ATRACURIUM

Administration by injection in adults Route of administration:

Intravenous injection or continuous infusion. Atracurium is administered by intravenous injection. 6 mg/kg (depending on the duration of full block required) and will provide adequate relaxation for about 15 to 35 minutes. 6 mg/kg. 2 mg/kg 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 can be rapidly reversed by standard doses of anticholinesterase agents, such as neostigmine and edrophonium, accompanied or preceded by atropine, with no evidence of recurarisation. 6mg/kg/hour.

Atracurium 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 therefore full neuromuscular block may be maintained by approximately half the original infusion rate at these low temperatures.

Children The dosage in children over the age of one month is similar to that in adults on a bodyweight basis. 1). Elderly Atracurium may be used at standard dosage in elderly patients. It is recommended, however, that the initial dose be at the lower end of the range and that it be administered slowly.

Reduced renal and/or hepatic function Atracurium may be used at standard dosage at all levels of renal or hepatic function, including end stage failure. Cardiovascular disease In patients with clinically significant cardiovascular disease, the initial dose of Atracurium should be administered over a period of 60 seconds.

78 mg/kg/hr). There may be wide inter-patient variability in dosage requirements and these may increase or decrease with time. 77 mg/kg/hr) are required in some patients. The rate of spontaneous recovery from neuromuscular block after infusion of Atracurium in ICU patients is independent of the duration of administration.

75 (the ratio of the height of the fourth to the first twitch in a train-off-our) can be expected to occur in approximately 60 minutes. A range of 32 to 108 minutes has been observed in clinical trials. Monitoring In common with all neuromuscular blocking agents, monitoring of neuromuscular function is recommended during the use of Atracurium in order to individualise dosage requirements.

The most commonly reported adverse reactions during treatment are hypotension (mild, transient) and skin flushing, these events are attributed to histamine release. Very rarely, severe anaphylactoid or anaphylactic reactions have been reported in patients receiving atracurium in conjunction with one or more anaesthetic agents.

Adverse reactions are listed below by system organ class and frequency. Frequencies are defined as: very common > 1/10, common >1/100 and < 1/10, uncommon >1/1000 and < 1/100, rare >1/10,000 and < 1/1000, very rare < 1/10,000. Very common, common and uncommon frequencies were determined from clinical trial data.

Rare and very rare frequencies were generally derived from spontaneous data. The frequency classification "Not known" has been applied to those reactions where a frequency could not be estimated from the available data. Clinical Trial Data Vascular Disorders Common Hypotension (mild, transient)#, Skin flushing# Respiratory, thoracic and mediastinal disorders Uncommon Bronchospasm# Post-Marketing Data Immune system disorders Very rare Anaphylactic reaction, anaphylactoid reaction including shock, circulatory failure and cardiac arrest 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 reports of seizures in ICU patients who have been receiving atracurium concurrently with several other agents. g. cranial trauma, cerebral oedema, viral encephalitis, hypoxic encephalopathy, uraemia).

A causal relationship to laudanosine has not been established. In clinical trials, 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. Events which have been attributed to histamine release are indicated by a hash (#) Reporting of suspected adverse reactions If you get any side effects, talk to your doctor, this includes any possible side effects not listed in this leaflet you can also report side effects directly for the following contacts.

By reporting side effects you can help provide more information on the safety of this medicine. uk/yellowcard

In common with all the other neuromuscular blocking agents, Atracurium paralyses the respiratory muscles as well as other skeletal muscles but has no effect on consciousness. Atracurium should be administered only with adequate general anaesthesia and only by or under the close supervision of an experienced anaesthetist with adequate facilities for endotracheal intubation and artificial ventilation.

The potential for histamine release exists in susceptible patients during Atracurium administration. Caution should be exercised in administering Atracurium to patients with a history suggestive of an increased sensitivity to the effects of histamine.

In particular, bronchospasm may occur in patients with a history of allergy and asthma. High rates of cross-sensitivity between neuromuscular blocking agents have been reported. Therefore, where possible, before administering atracurium, hypersensitivity to other neuromuscular blocking agents should be excluded.

Atracurium should only be used when absolutely essential in susceptible patients. Patients who experience a hypersensitivity reaction under general anaesthesia should be tested subsequently for hypersensitivity to other neuromuscular blockers.

Monitoring of serial creatinine phosphate (cpk) values should be considered in asthmatic patients receiving high dose corticosteroids and neuromuscular blocking agents in ICU. Atracurium does not have significant vagal or ganglionic blocking properties in the recommended dosage range.

Consequently, Atracurium as no clinically significant effects on heart rate in the recommended dosage range and it will not counteract the bradycardia produced by many anaesthetic agents or by vagal stimulation during surgery. In common with other non-depolarising neuromuscular blocking agents, increased sensitivity to atracurium may be expected in patients with myasthenia gravis and other forms of neuromuscular disease.

As with other neuromuscular blocking agents severe acid-base and/or serum electrolyte abnormalities may increase or decrease the sensitivity of patients to Atracurium. As with other non-depolarising neuromuscular blockers hypophosphataemia may prolong recovery.

Recovery may be hastened by correcting this condition. Atracurium 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 hypovolaemic.

Atracurium is inactivated by high pH and so must not be mixed in the same syringe with thiopental or any alkaline agent. When a small vein is selected as the injection site, Atracurium should be flushed through the vein with physiological saline after injection.

When other anaesthetic drugs are administered through the same in-dwelling needle or cannula as Atracurium it is important that each drug is flushed through with an adequate volume of physiological saline. Atracurium 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 hypothermia indicate that Atracurium does not trigger this syndrome. In common with other non-depolarising 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.

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, a causal relationship to laudanosine has not been established (see Undesirable Effects).

Atracurium is contraindicated in patients known to be hypersensitive to atracurium, cisatracurium or benzenesulfonic acid.