Rocuronium

M03A - Muscle relaxants, peripherally acting agents ATC M03AC09 Small molecule approved 1994 Parenteral Natural product

JFDA label: Rucoron 50mg/5ml Vial

Mechanism of Action

Blocks acetylcholine from binding to receptors on motor endplate inhibiting depolarization

Indications

Approved

Neuromuscular blockade

Off-label

Intensive care unit paralysis
Preinduction defasciculation

Contraindications

Source: Lexicomp

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

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (4)

Not Known hypertension · Increased peripheral vascular resistance · tachycardia · transient hypotension

Immune system disorders (1)

Not Known Anaphylaxis

Dosing

Source: Lexicomp

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).

(For additional information see "Rocuronium: Pediatric drug information") 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).

Refer to adult dosing.

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

Warnings & Precautions

Source: Lexicomp

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 & Lactation

Pregnancy

FDA category C Teratogenic

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.

Lactation

Information related to rocuronium use and breast-feeding has not been located. If present in breast milk, oral absorption by a nursing infant would be expected to be minimal (Lee, 1993).

Monitoring

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

Chemistry & Properties

Formula	C32H53N2O4+
Molecular weight	529.79 g/mol
IUPAC name	[(2S,3S,5S,8R,9S,10S,13S,14S,16S,17R)-3-hydroxy-10,13-dimethyl-2-morpholin-4-yl-16-(1-prop-2-enylpyrrolidin-1-ium-1-yl)-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl] acetate
CAS	143558-00-3
PubChem CID	441290
InChIKey	`YXRDKMPIGHSVRX-OOJCLDBCSA-N`
logP	4.41 (XLogP 5.0)
Polar surface area	59.0 Å²
H-bond acceptors / donors	5 / 1
Drug-likeness (QED)	0.32
Lipinski violations	1

SMILES

C=CC[N+]1([C@H]2C[C@H]3[C@@H]4CC[C@H]5C[C@H](O)[C@@H](N6CCOCC6)C[C@]5(C)[C@H]4CC[C@]3(C)[C@H]2OC(C)=O)CCCC1

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	70.0%
Half-life	1.585 h
Volume of distribution	0.232 L/kg
Protein binding	35.7%
BBB penetrant	Yes

Enzyme interactions

Enzyme	Role	Detail
CYP2B6	Inhibitor	—
CYP3A4	Substrate	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP3 (Inhibitor)MRP4 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OCT1 (Inhibitor)P-gp (Inhibitor)OATP (Substrate)OATP1A2 (Substrate)OCT1 (Substrate)P-gp (Substrate)

Drug–drug interactions (51, DDInter)

Interacting drug	Severity	Management
Amikacin	major
Amikacin (liposome)	major
Gentamicin	major
Kanamycin	major
Neomycin	major
Paromomycin	major
Polymyxin B	major
Streptomycin	major
Aminophylline	moderate
Amphotericin B	moderate
Amphotericin B (cholesteryl sulfate)	moderate
Amphotericin B (lipid complex)	moderate
Amphotericin B (liposomal)	moderate
Bacitracin	moderate
Betamethasone	moderate
Chloroquine	moderate
Clindamycin	moderate
Clindamycin (topical)	moderate
Cyclophosphamide	moderate
Cyclosporine	moderate
Demeclocycline	moderate
Dexamethasone	moderate
Doxycycline	moderate
Dyphylline	moderate
Fludrocortisone	moderate
Gentamicin (topical)	moderate
Hydrocortisone	moderate
Lidocaine	moderate
Magnesium chloride	moderate
Magnesium sulfate	moderate
Mannitol	moderate
Methylprednisolone	moderate
Metoclopramide	moderate
Minocycline	moderate
Neomycin (topical)	moderate
Oxtriphylline	moderate
Oxytetracycline	moderate
Oxytocin	moderate
Prednisolone	moderate
Prednisone	moderate

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Registered Products (5)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Esmeron	Vial 50 mg/5 ml	10 vial	Adatco Drug Store	—
MUSCOBLOC 50 mg/5 ml Solution for I.V. Injection	Injection 50 mg/5 ml	10 vial	JAWEDA INT. DRUD STORE	—
Rimexa 50mg/5ml Solution For Inj	Injection 10 mg/1 ml	10 vial	MS PHARMA/JORDAN	—
Rocalm	Vial 10 mg/1 ml	10 vial	ORIENT DRUG STORE CO	—
Rucoron	Vial 50 mg/5 ml	10 vial	Hikma Pharmaceuticals Co.Ltd/Jordan	—