Suxamethonium Chloride Injection BP Product Information 1 (8)

Suxamethonium Chloride Injection BP

PRODUCT INFORMATION

NAME OF DRUG

The Australian Approved Name is suxamethonium chloride.

The CAS number for suxamethonium chloride dihydrate is 6101-15-1.
The chemical structure is:

o
o N+(CH3)3 2 Cl-
(H3C)3+N o
o

DESCRIPTION

The chemical name for suxamethonium chloride is

2, 2-succinyldioxybis(ethyltrimethylammonium) dichloride dihydrate. It is a white or
almost white, crystalline powder. Suxamethonium Chloride Injection is a sterile
solution of suxamethonium chloride suitable for IV injection. Each mL of solution
contains 50 mg suxamethonium chloride in Water for Injections BP. The pH of the
solution is 3.0 - 5.0.

The presentation of Suxamethonium Chloride Injection is intended for single use

only. Any solution remaining from an opened container should be discarded.

PHARMACOLOGY

Suxamethonium is an ultra short-acting depolarising-type neuromuscular blocking

agent.

Suxamethonium combines with the cholinergic receptors of the motor end plate to
produce depolarisation. Neuromuscular transmission is inhibited so long as an
adequate concentration of suxamethonium remains at the receptor site.

Suxamethonium has no direct action on smooth muscle structures, including the

uterus. Suxamethonium may produce slowing of heart rate via vagal stimulation.

When suxamethonium is administered over a prolonged period the characteristics of

the neuromuscular block may change from the characteristic depolarising type to one
resembling a nondepolarising block.
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Pharmacokinetics

Absorption: Suxamethonium has a rapid onset and a short duration of action.

Following intravenous (IV) administration of a single therapeutic dose in healthy
adults, complete muscle relaxation occurs within 1/2 to 1 minute, persists for about
2 - 3 minutes, and gradually dissipates within 10 minutes.

Following intramuscular (IM) administration the onset of action occurs in about 2 - 3

minutes, with a duration ranging from 10 - 30 minutes.

The duration of action is prolonged in patients with low plasma pseudocholinesterase

concentration.

Distribution: Suxamethonium crosses the placenta, generally in small amounts.

Elimination: Plasma pseudocholinesterases hydrolyse suxamethonium to

succinylmonocholine (relatively inactive) and choline. Approximately 10% of drug is
excreted unchanged in the urine.

Patients with impaired renal function may occasionally experience prolonged apnoea
due to accumulation of succinylmonocholine.

INDICATIONS

For the production of skeletal muscle relaxation in anaesthesia. Suited for

procedures requiring only brief relaxation such as endotracheal intubation,
endoscopic examinations, orthopaedic manipulations, short surgical procedures and
electro-convulsive therapy.

CONTRAINDICATIONS

Patients with a personal or familial history of malignant hyperthermia, genetically

determined disorders of pseudocholinesterase, myopathies associated with elevated
creatinine phosphokinase (CPK) values, Duchenne's muscular dystrophy, known
hypersensitivity to suxamethonium, severe hyperkalaemia, acute narrow-angle
glaucoma, and the presence of penetrating eye injuries (suxamethonium may cause
a slight, transient increase in intraocular pressure).

It is also contraindicated in patients after the acute phase of injury following major
burns, or multiple trauma, *renal impairment with a raised plasma-potassium
concentration, or in those with extensive muscle degeneration such as recent
paraplegia and severe long-lasting sepsis because such patients may become
severely hyperkalaemic when given suxamethonium, resulting in cardiac arrhythmia
or arrest.
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PRECAUTIONS
Suxamethonium should only be administered under strict supervision of an
anaesthetist familiar with its actions, characteristics and hazards who is skilled in the
management of artificial respiration and only when facilities are instantly available for
endotracheal intubation and for providing adequate ventilation of the patient,
including the administration of oxygen under positive pressure. Be prepared to
assist or control respiration.

Suxamethonium has no effect on consciousness, pain threshold or cerebration. It

should therefore only be used with adequate anaesthesia.

Malignant Hyperthermia
The abrupt onset of malignant hyperthermia, a very rare hypermetabolic process of
skeletal muscle, may be triggered by suxamethonium. Early premonitory signs
include muscle rigidity, tachycardia, tachypnoea unresponsive to increased depth of
anaesthesia, evidence of increased oxygen requirement and carbon dioxide
production, rising temperature and metabolic acidosis.

On evidence of these symptoms the anaesthetic and suxamethonium should be

discontinued and supportive measures implemented including administration of
oxygen, sodium bicarbonate, lowering of temperature, restoration of fluids and
electrolyte balance, maintenance of adequate urinary output and administration of IV
dantrolene according to a standard protocol.

Hyperkalaemia
Administration of suxamethonium causes an immediate rise in serum potassium.
This rise is normally small but may be prolonged and exaggerated in patients taking
beta-blockers.

Great caution should also be observed in patients with pre-existing hyperkalaemia or

electrolyte imbalance, uraemia, hemiplegia, paraplegia, extensive burns, massive
trauma, diffuse intracranial lesions (head injury, encephalitis, ruptured cerebral
aneurysm), tetanus, acute anterior horn cell disease, extensive denervation of
skeletal muscle due to disease or injury of the CNS, or who have degenerative
neuromuscular disease and in severe long-lasting sepsis. Such patients may
become severely hyperkalaemic when given suxamethonium, resulting in cardiac
arrhythmia or arrest (see CONTRAINDICATIONS).

With burns or trauma the period of greatest risk is from about 10 - 90 days after the
injury, but may be prolonged further if there is delayed healing or persistent infection.
These patients may still react abnormally to suxamethonium 2 years after the injury.
In neuromuscular disease the greatest risk period is usually from 3 weeks to 6
months after onset, but severe hyperkalaemia may occur after 24 to 48 hours or later
than 6 months. Patients with severe sepsis for more than a week should be
considered at risk of hyperkalaemia and suxamethonium should not be given until
the infection has cleared.
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Hyperkalaemia Rhabdomyolysis
There is a risk of cardiac arrest from hyperkalaemia due to rhabdomyolysis,
particularly in male patients with muscular dystrophy.

Low plasma pseudocholinesterase

Recovery from suxamethonium may occasionally be delayed possibly due to a low
serum pseudocholinesterase level, this may occur in patients suffering from severe
liver disease, cancer, malnutrition, severe dehydration, collagen diseases, severe
anaemia, myxoedema, burns, pregnancy and the puerperium, severe infections,
myocardial infarction, renal impairment and abnormal body temperature.

Also exposure to neurotoxic insecticides or weed killers, anti-malarial or anti-cancer

drugs, monoamine oxidase (MAO) inhibitors, contraceptive pill, pancuronium,
chlorpromazine, ecothiopate or neostigmine may result in low levels of
pseudocholinesterase.

Suxamethonium should be administered with extreme caution and in reduced doses

in such patients. If low pseudocholinesterase concentration is suspected slow
administration of a small test dose of suxamethonium (5 - 10 mg as a 0.1% solution)
should be considered.

Antidysrhythmic drugs
Suxamethonium should be administered with great caution in patients receiving
quinidine and those who have been digitalised or who may have digitalis toxicity. In
these circumstances the rise in serum potassium due to suxamethonium may
possibly cause arrhythmias.

Delayed recovery
When recovery from suxamethonium is delayed, assisted respiration sufficient for full
oxygenation, yet avoiding excessive elimination of carbon dioxide, should be
maintained until paralysis ceases. This should be combined with light narcosis,
e.g. nitrous oxide/oxygen mixture.

Neostigmine should not be given when prolonged apnoea follows a single dose of
suxamethonium. Neostigmine and other anticholinesterase drugs may have the
effect of intensifying the depolarisation block caused by suxamethonium.

Nondepolarising blockade
If suxamethonium is given repeatedly or over a prolonged period the depolarising
block may change to one with characteristics of a nondepolarising block. This may
be associated with prolonged respiratory depression and apnoea. Following a
positive diagnosis of a nondepolarising blockade the administration of neostigmine
preceded by atropine may be considered.
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Debilitated Patients
Use with caution in patients who are hypoxic or those who have cardiovascular,
hepatic, pulmonary, metabolic or renal disorders or myasthenia gravis. The action of
suxamethonium may be altered in these patients. Its use is not advisable in patients
with phaeochromocytoma. As suxamethonium produces muscle contractions before
relaxation it should be used with caution in patients with bone fractures.

Suxamethonium should be avoided in patients with myotonias, as response is

unpredictable.

Use in eye surgery

Suxamethonium causes a slight transient increase in intraocular pressure
immediately after injection and during the fasciculation phase. It should therefore be
used cautiously if at all during intraocular surgery and in patients with glaucoma.

Use in pregnancy Category A

Safety of the use of suxamethonium in pregnancy has not been established with
respect to effects on fetal development. Therefore suxamethonium should not be
administered to pregnant women unless the potential benefit outweighs the possible
hazards.

Plasma pseudocholinesterase levels are decreased in pregnancy and several days

postpartum by approximately 25%, therefore a high proportion of these patients may
be expected to show prolonged apnoea.

Suxamethonium crosses the placenta, but generally only in small amounts. Residual
neuromuscular blockade may occasionally occur in the neonate after repeated high
doses of suxamethonium to the mother during delivery by caesarean section.

Interactions with other drugs

Co-administration of inhaled anaesthetics (cyclopane, diethylether, halothane and

nitrous oxide) may increase the incidence of dysrhythmias (especially bradycardia),
apnoea and the occurrence of malignant hyperthermia in susceptible persons.
Inhaled anaesthetics have little effect on the usual depolarising neuromuscular
blockade of suxamethonium but may enhance the Phase II block (nondepolarising)
that may be produced by repeated dosage of suxamethonium. Severe bradycardia
and asystole have occurred when suxamethonium is used in anaesthetic regimens
with propofol and opioids such as fentanyl.

Drugs which may enhance or prolong the effects of suxamethonium include

lignocaine, procaine, oxytocin, oral contraceptives, some non-penicillin antibiotics,
(streptomycin, neomycin, kanamycin, capreomycin, tobramycin, framycetin,
amikacin, gentamicin, colistin and polymyxins), tacrine, beta-adrenergic blockers,
trimethaphan, phenelzine, aprotinin, quinidine, promazine, lithium carbonate,
phenytoin, carbamazepine, magnesium salts, quinine, chloroquine, cimetidine,
terbutaline sulfate, high dose corticosteroids and cytostatic agents such as
cyclophosphamide, thiotepa and azathioprine. Diazepam may reduce the duration of
neuromuscular blockade produced by suxamethonium.
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Amphotericin B and thiazide diuretics may increase the effects of suxamethonium

secondary to induced electrolyte imbalance. Patients with hypokalemia or
hypocalcaemia require reduced doses of suxamethonium.

Inhibitors of plasma cholinesterases such as neostigmine, pyridostigmine bromide,

rivastigmine, donepezil, metoclopramide, physostigmine and phospholine iodide can
considerably prolong the depolarising action of suxamethonium. It is recommended
that long-acting anticholinesterase inhibitor (ecothiopate) eye drops should be
discontinued several months prior to administration of suxamethonium.

Administration of suxamethonium prior to or with a nondepolarising muscle relaxant

e.g. pancuronium, mivacurium can alter the intensity and/or duration of
neuromuscular blockade.

Simultaneous administration of suxamethonium and atracurium significantly reduces

the duration of suxamethonium.

Concomitant digoxin or verapamil, and suxamethonium therapy has been reported

to result in cardiac arrhythmias.

ADVERSE REACTIONS

The following adverse reactions have been reported following administration of

suxamethonium:

Neuromuscular: post-operative muscle pain, muscle fasciculation,

rhabdomyolysis, myoglobinuria, myoglobinaemia, elevated
creatine phosphokinase, hypertonia, trismus.
Cardiovascular: bradycardia, tachycardia, arrhythmias, cardiac arrest,
hypertension, hypotension, tachyphylaxis, ventricular
fibrillation as a result of hyperkalaemia.
Respiratory: apnoea, prolonged respiratory failure, bronchospasm,
increased bronchial secretions, pulmonary oedema in
infants.
Endocrine, metabolic: malignant hyperthermia, porphyria, hyperkalaemia,
excessive salivation.
Gastrointestinal: increased intragastric pressure, increased bowel
movements, increased gastric secretions, *possible
aspiration.
Special senses: increased intraocular pressure.
Other: Rise in intracranial pressure, renal failure, precipitation or
exacerbation of myasthenia gravis
Hypersensitivity reactions including circulatory collapse,
flushing, rash, urticaria, bronchospasm and shock, which
may lead to death.
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DOSAGE AND ADMINISTRATION

Dosage is individualised and its administration should be determined after careful

assessment of the patient. The dose of suxamethonium is dependent on
bodyweight, the degree of muscle relaxation required and the response of individual
patients. Suxamethonium causes paralysis of the respiratory muscles, therefore
after administration, respiration must be controlled. It should not be administered to
a conscious patient.

Suxamethonium should not be mixed with any neuromuscular blocking agent, nor
with general anaesthetics such as short acting barbiturates, nor any other
therapeutic agent in the same syringe.

Suxamethonium Chloride Injection contains no antimicrobial agent. It should be

used only once and any residue discarded.

An initial test dose of 0.1 mg/kg may be given intravenously to determine the patients
response.

Adult: For short procedures, such as endotracheal intubation the usual adult dose is
0.6 mg/kg (range 0.3 - 1.1 mg/kg) administered IV over 10 to 30 seconds. This dose
produces muscle relaxation in about 60 seconds and has a duration of approximately
4 to 6 minutes. Larger doses produce more prolonged muscle relaxation.

For more prolonged surgical procedures in an adult, suxamethonium is commonly

given by IV infusion at a rate of 2.5 - 4.3 mg/minute. When given by intravenous
infusion suxamethonium should be diluted to 0.1 to 0.2% (1 - 2 mg/mL) in 5%
dextrose solution or sterile isotonic saline.

Children: Neonates and premature infants may be relatively resistant to

suxamethonium.

The usual paediatric IV dose is 1 to 2 mg/kg. If necessary, additional doses maybe

administered in accordance with patients response. Continuous IV infusions of
suxamethonium are considered unsafe in neonates and children because of the risk
of inducing malignant hyperthermia.

Intravenous bolus in children may result in profound bradycardia or on occasion

asystole. This tends to be more common after a second dose. Pre-treatment with
atropine can reduce the risk of bradycardia.

When a suitable vein is inaccessible, suxamethonium may occasionally be given by

intramuscular injection. A suggested i.m. dose for adults and children may be up to
2.5 mg/kg but the total dose should not exceed 150 mg.

Diluted solutions of suxamethonium must be used within 24 hours of preparation.

Discard unused solutions.
Suxamethonium Chloride Injection BP Product Information 8 (8)

OVERDOSAGE

The most serious effects of overdosage are apnoea and prolonged muscle paralysis.
It is essential to maintain the airway and adequate ventilation until spontaneous
respiration is fully restored.

The use of neostigmine to reverse a nondepolarising block is a clinical decision

which depends on the subject, the experience, and the judgment of the clinician. If
neostigmine is used, its administration should be accompanied by an appropriate
dose of atropine.

PRESENTATION

PolyampDuoFit ampoules 100 mg/2 mL, in packs of 50

STORAGE

Store between 2 - 8C. REFRIGERATE - DO NOT FREEZE.

NAME AND ADDRESS OF THE SPONSOR

AstraZeneca Pty Ltd

ABN 54 009 682 311
Alma Road, North Ryde
NSW 2113 Australia

Polyamp DuoFit is a trade mark of the AstraZeneca group of companies

Date of TGA approval letter 4 September 1996

Date of Safety Related Notification: 20 Oct 2011