Cisatracurium Besylate

Class: Neuromuscular Blocking Agents
VA Class: MS300
Chemical Name: [1R - [1α,2α(1′R*,2′R*)]] - 2,2′ - [1,5 - pentanediyl - bis[oxy(3 - oxo - 3,1 - propanediyl)]]bis[1 - [(3,4 - dimethoxyphenyl)methyl] - 1,2,3,4 - tetrahydro - 6,7 - dimethoxy - 2 - methyl - isoquinolinium dibenzenesulfonate
Molecular Formula: C65H82N2O18S2
CAS Number: 96946-42-8
Brands: Nimbex

Warning(s)

  • Should be administered only under supervision of qualified clinicians experienced in the administration of neuromuscular blocking agent therapy.1

Introduction

Nondepolarizing neuromuscular blocking agent; isomer of atracurium.1 3 5 6 7 11 14 15 19

Uses for Cisatracurium Besylate

Skeletal Muscle Relaxation

Production of skeletal muscle relaxation during surgery after general anesthesia has been induced.1 5 11 21

Facilitation of tracheal intubation; however, succinylcholine generally is preferred in emergency situations where rapid intubation is required; cisatracurium is not recommended for rapid sequence endotracheal intubation because of its intermediate onset of action.1 5 11 21 22

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Treatment to increase pulmonary compliance during assisted or controlled respiration.2 3 21 45 46

Facilitation of mechanical ventilation in intensive care settings.1 3 5 8 10 14 Some experts prefer cisatracurium or atracurium (because elimination is not dependent on hepatic or renal function) for prolonged therapy in intensive care settings in patients with substantial hepatic or renal dysfunction.3 (See Elimination under Pharmacokinetics.)

In clinical studies, cisatracurium was administered at a rate of infusion one-third that of atracurium and exhibited a similar time to spontaneous recovery.1 7 8 9 13 Studies comparing cisatracurium with vecuronium showed a longer duration of action and faster time to spontaneous recovery with cisatracurium.1 10 11 12 13 14

Cisatracurium Besylate Dosage and Administration

General

  • Adjust dosage carefully according to individual requirements and response.1 21

  • Assess neuromuscular transmission during therapy and recovery; a peripheral nerve stimulator is recommended to accurately monitor the degree of muscle relaxation and to minimize the possibility of overdosage or underdosage.1 3 21 48

  • To avoid patient distress, administer only after unconsciousness has been induced.1 3

Facilitation of Endotracheal Intubation

  • Endotracheal intubation for nonemergency surgical procedures generally can be performed within 1.5 or 2 minutes following administration of a 0.2- or 0.15-mg/kg dose, respectively.1 (See Onset and also Duration under Pharmacokinetics.)

  • The interval between cisatracurium administration and intubation may be longer in geriatric patients and patients with renal impairment, because the onset of complete neuromuscular blockade may be slower in these patients.1 16 (See Absorption: Special Populations and also Onset, under Pharmacokinetics.)

Maintenance of Neuromuscular Blockade

  • Repeated administration of maintenance doses or continuous infusion for up to 3 hours is not associated with development of cumulative neuromuscular blocking effects; such administration has no effect on duration of blockade, providing partial recovery is allowed to occur between doses.1 48

  • Rate of spontaneous recovery from neuromuscular blockade following discontinuance of maintenance infusion is comparable to that following administration of a single IV injection.1 (See Onsetand also Duration under Pharmacokinetics.)

Reversal of Neuromuscular Blockade

  • To reverse neuromuscular blockade once recovery has started, administer a cholinesterase inhibitor (e.g., neostigmine, pyridostigmine, edrophonium) usually in conjunction with an antimuscarinic (e.g., atropine, glycopyrrolate) to block adverse muscarinic effects of the cholinesterase inhibitor.1 21 Time to recovery of neuromuscular function is dependent upon strength of neuromuscular blockade at time of reversal.1

Administration

Administer IV only; do not administer IM.1

20-mL vial intended for ICU use only.1

IV Administration

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

Consult specialized references for specific procedures and techniques of administration.23

Administer initial (intubating) dose by rapid IV injection;1 administer maintenance doses by intermittent IV injection or continuous IV infusion.1

Dilution

For continuous IV infusion, dilute to desired concentration (e.g., 0.1–0.4 mg/mL) in a compatible IV solution.1 48 (See Storage and also Compatibility, under Stability.)

Rate of Administration

Rapid IV injection: For initial (intubating) doses in children 1 month to 12 years of age, administer over 5–10 seconds.1

Continuous IV infusion in adults and children ≥2 years of age: Individualize infusion rate based on patient requirements and response to peripheral nerve stimulation.1 48 Accurate dosage is best achieved using a precision infusion device.1

Table 1. Infusion Rates Required to Deliver Selected Dosages of Cisatracurium from Solutions Containing 0.1 mg/mL of the Drug1

 

Drug Delivery Rate (mcg/kg per minute)

 

1

1.5

2

3

5

Weight (kg)

Infusion Delivery Rate (mL/hr)

10

6

9

12

18

30

45

27

41

54

81

135

70

42

63

84

126

210

100

60

90

120

180

300

Table 2. Infusion Rates Required to Deliver Selected Dosages of Cisatracurium from Solutions Containing 0.4 mg/mL of the Drug1

 

Drug Delivery Rate (mcg/kg per minute)

 

1

1.5

2

3

5

Weight (kg)

Infusion Delivery Rate (mL/hr)

10

1.5

2.3

3

4.5

7.5

45

6.8

10.1

13.5

20.3

33.8

70

10.5

15.8

21

31.5

52.5

100

15

22.5

30

45

75

Dosage

Available as cisatracurium besylate; dosage expressed in terms of cisatracurium.1

Pediatric Patients

Skeletal Muscle Relaxation
Initial (Intubating) Dosage
IV

Infants 1–23 months of age: 0.15 mg/kg when used concomitantly with halothane or opiate anesthesia.1 (See Onset and also see Duration under Pharmacokinetics.)

Children 2–12 years of age: 0.1–0.15 mg/kg when used concomitantly with halothane or opiate anesthesia.1 (See Onset and also see Duration under Pharmacokinetics.)

Adolescents ≥13 years of age: Manufacturer makes no specific dosage recommendations.1 48

Maintenance Dosage During Prolonged Surgical Procedures
Continuous IV Infusion

Children ≥2 years of age may receive continuous IV infusion of cisatracurium for maintenance of neuromuscular blockade; individualize dosage based on individual requirements and response to peripheral nerve stimulation.1 48

Initiate continuous IV infusion only after early spontaneous recovery from initial IV dose is evident.1

Initially, 3 mcg/kg per minute may be necessary to rapidly counteract spontaneous recovery from neuromuscular blockade.1 1–2 mcg/kg per minute generally maintains 89–99% neuromuscular blockade in most pediatric patients receiving balanced anesthesia.1

Consider reducing infusion rate by 30–40% if steady-state anesthesia has been induced with enflurane or isoflurane; greater reductions in cisatracurium infusion rate may be required with prolonged durations of enflurane or isoflurane administration.1 (See Specific Drugs under Interactions.)

Adults

Skeletal Muscle Relaxation
Initial (Intubating) Dosage
IV

0.15–0.2 mg/kg.1 (See Onset and also see Duration under Pharmacokinetics.)

Maintenance Dosage During Prolonged Surgical Procedures
Intermittent IV Injection

0.03 mg/kg as needed.1 (See Onset and also see Duration under Pharmacokinetics.)

Maintenance dosage generally required within 40–50 or 50–60 minutes following initial dose of 0.15 or 0.2 mg/kg, respectively.1 5

Each 0.03-mg/kg dose provides approximately 20 minutes of additional neuromuscular blockade.1 For shorter or longer durations of action, administer smaller or larger doses.1

Longer dosing intervals or lower doses of cisatracurium may be necessary when administered concomitantly with enflurane or isoflurane anesthesia during prolonged surgical procedures.1 No dosage adjustment appears to be necessary when dose is administered shortly (e.g., within 15–30 minutes) after initiation of enflurane or isoflurane anesthesia.1 (See Specific Drugs under Interactions.)

Continuous IV Infusion

Individualize dosage based on individual requirements and response.1

Initiate continuous IV infusion only after early spontaneous recovery from IV dose is evident.1

Initially, 3 mcg/kg per minute may be necessary to rapidly counteract spontaneous recovery from neuromuscular blockade.1 1–2 mcg/kg per minute generally maintains 89–99% neuromuscular blockade in most patients receiving balanced anesthesia.1

Consider reducing infusion rate by 30–40% if steady-state anesthesia has been induced with enflurane or isoflurane; greater reductions in cisatracurium infusion rate may be required with prolonged durations of enflurane or isoflurane administration.1 (See Specific Drugs under Interactions.)

Maintenance Dosage in Intensive Care Setting
Continuous IV Infusion

Individualize dosage based on individual requirements and response.1

Infusion rate of approximately 3 mcg/kg per minute (range: 0.5–10.2 mcg/kg per minute) generally is adequate.1 Dosage requirements may increase or decrease with time.1

Following recovery from neuromuscular blockade, readministration of an IV (“bolus”) dose to reestablish neuromuscular blockade prior to reinstitution of the infusion may be necessary.1

Use for >6 days during mechanical ventilation in an intensive care setting has not been evaluated in clinical studies.1 (See Intensive Care Setting under Cautions.)

Special Populations

Burn Patients

Substantially increased doses may be required due to development of resistance.1 However, no clinical studies to date in these patients, and no specific doses are recommended.1 (See Burn Patients under Cautions and also see Distribution: Special Populations, under Pharmacokinetics.)

Cardiopulmonary Bypass Patients with Induced Hypothermia

Infusion rate of atracurium required to maintain adequate surgical relaxation during hypothermia (i.e., 25–28°C) is approximately 50% of the infusion rate necessary in normothermic patients; a similar reduction in the infusion rate of cisatracurium may be expected.1 15

Other Populations

Patients in whom potentiation of neuromuscular blockade or difficulties with reversal of blockade may occur (e.g., neuromuscular disease, carcinomatosis): A dose of ≤0.02 mg/kg is recommended along with monitoring of subsequent dosage adjustments.1 (See Neuromuscular Disease and also see Carcinomatosis, under Cautions.)

Cautions for Cisatracurium Besylate

Contraindications

  • Known hypersensitivity to cisatracurium besylate, other bis-benzylisoquinolinium agents (e.g., atracurium, doxacurium, mivacurium, tubocurarine3 [the latter 3 drugs no longer commercially available in the US]), or any ingredient in the formulation.1

Warnings/Precautions

Warnings

Respiratory Effects

Neuromuscular blocking agents can severely compromise respiratory function and induce respiratory paralysis.23

Should be used only by individuals experienced in the use of neuromuscular blocking agents and in the maintenance of adequate airway and respiratory support.1 23 Facilities and personnel necessary for intubation, administration of oxygen, and assisted or controlled respiration should be immediately available.1 23

IV cholinesterase inhibitor (e.g., neostigmine, pyridostigmine, edrophonium) should be readily available.1 (See Reversal of Neuromuscular Blockade under Dosage and Administration.)

General Precautions

Neuromuscular Disease

Possible exaggerated neuromuscular blockade in patients with neuromuscular disease (e.g., myasthenia gravis, Eaton-Lambert syndrome).1 23

Monitor degree of neuromuscular blockade with a peripheral nerve stimulator; dosage reduction is recommended.1 (See Other Populations under Dosage and Administration.)

Burn Patients

Resistance to nondepolarizing neuromuscular blocking agents33 34 35 37 38 can develop in burn patients, particularly those with burns over 25–30% or more of body surface area.1 33 34 35 36 37 38 39

Resistance generally becomes apparent ≥1 week after the burn,33 34 35 36 37 38 39 peaks ≥2 weeks after the burn,34 35 36 38 persists for several months or longer,34 36 and decreases gradually with healing.33 34 36 38

Cisatracurium has not been studied in this population; however, based on its similarity to atracurium, consider the possible need for substantially increased doses.1

Intensive Care Setting

Possible prolonged paralysis and/or muscle weakness or atrophy with long-term administration of neuromuscular blocking agents.3 20

Continuous monitoring of neuromuscular transmission with a peripheral nerve stimulator is recommended.1 3 21 48 Do not administer additional doses before there is a definite response to nerve stimulation tests.1 If no response is elicited, discontinue administration until a response returns.1

Seizures reported rarely with other neuromuscular blocking agents (e.g., atracurium) in patients with predisposing factors (e.g., head trauma, cerebral edema, hypoxic encephalopathy, viral encephalitis, uremia) receiving continuous IV infusions for facilitation of mechanical ventilation in intensive care settings.1 20 Unclear whether laudanosine (metabolite of atracurium and cisatracurium) contributes to CNS excitation (see Metabolism under Pharmacokinetics).1

Cardiovascular Effects

No clinically important effects on heart rate; exhibits minimal, if any, cardiovascular effects;1 3 16 18 20 therefore, will not counteract the bradycardia induced by many anesthetic agents or by vagal stimulation.1

Electrolyte Disturbances

Acid-base and/or serum electrolyte abnormalities may potentiate or antagonize action of cisatracurium.1

Hemiparesis and Paraparesis

Resistance to therapy may develop in the affected limbs of patients with hemiparesis or paraparesis.1

Monitor neuromuscular transmission in a nonparetic limb to avoid inaccurate dosing.1

Malignant Hyperthermia

Malignant hyperthermia is rarely associated with use of neuromuscular blocking agents and/or potent inhalation anesthetics.1 20 Cisatracurium has not been studied in patients with increased susceptibility to malignant hyperthermia.1 Be vigilant for its possible development and prepared for its management in any patient undergoing general anesthesia.1

Histamine Release

Doses up to 8 times the recommended therapeutic dose did not result in dose-related elevations of mean plasma histamine;1 5 14 19 other studies indicate that cisatracurium does not cause systemic or cutaneous histamine release.11 17 19

Carcinomatosis

Possible exaggerated neuromuscular blockade in patients with carcinomatosis.1 Carefully monitor the degree of neuromuscular blockade with a peripheral nerve stimulator; dosage reduction is recommended.1 (See Other Populations under Dosage and Administration.)

Specific Populations

Pregnancy

Category B.1

Not known whether use during labor or delivery has effects on the fetus.1

Lactation

Not known whether cisatracurium is distributed into milk.1 Caution advised if used in nursing women.1

Pediatric Use

Safety and efficacy not established in neonates (<1 month of age).1

Tracheal intubation was facilitated more reliably in children 1–4 years of age when used in conjunction with halothane than when used in conjunction with opiates and nitrous oxide.1

Large amounts of benzyl alcohol (i.e., 100–400 mg/kg daily) have been associated with toxicity in infants;1 24 25 26 27 28 29 each mL of cisatracurium besylate injection in multiple-dose vials contains 9 mg of benzyl alcohol.1

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity of some older patients cannot be ruled out.1

Minor alterations in pharmacokinetics/pharmacodynamics, but no substantial differences in recovery profile.1 (See Pharmacokinetics.)

Hepatic Impairment

Minor alterations in pharmacokinetics, but no substantial differences in recovery profile.1 Concentration of metabolites may be increased after prolonged administration.1 (See Pharmacokinetics.)

Renal Impairment

Pharmacokinetic/pharmacodynamic profile similar to that in healthy adults;1 concentration of metabolites may be increased after prolonged administration.1 (See Pharmacokinetics.)

Common Adverse Effects

Surgical patients: None with incidence >1% in clinical trials.1

Intensive care patients: Prolonged recovery from neuromuscular blockade.1

Interactions for Cisatracurium Besylate

Specific Drugs

Drug

Interaction

Comments

Amphotericin B

May prolong neuromuscular blockade secondary to potassium depletion20 43

Monitor serum potassium43

Anesthetics, general (desflurane, enflurane, halothane, isoflurane)

Increased potency and prolonged duration of neuromuscular blockade1 21 32

Reduced cisatracurium dosage and/or infusion rate may be necessary1 32 (see Dosage under Dosage and Administration)

Anesthetics, local

Possible increased neuromuscular blockade1 3

Anticonvulsants (carbamazepine, phenytoin)

Decreased duration and/or degree of neuromuscular blockade1 3 30

Close monitoring recommended;1 adjust cisatracurium dosage accordingly30

Anti-infectives (aminoglycosides, bacitracin, clindamycin, lincomycin, polymyxins, tetracyclines)

Possible increased neuromuscular blockade1 3

Calcium-channel blocking agents (e.g., verapamil)

Possible increased neuromuscular blockade3 20 23 41 44

Reduction of the dosage of either or both drugs may be necessary23 41 44

Glucocorticoids

Possible increased risk of myopathy/polyneuropathy with concomitant high-dose glucocorticoid and prolonged neuromuscular blocking agent therapy3 42

Discontinue neuromuscular blocking agent as soon as possible3

Lithium

Possible increased neuromuscular blockade1 3

Magnesium salts

Increased neuromuscular blockade1 3 40

Use with caution; reduced cisatracurium dosage may be necessary40

Neuromuscular blocking agents, nondepolarizing

Potency and duration of nondepolarizing neuromuscular blocking agents may be altered by concurrent or prior administration of other nondepolarizing agents31

Procainamide

Possible increased neuromuscular blockade1 3

Propofol

No apparent effect on duration of neuromuscular blockade1

No dosage adjustment required1

Quinidine

Possible increased neuromuscular blockade1 3

Succinylcholine

Prior administration of succinylcholine may decrease time to maximum neuromuscular blockade with cisatracurium by about 2 minutes1

Prior administration of succinylcholine does not appear to alter duration of blockade induced by intermittent injections of cisatracurium; prior administration resulted in no change or only slight increase in cisatracurium infusion requirements1

Cisatracurium has been used safely following various degrees of recovery from succinylcholine-induced neuromuscular blockade1

Cisatracurium Besylate Pharmacokinetics

Absorption

Bioavailability

Poorly absorbed from GI tract.23

Onset

Intermediate onset of action.1 5 Generally, time to maximum neuromuscular blockade decreases as dose increases; time to maximum blockade is up to 2 minutes longer with cisatracurium than with equipotent doses of atracurium.1 5

Good to excellent conditions for tracheal intubation occur within 1.5–2 or 1.5 minutes following IV dose of 0.15 or 0.2 mg/kg, respectively.1 5

Onset is faster in pediatric patients than in adults; also faster in infants than in older children.1 Onset may be delayed in geriatric patients compared with younger adults.1 16

In adults, doses of 0.15 or 0.2 mg/kg administered under balanced anesthesia produce maximum neuromuscular blockade in about 3.5 (range: 1.6–6.8) or 2.9 (range: 1.9–5.2) minutes, respectively.1 Maximum neuromuscular blockade after 0.1-mg/kg dose occurs about 1 minute later in geriatric patients than in younger adults.1

In children, doses of 0.1 or 0.15 mg/kg administered under balanced anesthesia produce maximum neuromuscular blockade in about 2.8 (range: 1.8–6.7) or 3 (range: 1.5–8) minutes, respectively.1 In infants, doses of 0.15 mg/kg administered under balanced anesthesia produce maximum neuromuscular blockade in about 2 minutes (range: 1.3–4.3).1

Duration

Intermediate duration of action.1 5 6 20 Duration of maximum neuromuscular blockade increases as the dose increases; when the cisatracurium dose is doubled, the clinically effective duration of blockade increases by approximately 25 minutes.1 Clinically effective duration of action and rate of spontaneous recovery with equipotent doses of cisatracurium and atracurium are similar.1

Duration is longer in adults than in pediatric patients; also longer in infants than in older children.1 No substantial difference in recovery profiles between geriatric and younger adults.1 11 16 Recovery following reversal is faster in children than in adults.1

In adults, clinically effective duration of neuromuscular blockade (i.e., time to 25% recovery) after dose of 0.15 or 0.2 mg/kg is 55 (range: 44–74) or 65 (range: 43–103) minutes, respectively.1

In children 2–12 years of age, clinically effective duration of neuromuscular blockade after dose of 0.1 or 0.15 mg/kg is approximately 28 (range: 21–38) or 36 (range: 29–46) minutes, respectively.1 In infants, clinically effective duration of neuromuscular blockade after dose of 0.15 mg/kg is approximately 43 minutes (range: 34–58 minutes).1

Duration of neuromuscular blockade induced by 0.03-mg/kg maintenance dose is approximately 20 minutes.1

In studies in patients receiving long-term (i.e., up to 6 days) infusion during mechanical ventilation, recovery of neuromuscular function (train-of-four ratio ≥70%) occurred in approximately 50 (range: 20–175) or 55 (range: 20–270) minutes following infusion discontinuance.1

Special Populations

In patients with end-stage liver disease, onset may be slightly faster; however, hepatic dysfunction does not substantially alter rate of recovery from neuromuscular blockade.1 3 6 16

In patients with renal failure, onset may be slightly delayed; however, renal dysfunction does not substantially alter rate of recovery from neuromuscular blockade.1 3 6 16

Gender and obesity not associated with substantial changes in predicted onset or rate of recovery.1 47

Distribution

Extent

Neuromuscular blocking agents generally distribute into extracellular fluid and rapidly reach site of action at motor end-plate of myoneural junction.2

Neuromuscular blocking agents may cross placenta.2

Volume of distribution of cisatracurium may be limited by its large molecular size and increased polarity.47 Higher steady-state volume of distribution when nontraditional two-compartment model of elimination is used compared with a one-compartment model.5 47

Plasma Protein Binding

Plasma protein binding cannot be determined because of rapid metabolism of cisatracurium.47 (See Elimination under Pharmacokinetics.)

Special Populations

Based on a one-compartment model, volume of distribution at steady-state may be increased in the elderly, ICU patients, and in patients with end-stage hepatic failure.5 6

In burn patients, possible increased protein binding (possibly to α1-acid glycoprotein) of neuromuscular blocking agents with subsequent decreases in the free fraction of circulating drug.33 34 35 37

Elimination

Metabolism

Rapidly metabolized via Hofmann elimination (independent of liver) to form a monoquaternary acrylate metabolite (which undergoes nonspecific plasma esterase hydrolysis and subsequent Hofmann elimination) and laudanosine (which is demethylated and glucuronidated).1 3 6 11 14 15 19 47 Both metabolites lack neuromuscular blocking activity; laudanosine may have CNS excitatory activity when present in large amounts.1 6 47

Rate of Hofmann elimination is dependent on temperature and pH.1 6 15

Elimination Route

Eliminated principally by Hofmann elimination (77–80%) and to lesser extent by renal and hepatic elimination (20%).1 6 Metabolites are eliminated principally by renal and hepatic elimination.1 Following administration of radiolabeled dose of cisatracurium to healthy individuals, 95% of administered dose is recovered in urine and 4% in feces; <10% of the dose is recovered as unchanged drug.1 6

Half-life

22–30 minutes.1 6 47

Special Populations

Patients with renal or hepatic dysfunction may exhibit longer half-lives; concentrations of metabolites after prolonged administration may be higher.1

Cisatracurium half-life may be slightly prolonged in geriatric patients.1 6

Pediatric patients may exhibit faster clearance of cisatracurium than adults.1

Stability

Storage

Parenteral

Injection

Original carton at 2–8°C; protect from light.1 Do not freeze.1

Use within 21 days once removed from refrigeration, regardless of whether injection was subsequently returned to refrigeration.1

Following dilution to final concentration of 0.1 mg/mL in 5% dextrose, 0.9% sodium chloride, or 5% dextrose and 0.9% sodium chloride injection, store at room temperature or refrigerate; use within 24 hours.1

Compatibility

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

Parenteral

Solution CompatibilityHID

Compatible

Dextrose 5% in water

Dextrose 5% in sodium chloride 0.9%

Sodium chloride 0.9%

Incompatible

Ringer’s injection, lactated

Drug Compatibility
Y-Site CompatibilityHID

Compatible

Alfentanil HCl

Amikacin sulfate

Aztreonam

Bretylium tosylate

Bumetanide

Buprenorphine HCl

Butorphanol tartrate

Calcium gluconate

Ceftriaxone sodium

Chlorpromazine HCl

Cimetidine HCl

Ciprofloxacin

Clindamycin phosphate

Dexamethasone sodium phosphate

Dexmedetomidine HCl

Digoxin

Diphenhydramine HCl

Dobutamine HCl

Dopamine HCl

Doxycycline hyclate

Droperidol

Drotrecogin alfa (activated)

Enalaprilat

Epinephrine HCl

Esmolol HCl

Famotidine

Fenoldopam mesylate

Fentanyl citrate

Fluconazole

Gatifloxacin

Gentamicin sulfate

Haloperidol lactate

Hetastarch in lactated electrolyte injection (Hextend)

Hydrocortisone sodium succinate

Hydromorphone HCl

Hydroxyzine HCl

Imipenem-cilastatin sodium

Inamrinone lactate

Isoproterenol HCl

Lidocaine HCl

Linezolid

Lorazepam

Magnesium sulfate

Mannitol

Meperidine HCl

Metoclopramide HCl

Metronidazole

Midazolam HCl

Morphine sulfate

Nalbuphine HCl

Nitroglycerin

Norepinephrine bitartrate

Ondansetron HCl

Phenylephrine HCl

Potassium chloride

Procainamide HCl

Prochlorperazine edisylate

Promethazine HCl

Ranitidine HCl

Remifentanil HCl

Sufentanil citrate

Theophylline

Tobramycin sulfate

Vancomycin HCl

Zidovudine

Incompatible

Amphotericin B cholesteryl sulfate complex

Ketorolac tromethamine

Propofol

Variable

Acyclovir sodium

Aminophylline

Amphotericin B

Ampicillin sodium

Ampicillin sodium and sulbactam sodium

Cefazolin sodium

Cefotaxime sodium

Cefotetan disodium

Cefoxitin sodium

Ceftazidime

Ceftizoxime sodium

Cefuroxime sodium

Co-trimoxazole

Diazepam

Furosemide

Ganciclovir sodium

Heparin sodium

Methylprednisolone sodium succinate

Piperacillin sodium–tazobactam sodium

Sodium bicarbonate

Sodium nitroprusside

Thiopental sodium

Ticarcillin disodium-clavulanate potassium

Actions

  • Produces skeletal muscle relaxation by causing a decreased response to acetylcholine (ACh) at the myoneural (neuromuscular) junction of skeletal muscle.1 2

  • Exhibits high affinity for ACh receptor sites and competitively blocks access of ACh to motor end-plate of myoneural junction; may affect ACh release.1 2

  • Blocks the effects of both the small quantities of ACh that maintain muscle tone and the large quantities of ACh that produce voluntary skeletal muscle contraction; does not alter the resting electrical potential of the motor end-plate or cause muscular contractions.2

  • Neuromuscular blocking potency of cisatracurium is approximately threefold that of atracurium.1 7 14

  • Exhibits minimal, if any, cardiovascular effects.1 3 16 18 20

  • Exhibits little histamine-releasing activity at usual therapeutic doses.1 5 11 14 17 19

Advice to Patients

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., cardiovascular disease, neuromuscular disease).1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

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

Cisatracurium Besylate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IV use only

2 mg (of cisatracurium) per mL

Nimbex (preservative-free in single-use vials or with benzyl alcohol 0.9% w/v in multiple-dose vials)

Abbott

10 mg (of cisatracurium) per mL

Nimbex (preservative-free in single-use vials)

Abbott

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions May 1, 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Abbott Laboratories. Nimbex (cisatracurium besylate) injection prescribing information. North Chicago, IL; 2005 Feb.

2. AHFS Drug Information 2007. McEvoy GK, ed. Neuromuscular blocking agents general statement. Bethesda, MD: American Society of Health-System Pharmacists; 2007:1381-4.

3. Society of Critical Care Medicine and American Society of Health-System Pharmacists. Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient. Am J Health-Syst Pharm. 2002; 59:179-95. [PubMed 11826571]

4. Society of Critical Care Medicine and American Society of Health-System Pharmacists. Sedation, analgesia, and neuromuscular blockade of the critically ill adult: revised clinical practice guidelines for 2002. Am J Health-Syst Pharm. 2002; 59:147-9. [PubMed 11826569]

5. Bryson HM, Faulds D. Cisatracurium besilate: a review of its pharmacology and clinical potential in anaesthetic practice. Drugs. 1997; 53:848-66. [PubMed 9129870]

6. Kisor DF, Schmith VD. Clinical pharmacokinetics of cisatracurium besilate. Clin Pharmacokinet. 1999; 36:27-40. [PubMed 9989341]

7. Mellinghoff H, Radbruch L, Diefenbach C et al. A comparison of cisatracurium and atracurium: onset of neuromuscular block after bolus injection and recovery after subsequent infusion. Anesth Analg. 1996; 83:1072-5. [PubMed 8895288]

8. Newman PJ, Quinn AC, Grounds RM et al. A comparison of cisatracurium (51W89) and atracurium by infusion in critically ill patients. Crit Care Med. 1997; 25:1139-42. [PubMed 9233738]

9. Pearson AJ, Harper NJ, Pollard BJ. The infusion requirements and recovery characteristics of cisatracurium or atracurium in intensive care patients. Intensive Care Med. 1996; 22:694-8. [PubMed 8844237]

10. Burmester M, Mok Q. Randomised controlled trial comparing cisatracurium and vecuronium infusions in a paediatric intensive care unit. Intensive Care Med. 2005; 31:686-92. [PubMed 15815895]

11. Melloni C, Devivo P, Launo C et al. Cisatracurium versus vecuronium: a comparative, double blind, randomized, multicenter study in adult patients under propofol/fentanyl/N2O anesthesia. Minerva Anestesiol. 2006; 72:299-308. [PubMed 16675938]

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