Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/3457
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Atracurium Besylate (Injection, Solution)
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To avoid distress
to the patient, atracurium should not be administered before
unconsciousness has been induced. Atracurium should not be mixed in the
same syringe, or administered simultaneously through the same needle,
with alkaline solutions (e.g., barbiturate solutions). Atracurium besylate
should be administered intravenously. DO NOT GIVE ATRACURIUM BESYLATE BY
INTRAMUSCULAR ADMINISTRATION. Intramuscular administration of atracurium
may result in tissue irritation and there are no clinical data to
support this route of administration. The use of a
peripheral nerve stimulator to monitor muscle twitch suppression and
recovery will permit the most advantageous use of atracurium and
minimize the possibility of overdosage.<br/>Bolus Doses for
Intubation and Maintenance of Neuromuscular Block:<br/>Adults: An
atracurium besylate dose of 0.4 to 0.5 mg/kg (1.7 to 2.2
times the ED), given as an intravenous
bolus injection, is the recommended initial dose for
most patients. With this dose, good or excellent
conditions for nonemergency intubation can be expected
in 2 to 2.5 minutes in most patients, with maximum
neuromuscular block achieved approximately 3 to 5
minutes after injection. Clinically required
neuromuscular block generally lasts 20 to 35 minutes
under balanced anesthesia. Under balanced anesthesia, recovery to 25% of control is achieved approximately 35
to 45 minutes after injection, and recovery is usually
95% complete approximately 60 minutes after injection. Atracurium is potentiated by isoflurane or enflurane
anesthesia. The same initial atracurium besylate dose of
0.4 to 0.5 mg/kg may be used for intubation prior to
administration of these inhalation agents; however, if
atracurium is first administered under steady state of
isoflurane or enflurane, the initial atracurium besylate
dose should be reduced by approximately one-third, i.e.,
to 0.25 to 0.35 mg/kg, to adjust for the potentiating
effects of these anesthetic agents. With halothane,
which has only a marginal (approximately 20%)
potentiating effect on atracurium, smaller dosage
reductions may be considered. Atracurium besylate doses of 0.08 to 0.10 mg/kg are
recommended for maintenance of neuromuscular block
during prolonged surgical procedures. The first
maintenance dose will generally be required 20 to 45 minutes after the initial atracurium besylate injection,
but the need for maintenance doses should be determined
by clinicalcriteria. Because atracurium lacks
cumulative effects, maintenance doses may be
administered at relatively regular intervals for each
patient, ranging approximately from 15 to 25 minutes
under balanced anesthesia, slightly longer under
isoflurane or enflurane. Higher atracurium besylate
doses (up to 0.2 mg/kg) permit maintenance dosing at
longer intervals.<br/>Children
and Infants: No
atracurium dosage adjustments are required for pediatric
patients two years of age or older. An atracurium besylate dose of 0.3 to 0.4 mg/kg is recommended as the initial dose for infants (1 month to 2 years of age)
under halothane anesthesia. Maintenance doses may be
required with slightly greater frequency in infants and
children than in adults.<br/>Special
Considerations: An
initial atracurium besylate dose of 0.3 to 0.4 mg/kg,
given slowly or in divided doses over one minute, is
recommended for adults, children, or infants with
significant cardiovascular disease and for adults,
children, or infants with any history (e.g., severe
anaphylactoid reactions or asthma) suggesting a greater
risk of histamine release. Dosage reductions must be considered also in patients with neuromuscular disease, severe electrolyte
disorders, or carcinomatosis in which potentiation of
neuromuscular block or difficulties with reversal have
been demonstrated. There has been no clinical experience
with atracurium in these patients, and no specific
dosage adjustments can be recommended. No atracurium
dosage adjustments are required for patients with renal
disease. An
initial atracurium besylate dose of 0.3 to 0.4 mg/kg is
recommended for adults following the use of
succinylcholine for intubation under balanced
anesthesia. Further reductions may be desirable with the
use of potent inhalation anesthetics. The patient should
be permitted to recover from the effects of
succinylcholine prior to atracurium administration.
Insufficient data are available for recommendation of a
specific initial atracurium dose for administration
following the use of succinylcholine in children and
infants.<br/>Use by Continuous
Infusion:<br/>Infusion in
the Operating Room (OR): After administration of a recommended initial bolus
dose of Atracurium Besylate Injection (0.3 to 0.5
mg/kg), a diluted solution of atracurium besylate can be
administered by continuous infusion to adults and
children aged 2 or more years for maintenance of
neuromuscular block during extended surgical procedures.
Infusion of atracurium should be individualized for each
patient. The rate of administration should be adjusted
according to the patient's response as determined by
peripheral nerve stimulation. Accurate dosing is best
achieved using a precision infusion device. Infusion of atracurium should be initiated only after
early evidence of spontaneous recovery from the bolus
dose. An initial infusion rate of 9 to 10 mcg/kg/min may
be required to rapidly counteract the spontaneous
recovery of neuromuscular function. Thereafter, a rate
of 5 to 9 mcg/kg/min should be adequate to maintain
continuous neuromuscular block in the range of 89 to 99% in most pediatric and adult patients under balanced
anesthesia. Occasional patients may require infusion
rates as low as 2 mcg/kg/min or as high as 15
mcg/kg/min. The
neuromuscular blocking effect of atracurium administered
by infusion is potentiated by enflurane or isoflurane
and, to a lesser extent, by halothane. Reduction in the
infusion rate of atracurium should, therefore, be
considered for patients receiving inhalation anesthesia.
The rate of atracurium besylate infusion should be
reduced by approximately one-third in the presence of
steady-state enflurane or isoflurane anesthesia; smaller
reductions should be considered in the presence of
halothane. In
patients undergoing cardiopulmonary bypass with induced
hypothermia, the rate of infusion of atracurium required
to maintain adequate surgical relaxation during
hypothermia (25��to 28��C) has been shown to be
approximately half the rate required during
normothermia. Spontaneous recovery from neuromuscular block following
discontinuation of atracurium infusion may be expected
to proceed at a rate comparable to that following
administration of a single bolus dose.<br/>Infusion in
the Intensive Care Unit (ICU): The
principles for infusion of atracurium in the OR are also
applicable to use in the ICU. An
infusion rate of 11 to 13 mcg/kg/min (range 4.5 to 29.5)
should provide adequate neuromuscular block in adult
patients in an ICU. Limited information suggests that
infusion rates required for pediatric patients in the
ICU may be higher than in adult patients. There may be
wide interpatient variability in dosage requirements and
these requirements may increase or decrease with time
. Following
recovery from neuromuscular block, readministration of a
bolus dose may be necessary to quickly re-establish
neuromuscular block prior to reinstitution of the
infusion.<br/>Infusion Rate
Tables: The amount
of infusion solution required per minute will depend upon the
concentration of atracurium in the infusion solution, the
desired atracurium dose, and the patient's weight. The following
tables provide guidelines for delivery, in mL/hr (equivalent to
microdrops/min when 60 microdrops = 1 mL), of atracurium
solutions in concentrations of 0.2 mg/mL (20 mg in 100 mL) or
0.5 mg/mL (50 mg in 100 mL) with an infusion pump or a gravity
flow device.<br/>Compatibility and
Admixtures: Atracurium
besylate infusion solutions may be prepared by admixing
Atracurium Besylate Injection with an appropriate diluent such
as 5% Dextrose Injection USP, 0.9% Sodium Chloride Injection
USP, or 5% Dextrose and 0.9% Sodium Chloride Injection USP.
Infusion solutions should be used within 24 hours of
preparation. Unused solutions should be discarded. Solutions
containing 0.2 mg/mL or 0.5 mg/mL atracurium besylate in the
above diluents may be stored either under refrigeration or at
room temperature for 24 hours without significant loss of
potency. Care should be taken during admixture to prevent
inadvertent contamination. Visually inspect prior to
administration. Spontaneous
degradation of atracurium besylate has been demonstrated to
occur more rapidly in lactated Ringers solution than in 0.9%
sodium chloride solution. Therefore, it is recommended that Lactated Ringers Injection USP not be used as a diluent in
preparing solutions of Atracurium Besylate Injection for
infusion. Parenteral
drug products should be inspected visually for particulate
matter and discoloration prior to administration, whenever
solution and container permit.
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dailymed-instance:descripti... |
Atracurium Besylate
Injection is an intermediate-duration, non-depolarizing, skeletal muscle
relaxant for intravenous administration. Atracurium Besylate is designed
as 2,2'���[1,5-pentanediylbis[oxy(3-oxo-3,1-propanediyl)]]bis[1-[(3,4-dimethoxyphenyl)methyl]-1,2,3,4-tetrahydro-6,7-dimethoxy-2-methylisoquinolinium]
dibenzenesulfonate. It has a molecular weight of 1243.49, and its
molecular formula is
CHNOSThe structural formula is: Atracurium besylate
is a complex molecule containing four sites at which different
stereochemical configurations can occur. The symmetry of the molecule,
however, results in only ten, instead of sixteen, possible different
isomers. The manufacture of atracurium besylate results in these isomers being produced in unequal amounts but with a consistent ratio. Those
molecules in which the methyl group attached to the quaternary nitrogen
projects on the oppositeside to the adjacent substituted-benzyl moiety
predominate by approximately 3:1. Atracurium Besylate
Injection is a sterile, non-pyrogenic aqueous solution for intravenous
administration. Each mL contains 10 mg atracurium besylate. The pH is
adjusted to 3.25���3.65 with benzenesulfonic acid. The multiple dose
vial contains 0.9% benzyl alcohol added as a preservative. Atracurium Besylate Injection slowly loses potency with time at the rate of
approximately 6% per year under
refrigeration (5��C). Atracurium Besylate Injection should be
refrigerated at 2��to 8��C (36��to 46��F) to preserve potency. Rate of
loss in potency increases to approximately 5% per month at 25��C (77��F). Upon removal
from refrigeration to room temperature storage conditions (25��C/77��F),
use Atracurium Besylate Injection within 14 days even if
rerefrigerated.
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dailymed-instance:clinicalP... |
Atracurium besylate
is a nondepolarizing skeletal muscle relaxant. Nondepolarizing agents
antagonize the neurotransmitter action of acetylcholine by binding
competitively with cholinergic receptor sites on the motor end-plate.
This antagonism is inhibited, and neuromuscular block reversed, by
acetylcholinesterase inhibitors such as neostigmine, edrophonium and
pyridostigmine. Atracurium can be
used most advantageously if muscle twitch response to peripheral nerve
stimulation is monitored to assess degree of muscle relaxation. The duration of
neuromuscular block produced by atracurium is approximately one-third to
one-half the duration of block by d-tubocurarine, metocurine, and
pancuronium at initially equipotent doses. As with other nondepolarizing
neuromuscular blockers, the time to onset of paralysis decreases and the
duration of maximum effect increases with increasing atracurium doses. The ED(dose required to produce 95% suppression of the muscle twitch
response with balanced anesthesia) has averaged 0.23 mg/kg (0.11 to 0.26
mg/kg in various studies). An initial atracurium besylate dose of 0.4 to
0.5 mg/kg generally produces maximum neuromuscular block within 3 to 5
minutes of injection, with good or excellent intubation conditions
within 2 to 2.5 minutes in most patients. Recovery from neuromuscular
block (under balanced anesthesia) can be expected to begin approximately
20 to 35 minutes after injection. Under balanced anesthesia, recovery to
25% of control is achieved approximately 35 to 45 minutes after
injection, and recovery is usually 95% complete approximately 60 to 70
minutes after injection. The neuromuscular blocking action of atracurium
is enhanced in the presence of potent inhalation anesthetics. Isoflurane
and enflurane increase the potency of atracurium and prolong
neuromuscular block by approximately 35%; however, halothane's
potentiating effect (approximately 20%) is marginal (see DOSAGE AND
ADMINISTRATION). Repeated
administration of maintenance doses of atracurium has no cumulative
effect on the duration of neuromuscular block if recovery is allowed to
begin prior to repeat dosing. Moreover, the time needed to recover from
repeat doses does not change with additional doses. Repeat doses can
therefore be administered at relatively regular intervals with
predictable results. After an initial dose of 0.4 to 0.5 mg/kg under
balanced anesthesia, the first maintenance dose (suggested maintenance
dose is 0.08 to 0.10 mg/kg) is generally required within 20 to 45
minutes, and subsequent maintenance doses are usually required at
approximately 15 to 25 minute intervals. Once recovery from
atracurium's neuromuscular blocking effects begins, it proceeds more
rapidly than recovery from d-tubocurarine, metocurine, and pancuronium.
Regardless of atracurium dose, the time from start of recovery (from
complete block) to complete (95%) recovery is approximately 30 minutes
under balanced anesthesia, and approximately 40 minutes under halothane,
enflurane or isoflurane. Repeateddoses have no cumulative effect on
recovery rate. Reversal of
neuromuscular block produced by atracurium can be achieved with an
anticholinesterase agent such as neostigmine, edrophonium, or
pyridostigmine, in conjunction with an anti-cholinergic agent such as
atropine or glycopyrrolate. Under balanced anesthesia, reversal can
usually be attempted approximately 20 to 35 minutes after an initial
atracurium besylate dose of 0.4 to 0.5 mg/kg,or approximately 10 to 30
minutes after a 0.08 to 0.10 mg/kg maintenance dose, when recovery of
muscle twitch has started. Complete reversal is usually attained within
8 to 10 minutes of the administration of reversing agents. Rare
instances of breathing difficulties, possibly related to incompletereversal, have been reported following attempted pharmacologic
antagonism of atracurium-induced neuromuscular block. As with other
agents in this class, the tendency for residual neuromuscular block is
increasedif reversal is attempted at deep levels of block or if
inadequate doses of reversal agents are employed. The
pharmacokinetics of atracurium in man are essentially linear within the
0.3 to 0.6 mg/kg dose range. The elimination half-life is approximately
20 minutes. THE DURATION OF NEUROMUSCULAR BLOCK PRODUCED BY ATRACURIUM
BESYLATE DOES NOT CORRELATE WITH PLASMA PSEUDOCHOLINESTERASE LEVELS AND
IS NOT ALTERED BY THE ABSENCE OF RENAL FUNCTION.This is consistent with
the results of in vitro studies
which have shown that atracurium is inactivated in plasma via two
nonoxidative pathways: ester hydrolysis, catalyzed by nonspecific
esterases; and Hofmann elimination, a nonenzymatic chemical process
which occurs at physiological pH. Some placental transfer occurs in
humans. Radiolabel studies
demonstrated that atracurium undergoes extensive degradation in cats,
and that neither kidney nor liver plays a major role in its elimination. Biliary and urinary excretion were the major routes of excretion of
radioactivity (totaling>90% of the labeled dose within 7 hours
of dosing), of which atracurium represented only a minor fraction. The
metabolites in bile and urine were similar, including products of
Hofmann elimination and ester hydrolysis. Elderly patients
may have slightly altered pharmacokinetic parameters compared to younger
patients, with a slightly decreased total plasma clearance which is
offset by a corresponding increase in volume of distribution. The net
effect is that there has been no significant difference in clinical
duration and recovery from neuromuscular block observed between elderly
and younger patients receiving atracurium besylate. Atracurium is a
less potent histamine releaser than d-tubocurarine or metocurine.
Histamine release is minimal with initial atracurium besylate doses up
to 0.5 mg/kg, and hemodynamic changes are minimal within the recommended
dose range. A moderate histamine release and significant falls in blood
pressure have been seen following 0.6 mg/kg of atracurium besylate. The
histamine and hemodynamic responses were poorly correlated. The effects
were generally short-lived and manageable, but the possibility of
substantial histamine release in sensitive individuals or in patients in
whom substantial histamine release would be especially hazardous (e.g.,
patients with significant cardiovascular disease) must be considered. It is not known
whether the prior use of other nondepolarizing neuromuscular blocking
agents has any effect on the activity of atracurium. The prior use of
succinylcholine decreases by approximately 2 to 3 minutes the time to
maximum block induced by atracurium, and may increase the depth of
block. Atracurium should be administered only after a patient recovers
from succinylcholine-induced neuromuscular block.
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Atracurium besylate
is contraindicated in patients known to have a hypersensitivity to
it.
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dailymed-instance:supply |
Atracurium Besylate
Injection, 10mg/mL atracurium besylate in each mL. 5 mL SingleDose Vial (50 mg per vial) -
Packaged in 10s (NDC 10019-002-05) 10 mL Multiple Dose Vial (100 mg per vial).
Contains benzyl alcohol . Packaged in 10s (NDC 10019-001-10).<br/>Storage: Atracurium
Besylate Injection should be refrigerated at 2��to 8��C (36��to
46��F) to preserve potency. DO NOT FREEZE. Upon removal from
refrigeration to room temperature storage conditions
(25��C/77��F), use Atracurium Besylate Injection within 14 days
even if rerefrigerated. Manufactured for Baxter Healthcare
Corporation Deerfield,
IL 60015 USA By: MOVA
PHARMACEUTICAL CORPORATION Caguas, PR
00725 USA For Product
Inquiry 1 800 ANA DRUG (1-800-262-3784) Revised:
November 2001 MLT-01634/1.0
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dailymed-instance:precautio... |
General: Although
atracurium is a less potent histamine releaser than
d-tubocurarine or metocurine, the possibility of substantial
histamine release in sensitive individuals must be considered.
Special caution should be exercised in administering atracurium
to patients in whom substantial histamine release would be
especially hazardous (e.g., patients with clinically significant
cardiovascular disease) and in patients with any history (e.g.,
severe anaphylactoid reactions or asthma) suggesting a greater
risk of histamine release. In these patients, the recommended
initial atracurium besylate dose is lower (0.3 to 0.4 mg/kg)
than for other patients and should be administered slowly or in
divided doses over one minute. Since
atracurium has no clinically significant effects on heart rate
in the recommended dosage range, it will not counteract the
bradycardia produced by many anesthetic agents or vagal
stimulation. As a result, bradycardia during anesthesia may be
more common with atracurium than with other muscle relaxants. Atracurium
may have profound effects in patients with myasthenia gravis,
Eaton-Lambert syndrome, or other neuromuscular diseases in which
potentiation of nondepolarizing agents has been noted. The use
of a peripheral nerve stimulator is especially important for
assessing neuromuscular block in these patients. Similar
precautions should be taken in patients with severe electrolyte
disorders or carcinomatosis. Multiple
factors in anesthesia practice are suspected of triggering
malignant hyperthermia (MH), a potentially fatal hypermetabolic
state of skeletal muscle. Halogenated anesthetic agents and
succinylcholine are recognized as the principal pharmacologic
triggering agents in MH-susceptible patients; however, since MH
can develop in the absence of established triggering agents, the
clinician should be prepared to recognize and treat MH in any
patient scheduled for general anesthesia. Reports of MH have
been rare in cases in which atracurium has been used. In studies
of MH-susceptible animals (swine) and in a clinical study of MH-susceptible patients, atracurium did not trigger this
syndrome. Resistance
to nondepolarizing neuromuscular blocking agents may develop in
burn patients. Increased doses of nondepolarizing muscle
relaxants may be required in burn patients and are dependent on
the time elapsed since the burn injury and the size of the burn. The safety
of atracurium has not been established in patients with
bronchial asthma.<br/>Long-Term Use in
Intensive Care Unit (ICU): When there
is a need for long-term mechanical ventilation, the
benefits-to-risk ratio of neuromuscular block must be
considered. The long-term (1 to 10 days) infusion of atracurium
besylate during mechanical ventilation in the ICU has been
evaluated in several studies. Average infusion rates of 11 to 13
mcg/kg/min (range: 4.5 to 29.5) were required to achieve
adequate neuromuscular block. These data suggest that there is
wide interpatient variability in dosage requirements. In
addition, these studies have shown that dosage requirements may
decrease or increase with time. Following discontinuation of
infusion of atracurium in these ICU studies, spontaneous
recovery of four twitches in a train-of-four occurred in an
average of approximately 30 minutes (range: 15 to 75 min) and
spontaneous recovery to a train-of-four ratio>75% (the
ratio of the height of the fourth to the first twitch in a
train-of-four) occurred in an average of approximately 60
minutes (range: 32 to 108 min). Little
information is available on the plasma levels or clinical
consequences of atracurium metabolites that may accumulate
during days to weeks of atracurium administration in ICU
patients. Laudanosine, a major biologically active metabolite of
atracurium without neuromuscular blocking activity, produces
transient hypotension and, in higher doses, cerebral excitatory
effects (generalized muscle twitching and seizures) when
administered to several species of animals. There have been rare
spontaneous reports of seizures in ICU patients who have
received atracurium or other agents. These patients usually had
predisposing causes (such as head trauma, cerebral edema,
hypoxic encephalopathy, viral encephalitis, uremia). There are
insufficient data to determine whether or not laudanosine
contributes to seizures in ICU patients. WHENEVER
THE USE OF ATRACURIUM OR ANY NEUROMUSCULAR BLOCKING AGENT IS
CONTEMPLATED IN THE ICU, IT IS RECOMMENDED THAT NEUROMUSCULAR
TRANSMISSION BE MONITORED CONTINUOUSLY DURING ADMINISTRATION
WITH THE HELP OF A NERVE STIMULATOR. ADDITIONAL DOSES OF
ATRACURIUM OR ANY OTHER NEUROMUSCULAR BLOCKING AGENT SHOULD NOT
BE GIVEN BEFORE THERE IS A DEFINITE RESPONSE TO TOR TO THE FIRST TWITCH. IF NO RESPONSE IS ELICITED, INFUSION
ADMINISTRATION SHOULD BE DISCONTINUED UNTIL A RESPONSE RETURNS. Hemofiltration has a minimal effect on plasma levels of
atracurium and its metabolites, including laudanosine. The
effects of hemodialysis and hemoperfusion on plasma levels of
atracurium and its metabolites are unknown.<br/>Drug Interactions: Drugs which
may enhance the neuromuscular blocking action of atracurium
include: enflurane; isoflurane; halothane; certain antibiotics,
especially the aminoglycosides and polymyxins; lithium;
magnesium salts; procainamide; and quinidine. If other
muscle relaxants are used during the same procedure, the
possibility of a synergistic or antagonist effect should be
considered. The prior
administration of succinylcholine does not enhance the duration, but quickens the onset and may increase the depth, of
neuromuscular block induced by atracurium. Atracurium should not
be administered until a patient has recovered from succinylcholine-induced neuromuscular block.<br/>Carcinogenesis and
Mutagenesis and Impairment of Fertility: Carcinogenesis and fertility studies have not been performed.
Atracurium besylate was evaluated in a battery of three
short-term mutagenicity tests. It was non-mutagenic in both the
Ames Salmonella assay at concentrations up to 1000 mcg/plate,
and in a rat bone marrow cytogenicity assay at up to paralyzing
doses. A positive response was observed in the mouse lymphoma
assay under conditions (80 and 100 mcg/mL, in the absence of
metabolic activation) which killed over 80% of the treated
cells; there was no mutagenicity at 60 mcg/mL and lower,
concentrations which killed up to half of the treated cells. A
far weaker response was observed in the presence of metabolic activation at concentrations (1,200 mcg/mL and higher) which
also killed over 80% of the treated cells. Mutagenicity testing is intended to simulate chronic (years to
lifetime) exposure in an effort to determine potential
carcinogenicity. Thus, a single positive mutagenicity response
for a drug used infrequently and/or briefly is of questionable
clinical relevance.<br/>Pregnancy:<br/>Teratogenic
Effects:<br/>Labor and Delivery: It is not
known whether muscle relaxants administered during vaginal
delivery have immediate or delayed adverse effects on the fetus
or increase the likelihood that resuscitation of the newborn
will be necessary. The possibility that forceps delivery will be
necessary may increase. Atracurium
besylate (0.3 mg/kg) has been administered to 26 pregnant women
during delivery by cesarean section. No harmful effects were
attributable to atracurium in any of the newborn infants, although small amounts of atracurium were shown to cross the
placental barrier. The possibility of respiratory depression in
the newborn infant should always be considered following
cesarean section during which a neuromuscular blocking agent has
been administered. In patients receiving magnesium sulfate, the
reversal of neuromuscular block may be unsatisfactory and
atracurium besylate dose should be lowered as
indicated.<br/>Nursing Mothers: It is not
known whether this drug is excreted in human milk. Because many
drugs are excreted in human milk, caution should be exercised
when atracurium besylate is administered to a nursing
woman.<br/>Pediatric Use: Safety and effectiveness in pediatric patients below the age of 1 month
have not been established.<br/>Use in the Elderly: Since
marketing in 1983, uncontrolled clinical experience and limited
data from controlled trials have not identified differences in
effectiveness, safety, or dosage requirements between healthy
elderly and younger patients ; however, as with other neuromuscular blocking
agents, the use of a peripheral nerve stimulator to monitor
neuromuscular function is suggested (see DOSAGE
AND ADMINISTRATION).
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dailymed-instance:overdosag... |
There has been
limited experience with atracurium besylate overdosage. The possibility
of iatrogenic overdosage can be minimized by carefully monitoring muscle
twitch response to peripheral nerve stimulation. Excessive doses of
atracurium can be expected to produce enhanced pharmacological effects.
Overdosage may increase the risk of histamine release and cardiovascular
effects, especially hypotension. If cardiovascular support is necessary,
this should include proper positioning, fluid administration, and the
use of vasopressor agents if necessary. The patient's airway should be
assured, with manual or mechanical ventilation maintained as necessary.
A longer duration of neuromuscular block may result from overdosage and
a peripheral nerve stimulator should be used to monitor recovery.
Recovery may be facilitated by administration of an anticholinesterase
reversing agent such as neostigmine, edrophonium, or pyridostigmine, in
conjunction with an anticholinergic agent such as atropine or
glycopyrrolate. The appropriate package inserts should be consulted for
prescribing information. Three pediatric
patients (3 weeks, 4 and 5 months of age) unintentionally received doses
of 0.8 mg/kg to 1 mg/kg of atracurium besylate. The time to 25% recovery
(50 to 55 minutes) following these doses, which were 5 to 6 times the
EDdose, was moderately longer than the corresponding
time observed following doses 2.0 to 2.5 times the atracurium
EDdose in infants (22 to 36 minutes). Cardiovascular
changes were minimal. Nonetheless the possibility of cardiovascular
changes must be considered in the case of overdose. An adult patient
(17 years of age) unintentionally received an initial dose of 1.3 mg/kg of atracurium besylate. The time from injection to 25% recovery (83
minutes) was approximately twice that observed following maximum
recommended doses in adults (35-45 minutes). The patient experienced
moderate hemodynamic changes (13% increase in mean arterial pressure and
27% increase in heart rate)which persisted for 40 minutes and did not
require treatment. The intravenous
LD's determined in nonventilated male and female albino
mice and male Wistar rats were 1.9, 2.01 and 1.31 mg/kg, respectively.
Deaths occurred within 2 minutes and were caused by respiratory
paralysis. The subcutaneous LDdetermined in non-ventilated
male Wistar rats was 282.8 mg/kg. Tremors, ptosis, loss of reflexes and respiratory failure preceded death which occurred 45 to 120 minutes
after injection.
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dailymed-instance:genericMe... |
Atracurium Besylate
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dailymed-instance:fullName |
Atracurium Besylate (Injection, Solution)
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dailymed-instance:adverseRe... |
Observed in
Controlled Clinical Studies: Atracurium
was well tolerated and produced few adverse reactions during
extensive clinical trials. Most adverse reactions were
suggestive of histamine release. In studies including 875
patients, atracurium was discontinued in only one patient (who
required treatment for bronchial secretions), and six other
patients required treatment for adverse reactions attributable
to atracurium (wheezing in one, hypotension in five). Of the five patients who required treatment for hypotension, three had
a history of significant cardiovascular disease. The overall
incidence rate for clinically important adverse reactions,
therefore, was 7/875 or 0.8%. The table below includes all
adverse reactions reported attributable to atracurium during
clinical trials with 875 patients. Most
adverse reactions were of little clinical significance unless they were associated with significant hemodynamic changes. The
table below summarizes the incidences of substantial vital sign
changes noted during atracurium clinical trials with 530
patients, without cardiovascular disease, in whom these
parameters were assessed.<br/>Observed in
Clinical Practice: Based on
initial clinical practice experience in approximately 3 million
patients who received atracurium in the U.S. and in the United
Kingdom, spontaneously reported adverse reactions were uncommon
(approximately 0.01-0.02%). The following adverse reactions are
among the most frequently reported, but there are insufficient
data to support an estimate of their incidence:<br/>General: Allergic reactions (anaphylactic or anaphylactoid
responses) which, in rare instances, were severe (e.g.,
cardiac arrest)<br/>Musculoskeletal: Inadequate block, prolonged block<br/>Cardiovascular: Hypotension, vasodilatation (flushing), tachycardia,
bradycardia<br/>Respiratory: Dyspnea, bronchospasm, laryngospasm<br/>Integumentary: Rash, urticaria, reaction at injection site There have been rare spontaneous reports of seizures in
ICU patients following long-term infusion of atracurium
to support mechanical ventilation. There are
insufficient data to define the contribution, if any, of
atracurium and/or its metabolite laudanosine. (SeePRECAUTIONS, Long-Term Use in Intensive Care
Unit [ICU]).
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ATRACURIUM SHOULD
BE USED ONLY BY THOSE SKILLED IN AIRWAY MANAGEMENT AND RESPIRATORY
SUPPORT. EQUIPMENT AND PERSONNEL MUST BE IMMEDIATELY AVAILABLE FOR
ENDOTRACHEAL INTUBATION AND SUPPORT OF VENTILATION, INCLUDING
ADMINISTRATION OF POSITIVE PRESSURE OXYGEN. ADEQUACY OF RESPIRATION MUST
BE ASSURED THROUGH ASSISTED OR CONTROLLED VENTILATION.
ANTICHOLINESTERASE REVERSAL AGENTS SHOULD BE IMMEDIATELY AVAILABLE. DO NOT GIVE
ATRACURIUM BESYLATE BY INTRAMUSCULAR ADMINISTRATION. Atracurium besylate has no known effect on consciousness, pain threshold, or cerebration. It
should be used only with adequate anesthesia. Atracurium Besylate
Injection, which has an acid pH, should not be mixed with alkaline
solutions (e.g., barbiturate solutions) in the same syringe or administered simultaneously during intravenous infusion through the same
needle. Depending on the resultant pH of such mixtures, atracurium may
be inactivated and a free acid may be precipitated. Atracurium Besylate
Injection 10 mL multiple dose vials contain benzyl alcohol. Benzyl
alcohol has been associated with an increased incidence of neurological
and other complications in newborn infants which are sometimes fatal.
Atracurium Besylate Injection 5 mL single dose vials do not contain
benzyl alcohol.
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dailymed-instance:indicatio... |
Atracurium Besylate
Injection is indicated, as an adjunct to general anesthesia, to
facilitate endotracheal intubation and to provide skeletal muscle
relaxation during surgery or mechanical ventilation.
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dailymed-instance:name |
Atracurium Besylate
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