Nimbex

Serious side effects have been reported with cisatracurium.

Common side effects of cisatracurium include a slower heart beat, low blood pressure, and flushing.

This is not a complete list of cisatracurium side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Since this medicine is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

Tell your doctor about all medicines you use, and those you start or stop using during your treatment with cisatracurium, especially an injected antibiotic such as:

• amikacin, gentamicin, kanamycin, neomycin, paromomycin, streptomycin, tobramycin, and others.

This list is not complete. Other drugs may interact with cisatracurium, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Nondepolarizing neuromuscular blocking agent; isomer of atracurium.1 3 5 6 7 11 14 15 19

Absorption

Bioavailability

Poorly absorbed from GI tract.23

Onset

Intermediate onset of action.1 5 Generally, time to maximum neuromuscular blockade decreases as dose increases; time to maximum blockade is up to 2 minutes longer with cisatracurium than with equipotent doses of atracurium.1 5

Good to excellent conditions for tracheal intubation occur within 1.5–2 or 1.5 minutes following IV dose of 0.15 or 0.2 mg/kg, respectively.1 5

Onset is faster in pediatric patients than in adults; also faster in infants than in older children.1 Onset may be delayed in geriatric patients compared with younger adults.1 16

In adults, doses of 0.15 or 0.2 mg/kg administered under balanced anesthesia produce maximum neuromuscular blockade in about 3.5 (range: 1.6–6.8) or 2.9 (range: 1.9–5.2) minutes, respectively.1 Maximum neuromuscular blockade after 0.1-mg/kg dose occurs about 1 minute later in geriatric patients than in younger adults.1

In children, doses of 0.1 or 0.15 mg/kg administered under balanced anesthesia produce maximum neuromuscular blockade in about 2.8 (range: 1.8–6.7) or 3 (range: 1.5–8) minutes, respectively.1 In infants, doses of 0.15 mg/kg administered under balanced anesthesia produce maximum neuromuscular blockade in about 2 minutes (range: 1.3–4.3).1

Duration

Intermediate duration of action.1 5 6 20 Duration of maximum neuromuscular blockade increases as the dose increases; when the cisatracurium dose is doubled, the clinically effective duration of blockade increases by approximately 25 minutes.1 Clinically effective duration of action and rate of spontaneous recovery with equipotent doses of cisatracurium and atracurium are similar.1

Duration is longer in adults than in pediatric patients; also longer in infants than in older children.1 No substantial difference in recovery profiles between geriatric and younger adults.1 11 16 Recovery following reversal is faster in children than in adults.1

In adults, clinically effective duration of neuromuscular blockade (i.e., time to 25% recovery) after dose of 0.15 or 0.2 mg/kg is 55 (range: 44–74) or 65 (range: 43–103) minutes, respectively.1

In children 2–12 years of age, clinically effective duration of neuromuscular blockade after dose of 0.1 or 0.15 mg/kg is approximately 28 (range: 21–38) or 36 (range: 29–46) minutes, respectively.1 In infants, clinically effective duration of neuromuscular blockade after dose of 0.15 mg/kg is approximately 43 minutes (range: 34–58 minutes).1

Duration of neuromuscular blockade induced by 0.03-mg/kg maintenance dose is approximately 20 minutes.1

In studies in patients receiving long-term (i.e., up to 6 days) infusion during mechanical ventilation, recovery of neuromuscular function (train-of-four ratio ≥70%) occurred in approximately 50 (range: 20–175) or 55 (range: 20–270) minutes following infusion discontinuance.1

Special Populations

In patients with end-stage liver disease, onset may be slightly faster; however, hepatic dysfunction does not substantially alter rate of recovery from neuromuscular blockade.1 3 6 16

In patients with renal failure, onset may be slightly delayed; however, renal dysfunction does not substantially alter rate of recovery from neuromuscular blockade.1 3 6 16

Gender and obesity not associated with substantial changes in predicted onset or rate of recovery.1 47

Distribution

Extent

Neuromuscular blocking agents generally distribute into extracellular fluid and rapidly reach site of action at motor end-plate of myoneural junction.2

Neuromuscular blocking agents may cross placenta.2

Volume of distribution of cisatracurium may be limited by its large molecular size and increased polarity.47 Higher steady-state volume of distribution when nontraditional two-compartment model of elimination is used compared with a one-compartment model.5 47

Plasma Protein Binding

Plasma protein binding cannot be determined because of rapid metabolism of cisatracurium.47 (See Elimination under Pharmacokinetics.)

Special Populations

Based on a one-compartment model, volume of distribution at steady-state may be increased in the elderly, ICU patients, and in patients with end-stage hepatic failure.5 6

In burn patients, possible increased protein binding (possibly to α1-acid glycoprotein) of neuromuscular blocking agents with subsequent decreases in the free fraction of circulating drug.33 34 35 37

Elimination

Metabolism

Rapidly metabolized via Hofmann elimination (independent of liver) to form a monoquaternary acrylate metabolite (which undergoes nonspecific plasma esterase hydrolysis and subsequent Hofmann elimination) and laudanosine (which is demethylated and glucuronidated).1 3 6 11 14 15 19 47 Both metabolites lack neuromuscular blocking activity; laudanosine may have CNS excitatory activity when present in large amounts.1 6 47

Rate of Hofmann elimination is dependent on temperature and pH.1 6 15

Elimination Route

Eliminated principally by Hofmann elimination (77–80%) and to lesser extent by renal and hepatic elimination (20%).1 6 Metabolites are eliminated principally by renal and hepatic elimination.1 Following administration of radiolabeled dose of cisatracurium to healthy individuals, 95% of administered dose is recovered in urine and 4% in feces; <10% of the dose is recovered as unchanged drug.1 6

Half-life

22–30 minutes.1 6 47

Special Populations

Patients with renal or hepatic dysfunction may exhibit longer half-lives; concentrations of metabolites after prolonged administration may be higher.1

Cisatracurium half-life may be slightly prolonged in geriatric patients.1 6

Pediatric patients may exhibit faster clearance of cisatracurium than adults.1

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as a shot into a vein.
• It is given as an infusion into a vein over a period of time.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

Nimbex (cisatracurium besylate) is a nondepolarizing skeletal muscle relaxant for intravenous administration. Compared to other neuromuscular blocking agents, it is intermediate in its onset and duration of action. Cisatracurium besylate is one of 10 isomers of atracurium besylate and constitutes approximately 15% of that mixture. Cisatracurium besylate is [1R-[1α,2α(1'R*,2'R*)]]-2,2'-[1,5-pentanediylbis[oxy(3-oxo-3,1-propanediyl)]]bis[1-[(3,4-dimethoxyphenyl)methyl]-1,2,3,4-tetrahydro-6,7-dimethoxy-2-methylisoquinolinium] dibenzenesulfonate. The molecular formula of the cisatracurium parent bis-cation is C53H72N2O12 and the molecular weight is 929.2. The molecular formula of cisatracurium as the besylate salt is C65H82N2O18S2 and the molecular weight is 1243.50. The structural formula of cisatracurium besylate is:

The log of the partition coefficient of cisatracurium besylate is -2.12 in a 1-octanol/distilled water system at 25°C.

Nimbex Injection is a sterile, non-pyrogenic aqueous solution provided in 5 mL, 10 mL, and 20 mL vials. The pH is adjusted to 3.25 to 3.65 with benzenesulfonic acid. The 5 mL and 10 mL vials each contain cisatracurium besylate, equivalent to 2 mg/mL cisatracurium. The 20 mL vial, intended for ICU use only, contains cisatracurium besylate, equivalent to 10 mg/mL cisatracurium. The 10 mL vial, intended for multiple-dose use, contains 0.9% benzyl alcohol as a preservative. The 5 mL and 20 mL vials are single-use vials and do not contain benzyl alcohol.

Cisatracurium besylate slowly loses potency with time at a rate of approximately 5% per year under refrigeration (5°C). Nimbex should be refrigerated at 2° to 8°C (36° to 46°F) in the carton to preserve potency. The rate of loss in potency increases to approximately 5% per month at 25°C (77°F). Upon removal from refrigeration to room temperature storage conditions (25°C/77°F), use Nimbex within 21 days, even if rerefrigerated.

Nimbex is contraindicated in patients with known hypersensitivity to the product and its components. The 10 mL multiple-dose vials of Nimbex is contraindicated for use in premature infants because the formulation contains benzyl alcohol. (See WARNINGS and PRECAUTIONS – Pediatric Use).

Anaphylaxis

Severe anaphylactic reactions to neuromuscular blocking agents, including Nimbex, have been reported. These reactions have in some cases been life-threatening and fatal. Due to the potential severity of these reactions, the necessary precautions, such as the immediate availability of appropriate emergency treatment, should be taken. Precautions should also be taken in those individuals who have had previous anaphylactic reactions to other neuromuscular blocking agents since cross-reactivity between neuromuscular blocking agents, both depolarizing and non-depolarizing, has been reported in this class of drugs.

Administration

Nimbex SHOULD BE ADMINISTERED IN CAREFULLY ADJUSTED DOSAGE BY OR UNDER THE SUPERVISION OF EXPERIENCED CLINICIANS WHO ARE FAMILIAR WITH THE DRUG'S ACTIONS AND THE POSSIBLE COMPLICATIONS OF ITS USE. THE DRUG SHOULD NOT BE ADMINISTERED UNLESS PERSONNEL AND FACILITIES FOR RESUSCITATION AND LIFE SUPPORT (TRACHEAL INTUBATION, ARTIFICIAL VENTILATION, OXYGEN THERAPY), AND AN ANTAGONIST OF Nimbex ARE IMMEDIATELY AVAILABLE. IT IS RECOMMENDED THAT A PERIPHERAL NERVE STIMULATOR BE USED TO MEASURE NEUROMUSCULAR FUNCTION DURING THE ADMINISTRATION OF Nimbex IN ORDER TO MONITOR DRUG EFFECT, DETERMINE THE NEED FOR ADDITIONAL DOSES, AND CONFIRM RECOVERY FROM NEUROMUSCULAR BLOCK.

Nimbex HAS NO KNOWN EFFECT ON CONSCIOUSNESS, PAIN THRESHOLD, OR CEREBRATION. TO AVOID DISTRESS TO THE PATIENT, NEUROMUSCULAR BLOCK SHOULD NOT BE INDUCED BEFORE UNCONSCIOUSNESS.

Nimbex Injection is acidic (pH 3.25 to 3.65) and may not be compatible with alkaline solutions having a pH greater than 8.5 (e.g., barbiturate solutions).

The 10 mL multiple-dose vials of Nimbex contain benzyl alcohol, which is potentially toxic when administered locally to neural tissue. Exposure to excessive amounts of benzyl alcohol has been associated with toxicity (hypotension, metabolic acidosis), particularly in neonates, and an increased incidence of kernicterus, particularly in small preterm infants. There have been rare reports of deaths, primarily in preterm infants, associated with exposure to excessive amounts of benzyl alcohol. The amount of benzyl alcohol from medications is usually considered negligible compared to that received in flush solution containing benzyl alcohol. Administration of high dosages of medications containing this preservative must take into account the total amount of benzyl alcohol administered. The amount of benzyl alcohol at which toxicity may occur is not known. If the patient requires more than the recommended dosages or other medications containing this preservative, the practitioner must consider the daily metabolic load of benzyl alcohol from these combined sources. Single-use vials (5 mL and 20 mL) of Nimbex do not contain benzyl alcohol (see WARNINGS and PRECAUTIONS - Pediatric Use).

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:

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.

Nimbex® is a registered trademark of GlaxoSmithKline, licensed for use by AbbVie Inc.

©2016 AbbVie Inc.

Mfd. For: AbbVie Inc.

North Chicago, IL 60064 USA

EN-4453 December, 2016

NDC 0074–4378–05

Nimbex®

Cisatracurium Besylate Injection

10 mg/5 mL (2 mg/mL)

Single-dose vial

Rx only abbvie

NDC 0074–4380–10

Nimbex® Cisatracurium Besylate Injection

20 mg/10 mL (2 mg/mL)

Multiple-dose vial

0.9% benzyl alcohol (added as a preservative) Rx only

abbvie

NDC 0074–4382–20

Nimbex® Cisatracurium Besylate Injection

200 mg/20 mL (10 mg/mL)

Single-dose Vial

For ICU use only.

Rx only abbvie