Anectine Prescribing Information
• 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 PatientsThere have been reports of ventricular dysrhythmias, cardiac arrest, and death secondary to acute rhabdomyolysis with hyperkalemia in apparently healthy pediatric patients who received ANECTINE. Many of these pediatric patients were subsequently diagnosed with a skeletal muscle myopathy, such as Duchenne muscular dystrophy
This syndrome often presents as peaked T-waves and sudden cardiac arrest within minutes after the administration of ANECTINE in healthy appearing pediatric patients (usually, but not exclusively, males, and most frequently 8 years of age or younger). There have also been reports in adolescents.
Therefore, when a healthy appearing infant or child develops cardiac arrest soon after administration of ANECTINE not felt to be due to inadequate ventilation, oxygenation, or anesthetic overdose, immediate treatment for hyperkalemia should be instituted. This should include administration of intravenous calcium, bicarbonate, and glucose with insulin, with hyperventilation. Due to the abrupt onset of this syndrome, routine resuscitative measures are likely to be unsuccessful. However, extraordinary and prolonged resuscitative efforts have resulted in successful resuscitation in some reported cases. In addition, in the presence of signs of malignant hyperthermia, appropriate treatment should be instituted concurrently
[see Warnings and Precautions ].Since there may be no signs or symptoms to alert the practitioner to which patients are at risk, it is recommended that the use of ANECTINE in pediatric patients should be reserved 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 ANECTINE 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 PatientsThere have been reports of ventricular dysrhythmias, cardiac arrest, and death secondary to acute rhabdomyolysis with hyperkalemia in apparently healthy pediatric patients who received ANECTINE. Many of these pediatric patients were subsequently diagnosed with a skeletal muscle myopathy, such as Duchenne muscular dystrophy
This syndrome often presents as peaked T-waves and sudden cardiac arrest within minutes after the administration of ANECTINE in healthy appearing pediatric patients (usually, but not exclusively, males, and most frequently 8 years of age or younger). There have also been reports in adolescents.
Therefore, when a healthy appearing infant or child develops cardiac arrest soon after administration of ANECTINE not felt to be due to inadequate ventilation, oxygenation, or anesthetic overdose, immediate treatment for hyperkalemia should be instituted. This should include administration of intravenous calcium, bicarbonate, and glucose with insulin, with hyperventilation. Due to the abrupt onset of this syndrome, routine resuscitative measures are likely to be unsuccessful. However, extraordinary and prolonged resuscitative efforts have resulted in successful resuscitation in some reported cases. In addition, in the presence of signs of malignant hyperthermia, appropriate treatment should be instituted concurrently
[see Warnings and Precautions ].Since there may be no signs or symptoms to alert the practitioner to which patients are at risk, it is recommended that the use of ANECTINE in pediatric patients should be reserved 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 ANECTINE 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 PatientsThere have been reports of ventricular dysrhythmias, cardiac arrest, and death secondary to acute rhabdomyolysis with hyperkalemia in apparently healthy pediatric patients who received ANECTINE. Many of these pediatric patients were subsequently diagnosed with a skeletal muscle myopathy, such as Duchenne muscular dystrophy
This syndrome often presents as peaked T-waves and sudden cardiac arrest within minutes after the administration of ANECTINE in healthy appearing pediatric patients (usually, but not exclusively, males, and most frequently 8 years of age or younger). There have also been reports in adolescents.
Therefore, when a healthy appearing infant or child develops cardiac arrest soon after administration of ANECTINE not felt to be due to inadequate ventilation, oxygenation, or anesthetic overdose, immediate treatment for hyperkalemia should be instituted. This should include administration of intravenous calcium, bicarbonate, and glucose with insulin, with hyperventilation. Due to the abrupt onset of this syndrome, routine resuscitative measures are likely to be unsuccessful. However, extraordinary and prolonged resuscitative efforts have resulted in successful resuscitation in some reported cases. In addition, in the presence of signs of malignant hyperthermia, appropriate treatment should be instituted concurrently
[see Warnings and Precautions ].Since there may be no signs or symptoms to alert the practitioner to which patients are at risk, it is recommended that the use of ANECTINE in pediatric patients should be reserved 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.
4 CONTRAINDICATIONSANECTINE is contraindicated in patients with:
• Known or suspected genetic susceptibility to malignant hyperthermia[see WARNINGS, Malignant Hyperthermia , CLINICAL PHARMACOLOGY, Pharmacogenomics ]• Skeletal muscle myopathies[see WARNINGS, Ventricular Dysrhythmias, Cardiac Arrest, and Death From Hyperkalemic Rhabdomyolysis in Pediatric Patients ]• 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 severehyperkalemia, which may result in cardiac arrest
[see Warnings and Precautions (5.4)]
• 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• Known or suspected genetic susceptibility to malignant hyperthermia
5.5 Malignant HyperthermiaIn 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. Anectine 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.
ANECTINE 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.
• For intravenous or intramuscular use only ().2.1 Important Dosage and Administration Information• ANECTINE is for intravenous or intramuscular use only.• ANECTINE must be titrated to effect by or under supervision of experienced clinicians who are familiar with its actions and with appropriate neuromuscular monitoring techniques.• ANECTINE 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 carbon dioxide. The clinician must be prepared to assist or control respiration.• The dosage of ANECTINE should be individualized and should always be determined by the clinician after careful assessment of the patient.• To avoid distress to the patient, succinylcholine should not be administered before unconsciousness has been induced. In emergency situations, however, it may be necessary to administer succinylcholine before unconsciousness is induced.• The occurrence of bradyarrhythmias with administration of ANECTINE 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 ANECTINE by infusion[see Dosage and Administration (2.2)].• Visually inspect ANECTINE for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer solutions which are not clear and colorless.
Risk of Medication ErrorsAccidental administration of neuromuscular blocking agents may be fatal. Store ANECTINE 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)].• Individualize dosage after careful assessment of the patient ()2.1 Important Dosage and Administration Information• ANECTINE is for intravenous or intramuscular use only.• ANECTINE must be titrated to effect by or under supervision of experienced clinicians who are familiar with its actions and with appropriate neuromuscular monitoring techniques.• ANECTINE 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 carbon dioxide. The clinician must be prepared to assist or control respiration.• The dosage of ANECTINE should be individualized and should always be determined by the clinician after careful assessment of the patient.• To avoid distress to the patient, succinylcholine should not be administered before unconsciousness has been induced. In emergency situations, however, it may be necessary to administer succinylcholine before unconsciousness is induced.• The occurrence of bradyarrhythmias with administration of ANECTINE 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 ANECTINE by infusion[see Dosage and Administration (2.2)].• Visually inspect ANECTINE for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer solutions which are not clear and colorless.
Risk of Medication ErrorsAccidental administration of neuromuscular blocking agents may be fatal. Store ANECTINE 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)].• Accidental administration of neuromuscular blocking agents may be fatal. Store ANECTINE with the cap and ferrule intact and in a manner that minimizes the possibility of selecting the wrong product ().2.1 Important Dosage and Administration Information• ANECTINE is for intravenous or intramuscular use only.• ANECTINE must be titrated to effect by or under supervision of experienced clinicians who are familiar with its actions and with appropriate neuromuscular monitoring techniques.• ANECTINE 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 carbon dioxide. The clinician must be prepared to assist or control respiration.• The dosage of ANECTINE should be individualized and should always be determined by the clinician after careful assessment of the patient.• To avoid distress to the patient, succinylcholine should not be administered before unconsciousness has been induced. In emergency situations, however, it may be necessary to administer succinylcholine before unconsciousness is induced.• The occurrence of bradyarrhythmias with administration of ANECTINE 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 ANECTINE by infusion[see Dosage and Administration (2.2)].• Visually inspect ANECTINE for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer solutions which are not clear and colorless.
Risk of Medication ErrorsAccidental administration of neuromuscular blocking agents may be fatal. Store ANECTINE 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)].• See full prescribing information for ANECTINE dosage recommendations, preparation instructions, and administration information (,2.2 Dosage Recommendations for Intravenous Use in AdultsFor Short Surgical ProceduresThe average dose required to produce neuromuscular blockade and to facilitate tracheal intubation is 0.6 mg/kg ANECTINE given intravenously. The optimum intravenous dose will vary among patients and may be from 0.3 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. 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) [see Prolonged Neuromuscular Block due to Phase II Block and Tachyphylaxis , Overdose , and Pharmacodynamics ]. A 5 to 10 mg test dose may be used to determine the sensitivity of the patient and the individual recovery time
[see Warnings and Precautions ].For Long Surgical ProceduresContinuous Intravenous InfusionThe dose of ANECTINE administered by intravenous infusion depends upon the duration of the surgical procedure and the need for muscle relaxation. The average rate for an adult range between 2.5 and 4.3 mg per minute.
Diluted ANECTINE solutions containing from 1 to 2 mg/mL succinylcholine have commonly been used for continuous infusion
[seeDosage and Administration (2.4)]. The more dilute solution (1 mg/mL) is probably preferable from the standpoint of ease of control of the rate of administration of ANECTINE and hence, of relaxation. This diluted ANECTINE solution containing 1 mg/mL of succinylcholine may be administered at a rate of 0.5 mg (0.5 mL) 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 require. Monitor neuromuscular function with a peripheral nerve stimulator when using ANECTINE 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 InjectionIntermittent intravenous injections of ANECTINE may also be used to provide muscle relaxation for long procedures. An intravenous injection of 0.3 to 1.1 mg/kg may be given initially, followed, at appropriate intervals, by further intravenous injections of 0.04 to 0.07 mg/kg to maintain the degree of relaxation required.
,2.3 Dosage Recommendations for Intravenous Use in Pediatric PatientsFor emergency tracheal intubation or in instances where immediate securing of the airway is necessary, the intravenous dose of ANECTINE is 2 mg/kg for infants and other small pediatric patients; for older pediatric patients and adolescents the dose is 1 mg/kg
[see Warnings and Precautions and Use in Specific Populations ]. The effective dose of ANECTINE 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 ].,2.4 Dosage Recommendations for Intramuscular Use in Adults and Pediatric PatientsIf a suitable vein is inaccessible, ANECTINE may be given intramuscularly to infants, older pediatric patients, or adults. A dose of up to 3 to 4 mg/kg may be given, but not more than 150 mg total dose should be administered by this route. The onset of effect of succinylcholine given intramuscularly is usually observed in about 2 to 3 minutes.
).2.5 Drug PreparationANECTINE is supplied in a multi-dose vial and does not require dilution for intravenous or intramuscular bolus dosing.
ANECTINE 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 ANECTINE solution for single patient use only. Store the diluted ANECTINE 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 ANECTINE 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 ANECTINE solution.
ANECTINE (Succinylcholine Chloride Injection, USP) is supplied as a clear, colorless solution:
• 200 mg/10 mL (20 mg/mL) in multiple-dose vials contains: 20 mg of succinylcholine anhydrous (equivalent to 22.65 mg of Succinylcholine Chloride, USP).
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 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.
Plasma cholinesterase levels are decreased by approximately 24% during pregnancy and for several days postpartum which can prolong the effect of ANECTINE. Therefore, some pregnant or newly postpartum patients may experience prolonged apnea following administration of ANECTINE.
Apnea and flaccidity may occur in the newborn after repeated high doses to, or in the presence of atypical plasma cholinesterase in the mother.
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.