Note: Dose to effect; doses must be individualized due to interpatient variability. Ensure adequate pain control and sedation prior to and during administration of neuromuscular blockade to achieve deep sedation (Ref).
Mechanically ventilated patients in the ICU, neuromuscular blockade: Note: May use to facilitate mechanical ventilation (eg, moderate to severe acute respiratory distress syndrome; refractory, life-threatening status asthmaticus; or shivering from therapeutic hypothermia (Ref):
IV: 0.1 to 0.2 mg/kg loading dose, followed immediately by an infusion of 1 to 3 mcg/kg/minute (or 0.06 to 0.18 mg/kg/hour); adjust rate accordingly (Ref). Alternatively, in patients with acute respiratory distress syndrome to prevent ventilator asynchrony (off-label use), may administer a non-weight based dosing regimen of 15 mg (loading dose) followed immediately by 37.5 mg/hour for 48 hours; may administer 20 mg rapid boluses during infusion based on clinical parameters (eg, end-inspiratory plateau pressure remains >32 cm H2O) (Ref); dosage ranges of 0.5 to 10 mcg/kg/minute (or 0.03 to 0.6 mg/kg/hour) have been reported.
Mechanically ventilated patients during surgery or endotracheal intubation, neuromuscular blockade (adjunct to general anesthesia): Note: Inhaled anesthetic agents (eg, desflurane, isoflurane, enflurane, sevoflurane) prolong the duration of action of cisatracurium. Use lower end of the dosing range; redosing interval guided by monitoring with a peripheral nerve stimulator.
Operating room administration:
Intubating dose: IV: 0.15 to 0.2 mg/kg bolus as components of propofol or thiopental/nitrous oxide/oxygen induction-intubation technique; doses up to 0.4 mg/kg have been administered. Note: May produce generally good or excellent conditions for tracheal intubation in 1.5 to 2 minutes with clinically effective duration of action during propofol anesthesia of 55 to 61 minutes. In patients with neuromuscular diseases (eg, myasthenia gravis, myasthenic syndrome, carcinomatosis), maximum initial bolus dose is 0.02 mg/kg. Initial dose after succinylcholine for intubation: 0.1 mg/kg
Maintenance dose:
Intermittent bolus dosing: IV: 0.03 mg/kg 40 to 50 minutes (after initial dose of 0.15 mg/kg) or 50 to 60 minutes (after an initial dose of 0.2 mg/kg), then as needed based on clinical response.
Continuous infusion: IV: 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 (or 0.18 mg/kg/hour) may be required to rapidly counteract the spontaneous recovery of neuromuscular function; thereafter, a rate of 1 to 2 mcg/kg/minute (or 0.06 to 0.12 mg/kg/hour) should provide 89% to 99% neuromuscular blockade in most 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.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no specific dosage adjustments provided in the manufacturer's labeling. The half-life values of the metabolites are longer in patients with renal failure and concentrations may be higher after long-term administration. In patients with ESRD, consider extending the interval between the administration of cisatracurium and intubation attempt by at least 1 minute to achieve adequate intubation conditions (time to maximum neuromuscular blockade is ~1 minute slower in patients with ESRD).
There are no dosage adjustments provided in the manufacturer’s labeling. The half-life values of the metabolites are longer in patients with hepatic disease and concentrations may be higher after long-term administration.
The recommendations for dosing in patients with obesity are based upon the best available evidence and clinical expertise. Senior Editorial Team: Jeffrey F. Barletta, PharmD, FCCM; Manjunath P. Pai, PharmD, FCP; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC.
Class 1, 2 or 3 obesity (BMI ≥30 kg/m2):
IV: Use ideal body weight for weight-based dosing calculations, then titrate to clinical effect (Ref). In patients with extreme obesity (eg, BMI ≥50 kg/m2), or when underdosing is a concern, consider using adjusted body weight for weight-based dosing calculations, then titrate to clinical effect (Ref). Clinicians should not change dosing weight from one weight metric to another during therapy (ie, actual body weight to/from either adjusted body weight or ideal body weight) (Ref). Refer to adult dosing for indication-specific doses.
Rationale for recommendations: Nondepolarizing neuromuscular blocking agents (NMBAs) are hydrophilic compounds with a small Vd, thus distribution of cisatracurium into adipose tissue is limited (Ref). There are no studies evaluating the most appropriate weight metric in patients with obesity receiving sustained continuous infusions. Data with NMBAs in patients with obesity predominantly originate from studies evaluating either single bolus or incremental doses in patients undergoing surgical procedures. One study in patients undergoing bariatric laparoscopic gastric banding reported an ~26% prolonged duration of effect when cisatracurium dosing was based on actual body weight compared to ideal body weight (Ref). Another study suggested similar onset times but shorter recovery durations (~19% shorter) in patients with extreme obesity (mean BMI = 55 kg/m2) when cisatracurium was dosed using adjusted body weight versus a control group of patients without obesity (Ref).
Refer to adult dosing. Consider extending the interval between administration of cisatracurium and intubation attempt by at least 1 minute to achieve adequate intubation conditions (time to maximum neuromuscular blockade is ~1 minute slower in elderly patients).
(For additional information see "Cisatracurium: Pediatric drug information")
Note: Dosing in obese patients should be calculated using ideal body weight (Ref):
Neuromuscular blockade:
Intermittent dosing:
Infants and Children <2 years: IV: 0.15 mg/kg/dose over 5 to 10 seconds.
Children ≥2 years and Adolescents: IV: 0.1 to 0.15 mg/kg/dose over 5 to 10 seconds (Ref).
Continuous IV infusion: Infants, Children, and Adolescents: 1 to 4 mcg/kg/minute (0.06 to 0.24 mg/kg/hour); 3.9 ± 1.3 mcg/kg/minute (0.23 ± 0.08 mg/kg/hour) was the mean infusion rate needed to maintain neuromuscular blockade in 19 children (ages 3 months to 16 years) (Ref); higher doses have been reported with prolonged infusions (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling. 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.
There are no dosage adjustments provided in the manufacturer's labeling. The time to onset of action was ~1 minute faster in liver transplant patients but was not associated with clinically significant changes in recovery time.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Effects are minimal and transient.
<1%, postmarketing, and/or case reports: Bradycardia, bronchospasm, flushing, hypotension, muscle calcification (prolonged use), myopathy (acute quadriplegic syndrome; prolonged use), pruritus, skin rash
Hypersensitivity to cisatracurium or any component of the formulation; use of the 10 mL multiple-dose vials in neonates <1 month of age and low birth-weight infants (formulation contains benzyl alcohol).
Concern related to adverse effects:
• Anaphylaxis: Severe anaphylactic reactions have been reported (some life-threatening and fatal). Appropriate emergency treatment (including epinephrine 1 mg/mL) should be immediately available during use. Use caution in patients with previous anaphylactic reactions to other neuromuscular blocking agents.
• 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.
• Residual paralysis: Has been reported. Patients with neuromuscular diseases (eg, myasthenia gravis, myasthenic syndrome) and carcinomatosis may be at increased risk; a lower maximum initial bolus dose is recommended in these patients. Reversal agents may be considered, especially in cases where residual paralysis is more likely to occur. To prevent complications from residual paralysis, extubation is recommended only after the patient has sufficiently recovered from neuromuscular blockade.
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 that may antagonize neuromuscular blockade (decreased paralysis): Respiratory alkalosis, hypercalcemia, demyelinating lesions, peripheral neuropathies, denervation, and muscle trauma may result in antagonism of neuromuscular blockade (ACCM/SCCM/ASHP [Murray 2002]; Greenberg 2013; Miller 2010; Naguib 2002).
• Conditions that may potentiate neuromuscular blockade (increased paralysis): Electrolyte abnormalities (eg, severe hypocalcemia, severe hypokalemia, hypermagnesemia), neuromuscular diseases, metabolic acidosis, 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 paralysis (Greenberg 2013).
Special populations:
• Older adult: 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. All patients should receive eye care including liberal use of lubricating drops, gel, or ointment and eyelids should remain closed during continuous neuromuscular blockade to protect against damage to the cornea (ulceration and drying).
• Experienced personnel: Should be administered by adequately trained individuals familiar with its use.
• Risk of medication errors: Accidental administration may be fatal. Confirm proper selection of intended product, store vial so the cap and ferrule are intact and the possibility of selecting the wrong product is minimized, and ensure that the intended dose is clearly labeled and communicated, when applicable.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous, as besylate:
Nimbex: 20 mg/10 mL (10 mL) [contains benzyl alcohol]
Generic: 10 mg/5 mL (5 mL); 20 mg/10 mL (10 mL); 200 mg/20 mL (20 mL)
Solution, Intravenous, as besylate [preservative free]:
Nimbex: 10 mg/5 mL (5 mL); 200 mg/20 mL (20 mL)
Generic: 10 mg/5 mL (5 mL); 200 mg/20 mL (20 mL)
Yes
Solution (Cisatracurium Besylate (PF) Intravenous)
10 mg/5 mL (per mL): $0.78 - $3.61
200 mg/20 mL (per mL): $5.64 - $17.08
Solution (Cisatracurium Besylate Intravenous)
20 mg/10 mL (per mL): $1.20 - $3.16
Solution (Nimbex Intravenous)
10 mg/5 mL (per mL): $3.76
20 mg/10 mL (per mL): $3.30
200 mg/20 mL (per mL): $17.82
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous, as besylate:
Generic: 20 mg/10 mL (10 mL)
IV: Administer IV only; do not administer IM (excessive tissue irritation). Administer undiluted as bolus injection over 5 to 10 seconds. Continuous infusion administration requires the use of an infusion pump. Do not administer with alkaline solutions simultaneously in the same IV line.
Parenteral: Administer IV only; not for IM injection due to tissue irritation.
Rapid IV injection: Administer undiluted over 5 to 10 seconds.
Continuous IV infusion: Administer via infusion pump.
IV infusion: 100 mg in 250 mL (total volume) (concentration: 400 mcg/mL) of D5W or NS
Neuromuscular blockade for endotracheal intubation, surgery, or mechanical ventilation: As an adjunct to general anesthesia, to facilitate endotracheal intubation, and to relax skeletal muscles during surgery or mechanical ventilation in adequately sedated ICU patients
Note: Neuromuscular blockade does not provide pain control, sedation, or amnestic effects. Appropriate analgesic and sedative mediations should be used before and during administration of neuromuscular blockade to achieve deep sedation.
Acute respiratory distress syndrome; Shivering due to therapeutic hypothermia following cardiac arrest
Nimbex may be confused with NovoLOG
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
According to the 2020-2021 ISMP Targeted Medication Safety Best Practices for Hospitals, neuromuscular blockers should be segregated, sequestered, and differentiated from all other medication wherever they are stored. This includes:
Only storing in places within the hospital that they are routinely used.
Placing in sealed boxes or in rapid sequence intubation kits (preferred).
Limiting availability in automated dispensing cabinets to perioperative, labor and delivery, critical care, and emergency departments only.
Placing in separate lidded containers within the pharmacy refrigerator or other isolated pharmacy storage area.
Affixing an auxiliary label to clearly communicate respiratory paralysis will occur and ventilation required on all storage bins and/or automated dispensing pockets/drawers (exception anesthesia-prepared syringes) stating one of the following:
Warning: Causes Respiratory Arrest – Patient Must Be Ventilated
Warning: Paralyzing Agent – Causes Respiratory Arrest
Warning: Causes Respiratory Paralysis – Patient Must Be Ventilated
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Acetylcholinesterase Inhibitors: May diminish the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy
Aminoglycosides: May enhance the therapeutic effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Bacitracin (Systemic): May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Botulinum Toxin-Containing Products: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Bromperidol: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Calcium Channel Blockers: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy
Capreomycin: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
CarBAMazepine: May decrease the serum concentration of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy
Cardiac Glycosides: Neuromuscular-Blocking Agents may enhance the arrhythmogenic effect of Cardiac Glycosides. Risk C: Monitor therapy
Clindamycin (Topical): May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Colistimethate: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Management: If possible, avoid concomitant use of these products. Monitor for deeper, prolonged neuromuscular-blocking effects (respiratory paralysis) in patients receiving concomitant neuromuscular-blocking agents and colistimethate. Risk D: 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. Management: If concomitant therapy is required, use the lowest dose for the shortest duration to limit the risk of myopathy or neuropathy. Monitor for new onset or worsening muscle weakness, reduction or loss of deep tendon reflexes, and peripheral sensory decriments Risk D: Consider therapy modification
CycloSPORINE (Systemic): May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: 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). Risk C: Monitor therapy
Inhalational Anesthetics: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Management: When initiating a non-depolarizing neuromuscular blocking agent (NMBA) in a patient receiving an inhalational anesthetic, initial NMBA doses should be reduced 15% to 25% and doses of continuous infusions should be reduced 30% to 60%. Risk D: Consider therapy modification
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. Risk C: 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. Risk C: Monitor therapy
Lincosamide Antibiotics: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Lithium: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Local Anesthetics: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: 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. Risk C: Monitor therapy
Magnesium Salts: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Pholcodine: May enhance the adverse/toxic effect of Neuromuscular-Blocking Agents. Specifically, anaphylaxis has been reported. Risk C: Monitor therapy
Polymyxin B: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Management: If possible, avoid concomitant use of neuromuscular-blocking agents and polymyxin B. If concomitant use cannot be avoided, monitor for deeper, prolonged neuromuscular-blocking effects (eg, respiratory paralysis) in patients receiving this combination. Risk D: Consider therapy modification
Procainamide: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
QuiNIDine: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
QuiNINE: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk X: Avoid combination
Tetracyclines: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Thiazide and Thiazide-Like Diuretics: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy
Trimebutine: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy
Vancomycin: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Following administration of atracurium, laudanosine, an active metabolite of atracurium and cisatracurium, crosses the placenta (Atherton 1999; Fodale 2002).
Recommendations for using cisatracurium for sustained neuromuscular blockade in pregnant critically ill patients are not available due to insufficient evidence (SCCM [Murray 2016]).
Use with caution in patients treated for preeclampsia/eclampsia; the action of cisatracurium may be enhanced by concomitant medications (consult drug interactions database). Preparations may contain benzyl alcohol; avoid in pregnant patients due to association with gasping syndrome in premature infants.
It is not known if cisatracurium is present in breast milk.
In general, neuromuscular blocking agents may be used in lactating patients based on their physical characteristics and poor oral bioavailability (ABM [Reece-Stremtan 2017]). Preparations may contain benzyl alcohol; avoid in lactating patients due to association with gasping syndrome in premature infants. According to the manufacturer, the decision to breastfeed should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Vital signs (heart rate, blood pressure, respiratory rate); degree of muscle paralysis (eg, presence of spontaneous movement, ventilator asynchrony, shivering, and use of a peripheral nerve stimulator with train of four monitoring along with clinical assessments)
In the ICU setting, limiting the duration of paralysis and providing a physiotherapy regimen in patients requiring continuous paralysis is suggested.
Blocks neural transmission at the myoneural junction by binding with cholinergic receptor sites
Onset of action: IV: 2 to 3 minutes
Peak effect: 3 to 5 minutes
Duration: Dose dependent, 35 to 45 minutes after a single 0.1 mg/kg dose; recovery begins in 20 to 35 minutes when anesthesia is balanced; recovery is attained in 90% of patients in 25 to 93 minutes; hypothermia may prolong the duration of action (NCS [Madden 2017])
Distribution: Vdss: 145 mL/kg (21% larger Vdss when receiving inhalational anesthetics)
Protein binding: Not studied due to rapid degradation at physiologic pH
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
Half-life elimination: 22 to 29 minutes
Excretion: Urine (95%; <10% as unchanged drug); feces (4%)
Clearance: Children: 5.89 mL/kg/minute; Adults: 4.57 mL/kg/minute
Altered kidney function: 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.
Hepatic function impairment: The times to maximum block were approximately 1 minute faster in liver transplant recipients 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.
Pediatric: Minor differences in pharmacokinetic/pharmacodynamic parameters in children resulted in a faster time to onset and a shorter duration of neuromuscular block.
Older adult: The times to maximum block were approximately 1 minute slower in elderly patients.
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