Succinylcholine Chloride - Succinylcholine Chloride injection, Solution

• Acute rhabdomyolysis with hyperkalemia followed by ventricular dysrhythmias, cardiac arrest, and death has occurred after the administration of succinylcholine to apparently healthy pediatric patients who were subsequently found to have undiagnosed skeletal muscle myopathy, most frequently Duchenne muscular dystrophy

  [see

  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, USP, 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 INJECTION, USP 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.

  ]

  .
• When a healthy appearing pediatric patient develops cardiac arrest within minutes after administration of SUCCINYLCHOLINE CHLORIDE INJECTION, USP
  , not felt to be due to inadequate ventilation, oxygenation or anesthetic overdose, immediate treatment for hyperkalemia should be instituted. In the presence of signs of malignant hyperthermia, appropriate treatment should be instituted concurrently

  [see

  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, USP, 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 INJECTION, USP 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.

  ]

  .
• Reserve the use of SUCCINYLCHOLINE CHLORIDE INJECTION, USP 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

  [see

  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, USP, 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 INJECTION, USP 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 INJECTION, USP 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.

SUCCINYLCHOLINE CHLORIDE INJECTION, USP is supplied as a clear, colorless solution as follows:

• 200 mg/10 mL (20 mg/mL) in multiple-dose fliptop vials contains: 20 mg of succinylcholine anhydrous (equivalent to 22.65 mg of Succinylcholine Chloride, USP)

The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling:

• Ventricular Dysrhythmias, Cardiac Arrest, and Death from Hyperkalemic Rhabdomyolysis in Pediatric Patients
  [see

  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, USP, 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 INJECTION, USP 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.

  ]
• Anaphylaxis
  [see

  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 INJECTION, USP.

  ]
• Hyperkalemia
  [see

  5.4 Hyperkalemia

  SUCCINYLCHOLINE CHLORIDE INJECTION, USP 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 INJECTION, USP 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 INJECTION, USP administration. Consider avoiding use of SUCCINYLCHOLINE CHLORIDE INJECTION, USP in these patients or verify the patient’s baseline potassium levels are within the normal range prior to SUCCINYLCHOLINE CHLORIDE INJECTION, USP administration.

  ]
• Malignant Hyperthermia
  [see

  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, USP 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.

  ]
• Bradycardia
  [see

  5.6 Bradycardia

  Intravenous bolus administration of SUCCINYLCHOLINE CHLORIDE INJECTION, USP in pediatric patients (including infants) may result in profound bradycardia or, rarely, asystole. In both adult and pediatric patients the incidence of bradycardia, which may progress to asystole, is higher following a second dose of succinylcholine. The incidence and severity of bradycardia is higher in pediatric patients than adults. Whereas bradycardia is common in pediatric patients after an initial dose of 1.5 mg/kg, bradycardia is seen in adults only after repeated exposure. Pretreatment with anticholinergic agents (e.g., atropine) may reduce the occurrence of bradyarrhythmias.

  ]
• Increase in Intraocular Pressure
  [see

  5.7 Increased in Intraocular
  Pressure

  Succinylcholine causes an increase in intraocular pressure. Avoid SUCCINYLCHOLINE CHLORIDE INJECTION, USP in instances in which an increase in intraocular pressure is undesirable (e.g., narrow angle glaucoma, penetrating eye injury) unless the potential benefit of its use outweighs the potential risk.

  ]
• Prolonged Neuromuscular Block due to Phase II Block and Tachyphylaxis
  [see

  5.8 Prolonged Neuromuscular
  Block due to Phase II Block and Tachyphylaxis

  When SUCCINYLCHOLINE CHLORIDE INJECTION, USP is given over a prolonged period of time, the characteristic depolarization block of the myoneural junction (Phase I block) may change to a block with characteristics superficially resembling a non-depolarizing block (Phase II block). Prolonged respiratory muscle paralysis or weakness may be observed in patients manifesting this transition to Phase II block. Tachyphylaxis occurs with repeated administration [see Clinical Pharmacology (12.2)]

  .

  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.

  ]

The following adverse reactions associated with the use of succinylcholine were identified in clinical studies or post-marketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure:

SUCCINYLCHOLINE CHLORIDE INJECTION, USP 200 mg/10 mL (20 mg/mL) is intended for multiple-dose administration and contains preservative. Each 1 mL of SUCCINYLCHOLINE CHLORIDE INJECTION, USP 200 mg/10 mL (20 mg/mL) multiple-dose fliptop vials contains: 20 mg of succinylcholine anhydrous (equivalent to 22.65 mg of Succinylcholine Chloride, USP), 1.8 mg of methylparaben and 0.2 mg of propylparaben as preservatives, 4.65 mg of sodium chloride as iso-osmotic agent, and sodium hydroxide and hydrochloric acid as pH adjusters in water for injection. The pH of the solution is between 3.0 and 4.5, with an osmolarity of 0.338 mOsm/mL (calc.).