Composition:
Each 1 ml solution contains 2mg cisatracurium, (equivalent to 2.68mg Cisatracurium Besylate) (10mg/5ml)
Pharmaceutical Properties:
Atracil is a muscle relaxant and cholinesterase inhibitor.
Cisatracurium is a neuromuscular blocking agent and is an intermediate duration, nondepolarizing benzylisoquinolinium skeletal muscle relaxant.
Mechanism of Action
Cisatracurium besylate binds competitively to cholinergic receptors on the motor end-plate to antagonize the action of acetylcholine, resulting in blockade of neuromuscular transmission. This action is antagonized by acetylcholinesterase inhibitors such as neostigmine.
Pharmacokinetics:
Distribution: The volume of distribution of cisatracuriumis 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.
Elimination: The liver and kidney play a minor role in the elimination of cisatracurium but are primary pathways for the elimination of metabolites. Therefore, the t½β values of metabolites (including laudanosine) are longer in patients with renal or hepatic impairment and metabolite concentrations may be higher after long-term administration.
Metabolism: The degradation of cisatracurium was largely independent of liver metabolism.
Excretion: 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.
Indications:
Atracil is indicated for use during surgical and other procedures in adults and children aged 1 month and over. Atracil is also indicated for use in adults requiring intensive care. Atracil can be 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.
Contraindications:
This medication is contraindicated If the patient is hypersensitive to Cisatracurium or Benzenesulfonic acid.
Dosage and Administration:
- Atracil is for intravenous use only.
- Use Injection only if the following are immediately available: personnel and facilities for resuscitation and life support) tracheal intubation, artificial ventilation, oxygen therapy)
Recommended Cisatracurium Besylate Injection Dose for Performing Tracheal:
Tracheal Intubation in Adults: the recommended starting weight-based dose is between 0.15mg/kg and 0.2mg/kg administered by bolus intravenous injection. Doses up to 0.4mg/kg have been safely administered by bolus intravenous injection to healthy patients and patients with serious cardiovascular disease.
Patients with Neuromuscular Disease: The maximum recommended initial bolus dose is 0.02mg/kg in patients with neuromuscular diseases (e.g., myasthenia gravis and myasthenic syndrome and carcinomatosis).
Elderly and end-stage renal disease patients: Because the maximum duration of neuromuscular blockade is approximately one minute slower in elderly patients than in younger patients, and in patients with end-stage renal disease than in those with normal renal function, consideration should be given to extending the time interval between Cisatracurium injection and tracheal intubation to at least one minute.
Tracheal intubation in pediatric patients:
Infants 1 to 23 months of age: The recommended dose Injection for intubation of pediatric patients ages 1 month to 23 months is 0.15mg/kg administered over 5 to 10 seconds.
Pediatric Patients 2 to 12 years of age: The recommended weight-based bolus dose of Injection for pediatric patients 2 to 12 years of age is 0.1 to 0.15mg/kg administered over 5 to 10 seconds.
The recommended maintenance bolus dose of Cisatracurium Besylate Injection: is 0.03 mg/kg.
Dosage in burn patients: Burn patients have been shown to develop resistance to nondepolarizing neuromuscular blocking agents; therefore, consider increasing the Cisatracurium Besylate Injection dosages for intubation and maintenance.
Dosage for Continuous Infusion
Injection may be administered by continuous infusion to adults and pediatric patients aged 2 or more years if patients have spontaneous recovery after the initial Injection bolus dose.
Rate Tables for Continuous Infusion
|
Injection Infusion Rates for Maintenance of Neuromuscular Blockade During Opioid/Nitrous Oxide/Oxygen Anesthesia with a Concentration of 0.1mg/mL |
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|
Drug Delivery Rate (mcg/Kg/min) |
|
||||
|
5 |
3 |
2 |
1.5 |
1 |
|
|
Infusion Delivery Rate (mcg/Kg/min) |
Patient Weight (kg( |
||||
|
30 |
18 |
12 |
9 |
6 |
10 |
|
135 |
81 |
54 |
41 |
27 |
45 |
|
210 |
126 |
84 |
63 |
42 |
70 |
|
300 |
180 |
120 |
90 |
60 |
100 |
|
Injection Infusion Rates for Maintenance of Neuromuscular Blockade During Opioid/Nitrous Oxide/Oxygen Anesthesia with a Concentration of 0.4mg/mL |
|||||
|
Drug Delivery Rate (mcg/Kg/min) |
|
||||
|
5 |
3 |
2 |
1.5 |
1 |
|
|
Infusion Delivery Rate (mcg/Kg/min) |
Patient Weight (kg( |
||||
|
7.5 |
4.5 |
3.0 |
2.3 |
1.5 |
10 |
|
33.8 |
20.3 |
13.5 |
10.1 |
6.8 |
45 |
|
52.5 |
31.5 |
21.0 |
15.8 |
10.5 |
70 |
|
75.0 |
45.0 |
30.0 |
22.5 |
15.0 |
100 |
Studies have shown that Cisatracurium Injection is compatible with:
• 5% Dextrose Injection
• 0.9% Sodium Chloride Injection
• 5% Dextrose and 0.9% Sodium Chloride Injection
• Sufentanil Citrate Injection
• Alfentanil Hydrochloride Injection
• Fentanyl Citrate Injection
• Midazolam Hydrochloride Injection
• Droperidol Injection
Cisatracurium Besylate Injection is not compatible with propofol Injection, ketorolac injection.
Warnings and Precautions:
Residual Paralysis:
Patients with neuromuscular diseases (e.g., myasthenia gravis and myasthenic syndrome) and carcinomatosis may be at higher risk of residual paralysis; thus, a lower maximum initial bolus is recommended in these patients.
Risk of Seizure:
Patients with renal or hepatic impairment receiving extended administration of Cisatracurium Besylate Injection may be at higher risk of seizures.
Hypersensitivity Reactions Including Anaphylaxis:
Severe hypersensitivity reactions, including fatal and life-threatening anaphylactic reactions, have been reported. There have been reports of wheezing, laryngospasm, bronchospasm, rash and itching following Cisatracurium besylate administration in pediatric patients. 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.
Malignant Hyperthermia (MH):
Cisatracurium besylate 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.
Risks due to Inadequate Anesthesia:
Neuromuscular blockade in the conscious patient can lead to distress. Use Cisatracurium Besylate Injection in the presence of appropriate sedation or general anesthesia. Monitor patients to ensure that the level of anesthesia is adequate.
Risk of death due to Medication Errors:
Administration of Cisatracurium Besylate Injection results in paralysis, which may lead to respiratory arrest and death, a progression that may be more likely to occur in a patient for whom it is not intended. Confirm proper selection of intended product and avoid confusion with other injectable solutions that are present in critical care and other clinical settings. If another healthcare provider is administering the product, ensure that the intended dose is clearly labeled and communicated.
Potentiation of Neuromuscular Blockade:
Certain drugs may enhance the neuromuscular blocking action of cisatracurium besylate including inhalational anesthetics, antibiotics, magnesium salts, lithium, local anesthetics, procainamide and quinidine. Additionally, acid-base and/or serum electrolyte abnormalities may potentiate the action of neuromuscular blocking agents. Use peripheral nerve stimulation and monitor the clinical signs of neuromuscular blockade to determine the adequacy of the level of neuromuscular blockage and the need to adjust the Cisatracurium Besylate Injection dosage.
Resistance to Neuromuscular Blockade with Certain Drugs
Shorter durations of neuromuscular block may occur and cisatracurium besylate infusion rate requirements may be higher in patients chronically administered phenytoin or carbamazepine. Use peripheral nerve stimulation and monitor the clinical signs of neuromuscular blockade to determine the adequacy of neuromuscular blockage and the need to adjust the cisatracurium besylate dosage.
Side Effects:
These events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to cisatracurium besylate: anaphylaxis, histamine release, prolonged neuromuscular block, muscle weakness, myopathy.
Drug Interactions:
- The use of succinylcholine prior to Cisatracurium Besylate Injection administration may decrease the time to onset of maximum neuromuscular blockade but has no effect on the duration of neuromuscular blockade.
- Administration of inhalational anesthetics with nitrous oxide/oxygen for greater than 30 minutes may prolong the duration of action of initial and maintenance doses of Cisatracurium Besylate Injection. This may potentiate the neuromuscular blockade.
- Antibiotics, local anesthetics, magnesium salts, procainamide, lithium, quinidin: May prolong the neuromuscular blockade action of Cisatracurium Besylate Injection
- Phenytoin and carbamazepine: May increase resistance to the neuromuscular blockade action of Cisatracurium Besylate Injection resulting in shorter durations of neuromuscular blockade and infusion rate requirements may be higher.
Pregnancy:
There are no adequate and well-controlled studies of Cisatracurium Injection in pregnant women. Cisatracurium should not be used during pregnancy.
Breast-feeding:
It is not known whether cisatracurium besylate is present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Cisatracurium Besylate Injection and any potential adverse effects on the breastfed child from Cisatracurium Besylate Injection.
Overdosage:
Over dosage with neuromuscular blocking agents may result in neuromuscular blockade beyond the time needed for surgery and anesthesia.
The primary treatment is maintenance of a patent 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 a cholinesterase inhibitor (e.g., neostigmine, edrophonium) in conjunction with an appropriate cholinergic inhibitor. Cholinesterase inhibitors should not be administered when complete neuromuscular blockade is evident or suspected because the reversal of paralysis may not be sufficient to maintain a patent airway and support an appropriate level of spontaneous ventilation.