Succinylcholine Chloride 20 Mg/ml Injectable Solution

Accidental administration of neuromuscular blocking agents may be fatal. Store succinylcholine chloride injection with the cap and ferrule intact and in a manner that minimizes the possibility of selecting the wrong product [see Warnings and Precautions (5.3)].

The average dose required to produce neuromuscular blockade and to facilitate tracheal intubation is 0.6 mg/kg succinylcholine chloride injection given intravenously. The optimum intravenous dose of succinylcholine chloride injection 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 mg to 10 mg intravenous test dose of succinylcholine chloride injection may be used to determine the sensitivity of the patient and the individual recovery time [see Warnings and Precautions (5.9)].

For Long Surgical Procedures

Continuous Intravenous Infusion

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

Diluted succinylcholine chloride solutions containing from 1 mg/mL to 2 mg/mL succinylcholine have commonly been used for continuous intravenous infusion [see Dosage and Administration (2.5)]. The more dilute solution (1 mg/mL) is probably preferable from the standpoint of ease of control of the rate of administration of succinylcholine chloride and, hence, of relaxation. This diluted succinylcholine chloride 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 succinylcholine chloride injection 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 Warnings and Precautions (5.8)].

Intermittent Intravenous Injection

Intermittent intravenous injections of succinylcholine chloride 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.

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

The syndrome often presented as sudden cardiac arrest within minutes after the administration of succinylcholine. These pediatric patients were 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.

When a healthy-appearing pediatric patient develops cardiac arrest within minutes after administration of succinylcholine chloride injection, not felt to be due to inadequate ventilation, oxygenation or anesthetic overdose, immediate treatment for hyperkalemia should be instituted. 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 and Precautions (5.5)].

Because it is difficult to identify which patients are at risk, reserve the use of succinylcholine chloride 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.

Succinylcholine chloride is contraindicated after the acute phase of injury following major burns, multiple trauma, extensive denervation of skeletal muscle, or upper motor neuron injury [see Contraindications (4)]. 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 are at an increased risk of developing severe hyperkalemia after succinylcholine chloride administration. Consider avoiding use of succinylcholine in these patients or verify the patient's baseline potassium levels are within the normal range prior to succinylcholine administration.

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 patient, clinical pharmacology, and the experience and judgment of the clinician. 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 such as neostigmine 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.

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) [see Drug Interactions (7.1)].

Patients homozygous for atypical plasma cholinesterase gene (1 in 2,500 patients) are extremely sensitive to the neuromuscular blocking effect of succinylcholine. If succinylcholine chloride is administered to a patient homozygous for atypical plasma cholinesterase, resulting apnea or prolonged muscle paralysis should be treated with controlled respiration.

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 [see Warnings and Precautions (5.9)].

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

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 (see Clinical Considerations). Animal reproduction studies have not been conducted with succinylcholine chloride.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical Considerations

Maternal Adverse Reactions

Plasma cholinesterase levels are decreased by approximately 24% during pregnancy and for several days postpartum which can prolong the effect of succinylcholine. Therefore, some pregnant patients may experience prolonged apnea.

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.

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 succinylcholine chloride and any potential adverse effects on the breastfed infant from succinylcholine chloride or from the underlying maternal condition.

Intravenous bolus administration of succinylcholine chloride in pediatric patients (including infants) may result in profound bradycardia or, rarely, asystole. The incidence and severity of bradycardia is higher in pediatric patients than adults [see Warnings and Precautions (5.6)].

The effective dose of succinylcholine chloride in pediatric patients may be higher than that predicted by body weight dosing alone [see Dosage and Administration (2.3)].

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.

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.

Succinylcholine has no direct effect on the myocardium. Succinylcholine stimulates both autonomic ganglia and muscarinic receptors which may cause changes in cardiac rhythm, including cardiac arrest. Changes in rhythm, including cardiac arrest, may also result from vagal stimulation, which may occur during surgical procedures, or from hyperkalemia, particularly in pediatric patients [see Warnings and Precautions (5.1, 5.4, 5.6), Use in Specific Populations (8.4)]. These effects are enhanced by halogenated anesthetics.

Succinylcholine causes an increase in intraocular pressure immediately after its injection and during the fasciculation phase, and increases which may persist after onset of complete paralysis [see Warnings and Precautions (5.7)].

Succinylcholine may cause increases in intracranial pressure immediately after its injection and during the fasciculation phase [see Warnings and Precautions (5.11)].

As with other neuromuscular blocking agents, the potential for releasing histamine is present following succinylcholine administration. Signs and symptoms of histamine-mediated release such as flushing, hypotension and bronchoconstriction are, however, uncommon with normal clinical usage.

Succinylcholine has no effect on consciousness, pain threshold or cerebration [see Warnings and Precautions (5.14)].

Succinylcholine has no direct action on the uterus or other smooth muscle structures.

Succinylcholine levels were reported to be below the detection limit of 2 mcg/mL after 2.5 minutes of an intravenous bolus dose of 1 mg/kg 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.

Specific Populations

Pediatric Patients

Due to the relatively large volume of distribution in the pediatric patient versus the adult patient, the effective dose of succinylcholine chloride injection in pediatric patients may be higher than that predicted by body weight dosing alone [see Dosage and Administration (2.3)].

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

Mutagenesis

Adequate studies have not been completed to evaluate the genotoxic potential of succinylcholine.

Impairment of Fertility

There are no studies to evaluate the potential impact of succinylcholine on fertility.