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Full Prescribing Info
Suxamethonium Chloride.
Each mL contains: Suxamethonium Chloride, BP 20 mg.
Pharmacology: Pharmacokinetics: After injection, suxamethonium is rapidly hydrolyzed by plasma cholinesterase in plasma. One molecule of choline is split off rapidly to form succinylmonocholine which is then slowly hydrolyzed to succinic acid and choline. Only a small proportion of suxamethonium is excreted unchanged in the urine. Succinylmonocholine has weak muscle-relaxant properties mainly of a competitive nature.
The gene responsible for the expression of plasma cholinesterase exhibits polymorphism and enzyme activity varies between individuals.
Small amounts of suxamethonium do cross the placenta but clinical experience indicates that the neonate is not adversely affected when it has been used for caesarean section.
Suxamethonium is a depolarizing neuromuscular blocker used to produce muscle relaxation. It acts as an acetylcholine agonist at the neuromuscular unction, combining with cholinergic receptors of the motor end-plate to produce depolarization which may produce transient fasciculations. Succinylcholine is resistant to breakdown by acetylcholinesterase, the depolarization is prolonged, and the refractory period of the motor end-plate extended. This prevents repolarization and subsequent depolarization and a flaccid muscle paralysis occurs. This initial depolarization block is commonly known as a plate I block. The muscles that produce fine movements such as those of the face are the first to be affected followed by those of the limbs, abdomen, and chest; the diaphragm is affected last. Recovery occurs in reverse order. When excessive amounts of suxamethonium accumulate at the neuromuscular junction, for example following high or prolonged dosage, the nature of the block may change to one characteristics similar to competitive block.
This is commonly termed phase II block or dual block and may be associated with prolonged neuromuscular blockade and apnoea.
Dosage/Direction for Use
Following intravenous injection Suxamethonium acts in about 30 to 60 seconds and has a duration of action of about 2 to 6 minutes. Following intramuscular injection it acts in 2 to 3 minutes and has a duration of action to about 10 to 30 minutes. It is used in surgical and other procedures in which a rapid onset and brief duration of muscle relaxation is needed, including intubation, endoscopies, and electroconvulsive therapy. It is normally given by intravenous injection, usually as the chloride (but the bromide and iodine have also been used). Suxamethonium has to be given after induction of general anaesthesia because paralysis is usually preceded by painful muscle fasciculations. A competitive neuromuscular blocker may sometimes be given before suxamethonium to try to reduce some of the adverse effects on the muscles. Premedications with an antimuscarinic may be of value in reducing bradycardia and excessive salivation. Assisted respiration is necessary.
An initial test dose of 0.1 mg per kg of Suxamethonium may be given intravenously if increased sensitivity is suspected. Doses of neuromuscular blockers need to be carefully titrated for individual patients according to response and may vary with the procedure, the other drugs given, and the state of the patient; monitoring of the degree of block is recommended in order to reduce the risk of overdosage. The response to Suxamethonium varies considerably and the usual single dose of suxamethonium chloride for an adult is 0.3 to 1.1 mg per kg body-weight by intravenous injection with a usual range of 20 mg to a maximum total of 100 mg. Supplementary doses of 50 to 100% of the initial dose may be administered at 5 to 10 minute intervals if required but the total dose given by repeated intravenous injection or continuous infusion should not exceed 500 mg per hour. Infants and children are more resistant to Suxamethonium than adults. A recommended intravenous dose for infants under one year of age is 2 mg per kg; a dose of 1 mg per kg is recommended for children1 to 12 years old.
When a suitable vein is inaccessible Suxamethonium has been given by intramuscular injection in a dose of 3 to 4 mg per kg body-weight to a maximum total of 150 mg. The intramuscular dose for infants is up to a 4 to 5 mg per kg and for older children up to 4 mg per kg and for older children up to 4 mg per kg to a maximum total of 150 mg.
For prolonged procedures in adults sustained relaxation may be obtained by continuous intravenous infusion of a 0.1 to 0.2% solution. A rate of 2 to 5 mg per minute is usually adequate but may be adjusted as necessary. The total dose given by repeated intravenous injection or continuous infusion should not exceed 500 mg per hour. Or as prescribed by the Physician.
Special Precautions
Patients who have received a neuromuscular blocker should always have their respiration assisted or controlled until the drug has been inactivated or antagonized. Suxamethonium is contra-indicated in patients with atypical plasma cholinesterase and should be used with caution in patients with reduced plasma cholinesterase activity, which may occur in certain disease states and following exposure to certain drugs. Plasma cholinesterase concentrations fall during pregnancy and the puerperium and therefore maternal paralysis may be mildly prolonged. Suxamethonium is contraindicated in patients with burns, massive trauma, renal impairment with a raised plasma-potassium concentration, severe long-lasting sepsis, and severe hyperkalaemia, since suxamethonium-induced rises in plasma-potassium concentration can have serious consequences in such patients. It is contra-indicated in patients with a history of hypersensitivity to the drug and, because of the possibility of cross-sensitivity, should be used with caution when hypersensitivity to any neuromuscular blocker has previously occurred. Suxamethonium should be avoided in patients with a penetrating eye injury, raised intra-ocular pressure or glaucoma, or those about to undergo incision of the eyeball in eye surgery, because of the risks from increased intra-ocular pressure. Suxamethonium chloride procedures muscle concentrations before relaxation and should therefore be used with caution in patients with bone fractures. It is contraindicated in patients with a family history of malignant hyperthermia.
The response to suxamethonium is often unpredictable in patients with neuromuscular disorder and it should be used with great caution in these patients. Caution is also needed if it is given to a patient with cardiac or respiratory disease. Children may be at special risk from cardiac arrest associated with hyperkalaemia.
Hypothermia may enhance the neuromuscular blocking effects of suxamethonium and an increase in body temperature may reduce them.
Adverse Reactions
The neuromuscular blocking action of Suxamethonium is terminated by the enzyme plasma cholinesterase and prolonged apnoea may occur in patients with an atypical enzyme or with low enzyme activity. Apnoea may also occur following development of phase II block after high or repeated doses of suxamethonium chloride, although tachyphylaxis may also occur with repeated doses.
Administration of Suxamethonium results in transient fasciculations during the onset of depolarizing block. Rhabdomyolysis, myoglobinaemia, and myoglobinuria have been reported and may be associated with muscle damage following fasciculations. Postoperative muscle pain occurs in some patients but is not directly related to the degree of fasciculation. A transient rise in intra-gastric pressure may occur secondary to fasciculation of abdominal muscles. A transient increase in intra-ocular pressure often occurs. Depolarization of skeletal muscle procedures an immediate increase in plasma-potassium concentration and this can have serious consequences in some patients.
Stimulation of the vagus nerve and parasympathetic ganglia by suxamethonium chloride may be followed by bradycardia, other arrhythmias, and hypotension, and may be exacerbated by the raised plasma potassium concentration; cardiac arrest has been reported.
Tachycardia and an increase in blood pressure due to stimulation of ganglia have also been reported. Suxamethonium may cause an increase in salivary, bronchial, and gastric secretion and other muscarinic effects. Salivary gland enlargement has occurred.
Direct release of histamine from mast cells occurs but this is not the main mechanism of hypersensitivity reactions. Flushing, skin rash, bronchospasm, and shock have been reported.
Other reported effects include prolonged respiratory depression and apnoea.
Administration of suxamethonium chloride is implicated in the development of malignant hyperthermia in those patients with a genetic predisposition to the syndrome. Treatment of Adverse Effects: Following administration of suxamethonium assisted respiration should be maintained until spontaneous respiration has been fully restored. Transfusion of fresh whole blood, frozen plasma, or other source pf plasma cholinesterase will help the destruction of the suxamethonium when prolonged paralysis is a result of atypical or low serum concentrations of plasma cholinesterase. Anticholinesterases should not normally be used since they potentiate the usual phase I block. If the neuromuscular block ceases to be depolarizing in type and acquires some features of a competitive block (phase II block) the cautions use of an anticholinesterase may be considered. A short-acting anticholinesterase such as edrophonium may be given intravenously and if an obvious improvement is maintained for several minutes, neostigmine may be given with atropine.
Severe hypersensitivity reactions should be treated promptly with supportive and symptomatic measures. If malignant hyperthermia develops, it may be treated.
The muscarinic effects of suxamethonium chloride, such as bradycardia and excessive salivary secretin may be reduced by giving an antimuscarinic such a atropine before suxamethonium. A small dose of a competitive neuromuscular blocker given before suxamethonium has been to reduce some of the adverse effects of suxamethonium on the muscles.
Drug Interactions
A number of drugs may interact with depolarizing neuromuscular blockers such as suxamethonium. The mechanisms of interaction may include a direct effect on neuromuscular transmission or an alteration of enzyme activity and may result in potentiation or antagonism of neuromuscular block. In general, interactions with suxamethonium are potentially more serious in patients with impaired neuromuscular function and in patients with reduced activity of plasma cholinesterase.
Interactions common to competitive and depolarizing neuromuscular blockers are covered under Atracurium, whereas those specific for depolarizing blockers are discussed below.
Anticholinesterases: The action of suxamethonium can be markedly prolonged in patients using eye drops containing ecothiopate, a long-acting anticholinesterase which inhibits both acetylcholinesterase and plasma cholinesterase activity may rapidly be reduced to 5% or less of normal and prolonged apnoea after use of suxamethonium has occurred. On discontinuing ecothiopate, enzyme activity remains depressed for 1 to 2 months. If patient has used ecothiopate eye drops in the previous 2 months, suxamethonium should not be given unless normal plasma cholinesterase activity can be demonstrated; a competitive neuromuscular blocker is preferable. Exposure to organophosphorus insecticides may also reduce plasma cholinesterase activity resulting in prolonged paralysis after use of suxamethonium; enzyme activity may be totally abolished. Anticholinesterases including edrophonium, neostigmine, pyridostigmine, rivastigmine, tacrine, and possibly donepezil enhance the action of suxamethonium, although suxamethonium-induced phase II block can be reversed with an anticholinesterase. Care should be taken if there is a need to use suxamethonium for urgent short procedures after a competitive-neuromuscular-induced block has been antagonized with an anticholinesterase, as the resulting block may be greatly prolonged.
Antiepileptics: The mean time recovery from suxamethonium-induced neuromuscular block was 14.3 minutes in 9 patients receiving chronic treatment with phenytoin and/or carbamazepine compared with 10.0 minutes in 9 patients not receiving antiepileptics.
Antineoplastics: Cyclophosphamide has been reported to prolong the neuromuscular block produced by suxamethonium through reduction of plasma cholinesterase activity, possibly by alkylation of the enzyme.
Since enzyme activity may be reduced by up to 70% for several days to several weeks, it was suggested that suxamethonium should be avoided if possible in patients receiving cyclophosphamide. Other alkylating agents also reported to reduce plasma cholinesterase activity include mustine [chlormethine], thiotepa, and tretamine.
General anaesthetics: Tachyphylaxis and phase II block develop earlier, and after smaller total doses of suxamethonium, when inhalation anaesthetics are used. Halothane may increase the incidence of arrhythmias associated with suxamethonium and may potentiate suxamethonium-induced muscle damage. Suxamethonium should be used with caution with other drugs that might produce additive cardiovascular effects. Severe bradycardia and asystole have occurred when used in anaesthetic regimens with propofol and opioids such as fentanyl.
Local anaesthetics: Procaine, cocaine, and chloroprocaine are ester-type anaesthetics which are hydrolyzed by plasma cholinesterase and may competitively enhance the neuromuscular blocking activity of suxamethonium.
MAOIs: Reduction of plasma cholinesterase activity by phenelzine has been reported to cause significant prolongation of suxamethonium paralysis. Enzyme activity may reduced to 10% of normal and recovery may take up to a month. The dosage of suxamethonium may need to be substantially reduced or a competitive neuromuscular blocker used.
Metoclopramide: Dose-dependent prolongation of suxamethonium-induced neuromuscular blockade has been reported in patients given metoclopramide. The potent inhibitory effect of metoclopramide on plasma cholinesterase may account for this interaction.
Sex hormones: Oestrogens and oestrogen-containing oral contraceptives reduce plasma cholinesterase activity possibly due to suppression of hepatic synthesis of the enzyme, but little prolongation of suxamethonium paralysis may be expected since activity is reduced by only about 20%.
Sympathomimetics: Bambuterol can inhibit plasma cholinesterase activity and so prolong the activity of suxamethonium. Phase II block has been reported in some patients with abnormal plasma cholinesterase.
Store at temperatures between 2°C-8°C.
ATC Classification
M03AB01 - suxamethonium ; Belongs to the class of choline derivative agents used as peripherally-acting muscle relaxants.
Soln for inj (vial) 20 mg/mL x 10 mL x 10's.
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