Cisatracurium Besylate

Cisatracurium is an intermediate-onset/intermediate-duration neuromuscular blocking agent indicated for inpatients and outpatients as an adjunct to general anesthesia, to facilitate tracheal intubation, and to provide skeletal muscle relaxation during surgery or mechanical ventilation in the ICU

Adults: Initial Doses: One of two intubating doses of Cisatracurium may be chosen, based on the desired time to tracheal intubation and the anticipated length of surgery. In addition to the dose of neuromuscular blocking agent, the presence of co-induction agents (e.g., fentanyl and midazolam) and the depth of anesthesia are factors that can influence intubation conditions. Doses of 0.15 (3 × ED95 ) and 0.20 (4 × ED95 ) mg/kg Cisatracurium, as components of a propofol/nitrous oxide/oxygen induction-intubation technique, may produce generally GOOD or EXCELLENT conditions for intubation in 2.0 and 1.5 minutes, respectively. Similar intubation conditions may be expected when these doses of Cisatracurium are administered as components of a thiopental/nitrous oxide/oxygen induction-intubation technique. In two intubation studies using thiopental or propofol and midazolam and fentanyl as co-induction agents, EXCELLENT intubation conditions were most frequently achieved with the 0.2 mg/kg compared to 0.15 mg/kg dose of cisatracurium. The clinically effective durations of action for 0.15 and 0.20 mg/kg Cisatracurium during propofol anesthesia are 55 minutes (range: 44 to 74 minutes) and 61 minutes (range: 41 to 81 minutes), respectively. Lower doses may result in a longer time for the development of satisfactory intubation conditions. Doses up to 8 × ED95 Cisatracurium have been safely administered to healthy adult patients and patients with serious cardiovascular disease. These larger doses are associated with longer clinically effective durations of action.

Children: Initial Doses: The recommended dose of Cisatracurium for children 2 to 12 years of age is 0.10-0.15 mg/kg administered over 5 to 10 seconds during either halothane or opioid anesthesia. When administered during stable opioid/nitrous oxide/oxygen anesthesia, 0.10 mg/kg Cisatracurium produces maximum neuromuscular block in an average of 2.8 minutes (range: 1.8 to 6.7 minutes) and clinically effective block for 28 minutes (range: 21 to 38 minutes). When administered during stable opioid/nitrous oxide/oxygen anesthesia, 0.15 mg/kg Cisatracurium produces maximum neuromuscular block in about 3.0 minutes (range: 1.5 to 8.0 minutes) and clinically effective block (time to 25% recovery) for 36 minutes (range: 29 to 46 minutes).

Infants: Initial Doses: The recommended dose of Cisatracurium for intubation of infants 1 month to 23 months is 0.15 mg/kg administered over 5 to 10 seconds during either halothane or opioid anesthesia. When administered during stable opioid/nitrous oxide/oxygen anesthesia, 0.15 mg/kg Cisatracurium produces maximum neuromuscular block in about 2.0 minutes (range: 1.3 to 3.4 minutes) and clinically effective block (time to 25% recovery) for about 43 minutes (range: 34 to 58 minutes).

Cisatracurium has been used safely following varying degrees of recovery from succinylcholine-induced neuromuscular block. Administration of 0.1 mg/kg (2 × ED95 ) Cisatracurium at 10% or 95% recovery following an intubating dose of succinylcholine (1 mg/kg) produced ≥ 95% neuromuscular block. The time to onset of maximum block following Cisatracurium is approximately 2 minutes faster with prior administration of succinylcholine. Prior administration of succinylcholine had no effect on the duration of neuromuscular block following initial or maintenance bolus doses of Cisatracurium. Infusion requirements of Cisatracurium in patients administered succinylcholine prior to infusions of Cisatracurium were comparable to or slightly greater than when succinylcholine was not administered.

The use of Cisatracurium before succinylcholine to attenuate some of the side effects of succinylcholine has not been studied. Although not studied systematically in clinical trials, no drug interactions were observed when vecuronium, pancuronium, or atracurium were administered following varying degrees of recovery from single doses or infusions of Cisatracurium. Isoflurane or enflurane administered with nitrous oxide/oxygen to achieve 1.25 MAC may prolong the clinically effective duration of action of initial and maintenance doses of Cisatracurium and decrease the required infusion rate of Cisatracurium. The magnitude of these effects may depend on the duration of administration of the volatile agents. Fifteen to 30 minutes of exposure to 1.25 MAC isoflurane or enflurane had minimal effects on the duration of action of initial doses of Cisatracurium and therefore, no adjustment to the initial dose should be necessary when Cisatracurium is administered shortly after initiation of volatile agents. In long surgical procedures during enflurane or isoflurane anesthesia, less frequent maintenance dosing, lower maintenance doses, or reduced infusion rates of Cisatracurium may be necessary. The average infusion rate requirement may be decreased by as much as 30% to 40%. In clinical studies propofol had no effect on the duration of action or dosing requirements for Cisatracurium. Other drugs which may enhance the neuromuscular blocking action of nondepolarizing agents such as Cisatracurium include certain antibiotics (e.g., aminoglycosides, tetracyclines, bacitracin, polymyxins, lincomycin, clindamycin, colistin, and sodium colistemethate), magnesium salts, lithium, local anesthetics, procainamide, and quinidine. Resistance to the neuromuscular blocking action of nondepolarizing neuromuscular blocking agents has been demonstrated in patients chronically administered phenytoin or carbamazepine. While the effects of chronic phenytoin or carbamazepine therapy on the action of Cisatracurium are unknown, slightly shorter durations of neuromuscular block may be anticipated and infusion rate requirements may be higher.

Cisatracurium is contraindicated in patients with known hypersensitivity to the product and its components. The 10 mL multiple-dose vials of Cisatracurium is contraindicated for use in premature infants because the formulation contains benzyl alcohol.

Like all medicines, Cisatracurium Injection can cause side effects, although not everybody gets them. If you get any side effects, talk to your doctor, nurse or pharmacist. This includes any possible side effects not listed in this leaflet.

Allergic reactions (affects less than 1 in 10,000 people)

• sudden wheeziness, chest pain or chest tightness
• swelling of your eyelids, face, lips, mouth or tongue
• a lumpy skin rash anywhere on your body
• a collapse and shock.

Common (affects less than 1 in 10 people)

• decrease in heart rate
• decrease in blood pressure.

Uncommon (affects less than 1 in 100 people)

• a rash or redness of your skin
• wheezing or coughing.

Very rare (affects less than 1 in 10,000 people)

• weak or aching muscles.

Pregnancy Category B. It is not known whether cisatracurium besylate is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised following administration of Cisatracurium Besylate to a nursing woman.

Because of its intermediate onset of action, Cisatracurium is not recommended for rapid sequence endotracheal intubation. Recommended doses of Cisatracurium have no clinically significant effects on heart rate; therefore, Cisatracurium will not counteract the bradycardia produced by many anesthetic agents or by vagal stimulation. Neuromuscular blocking agents may have a profound effect in patients with neuromuscular diseases (e.g., myasthenia gravis and the myasthenic syndrome). In these and other conditions in which prolonged neuromuscular block is a possibility (e.g., carcinomatosis), the use of a peripheral nerve stimulator and a dose of not more than 0.02 mg/kg Cisatracurium is recommended to assess the level of neuromuscular block and to monitor dosage requirements. Patients with burns have been shown to develop resistance to nondepolarizing neuromuscular blocking agents, including atracurium. The extent of altered response depends upon the size of the burn and the time elapsed since the burn injury. Cisatracurium has not been studied in patients with burns; however, based on its structural similarity to atracurium, the possibility of increased dosing requirements and shortened duration of action must be considered if Cisatracurium is administered to burn patients. Patients with hemiparesis or paraparesis also may demonstrate resistance to nondepolarizing muscle relaxants in the affected limbs. To avoid inaccurate dosing, neuromuscular monitoring should be performed on a non-paretic limb. Acid-base and/or serum electrolyte abnormalities may potentiate or antagonize the action of neuromuscular blocking agents. No data are available to support the use of Cisatracurium by intramuscular injection.

Keep this medicine out of sight and reach of children. Do not use this medicine after the expiry date which is stated on the label and the carton after "Exp". The expiry date refers to the last day of that month. Store in a refrigerator (2°C - 8°C). Do not freeze. Keep the ampoules in the outer carton in order to protect from light.