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Cisatracurium

Pronunciation

(sis a tra KYOO ree um)

Index Terms

  • Cisatracurium Besylate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Nimbex: 10 mg/5 mL (5 mL)

Nimbex: 20 mg/10 mL (10 mL) [contains benzyl alcohol]

Nimbex: 200 mg/20 mL (20 mL)

Generic: 20 mg/10 mL (10 mL)

Solution, Intravenous [preservative free]:

Generic: 10 mg/5 mL (5 mL); 200 mg/20 mL (20 mL)

Brand Names: U.S.

  • Nimbex

Pharmacologic Category

  • Neuromuscular Blocker Agent, Nondepolarizing

Pharmacology

Blocks neural transmission at the myoneural junction by binding with cholinergic receptor sites

Distribution

Vdss: 145 mL/kg (21% larger Vdss when receiving inhalational anesthetics)

Metabolism

Undergoes rapid nonenzymatic degradation in the bloodstream (Hofmann elimination) to laudanosine and inactive metabolites; laudanosine may cause CNS stimulation (association not established in humans) and has less accumulation with prolonged use than atracurium due to lower requirements for clinical effect

Excretion

Urine (95%; <10% as unchanged drug); feces (4%)

Clearance: Children: 5.89 mL/kg/minute; Adults: 4.57 mL/kg/minute

Onset of Action

IV: 2-3 minutes; Peak effect: 3-5 minutes

Duration of Action

Dose dependent, 35 to 45 minutes after a single 0.1 mg/kg dose; recovery begins in 20-35 minutes when anesthesia is balanced; recovery is attained in 90% of patients in 25-93 minutes

Half-Life Elimination

22-29 minutes

Protein Binding

Not studied due to rapid degradation at physiologic pH

Special Populations: Renal Function Impairment

The times to 90% block were approximately 1 minute slower in patients with ESRD. The half-life values of the metabolites are longer in patients with renal failure and concentrations may be higher after long-term administration.

Special Populations: Hepatic Function Impairment

The times to maximum block were approximately 1 minute faster in liver transplant patients compared with healthy adults. The half-life values of the metabolites are longer in patients with hepatic disease and concentrations may be higher after long-term administration.

Special Populations: Elderly

The times to maximum block were approximately 1 minute slower in elderly patients.

Special Populations: Children

Minor differences in pharmacokinetic/pharmacodynamic parameters in children resulted in a faster time to onset and a shorter duration of neuromuscular block.

Use: Labeled Indications

Adjunct to general anesthesia to facilitate endotracheal intubation and to relax skeletal muscles during surgery; to facilitate mechanical ventilation in ICU patients; does not relieve pain or produce sedation

Contraindications

Hypersensitivity to cisatracurium besylate or any component of the formulation; use of the 10 mL multiple-dose vials in premature infants (formulation contains benzyl alcohol)

Dosing: Adult

Neuromuscular blockade: IV (not to be used IM):

Operating room administration:

Intubating dose: 0.15-0.2 mg/kg as components of propofol/nitrous oxide/oxygen induction-intubation technique. (Note: May produce generally good or excellent conditions for tracheal intubation in 1.5-2 minutes with clinically effective duration of action during propofol anesthesia of 55-61 minutes.) Initial dose after succinylcholine for intubation: 0.1 mg/kg; maintenance dose: 0.03 mg/kg 40-60 minutes after initial dose, then at ~20-minute intervals based on clinical criteria.

Continuous infusion: After an initial bolus, a diluted solution can be given by continuous infusion for maintenance of neuromuscular blockade during extended surgery; adjust the rate of administration according to the patient's response as determined by peripheral nerve stimulation. An initial infusion rate of 3 mcg/kg/minute (0.18 mg/kg/hour) may be required to rapidly counteract the spontaneous recovery of neuromuscular function; thereafter, a rate of 1-2 mcg/kg/minute (0.06-0.12 mg/kg/hour) should be adequate to maintain continuous neuromuscular block in the 89% to 99% range in most pediatric and adult patients. Consider reduction of the infusion rate by 30% to 40% when administering during stable isoflurane, enflurane, sevoflurane, or desflurane anesthesia. Spontaneous recovery from neuromuscular blockade following discontinuation of infusion of cisatracurium may be expected to proceed at a rate comparable to that following single bolus administration.

Intensive care unit administration:

Manufacturer's labeling: Loading dose: 0.15-0.2 mg/kg; at initial signs of recovery from bolus dose, begin the infusion at a dose of 3 mcg/kg/minute (0.18 mg/kg/hour) and adjust rate accordingly (follow the principles for infusion in the operating room); dosage ranges of 0.5-10 mcg/kg/minute (0.03-0.6 mg/kg/hour) have been reported. If patient is allowed to recover from neuromuscular blockade, readministration of a bolus dose may be necessary to quickly re-establish neuromuscular block prior to reinstituting the infusion.

or

Loading dose: 0.1 mg/kg (additional boluses of 0.05 mg/kg until train-of-four response is 3/4 or less can be used); then initiate an infusion at 2.5-3 mcg/kg/minute (0.15-0.18 mg/kg/hour) and adjust rate accordingly (Baumann, 2004; Lagneau, 2002).

or

Loading dose: 0.1 to 0.2 mg/kg; immediately following loading dose administration, begin an infusion at 1-3 mcg/kg/minute (0.06-0.18 mg/kg/hour) and adjust rate accordingly (Greenberg, 2013).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Neuromuscular blockade: IV (not to be used IM):

Operating room administration:

Infants 1-23 months: Intubating dose: 0.15 mg/kg over 5-10 seconds

Children 2-12 years: Intubating dose: 0.1-0.15 mg/kg over 5-10 seconds (Note: When given during stable opioid/nitrous oxide/oxygen anesthesia, 0.1 mg/kg produces maximum neuromuscular block in an average of 2.8 minutes and clinically effective block for 28 minutes.)

Children ≥2 years: Continuous infusion: Refer to adult dosing.

Intensive care unit administration: Refer to adult dosing.

Dosing: Renal Impairment

Because slower times to onset of complete neuromuscular block were observed in renal dysfunction patients, extending the interval between the administration of cisatracurium and intubation attempt may be required to achieve adequate intubation conditions.

Dosing: Hepatic Impairment

No dosage adjustment provided in manufacturer’s labeling. The time to onset of action was ~1 minute faster in patients with end-stage liver disease, but was not associated with clinically significant changes in recovery time.

Administration

Administer IV only; give undiluted as bolus injection over 5-10 seconds. Continuous infusion requires the use of an infusion pump. The use of a peripheral nerve stimulator will permit the most advantageous use of cisatracurium, minimize the possibility of overdosage or underdosage and assist in the evaluation of recovery.

Do not administer IM (excessive tissue irritation).

Compatibility

Stable in D5W, NS, D5NS; variable stability (consult detailed reference) in D5LR.

Y-site administration: Incompatible with amphotericin B cholesteryl sulfate complex, cefoperazone, micafungin.

Compatibility in syringe: Incompatible with ceftriaxone.

Storage

Refrigerate intact vials at 2°C to 8°C (36°F to 46°F). Use vials within 21 days upon removal from the refrigerator to room temperature of 25°C (77°F). Per the manufacturer, dilutions of 0.1 mg/mL in 0.9% sodium chloride (NS), dextrose 5% in water (D5W), or D5NS are stable for up to 24 hours at room temperature or under refrigeration; dilutions of 0.1-0.2 mg/mL in D5LR are stable for up to 24 hours in the refrigerator. Additional stability data: Dilutions of 0.1, 2, and 5 mg/mL in D5W or NS are stable in the refrigerator for up to 30 days; at room temperature (23°C), dilutions of 0.1 and 2 mg/mL began exhibiting substantial drug loss between 7-14 days; dilutions of 5 mg/mL in D5W or NS are stable for up to 30 days at room temperature (23°C) (Xu, 1998). Usual concentration: 0.1-0.4 mg/mL.

Drug Interactions

AbobotulinumtoxinA: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Acetylcholinesterase Inhibitors: May diminish the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Aminoglycosides: May enhance the respiratory depressant effect of Neuromuscular-Blocking Agents. Monitor therapy

Calcium Channel Blockers: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Capreomycin: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

CarBAMazepine: May decrease the serum concentration of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Cardiac Glycosides: Neuromuscular-Blocking Agents may enhance the arrhythmogenic effect of Cardiac Glycosides. Monitor therapy

Clindamycin (Topical): May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Colistimethate: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Consider therapy modification

Corticosteroids (Systemic): Neuromuscular-Blocking Agents (Nondepolarizing) may enhance the adverse neuromuscular effect of Corticosteroids (Systemic). Increased muscle weakness, possibly progressing to polyneuropathies and myopathies, may occur. Consider therapy modification

CycloSPORINE (Systemic): May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Fosphenytoin-Phenytoin: May diminish the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Fosphenytoin-Phenytoin may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Fosphenytoin-Phenytoin may decrease the serum concentration of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Inhalational Anesthetics: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Ketorolac (Nasal): May enhance the adverse/toxic effect of Neuromuscular-Blocking Agents (Nondepolarizing). Specifically, episodes of apnea have been reported in patients using this combination. Monitor therapy

Ketorolac (Systemic): May enhance the adverse/toxic effect of Neuromuscular-Blocking Agents (Nondepolarizing). Specifically, episodes of apnea have been reported in patients using this combination. Monitor therapy

Lincosamide Antibiotics: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Lithium: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Loop Diuretics: May diminish the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Loop Diuretics may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Magnesium Salts: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Minocycline: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

OnabotulinumtoxinA: Neuromuscular-Blocking Agents may enhance the neuromuscular-blocking effect of OnabotulinumtoxinA. Monitor therapy

Polymyxin B: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Consider therapy modification

Procainamide: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

QuiNIDine: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

QuiNINE: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Avoid combination

RimabotulinumtoxinB: Neuromuscular-Blocking Agents may enhance the neuromuscular-blocking effect of RimabotulinumtoxinB. Monitor therapy

Spironolactone: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Tetracycline Derivatives: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Trimebutine: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Vancomycin: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Adverse Reactions

Effects are minimal and transient.

<1% (Limited to important or life-threatening): Bradycardia, bronchospasm, flushing, hypotension, muscle calcification (prolonged use), myopathy (acute quadriplegic syndrome; prolonged use), pruritus, skin rash

Warnings/Precautions

Concern related to adverse effects:

• Bradycardia: May be more common with cisatracurium than with other neuromuscular-blocking agents since it has no clinically-significant effects on heart rate to counteract the bradycardia produced by anesthetics.

• Neuromuscular cross-sensitivity: Cross-sensitivity with other neuromuscular-blocking agents may occur; use extreme caution in patients with previous anaphylactic reactions to other neuromuscular-blocking agents.

Disease-related concerns:

• Burn injury: Resistance may occur in burn patients (≥20% of total body surface area), usually several days after the injury, and may persist for several months after wound healing (Han, 2009).

• Conditions which may antagonize neuromuscular blockade: Respiratory alkalosis, hypercalcemia, demyelinating lesions, peripheral neuropathies, denervation, and muscle trauma may result in antagonism of neuromuscular blockade (Greenberg, 2013; Miller, 2010; Murray, 2002; Naguib, 2002).

• Conditions which may potentiate neuromuscular blockade: Electrolyte abnormalities (eg, severe hypocalcemia, severe hypokalemia, hypermagnesemia), neuromuscular diseases, metabolic acidosis, metabolic alkalosis, respiratory acidosis, Eaton-Lambert syndrome and myasthenia gravis may result in potentiation of neuromuscular blockade (Greenberg, 2013; Miller, 2010; Naguib, 2002).

• Therapeutic hypothermia: Hypothermia may slow Hoffmann elimination thereby prolonging the duration of activity (Greenberg, 2013).

Special populations:

• Elderly: Use with caution in the elderly, effects and duration are more variable.

• Immobilized patients: Resistance may occur in patients who are immobilized.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse (AAP ["Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors, 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer’s labeling.

Other warnings/precautions:

• Appropriate use: Maintenance of an adequate airway and respiratory support is critical.

• Experienced personnel: Should be administered by adequately trained individuals familiar with its use.

Monitoring Parameters

Peripheral nerve stimulator measuring twitch response (when appropriate); vital signs (heart rate, blood pressure, respiratory rate)

Pregnancy Risk Factor

B

Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Have patient report immediately to prescriber bradycardia, severe dizziness, passing out, or flushing (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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