Nimbex (cisatracurium besylate)

Dosage of cisatracurium besylate is expressed in terms of cisatracurium.

Dosage of cisatracurium must be carefully adjusted according to individual requirements and response. The use of a peripheral nerve stimulator is recommended to accurately monitor the degree of muscle relaxation, determine the need for additional doses, determine the adequacy of spontaneous recovery or antagonism, and minimize the complications of overdosage if additional doses are administered.

Cisatracurium is administered IV only.

Commercially available 20-mL single-dose vials of cisatracurium besylate containing 10 mg/mL are intended for intensive care unit (ICU) use only.

There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Neuromuscular Blocking Agents/General Anesthetics (INHL)

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: General anesthetics enhance the pharmacologic effects of nondepolarizing muscle relaxants.

CLINICAL EFFECTS: May see an increase in the neuromuscular blocking effects of the nondepolarizing muscle relaxant including respiratory depression, bradycardia, hypotension, flushing, or muscle weakness.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: It may be necessary to decrease the dose of the nondepolarizing muscle relaxant. Monitor neuromuscular function and adjust the dose of the nondepolarizing muscle relaxant accordingly.

DISCUSSION: Concomitant administration of general anesthetics and nondepolarizing muscle relaxants has been shown to produce synergistic neuromuscular blocking effects of nondepolarizing muscle relaxants.

Neuromuscular Blocking Agents/Misc Antibiotics

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Aminoglycosides, bacitracin, clindamycin, lincomycin, and polymyxins may enhance the pharmacologic effects of neuromuscular blocking agents.

CLINICAL EFFECTS: May see an increase in the pharmacologic effects of neuromuscular blocking agents, including prolonged respiratory depression and apnea.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: If it is necessary to administer these drugs concurrently, do so with extreme caution. Monitor neuromuscular function and adjust the dose of the neuromuscular blocking agent accordingly.

DISCUSSION: Concomitant administration of aminoglycosides, bacitracin, clindamycin, lincomycin, and polymixins with neuromuscular blocking agents has been shown to produce synergism of the effects on skeletal muscles. Concurrent administration of these drugs has been associated with prolonged respiratory depression, respiratory paralysis, and fatal apnea. The interaction usually occurs when the antibiotic is given prior to or concurrently with the neuromuscular blocking drug, but it may also occur when given after administration. Any antibiotic dosage or route of administration may produce respiratory depression.

Neuromuscular Blocking Agents/Quinine Derivatives

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Synergistic or additive pharmacologic activity.

CLINICAL EFFECTS: May see an increase in the neuromuscular blocking effects, including profound sedation, respiratory depression, coma, and/or death.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Avoid concurrent administration of neuromuscular blocking agents and quinine derivatives during the first several hours of postoperative period. If administered, respiratory support may be needed. If concurrent use is necessary, monitor patients for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.

DISCUSSION: Administration of quinidine during the immediate postoperative period has been associated with respiratory paralysis and apnea.

Neuromuscular Blocking Agents/Verapamil

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Unknown.

CLINICAL EFFECTS: The neuromuscular blocking effect of nondepolarizing muscle relaxants may be extended, producing profound sedation, respiratory depression, coma, and/or death.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: If possible, avoid administration of nondepolarizing neuromuscular blocking agents to patients receiving verapamil. When both drugs must be given, carefully monitor respiratory function to avoid prolonged neuromuscular blockade. If needed, blockade may be reversed by giving edrophonium. If concurrent use is necessary, monitor patients for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.

DISCUSSION: Patients receiving verapamil have experienced prolonged skeletal muscle paralysis after administration of usual therapeutic doses of a nondepolarizing neuromuscular blocking agent. While muscle paralysis was unresponsive to treatment with neostigmine, reversal of blockade has been achieved by administration of edrophonium.

Moderate Interaction: Assess the risk to the patient and take action as needed.

Anesthesia Agents/Glp-1 Receptor Agonists

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: GLP-1 receptor agonists can cause delayed gastric emptying.(1,2)

CLINICAL EFFECTS: Gastric contents may remain in the stomach after preoperative fasting, which could increase the risk of regurgitation and aspiration.(1,2)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The American Society of Anesthesiologists (ASA) recommends the following for patients receiving elective procedures: - For patients on daily dosing, consider holding GLP-1 agonists on the day of the procedure. For patients on weekly dosing, consider holding GLP-1 agonists a week prior to the procedure. - Consult an endocrinologist for patients taking GLP-1 agonists for diabetes management if the GLP-1 agonist is held longer than the dosing schedule to avoid hyperglycemia. - For patients requiring urgent or emergent procedures, proceed and treat the patient as 'full stomach.'(3)

DISCUSSION: In one case report, a 31-year-old patient taking semaglutide followed preoperative fasting guidelines but food residue was discovered upon endoscopy, leading to cancellation of the surgical procedure.(4) In a case report, a semaglutide-treated patient experienced regurgitation upon induction of general anesthesia despite a 20 hour preoperative fasting period. The patient received semaglutide two days before the scheduled procedure.(5) A case report of a 42-year-old patient after fasting for 18 hours showed substantial gastric content upon endoscopy. The patient experienced intraoperative pulmonary aspiration of gastric contents which were suctioned from the trachea and bronchi using bronchoscopy.(6)

Neuromuscular Blocking Agents/Lincosamides

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Lincosamides appear to augment the neuromuscular blocking effects of nondepolarizing muscle relaxants.

CLINICAL EFFECTS: The effects of nondepolarizing neuromuscular relaxants may be prolonged leading to profound sedation, respiratory depression, coma, and/or death.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Monitor respiratory function of the patient and provide the necessary support. In patients who have received nondepolarizing muscle relaxants, avoid use of lincosamides in the recovery room. If concurrent use is necessary, monitor patients for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.

DISCUSSION: Lincomycin has been reported to augment the neuromuscular blocking effect of pancuronium in seven anesthetized patients. The effect was readily antagonized by neostigmine administration. In a case report, clindamycin produced prolonged neuromuscular blockade in a patient who had received pancuronium. Neostigmine was ineffective in antagonizing the blockade.

Neuromuscular Blocking Agents/Polypeptide Antibiotics

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Synergistic pharmacologic activity. Polymyxin B affects neuromuscular transmission by blocking acetylcholine receptors. Its action is thus post-synaptic and the neuromuscular block has no antagonists. Polymyxin B causes neostigmine resistance to d-tubocurarine blockade and calcium resistance to the blockade evoked by aminoglycoside antibiotics (1,2,3,4). A pre-synaptic mechanism may also be involved with decreased release of acetylcholine.

CLINICAL EFFECTS: May see an increase in the neuromuscular blocking effects, including profound sedation, respiratory depression, coma, and/or death.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: If it is necessary to administer these drugs concurrently, do so with extreme caution. Monitor neuromuscular function and adjust the dose of the neuromuscular blocking agent accordingly. If concurrent use is necessary, monitor patients for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.

DISCUSSION: Concomitant administration of polypeptide antibiotics and neuromuscular blocking agents has been shown to produce synergism of the effects on skeletal muscles. Concurrent administration of these drugs has been associated with prolonged respiratory depression, respiratory paralysis, and apnea. This interaction has been documented with colistimethate, polymyxin B, bacitracin, and vancomycin.

Neuromuscular Blocking Agents/Trimethaphan

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Additive pharmacologic effects.

CLINICAL EFFECTS: May see an increase in the neuromuscular blocking effects, including profound sedation, respiratory depression, coma, and/or death.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: If it is necessary to administer these drugs concurrently, do so with extreme caution. Monitor neuromuscular function and adjust the dose of the neuromuscular blocking agent accordingly. If concurrent use is necessary, monitor patients for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.

DISCUSSION: Available data indicate that the neuromuscular blocking effects of tubocurarine and trimethaphan may be additive.

Nondepolarizing Muscle Relaxants/Magnesium Salts, Injectable

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Magnesium may reduce postjunctional membrane neuromuscular blocking action of nondepolarizing muscle relaxants. Parenterally administered magnesium may potentiate the effects of the nondepolarizing muscle relaxants.

CLINICAL EFFECTS: Increased neuromuscular blockade with profound sedation, respiratory depression, coma, and/or death.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Monitor respiratory function when parenteral magnesium and nondepolarizing muscle relaxants are administered concurrently. Adjust the dose of the neuromuscular blocking agent accordingly. If concurrent use is necessary, monitor patients for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.

DISCUSSION: The effects of nondepolarizing muscle relaxants have been reported to be increased in laboratory animals and in humans by concomitant administration of magnesium sulfate. Respiratory depression has been reported.

Nondepolarizing Muscle Relaxants/Piperacillin

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Piperacillin may prolong the neuromuscular blockade of the nondepolarizing muscle relaxants.(1,2)

CLINICAL EFFECTS: Concurrent use of nondepolarizing muscle relaxants and piperacillin may result in prolonged neuromuscular blockade including profound sedation, respiratory depression, coma, and/or death.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients should be monitored for increased or unexpected prolongation of neuromuscular blockade when using piperacillin with nondepolarizing muscle relaxants. Assure monitoring protocols are in place for patients receiving neuromuscular blocking agents. If concurrent use is necessary, monitor patients for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.

DISCUSSION: Concurrent use of nondepolarizing muscle relaxants and piperacillin may result in increased or prolonged neuromuscular blockage.(1,2) If these agents are used together, patients should be monitored closely for increased neuromuscular blockage.

Select Neuromuscular Blocking Agents/Hydantoins

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: It has been suggested that phenytoin increases end-plate anticholinesterase activity, resulting in higher acetylcholine concentration at the neuromuscular junction.(1)

CLINICAL EFFECTS: A higher plasma concentration of the neuromuscular blocking agent was required to effect a given level of neuromuscular blockade in patients receiving phenytoin.(2,3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients receiving hydantoin anticonvulsants should be monitored for a decreased response to the neuromuscular blocking agent. The dose of the neuromuscular blocking agent may need to be increased and/or given more frequently.(9)

DISCUSSION: In a study, patients receiving phenytoin were administered metocurine, attained 83% of maximum neuromuscular blockade compared with 98% in the control group.(1) In another study, patients maintained on phenytoin for more than one week had a significantly higher pancuronium requirement than those patients not receiving phenytoin.(1) In two separate case reports, patients maintained on phenytoin demonstrated a resistance to pancuronium and a decreased duration of neuromuscular blockade.(3,4) In a study, patients maintained on phenytoin and receiving vecuronium had a significantly shorter total duration and effect of neuromuscular blockade compared to those patients not receiving phenytoin.(5) In contrast, neither the effect nor duration of atracurium's neuromuscular blockade was affected by phenytoin.(5) Two in vitro studies showed that the neuromuscular blockade of curare and tubocurarine was potentiated by the use of phenytoin.(6,7) Ten children received a bolus dose of vecuronium 0.15mg/Kg while on phenytoin and showed a significantly increased clearance of vecuronium compared to the control group, 15.1 and 9.0 ml/Kg/min, respectively.(8) In a case report, a 58 year-old male previously stabilized on phenytoin (400 mg daily) was given an injection of vecuronium (8 mg) to induce muscle blockade during bowel surgery. While monitoring the effectiveness of vecuronium only 75% twitch height blockade was noted after seven minutes. The medication, due to its short duration and impaired effectiveness, had to be given more frequently throughout the surgery in order to maintain adequate muscle block.(9) A separate case report records a decreased response to pancuronium in a 15 year-old male, previously stabilized on phenytoin (350 mg daily), while undergoing surgery to remove a parietal tumor. Pancuronium (0.7 mg/kg) was given as a relaxant during the surgery and monitored using the train-of-four method. Intermittent doses of pancuronium (0.17 mg/kg) were given for the first hour of surgery without successful blockade apparent by the return of all four twitches within ten minutes of each dose. A second attempt at muscular blockade was made with continuous infusion atracurium (0.26-0.55 mg/kg/hour) for the duration of the surgery. Only 16 minutes after stopping the infusion, all four twitches were visible.(10)

*Known hypersensitivity to cisatracurium or any of its components.

*Multiple-dose vials of cisatracurium containing benzyl alcohol are contraindicated in pediatric patients <1 month of age and low birth-weight infants.

There are no contraindication contraindications for this drug.

• Malignant hyperthermia

• Myasthenia gravis
• Pulmonary disease

The most common adverse reactions (occurring in 0.1-0.4% of patients receiving cisatracurium besylate in clinical trials) were bradycardia, hypotension, flushing, bronchospasm, and rash.

Less Frequent

• Bradycardia
• Bronchospastic pulmonary disease
• Hypotension
• Skin rash

Rare or Very Rare

• Anaphylaxis
• Seizure disorder

Less Frequent

• Flushing

Rare or Very Rare

• Muscle weakness
• Myopathy

No enhanced messaging available.

Safety and efficacy of cisatracurium have not been established in neonates (younger than 1 month of age).

Safety and efficacy of cisatracurium as an adjunct to general anesthesia to facilitate tracheal intubation and to provide skeletal muscle relaxation during surgery in pediatric patients 1 month to 12 years of age were established in 3 pediatric studies.

The 10-mL multiple-dose vials of cisatracurium besylate contain benzyl alcohol as a preservative. Serious and fatal adverse reactions, including ''gasping syndrome,'' can occur in neonates and infants treated with benzyl alcohol-preserved drugs. In reported cases of ''gasping syndrome,'' benzyl alcohol dosages of 99-234 mg/kg/day produced high levels of benzyl alcohol and its metabolites in the blood and urine; adverse reactions included gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. Preterm, low birth-weight infants are more likely to develop these reactions because they are less able to metabolize benzyl alcohol.

Use of the 10-mL multiple-dose vials is contraindicated in pediatric patients <1 month of age and in low birth-weight infants. When prescribing the 10 mL multiple-dose vials, consider the combined daily metabolic load of benzyl alcohol from all sources (multiple-dose vials of cisatracurium besylate contain 9 mg of benzyl alcohol per mL). The minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known. The 20 mL and 5 mL single-dose vials of cisatracurium besylate do not contain benzyl alcohol.

Pediatric patients may exhibit faster clearance of cisatracurium than adults. Onset of the drug is faster and duration is shorter in pediatric patients compared with adults.

There are no clinical trial data available to evaluate the risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes with cisatracurium besylate during pregnancy. No evidence of fetal harm was observed when cisatracurium was administered to pregnant rats during the period of organogenesis at 0.8 times the human exposure with a starting IV bolus dose of 0.2 mg/kg.

The 10-mL multiple-dose vial of cisatracurium besylate contains benzyl alcohol. If cisatracurium besylate is needed during pregnancy, consider using the 5-mL or 20-mL single-dose vials, which do not contain a preservative. Because benzyl alcohol is rapidly metabolized in pregnant women, benzyl alcohol exposure in the fetus is unlikely. However, adverse reactions have occurred in premature neonates and low birth-weight infants who received IV benzyl alcohol-containing drugs.

The action of neuromuscular blocking agents may be enhanced by magnesium salts administered for the management of preeclampsia or eclampsia.

It is not known whether cisatracurium is distributed into human milk. The effects on the breast-fed child and on milk production are also unknown. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for the drug and any potential adverse effects on the breast-fed child from the drug or from the underlying maternal condition.

The 10-mL multiple-dose vial of cisatracurium besylate contains benzyl alcohol. If cisatracurium besylate is needed during lactation, consider using the 5-mL or 20-mL single-dose vials, which do not contain a preservative. Because benzyl alcohol is rapidly metabolized in lactating women, benzyl alcohol exposure in the breast-fed infant is unlikely. However, adverse reactions have occurred in premature neonates and low birth-weight infants who received IV benzyl alcohol-containing drugs.

Since onset of complete neuromuscular blockade may be slower in geriatric patients, it may be necessary to extend the interval between administration of cisatracurium and the intubation attempt in such patients.

Of the 135 patients in clinical studies of cisatracurium besylate, 57, 63, and 15 patients were 65-70 years of age, 70-80 years of age, and >80 years of age, respectively. The geriatric population included a subset of patients with significant cardiovascular disease. No overall differences in safety and efficacy have been observed in geriatric patients relative to younger adults, but increased sensitivity of some older patients cannot be ruled out.

Because the time to maximum neuromuscular blockade is approximately 1 minute slower in geriatric patients compared to younger patients, consider extending the interval between cisatracurium administration and attempting intubation by at least 1 minute to achieve adequate intubation conditions. Minor alterations in cisatracurium pharmacokinetics have been observed in geriatric patients compared with younger individuals; however, these changes were not associated with substantial differences in recovery profile.

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