Rocuronium Bromide

Pronunciation: ROE-kure-OH-nee-um BROE-mide
Class: Nondepolarizing neuromuscular blocker

Trade Names

Zemuron
- Injection, solution 10 mg/mL

Pharmacology

Binds competitively to cholinergic receptors on motor end-plate to antagonize action of acetylcholine, resulting in block of neuromuscular transmission.

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Pharmacokinetics

Distribution

Rapid distribution half-life is 1 to 2 min and the slower distribution half-life is 14 to 18 min. Plasma protein binding is approximately 30%. Vd is 0.25 L/kg.

Elimination

Eliminated primarily by the liver. Half-life is approximately 1.4 h.

Special Populations

Renal Function Impairment

Patients with renal failure have clinical durations that are similar to but somewhat more variable than the duration that is expected in subjects with healthy renal function.

Hepatic Function Impairment

Patients with demonstrated liver cirrhosis have a marked increase in their Vd, resulting in a plasma half-life approximately twice that of patients with healthy hepatic function. Because of the large increase in volume, patients with hepatic impairment may demonstrate clinical durations approaching 1.5 times that of subjects with healthy hepatic function. In both populations, individualize the dose to the needs of the patient.

Elderly

Observed pharmacokinetic effects for patients 65 y and older were similar to other adult patients. Onset time and duration of action are slightly longer in elderly patients.

Children

Cl and Vd increase with body weight (kg) and age (years). As a result, the terminal half-life of rocuronium decreases with increasing age from 1.1 h to 0.7 to 0.8 h.

Gender

Studies with healthy adult subjects did not reveal any differences in the pharmacokinetics of rocuronium because of gender.

Indications and Usage

As an adjunct to general anesthesia for inpatients and outpatients to facilitate both rapid sequence and routine tracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation.

Contraindications

Hypersensitivity (eg, anaphylaxis) to rocuronium or other neuromuscular blocking agents.

Dosage and Administration

Continuous Infusion
Adults

IV 10 to 12 mg/kg/min initiated only after early evidence of spontaneous recovery from the intubating dose. Upon reaching the desired level of neuromuscular block, the infusion must be individualized to a dose range of 4 to 16 mcg/kg/min.

Rapid Sequence Intubation
Adults

IV 0.6 to 1.2 mg/kg.

Tracheal Intubation
Adults

IV 0.45 or 0.6 mg/kg initially. Maintenance dosing is 0.1, 0.15, and 0.2 mg/kg at 25% recovery of control T 1 (defined as 3 twitches of train-of-four). A large bolus dose of 0.9 or 1.2 mg/kg can be used as the initial dose along with opioid/nitrous oxide/oxygen anesthesia.

Children 17 y and younger (under sevoflurane [induction] and isoflurane/nitrous oxide [maintenance] anesthesia)

IV 0.45 or 0.6 mg/kg initially. Maintenance dosing of 0.15 mg/kg can be administered as bolus doses at reappearance of T 3 . Maintenance dosing at a rate of 7 to 10 mcg/kg/min can also be administered at the reappearance of T 2 with the lowest dose requirement for neonates (ie, birth to younger than 28 days) and the highest dose requirement for children (ie, older than 2 y to up to 11 y).

Children 14 y and older (under halothane anesthesia)

IV 0.45 or 0.6 mg/kg initially. Maintenance dosing is 0.1, 0.15, and 0.2 mg/kg at 25% recovery of control T 1 (defined as 3 twitches of train-of-four). A large bolus dose of 0.9 or 1.2 mg/kg can be used as the initial dose along with opioid/nitrous oxide/oxygen anesthesia.

Children 3 mo to 14 y of age (under halothane anesthesia)

IV 0.6 mg/kg initially. Maintenance dosing of 0.075 to 0.125 mg/kg can be administered as bolus doses upon return of T 1 to 0.25%. Alternatively, a continuous infusion initiated at a rate of 12 mcg/kg/min upon return of T 1 to 10% of control (1 twitch present in train-of-four) may also be used.

Special Risk Patients

Nondepolarizing neuromuscular blocking agents have been found to exhibit profound neuromuscular blocking effects in cachectic or debilitated patients, patients with neuromuscular diseases, and patients with carcinomatosis. In these or other patients in whom potentiation of neuromuscular block or difficulty with reversal may be anticipated, consider a decrease from the recommended initial dose. Resistance sometimes develops in patients with cerebral palsy or with long-term exposure to nondepolarizing agents. When rocuronium is administered to these patients, shorter durations of neuromuscular block may occur and infusion rates may be higher because of the development of resistance to nondepolarizing muscle relaxants.

Obesity

The initial dose of rocuronium 0.6 mg/kg should be based on the patient's actual body weight.

Prolonged Circulation Time

Do not increase the initial dosage in patients with prolonged circulation time to reduce onset time; instead, in these situations, when feasible, allow more time for the drug to achieve onset of effect.

Concomitant Therapy

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 45 to 60 min after the intubating dose.

Antibiotics, magnesium salts, lithium, local anesthetics, procainamide, and quinidine have been shown to increase the duration of the neuromuscular block and decrease infusion requirements of neuromuscular blocking agents.

General Advice

  • For IV use only. The rate of administration should be adjusted according to the patient's twitch response, as monitored with the use of a peripheral nerve stimulator. Refer to manufacturer's prescribing information for infusion rates.
  • Use a peripheral nerve stimulator to monitor drug effect, need for additional doses, and adequacy of spontaneous recovery or antagonism, and to decrease the complications of overdosage if additional doses are administered.
  • Infusion solutions can be prepared by mixing rocuronium with an appropriate infusion solution, such as sodium chloride 0.9% solution, sterile water for injection, glucose 5% in water, Ringer's lactate, or glucose 5% in saline.
  • Rocuronium is physically incompatible when mixed with amphotericin, amoxicillin, azathioprine, cefazolin, cloxacillin, dexamethasone, diazepam, erythromycin, famotidine, furosemide, hydrocortisone sodium succinate, insulin, intralipid, ketorolac, lorazepam, methohexital, methylprednisolone, thiopental, trimethoprim, and vancomycin.
  • Do not mix rocuronium with alkaline solutions in the same syringe, and do not administer simultaneously during IV infusion through the same needle.
  • Spontaneous recovery and reversal of neuromuscular blockade following discontinuation of rocuronium infusion may be expected to proceed at rates comparable with that following comparable total doses administered by repetitive bolus injections in adults, and at rates comparable with that following similar total exposure to single bolus doses in children.

Storage/Stability

Store in refrigerator (36° to 46°F). Do not freeze. May be removed from refrigerator and stored at controlled room temperature (less than 77°F), but must be used within 60 days. Once vial has been opened, use within 30 days. Use infusion solutions within 24 h of mixing; discard unused portions.

Drug Interactions

Antibiotics (eg, aminoglycoside antibiotics [eg, gentamicin], bacitracin, clindamycin, lincomycin, polymyxins, sodium colistimethate, tetracyclines, vancomycin), cyclosporine, ketamine, lithium, local anesthetics, magnesium salts, procainamide, quinidine, verapamil

May enhance the neuromuscular blocking action of rocuronium. Use with caution. Carefully titrate the dose of rocuronium and closely monitor neuromuscular function. Provide mechanical respiratory support as needed.

Carbamazepine, hydantoins (eg, phenytoin), thiopurines

Resistance to neuromuscular blocking action of rocuronium may occur. Use with caution. Dosage requirements for rocuronium may be increased. Monitor patients closely for more rapid recovery from neuromuscular blockade than expected. Adjust the rocuronium dose as needed.

Nitrous oxide/oxygen with either enflurane or isoflurane

May prolong the clinically effective duration of action of initial and maintenance doses of rocuronium and decrease the required infusion rate. It may be necessary to decrease the rate of infusion after the intubating dose.

Nondepolarizing muscle relaxants

There are no controlled studies documenting use of rocuronium before or after other nondepolarizing muscle relaxants. Interactions have been observed when other nondepolarizing muscle relaxants have been administered in succession. Use with caution. Closely monitor neuromuscular function. Provide mechanical respiratory support as needed.

Succinylcholine

Time of onset of maximum block following rocuronium may be faster with prior administration of succinylcholine. If succinylcholine is used before rocuronium, delay administration of rocuronium until recovery from succinylcholine has been observed.

Theophyllines

Neuromuscular blocking effects of rocuronium may be decreased by theophyllines. Cardiac arrhythmia may also occur with coadministration. Dosing requirements of rocuronium may be increased. Consider avoiding coadministration.

Thiazide diuretics (eg, chlorothiazide)

The neuromuscular blocking effects of rocuronium may be increased because of thiazide diuretic–induced hypokalemia. Prolonged respiratory depression with extended periods of apnea may occur. If hypokalemia cannot be corrected, a lower rocuronium dose may be needed.

Adverse Reactions

Cardiovascular

Increased pulmonary vascular resistance (24%); hypertension, hypotension (2%); tachycardia (1%); abnormal ECG, arrhythmia.

Hypersensitivity

Severe allergic reactions, including life-threatening and fatal anaphylactoid and anaphylactic reactions and shock (postmarketing).

Respiratory

Asthma (bronchospasm, rhonchi, wheezing).

Precautions

Monitor

It is strongly recommended that neuromuscular transmission be monitored continuously with the help of a nerve stimulator during administration and recovery.


Pregnancy

Category C . Rocuronium is not recommended for rapid sequence induction in cesarean section patients.

Lactation

Undetermined.

Children

Rocuronium has been studied in neonates and children up to 17 y of age under sevoflurane induction. Use in children younger than 3 mo under halothane anesthesia has not been studied. Rocuronium is not recommended for rapid sequence intubation in children.

Elderly

Onset time and duration of action are slightly longer.

Hypersensitivity

Rare, severe, or life-threatening anaphylactic reactions have been reported.

Renal Function

There may be substantial individual variability in duration (range, 22 to 90 min).

Hepatic Function

Use with caution in patients with clinically significant hepatic impairment. If used for rapid sequence induction in patients with ascites, an increased initial dosage may be necessary to ensure complete block. Duration will be prolonged in these cases.

Special Risk Patients

May have profound effect in patients with neuromuscular disease (eg, myasthenia gravis), in cachectic or debilitated patients, and in patients with carcinomatosis. Patients with burns, disuse atrophy, denervation, direct muscle trauma, cerebral palsy, hemiparesis, or paraparesis may have resistance to rocuronium. When rocuronium is administered to these patients, shorter durations of neuromuscular block may occur and infusion rates may be higher. Onset time may be delayed in patients with conditions associated with slower circulation time (eg, CV disease, advanced age).

Administration

Rocuronium has no known effect on consciousness, pain threshold, or cerebration; therefore, its administration must be accompanied by adequate anesthesia or sedation.

Acid-base/electrolyte abnormalities

Severe acid-base and/or electrolyte abnormalities may potentiate or cause resistance to the neuromuscular blocking action of rocuronium.

Malignant hyperthermia

May occur.

Myopathy

Myopathy after long-term administration of other nondepolarizing neuromuscular blocking agents in the intensive care unit alone or in combination with corticosteroid therapy has been reported; therefore, for patients receiving both neuromuscular blocking agents and corticosteroids, limit the period of use of the neuromuscular blocking agent as much as possible.

Pulmonary hypertension

Because rocuronium may be associated with increased pulmonary vascular resistance, use with caution in patients with pulmonary hypertension or valvular heart disease.

Residual paralysis

In order to prevent complications resulting from residual paralysis, it is recommended to extubate only after patient recovers sufficiently from neuromuscular block.

Tolerance

Tolerance may develop during long-term administration in the intensive care unit.

Overdosage

Symptoms

Prolonged neuromuscular block.

Patient Information

  • Advise patient, family, or caregiver that medication will be prepared and administered by health care provider in a health care setting.
  • Inform patients that severe anaphylactic reactions to neuromuscular blocking agents, including rocuronium, have been reported. Because allergic cross-reactivity has been reported in this class, request information from the patient about previous anaphylactic reactions to other neuromuscular blocking agents.
  • Reassure patient, family, or caregiver that breathing will be closely monitored and supported while medication is being administered and that breathing and muscle function will return to normal after medication has been discontinued.

Copyright © 2009 Wolters Kluwer Health.

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