RIMEXA

Rocuronium (rapid onset-curonium) is a desacetoxy analogue of vecuronium with a more rapid onset of action.

It is an aminosteroid non-depolarizing neuromuscular blocker or muscle relaxant used in modern anaesthesia, to facilitate endotracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation.

Introduced in 1994, rocuronium has rapid onset, and intermediate duration of action.

It is commonly marketed under the trade names Zemuron and Esmeron.

The drug is associated with the risk of developing allergic reactions in some high-risk patients, such as those with asthma.

However, there was a similar incidence of allergic reactions associated with other non-depolarizing neuromuscular blocking agents.

Sugammadex is a γ-cyclodextrin derivative that has been introduced as a novel agent to reverse the action of rocuronium.

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.

Neuromuscular blocking agents are drugs that cause skeletal muscle relaxation primarily by causing a decreased response to the neurotransmitter acetylcholine (ACh) at the myoneural (neuromuscular) junction of skeletal muscle.

At that site, ACh normally produces electrical depolarization of the postjunctional membrane of motor end-plate, which leads to conduction of muscle action potential and subsequently induces skeletal muscle contraction.

Neuromuscular agents are classified as depolarizing or nondepolarizing.

Rocuronium is a nondepolarizing neuromuscular blocking agent with a rapid to intermediate onset depending on dose and intermediate duration.

Rocuronium, like vecuronium is longer acting in infants than in children.

However, unlike vecuronium, rocuronium retains the characteristics of an intermediate-acting NMBD in infants.

Neuronal acetylcholine receptor subunit alpha-2 Antagonist Muscarinic acetylcholine receptor M2 Antagonist.

Poorly absorbed from the

GI tract.

Rocuronium is metabolized to a less active metabolite, 17-desacetyl-rocuronium, and is eliminated primarily by the liver.

Hover over products below to view reaction partners Rocuronium 17-desacetyl-rocuronium.

Studies of distribution, metabolism, and excretion in cats and dogs indicate that rocuronium is eliminated primarily by the liver.

The rapid distribution half-life is 1-2 minutes and the slower distribution half-life is 14-18 minutes.

Renal impairment has no net effect on half-life, however, half-life is almost doubled in patients with impaired liver function.

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No cases of significant accidental or intentional overdose have been reported.

Overdosage with neuromuscular blocking agents may result in neuromuscular block beyond the time needed for surgery and anesthesia.

Rocuronium bromide is contraindicated in patients known to have hypersensitivity (e.g., anaphylaxis) to rocuronium bromide or other neuromuscular blocking agents.

Hypersensitivity (e.g., anaphylaxis) to rocuronium bromide or other neuromuscular blocking agents.

To be administered only by experienced clinicians or adequately trained individuals supervised by an experienced clinician familiar with the use, actions, characteristics, and complications of neuromuscular blocking agents.

Individualize the dose for each patient.

Peripheral nerve stimulator recommended for determination of drug response and need for additional doses, and to evaluate recovery.

Store rocuronium bromide injection with cap and ferrule intact and in a manner that minimizes the possibility of selecting the wrong product.

Tracheal intubation

Recommended initial dose is 0.6 mg/kg. Rapid sequence intubation: 0.6 to 1.2 mg/kg. Maintenance doses: Guided by response to prior dose, not administered until recovery is evident.

Continuous infusion

Initial rate of to 12 mcg/kg/min. Start only after early evidence of spontaneous recovery from an intubating dose. 2.1 Important Dosing and Administration Information Rocuronium bromide injection is for intravenous use only.

This drug should only be administered by experienced clinicians or trained individuals supervised by an experienced clinician familiar with the use, actions, characteristics and complications of neuromuscular blocking agents.

Doses of rocuronium bromide injection should be individualized and a peripheral nerve stimulator should be used to monitor drug effect, need for additional doses, adequacy of spontaneous recovery or antagonism, and to decrease the complications of overdosage if additional doses are administered.

The dosage information which follows is derived from studies based upon units of drug per unit of body weight.

It is intended to serve as an initial guide to clinicians familiar with other neuromuscular blocking agents to acquire experience with rocuronium bromide.

In patients in whom potentiation of, or resistance to, neuromuscular block is anticipated, a dose adjustment should be considered.

Accidental administration of neuromuscular blocking agents may be fatal.

Store rocuronium bromide with the cap and ferrule intact and in a manner that minimizes the possibility of selecting the wrong product. 2.2 Dose for Tracheal Intubation The recommended initial dose of rocuronium bromide, regardless of anesthetic technique, is 0.6 mg/kg. Neuromuscular block sufficient for intubation (80% block or greater) is attained in a median (range) time of 1 (0.4 to 6) minute(s) and most patients have intubation completed within 2 minutes.

Maximum blockade is achieved in most patients in less than 3 minutes.

This dose may be expected to provide 31 (15 to 85) minutes of clinical relaxation under opioid/nitrous oxide/oxygen anesthesia.

Under halothane, isoflurane, and enflurane anesthesia, some extension of the period of clinical relaxation should be expected.

A lower dose of rocuronium bromide (0.45 mg/kg) may be used.

Neuromuscular block sufficient for intubation (80% block or greater) is attained in a median (range) time of 1.3 (0.8 to 6.2) minute(s) and most patients have intubation completed within 2 minutes.

Maximum blockade is achieved in most patients in less than 4 minutes.

This dose may be expected to provide 22 (12 to 31) minutes of clinical relaxation under opioid/nitrous oxide/oxygen anesthesia.

Patients receiving this low dose of 0.45 mg/kg who achieve less than 90% block (about 16% of these patients) may have a more rapid time to 25% recovery, 12 to 15 minutes.

A large bolus dose of 0.9 or 1.2 mg/kg can be administered under opioid/nitrous oxide/oxygen anesthesia without adverse effects to the cardiovascular system. 2.3 Rapid Sequence Intubation In appropriately premedicated and adequately anesthetized patients, rocuronium bromide 0.6 to 1.2 mg/kg will provide excellent or good intubating conditions in most patients in less than 2 minutes. 2.4 Maintenance Dosing Maintenance doses of 0.1, 0.15, and 0.2 mg/kg rocuronium bromide, administered at 25% recovery of control T 1 (defined as 3 twitches of train-of-four), provide a median (range) of 12 (2 to 31), 17 (6 to 50) and 24 (7 to 69) minutes of clinical duration under opioid/nitrous oxide/oxygen anesthesia.

In all cases, dosing should be guided based on the clinical duration following initial dose or prior maintenance dose and not administered until recovery of neuromuscular function is evident.

A clinically insignificant cumulation of effect with repetitive maintenance dosing has been observed. 2.5 Use by Continuous Infusion Infusion at an initial rate of to 12 mcg/kg/min of rocuronium bromide should be initiated only after early evidence of spontaneous recovery from an intubating dose.

Due to rapid redistribution and the associated rapid spontaneous recovery, initiation of the infusion after substantial return of neuromuscular function (more than 10% of control T 1 ), may necessitate additional bolus doses to maintain adequate block for surgery.

Upon reaching the desired level of neuromuscular block, the infusion of rocuronium bromide must be individualized for each patient.

The rate of administration should be adjusted according to the patient's twitch response as monitored with the use of a peripheral nerve stimulator.

In clinical trials, infusion rates have ranged from to 16 mcg/kg/min. Inhalation anesthetics, particularly enflurane and isoflurane, may enhance the neuromuscular blocking action of nondepolarizing muscle relaxants.

In the presence of steady-state concentrations of enflurane or isoflurane, it may be necessary to reduce the rate of infusion by 30% to 50%, at to 60 minutes after the intubating dose.

Spontaneous recovery and reversal of neuromuscular blockade following discontinuation of rocuronium bromide infusion may be expected to proceed at rates comparable to that following comparable total doses administered by repetitive bolus injections.

Infusion solutions of rocuronium bromide can be prepared by mixing rocuronium bromide with an appropriate infusion solution such as 5% glucose in water or lactated Ringers.

These infusion solutions should be used within 24 hours of mixing.

Unused portions of infusion solutions should be discarded.

Infusion rates of rocuronium bromide can be individualized for each patient using the following tables for 3 different concentrations of rocuronium bromide solution as guidelines: Table 1: Infusion Rates Using Rocuronium Bromide Injection (0.5 mg per mL) 50 mg rocuronium bromide in 100 mL solution.

Rate (mcg/kg/min) (kg) (lbs) 4 5 6 7 8 9 10 12 14 16 Infusion Delivery Rate (mL/hr) 10 22 4.8 6 7.2 8.4 9.6 10.8 12 14.4 16.8 19.2 15 33 7.2 9 10.8 12.6 14.4 16.2 18 21.6 25.2 28.8 20 44 9.6 12 14.4 16.8 19.2 21.6 24 28.8 33.6 38.4 25 55 12 15 18 21 24 27 30 36 42 48 35 77 16.8 21 25.2 29.4 33.6 37.8 42 50.4 58.8 67.2 50 110 24 30 36 42 48 54 60 72 84 96 60 132 28.8 36 43.2 50.4 57.6 64.8 72 86.4 100.8 115.2 70 154 33.6 42 50.4 58.8 67.2 75.6 84 100.8 117.6 134.4 80 176 38.4 48 57.6 67.2 76.8 86.4 96 115.2 134.4 153.6 90 198 43.2 54 64.8 75.6 86.4 97.2 108 129.6 151.2 172.8 100 220 48 60 72 84 96 108 120 144 168 192 Table 2: Infusion Rates Using Rocuronium Bromide Injection (1 mg per mL) 100 mg rocuronium bromide in 100 mL solution.

Rate (mcg/kg/min) (kg) (lbs) 4 5 6 7 8 9 10 12 14 16 Infusion Delivery Rate (mL/hr) 10 22 2.4 3 3.6 4.2 4.8 5.4 6 7.2 8.4 9.6 15 33 3.6 4.5 5.4 6.3 7.2 8.1 9 10.8 12.6 14.4 20 44 4.8 6 7.2 8.4 9.6 10.8 12 14.4 16.8 19.2 25 55 6 7.5 9 10.5 12 13.5 15 18 21 24 35 77 8.4 10.5 12.6 14.7 16.8 18.9 21 25.2 29.4 33.6 50 110 12 15 18 21 24 27 30 36 42 48 60 132 14.4 18 21.6 25.2 28.8 32.4 36 43.2 50.4 57.6 70 154 16.8 21 25.2 29.4 33.6 37.8 42 50.4 58.8 67.2 80 176 19.2 24 28.8 33.6 38.4 43.2 48 57.6 67.2 76.8 90 198 21.6 27 32.4 37.8 43.2 48.6 54 64.8 75.6 86.4 100 220 24 30 36 42 48 54 60 72 84 96 Table 3: Infusion Rates Using Rocuronium Bromide Injection (5 mg per mL) 500 mg rocuronium bromide in 100 mL solution.

Rate (mcg/kg/min) (kg) (lbs) 4 5 6 7 8 9 10 12 14 16 Infusion Delivery Rate (mL/hr) 10 22 0.5 0.6 0.7 0.8 1 1.1 1.2 1.4 1.7 1.9 15 33 0.7 0.9 1.1 1.3 1.4 1.6 1.8 2.2 2.5 2.9 20 44 1 1.2 1.4 1.7 1.9 2.2 2.4 2.9 3.4 3.8 25 55 1.2 1.5 1.8 2.1 2.4 2.7 3 3.6 4.2 4.8 35 77 1.7 2.1 2.5 2.9 3.4 3.8 4.2 5 5.9 6.7 50 110 2.4 3 3.6 4.2 4.8 5.4 6 7.2 8.4 9.6 60 132 2.9 3.6 4.3 5 5.8 6.5 7.2 8.6 10.1 11.5 70 154 3.4 4.2 5 5.9 6.7 7.6 8.4 10.1 11.8 13.4 80 176 3.8 4.8 5.8 6.7 7.7 8.6 9.6 11.5 13.4 15.4 90 198 4.3 5.4 6.5 7.6 8.6 9.7 10.8 13 15.1 17.3 100 220 4.8 6 7.2 8.4 9.6 10.8 12 14.4 16.8 19.2 2.6 Dosage in Specific Populations Pediatric Patients The recommended initial intubation dose of rocuronium bromide is 0.6 mg/kg; however, a lower dose of 0.45 mg/kg may be used depending on anesthetic technique and the age of the patient.

For sevoflurane (induction) rocuronium bromide doses of 0.45 mg/kg and 0.6 mg/kg in general produce excellent to good intubating conditions within 75 seconds.

When halothane is used, a 0.6 mg/kg dose of rocuronium bromide resulted in excellent to good intubating conditions within 60 seconds.

The time to maximum block for an intubating dose was shortest in infants (28 days up to 3 months) and longest in neonates (birth to less than 28 days).

The duration of clinical relaxation following an intubating dose is shortest in children (greater than 2 years up to 11 years) and longest in infants.

When sevoflurane is used for induction and isoflurane/nitrous oxide for maintenance of general anesthesia, maintenance dosing of rocuronium bromide can be administered as bolus doses of 0.15 mg/kg at reappearance of T in all pediatric age groups.

Maintenance dosing can also be administered at the reappearance of T at a rate of to 10 mcg/kg/min, with the lowest dose requirement for neonates (birth to less than 28 days) and the highest dose requirement for children (greater than 2 years up to 11 years).

When halothane is used for general anesthesia, patients ranging from 3 months old through adolescence can be administered rocuronium bromide maintenance doses of 0.075 to 0.125 mg/kg upon return of T to 0.25% to provide clinical relaxation for to 10 minutes.

Alternatively, a continuous infusion of rocuronium bromide initiated at a rate of 12 mcg/kg/min upon return of T to 10% (one twitch present in train-of-four), may also be used to maintain neuromuscular blockade in pediatric patients.

Additional information for administration to pediatric patients of all age groups is presented elsewhere in the label.

The infusion of rocuronium bromide must be individualized for each patient.

Spontaneous recovery and reversal of neuromuscular blockade following discontinuation of rocuronium bromide infusion may be expected to proceed at rates comparable to that following similar total exposure to single bolus doses.

Rocuronium bromide is not recommended for rapid sequence intubation in pediatric patients.

Geriatric patients (65 years or older) exhibited a slightly prolonged median (range) clinical duration of 46 (22 to 73), 62 (49 to 75), and 94 (64 to 138) minutes under opioid/nitrous oxide/oxygen anesthes.

Rocuronium Bromide Injection is supplied as follows: NDC Rocuronium Bromide Injection (10 mg per mL) Package Factor 25021-687-05 50 mg per 5 mL Multi-Dose Vial 10 vials per carton 25021-687-10 100 mg per 10 mL Multi-Dose Vial 10 vials per carton Storage Conditions Rocuronium Bromide Injection should be stored in a refrigerator, 2° to 8°C (36° to 46°F).

Do not freeze.

Upon removal from refrigeration to room temperature storage conditions (25°C/77°F), use rocuronium bromide within 60 days.

Use opened vials of rocuronium bromide within 30 days.

The container closure is not made with natural rubber latex.

Safety and Handling There is no specific work exposure limit for Rocuronium Bromide Injection.

In case of eye contact, flush with water for at least 10 minutes.

Injection should be stored in a refrigerator, 2° to 8°C (36° to 46°F).

Do not freeze.

Upon removal from refrigeration to room temperature storage conditions (25°C/77°F), use rocuronium bromide within 60 days.

Use opened vials of rocuronium bromide within 30 days.

The container closure is not made with natural rubber latex.

Safety and Handling There is no specific work exposure limit for Rocuronium Bromide Injection.

In case of eye contact, flush with water for at least 10 minutes.

Developmental toxicology studies have been performed with rocuronium bromide in pregnant, conscious, nonventilated rabbits and rats.

Inhibition of neuromuscular function was the endpoint for high-dose selection.

The maximum tolerated dose served as the high dose and was administered intravenously 3 times a day to rats (0.3 mg/kg, 15% to 30% of human intubation dose of 0.6 to 1.2 mg/kg based on the body surface unit of mg/m 2 ) from Day to 17 and to rabbits (0.02 mg/kg, 25% human dose) from Day to 18 of pregnancy.

High-dose treatment caused acute symptoms of respiratory dysfunction due to the pharmacological activity of the drug.

Teratogenicity was not observed in these animal species.

The incidence of late embryonic death was increased at the high dose in rats, most likely due to oxygen deficiency.

Therefore, this finding probably has no relevance for humans because immediate mechanical ventilation of the intubated patient will effectively prevent embryo-fetal hypoxia.

However, there are no adequate and well-controlled studies in pregnant women.

Rocuronium bromide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

The use of rocuronium bromide has been studied in pediatric patients 3 months to 14 years of age under halothane anesthesia.

Of the pediatric patients anesthetized with halothane who did not receive atropine for induction, about 80% experienced a transient increase (30% or greater) in heart rate after intubation.

One of the 19 infants anesthetized with halothane and fentanyl who received atropine for induction experienced this magnitude of change.

Rocuronium bromide was also studied in pediatric patients up to 17 years of age, including neonates, under sevoflurane (induction) and isoflurane/nitrous oxide (maintenance) anesthesia.

Onset time and clinical duration varied with dose, the age of the patient, and anesthetic technique.

The overall analysis of

ECG data in pediatric patients indicates that the concomitant use of rocuronium bromide with general anesthetic agents can prolong the QTc interval.

The data also suggest that rocuronium bromide may increase heart rate.

However, it was not possible to conclusively identify an effect of rocuronium bromide independent of that of anesthesia and other factors.

Additionally, when examining plasma levels of rocuronium bromide in correlation to QTc interval prolongation, no relationship was observed.

Rocuronium bromide is not recommended for rapid sequence intubation in pediatric patients.

Recommendations for use in pediatric patients are discussed in other sections.

Rocuronium bromide was administered to 140 geriatric patients (65 years or greater) in U.S. clinical trials and 128 geriatric patients in European clinical trials.

The observed pharmacokinetic profile for geriatric patients (n=20) was similar to that for other adult surgical patients.

Onset time and duration of action were slightly longer for geriatric patients (n=43) in clinical trials.

Clinical experiences and recommendations for use in geriatric patients are discussed in other sections.