Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: Mercury Pharmaceuticals Limited, Capital House, 85 King William Street, London EC4N 7BL, UK
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Suxamethonium should not be administered to a patient who is not fully anaesthetised. Neuromuscular function should be monitored when suxamethonium is being used over a prolonged period.
Suxamethonium causes a significant transient rise in intra-ocular pressure and therefore it should not be used in the presence of glaucoma, detached retina or open eye injury unless the potential benefit of its use outweighs the potential risk to the eye.
Suxamethonium is contra-indicated in patients with a 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.
Suxamethonium is contra-indicated in patients with inherited atypical or low serum level of pseudocholinesterase.
Prolonged and intensified neuromuscular blockade following a Suxamethonium, may occur secondary to reduced plasma cholinesterase in the following states or pathological conditions; end stage hepatic failure, acute or chronic renal failure.
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:
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.
Suxamethonium is also contra-indicated in patients with pre-existing hyperkalaemia. In the absence of hyperkalaemia and neuropathy, renal failure is not a contra-indication to the use of a normal single dose of suxamethonium, although multiple or large doses may cause clinically significant rises in serum potassium and should not be used.
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 is contra-indicated in patients with cerebral palsy.
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).
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.
High rates of cross-sensitivity (greater than 50%) between neuromuscular blocking agents have been reported. Therefore, where possible, before administering suxamethonium, hypersensitivity to other neuromuscular blocking agents should be excluded. 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.
Suxamethonium should not be mixed in the same syringe with any other agent, especially thiopental.
During prolonged administration of suxamethonium, it is recommended that the patient is fully monitored with a peripheral nerve stimulator in order to avoid overdosage.
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 (see section 4.3). In severe sepsis, the potential for hyperkalaemia may be related to the severity and duration of the infection.
In patients with low levels of plasma cholinesterase or with an abnormal pseudocholinesterase, suxamethonium should be used only with extreme caution and where the benefits of the drug are considered to outweigh the risks.
Suxamethonium is rapidly hydrolysed by plasma cholinesterase which thereby limits the intensity and duration of the neuromuscular blockade. Approximately 0.05% of the population has an inherited cause of reduced cholinesterase activity.
Deficiencies of this enzyme result in prolonged and intensified neuromuscular block. Deficiency may be
With prolonged use of suxamethonium, the characteristic depolarising blockade (Phase I block) may change to one with characteristics of a non-depolarising blockade (Phase II block), leading to prolonged respiratory depression or apnoea. 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 administration of suxamethonium.
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.
It is inadvisable to use suxamethonium in patients with advanced myasthenia gravis, neurological disorders, myotonia or muscular disease.
Although patients with advanced myasthenia gravis are resistant to suxamethonium they develop a state of Phase II block which can result in delayed recovery.
Patients with myasthenic (Eaton-Lambert) syndrome are more sensitive than normal to suxamethonium and the dose should be reduced. Patients in remission from myasthenic Eaton-Lambert syndrome may however demonstrate a normal response to suxamethonium.
Caution should be exercised when using suxamethonium in children, since paediatric patients are more likely to have an undiagnosed myopathy or an unknown predisposition to malignant hyperthermia and rhabdomyolysis, which places them at increased risk of serious adverse events following suxamethonium (see section 4.3 Contraindications and section 4.8 Adverse Reactions).
In healthy adults, suxamethonium occasionally causes a mild transient slowing of the heart rate on initial administration.
Bradycardias are more commonly observed in children and on repeated administration of suxamethonium in both children and adults. Pre-treatment with intravenous atropine or glycopyrrolate significantly reduces the incidence and severity of suxamethonium-related bradycardia.
In the absence of pre-existing or evoked hyperkalaemia, ventricular arrhythmias are rarely seen following suxamethonium administration. Cardiac arrhythmias can develop in patients receiving digitalis glycosides who are given suxamethonium. Patients taking digitalis-like drugs are however more susceptible to such arrhythmias. The action of suxamethonium on the heart may cause changes in cardiac rhythm including cardiac arrest.
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.
This agent should be used with caution in ill and cachectic patients, in patients with acid-base disturbances or electrolyte imbalance, parenchymatous liver disease, obstructive jaundice, carcinomatosis, in those in contact with certain insecticides, e.g. organophosphorous compounds and in those receiving therapeutic radiation.
Suxamethonium should be used with caution in patients with fractures or muscle spasms because the initial muscle fasciculations may cause additional trauma.
Muscarinic effects of this compound e.g. increased bronchial and salivary secretions may be prevented by atropine.
When this agent is given as an infusion, this should be monitored with care to avoid overdose.
Suxamethonium has no direct effect on the myocardium, but by stimulation of both autonomic ganglia and muscarinic receptors suxamethonium may cause changes in cardiac rhythm, including cardiac arrest.
Certain drugs or chemicals are known to reduce normal plasma cholinesterase activity and may therefore prolong the neuromuscular blocking effects of suxamethonium. These include:
Enhanced effects of suxamethonium with:
Enhanced effects of suxamethonium with:
Enhanced effects of suxamethonium with:
Enhanced effects of suxamethonium with:
Enhanced effects of suxamethonium with:
Enhanced effects of suxamethonium with:
In addition to the drugs listed above, certain other drugs and chemicals are known to reduce normal plasma cholinesterase activity and therefore may prolong the neuromuscular effect of suxamethonium.
These include:
The following have potentially adverse effects on plasma cholinesterase activity:
Liver disease, cancer, pregnancy, dehydration, electrolyte imbalances and overdosage (due to excessive production of succinylmonocholine) may also prolong the action of suxamethonium.
Suxamethonium has no direct action on the uterus or other smooth muscle structures. In normal therapeutic doses it does not cross the placental barrier in sufficient amounts to affect the respiration of the infant.
The benefits of the use of suxamethonium as part of a rapid sequence induction for general anaesthesia normally outweigh the possible risk to the foetus.
Plasma cholinesterase levels fall during the first trimester of pregnancy to about 70 to 80% of their pre-pregnancy values; a further fall to about 60 to 70% of the pre-pregnancy levels occurs within 2 to 4 days after delivery. Plasma cholinesterase levels then increase to reach normal over the next 6 weeks. Consequently, a high proportion of pregnant and puerperal patients may exhibit mildly prolonged neuromuscular blockade following Suxamethonium Injection.
Suxamethonium Chloride Injection should not be used unless clearly necessary.
It is not known whether suxamethonium is excreted in breast milk, therefore, caution should be exercised following administration of suxamethonium to nursing mothers.
No studies of the effect of suxamethonium on female fertility or pregnancy have been performed.
Suxamethonium chloride has a major influence on the ability of an individual to drive or operate machinery.
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.
There is limited clinical documentation that can be used as support for determining the frequency of adverse reactions. The frequency categories assigned to the adverse reactions are estimates. For most reactions, the frequency was determined from published data and the background incidence was not considered when determining the frequency groups.
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).
Very Rare: Anaphylactic reactions
Common: Increased intraocular pressure
Common: Bradycardia, tachycardia
Rare: Arrhythmias (including ventricular arrhythmias), cardiac arrest1
Common: Skin flushing. Hypertension and hypotension have also been reported.
Rare: Bronchospasm, prolonged respiratory depression2, apnoea.
Very Common: Increased intragastric pressure. Excessive salivation has also been reported
Common: Rash
Very common: Muscle fasciculation, post-operative muscle pains (please refer to section 4.4)
Common: Myoglobinaemia3, myoglobinuria3
Rare: Trismus
Vary rare: Malignant hyperthermia (please refer section 4.4)
Common: Transient blood potassium increase
1 There are case reports of hyperkalaemia-related cardiac arrests following the administration of suxamethonium to patients with congenital cerebral palsy, tetanus, Duchenne muscular dystrophy, and closed head injury. Such events have also been reported rarely in children with hitherto undiagnosed muscular disorders.
2 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 (Please refer to section 4.4 Special Warnings and Precautions for Use)
3 Rhabdomyolysis has also been reported (see section 4.3 and section 4.4)
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 or search for MHRA Yellow Card in the Google Play or Apple App Store.
This medicinal product must not be mixed in the same syringe with any other agent especially thiopentone.
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