Suxamethonium chloride

Overdose

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.

Shelf life

Unopened : 18 months

Contraindications

- 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).

Incompatibilities

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

List of excipients

Sodium Acetate B.P

Water for Injections BP

Pharmaceutical form

Clear, colourless, sterile solution, intended for parenteral administration to human beings.

Undesirable effects

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

Very rare

Anaphylactic reactions.

Eye disorders

Common

Increased intraocular pressure.

Cardiac disorders

Common	Bradycardia, tachycardia.
Rare	Arrhythmias (including ventricular arrhythmias), cardiac arrest.

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. Vascular disorders
Common	Skin flushing.
Hypertension and hypotension have also been reported. Respiratory, thoracic and mediastinal disorders
Rare	Bronchospasm, prolonged respiratory depressionâ€ , apnoea.
â€ 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 ) Gastrointestinal disorders
Very common	Increased intragastric pressure.
Excessive salivation has also been reported Skin and subcutaneous tissue disorders
Common	Rash.
Musculoskeletal and connective tissue disorders
Very common
Common	Myoglobinaemia#, myoglobinuria#.
Rare	Trismus
4 Special Warnings and Precautions for Use) General disorders and administration site conditions
Very rare
Investigations
Common	Transient blood potassium increase.

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.

Preclinical safety data

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 suxamethonium chloride.

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.

Therapeutic indications

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.

Pharmacotherapeutic group

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

Pharmacodynamic properties

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.

Pharmacokinetic properties

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.

Date of revision of the text

20/04/2017

Name of the medicinal product

Suxamethonium Chloride 50mg/ml Solution for Injection

Marketing authorisation holder

Mercury Pharma International Ltd

4045, Kingswood Road,

City West Business Park,

Co Dublin, Ireland

Special precautions for storage

Protect from light.

Store at 2 - 8°C.

Do not freeze.

Nature and contents of container

2ml, clear One point cut (OPC) glass ampoules, glass type 1 Ph.Eur. borosilicate glass, packed in cardboard cartons to contain 10 x 2ml ampoules.

Marketing authorisation number(s)

PL 02848/0140.

Fertility, pregnancy and lactation

Fertility and pregnancy:

No studies of the effect of suxamethonium on female fertility or pregnancy have been performed.

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.

Breast-feeding:

It is not known whether suxamethonium or its metabolites are excreted in human milk therefore, caution should be exercised following administration of suxamethonium to nursing mothers.

Qualitative and quantitative composition

Each 2ml of solution contains 100mg of suxamethonium chloride BP

Special warnings and precautions for use

. 4.3 Contraindications