ATRACURIUM BESYLATE Solution for injection Ref.[6334] Active ingredients: Atracurium besilate

Use as an adjunct to general anaesthesia

Atracurium Besilate Injection should only be administered by intravenous injection. Do not give Atracurium Besilate Injection intramuscularly since this may result in tissue irritation and there are no clinical data to support this route of administration.

To avoid distress to the patient, Atracurium Besilate Injection should not be administered before unconsciousness has been induced.

Atracurium Besilate Injection should not be mixed in the same syringe, or administered simultaneously through the same needle, with alkaline solutions (e.g. barbiturate solutions).

See section 6.6 for a list of compatible infusion solutions.

In common with all neuromuscular blocking agents, monitoring of neuromuscular function is recommended during the use of Atracurium Besilate Injection in order to individualise dosage requirements.

Initial bolus doses for intubation

An initial atracurium besilate dose of 0.3 to 0.6 mg/kg (depending on the duration of full block required), given as an intravenous bolus injection, is recommended. This will provide adequate relaxation for about 15 to 35 minutes.

Endotracheal intubation can usually be accomplished within 90 to 120 seconds of the intravenous injection of 0.5 to 0.6 mg/kg. Maximum neuromuscular blockade is generally achieved approximately 3 to 5 minutes after administration. 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.

Maintenance doses

Intermittent IV injection: During prolonged surgical procedures neuromuscular blockade may be maintained with atracurium besilate maintenance doses of 0.1 to 0.2 mg/kg. Successive supplementary dosing does not give rise to accumulation of neuromuscular blocking effect.

Use as an infusion: After the initial atracurium bolus dose, neuromuscular blockade may be maintained during prolonged surgical procedures by administering atracurium besilate as a continuous intravenous infusion at a rate of 0.3 to 0.6 mg/kg/hour. The infusion should not be commenced until early spontaneous recovery from the initial atracurium bolus dose is evident.

Atracurium Besilate Injection can be administered by infusion during cardiopulmonary bypass surgery at the recommended infusion rates. Induced hypothermia to a body temperature of 25 to 26°C reduces the rate of inactivation of atracurium, and therefore full neuromuscular block may be maintained with approximately half the original infusion rate at these temperatures.

Reversal of neuromuscular blockade

The neuromuscular blockade induced by atracurium can be reversed with an anticholinesterase agent such as neostigmine or pyridostigmine, usually in conjunction with an anticholinergic agent such as atropine or glycopyrronium to prevent the adverse muscarinic effects of the anticholinesterase. Under balanced anaesthesia, reversal can usually be attempted approximately 20 to 35 minutes after the initial atracurium dose, or approximately 10 to 30 minutes after the last atracurium maintenance dose, when recovery of muscle twitch has started. Complete reversal of neuromuscular blockade is usually achieved within 8 to 10 minutes after administration of the reversing agents.

Rare instances of breathing difficulties, possibly related to incomplete reversal, have been reported following attempted pharmacological antagonism of atracurium induced neuromuscular blockade. As with other agents in this class, the tendency for residual neuromuscular block is increased if reversal is attempted at deep levels of blockade or if inadequate doses of reversal agents are employed.

Facilitation of mechanical ventilation in intensive care unit (ICU) patients

After an optional initial bolus dose of 0.3 to 0.6 mg/kg, neuromuscular block may be maintained by administering a continuous atracurium besilate infusion at rates of between 11 and 13 microgram/kg/min (0.65 to 0.78 mg/kg/hr). There may be wide inter-patient variability in dosage requirements and these may increase or decrease with time. Infusion rates as low as 4.5 microgram/kg/min (0.27 mg/kg/hr) or as high as 29.5 microgram/kg/min (1.77 mg/kg/hr) 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 to 108 minutes has been observed in clinical trials.

Dosage considerations

Use in children

The dosage in children over the age of 1 month is similar to that in adults on a body weight basis, however, large individual variability in the neuromuscular response in paediatric patients indicates that neuromuscular monitoring is essential.

Use in neonates

The use of Atracurium is not recommended in neonates since there are insufficient data available (see section 5.1).

Use in the elderly

The standard dose of atracurium may be used in elderly patients, however, it is recommended that the initial dose be at the lower end of the range and it should be administered slowly

Use in patients with reduced renal and/or hepatic function

Standard dosages may be used at all levels of renal or hepatic function, including endstage failure.

Use in patients with cardiovascular disease

In patients with significant cardiovascular disease the initial dose of atracurium should be administered over a period of at least 60 seconds.

See also “Special warnings and special precautions for use”.

Prolonged muscle paralysis and its consequences are the main signs of overdose.

There is limited experience with atracurium overdosage following parenteral administration. The possibility of iatrogenic overdosage can be minimised by carefully monitoring muscle twitch response to peripheral nerve stimulation. Excessive doses of atracurium are likely to produce symptoms consistent with extensions of the usual pharmacological effects. Overdosage may increase the risk of histamine release and adverse cardiovascular effects, especially hypotension. If cardiovascular support is necessary, this should include proper positioning, fluid administration, and the use of vasopressor agents if necessary. It is essential to maintain a patent airway with assisted positive pressure ventilation until spontaneous respiration is adequate. Full sedation will be required since consciousness is not impaired. The duration of neuromuscular blockade may be prolonged and a peripheral nerve stimulator should be used to monitor recovery. Recovery may be hastened by the administration of an anticholinesterase agent such as neostigmine or pyridostigmine in conjunction with an anticholinergic agent such as atropine, once evidence of spontaneous recovery is present.

As packaged for sale – 18 months.

Information is presented below on chemical and physical stability following dilution with a number of infusion solutions:

Atracurium Besilate Injection diluted to 0.5 mg/ml with the following infusion solutions, and stored at 30°C protected from light, was shown to be stable for the times stated below.

Atracurium Besilate Injection diluted to 5 mg/ml with the following infusion solutions, and stored at 30°C protected from light in 50 ml plastic syringes, was shown to be stable for the times stated below.

However, from a microbiological point of view, the product should be used immediately. If not used immediately, in use storage times and conditions prior to use are the responsibility of the user.

Discard residue immediately after use.

Store in a refrigerator (2°C-8°C).

Do not freeze.

Keep container in the outer carton.

2.5 ml: Type I glass ampoule in packs of 5 ampoules.

5 ml: Type I glass ampoule in packs of 5 ampoules.

25 ml: Type I glass vial with rubber stopper in packs of 1 vial.

Contains no preservative. Discard residue immediately after use.

Do not use if cloudiness or precipitate is observed.

Atracurium besilate infusion solutions may be prepared by admixing Atracurium Besilate Injection with an appropriate diluent (see below) to give an atracurium besilate concentration of 0.5 mg/ml to 5 mg/ml.

Infusion Solutions:

Sodium Chloride 0.9% Intravenous Infusion
Glucose 5% Intravenous Infusion
Glucose 4% and Sodium Chloride 0.18% Intravenous Infusion
Ringer’s Injection USP
Compound Sodium Lactate Intravenous Infusion (Hartmann’s Solution for Injection)