Lysthenon

Suxamethonium is a short acting depolarising neuromuscular blocking agent for producing muscular relaxation during anaesthesia. It is used in anaesthesia as a muscle relaxant to facilitate endotracheal intubation, mechanical ventilation and a wide range of surgical and obstetric procedures.

It is also used to reduce the intensity of muscle contractions associated with pharmacologically or electrically-induced convulsions.

Usually by bolus intravenous injection

Adults: The dose is dependent on body weight, the degree of muscular relaxation required, the route of administration, and the response of individual patients.

To achieve endotracheal intubation, Suxamethonium is usually administered intravenously in a dose of 1mg/kg. This dose will usually produce muscular relaxation in about 30 to 60 seconds and has a duration of action of about 2 to 6 minutes. Larger doses will produce more prolonged muscular relaxation, but doubling the dose does not necessarily double the duration of relaxation. Supplementary doses of Suxamethonium of 50% to 100% of the initial dose administered at 5 to 10 minute intervals will maintain muscle relaxation during short surgical procedures performed under general anaesthesia.

For prolonged surgical procedures, Suxamethonium may be given by intravenous infusion as a 0.1% to 0.2% solution, diluted in 5% glucose solution or sterile isotonic saline solution, at a rate of 2.5 to 4 mg per minute. The infusion rate should be adjusted according to the response of individual patients.

The total dose of Suxamethonium given by repeated intravenous injection or continuous infusion should not exceed 500 mg per hour.

Children: Infants and young children are more resistant to suxamethonium compared with adults.

The recommended intravenous dose of Suxamethonium for neonates and infants is 2 mg/kg. A dose of 1 mg/kg in older children is recommended.

When Suxamethonium is given as intravenous infusion in children, the dosage is as for adults with a proportionately lower initial infusion rate based on body weight.

Suxamethonium may be given intramuscularly to infants at doses up to 4 to 5mg/kg and in older children up to 4 mg/kg. These doses produce muscular relaxation within about 3 minutes. A total dose of 150 mg should not be exceeded.

Use in older people: Dosage requirements of suxamethonium in older patients are comparable to those for younger adults.

The elderly may be more susceptible to cardiac arrhythmias, especially if digitalis-like drugs are also being taken. See also 'Special warnings and precautions for use.

- Conscious patients. Suxamethonium has no effect on the level of consciousness and should not be administered to a patient who is not fully anaesthetised.

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- Personal or family history of malignant hyperthermia. Suxamethonium can trigger sustained myofibrillar contractions in susceptible individuals. If this occurs, all anaesthetic agents known to be associated with it (including suxamethonium) must be stopped and full supportive measures implemented immediately. Intravenous dantrolene sodium is the primary specific therapeutic drug and should be given as soon as possible after the diagnosis is made.

- Patients with inherited atypical plasma cholinesterase activity

- An acute transient rise in serum potassium often occurs following the administration of suxamethonium in normal individuals; the magnitude of this rise is of the order of 0.5 mmol/litre. In certain pathological states or conditions this increase in serum potassium following suxamethonium administration may be excessive and cause serious cardiac arrhythmias and cardiac arrest.

For this reason the use of suxamethonium is contra-indicated in:

In patients recovering from major trauma or severe burns; the period of greatest risk of hyperkalaemia is from about 5 to 70 days after the injury and may be further prolonged if there is delayed healing due to persistent infection.

Patients with neurological deficits involving acute major muscle wasting (upper and/or lower motor neurone lesions); the potential for potassium release occurs within the first 6 months after the acute onset of the neurological deficit and correlates with the degree and extent of muscle paralysis. Patients who have been immobilised for prolonged periods of time may be at similar risk.

Patients with pre-existing hyperkalaemia. In the absence of hyperkalaemia and neuropathy, renal failure is not a contra-indication to the administration of a normal single dose of Suxamethonium Injection, but multiple or large doses may cause clinically significant rises in serum potassium and should not be used.

- Suxamethonium causes a significant transient rise in intra-ocular pressure, and should therefore not be used in the presence of open eye injuries or where an increase in intra-ocular pressure is undesirable unless the potential benefit of its use outweighs the potential risk to the eye.

- Patients with a personal or family history of congenital myotonic diseases such as myotonia congenita and dystrophia myotonica (risk of severe myotonic spasms and rigidity).

- Patients with skeletal muscle myopathies e.g. Duchenne muscular dystrophy (increased risk of malignant hyperthermia, ventricular dysrhythmias and cardiac arrest secondary to acute rhabdomyolysis with hyperkalaemia - see above).

- Conscious patients. Suxamethonium has no effect on the level of consciousness and should not be administered to a patient who is not fully anaesthetised.

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- Personal or family history of malignant hyperthermia. Suxamethonium can trigger sustained myofibrillar contractions in susceptible individuals. If this occurs, all anaesthetic agents known to be associated with it (including suxamethonium) must be stopped and full supportive measures implemented immediately. Intravenous dantrolene sodium is the primary specific therapeutic drug and should be given as soon as possible after the diagnosis is made.

- Patients with inherited atypical plasma cholinesterase activity

- An acute transient rise in serum potassium often occurs following the administration of suxamethonium in normal individuals; the magnitude of this rise is of the order of 0.5 mmol/litre. In certain pathological states or conditions this increase in serum potassium following suxamethonium administration may be excessive and cause serious cardiac arrhythmias and cardiac arrest.

For this reason the use of suxamethonium is contra-indicated in:

In patients recovering from major trauma or severe burns; the period of greatest risk of hyperkalaemia is from about 5 to 70 days after the injury and may be further prolonged if there is delayed healing due to persistent infection.

Patients with neurological deficits involving acute major muscle wasting (upper and/or lower motor neurone lesions); the potential for potassium release occurs within the first 6 months after the acute onset of the neurological deficit and correlates with the degree and extent of muscle paralysis. Patients who have been immobilised for prolonged periods of time may be at similar risk.

Patients with pre-existing hyperkalaemia. In the absence of hyperkalaemia and neuropathy, renal failure is not a contra-indication to the administration of a normal single dose of Suxamethonium Injection, but multiple or large doses may cause clinically significant rises in serum potassium and should not be used.

- Suxamethonium causes a significant transient rise in intra-ocular pressure, and should therefore not be used in the presence of open eye injuries or where an increase in intra-ocular pressure is undesirable unless the potential benefit of its use outweighs the potential risk to the eye.

- Patients with a personal or family history of congenital myotonic diseases such as myotonia congenita and dystrophia myotonica (risk of severe myotonic spasms and rigidity).

- Patients with skeletal muscle myopathies e.g. Duchenne muscular dystrophy (increased risk of malignant hyperthermia, ventricular dysrhythmias and cardiac arrest secondary to acute rhabdomyolysis with hyperkalaemia - see above).

Suxamethonium paralyses the respiratory muscles as well as other skeletal muscles but has no effect on consciousness.

Suxamethonium should be administered only by or under close supervision of an anaesthetist who is familiar with its actions, characteristics and hazards, who is skilled in the management of artificial respiration and only where there are adequate facilities for immediate endotracheal intubation with the administration of oxygen by intermittent positive pressure ventilation.

Cross-sensitivity

As there is a higher rate of cross-sensitivity with other neuromuscular blocking (both depolarising and non-depolarising) drugs, caution is advised where there is a history of sensitivity to neuromuscular blocking drugs.

Suxamethonium 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.

During prolonged administration of suxamethonium, it is recommended that the patient is fully monitored with a peripheral nerve stimulator in order to avoid overdosage.

Hyperkalaemia

Suxamethonium increases serum potassium by 0.5mmol/L in normal individuals. This may be significant with pre-existing elevated serum potassium. Patients with burns or certain neurological conditions may develop severe hyperkalaemia. In severe sepsis, the potential for hyperkalaemia may be related to the severity and duration of the infection.

Bradycardia and other cardiac dysrhythmias

In healthy adults, suxamethonium occasionally causes a mild transient slowing of the heart rate on initial administration.

Bradycardias are more commonly observed in children or if repeated doses are given (both adults and children). Pre-treatment with intravenous atropine or glycopyrrolate can significantly reduce the incidence and/or severity of suxamethonium-related bradycardia.

Suxamethonium can induce cardiac dysrhythmias and arrest. In the absence of hyperkalaemia, ventricular dysrhythmias are rare although patients on cardiac glycosides are at increased risk. The action of suxamethonium on the heart may cause changes in cardiac rhythm including cardiac arrest.

Raised intra-ocular pressure (IOP)

Suxamethonium causes a transient increase in intraocular pressure and should not be used in the presence of penetrating eye injury except where the potential benefits outweigh the injury to the eye.

Cholinesterase deficiency

Suxamethonium is rapidly hydrolysed by plasma cholinesterase which thereby limits the intensity and duration of the neuromuscular blockade.

Individuals with decreased plasma cholinesterase activity exhibit a prolonged response to suxamethonium. Approximately 0.05% of the population has an inherited cause of reduced cholinesterase activity.

Prolonged and intensified neuromuscular blockade following Suxamethonium Injection may occur secondary to reduced plasma cholinesterase activity in the following states or pathological conditions:

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- genetically determined abnormal plasma cholinesterase

- severe generalized tetanus, tuberculosis, other severe or chronic infections

- following severe burns

- chronic debilitating disease, malignancy, chronic anaemia and malnutrition

- end stage hepatic failure, acute or chronic renal failure ( see secton 4.2 Posology and Method of Administration)

- auto-immune diseases:myxoedema, collagen diseases;

- iatrogenic: following plasma exchange, plasmapheresis, cardiopulmonary bypass, and as a result of concomitant drug therapy.

Use in children

Muscle pains

Muscle pains are frequently experienced after administration of suxamethonium and most commonly occur in ambulatory patients undergoing short surgical procedures under general anaesthesia. There appears to be no direct connection between the degree of visible muscle fasciculation after Suxamethonium administration and the incidence or severity of pain. The use of small doses of non-depolarising muscle relaxants given minutes before suxamethonium administration has been advocated for the reduction of incidence and severity of suxamethonium-associated muscle pains. This technique may require the use of doses of suxamethonium in excess of 1mg/kg to achieve satisfactory conditions for endotracheal intubation.

Myasthenia gravis

It is inadvisable to administer suxamethonium to patients with advanced myasthenia gravis. Although these patients are resistant to suxamethonium they develop a state of atypical phase II block which can result in delayed recovery.

Myasthenic Eaton-Lambert syndrome

These patients are more sensitive than normal to suxamethonium - dose reduction required.

Prolonged use

If Suxamethonium is given over a prolonged period, the characteristic depolarizing neuromuscular (or Phase I) block may change to one with characteristics of a non-depolarising (or Phase II) block. Although the characteristics of a developing Phase II block resemble those of a true non-depolarising block, the former cannot always be fully or permanently reversed by anticholinesterase agents. When a Phase II block is fully established, its effects will then usually be fully reversible with standard doses of neostigmine accompanied by an anticholinergic agent.

Tachyphylaxis occurs after repeated doses.

Use with other solutions

Suxamethonium should not be mixed with any other agent in the same syringe (particularly thiopentone/thiopental).

This precaution is not relevant to the use of Suxamethonium Injection. Suxamethonium will always be used in combination with a general anaesthetic and therefore the usual precautions relating to performance of tasks following general anaesthesia apply.

Adverse reactions are listed below by system organ class and frequency. Estimated frequencies were determined from published data. Frequencies are defined as follows: very common (>1/10); common (>1/100 and <1/10), uncommon (>1/1,000 and <1/100); rare (>1/10,000 and <1/1,000); very rare (<1/10,000).

Immune system disorders

Eye disorders

Cardiac disorders

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard.

Apnoea and prolonged muscle paralysis are the main and serious effects of overdosage. It is essential to maintain the airway and to ensure adequate ventilation until spontaneous respiration occurs.

Neostigmine and other anticholinesterase drugs are not antidotes to suxamethonium but would normally intensify the depolarisation effect. However, in some cases when the action of suxamethonium is prolonged, the characteristic depolarising (Phase I) block may change to one with characteristics of a non-depolarising (Phase II) block.

The decision to use neostigmine to reverse a Phase II suxamethonium-induced block depends on the judgement of the clinician in the individual case. Valuable information in regard to this decision will be gained by monitoring neuromuscular function.

To investigate this possibility, the short-acting anticholinesterase drug, edrophonium, may be given intravenously. If an obvious improvement is maintained for several minutes, neostigmine may be given with atropine. Subsequently, the patient should be observed carefully and if apnoea recurs, a further dose of neostigmine is indicated.

Transfusion of fresh whole blood, frozen plasma, or other source of pseudocholinesterase will help the destruction of suxamethonium.

Pharmacotherapeutic group: Peripherally acting muscle relaxants, choline derivatives, ATC code: M03AB01.

Short-acting depolarising neuromuscular blocking agent.

A cholinester of succinic acid, the cation formed by the succinic acid radical with the quaternary ammonium group at each end of the molecule is the active part. Deteriorates in hot climates.

A depolarising neuromuscular blocking drug of brief duration, its action being prolonged by repeated doses. Its action can be prolonged by various drugs or by a deficiency of cholinesterase due to liver disease or an inherited enzyme deficiency.

It has certain adverse effects ranging from minor to grave consequences. Its beneficial effect is the rapidity in which the airway can be secured by endotracheal intubation.

The contraindications, precautions and warnings are well documented.

Following intravenous administration, there is rapid hydrolysis by pseudocholinesterase with the initial metabolite being succinylmonocholine a weak neuro-muscular drug. This is metabolised to succinic acid with only a small amount excreted in the urine.

Only a small fraction of suxamethonium reaches the neuromuscular junction. Its action is terminated by diffusion away from the end plate.

Succinylcholine does not readily cross the placenta.

Genotoxicity:

No bacterial mutation assays have been conducted.

There are some data to suggest a weak clastogenic effect in mice, but not in patients who had received Lysthenon.

Carcinogenicity:

Carcinogenicity studies have not been performed.

Embryo-foetal Development:

Animal reproduction studies have not been conducted with suxamethonium. It is also not known whether suxamethonium can affect reproductive capacity or cause foetal harm when administered to a pregnant woman.

Suxamethonium should not be mixed in the same syringe with any other agent especially thiopentone.

For I.M. and I.V. injection.

Use as directed by the physician.

Keep out of reach of children.

If only part used, discard the remaining solution.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.