COMPOSITION :
Belnium® Injection 50 mg/5 ml, each ml contains : Rocuronium bromide 10 mg.
DESCRIPTIONS :
Belnium® with Rocuronium bromide as active ingredient is available in 50 mg/5 ml injection.
INDICATIONS :
Adjunct to general anesthesia to facilitate both rapid sequence and routine tracheal intubation, to provide skeletal muscle relaxation during surgery or mechanical ventilation.
DOSAGE AND ADMINISTRATIONS :
As with other neuromuscular blocking agents, the dosage of Belnium® should be individualized in each patient. The method of anesthesia, and the expected duration of surgery, the method of sedation and the expected duration of mechanical ventilation, the possible interaction with other drugs that are administered concomitantly, and the condition of the patient should be taken into account when determining the dose.
The use of an appropriate neuromuscular monitoring technique is recommended for the evaluation of neuromuscular block and recovery.
Inhalational anesthetic do potentiate the neuromuscular blocking effect of Belnium®. This potentiation however, becomes clinically relevant in the course of anesthesia, when the volatile agents have reached the tissue concentrations required for this interaction. Consequently, adjustments with Belnium® should be made by administering smaller maintenance doses at less frequent intervals or by using lower infusion rates of Belnium® during long lasting procedures (longer than 1 hour) under inhalational anesthesia.
In adult patients the following dosage recommendations may serve as general guideline for tracheal intubation and short to long lasting muscle relaxation.
Tracheal intubation :
The standard intubating dose during routine anesthesia is 0.6 mg Belnium® per kg body weight, after which adequate conditions are established within 60 seconds in nearly all patients. A dose of 1.0 mg Belnium® per kg body weight is recommended for facilitating tracheal intubation during rapid sequence induction of anesthesia. If a dose of 0.6 mg Belnium® per kg body weight is used for rapid sequence induction af anesthesia, it is recommended to intubate the patient 90 seconds after administration of Belnium®.
In patients undergoing Cesarean section it is recommended to only use a dose of 0.6 mg Belnium® per kg body weight, since a 1.0 mg/kg body weight dose has not been investigated in this patient group.
Maintenance dosing :
The recommended maintenance dose is 0.15 mg Belnium® per kg body weight; in the case of long-term inhalational anesthesia this should be reduced to 0.075 – 0.1 mg Belnium® per kg body weight. The maintenance dose should best be given when twitch height has recovered to 25% of control twitch height or when 2 to 3 response to train of four stimulation are present.
Continuous infusion :
If Belnium® is administered by continuous infusion, it is recommended to give a loading dose of 0.6 mg Belnium® per kg body weight and when neuromuscular block starts to recover, to start administration by infusion. The infusion rate should be adjusted to maintain twitch response at 10% of control twitch height or to maintain 1 to 2 responses to train of four stimulation. In adults under intravenous anesthesia, the infusion rate required to maintain neuromuscular block at this level ranges from 0.3 – 0.6 mg.kg-1.h-1 and under inhalational anesthesia the infusion rate ranges from 0.3 – 0.4 mg.kg-1.h-1.
Continuous monitoring of neuromuscular block is recommended since infusion rate requirements vary from patient to patient and with the anesthetic method used.
Dosing in pediatric patients :
Children (1 – 14 years) and infants (1 – 12 months) under Halothane anesthesia manifest similar sensitivity to Belnium® as adults. Onset of action is faster in infants and children than in adults. Clinical duration is shorter in children than in adults. There are no data to support recommendations for the use of Belnium® in neonates (0 – 1 month).
Dosing in geriatric patients and patients with hepatic and/or biliary tract disease and/or renal failure :
The standard intubation dose for geriatric patients and patients with hepatic and/or biliary tract disease and/or renal failure during routine anesthesia is 0.6 mg Belnium® per kg body weight. A dose of 0.6 mg per kg body weight should be considered for rapid sequence induction of anesthesia in patients in which a prolonged duration of action is expected. Regardless of the anesthetic technique used, the recommended maintenance dose for these patients is 0.075 – 0.1 mg Belnium® per kg body weight and the recommended infusion rate is 0.3 – 0.4 mg.kg-1.h-1.
Dosing in overweight and obese patients :
When used in overweight or obese patients (defined as patients with a body weight of 30% or more above ideal body weight) doses should be reduced taking into account a lean body mass.
Dosing to facilitate mechanical ventilation :
The use of an initial loading dose of 0.6 mg Belnium® per kg body weight is recommended, followed by a continuous infusion as soon as twitch height recovers to 10% or upon reappearance of 1 to 2 twitches to train of four stimulation. Dosage should always be titrated to effect in the individual patient.
The recommended initial infusion rate for the maintenance of a neuromuscular block of 80-90% (1 to 2 twitches to TOF stimulation) in adult patients is 0.3 – 0.6 mg.kg-1.h-1 during the first hour of administration, which will need to be decreased during the following 6 – 12 hours, according to the individual response. Thereafter, individual dose requirements remain relatively constant. A large between patient variability in hourly infusion rates has been found in controlled clinical studies, with mean hourly infusion rates ranging from 0.2 – 0.5 mg.kg-1.h-1 depending on nature and extent of organ failure(s), concomitant medication and individual patient characteristics. To provide optimal individual patient control, monitoring of neuromuscular transmission is strongly recommended. Administration up to 7 days has been investigated. There are no data to support dose recommendation for the facilitation of mechanical ventilation in pediatric and geriatric patients.
Administration :
Belnium® is administered intravenously either as a bolus injection or as continuous infusion.
OVERDOSAGE :
The patient should continue to receive ventilatory support and sedation. Upon start of spontaneous recovery, an acetylcholinesterase inhibitor (e.g., Neostigmine, Edrophonium, Pyridostigmine) should be administered. If fails, ventilation must be continued until spontaneous breathing is restored. Repeated doses of acetylcholinesterase inhibitor can be dangerous.
CONTRAINDICATIONS :
Former anaphylactic reactions to Rocuronium or to the bromide ion.
WARNINGS AND PRECAUTIONS :
Since Rocuronium bromide causes paralysis of the respiratory muscles, ventilatory support is mandatory for patients treated with this drug until adequate spontaneous respiration is restored. As with all neuromuscular blocking agents, it is important to anticipated intubation difficulties, particularly when used as part of a rapid sequence induction technique.
Anaphylactic reactions can occur following the administration of neuromuscular blocking agents. Precautions for treating such reactions should always be taken. Particularly in the care of previous anaphylactic reactions to neuromuscular blocking agents, special precautions should be taken since allergic cross-reactivity to neuromuscular blocking agents has been reported.
Dose levels greater than 0.9 mg Rocuronium bromide per kg body weight may increase the heart rate, this effect could counteract the bradycardia produced by other anesthetic agents or by vagal stimulation.
In general, following long term use of muscle relaxants in the ICU, prolonged paralysis and/or skeletal muscle weakness has been noted.
In order to help preclude possible prolongation of neuromuscular block and/or overdosage it is strongly recommended that neuromuscular transmission is monitored throughout the use of muscle relaxants. In addition, patients should receive adequate analgesia and sedation. Furthermore, muscle relaxants should be titrated to effect in the individual patients by or under supervision of experienced clinicians who are familiar with their actions and with appropriate neuromuscular monitoring techniques.
Because Rocuronium bromide is always used with other agents and because the occurrence of malignant hyperthermia during anesthesia is possible, even in the absence of known triggering agents, clinicians should be familiar with early signs, confirmatory diagnosis and treatment of malignant hyperthermia prior to the start of any anesthesia.
The following conditions may influence the pharmacokinetics and/or pharmacodynamics of Rocuronium bromide:
Hepatic and/or biliary tract disease and renal failure
Because Rocuronium is excreted in urine and bile, Rocuronium bromide should be used with caution in patients with clinically significant hepatic and/or biliary diseases and/or renal failure. In these patients group, prolongation of action has been observed with doses of 0.6 mg Rocuronium bromide per kg body weight.
Prolonged circulation time
Conditions associated with prolonged circulation time such as cardiovascular disease, old age and oedematous state resulting in an increased volume of distribution, may contribute to a slower onset of action.
Neuromuscular disease
Like other neuromuscular blocking agents, Rocuronium bromide should be used with extreme caution in patients with a neuromuscular disease or after poliomyelitis since the response to neuromuscular blocking agents may be considerably altered in these cases. The magnitude and direction of this alteration may vary widely.
In patients with myasthenia gravis or with the myasthenic (Eaton-Lambert) syndrome, small doses of Rocuronium bromide may have profound effects and Rocuronium bromide should be titrated to the response.
Hypothermia
In surgery under hypothermic conditions, the neuromuscular blocking effect of Rocuronium bromide is increased and the duration prolonged.
Obesity
Like other neuromuscular blocking agents, Rocuronium bromide may exhibit a prolonged duration and a prolonged spontaneous recovery in obese patients, when the administered doses are calculated on actual body weight.
Burns
Patients with burns are known to develop resistance to non-depolarizing neuromuscular blocking agents. It is recommended that the dose is titrated to response.
Conditions which may increase the effects of Rocuronium bromide
Hypokalaemia (e.g. after severe vomiting, diarrhea and diuretic therapy), hypermagnesemia, hypocalcaemia (after massive transfusions), hypoproteinaemia, acidosis, hypercapnia, cachexia. Severe electrolyte disturbances, altered blood pH or dehydration should therefore be corrected when possible.
DRUG INTERACTIONS :
The following drugs have been shown to influence the magnitude and/or duration of action of non-depolarizing neuromuscular blocking agents.
Increased effect :
- Halogenated volatile anesthetics and ether; other nondepolarizing neuromuscular-blocking agents; high doses of Thiopental, Methohexital, Ketamine, Fentanyl, Gammahydroxybutyrate, Etomidate and Propofol; prior administration of Suxamethonium.
- Antibiotics : Aminoglycoside, Lincosamide and Polypeptide antibiotics, Acylamino-penicillin antibiotics, Tetracycline, high doses of Metronidazole.
- Diuretics, Thiamine, monoamine oxidase-inhibiting agents, Quinidine, Protamine, α-adrenergic-blocking agents, Magnesium salts, Calcium channel blocking agents, Lithium salts.
Decreased effect :
Neostigmin, Edrophonium, Pyridostigmine, Aminopyridine derivatives. Prior chronic administration of corticosteroids, Phenytoin or Carbamazepine. Noradrenaline, Azathioprine (only transient and limited effect), Theophylline, Calcium chloride, Potassium chloride.
ADVERSE REACTIONS :
Anaphylactic reactions
Although very rare, severe anaphylactic reactions to neuromuscular blocking agents, including Rocuronium bromide, have been reported. These reactions have, in some cases, been fatal. Due to the possible severity of these reactions, one should always assume that they may occur and take the necessary precautions.
Histamine release and histaminoid reactions
Since neuromuscular blocking agents are known to be capable of inducing histamine release both locally and systemically, the possible occurrence of itching and erythematous reactions at the site of injection and/or generalized histaminoid (anaphylactoid) reactions such as bronchospasm and cardiovascular changes e.g. hypotension and tachycardia should always be taken into consideration when administering these drugs.
Local injection site reactions
During rapid sequence induction of anesthesia, pain on injection has been reported, especially when the patient has not yet completely lost consciousness and particularly when Propofol is used as the induction agent.
Pregnancy and lactation
There are no data on the use of Rocuronium bromide during human pregnancy to assess potential harm to the fetus. Rocuronium bromide should be given to pregnant women only when the attending physician decides the outweigh the risks benefit.
In patients undergoing Cesarean section, Rocuronium bromide can be used as part of a rapid sequence induction technique, provided no intubation difficulties are anticipated and a sufficient dose of anesthetic agent is administered or following succinylcholine facilitated intubation. Rocuronium bromide, administered in doses of 0.6 mg per kg body weight, has been shown to be safe in parturients undergoing Cesarean Section.
Rocuronium bromide does not affect Apgar score, fetal muscle tone nor cardio respiratory adaptation. From umbilical cord blood sampling it is apparent that only limited placental transfer of Rocuronium bromide occurs which does not lead to the observation of clinical adverse effects in the newborn.
Note :
Doses of 1.0 mg.kg-1 have been investigated during rapid sequence induction of anesthesia, but not in Cesarean Section patients.
Reversal of neuromuscular block induced by neuromuscular blocking agents may be inhibited or unsatisfactory in patients receiving magnesium salts for toxemia of pregnancy because magnesium salts enhance neuromuscular blockade. Therefore, in these patients the dosage of Rocuronium bromide should be reduced and be titrated to twitch response.
Rocuronium bromide should be given to lactating women only when the attending physician decides that the benefits outweigh the risks.
Effects on the ability to drive and use machines
It is not recommended to use potentially dangerous machinery or drive a car within 24 hours after the full recovery from the neuromuscular blocking action or Rocuronium bromide.
PRESENTATION :
Belnium® Injection 50 mg/5 ml Box, 1 vial @ 5 ml Reg. No. DKL1202346043A1
STORAGE :
KEEP IN REFRIGERATOR (2 – 8)°C, PROTECT FROM LIGHT AND NO FREEZING
ON MEDICAL PRESCRIPTION ONLY
Manufactured by :
BERNOFARM
Sidoarjo – Indonesia
