Succinylcholine

RECENT MAJOR CHANGES SECTION Contraindications ( 4 ) 11/2022 Warnings and Precautions, Malignant Hyperthermia ( 5.5 ) 11/2022

1 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. Succinylcholine chloride 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 succinylcholine chloride injection with the cap and ferrule intact and in a manner that minimizes the possibility of selecting the wrong product. (2.1 ) See full prescribing information for succinylcholine chloride injection 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 titrated to effect by or 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 supplied in multiple- dose vials does not require dilution before use [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 cap and ferrule 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 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 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 injection 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/m …

3 DOSAGE FORMS AND STRENGTHS Succinylcholine chloride injection, USP is supplied as a clear, colorless solution as follows: 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). Injection: 200 mg/10 mL (20 mg/mL) in multiple-dose vials ( 3 )

4 CONTRAINDICATIONS Succinylcholine chloride injection is contraindicated: in patients with skeletal muscle myopathies [see Warnings and Precautions ( 5.1 )] in patients with known hypersensitivity to succinylcholine. Severe anaphylactic reactions to succinylcholine have been reported [see Warnings and Precautions ( 5.2) ] after the acute phase of injury following major burns, multiple trauma, extensive denervation of skeletal muscle, or upper motor neuron injury, which may result in severe hyperkalemia and cardiac arrest [see Warnings and Precautions ( 5.4 )] in patients with known or suspected genetic susceptibility to malignant hyperthermia [see Warnings and Precautions ( 5.5 ), Clinical Pharmacology ( 12.5 )] 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)

6 ADVERSE REACTIONS 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 Warnings and Precautions ( 5.1 )] Anaphylaxis [see Warnings and Precautions ( 5.2 )] Hyperkalemia [see Warnings and Precautions ( 5.4 )] Malignant Hyperthermia [see Warnings and Precautions ( 5.5 )] Bradycardia [see Warnings and Precautions ( 5.6 )] Increase in Intraocular Pressure [see Warnings and Precautions ( 5.7) ] Prolonged Neuromuscular Block due to Phase II Block and Tachyphylaxis [see Warnings and Precautions ( 5.8 )] The following adverse reactions associated with the use of succinylcholine were identified in clinical studies or postmarketing 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: 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 Adverse reactions reported with succinylcholine are cardiac arrest, malignant hyperthermia, arrhythmias, bradycardia, tachycardia, hypertension, hypotension, hyperkalemia, prolonged respiratory depression or apnea. (6) To report SUSPECTED ADVERSE REACTIONS, contact Dr. Reddy's Laboratories Inc., at 1-888-375-3784 or FDA at 1-800-FDA-1088 or www. fda.gov/medwatch.

7 DRUG INTERACTIONS Drugs that May Enhance the Neuromuscular Blocking Action of Succinylcholine: promazine, oxytocin, aprotinin, certain non-penicillin antibiotics, quinidine, β-adrenergic blockers, procainamide, lidocaine, trimethaphan, lithium carbonate, magnesium salts, quinine, chloroquine, isoflurane, desflurane, metoclopramide, terbutaline, and drugs that reduce plasma cholinesterase activity. ( 7.1) 7.1 Drugs that May Affect the Neuromuscular Blocking Action of Succinylcholine Chloride Injection 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 [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.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary 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. 8.2 Lactation Risk Summary 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. 8.4 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 succinylcholine chloride injection 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 Warnings and Precautions ( 5.1 )]. Intravenous bolus administration of succinylcholine chloride injection 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 injection in pediatric patients may be higher than that predicted by body weight dosing alone [see Dosage and Administration ( 2.3 )]. 8.5 Geriatric Use Clinical studies of succinylcholine chloride 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.

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.

11 DESCRIPTION Succinylcholine Chloride Injection, USP is a sterile, nonpyrogenic solution to be used as a short-acting, depolarizing neuromuscular blocker for intravenous or intramuscular use. Succinylcholine chloride injection contains succinylcholine chloride as the active pharmaceutical ingredient. Succinylcholine Chloride, USP is chemically designated C 14 H 30 C l2 N 2 O 4 .2H 2 O and its molecular weight is 397.34. The chemical name of succinylcholine chloride, USP is ethanaminium, 2,2'-[(1,4-dioxo-1,4 butanediyl)bis(oxy)]bis[N,N,N-trimethyl-], dichloride. Succinylcholine chloride, USP is a diquaternary base consisting of the dichloride salt of the dicholine ester of succinic acid. It is a white, or almost white odorless, crystalline powder, freely soluble in water. The drug is incompatible with alkaline solutions but relatively stablein acid solutions. Solutions of the drug lose potency unless refrigerated. It has the following structural formula: 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 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.).

10 OVERDOSAGE Overdosage with succinylcholine chloride injection 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 succinylcholine chloride injection administration, the characteristic depolarizing neuromuscular block (Phase I) may change to a block with characteristics superficially resembling a non-depolarizing block (Phase II) [see Warnings and Precautions ( 5.8 )].

HOW SUPPLIED Succinylcholine Chloride Injection, USP is supplied as a clear, colorless solution in the following concentrations and packages: NDC No. Container Size (mL) mg/mL mg (total ) mOsmol/mL Multiple-dose 43598-666-25 Vial 10 20 200 0.338 Refrigeration of the undiluted agent will assure full potency until expiration date. All units carry a date of expiration. Store in refrigerator 2° to 8°C (36° to 46°F). The multi-dose vials are stable for up to 14 days at room temperature without significant loss of potency. Rx Only Distributor: Dr. Reddy’s Laboratories Inc., Princeton, NJ 08540 Made in India Issued: 0220 To report SUSPECTED ADVERSE REACTIONS, contact Dr. Reddy's Laboratories Inc., at 1- 888-375-3784, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch