Succinylcholine

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.

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 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 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 succinylchol

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 Zydus Pharmaceuticals (USA) Inc. at 1-877-993-8779 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 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.