Atracurium Besilate Injection 25 mg/2.5 ml, each ml contains : Atracurium besilate 10 mg.
Atracurium Besilate contains Atracurium besilate as an active ingredient is available in 25 mg/2.5 ml and 50 mg/5 ml injection.
Atracurium Besilate is a highly selective, competitive or non-depolarizing neuromuscular blocking agent which is used as an adjunct to general anesthesia to enable tracheal intubation to be performed and to relax skeletal muscles during surgery or controlled ventilation and to facilitate mechanical ventilation in Intensive Care Unit (ICU) patients.
DOSAGE AND ADMINISTRATIONS :
IN COMMON WITH ALL NEUROMUSCULAR BLOCKING AGENTS MONITORING OF NEUROMUSCULAR FUNCTION IS RECOMMENDED DURING THE USE OF ATRACURIUM BESILATE IN ORDER TO INDIVIDUALISE DOSAGE REQUIREMENTS.
Use by injection in adults
- Atracurium Besilate is administered by intravenous injection. The dosage range for adults is 0.3 – 0.6 mg/kgBW (depending on the duration of full block required) and will provide adequate relaxation for 15 – 35 minutes.
- Endotracheal intubation can usually be accomplished within 90 seconds from the intravenous injection of 0.5 – 0.6 mg/kgBW.
- Full block can be prolonged with supplementary doses of 0.1 – 0.2 mg/kgBW as required. Successive supplementary dosing does not give rise to accumulation of neuromuscular blocking effect.
- Spontaneous recovery from the end of full block occurs in about 35 minutes as measured by the restoration of the tetanic response to 95% of normal neuromuscular function.
- The neuromuscular block produced by Atracurium Besilate can be rapidly reversed by standard doses of anticholinesterase agents, such as Neostigmine and Edrophonium, accompanied or preceded by Atropine, with no evidence of recurarization.
Use as an infusion in adults
- After an initial bolus dose of 0.3 – 0.6 mg/kgBW, Atracurium Besilate can be used to maintain neuromuscular block during long surgical procedures by administration as a continuous infusion at rates of 0.3 – 0.6 mg/kgBW/hour.
- Atracurium Besilate can be administered by infusion during cardiopulmonary bypass surgery at the recommended infusion rates. Induced hypothermia to a body temperature of 25ºC – 26ºC reduces the rate of inactivation of Atracurium Besilate, therefore full neuromuscular block may be maintained by approximately half the original infusion rate at these low temperatures.
- Atracurium Besilate is compatible with the following infusion solutions for the times stated below :
|Infusion solution||Period of stability|
|Sodium chloride intravenous infusion (0.9% w/v)||24 hours|
|Glucose intravenous infusion (5% w/v)||8 hours|
When diluted in these solutions to give Atracurium Besilate concentrations of 0.5 mg/ml and above, the resultant solutions will be stable in daylight for the stated periods at temperatures of up to 30ºC.
Use in children
The dosage in children over the age of 1 month is the same as that in adults on a body weight basis.
Use in the elderly
Atracurium Besilate may be used at standard dosage in elderly patients. It is recommended, however, that the initial dose be at lower end of the range and that it be administered slowly.
Use in patients with reduced renal and/or hepatic function
Atracurium Besilate may be used at standard dosage at all levels of renal or hepatic function, including endstage failure.
Use in patients with cardiovascular disease
In patients with clinically significant cardiovascular disease, the initial dose of Atracurium Besilate should be administered over a period of 60 seconds.
Use in Intensive Care Unit (ICU) patients
- After an initial bolus dose of Atracurium Besilate of 0.3 – 0.6 mg/kgBW, Atracurium Besilate can be used to maintain neuromuscular block by administering a continuous infusion at rates of between 11 and 13 mcg/kgBW/minute (0.65 – 0.78 mg/kgBW/hour). However, there is wide inter-patient variability in dosage requirements. Dosage requirements may change with time. Infusion rates as low as 4.5 mcg/kgBW/minute (0.27 mg/kgBW/hour) or as high as 29.5 mcg/kgBW/minute (1.77 mg/kgBW/hour) are required in some patients.
- The rate of spontaneous recovery from neuromuscular block after infusion of Atracurium Besilate in ICU patients is independent of the duration of administration. Spontaneous recovery to a train-of-four ratio > 0.75 (the ratio of the height of the fourth to the first twitch in a train-of-four) can be expected to occur in approximately 60 minutes. A range of 32 – 108 minutes has been observed in clinical trials.
Prolonged muscle paralysis and its consequences are the main signs of overdosage.
It is essential to maintain a patent airway together with assisted positive pressure ventilation until spontaneous respiration is adequate.
Full sedation will be required since consciousness is not impaired.
Recovery may be hastened by the administration of anticholinesterase agents accompanied by Atropine or Glycopyrrolate, once evidence of spontaneous recovery is present.
Atracurium besilate should not be administered to patients known to be hypersensitivity to Atracurium, Cisatracurium or Benzenesulfonic acid.
WARNINGS AND PRECAUTIONS :
- In common with all the other neuromuscular blocking agents, Atracurium besilate paralyses the respiratory muscles as well as other skeletal muscles, but has no effect on consciousness. Atracurium besilate should be administered only with adequate general anesthesia and only by or under the close supervision of an experienced anesthetist with adequate facilities for endotracheal intubation and artificial ventilation.
- In common with other neuromuscular blocking agents, the potential for histamine release exist in susceptible patients during Atracurium besilate administration. Caution should be exercised in administering Atracurium besilate to patients with a history suggestive of an increased sensitivity to the effects of histamine.
- Caution should also be exercised when administering Atracurium besilate to patients who have shown hypersensitivity to other neuromuscular blocking agents since a high rate of cross-sensitivity (greater than 50%) between neuromuscular blocking agents has been reported (see CONTRAINDICATION).
- Atracurium besilate does not have significant vagal or ganglionic blocking properties in the recommended dosage range. Consequently, Atracurium besilate has no clinically significant effects on heart rate in the recommended dosage range and it will not counteract the bradycardia produced by many anesthetic agents or by vagal stimulation during surgery.
- In common with other non-depolarizing neuromuscular blocking agents, increased sensitivity to Atracurium may be expected in patients with myasthenia gravis, other forms of neuromuscular disease and severe electrolyte imbalance.
- Atracurium besilate should be administered over a period of 60 seconds to patients who may be unusually sensitive to falls in arterial blood pressure, for example those who are hypovolemic.
- Atracurium besilate is inactivated by high pH and so must not be mixed in the same syringe with Thiopentone or any alkaline agent.
- When a small vein is selected as the injection site, Atracurium besilate should be flushed through the vein with physiological saline after injection. When other anesthetic drugs are administered through the same in-dwelling needle or cannula as Atracurium besilate, it is important that each drug is flushed through with an adequate volume of physiological saline.
- Atracurium besilate is hypotonic and must not be administered into the infusion line of a blood transfusion.
- Studies in malignant hyperthermia in susceptible animals (swine) and clinical studies in patients susceptible to malignant hyperthermia indicate that Atracurium besilate does not trigger this syndrome.
- In common with other non-depolarizing neuromuscular blocking agents, resistance may develop in patients suffering from burns. Such patients may require increased doses dependent on the time elapsed since the burn injury and the extent of the burn.
- Whenever the use of Atracurium besilate or any neuromuscular blocking agent is contemplated in the ICU, it is recommended that neuromuscular transmission be monitored continuously during administration with the help of nerve stimulator.
- Additional doses of Atracurium besilate or any other neuromuscular blocking agent should not be given before there is a definite response to T or to the first twitch, if no response is elicited, infusion administration should be discontinued until a response returns.
- One metabolite of Atracurium, Laudanosine, when administered alone to laboratory animals, has been associated with cerebral excitatory effects and produces transient hypotension.
- Intensive Care Unit (ICU) patients : When administered to laboratory animals in high doses, Laudanosine, a metabolite of Atracurium, has been associated with transient hypotension and in some species, cerebral excitatory effects. Although seizures have been seen in ICU patients receiving Atracurium, none have been considered attributable to Laudanosine or Atracurium even after weeks of prolonged infusion.
- Pregnancy and lactation :
Fertility studies have not been performed. Animal studies have indicated that Atracurium has no significant effects on foetal development. In common with all neuromuscular blocking agents, Atracurium besilate should be used during pregnancy only if the potential benefit to the mother outweighs any potential risk to the fetus. Atracurium besilate is suitable for maintenance of muscle relaxation during Caesarean section as it does not cross the placenta in clinically significant amounts following recommended doses.
It is not known whether Atracurium besilate is excreted in human milk.
- DO NOT GIVE ATRACURIUM BESILATE BY INTRAMUSCULAR ADMINISTRATION.
- Effects on ability to drive and use machines : This precaution is not relevant to use of Atracurium besilate. Atracurium besilate will always be used in combination with a general anaesthetic and therefore the usual precautions relating to performance of tasks following general anaesthetic apply.
DRUG INTERACTIONS :
- The neuromuscular block produced by Atracurium besilate may be increased by the concomitant use of inhalational anesthetics such as Halothane, Isoflurane and Enflurane.
- In common with all non-depolarizing neuromuscular blocking agent the magnitude and/or duration of a non-depolarizing neuromuscular block may be increased as a result of interaction with :
- Antibiotics : Including the Aminoglycosides, Polymyxins, Spectinomycin, Tetracyclines, Lincomycin and Clindamycin.
- Antiarrhythmic drugs : Propranolol, calcium channel blockers, Lignocaine, Procainamide and Quinidine.
- Diuretics : Furosemide and possibly Mannitol, Thiazide diuretics and Acetazolamide.
- Magnesium sulphate.
- Lithium salts.
- Ganglion blocking agents : Trimetaphan, Hexamethonium.
- Rarely, certain drugs may aggravate or unmask latent myasthenia gravis or actually induce a myasthenic syndrome; increased sensitivity to Atracurium besilate would be consequent on such a development. Such drugs include various antibiotics, beta blockers (Propranolol, Oxprenolol), antiarrhythmics drugs (Procainamide, Quinidine), antirheumatic drugs (Chloroquine, D-penicillamine), Trimetaphan, Chlorpromazine, steroids, Phenytoin and Lithium.
- The onset of non-depolarizing neuromuscular block is likely to be lengthened and the duration of block shortened in patients receiving chronic anticonvulsant therapy.
- The administration of combinations of non-depolarizing neuromuscular blocking agents in conjunction with Atracurium besilate may produce a degree of neuromuscular blockade in excess of that which might be expected were an equipotent total dose of Atracurium besilate administered. Any synergistic effect may vary between different drug combinations.
- A depolarizing muscle relaxant such as Suxamethonium chloride should not be administered to prolong the neuromuscular blocking effects of non-depolarizing agents such as Atracurium, as this may result in prolonged and complex block which can be difficult to reverse with anti-cholinesterase drugs.
- Treatment with anticholinesterases, commonly used in the treatment of Alzheimer’s disease e.g. Donepezil, may shorten the duration and diminish the magnitude of neuromuscular blockade with Atracurium.
ADVERSE REACTIONS :
- Vascular disorders
Events which have been attributed to histamine release (common) : Hypotension (mild, transient), skin flushing.
- Respiratory, thoracic and mediastinal disorders
Events which have been attributed to histamine release (uncommon) : Bronchospasm.
- Immune system disorders
Very rare : Anaphylactic reaction, anaphylactoid reaction. Very rarely, severe anaphylactoid or anaphylactic reactions have been reported in patients receiving Atracurium in conjunction with one or more anaesthetic agents.
- Nervous system disorder
Not known : Seizures. There have been rare reports of seizures in ICU patients who have been receiving Atracurium concurrently with several other agents. These patients usually had one or more medical conditions predisposing to seizures (e.g. cranial trauma, cerebral oedema, viral encephalitis, hypoxic encephalopathy, uraemia). A causal relationship to Laudanosine has not been established. There appears to be no correlation between plasma Laudanosine concentration and the occurrence of seizures.
- Skin and subcutaneous tissue disorders
Rare : Urticaria.
- Musculoskeletal and connective tissue disorders
Not known : Myopathy, muscle weakness. There have been some reports of muscle weakness and/or myopathy following prolonged use of muscle relaxants in severely ill patients in the ICU. Most patients were receiving concomitant corticosteroids. These events have been seen infrequently in association with Atracurium and a causal relationship has not been established.
Atracurium Besilate Injection 25 mg/2.5 ml Box, 10 ampoules @ 2.5 ml
Reg. No. : GKL1702353543A1
KEEP IN REFRIGERATOR (2 – 8)ºC, PROTECT FROM LIGHT AND DO NOT FREEZING
Injection solution diluted in NaCl 0.9% solution stable for 24 hours.
Injection solution diluted in Glucose 5% solution stable for 8 hours.
ON MEDICAL PRESCRIPTION ONLY
Manufactured by :
Sidoarjo – Indonesia