rate [0.05:99 mg/kg/day in neonates and low-birth-weight neonates. Additional symptoms may include gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. Although normal therapeutic doses of this product deliver amounts of benzyl alcohol that are substantially lower than those reported in association with the gasping syndrome , the minimum amount of benzyl alcohol at which toxicity may occur is not known. Premature and low-birth-weight infants, as well as patients receiving high dosages, may be more likely to develop toxicity. Practitioners administering this and other medications containing benzyl alcohol should consider the combined daily metabolic load of benzyl alcohol from all sources. Geriatric Use Of the total number of subjects in clinical studies of cisatracurium besylate, 57 were 65 and over, 63 were 70 and over, and 15 were 80 and over. The geriatric population included a subset of patients with significant cardiovascular disease (see CLINICAL PHARMACOLOGY - Hemodynamics Profile and Special Populations - Geriatric Patients subsections). No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between elderly and younger subjects, but greater sensitivity of some older individuals to cisatracurium besylate cannot be ruled out. Minor differences in the pharmacokinetics of cisatracurium between elderly and young adult patients are not associated with clinically significant differences in the recovery profile of cisatracurium besylate following a single 0.1 mg/kg dose; the time to maximum block is approximately 1 minute slower in elderly patients (see CLINICAL PHARMACOLOGY - Pharmacokinetics ). Adverse Reactions Observed in Clinical Trials of Surgical Patients Adverse experiences were uncommon among the 945 surgical patients who received cisatracurium besylate in conjunction with other drugs in US and European clinical studies in the course of a wide variety of procedures in patients receiving opioid, propofol, or inhalation anesthesia. The following adverse experiences were judged by investigators during the clinical trials to have a possible causal relationship to administration of cisatracurium besylate: Incidence Greater than 1% None. Incidence Less than 1% Cardiovascular bradycardia (0.4%) hypotension (0.2%) flushing (0.2%) Respiratory bronchospasm (0.2%) Dermatological rash (0.1%) Observed in Clinical Trials of Intensive Care Unit Patients Adverse experiences were uncommon among the 68 ICU patients who received cisatracurium besylate in conjunction with other drugs in US and European clinical studies. One patient experienced bronchospasm. In one of the two ICU studies, a randomized and double-blind study of ICU patients using TOF neuromuscular monitoring, there were two reports of prolonged recovery (167 and 270 minutes) among 28 patients administered cisatracurium besylate and 13 reports of prolonged recovery (range: 90 minutes to 33 hours) among 30 patients administered vecuronium. Observed During Clinical Practice In addition to adverse events reported from clinical trials, the following events have been identified during post-approval use of cisatracurium besylate in conjunction with one or more anesthetic agents in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to cisatracurium besylate. General Histamine release, hypersensitivity reactions including anaphylactic or anaphylactoid reactions which, in some cases have been life threatening and fatal. Because these reactions were reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency (see WARNINGS and PRECAUTIONS ). There are rare reports of wheezing, laryngospasm, bronchospasm, rash and itching following administration of cisatracurium besylate in children. These reported adverse events were not serious and their etiology could not be established with certainty. Musculoskeletal Prolonged neuromuscular block, inadequate neuromuscular block, muscle weakness, and myopathy. Overdosage Overdosage with neuromuscular blocking agents may result in neuromuscular block beyond the time needed for surgery and anesthesia. The primary treatment is maintenance of a patent airway and controlled ventilation until recovery of normal neuromuscular function is assured. Once recovery from neuromuscular block begins, further recovery may be facilitated by administration of an anticholinesterase agent (e.g., neostigmine, edrophonium) in conjunction with an appropriate anticholinergic agent (see Antagonism of Neuromuscular Block below). Antagonism of Neuromuscular Block ANTAGONISTS (SUCH AS NEOSTIGMINE AND EDROPHONIUM) SHOULD NOT BE ADMINISTERED WHEN COMPLETE NEUROMUSCULAR BLOCK IS EVIDENT OR SUSPECTED. THE USE OF A PERIPHERAL NERVE STIMULATOR TO EVALUATE RECOVERY AND ANTAGONISM OF NEUROMUSCULAR BLOCK IS RECOMMENDED. Administration of 0.04 to 0.07 mg/kg neostigmine at approximately 10% recovery from neuromuscular block (range: 0 to 15%) produced 95% recovery of the muscle twitch response and a T 4 :T 1 ratio 70% in an average of 9 to 10 minutes. The times from 25% recovery of the muscle twitch response to a T 4 :T 1 ratio 70% following these doses of neostigmine averaged 7 minutes. The mean 25% to 75% recovery index following reversal was 3 to 4 minutes. Administration of 1.0 mg/kg edrophonium at approximately 25% recovery from neuromuscular block (range: 16% to 30%) produced 95% recovery and a T 4 :T 1 ratio 70% in an average of 3 to 5 minutes. Patients administered antagonists should be evaluated for evidence of adequate clinical recovery (e.g., 5-second head lift and grip strength). Ventilation must be supported until no longer required. The onset of antagonism may be delayed in the presence of debilitation, cachexia, carcinomatosis, and the concomitant use of certain broad spectrum antibiotics, or anesthetic agents and other drugs which enhance neuromuscular block or separately cause respiratory depression (see PRECAUTIONS - Drug Interactions ). Under such circumstances the management is the same as that of prolonged neuromuscular block (see OVERDOSAGE ). Cisatracurium Besylate Injection Dosage and Administration NOTE: CONTAINS BENZYL ALCOHOL (see WARNINGS and PRECAUTIONS: Pediatric Use ) Cisatracurium Besylate Injection, USP SHOULD ONLY BE ADMINISTERED INTRAVENOUSLY. The dosage information provided below is intended as a guide only. Doses of Cisatracurium Besylate Injection, USP should be individualized (see CLINICAL PHARMACOLOGY - Individualization of Dosages ). The use of a peripheral nerve stimulator will permit the most advantageous use of Cisatracurium Besylate Injection, USP , minimize the possibility of overdosage or underdosage , and assist in the evaluation of recovery. Adults Initial Doses One of two intubating doses of cisatracurium besylate may be chosen, based on the desired time to tracheal intubation and the anticipated length of surgery. In addition to the dose of neuromuscular blocking agent, the presence of co-induction agents (e.g., fentanyl and midazolam) and the depth of anesthesia are factors that can influence intubation conditions. Doses of 0.15 (3 ED 95 ) mg/kg and 0.20 (4 ED 95 ) mg/kg cisatracurium besylate, as components of a propofol/nitrous oxide/oxygen induction-intubation technique, may produce generally GOOD or EXCELLENT conditions for intubation in 2.0 and 1.5 minutes, respectively. Similar intubation conditions may be expected when these doses of cisatracurium besylate are administered as components of a thiopental/nitrous oxide/oxygen induction-intubation technique. In two intubation studies using thiopental or propofol and midazolam and fentanyl as co-induction agents, EXCELLENT intubation conditions were most frequently achieved with the 0.2 mg/kg compared to 0.15 mg/kg dose of Cisatracurium Besylate Injection. The clinically effective durations of action for 0.15 mg/kg and 0.20 mg/kg Cisatracurium Besylate Injection during propofol anesthesia are 55 minutes (range: 44 to 74 minutes) and 61 minutes (range: 41 to 81 minutes), respectively. Lower doses may result in a longer time for the development of satisfactory intubation conditions. Doses up to 8 ED 95 Cisatracurium Besylate Injection have been safely administered to healthy adult patients and patients with serious cardiovascular disease. These larger doses are associated with longer clinically effective durations of action (see CLINICAL PHARMACOLOGY ). Because slower times to onset of complete neuromuscular block were observed in elderly patients and patients with renal dysfunction, extending the interval between administration of Cisatracurium Besylate Injection and the intubation attempt for these patients may be required to achieve adequate intubation conditions. A dose of 0.03 mg/kg cisatracurium besylate is recommended for maintenance of neuromuscular block during prolonged surgical procedures. Maintenance doses of 0.03 mg/kg each sustain neuromuscular block for approximately 20 minutes. Maintenance dosing is generally required 40 to 50 minutes following an initial dose of 0.15 mg/kg cisatracurium besylate and 50 to 60 minutes following an initial dose of 0.20 mg/kg cisatracurium besylate, but the need for maintenance doses should be determined by clinical criteria. For shorter or longer durations of action, smaller or larger maintenance doses may be administered. Isoflurane or enflurane administered with nitrous oxide/oxygen to achieve 1.25 MAC (Minimum Alveolar Concentration) may prolong the clinically effective duration of action of initial and maintenance doses. The magnitude of these effects may depend on the duration of administration of the volatile agents. Fifteen to 30 minutes of exposure to 1.25 MAC isoflurane or enflurane had minimal effects on the duration of action of initial doses of Cisatracurium Besylate Injection and therefore, no adjustment to the initial dose should be necessary when Cisatracurium Besylate Injection is administered shortly after initiation of volatile agents. In long surgical procedures during enflurane or isoflurane anesthesia, less frequent maintenance dosing or lower maintenance doses of Cisatracurium Besylate Injection may be necessary. No adjustments to the initial dose of Cisatracurium Besylate Injection are required when used in patients receiving propofol anesthesia. Children Initial Doses The recommended dose of cisatracurium besylate for children 2 to 12 years of age is 0.10 mg/kg-0.15 mg/kg administered over 5 to 10 seconds during either halothane or opioid anesthesia. When administered during stable opioid/nitrous oxide/oxygen anesthesia, 0.10 mg/kg cisatracurium besylate produces maximum neuromuscular block in an average of 2.8 minutes (range: 1.8 to 6.7 minutes) and clinically effective block for 28 minutes (range: 21 to 38 minutes). When administered during stable opioid/nitrous oxide/oxygen anesthesia, 0.15 mg/kg cisatracurium besylate produces maximum neuromuscular block in about 3.0 minutes (range: 1.5 to 8.0 minutes) and clinically effective block (time to 25% recovery) for 36 minutes (range: 29 to 46 minutes). Infants Initial Doses The recommended dose of cisatracurium besylate for intubation of infants 1 month to 23 months is 0.15 mg/kg administered over 5 to 10 seconds during either halothane or opioid anesthesia. When administered during stable opioid/nitrous oxide/oxygen anesthesia, 0.15 mg/kg cisatracurium besylate produces maximum neuromuscular block in about 2.0 minutes (range: 1.3 to 3.4 minutes) and clinically effective block (time to 25% recovery) for about 43 minutes (range: 34 to 58 minutes). Use by Continuous Infusion Infusion in the Operating Room (OR) After administration of an initial bolus dose of cisatracurium besylate, a diluted solution of Cisatracurium Besylate Injection can be administered by continuous infusion to adults and children aged 2 or more years for maintenance of neuromuscular block during extended surgical procedures. Infusion of Cisatracurium Besylate Injection, USP should be individualized for each patient. The rate of administration should be adjusted according to the patient's response as determined by peripheral nerve stimulation. Accurate dosing is best achieved using a precision infusion device. Infusion of Cisatracurium Besylate Injection, USP should be initiated only after early evidence of spontaneous recovery from the initial bolus dose. An initial infusion rate of 3 mcg/kg/min may be required to rapidly counteract the spontaneous recovery of neuromuscular function. Thereafter, a rate of 1 to 2 mcg/kg/min should be adequate to maintain continuous neuromuscular block in the range of 89% to 99% in most pediatric and adult patients under opioid/nitrous oxide/oxygen anesthesia. Reduction of the infusion rate by up to 30% to 40% should be considered when Cisatracurium Besylate Injection, USP is administered during stable isoflurane or enflurane anesthesia (administered with nitrous oxide/oxygen at the 1.25 MAC level). Greater reductions in the infusion rate of Cisatracurium Besylate Injection, USP may be required with longer durations of administration of isoflurane or enflurane. The rate of infusion of atracurium required to maintain adequate surgical relaxation in patients undergoing coronary artery bypass surgery with induced hypothermia (25 to 28 C) is approximately half the rate required during normothermia. Based on the structural similarity between Cisatracurium Besylate Injection, USP and atracurium, a similar effect on the infusion rate of Cisatracurium Besylate Injection, USP may be expected. Spontaneous recovery from neuromuscular block following discontinuation of infusion of cisatracurium besylate may be expected to proceed at a rate comparable to that following administration of a single bolus dose. Infusion in the Intensive Care Unit (ICU) The principles for infusion of Cisatracurium Besylate Injection, USP in the OR are also applicable to use in the ICU. An infusion rate of approximately 3 mcg/kg/min (range: 0.5 to 10.2 mcg/kg/min) should provide adequate neuromuscular block in adult patients in the ICU. There may be wide interpatient variability in dosage requirements and these may increase or decrease with time (see PRECAUTIONS - Long-Term Use in the Intensive Care Unit (ICU) ). Following recovery from neuromuscular block, readministration of a bolus dose may be necessary to quickly re-establish neuromuscular block prior to reinstitution of the infusion. Infusion Rate Tables The amount of infusion solution required per minute will depend upon the concentration of cisatracurium besylate in the infusion solution, the desired dose of cisatracurium besylate, and the patient's weight. The contribution of the infusion solution to the fluid requirements of the patient also must be considered. Tables 10 and Table 11 provide guidelines for delivery, in mL/hr (equivalent to microdrops/minute when 60 microdrops = 1 mL), of cisatracurium besylate solutions in concentrations of 0.1 mg/mL (10 mg/100 mL) or 0.4 mg/mL (40 mg/100 mL). Table 10. Infusion Rates of Cisatracurium Besylate for Maintenance of Neuromuscular Block During Opioid/Nitrous Oxide/Oxygen Anesthesia for a Concentration of 0.1 mg/mL Drug Delivery Rate (mcg/kg/min) 1.0 1.5 2.0 3.0 5.0 Patient Weight (kg) Infusion Delivery Rate (mL/ hr ) 10 6 9 12 18 30 45 27 41 54 81 135 70 42 63 84 126 210 100 60 90 120 180 300 Table 11. Infusion Rates of Cisatracurium Besylate for Maintenance of Neuromuscular Block During Opioid/Nitrous Oxide/Oxygen Anesthesia for a Concentration of 0.4 mg/mL Drug Delivery Rate (mcg/kg/min) 1.0 1.5 2.0 3.0 5.0 Patient Weight (kg) Infusion Delivery Rate (mL/ hr ) 10 1.5 2.3 3.0 4.5 7.5 45 6.8 10.1 13.5 20.3 33.8 70 10.5 15.8 21.0 31.5 52.5 100 15.0 22.5 30.0 45.0 75.0 Cisatracurium Besylate Injection, USP Compatibility and Admixtures Y-site Administration Cisatracurium Besylate Injection, USP is acidic (pH = 3.25 to 3.65) and may not be compatible with alkaline solution having a pH greater than 8.5 (e.g., barbiturate solutions). Studies have shown that Cisatracurium Besylate Injection, USP is compatible with: 5% Dextrose injection, USP 0.9% Sodium chloride injection, USP 5% Dextrose and 0.9% Sodium chloride injection, USP SUFENTA (sufentanil citrate) injection, diluted as directed ALFENTA (alfentanil hydrochloride) injection, diluted as directed SUBLIMAZE (fentanyl citrate) injection, diluted as directed VERSED (midazolam hydrochloride) injection, diluted as directed Droperidol injection, diluted as directed Cisatracurium Besylate Injection, USP is not compatible with DIPRIVAN (propofol) injection or TORADOL (ketorolac) injection for Y-site administration. Studies of other parenteral products have not been conducted. Dilution Stability Cisatracurium Besylate Injection, USP diluted in 5% Dextrose Injection, USP; 0.9% Sodium Chloride Injection, USP; or 5% Dextrose and 0.9% Sodium Chloride Injection, USP to 0.1 mg/mL may be stored either under refrigeration or at room temperature for 24 hours without significant loss of potency. Dilutions to 0.1 mg/mL or 0.2 mg/mL in 5% Dextrose and Lactated Ringer's Injection may be stored under refrigeration for 24 hours. Cisatracurium Besylate Injection, USP should not be diluted in Lactated Ringer's Injection, USP due to chemical instability. NOTE: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Solutions which are not clear, or contain visible particulates, should not be used. Cisatracurium Besylate Injection, USP is a colorless to slightly yellow or greenish-yellow solution. How is Cisatracurium Besylate Injection Supplied Cisatracurium Besylate Injection, USP, 2 mg cisatracurium per mL, is supplied in the following: NDC Container Size 57884-3062-1 Multiple-dose vial, individually boxed 10 mL NOTE: 10 mL Multiple-dose Vials contain 0.9% w/v benzyl alcohol as a preservative (see WARNINGS concerning newborn infants). Storage Cisatracurium Besylate Injection, USP should be refrigerated at 2 to 8 C (36 to 46 F) in the carton to preserve potency. Protect from light. DO NOT FREEZE. Upon removal from refrigeration to room temperature storage conditions (25 C/77 F), use Cisatracurium Besylate Injection, USP within 21 days even if rerefrigerated. Manufactured by: Jiangsu Hengrui Medicine Co., Ltd. Liangyungang, Jiangsu, 222047, China Distributed by: eVenus Pharmaceutical Laboratories, Inc.(eVenus) 506 Carnegie Center, Suite 100, Princeton, NJ 08540, USA Brands listed are the trademarks of their respective owners. 06/2017 Rev. 02 Principal Display Panel NDC 57884-3062-1 Cisatracurium Besylate Injection, USP For Intravenous Injection 10 mL Multiple Dose Vial 20 mg/10 mL* (2 mg/mL) 0.9% benzyl alcohol (added as a preservative) Rx only CISATRACURIUM BESYLATE Cisatracurium Besylate Injection Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:57884-3062 Route of Administration INTRAVENOUS DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CISATRACURIUM BESYLATE (CISATRACURIUM) CISATRACURIUM 2 mg in 1 mL Inactive Ingredients Ingredient Name Strength BENZYL ALCOHOL BENZENESULFONIC ACID WATER Packaging # Item Code Package Description 1 NDC:57884-3062-1 1 VIAL, MULTI-DOSE in 1 CARTON 1 10 mL in 1 VIAL, MULTI-DOSE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA209334 08/31/2017 Labeler - Jiangsu Hengrui Medicine Co., Ltd. (654147255) Revised: 06/2017 Jiangsu Hengrui Medicine Co., Ltd. Next Interactions Print this page Add to My Med List More about cisatracurium Side Effects Drug Interactions Support Group Pricing & Coupons En Español 0 Reviews Add your own review/rating Drug class: neuromuscular blocking agents Consumer resources Cisatracurium Professional resources Cisatracurium Besylate (AHFS Monograph) Cisatracurium (Wolters Kluwer) Other brands: Nimbex Related treatment guides Light Anesthesia Anesthesia]} FEATURED: CAR-T Cell Therapy Overview Mechanism of Action KTE-C19 Studies KTE-C19 Cancer Targets Adverse Events Manufacturing Drug Status Rx Availability Prescription only B Pregnancy Category No proven risk in humans N/A CSA Schedule Not a controlled drug Approval History Drug history at FDA Manufacturers Sandoz Inc. Fresenius Kabi USA, LLC Drug Class Neuromuscular blocking agents Related Drugs neuromuscular blocking agents succinylcholine , rocuronium , cisatracurium , vecuronium Anesthesia lidocaine , fentanyl , hyoscyamine , propofol , Levsin , ketamine , glycopyrrolate , Emla , Robinul , butorphanol , etomidate , succinylcholine , More... Light Anesthesia lorazepam , diazepam , Ativan , Valium , midazolam , Versed , Diastat , cisatracurium , Nimbex , Diastat AcuDial , More... Cisatracurium Rating No Reviews - Be the first! 5.0 /10 No Reviews - Be the first! 5.0 Rate it!} } geared toward
an inexpensive Cisatracurium Besylate Injection a chronic
EmoticonEmoticon