Neuromuscular Blocker Agent, Nondepolarizing

Adjunct to general anesthesia to facilitate tracheal intubation; to provide skeletal muscle relaxation during surgical procedures; does not relieve pain

C

Passage via placental transfer may occur. The risk to the developing fetus is unknown. Should not be used in pregnancy unless potential benefit outweighs potential risk. If administered during Cesarean section, the infant should be monitored closely for signs of neuromuscular weakness. Excretion in human breast milk is unknown. Use caution in breast-feeding women.

Hypersensitivity to rapacuronium bromide or any component of the formulation

For I.V. use only. Should be used only under the supervision of clinicians experienced in anesthesia. Use with caution in hepatic or renal disease. Hepatic disease has been associated with resistance to some neuromuscular-blocking agents. Onset may be delayed in patients with cardiac or renal disease. Ventilation must be supported during neuromuscular blockade; certain clinical conditions may result in potentiation or antagonism of neuromuscular blockade.

Potentiation:

Electrolyte abnormalities, severe hyponatremia, severe hypocalcemia, severe hypokalemia, hypermagnesemia, neuromuscular disease, acidosis, acute intermittent porphyria, renal failure

Antagonism:

Alkalosis, hypercalcemia, demyelinating lesions, peripheral neuropathies, diabetes mellitus

Should not be administered by infusion or during long surgical procedures. Repeat dosing may cause prolonged neuromuscular blockade. Repeat dosing after intubating doses >1.5 mg/kg, and repeat dosing in pediatric patients are not recommended. May cause EKG abnormalities. Increased sensitivity in patients with myasthenia gravis, Eaton-Lambert syndrome; resistance in burn patients (>30% of body) for period of 5-70 days postinjury; resistance in patients with muscle trauma, denervation, immobilization, infection; does not counteract bradycardia produced by anesthetics/vagal stimulation.

1% to 10%:

Cardiovascular: Hypotension (5.2%), tachycardia (3.2%), bradycardia (1.5%)

Dermatologic: Rash (erythematous) (>1%)

Gastrointestinal: Nausea (>1%), vomiting (>1%)

Respiratory: Bronchospasm (3.2%)

Miscellaneous: Histamine release (estimated - 5.1%-5.8%)

<1%: Fever, rigors, back pain, hypothermia, chest pain, peripheral edema, pain, asthenia, fatigue, swelling, hypertension, extrasystoles, abnormal EKG, arrhythmia, cerebrovascular disorder, ventricular fibrillation, ventricular tachycardia, atrial arrhythmia, cardiac failure, cardiopulmonary arrest, cardiac arrest, thrombophlebitis, supraventricular tachycardia, myocardial infarction, left bundle branch block, ileus, increased salivation, abdominal pain, cholelithiasis, rectal hemorrhage, esophagospasm, oral hemorrhage, tooth disorder, thrombosis, postoperative bleeding, epistaxis, abnormal coagulation, purpura, anemia, hemoperitoneum, acidosis, myalgia, muscle weakness, neonatal hypotonia, prolonged neuromuscular blockade, hypoesthesia, hemiplegia, hypertonia, prolonged anesthesia emergence, headache, cerebral hemorrhage, increased intracranial pressure, migraine, ptosis, tetany, confusion, anxiety, hypoxia, increased airway pressure, hypoventilation, laryngismus, coughing, apnea, respiratory depression, upper airway obstruction, neonatal respiratory distress syndrome, pneumothorax, pulmonary edema, respiratory insufficiency, stridor, pharyngitis, larynx edema, dyspnea, neonatal respiratory depression, hyperventilation, rhinitis, increased sputum production, injection site reaction, injection site pain, rash, urticaria, pruritus, increased sweating, paravenous injection, corneal ulceration, meiosis, hearing loss, urinary retention, oliguria, abnormal renal function, urinary tract infection, pelvic inflammation, vaginal bleeding

Overdose may result in neuromuscular blockage beyond the time needed for surgery and anesthesia. Treatment is supportive, particularly maintenance of airway and controlled ventilation until recovery of neuromuscular function is assured.

No specific drug interaction studies have been performed. A number of medications have been noted to alter the effects of nondeloparizing neuromuscular blocking agents. These include antibiotics (aminoglycosides, clindamycin), anesthetics (ketamine), magnesium sulfate, verapamil, quinidine, and furosemide. Neuromuscular blockade can be pharmacologically reversed with an anticholinesterase agent (neostigmine, edrophonium, pyridostigmine).

Anesthetics: Desflurane, sevoflurane, enflurane and isoflurane > halothane > nitrous, oxide-narcotics

Antibiotics: Aminoglycosides, polymyxins, clindamycin, vancomycin

Magnesium sulfate

Antiarrhythmics: Quinidine, procainamide, bretylium, and possibly lidocaine

Diuretics: Furosemide, mannitol

Amphotericin B (secondary to hypokalemia)

Local anesthetics

Dantrolene (directly depresses skeletal muscle)

Beta agonists

Beta blockers

Calcium channel blockers

Ketamine

Lithium

Succinylcholine (when administered prior to nondepolarizing NMB agent)

Antagonism:

Calcium

Carbamazepine

Phenytoin

Steroids (chronic administration)

Theophylline

Anticholinesterases*: Neostigmine, pyridostigmine, edrophonium, echothiophate ophthalmic solution

Caffeine

Azathioprine

*Can prolong the effects of acetylcholine

Store vials under refrigeration at 2°C to 25°C (36°F to 77°F). Reconstitute with appropriate volume (5 mL or 10 mL) sterile water for injection or other compatible solution. Compatible with 0.9 sodium chloride, 5% dextrose in water, 5% dextrose in saline, sterile water for injection, lactated Ringers, bacteriostatic water for injection. Solution may be stored under refrigeration or at room temperature and must be used within 24 hours of mixing. Incompatible when mixed with cefuroxime, danaparoid sodium, diazepam, nitroglycerin, and thiopental. Physically compatible with alfentanil, aminophylline, atropine, ceftazidime, droperidol, epinephrine, fentanyl, gentamicin, glycopyrrolate, heparin, ketamine, labetalol, lidocaine, methohexital, metoclopramide, midazolam, morphine, potassium chloride, propranolol, ranitidine, remifentanil, sufentanil, and verapamil.

Prevents depolarization of muscle membrane and subsequent muscle contraction by acting as a competitive antagonist to acetylcholine at the alpha subunits of the nicotinic cholinergic receptors on the motor endplates in skeletal muscle, also interferes with the mobilization of acetylcholine presynaptically; the neuromuscular blockade can be pharmacologically reversed with an anticholinesterase agent (neostigmine, edrophonium, pyridostigmine).

Onset: Rapid

Peak effect: 1-2 minutes

Duration: 15 minutes

Distribution: V_d: 0.29 L/kg

Protein Binding: 50% to 85%

Metabolism: Hydrolyzed to 3-hydroxy metabolite (active) - sites and identity of esterases not defined; does not involve activity of cytochrome P-450

Half-life: ~22 days

Elimination: Approximately equal elimination in urine and feces

I.V. (do not administer I.M.):

Children 13-17 years: Clinicians should consider the physical maturity, height and weight of the patient in determining the dose. Adults (1.5 mg/kg), pediatric (2 mg/kg) and Cesarean section (2.5 mg/kg) dosing recommendations may serve as a general guideline in determining an intubating dose in this age group.

Adults: Tracheal Intubation:

Initial: Short surgical procedures: 1.5 mg/kg; Cesarean section: 2.5 mg/kg

Repeat dosing: Up to three maintenance doses of 0.5 mg/kg, administered at 25% recovery of control T1 may be administered. Note: The duration of neuromuscular blockade increases with each additional dose.

Elderly: No dosing adjustment is recommended in geriatric patients

For I.V. use only; give undiluted I.V. injection as a single bolus

Degree of muscle relaxation (via peripheral nerve stimulator and presence of spontaneous movement); vital signs (heart rate, blood pressure, respiratory rate); renal function and liver function

Powder for injection: 100 mg (5 mL); 200 mg (10 mL)