5 ML succinylcholine chloride 20 MG/ML Prefilled Syringe

INDICATIONS AND USAGE Succinylcholine Chloride Injection is 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 INDICATIONS AND USAGE Succinylcholine Chloride Injection is a depolarizing neuromuscular blocker indicated in adults and pediatric patients: as an adjunct to general anesthesia ( 1 ) to facilitate tracheal intubation ( 1 ) to provide skeletal muscle relaxation during surgery or mechanical ventilation ( 1 )

2. DOSAGE AND ADMINISTRATION For intravenous or intramuscular use only. ( 2.1 ) Individualize dosage after careful assessment of the patient. ( 2.1 ) Accidental administration of neuromuscular blocking agents may be fatal. Store with the prefilled syringe and cap intact, and in a manner that minimizes the possibility of selecting the wrong product. ( 2.1 ) See full prescribing information for dosage recommendations, preparation instructions, and administration information. ( 2.2 , 2.3 , 2.4 , 2.5 , 2.6 ) 2.1 Important Dosage and Administration Information Succinylcholine Chloride Injection is for intravenous or intramuscular use only. Succinylcholine Chloride Injection must be administered under supervision of experienced clinicians who are familiar with its actions and with appropriate neuromuscular monitoring techniques. Succinylcholine Chloride Injection 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 CO 2 . The clinician must be prepared to assist or control respiration. The dosage of Succinylcholine Chloride Injection 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 Succinylcholine Chloride Injection before unconsciousness has been induced [see Warnings and Precautions (5.14) ]. The occurrence of bradyarrhythmias with administration of Succinylcholine Chloride Injection may be reduced by pretreatment with anticholinergics (e.g., atropine) [see Warnings and Precautions (5.6) ]. Monitor neuromuscular function with a peripheral nerve stimulator when using Succinylcholine Chloride Injection by infusion [see Dosage and Administration (2.2) , Warnings and Precautions (5.8) ]. Visually inspect Succinylcholine Chloride Injection for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer solutions that are not clear and colorless. Succinylcholine Chloride Injection must be diluted for continuous intravenous infusion [see Dosage and Administration (2.5) ]. Risk of Medication Errors Accidental administration of neuromuscular blocking agents may be fatal. Store Succinylcholine Chloride Injection with the prefilled syringe and cap intact, and in a manner that minimizes the possibility of selecting the wrong product [see Warnings and Precautions (5.3) ]. 2.2 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 Succinylcholine Chloride 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 to 10 mg 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 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 Injection and, hence, of relaxation. Succinylcholine Chloride Injection, 1 mg per mL, may be administered 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 Injection 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 injections of 0.04 mg/kg to 0.07 mg/kg to maintain the degree of relaxation required. 2.3 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 Succinylcholine Chloride Injection is 2 mg/kg for infants and other small pediatric patients; for older pediatric patients and adolescents the intravenous dose of Succinylcholine Chloride is 1 mg/kg [ see Warnings and Precautions (5.1) , Use in Specific Populations (8.4) ]. The effective dose of Succinylcholine Chloride Injection 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 [ see Clinical Pharmacology (12.3) ]. 2.4 Dosage Recommendations for Intramuscular Use in Adults and Pediatric Patients If a suitable vein is inaccessible, Succinylcholine Chloride Injection 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. 2.5 Preparation of Succinylcholine Chloride Injection Succinylcholine Chloride Injection is supplied in a single-dose, prefilled syringe, and does not require dilution for intravenous or intramuscular bolus dosing. Succinylcholine Chloride Injection may be diluted for continuous intravenous infusion 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 Succinylcholine Chloride solution for single patient use only. Store the diluted Succinylcholine Chloride 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 Succinylcholine Chloride Injection 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 Succinylcholine Chloride Injection solution. 2.6 Drug Incompatibility Succinylcholine Chloride Injection is acidic (pH 3.5) and may not be compatible with alkaline solutions having a pH greater than 8.5 (e.g., barbiturate solutions). Therefore, do not mix Succinylcholine Chloride Injection with alkaline solutions. 2.7 Instructions for Use of Prefilled Syringe CAUTION: Assure that the needle or Needleless Luer Access Device (NLAD) is securely attached before beginning the injection. Visually inspect the syringe-needle or syringe-NLAD connection before and during drug administration. Administration Technique Figure 1 Succinylcholine Chloride Injection may be ad

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. ( 5.2 ) Risk of Death due to Medication Errors : Unintended administration of succinylcholine chloride 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. ( 5.3 ) Hyperkalemia : Succinylcholine chloride may induce serious cardiac arrhythmias or cardiac arrest due to hyperkalemia. ( 5.4 ) Malignant Hyperthermia: Malignant hyperthermia may occur, especially in individuals with known or suspected susceptibility based on genetic factors or family history. Discontinue triggering agents, administer intravenous dantrolene sodium, and apply supportive therapies. ( 5.5 ) 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. ( 5.6 ) 5.1 Ventricular Dysrhythmias, Cardiac Arrest, and Death From Hyperkalemic Rhabdomyolysis in Pediatric Patients There have been reports of ventricular dysrhythmias, cardiac arrest, and death secondary to acute rhabdomyolysis with hyperkalemia in apparently healthy pediatric patients who received succinylcholine. Many of these pediatric patients were subsequently found to have a skeletal muscle myopathy such as Duchenne muscular dystrophy whose clinical signs were not obvious. 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. 5.2 Anaphylaxis 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. Allergic cross-reactivity between neuromuscular blocking agents, both depolarizing and non-depolarizing, has been reported in this class of drugs. Therefore, assess patients for previous anaphylactic reactions to other neuromuscular blocking agents before administering succinylcholine chloride. 5.3 Risk of Death due to Medication Errors Administration of succinylcholine chloride results in paralysis, which may lead to respiratory arrest and death; this progression may be more likely to occur in a patient for whom it is not intended. Confirm proper selection of intended product and avoid confusion with other injectable solutions that are present in critical care and other clinical settings. If another healthcare provider is administering the product, ensure that the intended dose is clearly labeled and communicated. 5.4 Hyperkalemia Succinylcholine chloride may induce serious cardiac arrhythmias or cardiac arrest due to hyperkalemia in patients with electrolyte abnormalities and those who may have digitalis toxicity. 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. 5.5 Malignant Hyperthermia In susceptible individuals, succinylcholine may trigger malignant hyperthermia, a skeletal muscle hypermetabolic state leading to high oxygen demand. Fatal outcomes of malignant hyperthermia have been reported. The risk of developing malignant hyperthermia increases with the concomitant administration of succinylcholine and volatile anesthetic agents. Succinylcholine chloride injection can induce malignant hyperthermia in patients with known or suspected susceptibility based on genetic factors or family history, including those with certain inherited ryanodine receptor (RYR1) or dihydropyridine receptor (CACNA1S) variants. [see Contraindications ( 4 ), Clinical Pharmacology ( 12.5 )] . Signs consistent with malignant hyperthermia may include hyperthermia, hypoxia, hypercapnia, muscle rigidity (e.g., jaw muscle spasm), tachycardia (e.g., particularly that unresponsive to deepening anesthesia or analgesic medication administration), tachypnea, cyanosis, arrhythmias, hypovolemia, and hemodynamic instability. Skin mottling, coagulopathies, and renal failure may occur later in the course of the hypermetabolic process. Successful treatment of malignant hyperthermia depends on early recognition of the clinical signs. If malignant hyperthermia is suspected, discontinue all triggering agents (i.e., volatile anesthetic agents and succinylcholine), administer intravenous dantrolene sodium, and initiate supportive therapies. Consult prescribing information for intravenous dantrolene sodium for additional information on patient management. Supportive therapies include administration of supplemental oxygen and respiratory support based on clinical need, maintenance of hemodynamic stability and adequate urinary output, management of fluid and electrolyte balance, correction of acid base derangements, and institution of measures to control rising temperature. 5.6 Bradycardia Intravenous bolus administration of succinylcholine chloride in pediatric patients (including infants) may result in profound bradycardia or, rarely, asystole. In both adult and pediatric patients the i

CONTRAINDICATIONS ANECTINE is contraindicated in patients with: • Known or suspected genetic susceptibility to malignant hyperthermia [see WARNINGS, Malignant Hyperthermia ( 5.5 ), CLINICAL PHARMACOLOGY, Pharmacogenomics ( 12.5 )] • Skeletal muscle myopathies [see WARNINGS, Ventricular Dysrhythmias, Cardiac Arrest, and Death From Hyperkalemic Rhabdomyolysis in Pediatric Patients ( 5.1 )] • Known hypersensitivity to succinylcholine [see Warnings and Precautions (5.2) ] . • After the acute phase of injury following major burns, multiple trauma, extensive denervation of the skeletal muscle, or upper neuron injury because succinylcholine administered to such individuals may result in severe hyperkalemia, which may result in cardiac arrest [see Warnings and Precautions (5.4) ] . • Skeletal muscle myopathies ( 4 ) • Known hypersensitivity to succinylcholine ( 4 ) • After the acute phase of injury following major burns, multiple trauma, extensive denervation of skeletal muscle, or upper motor neuron injury ( 4 ) • Known or suspected genetic susceptibility to malignant hyperthermia ( 4 )

CLINICAL PHARMACOLOGY 12.1 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. 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. 12.2 Pharmacodynamics Depending on the dose and duration of succinylcholine administration, the characteristic depolarizing neuromuscular block (Phase I block) may change to a block with characteristics superficially resembling a non-depolarizing block (Phase II block). This may be associated with prolonged respiratory muscle paralysis or weakness in patients who manifest the transition to Phase II block. Tachyphylaxis occurs with repeated administration [see Warnings and Precautions (5.8) ]. 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 2 O/O 2 /narcotic-thiopental) 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 [see Warnings and Precautions (5.8) ]. 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, 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. 12.3 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. 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) ]. 12.5 Pharmacogenomics RYR1 and CACNA1S are polymorphic genes and multiple pathogenic variants have been associated with malignant hyperthermia susceptibility (MHS) in patients receiving Succinylcholine Chloride Injection. Case reports as well as ex-vivo studies have identified multiple variants in RYR1 and CACNA1 S associated with MHS. Variant pathogenicity should be assessed based on prior clinical experience, functional studies, prevalence information, or other evidence [see Contraindications (4) , Warnings and Precautions (5.5) ] .