Anectine

1 INDICATIONS AND USAGE 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. ANECTINE 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 ANECTINE 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 ANECTINE dosage recommendations, preparation instructions, and administration information ( 2.2 , 2.3 , 2.4 , 2.5 ). 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 Errors 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 [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 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 ( 5.8 ), Overdose ( 10 ), and Pharmacodynamics ( 12.2 )]. 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 ( 5.9 )]. For Long Surgical Procedures Continuous Intravenous Infusion The 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 [see Dosage 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 Injection Intermittent 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 Patients For 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 ( 5.1 ) and Use in Specific Populations ( 8.4 )] . 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 ( 12.3 )]. 2.4 Dosage Recommendations for Intramuscular Use in Adults and Pediatric Patients If 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 Preparation ANECTINE 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. 2.6 Drug Incompatibility ANECTINE 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 ANECTINE with alkaline solutions.

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) ] • Increased 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 Sandoz Inc. at 1-800-525-8747 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 ANECTINE Drugs that may enhance the neuromuscular blocking action of succinylcholine include: promazine, oxytocin, aprotinin, certain non-penicillin antibiotics, β-adrenergic blockers, procainamide, lidocaine, trimethaphan, lithium carbonate, magnesium salts, quinine, chloroquine, diethylether, 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, the possibility of a synergistic or antagonistic effect should be considered.