Cisatracurium

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 Besylate Injection and attempting intubation by at least 1 minute to achieve adequate intubation conditions [see Dosage and Administration and Clinical Pharmacology] .

There was no clinically significant alteration in the recovery profile of Cisatracurium Besylate Injection in patients with end-stage renal disease following a 0.1 mg/kg dose of Cisatracurium Besylate Injection. The recovery profile of Cisatracurium Besylate Injection is unchanged in patients with renal impairment, which is consistent with predominantly organ-independent elimination [see Clinical Pharmacology] .

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 Besylate Injection. These minor differences in pharmacokinetics were not associated with clinically significant differences in the recovery profile of Cisatracurium Besylate Injection [see Clinical Pharmacology] .

Important Dosage and Administration Instructions 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] .

Important Administration Instructions 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] .

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.

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] .

Subsequently reduce the rate to 1 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

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 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. [See table below.] [See table below.]

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.

Discard unused portion of the single-dose vials. 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.

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) 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.