Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/932
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NIMBEX (Injection)
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| dailymed-instance:dosage |
NIMBEX SHOULD ONLY BE ADMINISTERED
INTRAVENOUSLY. The
dosage information provided below is intended as a guide only. Doses of NIMBEX
should be individualized (see CLINICAL PHARMACOLOGY - Individualization of
Dosages). The use of a peripheral nerve stimulator will permit the most advantageous
use of NIMBEX, minimize the possibility of overdosage or underdosage, and
assist in the evaluation of recovery.<br/>Adults:<br/>Initial Doses: One of two intubating doses of NIMBEX may be chosen,
based on the desired time to tracheal intubation and the anticipated length
of surgery. In addition to the dose of neuromuscular blocking agent, the
presence of co-induction agents (e.g., fentanyl and midazolam) and the depth
of anesthesia are factors that can influence intubation conditions. Doses
of 0.15 (3��ED) and 0.20 (4��ED) mg/kg
NIMBEX, as components of a propofol/nitrous oxide/oxygen induction-intubation
technique, may produce generally GOOD or EXCELLENT conditions for intubation
in 2.0 and 1.5 minutes, respectively. Similar intubation conditions
may be expected when these doses of NIMBEX are administered as components
of a thiopental/nitrous oxide/oxygen induction-intubation technique. In two
intubation studies using thiopental or propofol and midazolam and fentanyl
as co-induction agents, EXCELLENT intubation conditions were most frequently
achieved with the 0.2 mg/kg compared to 0.15 mg/kg dose of cisatracurium.
The clinically effective durations of action for 0.15 and 0.20 mg/kg NIMBEX
during propofol anesthesia are 55 minutes (range: 44 to 74 minutes) and 61 minutes
(range: 41 to 81 minutes), respectively. Lower doses may result in a longer
time for the development of satisfactory intubation conditions. Doses up
to8��EDNIMBEX have been safely administered to healthy
adult patients and patients with serious cardiovascular disease. These larger
doses are associated with longer clinically effective durations of action
(see CLINICAL PHARMACOLOGY). Because slower times to onset of complete neuromuscular
block were observed in elderly patients and patients with renal dysfunction,
extending the interval between administration of NIMBEX and the intubation
attempt for these patients may be required to achieve adequate intubation
conditions. A dose of 0.03 mg/kg NIMBEX is
recommended for maintenance of neuromuscular block during prolonged surgical
procedures. Maintenance doses of 0.03 mg/kg each sustain neuromuscular block
for approximately 20 minutes. Maintenance dosing is generally required 40
to 50 minutes following an initial dose of 0.15 mg/kg NIMBEX and 50 to 60
minutes following an initial dose of 0.20 mg/kg NIMBEX, but the need for maintenance
doses should be determined by clinical criteria. For shorter or longer durations
of action, smaller or larger maintenance doses may be administered. Isoflurane or enflurane administered with nitrous oxide/oxygen
to achieve 1.25 MAC (Minimum Alveolar Concentration) may prolong the clinically
effective duration of action of initial and maintenance doses. The magnitude
of these effects may depend on the duration of administration of the volatile
agents. Fifteen to 30 minutes of exposure to 1.25MAC isoflurane or enflurane
had minimal effects on the duration of action of initial doses of NIMBEX and
therefore, no adjustment to the initial dose should be necessary when NIMBEX
is administered shortly after initiation of volatile agents. In long surgical
procedures during enflurane or isoflurane anesthesia, less frequent maintenance
dosing or lower maintenance doses of NIMBEX may be necessary. No adjustments
to the initial dose of NIMBEX are required when used in patients receiving
propofol anesthesia.<br/>Children:<br/>Initial Doses: The recommended dose of NIMBEX for children 2
to 12 years of age is 0.10-0.15 mg/kg administered over 5 to 10 seconds during
either halothane or opioid anesthesia. When administered during stable opioid/nitrous
oxide/oxygen anesthesia, 0.10 mg/kg NIMBEX produces maximum neuromuscular
block in an average of 2.8 minutes (range: 1.8 to 6.7 minutes) and clinically
effective block for 28 minutes (range: 21 to 38 minutes). When administered
during stable opioid/nitrous oxide/oxygen anesthesia, 0.15 mg/kg NIMBEX produces
maximum neuromuscular block in about 3.0 minutes (range: 1.5 to 8.0
minutes) and clinically effective block (time to 25% recovery) for 36 minutes
(range: 29 to 46 minutes).<br/>Infants:<br/>Initial Doses: The recommended dose of NIMBEX for intubation
of infants 1 month to 23 months is 0.15 mg/kg administered over 5 to
10 seconds during either halothane or opioid anesthesia. When administered
during stable opioid/nitrous oxide/oxygen anesthesia, 0.15 mg/kg NIMBEX produces
maximum neuromuscular block in about 2.0 minutes (range: 1.3 to 3.4
minutes) and clinically effective block (time to 25% recovery) for about 43
minutes (range: 34 to 58 minutes).<br/>Use by Continuous Infusion:<br/>Infusion in the Operating Room (OR): After administration of an initial bolus dose
of NIMBEX, a diluted solution of NIMBEX 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 NIMBEX 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 NIMBEX should be initiated only after early
evidence of spontaneous recovery from the initial bolus dose. An initial
infusion rate of 3 mcg/kg/min may be required to rapidly counteract the spontaneous
recovery of neuromuscular function. Thereafter, a rate of 1 to 2 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 opioid/nitrous oxide/oxygen
anesthesia. Reduction of the infusion rate
by up to 30% to 40% should be considered when NIMBEX is administered during
stable isoflurane or enflurane anesthesia (administered with nitrous oxide/oxygen
at the 1.25 MAC level). Greater reductions in the infusion rate of NIMBEX
may be required with longer durations of administration of isoflurane or enflurane. The rate of infusion of atracurium required to maintain
adequate surgical relaxation in patients undergoing coronary artery bypass
surgery with induced hypothermia (25��to 28��C) is approximately
half the rate required during normothermia. Based on the structural similarity
between NIMBEX and atracurium, a similar effect on the infusion rate of NIMBEX
may be expected. Spontaneous recovery from
neuromuscular block following discontinuation of infusion of NIMBEX 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 NIMBEX in the OR
are also applicable to use in the ICU. An infusion rate of approximately
3 mcg/kg/min (range: 0.5 to 10.2 mcg/kg/min) should provide adequate
neuromuscular block in adult patients in the ICU. There may be wide interpatient
variability in dosage requirements and these may increase or decrease with
time (see PRECAUTIONS - Long-Term Use in the Intensive
Care Unit [ICU]). 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 NIMBEX in the infusion solution, the
desired dose of NIMBEX, and the patient's weight. The contribution of
the infusion solution to the fluid requirements of the patient also must be
considered. Tables 10 and 11 provide guidelines for delivery, in mL/hr (equivalent
to microdrops/minute when 60 microdrops = 1 mL), of NIMBEX solutions in concentrations
of 0.1 mg/mL (10 mg/100 mL) or 0.4 mg/mL (40 mg/100 mL).<br/>NIMBEX Injection Compatibility and Admixtures:<br/>Y-site Administration: NIMBEX Injection is acidic (pH = 3.25 to 3.65)
and may not be compatible with alkaline solution having a pH greater than
8.5 (e.g., barbiturate solutions). Studies
have shown that NIMBEX Injection is compatible with: NIMBEX Injection is not compatible with DIPRIVAN (propofol)
Injection or TORADOL (ketorolac) Injection for Y-site administration.
Studies of other parenteral products have not been conducted.<br/>Dilution Stability: NIMBEX Injection diluted in 5% Dextrose Injection,
USP; 0.9% Sodium Chloride Injection, USP; or 5% Dextrose and 0.9% Sodium Chloride
Injection, USP to 0.1 mg/mL may be stored either under refrigeration or at
room temperature for 24 hours without significant loss of potency. Dilutions
to 0.1 mg/mL or 0.2 mg/mL in 5% Dextrose and Lactated Ringer's Injection
may be stored under refrigeration for 24 hours. NIMBEX
Injection should not be diluted in Lactated Ringer's Injection, USP due
to chemical instability. NOTE: Parenteral drug products should be inspected visually for particulate
matter and discoloration prior to administration whenever solution and container
permit. Solutions which are not clear, or contain visible particulates, should
not be used. NIMBEX Injection is a colorless to slightly yellow or greenish-yellow
solution.
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| dailymed-instance:descripti... |
NIMBEX (cisatracurium besylate) is a nondepolarizing
skeletal muscle relaxant for intravenous administration. Compared to other
neuromuscular blocking agents, it is intermediate in its onset and duration
of action. Cisatracurium besylate is one of 10 isomers of atracurium
besylate and constitutes approximately 15% of that mixture. Cisatracurium
besylate is [1R-[1��,2��(1'R*,2'R*)]]-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. The molecular formula of the cisatracurium parent bis-cation
is CHNOand the molecular
weight is 929.2. The molecular formula of cisatracurium as the besylate salt
is CHNOSand
the molecular weight is 1243.50. The structural formula of cisatracurium
besylate is: The log of the partition
coefficient of cisatracurium besylate is -2.12 in a 1-octanol/distilled water
system at 25��C. NIMBEX Injection is a sterile,
non-pyrogenic aqueous solution provided in 5 mL, 10 mL, and 20 mL vials.
The pH is adjusted to 3.25 to 3.65 with benzenesulfonic acid. The 5 mL
and 10 mL vials each contain cisatracurium besylate, equivalent to 2 mg/mL
cisatracurium. The 20 mL vial, intended for ICU
use only, contains cisatracurium besylate, equivalent to 10 mg/mL
cisatracurium. The 10 mL vial, intended for multiple-dose use, contains 0.9%
benzyl alcohol as a preservative. The 5 mL and 20 mL vials are single-use
vials and do not contain benzyl alcohol. Cisatracurium
besylate slowly loses potency with time at a rate of approximately 5% per
year under refrigeration (5��C). NIMBEX should be refrigerated at 2��to 8��C (36��to 46��F) in the carton to preserve potency. The
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 NIMBEX within
21 days, even if rerefrigerated.
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| dailymed-instance:clinicalP... |
NIMBEX binds competitively to cholinergic receptors
on the motor end-plate to antagonize the action of acetylcholine, resulting
in block of neuromuscular transmission. This action is antagonized by acetylcholinesterase
inhibitors such as neostigmine.<br/>Pharmacodynamics: The neuromuscular blocking potency of NIMBEX is
approximately threefold that of atracurium besylate. The time to maximum
block is up to 2 minutes longer for equipotent doses of NIMBEX compared to
atracurium besylate. The clinically effective duration of action and rate
of spontaneous recovery from equipotent doses of NIMBEX and atracurium besylate
are similar. The average ED(dose
required to produce 95% suppression of the adductor pollicis muscle twitch
response to ulnar nerve stimulation) of cisatracurium is 0.05 mg/kg (range: 0.048
to 0.053) in adults receiving opioid/nitrous oxide/oxygen anesthesia. For
comparison, the average EDfor atracurium when also expressed
as the parent bis-cation is 0.17 mg/kg under similar anesthetic conditions. The pharmacodynamics of 2��EDto 8��EDdoses of cisatracurium administered over 5 to 10 seconds during
opioid/nitrous oxide/oxygen anesthesia are summarized in Table 1. When
the dose is doubled, the clinically effective duration of block increases
by approximately 25 minutes. Once recovery begins, the rate of recovery is
independent of dose. Isoflurane or enflurane
administered with nitrous oxide/oxygen to achieve 1.25 MAC [Minimum Alveolar
Concentration] may prolong the clinically effective duration of action of
initial and maintenance doses, and decrease the average infusion rate requirement
of NIMBEX. The magnitude of these effects may depend on the duration of administration
of the volatile agents. Fifteen to 30 minutes of exposure to 1.25 MAC isoflurane
or enflurane had minimal effects on the duration of action of initial doses
of NIMBEX and therefore, no adjustment to the initial dose should be necessary
when NIMBEX is administered shortly after initiation of volatile agents.
In long surgical procedures during enflurane or isoflurane anesthesia, less
frequent maintenance dosing, lower maintenance doses, or reduced infusion
rates of NIMBEX may be necessary. The average infusion rate requirement may
be decreased by as much as 30% to 40%. The
onset, duration of action, and recovery profiles of NIMBEX during propofol/oxygen
or propofol/nitrous oxide/oxygen anesthesia are similar to those during opioid/nitrous
oxide/oxygen anesthesia. When administered during the induction of adequate
anesthesia using propofol, nitrous oxide/oxygen, and co-induction agents (e.g.,
fentanyl and midazolam), GOOD or EXCELLENT conditions for tracheal intubation
occurred in 96/102 (94%) patients in 1.5 to 2.0 minutes following 0.15
mg/kg cisatracurium and in 97/110 (88%) patients in 1.5 minutes following
0.2 mg/kg cisatracurium. In one intubation
study during thiopental anesthesia in which fentanyl and midazolam were administered
two minutes prior to induction, intubation conditions were assessed at 120
seconds. Table 2 displays these results in this study of 51 patients. While GOOD or EXCELLENT intubation conditions
were achieved in the majority of patients in this setting, EXCELLENT intubation
conditions were more frequently achieved with the 0.2 mg/kg dose (60%) than
the 0.15 mg/kg dose (31%) when intubation was attempted 2.0 minutes following
cisatracurium. A second study evaluated intubation
conditions after 3 and 4��ED(0.15 mg/kg and 0.20 mg/kg)
following induction with fentanyl and midazolam and either thiopental or propofol
anesthesia. This study compared intubation conditions produced by these doses
of cisatracurium after 1.5 minutes. Table 3 displays these results. EXCELLENT intubation conditions were more frequently
observed with the 0.2 mg/kg dose when intubation was attempted 1.5 minutes
following cisatracurium. A third study in pediatric
patients (ages 1 month to 12 years) evaluated intubation conditions at 120
seconds after 0.15 mg/kg NIMBEX following induction with either halothane
(with halothane/nitrous oxide/oxygen maintenance) or thiopentone and fentanyl
(with thiopentone/fentanyl nitrous oxide/oxygen maintenance). The results
are summarized in Table 4. EXCELLENT or GOOD intubating conditions were produced
120 seconds following 0.15 mg/kg NIMBEX in 88/90 (98%) of patients induced
with halothane and in 85/90 (94%) of patients induced with thiopentone
and fentanyl. There were no patients for whom intubation was not possible,
but there were 7/120 patients ages 1-12 years for whom intubating conditions
were described as poor. Repeated administration
of maintenance doses or a continuous infusion of NIMBEX for up to 3 hours
is not associated with development of tachyphylaxis or cumulative neuromuscular
blocking effects. The time needed to recover from successive maintenance
doses does not change with the number of doses administered as long as partial
recovery is allowed to occur between doses. Maintenance doses can therefore
be administered at relatively regular intervals with predictable results.
The rate of spontaneous recovery of neuromuscular function after infusion
is independent of the duration of infusion and comparable to the rate of recovery
following initial doses (Table 1). Long-term
infusion (up to 6 days) of NIMBEX during mechanical ventilation in the ICU
has been evaluated in two studies. In a randomized, double-blind study using
presence of a single twitch during train-of-four (TOF) monitoring to regulate
dosage, patients treated with NIMBEX (n = 19) recovered neuromuscular function
(T:Tratio���70%) following termination
of infusion in approximately 55 minutes (range: 20 to 270) whereas those
treated with vecuronium (n = 12) recovered in 178 minutes (range: 40 minutes
to 33 hours). In another study comparing NIMBEX and atracurium, patients
recovered neuromuscular function in approximately 50 minutes for both NIMBEX
(range: 20 to 175; n = 34) and atracurium (range: 35 to 85; n = 15). The neuromuscular block produced by NIMBEX is readily antagonized
by anticholinesterase agents once recovery has started. As with other nondepolarizing
neuromuscular blocking agents, the more profound the neuromuscular block at
the time of reversal, the longer the time required for recovery of neuromuscular
function. In children (2 to 12 years) cisatracurium
has a lower EDthan in adults (0.04 mg/kg, halothane/nitrous
oxide/oxygen anesthesia). At 0.1 mg/kg during opioid anesthesia, cisatracurium
had a faster onset and shorter duration of action in children than in adults
(Table 1). Recovery following reversal is faster in children than in adults. At 0.15 mg/kg during opioid anesthesia, cisatracurium had
a faster onset and longer clinically effective duration of action in infants
aged 1-23 months compared to children aged 2-12 years (Table 1). Studies were conducted during both opioid-based and halothane-based
anesthesia in children aged 1-11 months, 1-4 years, and 5-12 years. Cisatracurium
had a faster onset and longer duration of action in infants 1-11 months compared
to children 1-4 years, who in turn have a faster onset and longer duration
of action for cisatracurium compared to children 5-12 years. The mean time to onset of maximum Tsuppression
was generally faster for pediatric patients induced with halothane compared
to thiopentone/fentanyl and the clinically effective duration (time to 25%
recovery) was longer (by up to 15%) for pediatric patients under halothane
anesthesia.<br/>Hemodynamics Profile: The cardiovascular profile of NIMBEX allows it to
be administered by rapid bolus at higher multiples of the EDthan
atracurium. NIMBEX has no dose-related effects on mean arterial blood pressure
(MAP) or heart rate (HR) following doses ranging from 2 to 8��ED(>0.1 to>0.4 mg/kg), administered over 5 to 10 seconds, in healthy adult patients
(Figure 1) or in patients with serious cardiovascular disease (Figure 2). A total of 141 patients undergoing coronary artery bypass
grafting (CABG) have been administered NIMBEX in three active controlled clinical
trials and have received doses ranging from 2 to 8��ED.
While the hemodynamic profile was comparable in both the NIMBEX and active
control groups, data for doses above 0.3 mg/kg in this population are limited. Unlike atracurium, NIMBEX, at therapeutic doses of 2��EDto 8��ED(0.1 to 0.4 mg/kg), administered
over 5 to 10 seconds, does not cause dose-related elevations in mean plasma
histamine concentration. No clinically
significant changes in MAP or HR were observed following administration of
doses up to 0.1 mg/kg NIMBEX over 5 to 10 seconds in 2- to 12-year-old children
receiving either halothane/nitrous oxide/oxygen or opioid/nitrous oxide/oxygen
anesthesia. Doses of 0.15 mg/kg NIMBEX administered over 5 seconds were not
consistently associated with changes in HR and MAP in pediatric patients aged
1 month to 12 years receiving opioid/nitrous oxide/oxygen or halothane/nitrous
oxide/oxygen anesthesia. 1-11 Months 1-5 Years 5-13 Years 1-11 Months 1-5 Years 5-13 Years<br/>Pharmacokinetics:<br/>General: The neuromuscular blocking activity of NIMBEX
is due to parent drug. Cisatracurium plasma concentration-time data following
IV bolus administration are best described by a two-compartment open model
(with elimination from both compartments) with an elimination half-life (t��)
of 22 minutes, a plasma clearance (CL) of 4.57 mL/min/kg, and a volume of
distribution at steady state (V) of 145 mL/kg. Cisatracurium
undergoes organ-independent Hofmann elimination (a chemical process dependent
on pH and temperature) to form the monoquaternary acrylate metabolite and
laudanosine, neither of which has any neuromuscular blocking activity (see Pharmacokinetics - Metabolism section). Following
administration of radiolabeled cisatracurium, 95% of the dose was recovered
in the urine; less than 10% of the dose was excreted as unchanged parent drug.
Laudanosine, a metabolite of cisatracurium (and atracurium) has been noted
to cause transient hypotension and, in higher doses, cerebral excitatory effects
when administered to several animal species. The relationship between CNS
excitation and laudanosine concentrations in humans has not been established
(see PRECAUTIONS - Long-term Use in the Intensive
Care Unit). Because cisatracurium is three times more potent than
atracurium and lower doses are required, the corresponding laudanosine concentrations
following cisatracurium are one third of those that would be expected following
an equipotent dose of atracurium (see Pharmacokinetics
- Special Populations - Intensive Care
Unit Patients). Results from population
pharmacokinetic/pharmacodynamic (PK/PD) analyses from 241 healthy surgical
patients are summarized in Table 5. The magnitude of interpatient variability in
CL was low (16%), as expected based on the importance of Hofmann elimination
(see Pharmacokinetics - Elimination).
The magnitudes of interpatient variability in CL and volume of distribution
were low in comparison to those for kand EC. This
suggests that any alterations in the time course of cisatracurium-induced
block are more likely to be due to variability in the pharmacodynamic parameters
than in the pharmacokinetic parameters. Parameter estimates from the population
pharmacokinetic analyses were supported by noncompartmental pharmacokinetic
analyses on data from healthy patients and from special patient populations. Conventional pharmacokinetic analyses have shown that
the pharmacokinetics of cisatracurium are proportional to dose between 0.1
(2��ED) and 0.2 (4��ED) mg/kg cisatracurium.
In addition, population pharmacokinetic analyses revealed no statistically
significant effect of initial dose on CL for doses between 0.1 (2��ED)
and 0.4 (8��ED) mg/kg cisatracurium.<br/>Distribution: The volume of distribution of cisatracurium is
limited by its large molecular weight and high polarity. The Vwas
equal to 145 mL/kg (Table 4) in healthy 19- to 64-year-old surgical patients
receiving opioid anesthesia. The Vwas 21% larger in similar
patients receiving inhalation anesthesia (see Pharmacokinetics
- Special Populations - Other Patient
Factors).<br/>Protein Binding: The binding of cisatracurium to plasma proteins
has not been successfully studied due to its rapid degradation at physiologic
pH. Inhibition of degradation requires nonphysiological conditions of temperature
and pH which are associated with changes in protein binding.<br/>Metabolism: The degradation of cisatracurium is largely independent
of liver metabolism. Results from in vitro experiments
suggest that cisatracurium undergoes Hofmann elimination (a pH and temperature-dependent
chemical process) to form laudanosine (see PRECAUTIONS
- Long-term Use in the Intensive Care Unit) and the monoquaternary
acrylate metabolite. The monoquaternary acrylate undergoes hydrolysis by
non-specific plasma esterases to form the monoquaternary alcohol (MQA) metabolite.
The MQA metabolite can also undergo Hofmann elimination but at a much slower
rate than cisatracurium. Laudanosine is further metabolized to desmethyl
metabolites which are conjugated with glucuronic acid and excreted in the
urine. Organ-independent Hofmann elimination
is the predominant pathway for the elimination of cisatracurium. The liver
and kidney play a minor role in the elimination of cisatracurium but are primary
pathways for the elimination of metabolites. Therefore, the t��values of metabolites (including laudanosine) are longer in patients with
kidney or liver dysfunction and metabolite concentrations may be higher after
long-term administration (see PRECAUTIONS - Long-term
Use in the Intensive Care Unit). Most importantly, Cvalues
of laudanosine are significantly lower in healthy surgical patients receiving
infusions of NIMBEX than in patients receiving infusions of atracurium (mean��SD C: 60��52 and 342��93 ng/mL, respectively).<br/>Elimination:<br/>Special Populations:<br/>Individualization of Dosages: DOSES OF NIMBEX SHOULD
BE INDIVIDUALIZED AND A PERIPHERAL NERVE STIMULATOR SHOULD BE USED TO MEASURE
NEUROMUSCULAR FUNCTION DURING ADMINISTRATION OF NIMBEX IN ORDER TO MONITOR DRUG EFFECT, TO DETERMINE THE NEED FOR ADDITIONAL
DOSES, AND TO CONFIRM RECOVERY FROM NEUROMUSCULAR BLOCK. Based on the known action of NIMBEX and other neuromuscular
blocking agents, the following factors should be considered when administering
NIMBEX.<br/>Renal and Hepatic Disease: See PRECAUTIONS section.<br/>Long-Term Use in the Intensive Care Unit (ICU): The long-term infusion (up to 6 days) of NIMBEX
during mechanical ventilation in the ICU has been evaluated in two studies.
Average infusion rates of approximately 3 mcg/kg/min (range: 0.5 to
10.2) were required to achieve adequate neuromuscular block. As with other
neuromuscular blocking agents, these data indicate the presence of wide interpatient
variability in dosage requirements. In addition, dosage requirements may
increase or decrease with time (see PRECAUTIONS). Use of NIMBEX in the ICU for longer than 6 days has not been
studied.<br/>Drugs or Conditions Causing Potentiation of or Resistance to Neuromuscular
Block: Persons with certain pre-existing conditions or
receiving certain drugs may require individualization of dosing (see PRECAUTIONS).<br/>Burns: Patients with burns have been shown to develop
resistance to nondepolarizing neuromuscular blocking agents, and may require
individualization of dosing (see PRECAUTIONS).
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| dailymed-instance:contraind... |
NIMBEX is contraindicated in patients known to have
an allergic hypersensitivity to NIMBEX or other bis-benzylisoquinolinium agents.
Use of NIMBEX from vials containing benzyl alcohol as a preservative is contraindicated
in patients with a known hypersensitivity to benzyl alcohol.
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| dailymed-instance:supply |
NIMBEX Injection, 2 mg cisatracurium per mL, is supplied
in the following: NOTE:10
mL Multiple-dose Vials contain 0.9% w/v benzyl alcohol as a preservative (see WARNINGS concerning newborn infants). NIMBEX Injection, 10 mg cisatracurium per mL is supplied in
the following: Intended only
for use in the ICU.<br/>Storage: NIMBEX Injection should be refrigerated at 2��to 8��C (36��to 46��F) in the carton to preserve potency. Protect
from light. DO NOT FREEZE. Upon removal from refrigeration to room temperature
storage conditions (25��C/77��F), use NIMBEX Injection within 21 days
even if rerefrigerated.
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| dailymed-instance:inactiveI... | |
| dailymed-instance:overdosag... |
Overdosage with neuromuscular blocking agents may
result in neuromuscular block beyond the time needed for surgery and anesthesia.
The primary treatment is maintenance of a patent airway and controlled ventilation
until recovery of normal neuromuscular function is assured. Once recovery
from neuromuscular block begins, further recovery may be facilitated by administration
of an anticholinesterase agent (e.g., neostigmine, edrophonium) in conjunction
with an appropriate anticholinergic agent (see Antagonism of Neuromuscular
Block below).<br/>Antagonism of Neuromuscular Block: ANTAGONISTS (SUCH AS NEOSTIGMINE AND EDROPHONIUM)
SHOULD NOT BE ADMINISTERED WHEN COMPLETE NEUROMUSCULAR BLOCK IS EVIDENT OR
SUSPECTED. THE USE OF A PERIPHERAL NERVE STIMULATOR TO EVALUATE RECOVERY
AND ANTAGONISM OF NEUROMUSCULAR BLOCK IS RECOMMENDED. Administration
of 0.04 to 0.07 mg/kg neostigmine at approximately 10% recovery from neuromuscular
block (range: 0 to 15%) produced 95% recovery of the muscle twitch response
and a T:Tratio���70% in an average of 9 to
10 minutes. The times from 25% recovery of the muscle twitch response to
a T:Tratio���70% following these doses of
neostigmine averaged 7 minutes. The mean 25% to 75% recovery index following
reversal was 3 to 4 minutes. Administration
of 1.0 mg/kg edrophonium at approximately 25% recovery from neuromuscular
block (range: 16% to 30%) produced 95% recovery and a T:Tratio���70% in an average of 3 to 5 minutes. Patients
administered antagonists should be evaluated for evidence of adequate clinical
recovery (e.g., 5-second head lift and grip strength). Ventilation must be
supported until no longer required. The onset
of antagonism may be delayed in the presence of debilitation, cachexia, carcinomatosis,
and the concomitant use of certain broad spectrum antibiotics, or anesthetic
agents and other drugs which enhance neuromuscular block or separately cause
respiratory depression (see PRECAUTIONS - Drug Interactions ). Under such circumstances the management is the same as that
of prolonged neuromuscular block (see OVERDOSAGE ).
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| dailymed-instance:genericMe... |
cisatracurium besylate
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| dailymed-instance:fullName |
NIMBEX (Injection)
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| dailymed-instance:adverseRe... |
Observed in Clinical Trials of Surgical Patients: Adverse experiences were uncommon among the 945
surgical patients who received NIMBEX in conjunction with other drugs in US
and European clinical studies in the course of a wide variety of procedures
in patients receiving opioid, propofol, or inhalation anesthesia. The following
adverse experiences were judged by investigators during the clinical trials
to have a possible causal relationship to administration of NIMBEX:<br/>Incidence Greater than 1%: None.<br/>Incidence Less than 1%:<br/>Observed in Clinical Trials of Intensive Care Unit Patients: Adverse experiences were uncommon among the 68 ICU
patients who received NIMBEX in conjunction with other drugs in US and European
clinical studies. One patient experienced bronchospasm. In one of the two
ICU studies, a randomized and double-blind study of ICU patients using TOF
neuromuscular monitoring, there were two reports of prolonged recovery (167
and 270 minutes) among 28 patients administered NIMBEX and 13 reports of prolonged
recovery (range: 90 minutes to 33 hours) among 30 patients administered vecuronium.<br/>Observed During Clinical Practice: In addition to adverse events reported from clinical
trials, the following events have been identified during post-approval use
of cisatracurium besylate in conjunction with one or more anesthetic agents
in clinical practice. Because they are reported voluntarily from a population
of unknown size, estimates of frequency cannot be made. These events have
been chosen for inclusion due to a combination of their seriousness, frequency
of reporting, or potential causal connection to cisatracurium besylate.<br/>General: Histamine release, hypersensitivity reactions
including anaphylactic or anaphylactoid responses which, in rare instances,
were severe. There are rare reports of wheezing, laryngospasm, bronchospasm,
rash and itching following administration of NIMBEX in children. These reported
adverse events were not serious and their etiology could not be established
with certainty.<br/>Musculoskeletal: Prolonged neuromuscular block, inadequate neuromuscular
block, muscle weakness, and myopathy.
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| dailymed-instance:warning |
NIMBEX SHOULD
BE ADMINISTERED IN CAREFULLY ADJUSTED DOSAGE BY OR UNDER THE SUPERVISION OF
EXPERIENCED CLINICIANS WHO ARE FAMILIAR WITH THE DRUG'S ACTIONS AND THE
POSSIBLE COMPLICATIONS OF ITS USE. THE DRUG SHOULD NOT BE ADMINISTERED UNLESS
PERSONNEL AND FACILITIES FOR RESUSCITATION AND LIFE SUPPORT (TRACHEAL INTUBATION,
ARTIFICIAL VENTILATION, OXYGEN THERAPY), AND AN ANTAGONIST OF NIMBEX ARE IMMEDIATELY AVAILABLE. IT IS RECOMMENDED THAT A PERIPHERAL
NERVE STIMULATOR BE USED TO MEASURE NEUROMUSCULAR FUNCTION DURING THE ADMINISTRATION
OF NIMBEX IN ORDER TO MONITOR DRUG EFFECT,
DETERMINE THE NEED FOR ADDITIONAL DOSES, AND CONFIRM RECOVERY FROM NEUROMUSCULAR
BLOCK. NIMBEX HAS
NO KNOWN EFFECT ON CONSCIOUSNESS, PAIN THRESHOLD, OR CEREBRATION. TO AVOID
DISTRESS TO THE PATIENT, NEUROMUSCULAR BLOCK SHOULD NOT BE INDUCED BEFORE
UNCONSCIOUSNESS. NIMBEX Injection is acidic (pH
3.25 to 3.65) and may not be compatible with alkaline solutions having a pH
greater than 8.5 (e.g., barbiturate solutions). The
10 mL multiple-dose vials of NIMBEX contain benzyl alcohol. In newborn infants,
benzyl alcohol has been associated with an increased incidence of neurological
and other complications which are sometimes fatal. Single-use vials (5 mL
and 20 mL) of NIMBEX do not contain benzyl alcohol (see PRECAUTIONS
- Pediatric Use).
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| dailymed-instance:indicatio... |
NIMBEX is an intermediate-onset/intermediate-duration
neuromuscular blocking agent indicated for inpatients and outpatients as an
adjunct to general anesthesia, to facilitate tracheal intubation, and to provide
skeletal muscle relaxation during surgery or mechanical ventilation in the
ICU.
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| dailymed-instance:represent... | |
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| dailymed-instance:name |
NIMBEX
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