Rocuronium Bromide Main Life

Description: A white to yellowish white powder. Very soluble in water, acetonitrile, N, N-dimethylformamide, methanol and ethanol (99.5). Hygroscopic. (See Table 1.)

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Physicochemistry: Non-proprietary name: Rocuronium bromide.
Chemical name: (+)-(17β-acetoxy-3α-hydroxy-2β-morpholino-5α -androstan-16β-yl)-1-allyl-1-pyrrolidinium bromide.
Molecular formula: C32H53BrN2O4.
Molecular weight: 609.68.
Composition: See Table 2.

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Pharmacology: Pharmacokinetics: Non-depolarizing muscle relaxants have been shown to exhibit muscle relaxing action by inhibiting or blocking neurotransmission by competitively blocking the binding of acetylcholine to receptors at the neuromuscular junction.

Muscle relaxation as an adjunct to anesthesia, muscle relaxation for tracheal intubation.

The standard dose for intubation of adults is 0.6 mg/kg of rocuronium bromide intravenously, and maintenance doses of 0.1 - 0.2 mg/kg may be added during surgery as needed. In the case of continuous infusion, initial rate should be 7 μg/kg/minute. Doses may be varied according to age and symptoms, however maximum intubation dosage is 0.9 mg/kg.
Administration to elderly: While monitoring the patient's condition, carefully administer at intubation dose of 0.6 mg/kg. If additional doses are given during surgery, determine the dose taking into consideration the duration of action of the intubation dose. When a different rocuronium bromide preparation was administered at 0.6 mg/kg, the elderly had about 16% reduced clearance compared with non-elderly (elderly: 3.45 mL/min/kg, non-elderly: 4.11 mL/min/kg) and the duration of action in elderly was 1.5 times longer compared to non-elderly (elderly: 42.4 minutes, non-elderly: 27.5 minutes).
Administration to paediatrics: Safety for neonates has not been established [Limited clinical experience]. Exercise caution when administering to neonates, infants and children. The onset of action is fast, and duration of action is short.

In the event of overdosage, exercise respiratory control until spontaneous breathing is restored, as muscle relaxation action may be prolonged. Monitor muscle relaxation as needed.

Do not use in the following patients: Patients having a history of hypersensitivity to the ingredient of this drug or to the bromide ion; Patients with severe myasthenia gravis and myasthenic syndrome, those with a history of hypersensitivity to sugammadex sodium. The muscle relaxation is prolonged because sugammadex sodium cannot be used for recovery.

Caution: Only for use by clinicians with full knowledge of the actions and usage of this drug.
Precautions related to Dosage and Administration: As the duration of action becomes longer with increased dosage, caution should be exercised when administrating 0.9 mg/kg for intubation.
In the case of continuous infusion, use a muscle relaxation monitoring device and adjust the infusion speed appropriately.
Precautions on Use: Careful administration (Administer with care to the following patients): Patients with dyspnea and airway obstruction [Ventilation failure may delay the patient's recovery of spontaneous breathing.]; Patients with liver disease, biliary disease or kidney disease [Due to delayed excretion of the drug, the duration of action may be prolonged.]; Patients with bronchial asthma [May cause asthma attack or bronchospasm.]; Patients with electrolyte abnormalities (hypokalemia, hypocalcemia, hypermagnesemia etc.), hypoproteinemia, dehydration, acidosis, hypercapnia patients [Action may be potentiated.]; Patients who use cardiopulmonary bypass by hypothermic anesthesia and hypothermic perfusion [Action may be potentiated, and duration of action may be prolonged.]; Patients with myasthenia gravis and myasthenic syndrome [These patients are extremely sensitive to non-depolarizing muscle relaxants.] (see Important Precautions as follows); Patients with neuromuscular disease except those with myasthenia gravis and myasthenic syndrome (muscular dystrophy, myotonic syndrome, congenital myopathy, spinal muscular atrophy, Guillain-Barre syndrome etc.) or patients after polio disease [May potentiate or reduce the magnitude of action]; Patients with reduced cardiac output [The onset of action may be delayed, or duration of action may be prolonged.]; Obese patients [If dose is calculated by actual weight, the duration of action may be prolonged and recovery may be delayed.]; Burn patients [It is known that the action of muscle relaxants are suppressed.]; Elderly [The duration of action may be prolonged due to delay in excretion.] (see Administration to elderly under Dosage & Administration); Patients who are or may be pregnant (see Use in Pregnancy & Lactation); Neonates, infants, toddlers or children (see Administration to paediatrics under Dosage & Administration).
Important Precautions: Because this drug causes respiratory depression, breathing should be regulated (use gas anesthetic machine or respirator) until adequate spontaneous breathing is restored.
Patients with myasthenia gravis and myasthenic syndrome are highly sensitive to non-depolarising muscle relaxants, and the muscle relaxation action is likely to be potentiated or prolonged. Always use a muscle relaxation monitor, pay careful attention to the patient's respiratory condition etc., and use sugammadex sodium as necessary to recover from muscle relaxation state. In these patients do not use anticholinesterase agents to recover from muscle relaxation.
In patients other than myasthenia gravis and myasthenic syndrome, sugammadex sodium or an anticholinesterase agent and atropine sulfate hydrate (to prevent the side effects of the anticholinesterase agent) can be administered by intravenous infusion for recovery from the muscle relaxation state induced by this drug. When administering an anticholinesterase agent, administer after confirming recovery by way of the muscle relaxation monitor or confirming spontaneous breathing. Confirm the usage, dosage, and precautions described in the package insert of each drug.
After induction of anesthesia, if suxamethonium chloride hydrate is administered for the purpose of tracheal intubation prior to administration of this drug, administer this drug after confirming that the effect of suxamethonium chloride hydrate has diminished (patient's spontaneous breathing has recovered).
In order to objectively evaluate the degree of muscle relaxation, and to use this drug safely and appropriately, use a muscle relaxation monitor as required.
Exercise caution in patients who have experienced anaphylactic reactions with suxamethonium chloride hydrate in the past, as anaphylactic reactions may also occur with this drug.
In order to prevent complications such as respiratory depression and aspiration due to the residual muscle relaxation action, extubate only after confirming that the patient's muscle relaxation has fully recovered.
If it is necessary to re-administer this drug after administration of sugammadex sodium, there is a possibility that a delay of onset of action of this drug may be observed. Therefore, exercise caution while administering this drug while sufficiently observing the patient's condition.
Precautions on applications: As sediments will form when mixed with amphotericin B, hydrocortisone succinate sodium, methylprednisolone sodium succinate, thiamylal sodium, thiopental sodium, or furosemide, either use different administration routes or, when using the same infusion line, flush the inside with a neutral solution such as saline and ensure not to mix with this drug.
Other precautions: There have been reports of prolonged muscle relaxation or quadriplegia etc. when using a different rocuronium bromide preparation continuously over long-term for an un-approved indication of respiratory control. There are also reports of other non-depolarizing muscle relaxants used in a similar manner in neonates and infants, causing deafness.

Use only when it is judged that the therapeutic benefit outweighs the risk to pregnant women or women who may be pregnant. The safety of administration during pregnancy has not been established.
It is desirable to avoid administration to lactating women etc., but in the case that administration becomes necessary, advise the patient to refrain from breastfeeding. Transfer to breastmilk has been reported in animal experiments (rats).

No survey to investigate the frequency of side effects has been conducted with this drug.
Serious side effects (frequency unknown): Shock, anaphylaxis: As shock or anaphylaxis (elevated airway pressure, decreased blood pressure, tachycardia, generalised flushing of skin, etc.) may occur, patients should be observed sufficiently. If any abnormalities are found, administration should be stopped immediately and appropriate treatment should be performed.
Prolonged respiratory depression: Prolonged respiratory depression may occur. In such cases, exercise respiratory control until the spontaneous breathing is restored.
Rhabdomyolysis: Rhabdomyolysis, characterized by muscle pain, weakness, increased CK (CPK), and elevated blood and urine myoglobin, has been reported in similar drugs. In such cases, take appropriate measures such as discontinuing administration immediately.
Bronchospasm: Because bronchospasm may occur, the patient should be carefully monitored. If any abnormalities are observed, discontinue administration and take appropriate measures.
Other side effects: See Table 3.

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Precautions for coadministration: Exercise caution on coadministration: See Table 4.

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Precautions for Handling: Stability of unopened vial: According to the results of a long-term stability test (25°C±2°C/60% RH±5%RH, 36 months) it was confirmed that Rocuronium Bromide solution for injection/infusion 50 mg/5 mL are stable under normal market circulation for 3 years.
Compatibility with infusion solutions: Compatibility studies with the following infusion fluids have been performed: Rocuronium bromide solution for injection/infusion 50 mg/5 mL has been shown to be compatible with the following when 1 vial is added to 0.9% NaCl (50 mL), 5% glucose (20 mL), Lactated Ringers (250 mL), 5% glucose acetated Ringers (200 mL) solutions. Administration should be begun immediately after mixing. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Use immediately after opening the vial: After dilution with infusion fluids (see Important Precautions under Precautions), chemical and physical in-use stability has been demonstrated for 24 hours at room temperature (below 30°C). From a microbiological point of view, the diluted product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user/administrator and would normally not be longer than 24 hours.

At or below 25°C.
Expiry date: 3 years.

Neuromuscular Blocking Agents

M03AC09 - rocuronium bromide ; Belongs to the class of other quaternary ammonium-containing agents used as peripherally-acting muscle relaxants.

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