Cisatracurium Kabi

Cisatracurium Kabi

cisatracurium

Manufacturer:

Fresenius Kabi

Distributor:

Zuellig Pharma
Full Prescribing Info
Contents
Cisatracurium besylate.
Description
Each ml contains cisatracurium besylate equivalent to 2 mg cisatracurium.
Action
Pharmacology: Pharmacodynamics: Cisatracurium is a nondepolarizing skeletal muscle relaxant. Cisatracurium binds competitively to Cholinergic receptors on the motor end-plate to antagonize the action of acetylcholine, resulting in block of neuromuscular transmission. This action is antagonized by acetyl cholinesterase inhibitors, such as neostigmine.
Pharmacokinetics: Absorption: During infusion of cisatracurium peak plasma concentrations of laudanosine and the monoquaternary alcohol metabolites are approximately 6% and 11% of the parent compound, respectively.
Distribution: The volume of distribution of cisatracurium is limited by its large molecular weight and high polarity. The Vss was equal to 145 ml/kg in healthy 19-to 64-year-old surgical patients receiving opioid anesthesia. The Vss was 21% larger in similar patients receiving inhalation anesthesia.
Protein binding: The binding of cisatracurium to plasma proteins has not been successfully studied due to its rapid degradation at physiologic pH. Inhibitor of degradation requires nonphysiological conditions of temperature and pH which are associated with changes in protein binding.
Metabolism: The degradation of cisatracurium is largely independent of liver metabolism. Results from in vitro Experiments suggest the cisatracurium undergoes Hofmann elimination (a pH- and temperature-dependent chemical process) to form laudanosine and the monoquaternary acrylate metabolite. The monoquaternary acrylate undergoes hydrolysis by non-specific plasma esterases to form the monoquaternary alcohol (MQA) metabolite. The MQA metabolite can also undergo Hofmann elimination but at a much slower rate than cisatracurium. Laudanosine is further metabolized to desmethyl metabolites which are conjugated with glucuronic acid and excreted in the urine.
Organ-independent Hofmann elimination is the predominant pathway for the elimination of cisatracurium. The liver and kidney play a minor role in the elimination of cisatracurium but are primary pathways for the elimination of metabolites. Because cisatracurium is 3 times more potent than atracurium and lower dose are required, the corresponding laudanosine concentrations following cisatracurium one-third of those that would be expected following an equipotent dose of atracurium.
Elimination: Mean clearance values for cisatracurium ranged from 4.5 to 5.7 mL/min/kg in studies of healthy surgical patients. Compartmental pharmacokinetic modeling suggests that approximately 80% of the clearance is accounted for the Hofmann elimination and the remaining 20% by renal and hepatic elimination. These findings are consistent with the low magnitude of interpatient variability in clearance (16%) estimated as part of the population pharmacokinetic/pharmacodynamics analyses and with the recovery of parent and metabolites in urine. Following 14C-cisatracurium administration to 6 healthy male patients, 95% of the dose was recovered in the urine (mostly as conjugated metabolites) and 4% in the feces; less than 10% of the dose was excreted as unchanged parent drug in the urine. In 12 healthy surgical patients receiving non-radiolabeled cisatracurium who had Foley catheters placed for surgical management, approximately 15% of the dose was excreted unchanged in the urine.
Special populations: Renal function impairment: Pharmacokinetic/pharmacodynamics profile similar to that in healthy adults; concentration of metabolites may be increased after prolonged administration.
Hepatic function impairment: Minor alterations in pharmacokinetics, but no substantial differences in recovery profile. Concentration of metabolites may be increased after prolonged administration.
Pharmacokinetic/pharmacodynamics profile similar to that in healthy adults; concentration of metabolites may be increased after prolonged administration.
Elderly: The minor differences in pharmacokinetic/pharmacodynamics parameters of cisatracurium between elderly patients and young patients were not associated with clinically significant differences in the recovery profile of cisatracurium.
Indications/Uses
Cisatracurium Kabi is indicated for use during surgical procedures including cardiac surgery, other procedures and in intensive care. It is used as an adjunct to general anaesthesia, or sedation in the Intensive Care Unit (ICU), to relax skeletal muscles, and to facilitate tracheal intubation and mechanical ventilation.
Dosage/Direction for Use
Use by intravenous bolus injection: Dosage in adults: Endotracheal Intubation: The recommended intubation dose of cisatracurium for adults is 0.15 mg/kg. Endotracheal intubation can be accomplished 120 seconds after administration of Cisatracurium Kabi.
Higher doses will shorten the time to onset of neuromuscular block.
Table 1 summarises mean pharmacodynamic data when cisatracurium was administered at doses of 0.1 to 0.4 mg/kg to healthy adult patients during opioid (thiopentone/fentanyl/midazolam) or propofol anaesthesia. (See Table 1.)

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Enflurane or isoflurane anaesthesia may extend the clinically effective duration of an initial dose of cisatracurium by up to 15%.
Maintenance: Neuromuscular block can be extended with maintenance doses of cisatracurium. A dose of 0.03 mg/kg provides approximately 20 minutes of additional clinically effective neuromuscular block during opioid or propofol anaesthesia.
Successive supplementary dosing does not produce accumulation in neuromuscular blocking effect.
Spontaneous recovery: Once evidence of spontaneous recovery from neuromuscular block is present, the duration until complete reversal is independent of the cisatracurium dose administered. During opioid or propofol anaesthesia, the mean duration for recovery from 25 to 75% and from 5 to 95% is approximately 13 and 30 minutes, respectively.
Reversal: Neuromuscular block following cisatracurium administration is readily reversible with standard doses of anticholinesterase agents. The mean duration of recovery from 25 to 75% and to full clinical recovery (T4:T1 ratio ≥ 0.7) are approximately 2 and 5 minutes, respectively, following administration of the reversal agent at an average of 13% T1 recovery.
Dosage in paediatric population: Endotracheal Intubation (paediatric patients aged 1 month to 12 years): As in adults, the recommended intubation dose of cisatracurium is 0.15 mg/kg administered rapidly over 5 to 10 seconds. Endotracheal intubation can be accomplished 120 seconds after administration of cisatracurium.
In paediatric patients aged 1 month to 12 years, cisatracurium has a shorter clinically effective duration and a faster spontaneous recovery profile than those observed in adults under similar anaesthetic conditions. Small differences in the pharmacodynamic profile were observed between the age ranges 1 to 11 months and 1 to 12 years which are summarised in the following tables. (See Tables 2 and 3.)

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Click on icon to see table/diagram/image

Halothane may extend the clinically effective duration of a dose of cisatracurium by up to 20%. No information is available on the use of cisatracurium in children during isoflurane or enflurane anaesthesia. Nevertheless, these agents may also be expected to extend the clinically effective duration of a cisatracurium dose by up to 20%.
Maintenance: Neuromuscular block can be extended with maintenance doses of cisatracurium. A dose of 0.02 mg/kg provides approximately 9 minutes of additional clinically effective neuromuscular block during halothane anaesthesia. Consecutive maintenance doses do not result in progressive prolongation of effect.
Spontaneous recovery: Once recovery from neuromuscular block is underway, the rate is independent of the cisatracurium dose administered. During opioid or halothane anaesthesia, the mean duration for recovery from 25 to 75% and from 5 to 95% are approximately 11 and 28 minutes, respectively.
Reversal: Neuromuscular block following cisatracurium administration is readily reversible with standard doses of anti-cholinesterase agents. The mean duration of recovery from 25 to 75% and to full clinical recovery (T4:T1 ratio more than or equal to 0.7) are approximately 2 and 5 minutes respectively, following administration of the reversal agent at an average T1 recovery of 13%.
Use by intravenous infusion: Dosage in adults and children aged 1 month to 12 years: Maintenance of neuromuscular block may be achieved by infusion of Cisatracurium Kabi. Following evidence of spontaneous recovery, an initial infusion rate of 3 μg/kg/min (0.18 mg/kg/h) is recommended to restore 89 to 99% T1 suppression. After a primary stabilisation period of the neuromuscular block, an infusion rate of 1 to 2 μg/kg/min (0.06 to 0.12 mg/kg/h) should be adequate to maintain block in this range in most patients.
Reduction of the infusion rate by up to 40% may be required when cisatracurium is administered during isoflurane or enflurane anaesthesia.
The infusion rate depends on the concentration of cisatracurium in the infusion solution, the desired degree of neuromuscular block, and the patient's body weight. Table 4 provides guidelines for infusion of undiluted Cisatracurium Kabi. (See Table 4.)

Click on icon to see table/diagram/image

Steady rate continuous infusion is not associated with a progressive increase or decrease in neuromuscular blocking effect.
Following termination of infusion, spontaneous recovery from neuromuscular block proceeds at a rate comparable to that following administration of a single bolus injection.
Special populations: Dosage in new-born infants (aged less than 1 month): The use of cisatracurium in new-born infants is not recommended as it has not been studied in this patient population.
Dosage in elderly patients: No dosing alterations are required in elderly patients. In these patients a pharmacodynamic profile similar to young adult patients is observed but, as with other neuromuscular blocking agents, a delayed onset might occur.
Dosage in patients with renal impairment: No dosing alterations are required in patients with renal failure. In these patients a similar pharmacodynamic profile to that in patients with normal renal function is observed but a delayed onset might occur.
Dosage in patients with hepatic impairment: No dosing alterations are required in patients with end-stage liver disease. In these patients a similar pharmacodynamic profile to that in patients with normal hepatic function is observed but a slightly accelerated onset might occur.
Dosage in patients with cardiovascular disease: Cisatracurium has been used effectively to provide neuromuscular block in patients undergoing cardiac surgery. When administered by rapid bolus injection (over 5 to 10 seconds) to adult patients with serious cardiovascular disease, cisatracurium has not been associated with clinically significant cardiovascular effects at any dose studied (maximal 0.4 mg/kg (8x ED95)).
Intensive Care Unit (ICU): Cisatracurium Kabi may be administered by bolus dose and/or infusion to adult patients in the ICU.
An initial infusion rate of 3 μg/kg/min (0.18 mg/kg/h) is recommended for adult ICU patients. There may be wide inter-patient variation in dosage requirements and these may increase or decrease with time. In clinical studies the average infusion rate was 3 μg/kg/min [range 0.5 to 10.2 μg/kg/min (0.03 to 0.6 mg/kg/h)].
The mean duration to full spontaneous recovery following long-term (up to 6 days) infusion of cisatracurium in ICU patients was approximately 50 minutes.
The recovery profile after infusions of cisatracurium to ICU patients is independent of the duration of the infusion.
Mode of administration: Cisatracurium Kabi should only be administered intravenously.
Overdosage
Symptoms: Overdosage with neuromuscular blocking agents may result in neuromuscular block beyond the time needed for surgery and anesthesia.
Treatment: The primary treatment is maintenance of an airway and controlled ventilation until recovery of normal neuromuscular function is assured. Once recovery from neuromuscular block begins, further recovery may be facilitated by administration of an anticholinesterase agent (e.g. neostigmine) in conjunction with an appropriate anticholinergic agent.
Contraindications
Cisatracurium Kabi is contraindicated in patients with known hypersensitivity to cisatracurium besylate, other bis-benzylisoquinolinium agents (e.g., atracurium), or any ingredient in the formulation.
Special Precautions
Administration: Administer cisatracurium in carefully adjusted dosage by or under the supervision of experienced clinicians who are familiar with the drug’s actions and the possible complications of its use. Facilities for tracheal intubation, and maintenance of pulmonary ventilation and adequate arterial oxygenation should be available.
Malignant hyperthermia: Cisatracurium has not been studied in malignant hyperthermia-susceptible patients. In a study of malignant hyperthermia-susceptible pigs, cisatracurium did not trigger malignant hyperthermia.
Acid-base/electrolyte abnormalities: Acid-base or serum electrolyte abnormalities may potentiate or antagonize the action of cisatracurium.
Intensive Care Unit (ICU) Patients: Seizures reported rarely with other neuromuscular blocking agents (e.g. atracurium) in patients with predisposing factors (e.g. head trauma, cerebral edema, hypoxic encephalopathy, viral encephalitis, uremia) receiving continuous IV infusions for facilitation of mechanical ventilation in intensive care settings. Unclear whether laudanosine (metabolite of atracurium and cisatracurium) contributes to CNS excitation.
Neuromuscular disease: Neuromuscular-blocking agents may have a profound effect in patients with neuromuscular disease (e.g. myasthenia gravis, 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 cisatracurium 0.02 mg/kg is recommended to assess the level of neuromuscular block and to monitor dosage requirement.
Burn patients: 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.
Hypersensitivity reactions: Caution should be exercised when administering cisatracurium to patients who have shown hypersensitivity to other neuromuscular blocking agents since cross-reactivity between neuromuscular blocking agents has been reported.
Use In Pregnancy & Lactation
Pregnancy: There are no adequate and well-controlled studies of cisatracurium in pregnant women. Cisatracurium should be used during pregnancy only if the expected benefit to the mother outweighs any potential risk to the foetus.
Lactation: It is not known whether cisatracurium is excreted in human milk.
Adverse Reactions
Surgical patients: Cardiac disorders: Bradycardia.
Vascular disorders: Hypotension, flushing.
Respiratory, thoracic and mediastinal disorders: Bronchospasm.
Skin and subcutaneous tissue disorders: Rash.
Postmarketing Data: Hypersensitivity: Anaphylactic or anaphylactoid reaction.
Musculoskeletal: Muscle weakness, myophathy.
Drug Interactions
Antibiotics (e.g. aminoglycosides, clindamycin, lincomycin): Certain antibiotics may enhance the neuromuscular blocking action of cisatracurium.
Carbamazepine: The effects of long-term carbamazepine therapy on the action of cisatracurium are unknown, slightly shorter durations of neuromuscular block may be anticipated an infusion rate requirements may be higher.
Cyclosporin: Cyclosporin may enhance the neuromuscular blocking action of cisatracurium.
General anesthetics (e.g. enflurane, isoflurane): General anesthetics may potentiate the actions of cisatracurium.
Hydantoins (e.g. phenytoin): Resistance to the neuromuscular blocking agents has been demonstrated in patients administered phenytoin long term.
Ketamine: Ketamine may enhance the neuromuscular blocking action of cisatracurium.
Lithium: Lithium may enhance the neuromuscular blocking action of cisatracurium.
Local anesthetics (e.g. lidocaine): Local anesthetics may enhance the neuromuscular blocking action of cisatracurium.
Magnesium salts: Magnesium salts may enhance the neuromuscular blocking action of cisatracurium.
Quinidine: Quinidine may enhance the neuromuscular blocking action of cisatracurium.
Procainamide: Procainamide may enhance the neuromuscular blocking action of cisatracurium.
Theophyllines: Neuromuscular blocking effects of cisatracurium may be decreased by theophyllines. Cardiac arrhythmia may be occurred. Consider avoiding coadministration.
Thiazide diuretics (e.g. chlorothiazide): The neuromuscular-blocking effects of cisatracurium may be increased because of thiazide diuretic-induced hypokalemia.
Verapamil: Verapamil may enhance the neuromuscular blocking action of cisatracurium.
Storage
Store in a refrigerator at 2°C - 8°C. Do not freeze. Protect from light.
ATC Classification
M03AC11 - cisatracurium ; Belongs to the class of other quaternary ammonium-containing agents used as peripherally-acting muscle relaxants.
Presentation/Packing
Inj (amp) (clear, colourless to pale yellow or greenish yellow solution) 2 mg/mL x 5 mL x 5 x 1's.
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