Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/3669
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Pancuronium Bromide (Injection, Solution)
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dailymed-instance:dosage |
Pancuronium Bromide Injection is for intravenous use only.
This drug should be administered by or under the supervision of experienced
clinicians familiar with the use of neuromuscular blocking agents. DOSAGE
MUST BE INDIVIDUALIZED IN EACH CASE. The dosage information which follows
is derived from studies based upon units of drug per unit of body weight and
is intended to serve as a guide only. Since potent inhalational anesthetics
or prior use of succinylcholine may enhance the intensity and duration of
pancuronium bromide (see PRECAUTIONS: Drug Interactions), the lower end of the recommended
initial dosage range may suffice when pancuronium bromide is first used after
intubation with succinylcholine and/or after maintenance doses of volatile
liquid inhalational anesthetics are started. To obtain maximum clinical benefits
of Pancuronium Bromide Injection and to minimize the possibility of overdosage,
the monitoring of muscle twitch response to a peripheral nerve stimulator
is advised. In adults under balanced anesthesia the
initial intravenous dosage range is 0.04 to 0.1 mg/kg. Later incremental doses
starting at 0.01 mg/kg may be used. These increments slightly increase the
magnitude of the blockade and significantly increase the duration of blockade
because a significant number of myoneural junctions are still blocked when
there is clinical need for more drug. If Pancuronium
Bromide Injection is used to provide skeletal muscle relaxation for endotracheal
intubation, a bolus dose of 0.06 to 0.1 mg/kg is recommended. Conditions satisfactory
for intubation are usually present within 2 to 3 minutes (see PRECAUTIONS). Dosage in Children Dose response studies in children indicate
that, with the exception of neonates, dosage requirements are the same as
for adults. Neonates are especially sensitive to nondepolarizing neuromuscular
blocking agents, such as Pancuronium Bromide Injection, during the first month
of life. It is recommended that a test dose of 0.02 mg/kg be given first in
this group to measure responsiveness. Caesarean
Section The dosage to provide relaxation for
intubation and operation is the same as for general surgical procedures. The
dosage to provide relaxation, following usage of succinylcholine for intubation
(see PRECAUTIONS: Drug
Interactions), is the same as for general surgical procedures. Compatibility Pancuronium
Bromide Injection is compatible in solution with: 0.9% sodium chloride injection 5% dextrose injection 5% dextrose and sodium chloride injection Lactated
Ringer's injection Parenteral
drug products should be inspected visually for particulate matter and discoloration
prior to administration, whenever solution and container permit. When
mixed with the above solutions in glass or plastic containers, Pancuronium
Bromide Injection will remain stable in solution for 48 hours with no alteration
in potency or pH; no decomposition is observed and there is no absorption
to either the glass or plastic container.
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dailymed-instance:descripti... |
Pancuronium Bromide is a nondepolarizing neuromuscular blocking
agent chemically designated as the aminosteroid 2��, 16��- dipiperidino-5��-androstane-3��,
17-��diol diacetate dimethobromide, CHBrNO.
It is a fine white odorless powder which is soluble in water, alcohol and
chloroform. It has the following structural formula: Pancuronium
Bromide Injection is available in sterile, isotonic, nonpyrogenic solution
for injection. Each mL contains pancuronium bromide 1 mg; sodium acetate,
anhydrous 1.2 mg; benzyl alcohol 10 mg as preservative. Sodium chloride added
to adjust tonicity. May contain acetic acid and/or sodium hydroxide for pH
adjustment. pH is 4.0 (3.8 to 4.2).
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dailymed-instance:clinicalP... |
Pancuronium bromide is a nondepolarizing neuromuscular blocking
agent possessing all of the characteristic pharmacological actions of this
class of drugs (curariform). It acts by competing for cholinergic receptors
at the motor end-plate. The antagonism to acetylcholine is inhibited; and
neuromuscular block is reversed by anticholinesterase agents such as pyridostigmine,
neostigmine, and edrophonium. Pancuronium bromide is approximately 1/3 less
potent than vecuronium and approximately 5 times as potent as d-tubocurarine:
the duration of neuromuscular blockage produced by pancuronium bromide is
longer than that of vecuronium at initially equipotent doses. The
ED(dose required to produce 95% suppression of muscle twitch
response) is approximately 0.05 mg/kg under balanced anesthesia and 0.03 mg/kg
under halothane anesthesia. These doses produce effective skeletal muscle
relaxation (as judged by time from maximum effect to 25% recovery of control
twitch height) for approximately 22 minutes; the duration from injection to
90% recovery of control twitch height is approximately 65 minutes. The intubating
dose of 0.1 mg/kg (balanced anesthesia) will effectively abolish twitch response
within approximately 4 minutes; time from injection to 25% recovery from this
dose is approximately 100 minutes. Supplemental doses
to maintain muscle relaxation slightly increase the magnitude of block and
significantly increase the duration of block. The use of a peripheral nerve
stimulator is of benefit in assessing the degree of neuromuscular blockade. The
most characteristic circulatory effects of pancuronium, studied under halothane
anesthesia, are a moderate rise in heart rate, mean arterial pressure and
cardiac output; systemic vascular resistance is not changed significantly,
and central venous pressure may fall slightly. The heart rate rise is inversely
related to the rate immediately before administration of pancuronium, is blocked
by prior administration of atropine, and appears unrelated to the concentration
of halothane or dose of pancuronium. Data on histamine
assays and available clinical experience indicate that hypersensitivity reactions
such as bronchospasm, flushing, redness, hypotension, tachycardia, and other
reactions commonly associated with histamine release are rare. (See ADVERSE REACTIONS). Pharmacokinetics The elimination
half-life of pancuronium has been reported to range between 89-161 minutes.
The volume of distribution ranges from 241-280 mL/kg; and plasma clearance
is approximately 1.1���1.9 mL/minute/kg. Approximately 40% of the total
dose of pancuronium has been recovered in urine as unchanged pancuronium and
its metabolites while approximately 11% has been recovered in bile. As much
as 25% of an injected dose may be recovered as 3-hydroxy metabolite, which
is half as potent a blocking agent as pancuronium. Less than 5% of the injected
dose is recovered as 17-hydroxy metabolite and 3,17-dihydroxy metabolite,
which have been judged to be approximately 50 times less potent than pancuronium.
Pancuronium exhibits strong binding to gamma globulin and moderate binding
to albumin. Approximately 13% is unbound to plasma protein. In patients with
cirrhosis the volume of distribution is increased by approximately 50%, the
plasma clearance is decreased by approximately 22%, and the elimination half-life
is doubled. Similar results were noted in patients with biliary obstruction,
except that plasma clearance was less than half the normal rate. The initial
total dose to achieve adequate relaxation may, thus, be high in patients with
hepatic and/or biliary tract dysfunction, while the duration of action is
greater than usual. The elimination half-life is doubled,
and the plasma clearance is reduced by approximately 60% in patients with
renal failure. The volume of distribution is variable, and in some cases elevated.
The rate of recovery of neuromuscular blockade, as determined by peripheral
nerve stimulation is variable and sometimes very much slower than normal.
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Pancuronium Bromide Injection is contraindicated in patients
known to be hypersensitive to the drug.
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dailymed-instance:supply |
Pancuronium Bromide Injection is supplied as follows: STORAGE Store in refrigerator 2��to 8��C (36��to 46��F). The 10mL vial will maintain full clinical
potency for up to six months at room temperature. November, 2004 HOSPIRA, INC., LAKE FOREST,
IL 60045 USA
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THIS DRUG SHOULD BE ADMINISTERED
BY ADEQUATELY TRAINED INDIVIDUALS FAMILIAR WITH ITS ACTIONS, CHARACTERISTICS,
AND HAZARDS.
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dailymed-instance:precautio... |
USE OF A PERIPHERAL NERVE STIMULATOR WILL USUALLY BE OF VALUE
FOR MONITORING OF NEUROMUSCULAR BLOCKING EFFECT, AVOIDING OVERDOSAGE AND ASSISTING
IN EVALUATION OF RECOVERY.<br/>General: Although Pancuronium Bromide Injection has been used successfully
in many patients with pre-existing pulmonary, hepatic, or renal disease, caution
should be exercised in these situations. Renal
Failure A major portion of pancuronium, as
well as an active metabolite, are recovered in urine. The elimination half-life
is doubled and the plasma clearance is reduced in patients with renal failure;
at the same time, the rate of recovery of neuromuscular blockade is variable
and sometimes very much slower than normal (see Pharmacokinetics). This information should be taken into consideration if pancuronium
is selected, for other reasons, to be used in a patient with renal failure. Altered Circulation Time Conditions
associated with slower circulation time in cardiovascular disease, old age,
edematous states resulting in increased volume of distribution may contribute
to a delay in onset time; therefore, dosage should not be increased. Hepatic and/or Biliary Tract Disease The
doubled elimination half-life and reduced plasma clearance determined in patients
with hepatic and/or biliary tract disease, as well as limited data showing
that recovery time is prolonged an average of 65% in patients with biliary
tract obstruction, suggests that prolongation of neuromuscular blockade may
occur. At the same time, these conditions are characterized by an approximately
50% increase in volume of distribution of pancuronium, suggesting that the
total initial dose to achieve adequate relaxation may in some cases be high.
The possibility of slower onset, higher total dosage and prolongation of neuromuscular
blockade must be taken into consideration when pancuronium is used in these
patients. (See also Pharmacokinetics). Long-term Use in I.C.U. In
the intensive care unit, in rare cases, long-term use of neuromuscular blocking
drugs to facilitate mechanical ventilation 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. Typically, such patients receive
other drugs such as broad spectrum antibiotics, narcotics and/or steroids
and may have electrolyte imbalance and diseases which lead to electrolyte
imbalance, hypoxic episodes of varying duration, acid-base imbalance, and
extreme debilitation, any of which may enhance the actions of a neuromuscular
blocking agent. Additionally, patients immobilized for extended periods frequently
develop symptoms consistent with disuse muscle atrophy. Therefore, when there
is a need for long-term mechanical ventilation, the benefits-to-risk ratio
of neuromuscular blockade must be considered. Continuous
infusion or intermittent bolus dosing to support mechanical ventilation has
not been studied sufficiently to support dosage recommendations. UNDER
THE ABOVE CONDITIONS, APPROPRIATE MONITORING, SUCH AS USE OF A PERIPHERAL
NERVE STIMULATOR, TO ASSESS THE DEGREE OF NEUROMUSCULAR BLOCKADE, MAY PRECLUDE
INADVERTENT EXCESS DOSING. Severe
Obesity or Neuromuscular Disease Patients
with severe obesity or neuromuscular disease may pose airway and/or ventilatory
problems requiring special care before, during, and after the use of neuromuscular
blocking agents such as pancuronium bromide. CNS Pancuronium bromide has
no known effect on consciousness, the pain threshold or cerebration. Administration
should be accompanied by adequate anesthesia or sedation.<br/>Drug Interactions: Prior administration of succinylcholine may enhance the neuromuscular
blocking effect of pancuronium and increase its duration of action. If succinylcholine
is used before pancuronium bromide, the administration of pancuronium bromide
should be delayed until the patient starts recovering from succinylcholine-induced
neuromuscular blockade. If a small dose of pancuronium
bromide is given at least 3 minutes prior to the administration of succinylcholine,
in order to reduce the incidence and intensity of succinylcholine-induced
fasciculations, this dose may induce a degree of neuromuscular block sufficient
to cause respiratory depression in some patients. Other
nondepolarizing neuromuscular blocking agents (vecuronium, atracurium, d-tubocurarine,
metocurine, and gallamine) behave in a clinically similar fashion to pancuronium
bromide. The combination of pancuronium bromide-metocurine and pancuronium
bromide-d-tubocurarine are significantly more potent than the additive effects
of each of the individual drugs given alone, however, the duration of blockade
of these combinations is not prolonged. There are insufficient data to support
concomitant use of pancuronium and the other three above mentioned muscle
relaxants in the same patient.<br/>Inhalational Anesthetics: Use of volatile inhalational anesthetics such as enflurane,
isoflurane, and halothane with pancuronium bromide will enhance neuromuscular
blockade. Potentiation is most prominent with use of enflurane and isoflurane. With
the above agents, the intubating dose of pancuronium bromide 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 taken into
consideration when the drug is selected for intubation in these circumstances. Clinical
experience and animal experiments suggest that pancuronium should be given
with caution to patients receiving chronic tricyclic antidepressant therapy
who are anesthetized with halothane because severe ventricular arrhythmias
may result from this combination. The severity of the arrhythmias appear in
part related to the dose of pancuronium.<br/>Antibiotics: Parenteral/intraperitoneal administration of high doses of
certain antibiotics may intensify or produce neuromuscular block on their
own. The following antibiotics have been associated with various degrees of
paralysis: aminoglycosides (such as neomycin, streptomycin, kanamycin, gentamicin,
and dihydrostreptomycin); tetracyclines; bacitracin; polymyxin B; colistin;
and sodium colistimethate. If these or other newly introduced antibiotics
are used preoperatively or in conjunction with pancuronium bromide, unexpected
prolongation of neuromuscular block should be considered a possibility.<br/>Other: Experience concerning 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 bromide. Electrolyte
imbalance and diseases which lead to electrolyte imbalance, such as adrenal
cortical insufficiency, have been shown to alter neuromuscular blockade. Depending
on the nature of the imbalance, either enhancement or inhibition may be expected.
Magnesium salts, administered for the management of toxemia of pregnancy,
may enhance the neuromuscular blockade.<br/>Drug/Laboratory Test Interactions: None known.<br/>Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term studies in animals have not been performed to evaluate
carcinogenic or mutagenic potential or impairment of fertility.<br/>Pregnancy: Pregnancy Category C: Animal reproduction studies have not been performed. It is
not known whether pancuronium bromide can cause fetal harm when administered
to a pregnant woman or can affect reproduction capacity. Pancuronium bromide
should be given to a pregnant woman only if the administering clinician decides
that the benefits outweigh the risks. Pancuronium bromide
may be used in operative obstetrics (Caesarean Section), but reversal of pancuronium may be unsatisfactory in patients
receiving magnesium sulfate for toxemia of pregnancy because magnesium salts
enhance neuromuscular blockade. Dosage should usually be reduced, as indicated,
in such cases. It is also recommended that the interval between use of pancuronium
and delivery be reasonably short to avoid clinically significant placental
transfer.<br/>Pediatric Use: Dose response studies in children indicate that, with the
exception of neonates, dosage requirements are the same as for adults. Neonates
are especially sensitive to nondepolarizing neuromuscular blocking agents,
such as pancuronium bromide, during the first month of life. It is recommended
that a test dose of 0.02 mg/kg be given first in this group to measure responsiveness. The
prolonged use of pancuronium bromide for the management of neonates undergoing
mechanical ventilation has been associated in rare cases with severe skeletal
muscle weakness that may first be noted during attempts to wean such patients
from the ventilator; such patients usually receive other drugs such as antibiotics
which may enhance neuromuscular blockade. Microscopic changes consistent with
disuse atrophy have been noted at autopsy. Although a cause-and-effect relationship
has not been established, the benefits-to-risk ratio must be considered when
there is a need for neuromuscular blockade to facilitate long-term mechanical
ventilation of neonates. Rare cases of unexplained,
clinically significant methemoglobinemia have been reported in premature neonates
undergoing emergency anesthesia and surgery which included combined use of
pancuronium, fentanyl and atropine. A direct cause-and-effect relationship
between the combined use of these drugs and the reported cases of methemoglobinemia
has not been established.
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dailymed-instance:overdosag... |
The possibility of iatrogenic overdosage can be minimized
by carefully monitoring the muscle twitch response to peripheral nerve stimulation. Excessive
doses of pancuronium bromide can be expected to produce enhanced pharmacological
effects. Residual neuromuscular blockade beyond the time period needed may
occur with pancuronium bromide as with other neuromuscular blockers. This
may be manifested by skeletal muscle weakness, decreased respiratory reserve,
low tidal volume, or apnea. A peripheral nerve stimulator may be used to assess
the degree of residual neuromuscular blockade and help to differentiate residual
neuromuscular blockade from other causes of decreased respiratory reserve. Pyridostigmine
bromide, neostigmine, or edrophonium, in conjunction with atropine or glycopyrrolate,
will usually antagonize the skeletal muscle relaxant action of pancuronium
bromide. Satisfactory reversal can be judged by adequacy of skeletal muscle
tone and by adequacy of respiration. A peripheral nerve stimulator may also
be used to monitor restoration of twitch response. Failure
of prompt reversal (within 30 minutes) may occur in the presence of extreme
debilitation, carcinomatosis, and with concomitant use of certain broad spectrum
antibiotics, or anesthetic agents and other drugs which enhance neuromuscular
blockade or cause respiratory depression of their own. Under such circumstances,the management is the same as that of prolonged neuromuscular blockade. Ventilation
must be supported by artificial means until the patient has resumed control
of his respiration. Prior to the use of reversal agents, reference should
be made to the specific package insert of the reversal agent.
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dailymed-instance:genericMe... |
Pancuronium Bromide
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dailymed-instance:fullName |
Pancuronium Bromide (Injection, Solution)
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dailymed-instance:adverseRe... |
Neuromuscular The
most frequent adverse reaction to nondepolarizing blocking agents as a class
consists of an extension of the drug's pharmacological action beyond
the time period needed. This may vary from skeletal muscle weakness to profound
and prolonged skeletal muscle paralysis resulting in respiratory insufficiency
or apnea. (See PRECAUTIONS: Pediatric Use). Inadequate
reversal of the neuromuscular blockade is possible with pancuronium bromide
as with all curariform drugs. These adverse experiences are managed by manual
or mechanical ventilation until recovery is judged adequate. Prolonged
paralysis and/or skeletal muscle weakness have been reported after long-term
use to support mechanical ventilation in the intensive care unit. Cardiovascular See discussion
of circulatory effects in CLINICAL PHARMACOLOGY. Gastrointestinal Salivation is sometimes noted during very
light anesthesia, especially if no anticholinergic premedication is used. Skin An occasional transient
rash is noted accompanying the use of pancuronium bromide. Other Although histamine
release is not a characteristic action of pancuronium bromide, rare hypersensitivity
reactions such as bronchospasm, flushing, redness, hypotension, tachycardia
and other reactions possibly mediated by histamine release have been reported.
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dailymed-instance:warning |
PANCURONIUM BROMIDE INJECTION SHOULD BE ADMINISTERED IN CAREFULLY
ADJUSTED DOSES BY OR UNDER THE SUPERVISION OF EXPERIENCED CLINICIANS WHO ARE
FAMILIAR WITH ITS ACTIONS AND THE POSSIBLE COMPLICATIONS THAT MIGHT OCCUR
FOLLOWING ITS USE. THE DRUG SHOULD NOT BE ADMINISTERED UNLESS FACILITIES FOR
INTUBATION, ARTIFICIAL RESPIRATION, OXYGEN THERAPY, AND REVERSAL AGENTS ARE
IMMEDIATELY AVAILABLE. THE CLINICIAN MUST BE PREPARED TO ASSIST OR CONTROL
RESPIRATION. In patients who are known to have myasthenia
gravis or the myasthenic (Eaton-Lambert) syndrome, small doses of pancuronium
bromide may have profound effects. In such patients, a peripheral nerve stimulator
and use of a small test dose may be of value in monitoring the response to
administration of muscle relaxants. Benzyl alcohol has
been reported to be associated with a fatal���gasping syndrome���in premature infants. Exposure to excessive amounts
of benzyl alcohol has been associated with toxicity (hypotension, metabolic
acidosis), particularly in neonates, and an increased incidence of kernicterus,
particularly in small preterm infants. There have been rare reports of deaths,
primarily in preterm infants, associated with exposure to excessive amounts
of benzyl alcohol. The amount ofbenzyl alcohol from medications is usually
considered negligible compared to those received in flush solutions containing
benzyl alcohol. Administration of high dosages of medications (including pancuronium)
containing this preservative must take into account the total amount of benzyl
alcohol administered. The recommended dosage range of pancuronium bromide
for preterm and term infants includes amounts of benzyl alcohol well below
that associated with toxicity; however, the amount of benzyl alcohol at which
toxicity may occur is not known. If the patient requires more than the recommended
dosages or other medications containing this preservative, the practitioner
must consider the daily metabolic load of benzyl alcohol from these combined
sources.
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dailymed-instance:indicatio... |
Pancuronium bromide is indicated as an adjunct to general
anesthesia to facilitate tracheal intubation and to provide skeletal muscle
relaxation during surgery or mechanical ventilation.
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dailymed-instance:name |
Pancuronium Bromide
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