and maintain an adequate airway {01}.

The ED 95 (dose of pipecuronium that will produce a 95% suppression of the twitch response to peripheral nerve stimulation) during balanced anesthesia in adults (geriatric patients as well as younger adults) may range from 21 to 77 (average, 41) mcg per kg of body weight (mcg/kg) {01} {05} {07} {09} {12} {14}. In infants < 1 year of age, the ED 95 is within the same range as for adults (generally about 33 to 48 mcg/kg) {01} {11} {12} {13}. In children 1 to 14 years of age, the ED 95 may range from 47 to 80 mcg/kg {11} {12} {13}. In patients of all ages, the ED 95 is significantly reduced with enflurane or isoflurane, but not halothane, anesthesia (as compared with balanced or neurolept anesthesia) {01} {09} {12} {15}.

For obese patients (> 30% above ideal body weight for height), dosage of pipecuronium should be calculated on the basis of ideal body weight. Administration of pipecuronium to obese patients in doses based on actual body weight significantly prolongs the medication's effects {01}.

When nondepolarizing neuromuscular blocking agents are administered concurrently with potent general anesthetics such as enflurane, ether, isoflurane, methoxyflurane, or cyclopropane, a reduction in dosage, as determined using a peripheral nerve stimulator, may be required. However, halothane has not been shown to potentiate significantly the effect of pipecuronium {01} {05} {13}.

It is recommended that reversal of pipecuronium-induced neuromuscular blockade with an antagonist (e.g., neostigmine) be attempted only after some spontaneous recovery, as demonstrated using a peripheral nerve stimulator, has first taken place. Recovery will not occur as rapidly if the antagonist is administered earlier {30}.


Parenteral Dosage Forms

PIPECURONIUM BROMIDE FOR INJECTION

Usual adult dose


Skeletal muscle paralysis, initial:
For intubation: Intravenous, 70 to 85 mcg (0.07 to 0.085 mg) per kg of actual body weight (normal weight patients) or ideal body weight (obese patients) {01} to provide good to excellent intubating conditions in two and one-half to three minutes {01}. The lowest dose recommended to provide {39} adequate intubation conditions is 50 mcg per kg of body weight {01}, but the onset of action may be delayed with this dose {25}.

For administration following recovery from succinylcholine-facilitated endotracheal intubation: Intravenous, 50 mcg (0.05 mg) per kg of actual body weight (normal weight patients) or ideal body weight (obese patients) to provide about 45 minutes of relaxation, or 70 to 85 mcg (0.07 to 0.085 mg) per kg of body weight to provide about 1 to 2 hours of muscle paralysis {01} {28}.



Skeletal muscle paralysis, maintenance:
Intravenous, after recovery of the twitch response to peripheral nerve stimulation to 25% of control, 10 to 15 mcg (0.01 to 0.015 mg) per kg of body weight. Lower doses may be sufficient for patients receiving inhalation anesthesia {01}.


Note: For patients with renal function impairment, dosage should be based on creatinine clearance as well as body weight. The following initial doses are recommended:

Creatinine
clearance
(mL/min)
Dose
(mcg/kg ideal
body weight)
< 40
50
60
55
80
70
100
85
> 100
Up to 100



Usual adult prescribing limits
Intravenous, 100 mcg (0.1 mg) per kg of actual body weight (normal weight patients) or ideal body weight (obese patients) {01}.

Usual pediatric and adolescent dose
Skeletal muscle paralysis, initial
Infants up to 3 months of age: Dosage has not been established {01}.

Infants 3 to 12 months of age: Intravenous, 40 mcg (0.04 mg) per kg of body weight (provides about 10 to 44 minutes of clinical relaxation) {01}.

Children 1 to 14 years of age: Intravenous, 57 mcg (0.057 mg) per kg of body weight (provides 18 to 52 minutes of clinical relaxation) {01}.

Adolescents older than 14 years of age: See Usual adult dose.

Skeletal muscle paralysis, maintenance
Dosage has not been established {01}.


Usual geriatric dose
See Usual adult dose {14}.

Size(s) usually available:

Note: Withdrawn from the U.S. market in October 1999.

U.S.—
Not commercially available.

Canada—
Not commercially available.

Packaging and storage:


Before reconstitution:
Store between 2 and 30 °C (36 and 86 °F), protected from light {01}, unless otherwise specified by manufacturer.



After reconstitution {01}:
Bacteriostatic water for injection as diluent: Store at room temperature (15 to 30 °C [59 to 86 °F]) or in a refrigerator (2 to 8 °C [36 to 46 °F]).

Other injections as diluent: Store in a refrigerator.


Preparation of dosage form:
Pipecuronium bromide for injection may be reconstituted with 0.9% sodium chloride injection, 5% dextrose and 0.9% sodium chloride injection, 5% dextrose injection, lactated Ringer"s injection, sterile water for injection, or bacteriostatic water for injection. Reconstitution using 10 mL of diluent provides a solution containing 1 mg per mL of pipecuronium bromide {01}.

Stability:
The vial of pipecuronium bromide is intended for single-dose use only; unused portions of the reconstituted solution should be discarded {01}.

After reconstitution with bacteriostatic water for injection, pipecuronium should be administered within 5 days {01}.

After reconstitution with injections other than bacteriostatic water for injection, pipecuronium should be administered within 24 hours {01}.



Revised: 10/13/2000



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  1. Meretoja OA, Erkola O. Pipecuronium revisited: dose-response and maintenance requirement in infants, children, and adults. J Clin Anesth 1997; 9: 125-9.
  1. Denman WT, Goudsouzian NG, Gelb C. Comparison of neuromuscular, cardiovascular, and histamine-releasing properties of doxacurium and pipecuronium. J Clin Anesth 1996; 8: 113-8.
  1. Cameron EM, Lisbon A, Moorman R, et al. Prolonged neuromuscular blockade with pipecuronium in a patient with renal insufficiency. Eur J Anaesthesiol 1994; 11: 237-9.
  1. Naguib M, Abdulatif M. Dose-response relationships for edrophonium and neostigmine antagonism of pipecuronium-induced neuromuscular block. Anesth Analg 1994; 78: 306-11.
  1. Standard statement, per Geriatrics panel.
  1. Sufentanil package insert (Elkins-Sinn—US), Rev 1/96, Rec 7/98.
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