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Rocuronium


General


Pronunciation

(roe kyoor OH nee um)


Brand Names: U.S.

  • Zemuron [DSC]

Indications


Use: Labeled Indications

Neuromuscular blockade: As an adjunct to general anesthesia to facilitate rapid sequence and routine tracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation.


Contraindications


Hypersensitivity (eg, anaphylaxis) to rocuronium, other neuromuscular-blocking agents, or any component of the formulation


Dosing and Administration


Dosing: Adult

Dose to effect; doses will vary due to interpatient variability. Dosing also dependent on anesthetic technique and age of patient.

Rapid sequence intubation: IV: 0.6 to 1.2 mg/kg

Obesity: In adult patients with morbid obesity (BMI >40 kg/m2), the use of 1.2 mg/kg using ideal body weight (IBW) provided a short onset of action and excellent or good intubating conditions at 60 seconds in one study (Gaszynski, 2011).

Tracheal intubation: IV:

Initial: 0.45 to 0.6 mg/kg; administration of 0.3 mg/kg may also provide optimal conditions for tracheal intubation (Barclay, 1997)

Obesity: May use ideal body weight (IBW) for morbidly obese (BMI >40 kg/m2) adult patients (Leykin, 2004); onset time may be slightly delayed using IBW. The manufacturer recommends dosing based on actual body weight in all obese patients.

Maintenance for continued surgical relaxation: 0.1 to 0.2 mg/kg; repeat as needed or a continuous infusion of 10 to 12 mcg/kg/minute (0.6 to 0.72 mg/kg/hour) only after recovery of neuromuscular function is evident; infusion rates have ranged from 4 to 16 mcg/kg/minute (0.24 to 0.96 mg/kg/hour)

Note: Inhaled anesthetic agents prolong the duration of action of rocuronium. Use lower end of the dosing range; redosing interval guided by monitoring with a peripheral nerve stimulator.

Preinduction defasciculation (off-label use): IV: 0.03 to 0.06 mg/kg given 1.5 to 3 minutes before administration of succinylcholine (Harvey, 1998; Martin, 1998)

ICU paralysis (eg, facilitate mechanical ventilation) in adequately sedated patients (off-label use): Initial bolus dose: 0.6 to 1 mg/kg, then a continuous IV infusion of 8 to 12 mcg/kg/minute (0.48 to 0.72 mg/kg/hour); monitor depth of blockade every 2 to 3 hours initially until stable dose, then every 8 to 12 hours; adjust rate of administration by 10% increments according to peripheral nerve stimulation response or desired clinical response (Greenberg, 2013; Murray, 2002; Rudis, 1996; Sparr, 1997; Warr, 2011).

Note: When possible, minimize depth and duration of paralysis. Stopping the infusion for some time until forced to restart based on patient condition is recommended to reduce post-paralytic complications (eg, acute quadriplegic myopathy syndrome [AQMS]) (Murray, 2002).

Intermittent dosing has also been described with an initial loading dose of 50 mg followed by 25 mg given when peripheral nerve stimulation returns (Sparr, 1997).


Dosing: Geriatric

Refer to adult dosing.


Dosing: Pediatric

Dose to effect; doses will vary due to interpatient variability. Dosing also dependent on anesthetic technique and age of patient.

Neonates, Infants, Children, and Adolescents: Note: In general, onset is shortened and duration is prolonged as dose increases. Duration is shortest in children >2 to ≤11 years and longest in neonates and infants.

Tracheal intubation: IV: 0.45 mg/kg or 0.6 mg/kg

Maintenance for continued surgical relaxation: IV: 0.075 to 0.15 mg/kg; redosing interval is guided by monitoring with a peripheral nerve stimulator or 7 to 12 mcg/kg/minute (0.42 to 0.72 mg/kg/hour) as a continuous infusion; use lower end of the continuous infusion dosing range for neonates and the upper end for children >2 to ≤11 years

Rapid sequence intubation (off-label use): IV: 0.9 mg/kg or 1.2 mg/kg. Not recommended, per the manufacturer, for rapid sequence intubation in pediatric patients; however, it has been used successfully in clinical trials for this indication in children >1 year (Cheng, 2002; Fuchs-Buder, 1996; Mazurek, 1998; Naguib, 1997).


Dosing: Renal Impairment

No dosage adjustment necessary. Duration of neuromuscular blockade may vary in patients with renal impairment.


Dosing: Hepatic Impairment

No dosage adjustment provided in manufacturer 's labeling. However, dosage reductions may be necessary in patients with liver disease; duration of neuromuscular blockade may be prolonged due to increased volume of distribution. When rapid sequence intubation is required in adult patients with ascites, a dose on the higher end of the dosage range may be necessary to achieve adequate neuromuscular blockade.


Reconstitution

May be diluted in D5NS, D5W, LR or NS at concentrations up to 5 mg/mL; use within 24 hours of preparation.


Administration

Administer IV only; may be administered as a bolus injection (undiluted) or via a continuous infusion.


Storage

Store unopened/undiluted vials under refrigeration at 2 ‚ °C to 8 ‚ °C (36 ‚ °F to 46 ‚ °F); do not freeze. When stored at room temperature (25 ‚ °C [77 ‚ °F]), it is stable for 60 days; once opened, use within 30 days. Dilutions up to 5 mg/mL in 0.9% sodium chloride, dextrose 5% in water, 5% dextrose in sodium chloride 0.9%, or lactated Ringers are stable for up to 24 hours at room temperature.


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous, as bromide:

Zemuron: 50 mg/5 mL (5 mL [DSC]); 100 mg/10 mL (10 mL [DSC])

Generic: 50 mg/5 mL (5 mL); 100 mg/10 mL (10 mL)

Solution, Intravenous, as bromide [preservative free]:

Generic: 50 mg/5 mL (5 mL); 100 mg/10 mL (10 mL)


Compatibility

Stable in D5NS, D5W, LR, NS; do not mix with alkaline solutions.

Y-site administration: Incompatible with micafungin.


Drug Interactions

AbobotulinumtoxinA: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Acetylcholinesterase Inhibitors: May diminish the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Aminoglycosides: May enhance the respiratory depressant effect of Neuromuscular-Blocking Agents. Monitor therapy

Calcium Channel Blockers: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Capreomycin: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Cardiac Glycosides: Neuromuscular-Blocking Agents may enhance the arrhythmogenic effect of Cardiac Glycosides. Monitor therapy

Clindamycin (Topical): May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Colistimethate: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Consider therapy modification

Corticosteroids (Systemic): Neuromuscular-Blocking Agents (Nondepolarizing) may enhance the adverse neuromuscular effect of Corticosteroids (Systemic). Increased muscle weakness, possibly progressing to polyneuropathies and myopathies, may occur. Consider therapy modification

CycloSPORINE (Systemic): May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

EPHEDrine (Systemic): May enhance the therapeutic effect of Rocuronium. Monitor therapy

Fosphenytoin-Phenytoin: May diminish the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Fosphenytoin-Phenytoin may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Fosphenytoin-Phenytoin may decrease the serum concentration of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Inhalational Anesthetics: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Ketorolac (Nasal): May enhance the adverse/toxic effect of Neuromuscular-Blocking Agents (Nondepolarizing). Specifically, episodes of apnea have been reported in patients using this combination. Monitor therapy

Ketorolac (Systemic): May enhance the adverse/toxic effect of Neuromuscular-Blocking Agents (Nondepolarizing). Specifically, episodes of apnea have been reported in patients using this combination. Monitor therapy

Lincosamide Antibiotics: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Lithium: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Loop Diuretics: May diminish the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Loop Diuretics may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Magnesium Salts: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Minocycline: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

OnabotulinumtoxinA: Neuromuscular-Blocking Agents may enhance the neuromuscular-blocking effect of OnabotulinumtoxinA. Monitor therapy

Polymyxin B: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Consider therapy modification

Procainamide: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

QuiNIDine: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

QuiNINE: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Avoid combination

RimabotulinumtoxinB: Neuromuscular-Blocking Agents may enhance the neuromuscular-blocking effect of RimabotulinumtoxinB. Monitor therapy

Spironolactone: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Tetracycline Derivatives: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Trimebutine: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Vancomycin: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy


Monitoring Parameters

Peripheral nerve stimulator measuring twitch response, heart rate, blood pressure, assisted ventilation status


Adverse Reactions


Frequency not always defined.

Cardiovascular: Increased peripheral vascular resistance (abdominal aortic surgery: 24%, frequency not defined during other procedures), tachycardia ( ≤5%; incidence greater in children), hypertension, transient hypotension

Hypersensitivity: Anaphylaxis

<1% (Limited to important or life-threatening): Anaphylactoid reaction, asthma, cardiac arrhythmia, ECG abnormality, hiccups, injection site edema, nausea, vomiting


Warnings/Precautions


Special Populations: Renal Function Impairment

Patients with renal failure have clinical durations that are similar to but somewhat more variable than what is expected in patients with normal renal function.


Special Populations: Hepatic Function Impairment

Patients with clinically significant hepatic impairment had moderately prolonged clinical duration; patients with cirrhosis had increased Vd, prolonged plasma half-life, and >2.5 times the recovery time compared to patients with normal hepatic function.


Special Populations: Elderly

Onset time and duration of action are slightly longer in elderly patients.


Warnings/Precautions

Concerns related to adverse effects:

- Anaphylactoid/hypersensitivity reactions: Immediate treatment (including epinephrine 1 mg/mL) for anaphylactoid and/or hypersensitivity reactions should be available during use.

- Neuromuscular cross-sensitivity: Cross-sensitivity with other neuromuscular-blocking agents may occur; use is contraindicated in patients with previous anaphylactic reactions to other neuromuscular blockers.

- Prolonged paralysis: Some patients may experience prolonged recovery of neuromuscular function after administration (especially after prolonged use). Patients should be adequately recovered prior to extubation. Other factors associated with prolonged recovery should be considered (eg, corticosteroid use, patient condition).

Disease-related concerns:

- Burn injury: Resistance may occur in burn patients ( ≥20% of total body surface area), usually several days after the injury, and may persist for several months after wound healing (Han, 2009).

- Cardiovascular disease: Use with caution in patients with cardiovascular disease (eg, heart failure); onset of action may be delayed and duration of action may be prolonged.

- Conditions that may antagonize neuromuscular blockade: Respiratory alkalosis, hypercalcemia, demyelinating lesions, peripheral neuropathies, denervation, and muscle trauma may result in antagonism of neuromuscular blockade (Greenberg, 2013; Miller, 2010; Murray, 2002; Naguib, 2002).

- Conditions that may potentiate neuromuscular blockade: Electrolyte abnormalities (eg, severe hypocalcemia, severe hypokalemia, hypermagnesemia), cachexia, neuromuscular diseases, metabolic acidosis, metabolic alkalosis, respiratory acidosis, Eaton-Lambert syndrome, and myasthenia gravis may result in potentiation of neuromuscular blockade (Greenberg, 2013; Miller, 2010; Naguib, 2002).

- Hepatic impairment: Use with caution in patients with hepatic impairment; clinical duration may be prolonged.

- Pulmonary hypertension: Use with caution in patients with pulmonary hypertension; use may increase pulmonary vascular resistance worsening symptoms of right heart failure.

- Respiratory disease: Use with caution in patients with respiratory disease.

- Valvular heart disease: Use with caution in patients with valvular heart disease; use may increase pulmonary vascular resistance.

Concurrent drug therapy issues:

- Corticosteroids: In addition to prolonging recovery from neuromuscular blockade, concomitant use with corticosteroids has been associated with development of acute quadriplegic myopathy syndrome (AQMS). Current guidelines recommend neuromuscular blockers be discontinued as soon as possible in patients receiving corticosteroids or interrupted daily until necessary to restart them based on clinical condition (Murray, 2002).

- High potential for interactions: Numerous drugs either antagonize (eg, acetylcholinesterase inhibitors) or potentiate (eg, calcium channel blockers, certain antimicrobials, inhalation anesthetics, lithium, magnesium salts, procainamide, and quinidine) the effects of neuromuscular blockade; use with caution in patients receiving these agents.

Special populations:

- Elderly: Use with caution in the elderly, effects and duration are more variable.

- Immobilized patients: Resistance may occur in patients who are immobilized.

- Pediatric: Not recommended by the manufacturer for rapid sequence intubation in pediatric patients; however, it has been used successfully in clinical trials for this indication (Cheng, 2002; Fuchs-Buder, 1996; Mazurek, 1998; Naguib, 1997).

Other warnings/precautions:

- Appropriate use: Maintenance of an adequate airway and respiratory support is critical. Rocuronium does not relieve pain or produce sedation; use should include appropriate anesthesia, pain control, and sedation. In patients requiring long-term administration in the ICU, tolerance to rocuronium may develop; use of a peripheral nerve stimulator to monitor drug effects is strongly recommended. Additional doses of rocuronium or any other neuromuscular-blocking agent should be avoided unless definite excessive response to nerve stimulation is present.

- Experienced personnel: Should be administered by adequately trained individuals familiar with its use.

- Extravasation: If extravasation occurs, local irritation may ensue; discontinue administration immediately and restart in another vein.


Pregnancy Risk Factor

C


Pregnancy Considerations

Teratogenic effects were not observed in animal reproduction studies. Rocuronium crosses the placenta; umbilical venous plasma levels are ~18% of the maternal concentration following a maternal dose of 0.6 mg/kg (Abouleish, 1994). The manufacturer does not recommend use for rapid sequence induction during cesarean section.


Actions


Pharmacology

Blocks acetylcholine from binding to receptors on motor endplate inhibiting depolarization


Distribution

Vd:

Children: 0.21-0.3 L/kg

Adults: 0.22-0.26 L/kg

Hepatic dysfunction: 0.53 L/kg

Renal dysfunction: 0.34 L/kg


Metabolism

Minimally hepatic; 17-desacetylrocuronium (5% to 10% activity of parent drug)


Excretion

Feces (31%); urine (26%) (Proost 2000)

Clearance: Pediatric patients:

Infants 3 to <12 months: 0.35 L/kg/hour

Children 1 to <3 years: 0.32 L/kg/hour

Children 3 to <8 years: 0.44 L/kg/hour


Onset of Action

Infants ≥3 months and Children: 30 seconds to 1 minute

Adults: Good intubation conditions within 1-2 minutes (depending on dose administered); maximum neuromuscular blockade within 4 minutes


Duration of Action

Infants: 3-12 months: 40 minutes

Children: 1-12 years: 26-30 minutes

Adults: ~30 minutes (with standard doses, increases with higher doses and inhalational anesthetic agents)


Half-Life Elimination

Alpha elimination: 1 to 2 minutes

Beta elimination:

Infants 3 to 12 months: 1.3 ‚ ± 0.5 hours

Children 1 to <3 years: 1.1 ‚ ± 0.7 hours

Children 3 to <8 years: 0.8 ‚ ± 0.3 hours

Adults: 1.4 to 2.4 hours

Hepatic impairment: 4.3 hours

Renal impairment: 2.4 hours


Protein Binding

~30%


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Have patient report immediately to prescriber severe injection site pain; burning, edema, or irritation; or arrhythmia (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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