Suxamethonium-vista

Ukraine
Brand name Suxamethonium-vista
Form powder for injection solution or infusion solution
Active substance / Dosage
succinylcholine chloride · 100 mg
Prescription type prescription only
ATC code
M03AB01
Registration number UA/20046/01/01
Manufacturer VUAB Pharma a.s.

Table of Contents

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT SUXAMETHONIUM-VISTA (SUXAMETHONIUM-VISTA)

Composition:

Active substance: suxamethonium chloride;

1 vial contains suxamethonium chloride dihydrate 110 mg, corresponding to suxamethonium chloride 100 mg.

Pharmaceutical form. Lyophilized powder for solution for injection or infusion.

Main physicochemical properties: white or almost white lyophilized powder.

Pharmacotherapeutic group. Muscle relaxants. Choline derivatives. Suxamethonium.

ATC code M03AB01.

Pharmacological properties.

Pharmacodynamics.

Suxamethonium chloride is a short-acting depolarizing muscle relaxant. It displaces acetylcholine at cholinoreceptors and, by depolarization, prevents stimulation of muscle fibers. The state of depolarization is also directly maintained by preventing repolarization, so that subsequently released acetylcholine binds but thus becomes ineffective.

Pharmacokinetics.

Available data on the pharmacokinetics of suxamethonium chloride are limited, mainly due to its extremely rapid metabolism. Suxamethonium chloride is rapidly and extensively metabolized in healthy individuals by plasma cholinesterase, primarily to monosuxamethonium, which has weak relaxant activity, and succinic acid and choline, which are excreted by the kidneys and further broken down in the body in the subsequent phase. Overall, 80% of the administered drug is hydrolyzed before reaching neuromuscular junctions. Approximately 10% of suxamethonium chloride is excreted unchanged in urine. Muscle relaxation usually occurs within 60 seconds after intravenous administration. The effect disappears within 3–6 minutes. After intramuscular administration, muscle relaxation usually occurs within 5 minutes.

Clinical characteristics.

Indications.

The medicinal product is used as a muscle relaxant under general anesthesia. It is applied as a skeletal muscle relaxant to facilitate endotracheal intubation, particularly so-called rapid sequence intubation, mechanical ventilation, and a wide range of surgical and obstetric procedures.

It is also used in severe laryngospasm and to reduce the intensity of muscle contractions associated with pharmacologically or electrically induced convulsions.

Contraindications.

The medicinal product does not affect the level of consciousness; therefore, it must not be administered to patients who are not under general anesthesia.

Do not use in patients with hypersensitivity to the active substance or to any of the excipients.

Succinylcholine chloride may cause sustained myofibrillar contractions in susceptible individuals; therefore, this medicinal product is contraindicated in patients with a personal or family history of malignant hyperthermia. If this condition occurs unexpectedly, all anesthetics capable of triggering this reaction (including succinylcholine chloride) must be discontinued immediately, and appropriate supportive measures should be initiated. As soon as possible after diagnosis, intravenous dantrolene sodium should be administered as the primary specific therapeutic agent.

The medicinal product is contraindicated in patients with inherited atypical plasma cholinesterase activity.

In healthy individuals, acute transient elevation of serum potassium levels is frequently observed after administration of succinylcholine; the increase is approximately 0.5 mmol/L. In certain pathological conditions, the rise in serum potassium after administration may be extreme and may lead to serious cardiac arrhythmias and cardiac arrest. For these reasons, the medicinal product is contraindicated in the following cases:

  • Patients recovering from severe trauma or major burns. The period of highest risk for hyperkalemia ranges from 5 to 70 days after injury and may be even longer if healing is delayed due to chronic illness.
  • Patients with neurological deficits, including acute atrophy of large muscles (upper and/or lower motor neuron lesions). The risk of potassium release exists during the first 6 months following the acute onset of neurological deficit and correlates with the degree and duration of muscle paralysis. Patients who have been immobilized for prolonged periods also fall into this risk group.
  • Patients with hyperkalemia. In the absence of hyperkalemia and neuropathy, renal insufficiency is not a contraindication to the administration of a standard single dose; however, repeated or higher doses may cause clinically significant elevation of serum potassium levels and should therefore not be used.

Succinylcholine chloride causes a marked transient increase in intraocular pressure; therefore, it should not be used in decompensated glaucoma, open eye injuries, or when an increase in intraocular pressure is undesirable. The product should be used only if the potential benefit outweighs the potential risk to the eyes.

The medicinal product should not be used in patients with a personal or family history of congenital myotonic disorders such as congenital myotonia and myotonic dystrophy, as this may occasionally be associated with severe myotonic spasms and rigidity.

Do not use in patients with skeletal muscle myopathies such as Duchenne muscular dystrophy, as this may be associated with malignant hyperthermia, ventricular dysrhythmias, cardiac arrest, and may secondarily lead to acute rhabdomyolysis with hyperkalemia.

The product must not be used in patients with intracranial aneurysm, severe intracranial hypertension, severe bradycardia, spinal cord compression, spinal cord injury, vertebral dislocation, paraplegia, dehydration with electrolyte imbalance, or impaired lung function.

Interaction with other medicinal products and other forms of interaction.

Reduced effect of succinylcholine chloride:

  • When small doses of non-depolarizing muscle relaxants are used, a delayed onset and reduced effect of succinylcholine chloride may be observed.
  • The parasympathomimetic effects of succinylcholine chloride may be attenuated by atropine.

Enhanced effect of succinylcholine chloride:

  • Concomitant use of digoxin may increase the risk of cardiac arrhythmias due to increased myocardial excitability. This is caused by digoxin-induced ventricular excitability and effects on conduction and/or potassium movement in myocardial cells.
  • The effect of succinylcholine chloride is prolonged when plasma cholinesterase and acetylcholinesterase activity is reduced by clinical conditions or by medicinal products (e.g., neostigmine, physostigmine, tacrine, and other acetylcholinesterase inhibitors).
  • Administration of amphotericin B or aminoglycoside antibiotics (such as gentamicin, neomycin, kanamycin, streptomycin) and thiopental may prolong the action of succinylcholine chloride and enhance neuromuscular blockade.
  • When used concomitantly with inhaled general anesthetics (such as enflurane, desflurane, isoflurane), neuromuscular blockade may be enhanced in a dose-dependent manner.
  • Antiarrhythmic drugs: quinidine, procainamide, beta-blockers, calcium channel blockers (verapamil), and loop diuretics may enhance or prolong the neuromuscular blocking effect of succinylcholine chloride.
  • Lithium may enhance or prolong the neuromuscular blocking effect of succinylcholine chloride.
  • Experimental data confirm that azathioprine potentiates the neuromuscular blockade induced by succinylcholine chloride.
  • Corticosteroids may enhance or prolong the effect of succinylcholine chloride.
  • Hormonal contraceptives and estrogens may prolong or enhance the effect of succinylcholine chloride by reducing plasma cholinesterase activity.

The effect of succinylcholine chloride may also be prolonged when used concomitantly with:

  • Local anesthetics (such as procaine, lidocaine), as they are hydrolyzed by plasma cholinesterases, leading to competitive potentiation of succinylcholine chloride.
  • Metoclopramide (antiemetic), as it reduces plasma cholinesterase activity.
  • Terbutaline and bambuterol (terbutaline prodrugs), as they cause reversible inhibition of plasma cholinesterase activity.
  • Cyclophosphamide (cytostatic), as it leads to reduced metabolism of succinylcholine chloride through irreversible inhibition of cholinesterase activity, possibly via enzyme alkylation.
  • Parathion and malathion (insecticides), as they inhibit acetylcholinesterase and pseudocholinesterase activity.
  • Magnesium sulfate, as it inhibits acetylcholine release and reduces postsynaptic membrane sensitivity. Therefore, magnesium administration should be discontinued 20–30 minutes before the administration of the muscle relaxant.

Special precautions for use.

Succinylcholine chloride should be used only in a specialized hospital department under the decision and close supervision of an experienced anesthesiologist, with equipment available for immediate tracheal intubation, oxygen inhalation, and artificial ventilation of the lungs.

High rates of cross-sensitivity (over 50%) between neuromuscular blockers have been reported. Therefore, if possible, hypersensitivity to other neuromuscular blockers should be excluded before administering succinylcholine chloride. Succinylcholine chloride should be administered to patients only when absolutely necessary. Use with caution in patients with known hypersensitivity to other myorelaxants or to any component of general anesthesia.

Succinylcholine chloride must not be mixed in the same syringe with any other substance, especially thiopental.

During prolonged administration, full patient monitoring using a peripheral nerve stimulator is recommended to avoid overdosage. Succinylcholine is rapidly hydrolyzed by plasma cholinesterase, which limits the intensity and duration of neuromuscular blockade.

Approximately 0.05% of the population has an inherited deficiency in plasma cholinesterase activity. The action of succinylcholine may be prolonged in the cases listed below, as well as in conditions associated with reduced cholinesterase activity: pregnancy and the postpartum period; severe tetanus, tuberculosis, and other severe and/or chronic infectious diseases; extensive burns; malignant tumors; chronic anemia and malnutrition; terminal stages of liver failure; acute or chronic renal failure; autoimmune diseases: myxedema, collagen diseases; after massive plasma transfusion; after plasmapheresis, cardiopulmonary bypass, and as a consequence, simultaneous use of other medicinal products (see section "Interaction with other medicinal products and other forms of interaction"). Repeated administration of succinylcholine may lead to development of tolerance to the drug.

If succinylcholine chloride is administered for a prolonged period, the typical depolarizing neuromuscular blocker effect (Phase I) may shift to a non-depolarizing blocker effect (Phase II). Although Phase II blockade resembles non-depolarizing blockade, the reversal effect of cholinesterase inhibitors on this blockade may not always be complete or sustained. When Phase II block is fully established, its effects can usually be completely reversed by treatment with standard doses of neostigmine together with cholinesterase inhibitors.

Tachyphylaxis may occur after repeated administration of succinylcholine chloride. Muscle pain frequently occurs after administration of succinylcholine chloride, most commonly in ambulatory patients who have undergone minor surgery under general anesthesia. There is no direct correlation between the degree of visible muscle fasciculations after administration and the occurrence or severity of pain. The use of small doses of non-depolarizing myorelaxants administered several minutes before succinylcholine chloride is justified to reduce the frequency and severity of muscle pain associated with succinylcholine chloride. This technique may require doses of succinylcholine chloride exceeding 1 mg/kg to achieve satisfactory conditions for endotracheal intubation. Use of succinylcholine chloride in children should be approached with caution, as this patient group more frequently has undiagnosed myopathy or unknown predisposition to malignant hyperthermia and rhabdomyolysis, thus increasing the risk of serious adverse reactions after succinylcholine chloride administration. Intravenous administration of succinylcholine chloride may cause cardiac arrhythmias in children. The risk increases with the number of doses administered. Hypoxia also increases the risk of cardiac arrhythmias in children. Prolonged intravenous administration to children is not recommended due to the risk of malignant hyperthermia. The use of succinylcholine chloride is associated with an increased risk of cardiac arrest in children with hyperkalemia. Cases of irreversible cardiac arrest in children and adolescents after succinylcholine chloride administration have been reported. Some of these patients had previously unrecognized neuromuscular disorders. Due to the seriousness of adverse effects, the use of succinylcholine chloride is recommended to be restricted even in apparently healthy children and adolescents to situations requiring immediate intubation or airway support.

In patients with severe sepsis, there is a potential risk of hyperkalemia, possibly related to the severity and duration of infection.

Succinylcholine chloride is not recommended for patients with myasthenia gravis due to the high risk of developing a "dual block." Patients with Eaton–Lambert myasthenic syndrome are more sensitive to the effects of succinylcholine, which may require a reduced dose of the drug.

It should be considered that in patients with genetically determined cholinesterase deficiency, as well as in those with hypokalemia, succinylcholine may cause prolonged respiratory depression. The drug should be used with caution in patients with liver disease, anemia, or cachexia.

In healthy patients (adults and children), succinylcholine may occasionally cause bradycardia, which can be prevented by prior intravenous administration of atropine or glycopyrrolate. Ventricular arrhythmias related to succinylcholine administration are rare but possible in the absence of hyperkalemia. Patients taking digitalis preparations are more prone to developing such arrhythmias. The effect of succinylcholine on the heart may lead to changes in cardiac rhythm, including cardiac arrest.

Use during pregnancy or breastfeeding.

Fertility.

No studies on the effect of succinylcholine chloride on female fertility have been conducted.

Pregnancy.

No studies on the effect of succinylcholine chloride on pregnancy have been conducted. Succinylcholine chloride has no direct effect on the uterus or other smooth muscles. In usual therapeutic doses, it crosses the placental barrier in amounts insufficient to affect the newborn's respiration.

In cases of extreme necessity, the possibility of using succinylcholine chloride during pregnancy may be considered.

Plasma cholinesterase levels decrease during the first trimester of pregnancy to approximately 70–80% of pre-pregnancy levels; a further reduction to about 60–70% of pre-pregnancy values occurs within 2–4 days after delivery. Plasma cholinesterase levels return to normal within the following 6 weeks. As a result, a somewhat prolonged neuromuscular blockade after drug administration may be observed in a large number of women during pregnancy and in the postpartum period.

Breastfeeding.

There is no information on the use of succinylcholine chloride in breastfeeding mothers, and no data on the ability of the drug to pass into breast milk.

Ability to affect reaction speed when driving or operating machinery.

Succinylcholine chloride is intended for use in a healthcare setting in combination with general anesthetic agents; therefore, all precautions related to the use of general anesthetics must be considered.

Method of Administration and Dosage.

Route of Administration.

The medicinal product is usually administered by intravenous injection or infusion, or by intramuscular injection. In cases of pronounced laryngospasm, the medicinal product may be administered intramuscularly or intraosseously. Administration of the medicinal product is permitted only when all conditions for artificial ventilation of the lungs are available.

Dosage for adults and elderly patients: dosage depends on body weight, required degree of muscle relaxation, route of administration, and individual patient response. The single intravenous dose of succinylcholine chloride is 1.0–1.5 mg/kg body weight.

Elderly patients are more prone to cardiac arrhythmias, especially if they are taking cardiac glycosides.

During prolonged (intermittent or continuous) administration, the intensity and nature of neuromuscular blockade should be monitored using a neurostimulator, as there is a risk of phase II blockade.

Infants and young children are more resistant to succinylcholine compared to adults.

Dosage for children aged 1 month to 1 year: the recommended dose for intravenous administration is 2 mg/kg body weight.

Dosage for children aged 1 to 12 years: the recommended dose for intravenous administration is 1–2 mg/kg body weight. When administering the medicinal product to children by intravenous infusion, the dose should be determined as for adults, but the initial infusion rate should be reduced proportionally to body weight.

Recommended dosage for intramuscular administration: this dose produces muscle relaxation within approximately 3 minutes. The medicinal product may be administered intramuscularly at a dose of 2–3 mg of succinylcholine chloride per kilogram of body weight. During prolonged use (intermittent or continuous), the intensity and nature of neuromuscular blockade should be monitored using a nerve stimulator, as there is a risk of phase II blockade. The total dose should not exceed 150 mg.

Dosage in renal impairment: the usual single dose of succinylcholine chloride may be administered to patients with renal insufficiency in the absence of hyperkalemia. Repeated or higher doses may cause clinically significant elevation of serum potassium levels and therefore should not be administered.

Dosage in hepatic impairment: the termination of succinylcholine action depends on plasma cholinesterase, which is synthesized in the liver. Although plasma cholinesterase levels are often reduced in patients with liver disease, except in cases of severe hepatic insufficiency, levels are rarely low enough to significantly prolong succinylcholine-induced apnea. See also section "Special Warnings and Precautions for Use."

Method of Administration.

For intravenous injection, the contents of the vial should be reconstituted with 4 mL of water for injections or sterile physiological saline solution to achieve a final concentration of 2.5%. For infusion, further dilution with sterile physiological saline solution to 0.1–0.2% is required. The infusion rate should be adjusted according to each patient's response. The recommended infusion rate is 2.5–4 mg/min. The total dose of succinylcholine chloride administered via repeated injections or infusions should not exceed 500 mg per hour. The medicinal product is compatible with other muscle relaxants and opioid analgesics.

Children.

The medicinal product should be used in children according to the section "Method of Administration and Dosage." Caution should be exercised when administering the medicinal product to this age group, as children have a higher incidence of myopathy, are more prone to developing malignant hyperthermia and rhabdomyolysis, and have an increased risk of serious adverse reactions following succinylcholine administration.

Overdose.

Symptoms: the most serious consequences of overdose include respiratory arrest and prolonged muscle paralysis.

Treatment: ensure airway patency and provide artificial ventilation of the lungs until spontaneous respiration is restored. The decision to use neostigmine to prevent phase II blockade induced by succinylcholine chloride should be made by the physician on a case-by-case basis. To make this decision, neuromuscular function must be monitored. If neostigmine is used, its administration should be accompanied by appropriate doses of an anticholinergic agent, such as atropine.

Adverse reactions

Adverse events are classified by organ system and frequency of occurrence. The frequency of adverse reactions was determined from published data according to the following criteria: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000), frequency not known (cannot be estimated from available data).

Cardiovascular system: very common – arrhythmias (disturbances of heart rhythm), such as: bradycardia (slowed pulse); AV nodal arrhythmias; ectopic heartbeats, which may occur after the first intravenous injection, especially in neonates and young children. The risk increases with administration of a second dose within 15 minutes; common – transient bradycardia, tachycardia, skin flushing (hot flushes), arterial hypertension or hypotension; rare – arrhythmias (including ventricular arrhythmias), disturbances of cardiac conduction, cardiogenic shock, collapse, cardiac arrest (asystole); very rare – cases of cardiac arrest due to hyperkalemia have been reported after administration of succinylcholine chloride to patients with congenital cerebral palsy, tetanus, Duchenne muscular dystrophy, and closed head injury. Similar cases have also been rarely reported in children with previously undiagnosed muscular disorders; cardiovascular complications (hyperventilation, unstable blood pressure). Uncommon – cardiac arrhythmias such as ventricular arrhythmia, bradycardia with AV nodal rhythm disturbance; transient disturbances in blood pressure such as hypertension, hypotension, tachycardia.

Eye disorders: common – increased intraocular pressure.

Respiratory, thoracic and mediastinal disorders: rare – bronchospasm, prolonged apnea (respiratory arrest), prolonged paralysis of respiratory muscles (associated with genetically determined deficiency in pseudocholinesterase production); very rare – bronchospasm due to allergic reactions; laryngeal and pulmonary edema (fluid accumulation in the larynx or lungs).

Gastrointestinal disorders: very common – increased salivation, increased intragastric pressure (and consequently increased risk of regurgitation and aspiration of gastric contents into the airways), increased risk of vomiting in pregnant women, patients with hiatal hernia (diaphragmatic hernia), patients with gastrointestinal distension, ascites, or intra-abdominal tumors); uncommon – increased salivation.

Hepatobiliary disorders: rare – liver function abnormalities.

Skin and subcutaneous tissue disorders: common – skin allergic reactions, skin flushing due to histamine release, rash; frequency not known – systemic contact dermatitis.

Musculoskeletal and connective tissue disorders: very common – muscle pain, including postoperative muscle pain; myalgia following muscle fasciculations (muscle twitching, often in the neck, chest, shoulders, and back, particularly affecting women aged 20 to 50 years); muscle fasciculations; common – myoglobinemia, myoglobinuria (cases of acute rhabdomyolysis have been reported in patients with diagnosed or occult neuromuscular disorders); rare – trismus, muscle contractions (usually associated with existing muscular dystrophies such as myotonic dystrophy or genetic myotonia); myoglobinuria and subsequent renal failure or acute cardiac failure (mainly in children and adolescents receiving succinylcholine chloride and halothane due to loss of potassium, creatine phosphokinase, and myoglobin from muscle cells after administration of succinylcholine chloride); very rare – malignant hyperthermia with or without muscle rigidity (severe jaw muscle spasms), myoglobinuria, also with subsequent renal failure (mainly in patients with latent muscular dystrophy).

Immune system disorders: common – allergic reactions, skin flushing, urticaria; rare – anaphylactic shock; very rare – hypersensitivity reactions, including urticaria; very rare – allergic (anaphylactoid) reactions, anaphylactic shock with erythema, with or without bronchospasm and hypotension, which may progress to full shock; severe hypotension due to anaphylactic (allergic) reactions.

General disorders and administration site conditions: very rare – malignant hyperthermia.

Nervous system disorders: rare – prolonged paralysis (due to development of a dual block), especially in patients with neuromuscular disorders, idiosyncrasy (enzymatic and metabolic disorders), or reduced plasma cholinesterase levels; uncommon – trismus (up to 60 seconds); very rare – hyperthermia; frequency not known – increased intracranial pressure.

Investigations (laboratory parameters): very common – myoglobinemia (elevated myoglobin levels in blood, especially in children); elevated serum potassium levels (usually mild increase by 0.5 mmol/L); common – transient elevation of blood potassium, hyperglycemia; very rare – porphyria; marked acidosis, hemoglobinuria (excretion of hemoglobin (blood pigment) in urine); not known – elevated CK (creatine phosphokinase) levels, occurring predominantly in children and adolescents receiving succinylcholine chloride and halothane.

Reporting of suspected adverse reactions.

Reporting of adverse reactions after marketing authorization of the medicinal product is of great importance. It enables continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, or their legal representatives should report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua

Shelf life. 3 years.

Storage conditions.

Store in the original packaging protected from light at temperatures not exceeding 25 °C. Keep out of reach of children.

Incompatibilities.

Succinylcholine chloride is rapidly inactivated in alkaline solutions and may form a precipitate; therefore, it must not be mixed with thiopental solutions or diluted alkaline solutions such as lactated Ringer's solution or Hartmann's solution.

Packaging.

100 mg of powder in a vial; 1, 10, or 20 vials per cardboard box.

Prescription status. Prescription only.

Manufacturer.

VUAB Pharma a.s.

Manufacturer's address and location of operations.

Vltavska 53, Roztoky, 252 63, Czech Republic