Suxamethonium Chloride Injection BP 100mg/2ml.

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

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

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.

Suxamethonium chloride is usually administered by the intravenous route. It is given intravenously after anaesthesia has been induced and should not be administered to the conscious patient. Assisted respiration is necessary.

The dosage for adults and children is dependent on body weight and the degree of muscular relaxation required. The usual single dose for an adult is in the range of 20 to 100mg intravenously, depending on the patient's body weight and the degree of muscular relaxation required. Infants and younger children are relatively resistant to suxamethonium. A suggested dose for children is in the range of 1 to 2mg/kg body weight, intravenously.

If necessary, the intramuscular route may be used and a dose up to 2.5mg/kg body weight may be given intramuscularly to adults or children to a maximum total of 150mg.

For administration by continuous intravenous infusion, a 0.1 to 0.2% solution may be used and the adult dose ranges from 2 to 5mg per minute.

• Conscious patients (see section 4.2)

• Hypersensitivity to the drug.

• 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 (prolonged and/or intensified response occurs - see section 4.4)

• Patients with or who are susceptible to hyperkalaemia (see also section 4.4) such as those

- with pre-existing hyperkalaemia.

- recovering from major trauma or severe burns (greatest risk about 5 to 70 days after the injury: may be further prolonged if there is persistent infection with delayed healing)

- with neurological deficits and acute major muscle wasting (eg upper and/or lower motor neurone lesions and paraplegia).

- immobilized for long periods

• 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 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.

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 (see section 4.3). In severe sepsis, the potential for hyperkalaemia may be related to the severity and duration of the infection.

Bradycardia and other cardiac dysrhythmias

Bradycardias occurs particularly in children or if repeated doses are given (both adults and children).Pre-treatment with intravenous atropine or glycopyrrolate can reduce the incidence and/or severity.

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 (see section 4.5).

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. Deficiencies of this enzyme result in prolonged and intensified neuromuscular block. Deficiency may be

• congenital (1/3,000 of the population)

• physiological (during pregnancy and purpurium)

• acquired (in conjunction with liver disease, malnutrition, carcinomatosis, pregnancy, uraemia/renal disease, connective tissue disorders, thyroid disorders, severe burns, tetanus, tuberculosis and other severe infections). Recovery from suxamethonium may be delayed in liver disease due to low serum pseudocholinesterase levels, caution is advised.

• .iatrogenic (during cardiopulmonary bypass, following plasma exchange/ plasmapheresis, and with other drugs - see section 4.5).

Use in children

Caution as children are more likely to have undiagnosed myopathies or pre-disposition to malignant hyperthermia (see section 4). Susceptible to bradycardia (see above).

Muscle pains

Muscle pains frequently occur particularly in patients who are ambulatory following short procedures. These may be reduced by a small doses of a non-depolarizing muscle relaxant immediately before suxamethonium however, this reduces the potency of suxamethonium and a larger dose (in excess of 1mg/kg ) is required for the same effect.

Myasthenia gravis

Patient with myasthenia gravis are resistant to suxamethonium and go on to develop an atypical phase II block (delayed recovery).

Myasthenic Eaton-Lambert syndrome

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

Prolonged use

Tachyphylaxis occurs after repeated doses. If to be used long-term, full monitoring with a peripheral nerve stimulator is recommended. Phase I block may develop into an atypical non-depolarizing (phase II or dual) block that may not be fully or permanently reversed by anticholinesterases.

Use with other solutions

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

Antibacterials

Enhanced effects of suxamethonium with

• Aminoglycosides

• Clindamycin, polymyxins and vancomycin

• Piperacillin

Antimalarials

• Quinine - effects of suxamethonium possibly enhanced

Antipsychotics

Enhanced effects of suxamethonium with

• Promazine

• Promethazine

• Chlorpromazine

• Phenelzine

• Lithium carbonate

General anaesthetic agents

• Propofol – increased risk of myocardial depression and bradycardia

• Volatile liquid GAs – enhanced effects of suxamethonium

• Ketamine and propanidid – possible prolonged block

Analgesics

Enhanced effects of suxamethonium with

• Morphine, morphine antagonists, pethidine

Anti-arrhythmics

• Lidocaine (lignocaine) – enhanced and prolonged neuromuscular blockade

Local anaesthetics

Enhanced effects of suxamethonium with

• Procaine

• Cocaine

• Chloroprocaine

• Lidocaine (see above)

Cardiac glycosides

• Possible increased risk of bradycardia and other dysrhythmias, including ventricular dysrhythmias and cardiac arrest (also see sections 4.4 and 4.8).

• More susceptible to the effects of suxamethonium exacerbated by hyperkalaemia

Cytotoxics

Enhanced effects of suxamethonium with

• Cyclophosphamide

• Thiotepa

• Other alkylating agents (chlorethamine: tretamine)

Immunomodulators

• Azathioprine – prolonged neuromuscular blockade

Magnesium

• Parenteral magnesium – enhanced neuromuscular blockade

Metoclopramide

• Enhanced effects of suxamethonium

Parasympathetics

Enhanced effects of suxamethonium with

• Donepezil

• Edrophonium, galantamine, neostigmine, pyridostigmine and rivastigmine

• Tacrine hydrochloride

Sympathamomimetics (beta agonists)

• Bambuterol and terbutaline – enhanced effects of suxamethonium

Beta-blockers

Enhanced/prolonged neuromuscular blockade

Anti-histamines

• Diphenhydramine – enhanced effects of suxamethonium

Drugs known to reduce normal plasma cholinesterase

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

• Organophosphorous insecticides and metriphonate

• Ecothiopate eye drops (prolonged apnoea after suxamethonium has occurred)

• Trimetaphan

The following have potentially adverse effects on plasma cholinesterase activity

• Aprotinin

• Oestrogens and oral contraceptives

• Oxytocin

• High-dose steroids

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.

It is not known whether suxamethonium or its metabolites are excreted in human milk.

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).

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.

Hypertension and hypotension have also been reported.

Please refer to section 4.4 Special Warnings and Precautions for Use

Excessive salivation has also been reported

# Rhabdomyolysis has also been reported (see section 4.3 Contraindications and section 4.4 Special Warnings and Precautions for Use)

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. 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.

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.

No further relevant information other than that which is included in other sections of the Summary of Product Characteristics.

Sodium Acetate B.P

Water for Injections BP

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

Unopened : 18 months

Protect from light.

Store at 2 - 8°C.

Do not freeze.

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.

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.

Antigen International Ltd.,

Roscrea,

Co. Tipperary,

Ireland.

PL 2848/0140.

04 September 1990 / 22 August 1996.

16/04/2012