Data from FDA (Food and Drug Administration, USA) - Curated by EPG Health - Last updated 18 December 2019

Indication(s)

1 INDICATIONS AND USAGE Cisatracurium Besylate Injection is indicated: as an adjunct to general anesthesia to facilitate tracheal intubation in adults and in pediatric patients 1 month to 12 years of age to provide skeletal muscle relaxation in adults during surgical procedures or during mechanical ventilation in the ICU to provide skeletal muscle relaxation during surgical procedures via infusion in pediatric patients 2 years and older Limitations of Use Cisatracurium Besylate Injection is not recommended for rapid sequence endotracheal intubation due to the time required for its onset of action. Cisatracurium Besylate Injection is a nondepolarizing neuromuscular blocker indicated: as an adjunct to general anesthesia to facilitate tracheal intubation in adults and in pediatric patients 1 month to 12 years of age (1) to provide skeletal muscle relaxation during surgery in adults and in pediatric patients 2 to 12 years of age as a bolus or infusion maintenance (1) for mechanical ventilation in the ICU in adults (1) Limitations of Use: Cisatracurium Besylate Injection is not recommended for rapid sequence endotracheal intubation due to the time required for its onset of action (1)

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Advisory information

contraindications
4 CONTRAINDICATIONS Cisatracurium besylate injection is contraindicated in patients with known hypersensitivity to cisatracurium. Severe anaphylactic reactions to cisatracurium have been reported [see Warnings and Precautions (5.4 )]. The use of 10 mL cisatracurium multiple-dose vials is contraindicated for use in pediatric patients less than 1 month of age and low birth-weight infants because the formulation contains benzyl alcohol [see Warnings and Precautions (5.2 ) and Use in Specific Populations (8.4 )]. Known hypersensitivity to cisatracurium (4) 10 mL multiple-dose vials contain benzyl alcohol and are contraindicated in pediatric patients less than 1 month of age and low birth-weight infants (4)
Adverse reactions
6 ADVERSE REACTIONS The most common adverse reactions (0.1% to 0.4%) were bradycardia, hypotension, flushing, bronchospasm, and rash. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Teva Pharmaceuticals USA, Inc. at 1-888-838-2872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. Adverse Reactions in Clinical Trials of Cisatracurium in Surgical Patients The data presented below are based on studies involving 945 surgical patients who received cisatracurium in conjunction with other drugs in US and European clinical studies in a variety of procedures [see Clinical Studies (14.1 )]. Table 3 displays adverse reactions that occurred at a rate of less than 1%. Table 3. Adverse Reactions in Clinical Trials of Cisatracurium in Surgical Patients Adverse Reaction Incidence Bradycardia 0.4% Hypotension 0.2% Flushing 0.2% Bronchospasm 0.2% Rash 0.1% Adverse Reactions in Clinical Trials of Cisatracurium in Intensive Care Unit Patients The adverse reactions presented below were from studies involving 68 adult ICU patients who received cisatracurium in conjunction with other drugs in US and European clinical studies [see Clinical Studies (14.3 )]. 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 (range: 167 and 270 minutes) among 28 patients administered cisatracurium and 13 reports of prolonged recovery (range: 90 minutes to 33 hours) among 30 patients administered vecuronium. 6.2 Postmarketing Experience The following events have been identified during post-approval use of cisatracurium 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: anaphylaxis, histamine release, prolonged neuromuscular block, muscle weakness, myopathy.

Usage information

Dosing and administration
2 DOSAGE AND ADMINISTRATION Administer intravenously only by or under the supervision of experienced clinicians familiar with drug’s actions and possible complications (2.1) Use only if personnel and facilities for resuscitation and life support, and a cisatracurium besylate injection antagonist are immediately available (2.1) Use a peripheral nerve stimulator to determine adequacy of blockade (e.g., need for additional doses), minimize risk of overdosage or underdosage, assess extent of recovery from blockade, potentially limit exposure to toxic metabolites through dose titration, and facilitate more rapid reversal of cisatracurium besylate injection -induced paralysis (2.1) See the Full Prescribing Information for: Dosage and administration instructions in adults, pediatric patients, geriatric patients, patients with neuromuscular disease, burns, end-stage renal disease, and patients undergoing coronary artery bypass graft surgery with induced hypothermia (2.2, 2.3, 2.4, 2.5) Continuous infusion rates (2.6) Preparation instructions (2.7) Drug compatibility (2.8) 2.1 Important Dosage and Administration Instructions Important administration instructions include: Cisatracurium besylate injection is for intravenous use only. Administer cisatracurium besylate injection in carefully adjusted dosage by or under the supervision of experienced clinicians who are familiar with the drug’s actions and the possible complications. Use cisatracurium besylate injection only if the following are immediately available: personnel and facilities for resuscitation and life support (tracheal intubation, artificial ventilation, oxygen therapy); and an antagonist of cisatracurium besylate injection [see Overdosage (10)]. The dosage information which follows is intended to serve as an initial guide for individual patients; base subsequent cisatracurium besylate injection dosage on the patients’ responses to the initial doses. Use a peripheral nerve stimulator to: Determine the adequacy of neuromuscular blockade (e.g., need for additional cisatracurium besylate injection doses, reduction of the infusion rate). Minimize risk of overdosage or underdosage. Assess the extent of recovery from neuromuscular blockade (e.g., spontaneous recovery or recovery after administration of a reversal agent, e.g., neostigmine). Appropriately titrate doses to potentially limit exposure to toxic metabolites. Facilitate more rapid reversal of the cisatracurium besylate injection -induced paralysis. Risk of Medication Errors Accidental administration of neuromuscular blocking agents may be fatal. Store cisatracurium besylate injection with the cap and ferrule intact and in a manner that minimizes the possibility of selecting the wrong product [see Warnings and Precautions (5.5 )]. 2.2 Recommended Cisatracurium Besylate Injection Dose for Performing Tracheal Intubation Tracheal Intubation in Adults Prior to selecting the initial cisatracurium besylate injection bolus dose, consider the desired time to tracheal intubation and the anticipated length of surgery, factors affecting time to onset of complete neuromuscular block such as age and renal function, and factors that may influence intubation conditions such as the presence of co-induction agents (e.g., fentanyl and midazolam) and the depth of anesthesia. In conjunction with a propofol/nitrous oxide/oxygen induction-intubation technique or a thiopental/nitrous oxide/oxygen induction-intubation technique, the recommended starting weight-based dose of cisatracurium besylate injection is between 0.15 mg/kg and 0.2 mg/kg administered by bolus intravenous injection. Doses up to 0.4 mg/kg have been safely administered by bolus intravenous injection to healthy patients and patients with serious cardiovascular disease [see Clinical Pharmacology (12.2 )]. Patients with Neuromuscular Disease The maximum recommended initial bolus dose of cisatracurium besylate injection is 0.02 mg/kg in patients with neuromuscular diseases (e.g., myasthenia gravis and myasthenic syndrome and carcinomatosis) [see Warnings and Precautions (5.1 )]. Geriatric Patients and Patients with End-Stage Renal Disease Because the time to maximum neuromuscular blockade is approximately 1 minute slower in geriatric patients compared to younger patients (and in patients with end-stage renal disease than in patients with normal renal function), consider extending the interval between administering cisatracurium besylate injection and attempting intubation by at least 1 minute to achieve adequate intubation conditions in geriatric patients and patients with end-stage renal disease. A peripheral nerve stimulator should be used to determine the adequacy of muscle relaxation for the purposes of intubation and the timing and amounts of subsequent doses [see Use in Specific Populations (8.5, 8.6 ) and Clinical Pharmacology (12.3 )]. Tracheal Intubation in Pediatric Patients Infants 1 to 23 Months of Age The recommended dose of cisatracurium besylate injection for intubation of pediatric patients ages 1 month to 23 months is 0.15 mg/kg administered over 5 to 10 seconds. When administered during stable opioid/nitrous oxide/oxygen anesthesia, 0.15 mg/kg of cisatracurium besylate injection produced maximum neuromuscular blockade in about 2 minutes (range: 1.3 to 4.3 minutes) with a clinically effective block (time to 25% recovery) for about 43 minutes (range: 34 to 58 minutes) [see Clinical Studies (14.2 )]. Pediatric Patients 2 to 12 Years of Age The recommended weight-based bolus dose of cisatracurium besylate injection for pediatric patients 2 to 12 years of age is 0.1 mg/kg to 0.15 mg/kg administered over 5 to 10 seconds. When administered during stable opioid/nitrous oxide/oxygen anesthesia, 0.1 mg/kg cisatracurium besylate injection produced maximum neuromuscular blockade in an average of 2.8 minutes (range: 1.8 to 6.7 minutes) with a clinically effective block (time to 25% recovery) for 28 minutes (range: 21 to 38 minutes). When administered during stable opioid/nitrous oxide/oxygen anesthesia, 0.15 mg/kg cisatracurium besylate injection produced maximum neuromuscular blockade in an average of about 3 minutes (range: 1.5 to 8 minutes) with a clinically effective block for 36 minutes (range: 29 to 46 minutes) [see Clinical Studies (14.2 )]. 2.3 Recommended Maintenance Bolus Cisatracurium Besylate Injection Doses in Adult Surgical Procedures Determine if maintenance bolus doses are needed based on clinical criteria including the response to peripheral nerve stimulation. The recommended maintenance bolus dose of cisatracurium besylate injection is 0.03 mg/kg; however, smaller or larger maintenance doses may be administered based on the required duration of action. Administer the first maintenance bolus dose starting: 40 to 50 minutes after an initial dose of cisatracurium besylate injection 0.15 mg/kg; 50 to 60 minutes after an initial dose of cisatracurium besylate injection 0.2 mg/kg. For long surgical procedures using inhalational anesthetics administered with nitrous oxide/oxygen at the 1.25 MAC level for at least 30 minutes, consider administering less frequent maintenance bolus doses or lower maintenance bolus doses of cisatracurium besylate injection [see Clinical Pharmacology (12.2 )]. No adjustment to the initial cisatracurium besylate injection maintenance bolus dose should be necessary when cisatracurium besylate injection is administered shortly after initiation of volatile agents or when used in patients receiving propofol anesthesia. 2.4 Dosage in Burn Patients Burn patients have been shown to develop resistance to nondepolarizing neuromuscular blocking agents; therefore, consider increasing the cisatracurium besylate injection dosages for intubation and maintenance [see Use in Specific Populations (8.8 )]. 2.5 Dosage for Continuous Infusion Continuous Infusion for Surgical Procedures in Adults and Pediatric Patients During extended surgical procedures, cisatracurium besylate injection may be administered by continuous infusion to adults and pediatric patients aged 2 or more years if patients have spontaneous recovery after the initial cisatracurium besylate injection bolus dose. Following recovery from neuromuscular blockade, it may be necessary to re-administer a bolus dose to quickly re-establish neuromuscular blockade prior to starting the continuous infusion. If patients have had recovery of neuromuscular function, the recommended initial cisatracurium besylate injection infusion rate is 3 mcg/kg/minute [see Dosage and Administration (2.6 )]. Subsequently reduce the rate to 1 mcg/kg/minute to 2 mcg/kg/minute to maintain continuous neuromuscular blockade. Use peripheral nerve stimulation to assess the level of neuromuscular blockade and to appropriately titrate the cisatracurium besylate injection infusion rate. If no response is elicited to peripheral nerve stimulation, discontinue the infusion until a response returns. Consider reducing the infusion rate by up to 30% to 40% when cisatracurium besylate injection is administered during stable isoflurane anesthesia for at least 30 minutes (administered with nitrous oxide/oxygen at the 1.25 MAC level) [see Clinical Pharmacology (12.2 )]. Greater reductions in the cisatracurium besylate injection infusion rate may be required with longer durations of administration of isoflurane or with the administration of other inhalational anesthetics. Patients Undergoing Coronary Artery Bypass Graft (CABG) Surgery Consider reducing the infusion rate in patients undergoing CABG with induced hypothermia to half the rate required during normothermia [see Clinical Pharmacology (12.2 )]. Spontaneous recovery from neuromuscular block following discontinuation of infusion of cisatracurium besylate injection infusion is expected to proceed at a rate comparable to that following administration of a single bolus dose. Continuous Infusion for Mechanical Ventilation in the Intensive Care Unit in Adults During extended need for mechanical ventilation and skeletal muscle relaxation in the intensive care unit (ICU), cisatracurium besylate injection may be administered by continuous infusion to adults if a patient has spontaneous recovery of neuromuscular function after the initial cisatracurium besylate injection bolus dose. Following recovery from neuromuscular blockade, it may be necessary to re-administer a bolus dose to quickly re-establish neuromuscular blockade prior to starting the continuous infusion. The recommended cisatracurium besylate injection infusion rate in adult patients in the ICU is 3 mcg/kg/minute (range: 0.5 mcg/kg/minute to 10.2 mcg/kg/minute) [see Dosage and Administration (2.6 )]. Use peripheral nerve stimulation to assess the level of neuromuscular blockade and to appropriately titrate the cisatracurium besylate injection infusion rate. 2.6 Rate Tables for Continuous Infusion The intravenous infusion rate depends upon the cisatracurium besylate injection concentration, the desired dose, the patient's weight, and the contribution of the infusion solution to the fluid requirements of the patient. Tables 1 and Table 2 provide guidelines for the cisatracurium besylate injection infusion rate, in mL/hour (equivalent to microdrops/minute when 60 microdrops = 1 mL), in concentrations of 0.1 mg/mL or 0.4 mg/mL, respectively. Table 1. Cisatracurium Besylate Injection Infusion Rates for Maintenance of Neuromuscular Blockade During Opioid/Nitrous Oxide/Oxygen Anesthesia with a Concentration of 0.1 mg/mL Drug Delivery Rate (mcg/kg/minute) 1 1.5 2 3 5 Patient Weight Infusion Delivery Rate (mL/hour) 10 kg 6 9 12 18 30 45 kg 27 41 54 81 135 70 kg 42 63 84 126 210 100 kg 60 90 120 180 300 Table 2. Cisatracurium Besylate Injection Infusion Rates for Maintenance of Neuromuscular Blockade During Opioid/Nitrous Oxide/Oxygen Anesthesia with a Concentration of 0.4 mg/mL Drug Delivery Rate (mcg/kg/minute) 1 1.5 2 3 5 Patient Weight Infusion Delivery Rate (mL/hour) 10 kg 1.5 2.3 3 4.5 7.5 45 kg 6.8 10.1 13.5 20.3 33.8 70 kg 10.5 15.8 21 31.5 52.5 100 kg 15 22.5 30 45 75 2.7 Preparation of Cisatracurium Besylate Injection Visually inspect cisatracurium besylate injection for particulate matter and discoloration prior to administration. If a cisatracurium besylate injection solution is cloudy or contains visible particulates, do not use cisatracurium besylate injection. cisatracurium besylate injection is a colorless to slightly yellow or greenish-yellow solution. Cisatracurium besylate injection may be diluted to 0.1 mg/mL in the following solutions: 5% Dextrose Injection, USP 0.9% Sodium Chloride Injection, USP, or 5% Dextrose and 0.9% Sodium Chloride Injection, USP Store these diluted cisatracurium besylate injection solutions either in a refrigerator or at room temperature for 24 hours without significant loss of potency. Cisatracurium besylate injection also may be diluted to 0.1 mg/mL or 0.2 mg/mL in the following solution: Lactated Ringer’s and 5% Dextrose Injection Store this diluted cisatracurium besylate injection solution under refrigeration for no more than 24 hours. Do not dilute cisatracurium besylate injection in Lactated Ringer’s Injection, USP due to chemical instability. 2.8 Drug Compatibility Cisatracurium besylate injection is compatible and may be administered with the following solutions through Y-site administration: 5% Dextrose Injection, USP 0.9% Sodium Chloride Injection, USP 5% Dextrose and 0.9% Sodium Chloride Injection, USP Sufentanil Citrate Injection, diluted as directed Alfentanil Hydrochloride Injection, diluted as directed Fentanyl Citrate Injection, diluted as directed Midazolam Hydrochloride Injection, diluted as directed Droperidol Injection, diluted as directed Cisatracurium besylate injection is acidic (pH 3.25 to 3.65 for 10 mL vials and pH 3.0 to 3.7 for 5 mL and 20 mL vials) and may not be compatible with alkaline solution having a pH greater than 8.5 (e.g., barbiturate solutions). Therefore, do not administer cisatracurium besylate injection and alkaline solutions simultaneously in the same intravenous line. Cisatracurium besylate injection is not compatible with propofol injection or ketorolac injection for Y-site administration. Compatibility studies with other parenteral products have not been conducted.
Use in special populations
8 USE IN SPECIFIC POPULATIONS Patients with Hemiparesis or Paraparesis: Perform neuromuscular monitoring on non-paretic limb (8.9) 8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies of cisatracurium in pregnant women. Animal studies conducted in rats administered cisatracurium besylate during organogenesis found no evidence of fetal harm at 0.8 times (ventilated rats) the exposure from a human starting IV bolus dose of 0.2 mg/kg. The background risk for major birth defects and miscarriage in 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 Labor or Delivery The action of neuromuscular blocking agents may be enhanced by magnesium salts administered for the management of preeclampsia or eclampsia of pregnancy. Data Animal Data Two embryofetal developmental reproductive toxicity studies were conducted in rats. In a non- ventilated rat study, pregnant animals were treated with cisatracurium besylate subcutaneously twice per day from Gestational Day 6 to 15 using subparalyzing doses (2 mg/kg and 4 mg/kg daily; equivalent to 6- and 12-times, respectively, the AUC exposure in humans following a bolus dose of 0.2 mg/kg IV). In the ventilated rat study, pregnant animals were treated with cisatracurium besylate intravenously once a day between Gestational Day 6 to 15 using paralyzing doses (0.5 mg/kg and 1 mg/kg; equivalent to 0.4- and 0.8-times, respectively, the exposure in humans following a bolus dose of 0.2 mg/kg IV based on mg/m2 comparison). Neither of these studies revealed maternal or fetal toxicity or teratogenic effects. 8.2 Lactation It is not known whether cisatracurium besylate is present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for cisatracurium and any potential adverse effects on the breastfed child from cisatracurium or from the underlying maternal condition. 8.4 Pediatric Use The safety and effectiveness of cisatracurium as an adjunct to general anesthesia to facilitate tracheal intubation, and to provide skeletal muscle relaxation during surgery in pediatric patients 1 month through 12 years of age were established from three studies in pediatric patients [see Dosing and Administration (2.2, 2.5 ) and Clinical Studies (14.2 )]. The three open-label studies are summarized below. The safety and effectiveness of cisatracurium have not been established in pediatric patients less than 1 month of age. Tracheal Intubation A study of 0.15 mg/kg cisatracurium evaluated 230 pediatric patients (ages 1 month to 12 years). Excellent or good intubating conditions were produced 120 seconds following 0.15 mg/kg of cisatracurium in 88 of 90 of patients induced with halothane and in 85 of 90 of patients induced with thiopentone and fentanyl. The study also evaluated 50 pediatric patients during opioid anesthesia, with maximum neuromuscular blockade achieved in an average of about 3 minutes and a clinically effective block for 36 minutes in patients ages 2 to 12 years, and maximum neuromuscular block in about 2 minutes and a clinically effective block for about 43 minutes in infants 1 to 23 months [see Clinical Studies (14.2 )]. In a study of 0.1 mg/kg cisatracurium administered in 16 pediatric patients (ages 2 to 12 years) during opioid/nitrous oxide/oxygen anesthesia, maximum neuromuscular blockade was achieved in an average of 2.8 minutes with a clinically effective block for 28 minutes [see Clinical Studies (14.2 )]. Skeletal Muscle Relaxation During Surgery In a study of cisatracurium administered during halothane/nitrous oxide/oxygen anesthesia, 18 pediatric patients (ages 2 to 12 years) were scheduled for surgical procedures that required neuromuscular block for 60 minutes or longer. The average duration of continuous infusion was 62.8 minutes (range: 17 to 145 minutes). The overall mean infusion rate for 9 patients whose infusion was 45 minutes or longer was 1.7 mcg/kg/minute (range: 1.19 mcg/kg/minute to 2.14 mcg/kg/minute). Serious Adverse Reactions in Infants Due to Benzyl Alcohol Preservative in 10 mL Multiple-Dose Vials Serious adverse reactions including fatal reactions and the “gasping syndrome” occurred in premature neonates and infants in the neonatal intensive care unit who received drugs containing benzyl alcohol as a preservative. In these cases, benzyl alcohol dosages of 99 to 234 mg/kg/day produced high levels of benzyl alcohol and its metabolites in the blood and urine (blood levels of benzyl alcohol were 0.61 to 1.378 mmol/L). Additional adverse reactions included gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. Preterm, low-birth weight infants may be more likely to develop these reactions because they may be less able to metabolize benzyl alcohol. When prescribing the 10 mL multiple-dose cisatracurium vials in infants consider the combined daily metabolic load of benzyl alcohol from all sources including cisatracurium (multiple-dose vials contain 9 mg of benzyl alcohol per mL) and other drugs containing benzyl alcohol. The minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known [see Warnings and Precautions (5.2 )]. This warning is not applicable to the 5 mL and 20 mL cisatracurium single-dose vials because these vials do not contain benzyl alcohol. The use of 10 mL cisatracurium multiple-dose vials is contraindicated in pediatric patients less than 1 month of age and low birth-weight infants because these patients are more likely to develop benzyl alcohol toxicity. 8.5 Geriatric Use Of the total number of subjects (135) in clinical studies of cisatracurium, 57, 63, and 15 subjects were 65-70 years old, 70-80 years old, and greater than 80 years old, respectively. The geriatric population included a subset of patients with significant cardiovascular disease [see Clinical Pharmacology (12.3 )]. Because the time to maximum neuromuscular blockade is approximately 1 minute slower in geriatric patients compared to younger patients, consider extending the interval between administering cisatracurium and attempting intubation by at least 1 minute to achieve adequate intubation conditions [see Dosage and Administration (2.2 ) and Clinical Pharmacology (12.2 )]. The time to maximum neuromuscular blockade is approximately 1 minute slower in geriatric patients, a difference that should be taken into account when selecting a neuromuscular blocking agent (e.g., the need to rapidly secure the airway) and when initiating laryngoscopy [see Clinical Pharmacology (12.3 )]. Minor differences in the pharmacokinetics of cisatracurium between elderly and young adult patients were not associated with clinically significant differences in the recovery profile of cisatracurium following a single 0.1 mg/kg dose. Besides the differences noted above, no overall differences in safety or effectiveness were observed between geriatric and younger subjects, and other reported clinical experience has not identified differences in responses between geriatric and younger subjects, but greater sensitivity of some older individuals to cisatracurium cannot be ruled out. 8.6 Patients with Renal Impairment The time to 90% neuromuscular blockade was 1 minute slower in patients with end-stage renal disease than in patients with normal renal function. Therefore, consider extending the interval between administering cisatracurium and attempting intubation by at least 1 minute to achieve adequate intubation conditions [see Dosage and Administration (2.2 ) and Clinical Pharmacology (12.2 )]. There was no clinically significant alteration in the recovery profile of cisatracurium in patients with end-stage renal disease following a 0.1 mg/kg dose of cisatracurium. The recovery profile of cisatracurium is unchanged in patients with renal impairment, which is consistent with predominantly organ-independent elimination [see Clinical Pharmacology (12.3 )]. 8.7 Patients with Hepatic Impairment The pharmacokinetic study analysis in patients with end-stage liver disease undergoing liver transplantation and healthy subjects undergoing elective surgery indicated slightly larger volumes of distribution in liver transplant patients with slightly higher plasma clearances of cisatracurium. The times to maximum neuromuscular blockade were approximately one minute faster in liver transplant patients than in healthy adult patients receiving 0.1 mg/kg cisatracurium. These minor differences in pharmacokinetics were not associated with clinically significant differences in the recovery profile of cisatracurium [see Clinical Pharmacology (12.3 )]. 8.8 Burn Patients Patients with burns have been shown to develop resistance to nondepolarizing neuromuscular blocking agents. The extent of altered response depends upon the size of the burn and the time elapsed since the burn injury. Cisatracurium has not been studied in patients with burns. However, based on its structural similarity to another neuromuscular blocking agent, consider the possibility of increased dosage requirements and shortened duration of action if cisatracurium is administered to burn patients. 8.9 Patients with Hemiparesis or Paraparesis Patients with hemiparesis or paraparesis may demonstrate resistance to nondepolarizing muscle relaxants in the affected limbs. To avoid inaccurate dosing, perform neuromuscular monitoring on a non-paretic limb. 8.10 Patients with Neuromuscular Disease Profound and prolonged neuromuscular blockade may occur in patients with neuromuscular diseases (e.g., myasthenia gravis and myasthenic syndrome) and carcinomatosis. Therefore, a lower maximum initial bolus is recommended in these patients [see Dosage and Administration (2.2 )].

Interactions

7 DRUG INTERACTIONS Succinylcholine: May decrease time to onset of maximum neuromuscular blockade (7.1) Inhalational anesthetics, antibiotics, local anesthetics, magnesium salts, procainamide, lithium, quinidine: May potentiate or prolong neuromuscular blockade action of cisatracurium. Use peripheral nerve stimulator and monitor clinical signs of neuromuscular blockade. (5.8, 7.1) Phenytoin and Carbamazepine: May shorten duration of neuromuscular blockade. Use peripheral nerve stimulator and monitor clinical signs of neuromuscular blockade. (5.9, 7.1) 7.1 Clinically Significant Drug Interactions Table 4 displays clinically significant drug interactions with cisatracurium. Table 4. Clinically Significant Drug Interactions with Cisatracurium Drug or Drug Class Clinical Implications* Succinylcholine The use of succinylcholine prior to cisatracurium administration may decrease the time to onset of maximum neuromuscular blockade but has no effect on the duration of neuromuscular blockade. Inhalational Anesthetics Administration of inhalational anesthetics with nitrous oxide/oxygen for greater than 30 minutes to achieve 1.25 Minimum Alveolar Concentration (MAC) may prolong the duration of action of initial and maintenance doses of cisatracurium. This may potentiate the neuromuscular blockade. Antibiotics† Local anesthetics Magnesium salts Procainamide Lithium Quinidine May prolong the neuromuscular blockade action of cisatracurium Phenytoin, Carbamazepine May increase resistance to the neuromuscular blockade action of cisatracurium resulting in shorter durations of neuromuscular blockade and infusion rate requirements may be higher. * The use of peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of cisatracurium, and to determine whether adjustments need to be made to the dose with subsequent administration. † Examples: aminoglycosides, tetracyclines, bacitracin, polymyxins, lincomycin, clindamycin, colistin, sodium colistimethate 7.2 Drugs Without Clinically Significant Drug Interactions With Cisatracurium In clinical studies, propofol had no effect on the duration of action or dosing requirements for cisatracurium. Cisatracurium is not compatible with propofol for Y-site administration.

More information

Category Value
Authorisation number ANDA204960
Agency product number 80YS8O1MBS
Orphan designation No
Product NDC 0703-2045,0703-2056,0703-2033
Date Last Revised 16-01-2019
Type HUMAN PRESCRIPTION DRUG
RXCUI 199212
Marketing authorisation holder Teva Parenteral Medicines, Inc.