Suxametónio labesfal

Overdose

Overdosage with succinylcholine may result in neuromuscular block beyond the time needed for surgery and anesthesia. This may be manifested by skeletal muscle weakness, decreased respiratory reserve, low tidal volume, or apnea. The primary treatment is maintenance of a patent airway and respiratory support until recovery of normal respiration is assured. Depending on the dose and duration of succinylcholine administration, the characteristic depolarizing neuromuscular block (Phase I) may change to a block with characteristics superficially resembling a non-depolarizing block (Phase II) (see PRECAUTIONS).

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.

Contraindications

Succinylcholine is contraindicated in persons with personal or familial history of malignant hyperthermia, skeletal muscle myopathies and known hypersensitivity to the drug. It is also contraindicated in patients after the acute phase of injury following major burns, multiple trauma, extensive denervation of skeletal muscle, or upper motor neuron injury, because succinylcholine administered to such individuals may result in severe hyperkalemia which may result in cardiac arrest (see WARNINGS). The risk of hyperkalemia in these patients increases over time and usually peaks at 7 to 10 days after the injury. The risk is dependent on the extent and location of the injury. The precise time of onset and the duration of the risk period are not known.

- Conscious patients. Suxamethonium has no effect on the level of consciousness and should not be administered to a patient who is not fully anaesthetised.

-

- 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.

Undesirable effects

Adverse reactions to succinylcholine consist primarily of an extension of its pharmacological actions. Succinylcholine causes profound muscle relaxation resulting in respiratory depression to the point of apnea; this effect may be prolonged. Hypersensitivity reactions, including anaphylaxis, may occur in rare instances. The following additional adverse reactions have been reported: cardiac arrest, malignant hyperthermia, arrhythmias, bradycardia, tachycardia, hypertension, hypotension, hyperkalemia, prolonged respiratory depression or apnea, increased intraocular pressure, muscle fasciculation, jaw rigidity, postoperative muscle pain, rhabdomyolysis with possible myoglobinuric acute renal failure, excessive salivation, and rash.

There have been post-marketing reports of severe allergic reactions (anaphylactic and anaphylactoid reactions) associated with use of neuromuscular blocking agents, including succinylcholine. These reactions, in some cases, have been life threatening and fatal. Because these reactions were reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency (See WARNINGS and PRECAUTIONS).

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

Eye disorders

Cardiac disorders

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 Suxametónio Labesfal.

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

Succinylcholine chloride is indicated as an adjunct to general anesthesia, to facilitate tracheal intubation, and to provide skeletal muscle relaxation during surgery or mechanical ventilation.

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

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.

Name of the medicinal product

Qualitative and quantitative composition

Special warnings and precautions for use

SUCCINYLCHOLINE SHOULD BE USED ONLY BY THOSE SKILLED IN THE MANAGEMENT OF ARTIFICIAL RESPIRATION AND ONLY WHEN FACILITIES ARE INSTANTLY AVAILABLE FOR TRACHEAL INTUBATION AND FOR PROVIDING ADEQUATE VENTILATION OF THE PATIENT, INCLUDING THE ADMINISTRATION OF OXYGEN UNDER POSITIVE PRESSURE AND THE ELIMINATION OF CARBON DIOXIDE. THE CLINICIAN MUST BE PREPARED TO ASSIST OR CONTROL RESPIRATION.

TO AVOID DISTRESS TO THE PATIENT, SUCCINYLCHOLINE SHOULD NOT BE ADMINISTERED BEFORE UNCONSCIOUSNESS HAS BEEN INDUCED. IN EMERGENCY SITUATIONS, HOWEVER, IT MAY BE NECESSARY TO ADMINISTER SUCCINYLCHOLINE BEFORE UNCONSCIOUSNESS IS INDUCED.

SUCCINYLCHOLINE IS METABOLIZED BY PLASMA CHOLINESTERASE AND SHOULD BE USED WITH CAUTION, IF AT ALL, IN PATIENTS KNOWN TO BE OR SUSPECTED OF BEING HOMOZYGOUS FOR THE ATYPICAL PLASMA CHOLINESTERASE GENE.

(See BOX WARNING) Succinylcholine should be administered with GREAT CAUTION to patients suffering from electrolyte abnormalities and those who may have massive digitalis toxicity, because in these circumstances succinylcholine may induce serious cardiac arrhythmias or cardiac arrest due to hyperkalemia.

GREAT CAUTION should be observed if succinylcholine is administered to patients during the acute phase of injury following major burns, multiple trauma, extensive denervation of skeletal muscle, or upper motor neuron injury (see CONTRAINDICATIONS). The risk of hyperkalemia in these patients increases over time and usually peaks at 7 to 10 days after the injury. The risk is dependent on the extent and location of the injury. The precise time of onset and the duration of the risk period are undetermined. Patients with chronic abdominal infection, subarachnoid hemorrhage, or conditions causing degeneration of central and peripheral nervous systems should receive succinylcholine with GREAT CAUTION because of the potential for developing severe hyperkalemia.

Severe anaphylactic reactions to neuromuscular blocking agents, including succinylcholine, have been reported. These reactions have, in some cases, been life-threatening and fatal. Due to the potential severity of these reactions, the necessary precautions, such as the immediate availability of appropriate emergency treatment, should be taken. Precautions should also be taken in those individuals who have had previous anaphylactic reactions to other neuromuscular blocking agents since cross-reactivity between neuromuscular blocking agents, both depolarizing and non-depolarizing, has been reported in this class of drugs.

 Succinylcholine administration has been associated with acute onset of malignant hyperthermia, a potentially fatal hypermetabolic state of skeletal muscle. The risk of developing malignant hyperthermia following succinylcholine administration increases with the concomitant administration of volatile anesthetics. Malignant hyperthermia frequently presents as intractable spasm of the jaw muscles (masseter spasm) which may progress to generalized rigidity, increased oxygen demand, tachycardia, tachypnea and profound hyperpyrexia. Successful outcome depends on recognition of early signs, such as jaw muscle spasm, acidosis, or generalized rigidity to initial administration of succinylcholine for tracheal intubation, or failure of tachycardia to respond to deepening anesthesia. Skin mottling, rising temperature and coagulopathies may occur later in the course of the hypermetabolic process. Recognition of the syndrome is a signal for discontinuance of anesthesia, attention to increased oxygen consumption, correction of acidosis, support of circulation, assurance of adequate urinary output and institution of measures to control rising temperature. Intravenous dantrolene sodium is recommended as an adjunct to supportive measures in the management of this problem. Consult literature references and the dantrolene prescribing information for additional information about the management of malignant hyperthermic crisis. Continuous monitoring of temperature and expired CO is recommended as an aid to early recognition of malignant hyperthermia.

In both adults and pediatric patients the incidence of bradycardia, which may progress to asystole, is higher following a second dose of succinylcholine. The incidence and severity of bradycardia is higher in pediatric patients than adults. Whereas bradycardia is common in pediatric patients after an initial dose of 1.5 mg/kg, bradycardia is seen in adults only after repeated exposure. Pretreatment with anticholinergic agents (e.g., atropine) may reduce the occurrence of bradyarrhythmias.

Succinylcholine causes an increase in intraocular pressure. It should not be used in instances in which an increase in intraocular pressure is undesirable (e.g., narrow angle glaucoma, penetrating eye injury) unless the potential benefit of its use outweighs the potential risk. Succinylcholine is acidic (pH = 3.5) and should not be mixed with alkaline solutions having a pH greater than 8.5 (e.g., barbiturate solutions).

(See BOX WARNING)

When succinylcholine is given over a prolonged period of time, the characteristic depolarization block of the myoneural junction (Phase I block) may change to a block with characteristics superficially resembling a non-depolarizing block (Phase II block). Prolonged respiratory muscle paralysis or weakness may be observed in patients manifesting this transition to Phase II block. The transition from Phase I to Phase II block has been reported in 7 of 7 patients studied under halothane anesthesia after an accumulated dose of 2 to 4 mg/kg succinylcholine (administered in repeated, divided doses). The onset of Phase II block coincided with the onset of tachyphylaxis and prolongation of spontaneous recovery. In another study, using balanced anesthesia (N O/O /narcoticthiopental) and succinylcholine infusion, the transition was less abrupt, with great individual variability in the dose of succinylcholine required to produce Phase II block. Of 32 patients studied, 24 developed Phase II block. Tachyphylaxis was not associated with the transition to Phase II block, and 50% of the patients who developed Phase II block experienced prolonged recovery.

When Phase II block is suspected in cases of prolonged neuromuscular blockade, positive diagnosis should be made by peripheral nerve stimulation, prior to administration of any anticholinesterase drug. Reversal of Phase II block is a medical decision which must be made upon the basis of the individual, clinical pharmacology and the experience and judgment of the physician. The presence of Phase II block is indicated by fade of responses to successive stimuli (preferably “train of four”). The use of an anticholinesterase drug to reverse Phase II block should be accompanied by appropriate doses of an anticholinergic drug to prevent disturbances of cardiac rhythm. After adequate reversal of Phase II block with an anticholinesterase agent, the patient should be continually observed for at least 1 hour for signs of return of muscle relaxation. Reversal should not be attempted unless: (1) a peripheral nerve stimulator is used to determine the presence of Phase II block (since anticholinesterase agents will potentiate succinylcholine-induced Phase I block), and (2) spontaneous recovery of muscle twitch has been observed for at least 20 minutes and has reached a plateau with further recovery proceeding slowly; this delay is to ensure complete hydrolysis of succinylcholine by plasma cholinesterase prior to administration of the anticholinesterase agent. Should the type of block be misdiagnosed, depolarization of the type initially induced by succinylcholine (i.e., Phase I block) will be prolonged by an anticholinesterase agent.

Succinylcholine should be employed with caution in patients with fractures or muscle spasm because the initial muscle fasciculations may cause additional trauma.

Succinylcholine may cause a transient increase in intracranial pressure; however, adequate anesthetic induction prior to administration of succinylcholine will minimize this effect.

Succinylcholine may increase intragastric pressure, which could result in regurgitation and possible aspiration of stomach contents.

Neuromuscular blockade may be prolonged in patients with hypokalemia or hypocalcemia.

Since allergic cross-reactivity has been reported in this class, request information from your patients about previous anaphylactic reactions to other neuromuscular blocking agents. In addition, inform your patients that severe anaphylactic reactions to neuromuscular blocking agents, including succinylcholine have been reported.

 Succinylcholine should be used carefully in patients with reduced plasma cholinesterase (pseudocholinesterase) activity. The likelihood of prolonged neuromuscular block following administration of succinylcholine must be considered in such patients (see DOSAGE AND ADMINISTRATION).

Plasma cholinesterase activity may be diminished in the presence of genetic abnormalities of plasma cholinesterase (e.g., patients heterozygous or homozygous for atypical plasma cholinesterase gene), pregnancy, severe liver or kidney disease, malignant tumors, infections, burns, anemia, decompensated heart disease, peptic ulcer, or myxedema. Plasma cholinesterase activity may also be diminished by chronic administration of oral contraceptives, glucocorticoids, or certain monoamine oxidase inhibitors and by irreversible inhibitors of plasma cholinesterase (e.g., organophosphate insecticides, echothiophate, and certain antineoplastic drugs).

Patients homozygous for atypical plasma cholinesterase gene (1 in 2500 patients) are extremely sensitive to the neuromuscular blocking effect of succinylcholine. In these patients, a 5 to 10 mg test dose of succinylcholine may be administered to evaluate sensitivity to succinylcholine, or neuromuscular blockade may be produced by the cautious administration of a 1 mg/mL solution of succinylcholine by slow intravenous infusion. Apnea or prolonged muscle paralysis should be treated with controlled respiration.

There have been no long-term studies performed in animals to evaluate carcinogenic potential.

Pregnancy Category C.

Animal reproduction studies have not been conducted with succinylcholine chloride. It is also not known whether succinylcholine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Succinylcholine should be given to a pregnant woman only if clearly needed.

Plasma cholinesterase levels are decreased by approximately 24% during pregnancy and for several days postpartum. Therefore, a higher proportion of patients may be expected to show increased sensitivity (prolonged apnea) to succinylcholine when pregnant than when nonpregnant.

Succinylcholine is commonly used to provide muscle relaxation during delivery by caesarean section. While small amounts of succinylcholine are known to cross the placental barrier, under normal conditions the quantity of drug that enters fetal circulation after a single dose of 1 mg/kg to the mother should not endanger the fetus. However, since the amount of drug that crosses the placental barrier is dependent on the concentration gradient between the maternal and fetal circulations, residual neuromuscular blockade (apnea and flaccidity) may occur in the newborn after repeated high doses to, or in the presence of atypical plasma cholinesterase in, the mother.

It is not known whether succinylcholine is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised following succinylcholine administration to a nursing woman.

Safety and effectiveness of succinylcholine chloride have been established in pediatric patient age groups, neonate to adolescent. There are rare reports of ventricular dysrhythmias and cardiac arrest secondary to acute rhabdomyolysis with hyperkalemia in apparently healthy pediatric patients who receive succinylcholine (see BOX WARNING). Many of these pediatric patients were subsequently found to have a skeletal muscle myopathy such as Duchenne's muscular dystrophy whose clinical signs were not obvious. The syndrome often presents as sudden cardiac arrest within minutes after the administration of succinylcholine. These pediatric patients are usually, but not exclusively, males, and most frequently 8 years of age or younger. There have also been reports in adolescents. There may be no signs or symptoms to alert the practitioner to which patients are at risk. A careful history and physical may identify developmental delays suggestive of a myopathy. A preoperative creatine kinase could identify some but not all patients at risk. Due to the abrupt onset of this syndrome, routine resuscitative measures are likely to be unsuccessful. Careful monitoring of the electrocardiogram may alert the practitioner to peaked T-waves (an early sign). Administration of intravenous calcium, bicarbonate, and glucose with insulin, with hyperventilation have resulted in successful resuscitation in some of the reported cases. Extraordinary and prolonged resuscitative efforts have been effective in some cases. In addition, in the presence of signs of malignant hyperthermia, appropriate treatment should be initiated concurrently (see WARNINGS). Since it is difficult to identify which patients are at risk, it is recommended that the use of succinylcholine in pediatric patients should be reserved for emergency intubation or instances where immediate securing of the airway is necessary, e.g., laryngospasm, difficult airway, full stomach, or for intramuscular use when a suitable vein is inaccessible.

As in adults, the incidence of bradycardia in pediatric patients is higher following the second dose of succinylcholine. The incidence and severity of bradycardia is higher in pediatric patients than adults. Pre-treatment with anticholinergic agents, e.g., atropine, may reduce the occurrence of bradyarrhythmias.

Clinical studies of Suxametónio Labesfal did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

- Conscious patients. Suxamethonium has no effect on the level of consciousness and should not be administered to a patient who is not fully anaesthetised.

-

- 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).

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.

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.

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.

During prolonged administration of suxamethonium, it is recommended that the patient is fully monitored with a peripheral nerve stimulator in order to avoid overdosage.

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. In severe sepsis, the potential for hyperkalaemia may be related to the severity and duration of the infection.

Bradycardia and other cardiac dysrhythmias

In healthy adults, suxamethonium occasionally causes a mild transient slowing of the heart rate on initial administration.

Bradycardias are more commonly observed in children or if repeated doses are given (both adults and children). Pre-treatment with intravenous atropine or glycopyrrolate can significantly reduce the incidence and/or severity of suxamethonium-related bradycardia.

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. The action of suxamethonium on the heart may cause changes in cardiac rhythm including cardiac arrest.

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 which thereby limits the intensity and duration of the neuromuscular blockade.

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.

Prolonged and intensified neuromuscular blockade following Suxamethonium Injection may occur secondary to reduced plasma cholinesterase activity in the following states or pathological conditions:

- )

- genetically determined abnormal plasma cholinesterase

- severe generalized tetanus, tuberculosis, other severe or chronic infections

- following severe burns

- chronic debilitating disease, malignancy, chronic anaemia and malnutrition

- end stage hepatic failure, acute or chronic renal failure ( see secton 4.2 Posology and Method of Administration)

- auto-immune diseases:myxoedema, collagen diseases;

- iatrogenic: following plasma exchange, plasmapheresis, cardiopulmonary bypass, and as a result of concomitant drug therapy.

Use in children

Muscle pains

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.

Myasthenia gravis

It is inadvisable to administer suxamethonium to patients with advanced myasthenia gravis. Although these patients are resistant to suxamethonium they develop a state of atypical phase II block which can result in delayed recovery.

Myasthenic Eaton-Lambert syndrome

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

Prolonged use

If Suxamethonium is given over a prolonged period, the characteristic depolarizing neuromuscular (or Phase I) block may change to one with characteristics of a non-depolarising (or Phase II) block. 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 doses.

Use with other solutions

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

Effects on ability to drive and use machines

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.

Dosage (Posology) and method of administration

The dosage of succinylcholine should be individualized and should always be determined by the clinician after careful assessment of the patient (see WARNINGS).

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Solutions which are not clear and colorless should not be used.

Adults

The average dose required to produce neuromuscular blockade and to facilitate tracheal intubation is 0.6 mg/kg Suxametónio Labesfal (succinylcholine chloride) Injection given intravenously. The optimum dose will vary among individuals and may be from 0.3 to 1.1 mg/kg for adults. Following administration of doses in this range, neuromuscular blockade develops in about 1 minute; maximum blockade may persist for about 2 minutes, after which recovery takes place within 4 to 6 minutes. However, very large doses may result in more prolonged blockade. A 5 to 10 mg test dose may be used to determine the sensitivity of the patient and the individual recovery time (see PRECAUTIONS).

The dose of succinylcholine administered by infusion depends upon the duration of the surgical procedure and the need for muscle relaxation. The average rate for an adult ranges between 2.5 and 4.3 mg per minute.

Solutions containing from 1 to 2 mg per mL succinylcholine have commonly been used for continuous infusion. The more dilute solution (1 mg per mL) is probably preferable from the standpoint of ease of control of the rate of administration of the drug and, hence, of relaxation. This intravenous solution containing 1 mg per mL may be administered at a rate of 0.5 mg (0.5 mL) to 10 mg (10 mL) per minute to obtain the required amount of relaxation. The amount required per minute will depend upon the individual response as well as the degree of relaxation required. Avoid overburdening the circulation with a large volume of fluid. It is recommended that neuromuscular function be carefully monitored with a peripheral nerve stimulator when using succinylcholine by infusion in order to avoid overdose, detect development of Phase II block, follow its rate of recovery, and assess the effects of reversing agents (see PRECAUTIONS).

Intermittent intravenous injections of succinylcholine may also be used to provide muscle relaxation for long procedures. An intravenous injection of 0.3 to 1.1 mg/kg may be given initially, followed, at appropriate intervals, by further injections of 0.04 to 0.07 mg/kg to maintain the degree of relaxation required.

For emergency tracheal intubation or in instances where immediate securing of the airway is necessary, the intravenous dose of succinylcholine is 2 mg/kg for infants and small pediatric patients; for older pediatric patients and adolescents the dose is 1 mg/kg (see BOX WARNING and PRECAUTIONS: Pediatric Use). It is currently known that the effective dose of succinylcholine in pediatric patients may be higher than that predicted by body weight dosing alone. For example, the usual adult IV dose of 0.6 mg/kg is comparable to a dose of 2-3 mg/kg in neonates and infants to 6 months and 1-2 mg/kg in infants up to 2 years of age. This is thought to be due to the relatively large volume of distribution in the pediatric patient versus the adult patient.

Rarely, I.V. bolus administration of succinylcholine in infants and pediatric patients may result in malignant ventricular arrythmias and cardiac arrest secondary to acute rhabdomyolysis with hyperkalemia. In such situations, an underlying myopathy should be suspected.

Intravenous bolus administration of succinylcholine in infants or pediatric patients may result in profound bradycardia or, rarely, asystole. As in adults, the incidence of bradycardia in pediatric patients is higher following a second dose of succinylcholine. Whereas bradycardia is common in pediatric patients after an initial dose of 1.5 mg/kg, bradycardia is seen in adults only after repeated exposure. The occurrence of bradyarrhythmias may be reduced by pretreatment with atropine (see PRECAUTIONS: Pediatric Use).

If necessary, succinylcholine may be given intramuscularly to infants, older pediatric patients or adults when a suitable vein is inaccessible. A dose of up to 3 to 4 mg/kg may be given, but not more than 150 mg total dose should be administered by this route. The onset of effect of succinylcholine given intramuscularly is usually observed in about 2 to 3 minutes.

Succinylcholine is acidic (pH 3.5) and should not be mixed with alkaline solutions having a pH greater than 8.5 (e.g., barbiturate solutions). Admixtures containing 1 to 2 mg/mL may be prepared by adding 1 g Suxametónio Labesfal to 1000 or 500 mL sterile solution, such as 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP. Admixtures of Suxametónio Labesfal must be used within 24 hours after preparation. Aseptic techniques should be used to prepare the diluted product. Admixtures of Suxametónio Labesfal should be prepared for single patient use only. The unused portion of diluted Suxametónio Labesfal should be discarded.

To prevent needle-stick injuries, needles should not be recapped, purposely bent, or broken by hand.

Usually by bolus intravenous injection

Adults: The dose is dependent on body weight, the degree of muscular relaxation required, the route of administration, and the response of individual patients.

To achieve endotracheal intubation, Suxamethonium is usually administered intravenously in a dose of 1mg/kg. This dose will usually produce muscular relaxation in about 30 to 60 seconds and has a duration of action of about 2 to 6 minutes. Larger doses will produce more prolonged muscular relaxation, but doubling the dose does not necessarily double the duration of relaxation. Supplementary doses of Suxamethonium of 50% to 100% of the initial dose administered at 5 to 10 minute intervals will maintain muscle relaxation during short surgical procedures performed under general anaesthesia.

For prolonged surgical procedures, Suxamethonium may be given by intravenous infusion as a 0.1% to 0.2% solution, diluted in 5% glucose solution or sterile isotonic saline solution, at a rate of 2.5 to 4 mg per minute. The infusion rate should be adjusted according to the response of individual patients.

The total dose of Suxamethonium given by repeated intravenous injection or continuous infusion should not exceed 500 mg per hour.

Children: Infants and young children are more resistant to suxamethonium compared with adults.

The recommended intravenous dose of Suxamethonium for neonates and infants is 2 mg/kg. A dose of 1 mg/kg in older children is recommended.

When Suxamethonium is given as intravenous infusion in children, the dosage is as for adults with a proportionately lower initial infusion rate based on body weight.

Suxamethonium may be given intramuscularly to infants at doses up to 4 to 5mg/kg and in older children up to 4 mg/kg. These doses produce muscular relaxation within about 3 minutes. A total dose of 150 mg should not be exceeded.

Use in older people: Dosage requirements of suxamethonium in older patients are comparable to those for younger adults.

The elderly may be more susceptible to cardiac arrhythmias, especially if digitalis-like drugs are also being taken. See also 'Special warnings and precautions for use.

Special precautions for disposal and other handling

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.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.