Drugs List

Therapeutic Indications

Uses

Atracurium besilate is used as an adjunct to general anaesthesia during surgery to relax skeletal muscles and to facilitate endotracheal intubation and mechanical ventilation. It may also be used to facilitate mechanical ventilation for patients in intensive care units.

Atracurium besilate is a non-depolarising neuromuscular blocking agent which blocks transmission of motor nerve impulses to the striated muscle receptors. It has an intermediate duration of action.

Administration

Administer by intravenous injection or by intravenous infusion after dilution.

Atracurium must not be given intramuscularly as this may cause tissue irritation and there is no data to support this route of administration.

Atracurium should not be administered until the patient is unconscious in order to avoid distress for the patient.

When a small vein is injected, atracurium injection should be followed by a physiological saline flush. When other anaesthetic agents are administered through he same indwelling needle or cannula as atracurium, each drug should be flushed through with an adequate amount of physiological saline.

Handling

Once diluted with a recommended infusion solution, store at 30 degrees C and protect from light. Stability times may vary between the preparations available.

Reconstitution

Intravenous infusion

Atracurium besilate must be diluted to 0.5 to 5mg/ml before administration with one of the following infusion solutions:
Sodium chloride 0.9% infusion
Glucose 5% infusion
Glucose 4% and sodium chloride 0.18% infusion
Ringer's injection
Compound sodium lactate infusion (Hartmann's)

Incompatibilities

Atracurium besilate should not be mixed in the same syringe or administered simultaneously through the same needle as alkaline solutions (e.g. barbiturate solutions). The resulting pH of mixtures with alkaline solutions may inactivate atracurium and precipitate a free acid.

Atracurium besilate is hypotonic and must not be administered into the infusion line of a blood transfusion.

Contraindications

None known

Precautions and Warnings

Atracurium should be administered under the supervision of an anaesthetist and only when facilities for controlled ventilation, insufflation with oxygen and endotracheal intubation are immediately available.

Respiration must be assisted in all patients as atracurium relaxes the respiratory muscles. Before leaving the theatre following anaesthesia, is it essential to ensure that the patient is breathing spontaneously, deeply and regularly.

Anticholinesterase agents should be immediately available to reverse neuromuscular blockade.

Atracurium should only be used with adequate general anaesthesia. Atracurium has no known effect on consciousness, pain threshold or cerebration.

Neuromuscular function should be monitored throughout the use of atracurium in order to establish individual dose requirements.

For intravenous injection or infusion only. Atracurium must not be given intramuscularly as this may cause tissue irritation and there is no data to support this route of administration.

Not licensed in neonates - (See Dosage Neonate section). Neonates are particularly sensitive to the non-depolarising neuromuscular blocking agents.

Use with caution in patients with increased sensitivity to histamines as atracurium may cause histamine release in susceptible patients.

Atracurium may have profound effects in patients with myasthenia gravis, Eaton-Lambert syndrome or other neuromuscular disease as the potentiation of non-depolarising agents has been noted. Dosages of atracurium should be reduced and it is especially important to use a peripheral nerve stimulator to monitor neuromuscular blockade in these patients. Similar precautions should be taken in patients with severe electrolyte disorders.

Activity is prolonged in patients with hypothermia therefore lower doses may be required.

Resistance to atracurium may develop in patients with burns. These patients may require increased doses depending on the time since the burn injury and the extent of the burn.

A prolonged recovery may occur in patients with hypophosphataemia. Recovery time may be reduced in these patients by correcting their condition.

The initial dose of atracurium should be administered over at least 60 seconds in patients with severe cardiovascular disease and patients who may be unusually sensitive to falls in arterial blood pressure (e.g. hypovolaemic patients).

In obese patients, the dose of atracurium based on a microgram/kg basis may lead to overdosage. Dose must therefore be adjusted according to response in these patients and based on the ideal body weight of the patient.

Atracurium besilate should not be mixed in the same syringe or administered simultaneously through the same needle as alkaline solutions (e.g. barbiturate solutions). The resulting pH of mixtures with alkaline solutions may inactivate atracurium and precipitate a free acid.

Atracurium is hypotonic and must NOT be administered via the infusion system of a blood transfusion because it might cause haemolysis.

Serum creatinine phosphokinase levels should be monitored in asthmatic patients receiving high dose corticosteroids and neuromuscular blocking agents in intensive care units.

Pregnancy - see Pregnancy section

Breastfeeding - see Lactation section

Patients should not drive or operate machinery for at least 24 hours following full recovery from the effects of atracurium.

Prolonged co-administration of high-dose corticosteroids and neuromuscular blockers such as atracurium besilate may increase the risk of myopathy, resulting in prolonged paralysis and muscle weakness following discontinuation of the neuromuscular blocker.
High-dose corticosteroids may also antagonise the neuromuscular-blocking effects of atracurium and dose adjustment may be necessary.

High rates of cross-sensitivity have been reported between neuromuscular blocking agents. Where possible, hypersensitivity to other neuromuscular blocking agents should be excluded before administration of atracurium. Patients who develop a hypersensitivity reaction under general anaesthesia should be tested for hypersensitivity to other neuromuscular blocks.

Pregnancy and Lactation

Pregnancy

Atracurium should only be administered during pregnancy if the potential benefits to the mother outweighs the possible risks to the foetus. It is not recommended for use during the first trimester of pregnancy.

Atracurium crosses the placenta, although adverse effects in the foetus or neonate have not been reported. It is not known if muscle relaxants administered during vaginal delivery have immediate or delayed effects on the foetus or whether they increase the need for resuscitation of the neonate. The need for a forceps delivery may be increased following atracurium administration.

Atracurium besilate is suitable for muscle relaxation during Caesarean section as it does not cross the placenta in clinically significant amounts following recommended doses.
One study involved the administration of atracurium (300 microgram/kg) to 26 pregnant women during Caesarean section. No harmful effects were attributable to atracurium in any of the neonates, although small amounts were shown to cross the placental barrier. However, the potential for respiratory depression in the neonate following Caesarean section involving neuromuscular blocking agents should be considered.
In patients receiving magnesium sulfate, the reversal of neuromuscular block may not be satisfactory and lower doses of atracurium are required.

Animal studies have indicated that atracurium does not effect foetal development.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Licensed in pregnancy? - Yes, for use in caesarean section

Crosses placenta? - Yes

Effects on foetus - None reported

Lactation

It is not known if atracurium is excreted in human breast milk. However, atracurium has a short half-life (approx. 20 minutes) and a relatively high molecular weight, these factors may reduce transfer into milk (Briggs, 2011). Metabolites of atracurium are not considered biologically active. An influence on the nursing infant is not expected if the mother starts or continues breastfeeding after all effects of atracurium have worn off. As a precaution, breastfeeding should only occur 24 hours after administration of atracurium. In view of the potential respiratory depressant effect on the neonate it is recommended that the neonate is monitored closely if breastfeeding is started within 24 hours of administration.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Flushing
Hypotension
Bronchospasm
Tachycardia
Anaphylactic reaction
Anaphylactoid reaction
Hypertension
Bradycardia
Shock
Circulatory failure
Cardiac arrest
Angioedema
Transient hypoxaemia
Dyspnoea
Laryngospasm
Wheezing
Rash
Urticaria
Erythema
Injection site reactions

Following prolonged administration of atracurium in intensive care, muscle weakness and myopathy have been observed although a causal relationship with atracurium has not been established.

Seizures have occurred rarely in patients in intensive care receiving atracurium and many other concurrent medications. These patients usually one or more medical factors that predisposed them to seizures.

Presentation

Solution for injection containing 25mg/2.5ml of atracurium besilate (equivalent to atracurium 7.5mg/ml)

Solution for injection containing 50mg/5ml of atracurium besilate (equivalent to atracurium 7.5mg/ml)

Solution for injection containing 250mg/25ml of atracurium besilate (equivalent to atracurium 7.5mg/ml)

Drugs List

Therapeutic Indications

Uses

Atracurium besilate is used as an adjunct to general anaesthesia during surgery to relax skeletal muscles and to facilitate endotracheal intubation and mechanical ventilation. It may also be used to facilitate mechanical ventilation for patients in intensive care units.

Atracurium besilate is a non-depolarising neuromuscular blocking agent which blocks transmission of motor nerve impulses to the striated muscle receptors. It has an intermediate duration of action.

Dosage

Atracurium should be administered under the supervision of an anaesthetist and only when facilities for controlled ventilation, insufflation with oxygen and endotracheal intubation are immediately available.

Respiration must be assisted in all patients as atracurium relaxes the respiratory muscles. Before leaving the theatre following anaesthesia, is it essential to ensure that the patient is breathing spontaneously, deeply and regularly.

Anticholinesterase agents should be immediately available to reverse neuromuscular blockade (see Additional Dosage) .

Atracurium should not be administered until the patient is unconscious in order to avoid distress for the patient.

Neuromuscular function should be monitored throughout the use of atracurium in order to establish individual dose requirements.

The dose required is dependent upon the anaesthetic method used, the expected duration of surgery, possible interactions with concurrent medications, and the condition of the patient.

If suxamethonium is used for intubation, atracurium dosage should be reduced and it should not be administered until the patient has clinically recovered from its neuromuscular blockade.

Adults

Children

Neonates

Additional Dosage Information

Administration

Administer by intravenous injection or by intravenous infusion after dilution.

Atracurium must not be given intramuscularly as this may cause tissue irritation and there is no data to support this route of administration.

Atracurium should not be administered until the patient is unconscious in order to avoid distress for the patient.

When a small vein is injected, atracurium injection should be followed by a physiological saline flush. When other anaesthetic agents are administered through he same indwelling needle or cannula as atracurium, each drug should be flushed through with an adequate amount of physiological saline.

Handling

Once diluted with a recommended infusion solution, store at 30 degrees C and protect from light. Stability times may vary between the preparations available.

Reconstitution

Intravenous infusion

Atracurium besilate must be diluted to 0.5 to 5mg/ml before administration with one of the following infusion solutions:
Sodium chloride 0.9% infusion
Glucose 5% infusion
Glucose 4% and sodium chloride 0.18% infusion
Ringer's injection
Compound sodium lactate infusion (Hartmann's)

Incompatibilities

Atracurium besilate should not be mixed in the same syringe or administered simultaneously through the same needle as alkaline solutions (e.g. barbiturate solutions). The resulting pH of mixtures with alkaline solutions may inactivate atracurium and precipitate a free acid.

Atracurium besilate is hypotonic and must not be administered into the infusion line of a blood transfusion.

Contraindications

None known

Precautions and Warnings

Atracurium should be administered under the supervision of an anaesthetist and only when facilities for controlled ventilation, insufflation with oxygen and endotracheal intubation are immediately available.

Respiration must be assisted in all patients as atracurium relaxes the respiratory muscles. Before leaving the theatre following anaesthesia, is it essential to ensure that the patient is breathing spontaneously, deeply and regularly.

Anticholinesterase agents should be immediately available to reverse neuromuscular blockade.

Atracurium should only be used with adequate general anaesthesia. Atracurium has no known effect on consciousness, pain threshold or cerebration.

Neuromuscular function should be monitored throughout the use of atracurium in order to establish individual dose requirements.

For intravenous injection or infusion only. Atracurium must not be given intramuscularly as this may cause tissue irritation and there is no data to support this route of administration.

Not licensed in neonates - (See Dosage Neonate section). Neonates are particularly sensitive to the non-depolarising neuromuscular blocking agents.

Use with caution in patients with increased sensitivity to histamines as atracurium may cause histamine release in susceptible patients.

Atracurium may have profound effects in patients with myasthenia gravis, Eaton-Lambert syndrome or other neuromuscular disease as the potentiation of non-depolarising agents has been noted. Dosages of atracurium should be reduced and it is especially important to use a peripheral nerve stimulator to monitor neuromuscular blockade in these patients. Similar precautions should be taken in patients with severe electrolyte disorders.

Activity is prolonged in patients with hypothermia therefore lower doses may be required.

Resistance to atracurium may develop in patients with burns. These patients may require increased doses depending on the time since the burn injury and the extent of the burn.

A prolonged recovery may occur in patients with hypophosphataemia. Recovery time may be reduced in these patients by correcting their condition.

The initial dose of atracurium should be administered over at least 60 seconds in patients with severe cardiovascular disease and patients who may be unusually sensitive to falls in arterial blood pressure (e.g. hypovolaemic patients).

In obese patients, the dose of atracurium based on a microgram/kg basis may lead to overdosage. Dose must therefore be adjusted according to response in these patients and based on the ideal body weight of the patient.

Atracurium besilate should not be mixed in the same syringe or administered simultaneously through the same needle as alkaline solutions (e.g. barbiturate solutions). The resulting pH of mixtures with alkaline solutions may inactivate atracurium and precipitate a free acid.

Atracurium is hypotonic and must NOT be administered via the infusion system of a blood transfusion because it might cause haemolysis.

Serum creatinine phosphokinase levels should be monitored in asthmatic patients receiving high dose corticosteroids and neuromuscular blocking agents in intensive care units.

Pregnancy - see Pregnancy section

Breastfeeding - see Lactation section

Patients should not drive or operate machinery for at least 24 hours following full recovery from the effects of atracurium.

Prolonged co-administration of high-dose corticosteroids and neuromuscular blockers such as atracurium besilate may increase the risk of myopathy, resulting in prolonged paralysis and muscle weakness following discontinuation of the neuromuscular blocker.
High-dose corticosteroids may also antagonise the neuromuscular-blocking effects of atracurium and dose adjustment may be necessary.

High rates of cross-sensitivity have been reported between neuromuscular blocking agents. Where possible, hypersensitivity to other neuromuscular blocking agents should be excluded before administration of atracurium. Patients who develop a hypersensitivity reaction under general anaesthesia should be tested for hypersensitivity to other neuromuscular blocks.

Pregnancy and Lactation

Pregnancy

Atracurium should only be administered during pregnancy if the potential benefits to the mother outweighs the possible risks to the foetus. It is not recommended for use during the first trimester of pregnancy.

Atracurium crosses the placenta, although adverse effects in the foetus or neonate have not been reported. It is not known if muscle relaxants administered during vaginal delivery have immediate or delayed effects on the foetus or whether they increase the need for resuscitation of the neonate. The need for a forceps delivery may be increased following atracurium administration.

Atracurium besilate is suitable for muscle relaxation during Caesarean section as it does not cross the placenta in clinically significant amounts following recommended doses.
One study involved the administration of atracurium (300 microgram/kg) to 26 pregnant women during Caesarean section. No harmful effects were attributable to atracurium in any of the neonates, although small amounts were shown to cross the placental barrier. However, the potential for respiratory depression in the neonate following Caesarean section involving neuromuscular blocking agents should be considered.
In patients receiving magnesium sulfate, the reversal of neuromuscular block may not be satisfactory and lower doses of atracurium are required.

Animal studies have indicated that atracurium does not effect foetal development.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Licensed in pregnancy? - Yes, for use in caesarean section

Crosses placenta? - Yes

Effects on foetus - None reported

Lactation

It is not known if atracurium is excreted in human breast milk. However, atracurium has a short half-life (approx. 20 minutes) and a relatively high molecular weight, these factors may reduce transfer into milk (Briggs, 2011). Metabolites of atracurium are not considered biologically active. An influence on the nursing infant is not expected if the mother starts or continues breastfeeding after all effects of atracurium have worn off. As a precaution, breastfeeding should only occur 24 hours after administration of atracurium. In view of the potential respiratory depressant effect on the neonate it is recommended that the neonate is monitored closely if breastfeeding is started within 24 hours of administration.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Effects on Ability to Drive and Operate Machinery

Patients should not drive or operate machinery for at least 24 hours following full recovery from the effects of atracurium.

Counselling

Advise patient not drive or operate machinery for at least 24 hours following full recovery from the effects of atracurium.

Side Effects

Flushing
Hypotension
Bronchospasm
Tachycardia
Anaphylactic reaction
Anaphylactoid reaction
Hypertension
Bradycardia
Shock
Circulatory failure
Cardiac arrest
Angioedema
Transient hypoxaemia
Dyspnoea
Laryngospasm
Wheezing
Rash
Urticaria
Erythema
Injection site reactions

Following prolonged administration of atracurium in intensive care, muscle weakness and myopathy have been observed although a causal relationship with atracurium has not been established.

Seizures have occurred rarely in patients in intensive care receiving atracurium and many other concurrent medications. These patients usually one or more medical factors that predisposed them to seizures.

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Shelf Life and Storage

Store at 2 - 8 degrees C
Do not freeze
Keep container in outer carton (protected from light)

Once diluted with a recommended infusion solution, store at 30 degrees C.

Further Information

Last Full Review Date: February 2012

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Summary of Product Characteristics: Atracurium 10mg/ml solution for injection/infusion. Actavis UK Limited. Revised November 2013.
Summary of Product Characteristics: Atracurium Besilate 10mg/ml Injection. Hospira UK Limited. Revised January 2017.
Summary of Product Characteristics: Atracurium Besilate Injection10mg/ml solution for injection. Hameln pharmaceuticals GmbH. Revised December 2015.
Summary of Product Characteristics: Tracrium Injection. Aspen Pharma Trading Limited. Revised August 2017.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 22 August 2017