Nimbex ® -cisatracurium

Cisatracurium - Nimbex ®

Usual Diluents

Standard Dilutions   [Amount of drug] [Infusion volume] [Infusion rate]

(Using 2 mg/ml vials)
Titrate
[40 mg/ 80 ml] (Total vol=100 ml)
[100 mg/ 200 ml] (Total vol=250 ml)
[200 mg/ 400 ml] (Total vol=500 ml)
(Concentration= 0.4 mg/ml)

(May also be given undiluted)

Stability / Miscellaneous

EXP: 1 DAY (RT/REF). [Supplied: 10mg/ 5ml and 20 mg/10 ml vials (In refrigerator)]. Usual dilution: 0.1 to 0.4 mg/ml.

Other: Stability: Refrigerate intact vials at 2°C to 8°C/36°F to 46°F; use vials within 21 days upon removal from the refrigerator to room temperature (25°C to 77°F). Dilutions of 0.1-0.2 mg/mL in 0.9% sodium chloride or dextrose 5% in water are stable for up to 24 hours at room temperature.

Dosing:
Intermittent: initial dose: 0.15 to 0.2 mg/kg IV bolus followed by 0.03 mg/kg IV q40-60min.
Continuous infusion: 0.1 to 0.2 mg/kg IV bolus followed by 1 to 3 mcg/kg/min. The average infusion rate for long term use in the ICU is approximately 3 mcg/kg/min (range: 0.5 to 10.2 mcg/kg/min). In some cases, re-administration of the bolus dose may be req'd while titrating. Dosage reductions are not required in renal or hepatic failure.

Drug of choice in the following cases (1) hemodynamically significant increases in HR (e.g. >20%) while paralyzed with pancuronium or MAP>110. (2) Concurrent corticosteroid administration (>72hrs) (3) Significant renal dysfunction (CRCL < 30 ml/min) (4) History of asthma or bronchospasm.

DOSAGE AND ADMINISTRATION
NIMBEX SHOULD ONLY BE ADMINISTERED INTRAVENOUSLY.

The dosage information provided below is intended as a guide only. Doses of NIMBEX should be individualized (see package insert for CLINICAL PHARMACOLOGY - Individualization of Dosages). The use of a peripheral nerve stimulator will permit the most advantageous use of NIMBEX, minimize the possibility of overdosage or underdosage, and assist in the evaluation of recovery.

Adults
Initial Doses
One of two intubating doses of NIMBEX 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 × ED95) and 0.20 (4 × ED95) mg/kg NIMBEX, 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 NIMBEX 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. The clinically effective durations of action for 0.15 and 0.20 mg/kg NIMBEX 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 × ED95 NIMBEX 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.

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 NIMBEX and the intubation attempt for these patients may be required to achieve adequate intubation conditions.

A dose of 0.03 mg/kg NIMBEX 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 NIMBEX and 50 to 60 minutes following an initial dose of 0.20 mg/kg NIMBEX, 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 NIMBEX and therefore, no adjustment to the initial dose should be necessary when NIMBEX 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 NIMBEX may be necessary. No adjustments to the initial dose of NIMBEX are required when used in patients receiving propofol anesthesia.

Children
Initial Doses
The recommended dose of NIMBEX for children 2 to 12 years of age is 0.10-0.15 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 NIMBEX 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 NIMBEX 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 NIMBEX 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 NIMBEX 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 NIMBEX, a diluted solution of NIMBEX 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 NIMBEX 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 NIMBEX 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 NIMBEX 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 NIMBEX 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 NIMBEX and atracurium, a similar effect on the infusion rate of NIMBEX may be expected.

Spontaneous recovery from neuromuscular block following discontinuation of infusion of NIMBEX 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 NIMBEX 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 NIMBEX in the infusion solution, the desired dose of NIMBEX, 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 11 provide guidelines for delivery, in mL/hr (equivalent to microdrops/minute when 60 microdrops = 1 mL), of NIMBEX 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 NIMBEX for Maintenance of Neuromuscular Block During Opioid/Nitrous Oxide/Oxygen Anesthesia for a Concentration of 0.1 mg/mL

NIMBEX Injection Compatibility and Admixtures
Y-site Administration

NIMBEX 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).

Studies have shown that NIMBEX Injection 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

NIMBEX Injection 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
NIMBEX Injection 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.

NIMBEX Injection 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. NIMBEX Injection is a colorless to slightly yellow or greenish-yellow solution.

HOW SUPPLIED
NIMBEX Injection, 2 mg cisatracurium per mL, is supplied in the following:

NOTE:10 mL Multiple-dose Vials contain 0.9% w/v benzyl alcohol as a preservative (see WARNINGS concerning newborn infants).

NIMBEX Injection, 10 mg cisatracurium per mL is supplied in the following:
4382 Single-dose Vial 20 mL

Intended only for use in the ICU.

Storage
NIMBEX Injection 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 NIMBEX Injection within 21 days even if rerefrigerated.

U.S. Patent No. 5,453,510
Registered trademark of GlaxoSmithKline, licensed for use by Abbott Laboratories.

Mfd By: Hospira, Inc.
Lake Forest, IL 60045 USA
For: Abbott Laboratories
North Chicago, IL 60064 USA