INDICATIONS AND USAGE Atracurium besylate injection is indicated, as an adjunct to general anesthesia, to facilitate endotracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation.

WARNINGS ATRACURIUM SHOULD BE USED ONLY BY THOSE SKILLED IN AIRWAY MANAGEMENT AND RESPIRATORY SUPPORT.

EQUIPMENT AND PERSONNEL MUST BE IMMEDIATELY AVAILABLE FOR ENDOTRACHEAL INTUBATION AND SUPPORT OF VENTILATION, INCLUDING ADMINISTRATION OF POSITIVE PRESSURE OXYGEN.

ADEQUACY OF RESPIRATION MUST BE ASSURED THROUGH ASSISTED OR CONTROLLED VENTILATION.

ANTICHOLINESTERASE REVERSAL AGENTS SHOULD BE IMMEDIATELY AVAILABLE.

DO NOT GIVE ATRACURIUM BESYLATE BY INTRAMUSCULAR ADMINISTRATION.

Atracurium has no known effect on consciousness, pain threshold, or cerebration.

It should be used only with adequate anesthesia.

Atracurium besylate injection, which has an acid pH, should not be mixed with alkaline solutions (e.g., barbiturate solutions) in the same syringe or administered simultaneously during intravenous infusion through the same needle.

Depending on the resultant pH of such mixtures, atracurium may be inactivated and a free acid may be precipitated.

Atracurium besylate injection 10 mL multiple dose vials contain benzyl alcohol.

In neonates, benzyl alcohol has been associated with an increased incidence of neurological and other complications which are sometimes fatal.

Atracurium besylate 5 mL single use vials do not contain benzyl alcohol (see PRECAUTIONS, Pediatric Use ).

Anaphylaxis Severe anaphylactic reactions to neuromuscular blocking agents, including atracurium besylate, 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.

Risk of Death Due to Medication Errors Administration of atracurium besylate injection results in paralysis, which may lead to respiratory arrest and death; this progression may be more likely to occur in a patient for whom it is not intended.

Confirm proper selection of intended product and avoid confusion with other injectable solutions that are present in critical care and other clinical settings.

If another healthcare provider is administering the product, ensure that the intended dose is clearly labeled and communicated.

ADVERSE REACTIONS Observed in Controlled Clinical Studies Atracurium was well tolerated and produced few adverse reactions during extensive clinical trials.

Most adverse reactions were suggestive of histamine release.

In studies including 875 patients, atracurium was discontinued in only one patient (who required treatment for bronchial secretions) and six other patients required treatment for adverse reactions attributable to atracurium (wheezing in one, hypotension in five).

Of the five patients who required treatment for hypotension, three had a history of significant cardiovascular disease.

The overall incidence rate for clinically important adverse reactions, therefore, was 7/875 or 0.8%.

Table 1 includes all adverse reactions reported attributable to atracurium during clinical trials with 875 patients.

Table 1: Percent of Patients Reporting Adverse Reactions * Includes the recommended initial dosage range for most patients.

Adverse Reaction Initial Atracurium Dose (mg/kg) 0.00-0.30 (n = 485) 0.31-0.50* (n = 366) ≥0.60 (n = 24) Total (n = 875) Skin Flush 1.0% 8.7% 29.2% 5.0% Erythema 0.6% 0.5% 0% 0.6% Itching 0.4% 0% 0% 0.2% Wheezing/Bronchial Secretions 0.2% 0.3% 0% 0.2% Hives 0.2% 0% 0% 0.1% Most adverse reactions were of little clinical significance unless they were associated with significant hemodynamic changes.

Table 2 summarizes the incidences of substantial vital sign changes noted during atracurium clinical trials with 530 patients, without cardiovascular disease, in whom these parameters were assessed.

Table 2: Percent of Patients Showing >30% Vital Sign Changes Following Administration of Atracurium * Includes the recommended initial dosage range for most patients.

Vital Sign Change Initial Atracurium Dose (mg/kg) 0.00-0.30 (n = 365) 0.31-0.50* (n = 144) ≥0.60 (n = 21) Total (n = 530) Mean Arterial Pressure Increase 1.9% 2.8% 0% 2.1% Decrease 1.1% 2.1% 14.3% 1.9% Heart Rate Increase 1.6% 2.8% 4.8% 2.1% Decrease 0.8% 0% 0% 0.6% Observed in Clinical Practice Based on initial clinical practice experience in approximately 3 million patients who received atracurium in the U.S.

and in the United Kingdom, spontaneously reported adverse reactions were uncommon (approximately 0.01% to 0.02%).

The following adverse reactions are among the most frequently reported, but there are insufficient data to support an estimate of their incidence: General: Allergic reactions (anaphylactic or anaphylactoid responses) which, in rare instances, were severe (e.g., cardiac arrest) Musculoskeletal: Inadequate block, prolonged block Cardiovascular: Hypotension, vasodilatation (flushing), tachycardia, bradycardia Respiratory: Dyspnea, bronchospasm, laryngospasm Integumentary: Rash, urticaria, reaction at injection site There have been rare spontaneous reports of seizures in ICU patients following long-term infusion of atracurium to support mechanical ventilation.

There are insufficient data to define the contribution, if any, of atracurium and/or its metabolite laudanosine (see PRECAUTIONS, Long-Term Use in Intensive Care Unit (ICU) ).

There have been post-marketing reports of severe allergic reactions (anaphylactic and anaphylactoid reactions) associated with use of neuromuscular blocking agents, including atracurium besylate.

These reactions, 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 ).

To report SUSPECTED ADVERSE REACTIONS, contact Meitheal Pharmaceuticals Inc.

at 1-844-824-8426 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .