100 mg/2 ml,
500 mg/10 ml
For the use of a Registered Medical Practitioner or a Hospital or a Institution only.
SUCCIFLEX (Succinylcholine Chloride Injection USP) is an ultra short-acting depolarizing type, skeletal muscle relaxant for intravenous administration. Chemically, succinylcholine chloride is Ethanaminium, 2,2-[(1,4-dioxo-1,4-butanediyl)bis(oxy)]bis[N,N,N-trimethyl]-, dichloride. The molecular formula is C14H30Cl2N2O4 and molecular weight is 361.3
STRUCTURAL FORMULA :
Its structural formula is :
SUCCIFLEX is a clear, colourless, sterile solution filled in vial or ampoule of suitable size.
Each ml contains :
Succinylcholine Chloride USP 50 mg
Benzyl Alcohol USP 0.02 ml
Water for Injection USP q.s.
Succinylcholine chloride is an ultra short - acting depolarizing type neuromuscular blocking agent. Succinylcholine chloride combines with the cholinergic receptors of the motor end plate to produce depolarisation. Neuromuscular transmission is inhibited so long as an adequate concentration of succinylcholine chloride remains at the receptor site. Succinylcholine chloride has no direct action on smooth muscle structures, including the uterus. Succinylcholine chloride may produce slowing of heart rate via vagal stimulation. When succinylcholine chloride 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.
Succinylcholine chloride has a rapid onset and a short duration of action. Following I.V. administration of a single therapeutic dose in healthy adults, complete muscle relaxation occurs within ½ to 1 minute, persists for about 2 - 3 minutes, and gradually dissipates within 10 minutes. Following I.M. 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.
Succinylcholine chloride crosses the placenta, generally in small amounts.
Plasma pseudocholinesterase hydrolyses succinylcholine 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.
SUCCIFLEX 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 muscular contractions associated with pharmacologically or electrically-induced convulsions.
SUCCIFLEX is usually given by bolus intravenous injection for prolonged surgical procedure in an adult. SUCCIFLEX is commonly given by I.V. infusion. If necessary, SUCCIFLEX may be given intramuscularly to infants, older children or adult when a suitable vein is inaccessible.
INSTRUCTIONS FOR USE OF AMPOULE :
The ampoule used in this product is equipped with O.P.C (One Point Cut) opening system. No ampoule file is needed to open the ampoule. The neck of the ampoule is prescored at the point of constriction. A coloured dot on the ampoule head helps to orientate the ampoule. Take the ampoule and face the coloured dot. Let the solution at the head of the ampoule to flow down by shaking or a gentle stroke. The ampoule opens easily by placing the thumb on the coloured dot and gently pressing downwards as shown.
Dosage is individualised and its administration should be determined after careful assessment of the patient. The dose of SUCCIFLEX is dependent on bodyweight, the degree of muscle relaxation required and the response of individual patients. SUCCIFLEX causes paralysis of the respiratory muscles, therefore after administration, respiration must be controlled. It should not be administered to a conscious patient. SUCCIFLEX should not be mixed with any neuromuscular blocking agent with general anaesthetics such as short acting barbiturates nor any other therapeutic agent in the same syringe. An initial test dose of 0.1 mg/kg may be given intravenously to determine the patients response. 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 SUCCIFLEX is usually administered intravenously in a dose of 1 mg/kg. This dose will usually produce muscular relaxation in about 30 to 60 seconds and has 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 SUCCIFLEX 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 SUCCIFLEX 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 SUCCIFLEX given by repeated intravenous injection or continuous infusion should not exceed 500 mg per hour. Children : Infants and young children are more resistant to SUCCIFLEX compared with adults. The recommended intravenous dose of SUCCIFLEX for neonates and infants is 2 mg/kg. A dose of 1 mg/kg in older children is recommended. When SUCCIFLEX is given as intravenous infusion in children, the dosage is as for adults with a proportionately lower initial infusion rate based on body weight.
SUCCIFLEX may be given intramuscularly to infants at doses up to 4 to 5 mg/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 the elderly : Dosage requirements of SUCCIFLEX in the elderly 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.
COMPATIBILITY WITH OTHER SOLUTION :
Solutions : Dextrose 5 % in water, Sodium chloride 0.9 % dextrose 5 % in sodium chloride 0.9 % and sodium lactate 1/6 M have been recommended as diluents for infusing succinylcholine chloride. Barbiturates - Succinylcholine chloride is unstable in alkaline solutions and decomposes in solutions with pH greater than 4.5. In combination with barbiturates, either free barbituric acid will precipitate or the succinylcholine chloride will be hydrolyzed depending on the final pH of the admixture. Succinylcholine chloride should not be mixed with barbiturates in the same syringe or given simultaneously through the same needle. A haze forms in 30 minutes when succinylcholine chloride 0.5 or 1 gm in 4 ml is mixed with methohexial sodium 100 mg in 10 ml.
SUCCIFLEX has no effect on the level of consciousness and should not be administered to a patient who is not fully anaesthetised. Hypersensitivity to succinylcholine may exist in rare instances, and SUCCIFLEX should not be administered to patients known to be hypersensitive to the drug. As SUCCIFLEX can act as a trigger of sustained myofibrillar contraction in susceptible individuals, SUCCIFLEX is contra-indicated in patients with a personal or family history of malignant hyperthermia. If this condition occurs unexpectedly, all anaesthetic agents known to be associated with its development (including SUCCIFLEX) must be immediately discontinued, and full supportive measures must be immediately instituted. Intravenous dantrolene sodium is the primary specific therapeutic drug and is recommended as soon as possible after the diagnosis is made. SUCCIFLEX is contra-indicated in patients known to have an inherited atypical plasma cholinesterase activity. An acute transient rise in serum potassium often occurs following the administration of SUCCIFLEX 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 SUCCIFLEX administration may be excessive and cause serious cardiac arrhythmias and cardiac arrest. For this reason the use of SUCCIFLEX 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 SUCCIFLEX, but multiple or large doses may cause clinically significant rises in serum potassium and should not be used. SUCCIFLEX 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. SUCCIFLEX should be avoided in patients with a personal or family history of congenital myotonic diseases such as myotonia congenita and dystrophia myotonica since its administration may on occasion be associated with severe myotonic spasms and rigidity. SUCCIFLEX should be avoided in patients with Duchenne muscular dystrophy since its administration may be associated with rigidity, hyperthermia, hyperkalaemia, myoglobinaemia, cardiac arrest, and post-operative respiratory depression.
SUCCIFLEX contains benzyl alcohol as preservative. Benzyl alcohol has been reported to be associated with a fatal "Gasping Syndrome" in premature infants. Symptoms include a striking onset of gasping syndrome, hypotension, bradycardia and cardiovascular collapse. SUCCIFLEX should only be administered under strict supervision of an anaesthetist familiar with its actions, characteristics and hazards who is skilled in the management of artifical 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. SUCCIFLEX 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 SUCCIFLEX. 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 SUCCIFLEX 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.
Low Plasma Pseudocholinesterase :
Recovery from SUCCIFLEX may occassionally 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, myxoedem, burns, pregnancy and the puerperium, severe infections, myocardial infarction, renal impairment and abnormal body temperature. Also exposure to neurotoxic insecticides or weed killers, antimalarial or anti-cancer agents, monoamine oxidase (MAO) inhibitors, the contraceptive pill, pancuronium, chlorpromazine, ecothiopate or neostigmine may result in low levels of pseudocholinesterase. SUCCIFLEX 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 SUCCIFLEX (5 to 10 mg as a 0.1 % solution) should be considered.
Administration of SUCCIFLEX 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 SUCCIFLEX, resulting in cardiac arrhythmia or arrest 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 SUCCIFLEX 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 succinylcholine should not be given until the infection has cleared.
Hyperkalaemia Rhabdomyolysis :
There is a risk of cardiac arrest from hyperkalaemia due to rhabdomyolysis, particularly in male patients with muscular dystrophy.
Antidysrhythmic agents :
SUCCIFLEX 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 succinylcholine may possible cause arrhythmias.
Delayed recovery :
When recovery from SUCCIFLEX 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 narcoisis, e.g. nitrous oxide/oxygen mixutre. Neostigmine should not be given when prolonged apnoea follows a single dose of SUCCIFLEX. Neostigmine and other anticholinesterase agents may have the effect of intensifying the depolarisation block caused by SUCCIFLEX.
Nondepolarising blockade :
If SUCCIFLEX 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.
Debilitated patients :
Use with caution in patients who are hypoxic or those who have cardiovascular, hepatic, pulmonary, metabolic or renal disorders of myasthenia gravis. The action of SUCCIFLEX may be altered in these patients. Its use is not advisable in patients with phaeochromocytoma. As SUCCIFLEX produces muscle contractions before relaxation it should be used with caution in patients with bone fractures. SUCCIFLEX should be avoided in patients with myotonias, as response is unpredictable.
Use in eye surgery :
SUCCIFLEX 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.
Teratogenic Effects : Pregnancy Category C
Animal reproduction studies have not been conducted with succinylcholine chloride. It is also not known whether succinlycholine can cause foetal harm when administered to a pregnant woman or can affect reproduction capacity. Succinylcholine should be given to a pregnant woman only if clearly needed.
Nonteratogenic Effects :
Pseudocholinesterase levels are decreased by approximately 24 % during pregnancy and for several days postpartum. Therefore, a higher proportion of patients may be expected to show sensitivity (prolonged apnea) to succinylcloline when pregnant than when non-pregnant.
Labor and Delivery :
Succinylcholine is commonly used to provide muscle relaxant 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 foetal circulation after a single dose of 1 mg/kg to the mother will not endanger the foetus. However, since the amount of drug that crosses the placental barrier is dependent on the concentration gradient between the maternal and foetal circulations, residual neuromuscular blockade (apnea and flaccidity) may occur in the neonate after repeated high doses to, or in the presence of atypical psedudocholinesterase in the mother.
Nursing mothers :
It is not known whether SUCCIFLEX or its metabolites are excreted in human milk.
INTERACTIONS AND INCOMPATIBILITIES :
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 SUCCIFLEX but may enhance the Phase II block (nondepolarising) that may be produced by repeated dosage of SUCCIFLEX. Severe bradycardia and asystole have occurred when SUCCIFLEX is used in anaesthetic regimens with propofol and opioids such as fentanyl.
Agents which may enhance or prolong the effects of SUCCIFLEX include lignocaine, procaine, oxytocin, oral contraceptives, some nonpenicillin 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 SUCCIFLEX. Amphotericin B and thiazide diuretics may increase the effect of SUCCIFLEX secondary to induced electrolyte imbalance. Patients with hypokalaemia or hypocalcaemia require reduced doses of SUCCIFLEX.
Inhibitors of plasma cholinesterases such as neostigmine pyridostigmine bromide, rivastigmine, donepezil, metoclopramide, physostigmine and phospholine iodide can considerably prolong the depolarising action of SUCCIFLEX. It is recommended that long-acting anticholinesterase inhibitor (ecothiopate) eye drops, should be discontinued several months prior to administration of SUCCIFLEX. Administration of SUCCIFLEX 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 succinylcholine and atracurium significantly reduces the duration of succinylcholine. Concomitant digoxin or verapamil and succinycholine therapy has been reported to result in cardiac arrhythmias.
SIDE EFFECTS :
The following adverse reactions have been reported following administration of succinylcholine :
Neuromuscular : Post operative muscle pain, muscle fasciculation, rhabdomyolysis, myoglobinuria, myoglobinaemia, elevated creatine phosphokinase, hypertonia.
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.
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.
TREATMENT OF OVERDOSAGE :
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.
PHARMACEUTICAL PRECAUTIONS :
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Store in a refrigerator between 2°C to 8°C (36°F to 46°F), protected from light.
Do not freeze.
SHELF LIFE :
24 months from the date of manufacture.
Disclaimer : For the use of a Registered Medical Practitioner or a Hospital or a Institution only. Also it is not intended to be used by healthcare professionals or patients for the purpose of prescribing or administering these products. Questions regarding the complete and current content of product labeling / specification / presentation should be directed to SGPharma.