QUELICIN™ (succinylcholine chloride)

QUELICIN™ (succinylcholine chloride) injection

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QUELICIN™ (succinylcholine chloride)

QUELICIN (Succinylcholine Chloride Injection, USP) is a sterile, nonpyrogenic solution to be used as a short-acting, depolarizing neuromuscular blocker for intravenous or intramuscular use. QUELICIN contains succinylcholine chloride as the active pharmaceutical ingredient.

Succinylcholine Chloride, USP is chemically designated C14H30Cl2N2O4 and its molecular weight is 361.31. The chemical name of succinylcholine chloride is ethanaminium, 2,2′-[(1,4-dioxo-1,4 butanediyl)bis(oxy)]bis[N,N,N-trimethyl-], dichloride. Succinylcholine chloride is a diquaternary base consisting of the dichloride salt of the dicholine ester of succinic acid. It is a white, odorless, slightly bitter powder, very soluble in water.

Indications and usage

QUELICIN is a depolarizing neuromuscular blocker indicated in adults and pediatric patients:

  • as an adjunct to general anesthesia
  • to facilitate tracheal intubation
  • to provide skeletal muscle relaxation during surgery or mechanical ventilation.

Dosage and administration

Important Dosage and Administration Information

  • QUELICIN is for intravenous or intramuscular use only.
  • QUELICIN must be titrated to effect by or under supervision of experienced clinicians who are familiar with its actions and with appropriate neuromuscular monitoring techniques.
  • QUELICIN should be administered 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 CO2. The clinician must be prepared to assist or control respiration.
  • The dosage of QUELICIN should be individualized and should always be determined by the clinician after careful assessment of the patient.
  • To avoid distress to the patient, do not administer QUELICIN before unconsciousness has been induced
  • The occurrence of bradyarrhythmias with administration of QUELICIN may be reduced by pretreatment with anticholinergics (e.g., atropine)
  • Monitor neuromuscular function with a peripheral nerve stimulator when using QUELICIN by infusion.
  • Visually inspect QUELICIN for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer solutions that are not clear and colorless.
  • QUELICIN supplied in single-dose vials must be diluted before use. QUELICIN supplied in multipledose vials does not require dilution before use

Dosage Recommendations for Intravenous Use in Adults

For Short Surgical Procedures

The average dose required to produce neuromuscular blockade and to facilitate tracheal intubation is 0.6 mg/kg QUELICIN given intravenously. The optimum intravenous dose of QUELICIN will vary among patients and may be from 0.3 mg/kg to 1.1 mg/kg for adults. Following intravenous 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. A 5 to 10 mg intravenous test dose of QUELICIN may be used to determine the sensitivity of the patient and the individual recovery time.

For Long Surgical Procedures

Continuous Intravenous Infusion

The dosage of QUELICIN administered by continuous intravenous infusion depends upon the duration of the surgical procedure and the need for muscle relaxation.

Diluted QUELICIN solutions containing from 1 mg/mL to 2 mg/mL succinylcholine have commonly been used for continuous intravenous infusion. The more dilute solution (1 mg/mL) is probably preferable from the standpoint of ease of control of the rate of administration of QUELICIN and, hence, of relaxation. This diluted QUELICIN solution containing 1 mg/mL succinylcholine may be administered intravenously at a rate of 0.5 mg (0.5 mL) per minute 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. The average rate of continuous intravenous infusion for an adult ranges between 2.5 mg per minute and 4.3 mg per minute.

Monitor neuromuscular function with a peripheral nerve stimulator when using QUELICIN 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.

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

Dosage Recommendations for Intravenous Use in Pediatric Patients

For emergency tracheal intubation or in instances where immediate securing of the airway is necessary, the intravenous dose of QUELICIN is 2 mg/kg for infants and other small pediatric patients; for older pediatric patients and adolescents the intravenous dose is 1 mg/kg. The effective dose of QUELICIN in pediatric patients may be higher than that predicted by body weight dosing alone. For example, the usual adult intravenous dose of 0.6 mg/kg is comparable to a dose of 2 mg/kg to 3 mg/kg in neonates and infants up to 6 months of age and 1 mg/kg to 2 mg/kg in infants up to 2 years of age.

Dosage Recommendations for Intramuscular Use in Adults and Pediatric Patients

If a suitable vein is inaccessible, QUELICIN may be administered intramuscularly at a dose of up to 3 mg/kg to 4 mg/kg to infants, older pediatric patients, or adults. The total dose administered by the intramuscular route should not exceed 150 mg. The onset of effect of succinylcholine given intramuscularly is usually observed in about 2 to 3 minutes.

Preparation of QUELICIN

QUELICIN supplied in single-dose vials must be diluted before use. QUELICIN supplied in multiple-dose vials does not require dilution before use.

QUELICIN may be diluted to 1 mg/mL or 2 mg/mL in a solution such as:

  • 5% Dextrose Injection, USP, or
  • 0.9% Sodium Chloride Injection, USP

Prepare the diluted QUELICIN solution for single patient use only. Store the diluted QUELICIN solution in a refrigerator [2 °C to 8 °C (36 °F to 46 °F)] and use within 24 hours after preparation. Visually inspect the diluted QUELICIN solution for particulate matter and discoloration prior to administration. Do not administer solutions that are not clear and colorless. Discard any unused portion of the diluted QUELICIN solution.

Mechanism of Action

Succinylcholine is a depolarizing neuromuscular blocker. As does acetylcholine, it combines with the cholinergic receptors of the motor end plate to produce depolarization. This depolarization may be observed as fasciculations. Subsequent neuromuscular transmission is inhibited so long as adequate concentration of succinylcholine remains at the receptor site. Onset of flaccid paralysis is rapid (less than one minute after intravenous administration), and with single administration lasts approximately 4 to 6 minutes.

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The paralysis following administration of succinylcholine is progressive, with differing sensitivities of different muscles. This initially involves consecutively the levator muscles of the face, muscles of the glottis and finally the intercostals and the diaphragm and all other skeletal muscles.

Pharmacokinetics

Elimination: Succinylcholine levels were reported to be below the detection limit of 2 µg/mL after 2.5 minutes of an intravenous bolus dose of 1 or 2 mg/kg in 14 anesthetized patients.

Metabolism: Succinylcholine is rapidly hydrolyzed by plasma cholinesterase to succinylmonocholine (which possesses clinically insignificant depolarizing muscle relaxant properties) and then more slowly to succinic acid and choline.

Excretion: About 10% of the drug is excreted unchanged in the urine.

Adverse reactions

Cardiovascular disorders: Cardiac arrest, arrhythmias, bradycardia, tachycardia, hypertension, hypotension

Electrolyte disorders: Hyperkalemia

Eye disorders: Increased intraocular pressure

Gastrointestinal disorders: Excessive salivation

Immune system disorders: Hypersensitivity reactions including anaphylaxis (in some cases life-threatening and fatal)

Musculoskeletal disorders: Malignant hyperthermia, rhabdomyolysis with possible myoglobinuric acute renal failure, muscle fasciculation, jaw rigidity, postoperative muscle pain

Respiratory disorders: Prolonged respiratory depression or apnea

Skin disorders: Rash

Contraindications

  • Skeletal muscle myopathies
  • Known hypersensitivity to succinylcholine
  • After the acute phase of injury following major burns, multiple trauma, extensive denervation of skeletal muscle, or upper motor neuron injury
  • Personal or familial history of malignant hyperthermia

Warnings and precautions

Anaphylaxis: Severe anaphylactic reactions to neuromuscular blocking agents, including succinylcholine, have been reported. Some cases have been life-threatening and fatal. Take necessary precautions, such as the immediate availability of appropriate emergency treatment.

Risk of Death due to Medication Errors: Unintended administration of QUELICIN may result in paralysis, respiratory arrest and death. Confirm proper selection of intended product and avoid confusion with other injectable solutions that are present in critical care and other clinical settings.

Hyperkalemia: QUELICIN may induce serious cardiac arrhythmias or cardiac arrest due to hyperkalemia.

Malignant Hyperthermia: Succinylcholine administration has been associated with acute onset of malignant hyperthermia. Continuously monitor temperature and expired CO2. Intravenous dantrolene sodium is recommended as an adjunct to supportive measures in the management of malignant hyperthermia.

Bradycardia: Intravenous bolus administration may result in profound bradycardia or, rarely, asystole. The incidence is higher following a second dose of succinylcholine. Pretreatment with anticholinergic agents (e.g., atropine) may reduce the occurrence of bradyarrhythmias

Drug interactions

Drugs that may enhance the neuromuscular blocking action of succinylcholine include: promazine, oxytocin, aprotinin, certain non-penicillin antibiotics, quinidine, β-adrenergic blockers, procainamide, lidocaine, trimethaphan, lithium carbonate, magnesium salts, quinine, chloroquine, isoflurane, desflurane, metoclopramide, and terbutaline.

The neuromuscular blocking effect of succinylcholine may be enhanced by drugs that reduce plasma cholinesterase activity (e.g., chronically administered oral contraceptives, glucocorticoids, or certain monoamine oxidase inhibitors) or by drugs that irreversibly inhibit plasma cholinesterase.

If other neuromuscular blocking agents are to be used during the same procedure, consider the possibility of a synergistic or antagonistic effect.

Use in specific populations

Pregnancy: Available data from published literature from case reports and case series over decades of use with succinylcholine during pregnancy have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Succinylcholine is used commonly during delivery by caesarean section to provide muscle relaxation. If succinylcholine is used during labor and delivery, there is a risk for prolonged apnea in some pregnant women.

Fetal/Neonatal Adverse Reactions: Apnea and flaccidity may occur in the newborn after repeated high doses to, or in the presence of atypical plasma cholinesterase in, the mother.

Labor or Delivery: Succinylcholine is commonly used to provide muscle relaxation during delivery by caesarean section. Succinylcholine is known to cross the placental barrier in an amount that is dependent on the concentration gradient between the maternal and fetal circulation.

Lactation: There are no data on the presence of succinylcholine or its metabolite in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for QUELICIN and any potential adverse effects on the breastfed infant from QUELICIN or from the underlying maternal condition.

Pediatric Use: Safety and effectiveness of succinylcholine chloride have been established in pediatric patient age groups, neonate to adolescent. Because of a risk of ventricular dysrhythmias, cardiac arrest, and death from hyperkalemic rhabdomyolysis in pediatric patients, reserve the use of QUELICIN in pediatric patients 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.

Geriatric Use: Clinical studies of QUELICIN did not include sufficient numbers of subjects aged 65 years 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.

Overdosage

Overdosage with QUELICIN 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 QUELICIN administration, the characteristic depolarizing neuromuscular block (Phase I) may change to a block with characteristics superficially resembling a non-depolarizing block (Phase II)

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