Cisatracurium Besylate
Cisatracurium Besylate Prescribing Information
Cisatracurium Besylate Injection is indicated:
- as an adjunct to general anesthesia to facilitate tracheal intubation in adults and in pediatric patients 1 month to 12 years of age
- to provide skeletal muscle relaxation in adults during surgical procedures or during mechanical ventilation in the ICU
- to provide skeletal muscle relaxation during surgical procedures via infusion in pediatric patients 2 years and older
Cisatracurium Besylate Injection is not recommended for rapid sequence endotracheal intubation due to the time required for its onset of action.
Cisatracurium Besylate Injection is compatible and may be administered with the following solutions through Y-site administration:
- 5% Dextrose Injection, USP
- 0.9% Sodium Chloride Injection, USP
- 5% Dextrose and 0.9% Sodium Chloride Injection, USP
- Sufentanil Citrate Injection, diluted as directed
- Alfentanil Hydrochloride Injection, diluted as directed
- Fentanyl Citrate Injection, diluted as directed
- Midazolam Hydrochloride Injection, diluted as directed
- Droperidol Injection, diluted as directed
Cisatracurium Besylate Injection is acidic (pH = 3.25 to 3.65) and may not be compatible with alkaline solution having a pH greater than 8.5 (e.g., barbiturate solutions). Therefore, do not administer Cisatracurium Besylate Injection and alkaline solutions simultaneously in the same intravenous line.
Cisatracurium Besylate Injection is not compatible with propofol injection or ketorolac injection for Y-site administration. Compatibility studies with other parenteral products have not been conducted.
Cisatracurium Besylate Injection, USP is available as a colorless to slightly yellow or greenish-yellow solution in the following strength:
- 20 mg of cisatracurium per 10 mL (2 mg/mL) in multiple-dose vials (equivalent to 2.68 mg/mL cisatracurium besylate) with benzyl alcohol as a preservative.
Profound and prolonged neuromuscular blockade may occur in patients with neuromuscular diseases (e.g., myasthenia gravis and myasthenic syndrome) and carcinomatosis. Therefore, a lower maximum initial bolus is recommended in these patients
Prior to selecting the initial Cisatracurium Besylate Injection bolus dose, consider the desired time to tracheal intubation and the anticipated length of surgery, factors affecting time to onset of complete neuromuscular block such as age and renal function, and factors that may influence intubation conditions such as the presence of co-induction agents (e.g., fentanyl and midazolam) and the depth of anesthesia.
In conjunction with a propofol/nitrous oxide/oxygen induction-intubation technique or a thiopental/nitrous oxide/oxygen induction-intubation technique, the recommended starting weight-based dose of Cisatracurium Besylate Injection is between 0.15 mg/kg and 0.2 mg/kg administered by bolus intravenous injection. Doses up to 0.4 mg/kg have been safely administered by bolus intravenous injection to healthy patients and patients with serious cardiovascular disease
The maximum recommended initial bolus dose of Cisatracurium Besylate Injection is 0.02 mg/kg in patients with neuromuscular diseases (e.g., myasthenia gravis and myasthenic syndrome and carcinomatosis)
Because the time to maximum neuromuscular blockade is approximately 1 minute slower in geriatric patients compared to younger patients (and in patients with end-stage renal disease than in patients with normal renal function), consider extending the interval between administering Cisatracurium Besylate Injection and attempting intubation by at least 1 minute to achieve adequate intubation conditions in geriatric patients and patients with end-stage renal disease. A peripheral nerve stimulator should be used to determine the adequacy of muscle relaxation for the purposes of intubation and the timing and amounts of subsequent doses
The recommended dose of Cisatracurium Besylate Injection for intubation of pediatric patients ages 1 month to 23 months is 0.15 mg/kg administered over 5 to 10 seconds. When administered during stable opioid/nitrous oxide/oxygen anesthesia, 0.15 mg/kg of Cisatracurium Besylate Injection produced maximum neuromuscular blockade in about 2 minutes (range: 1.3 to 4.3 minutes) with a clinically effective block (time to 25% recovery) for about 43 minutes (range: 34 to 58 minutes)
The recommended weight-based bolus dose of Cisatracurium Besylate Injection for pediatric patients 2 to 12 years of age is 0.1 to 0.15 mg/kg administered over 5 to 10 seconds. When administered during stable opioid/nitrous oxide/oxygen anesthesia, 0.1 mg/kg Cisatracurium Besylate Injection produced maximum neuromuscular blockade in an average of 2.8 minutes (range: 1.8 to 6.7 minutes) with a clinically effective block (time to 25% recovery) for 28 minutes (range: 21 to 38 minutes). When administered during stable opioid/nitrous oxide/oxygen anesthesia, 0.15 mg/kg Cisatracurium Besylate Injection produced maximum neuromuscular blockade in an average of about 3 minutes (range: 1.5 to 8 minutes) with a clinically effective block for 36 minutes (range: 29 to 46 minutes)
- Cisatracurium Besylate Injection is contraindicated in patients with known hypersensitivity to cisatracurium. Severe anaphylactic reactions to Cisatracurium Besylate Injection have been reported[see Warnings and Precautions (.)]
5.4 Hypersensitivity Reactions Including AnaphylaxisSevere hypersensitivity reactions, including fatal and life-threatening anaphylactic reactions, have been reported
[see Contraindications ]. There have been reports of wheezing, laryngospasm, bronchospasm, rash and itching following Cisatracurium Besylate Injection administration in pediatric patients. Due to the potential severity of these reactions, appropriate precautions such as the immediate availability of appropriate emergency treatment should be taken. Precautions should also be taken in those patients who have had previous anaphylactic reactions to other neuromuscular blocking agents since cross-reactivity between neuromuscular blocking agents, both depolarizing and non-depolarizing, has been reported. - The use of 10 mL Cisatracurium Besylate Injection multiple-dose vials is contraindicated for use in pediatric patients less than 1 month of age and low birth-weight infants because the formulation contains benzyl alcohol[see Warnings and Precautions (.) and Use in Specific Populations (
5.2 Risk of Serious Adverse Reactions in Infants due to Benzyl Alcohol Preservative in 10 mL Multiple-Dose VialsSerious and fatal adverse reactions including “gasping syndrome” can occur in neonates and infants treated with benzyl alcohol-preserved drugs, including Cisatracurium Besylate Injection (10 mL multiple-dose vials). This warning is not applicable to the 5 mL and 20 mL Cisatracurium Besylate Injection single-dose vials because these vials do not contain benzyl alcohol. The “gasping syndrome” is characterized by central nervous system depression, metabolic acidosis, and gasping respirations.
When prescribing the 10 mL multiple-dose Cisatracurium Besylate Injection vials in infants consider the combined daily metabolic load of benzyl alcohol from all sources including Cisatracurium Besylate Injection (multiple-dose vials contain 9 mg of benzyl alcohol per mL) and other drugs containing benzyl alcohol. The minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known
[see Use in Specific Populations ].The use of 10 mL Cisatracurium Besylate Injection multiple-dose vials is contraindicated in pediatric patients less than 1 month of age and low birth-weight infants because these patients are more likely to develop benzyl alcohol toxicity
[see Contraindications ].)]8.4 Pediatric UseThe safety and effectiveness of Cisatracurium Besylate Injection as an adjunct to general anesthesia to facilitate tracheal intubation, and to provide skeletal muscle relaxation during surgery in pediatric patients 1 month through 12 years of age were established from three studies in pediatric patients
[see Dosing and Administration and Clinical Studies ]. The three open-label studies are summarized below.The safety and effectiveness of Cisatracurium Besylate Injection have not been established in pediatric patients less than 1 month of age.
Tracheal IntubationA study of 0.15 mg/kg Cisatracurium Besylate Injection evaluated 230 pediatric patients (ages 1 month to 12 years). Excellent or good intubating conditions were produced 120 seconds following 0.15 mg/kg of Cisatracurium Besylate Injection in 88 of 90 of patients induced with halothane and in 85 of 90 of patients induced with thiopentone and fentanyl. The study also evaluated 50 pediatric patients during opioid anesthesia, with maximum neuromuscular blockade achieved in an average of about 3 minutes and a clinically effective block for 36 minutes in patients ages 2 to 12 years, and maximum neuromuscular block in about 2 minutes and a clinically effective block for about 43 minutes in infants 1 to 23 months
[see Clinical Studies ].In a study of 0.1 mg/kg Cisatracurium Besylate Injection administered in 16 pediatric patients (ages 2 to 12 years) during opioid/nitrous oxide/oxygen anesthesia, maximum neuromuscular blockade was achieved in an average of 2.8 minutes with a clinically effective block for 28 minutes
[see Clinical Studies ].Skeletal Muscle Relaxation During SurgeryIn a study of Cisatracurium Besylate Injection administered during halothane/nitrous oxide/oxygen anesthesia, 18 pediatric patients (ages 2 to 12 years) were scheduled for surgical procedures that required neuromuscular block for 60 minutes or longer. The average duration of continuous infusion was 62.8 minutes (range: 17 to 145 minutes). The overall mean infusion rate for 9 patients whose infusion was 45 minutes or longer was 1.7 mcg/kg/minute (range: 1.19 to 2.14 mcg/kg/minute).
Serious Adverse Reactions in Infants Due to Benzyl Alcohol Preservative in 10 mL Multiple-Dose VialsSerious adverse reactions including fatal reactions and the “gasping syndrome” occurred in premature neonates and infants in the neonatal intensive care unit who received drugs containing benzyl alcohol as a preservative. In these cases, benzyl alcohol dosages of 99 to 234 mg/kg/day produced high levels of benzyl alcohol and its metabolites in the blood and urine (blood levels of benzyl alcohol were 0.61 to 1.378 mmol/L). Additional 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 may be more likely to develop these reactions because they may be less able to metabolize benzyl alcohol.
When prescribing the 10 mL multiple-dose Cisatracurium Besylate Injection vials in infants consider the combined daily metabolic load of benzyl alcohol from all sources including Cisatracurium Besylate Injection (multiple-dose vials contain 9 mg of benzyl alcohol per mL) and other drugs containing benzyl alcohol. The minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known
[see Warnings and Precautions ]. This warning is not applicable to the 5 mL and 20 mL Cisatracurium Besylate Injection single-dose vials because these vials do not contain benzyl alcohol.The use of 10 mL Cisatracurium Besylate Injection multiple-dose vials is contraindicated in pediatric patients less than 1 month of age and low birth-weight infants because these patients are more likely to develop benzyl alcohol toxicity.
Cisatracurium Besylate Injection has not been studied in MH-susceptible patients. Because MH can develop in the absence of established triggering agents, the clinician should be prepared to recognize and treat MH in any patient undergoing general anesthesia.