PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

SERIALIZATION IMAGE


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RECENT MAJOR CHANGES SECTION

RECENT MAJOR CHANGES

Dosage and Administration

Important Dosing and Administration Information (2.1) 11/2018

Warnings and Precautions

Risk of Death due to Medication Errors (5.3) 11/2018

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DESCRIPTION SECTION

11 DESCRIPTION

Rocuronium Bromide Injection is a nondepolarizing neuromuscular blocking agent with a rapid to intermediate onset depending on dose and intermediate duration. Rocuronium bromide is chemically designated as 1-[17β-(acetyloxy)-3α-hydroxy-2β-(4-morpholinyl)-5α-androstan-16β-yl]-1-(2-propenyl)pyrrolidinium bromide.

The structural formula is:


The chemical formula is C32H53BrN2O4 with a molecular weight of 609.70. The partition coefficient of rocuronium bromide in n-octanol/water is 0.5 at 20°C.

Rocuronium Bromide is supplied as a sterile, nonpyrogenic, isotonic solution that is clear, colorless to yellow/orange, for intravenous injection only. Each mL contains 10 mg rocuronium bromide and 2 mg sodium acetate. The aqueous solution is adjusted to isotonicity with sodium chloride and to a pH of 4 with acetic acid and/or sodium hydroxide.

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INDICATIONS & USAGE SECTION

Highlight: Rocuronium Bromide is a nondepolarizing neuromuscular blocking agent indicated as an adjunct to general anesthesia to facilitate both rapid sequence and routine tracheal intubation, and to provide skeletal muscle relaxation during surgery or mechanical ventilation. (1)

1 INDICATIONS AND USAGE

Rocuronium Bromide Injection is indicated for inpatients and outpatients as an adjunct to general anesthesia to facilitate both rapid sequence and routine tracheal intubation, and to provide skeletal muscle relaxation during surgery or mechanical ventilation.

DOSAGE FORMS & STRENGTHS SECTION

Highlight: * 5 mL multiple dose vials containing 50 mg Rocuronium Bromide Injection (10 mg/mL). (3)

• 10 mL multiple dose vials containing 100 mg Rocuronium Bromide Injection (10 mg/mL). (3)

3 DOSAGE FORMS AND STRENGTHS

Rocuronium Bromide Injection is available as

• 5 mL multiple dose vials containing 50 mg Rocuronium Bromide Injection (10 mg/mL)
• 10 mL multiple dose vials containing 100 mg Rocuronium Bromide Injection (10 mg/mL)

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CONTRAINDICATIONS SECTION

Highlight: * Hypersensitivity (e.g., anaphylaxis) to Rocuronium Bromide or other neuromuscular blocking agents. (4)

4 CONTRAINDICATIONS

Rocuronium Bromide is contraindicated in patients known to have hypersensitivity (e.g., anaphylaxis) to rocuronium bromide or other neuromuscular blocking agents [see Warnings and Precautions (5.2)].

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ADVERSE REACTIONS SECTION

Highlight: Most common adverse reactions (2%) are transient hypotension and hypertension. (6)

To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-877-845-0689 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6 ADVERSE REACTIONS

In clinical trials, the most common adverse reactions (2%) are transient hypotension and hypertension.

The following adverse reactions are described, or described in greater detail, in other sections:

• Anaphylaxis [see Warnings and Precautions (5.2)]
• Residual paralysis [see Warnings and Precautions (5.5)]
• Myopathy [see Warnings and Precautions (5.6)]
• Increased pulmonary vascular resistance [see Warnings and Precautions (5.12)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Clinical studies in the US (n=1137) and Europe (n=1394) totaled 2531 patients. The patients exposed in the US clinical studies provide the basis for calculation of adverse reaction rates. The following adverse reactions were reported in patients administered Rocuronium Bromide (all events judged by investigators during the clinical trials to have a possible causal relationship):

Adverse reactions in greater than 1% of patients: None

Adverse reactions in less than 1% of patients (probably related or relationship unknown):

Cardiovascular: arrhythmia, abnormal electrocardiogram, tachycardia

Digestive: nausea, vomiting

Respiratory: asthma (bronchospasm, wheezing, or rhonchi), hiccup

Skin and Appendages: rash, injection site edema, pruritus

In the European studies, the most commonly reported reactions were transient hypotension (2%) and hypertension (2%); these are in greater frequency than the US studies (0.1% and 0.1%). Changes in heart rate and blood pressure were defined differently from in the US studies in which changes in cardiovascular parameters were not considered as adverse events unless judged by the investigator as unexpected, clinically significant, or thought to be histamine related.

In a clinical study in patients with clinically significant cardiovascular disease undergoing coronary artery bypass graft, hypertension and tachycardia were reported in some patients, but these occurrences were less frequent in patients receiving beta or calcium channel-blocking drugs. In some patients, Rocuronium Bromide was associated with transient increases (30% or greater) in pulmonary vascular resistance. In another clinical study of patients undergoing abdominal aortic surgery, transient increases (30% or greater) in pulmonary vascular resistance were observed in about 24% of patients receiving Rocuronium Bromide 0.6 or 0.9 mg/kg.

In pediatric patient studies worldwide (n=704), tachycardia occurred at an incidence of 5.3% (n=37), and it was judged by the investigator as related in 10 cases (1.4%).

6.2 Postmarketing Experience

In clinical practice, there have been reports of severe allergic reactions (anaphylactic and anaphylactoid reactions and shock) with Rocuronium Bromide, including some that have been life-threatening and fatal [see Warnings and Precautions (5.2)].

Because these reactions were reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency.

To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-877-845-0689 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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OVERDOSAGE SECTION

10 OVERDOSAGE

Overdosage with neuromuscular blocking agents may result in neuromuscular block beyond the time needed for surgery and anesthesia. The primary treatment is maintenance of a patent airway, controlled ventilation, and adequate sedation until recovery of normal neuromuscular function is assured. Once evidence of recovery from neuromuscular block is observed, further recovery may be facilitated by administration of an anticholinesterase agent in conjunction with an appropriate anticholinergic agent.

Reversal of Neuromuscular Blockade:** Anticholinesterase agents should not be administered prior to the demonstration of some spontaneous recovery from neuromuscular blockade. The use of a nerve stimulator to document recovery is recommended.**

Patients should be evaluated for adequate clinical evidence of neuromuscular recovery, e.g., 5-second head lift, adequate phonation, ventilation, and upper airway patency. Ventilation must be supported while patients exhibit any signs of muscle weakness.

Recovery may be delayed in the presence of debilitation, carcinomatosis, and concomitant use of certain drugs which enhance neuromuscular blockade or separately cause respiratory depression. Under such circumstances the management is the same as that of prolonged neuromuscular blockade.

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INFORMATION FOR PATIENTS SECTION

17 PATIENT COUNSELING INFORMATION

Obtain information about your patient's medical history, current medications, any history of hypersensitivity to Rocuronium Bromide or other neuromuscular blocking agents. If applicable, inform your patients that certain medical conditions and medications might influence how Rocuronium Bromide works.

In addition, inform your patient that severe anaphylactic reactions to neuromuscular blocking agents, including Rocuronium Bromide, have been reported. Since allergic cross-reactivity has been reported in this class, request information from your patients about previous anaphylactic reactions to other neuromuscular blocking agents.

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Manufactured by:
****HIKMA FARMACÊUTICA (PORTUGAL), S.A.
Estrada do Rio da Mó, 8, 8A e 8B - Fervença - 2705-906 Terrugem SNT, PORTUGAL

Distributed by:
Hikma Pharmaceuticals USA Inc.
Berkeley Heights, NJ 07922

Revised May 2023

PIN452-WES/6

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