Each ml of solution for injection / infusion contains 10 mg rocuronium bromide.
Each vial with 5 ml contains 50 mg rocuronium bromide.
pH of the solution: 3.8 to 4.2.
Osmolarity: 271 - 312 mOsmol/l.
Excipients/Inactive Ingredients: Also contains sodium chloride, sodium acetate trihydrate, glacial acetic acid, water for injections.
Rocuronium Kabi is indicated in adult and paediatric patients (from term neonates to adolescents (0 to < 18 years) as an adjunct to general anaesthesia to facilitate tracheal intubation during routine sequence induction and to provide skeletal muscle relaxation, during surgery. In adults Rocuronium Kabi is also indicated to facilitate tracheal intubation during rapid sequence induction and as an adjunct in the intensive care unit (ICU) (e.g. to facilitate intubation), for short term use.
As with other neuromuscular blocking agents, the dosage of rocuronium bromide should be individualised in each patient. The method of anaesthesia and the expected duration of surgery, the method of sedation and the expected duration of mechanical ventilation, the possible interaction with other medicinal products 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 the neuromuscular block and recovery.
Inhalational anaesthetics potentiate the neuromuscular blocking effects of rocuronium bromide. This potentiation becomes clinically relevant during the course of anaesthesia when a certain tissue concentration of the volatile agents is reached. Consequently, adjustments should be made by administering smaller maintenance doses at less frequent intervals or by using lower infusion rates of rocuronium bromide during long lasting procedures (longer than 1 hour) under inhalational anaesthesia.
In adult patients the following dosage recommendations may serve as a general guidance for tracheal intubation and muscle relaxation for short to long lasting surgical procedures and for use in the intensive care unit.
This medicinal product is for single use only.
Surgical Procedures: Tracheal intubation: The standard intubating dose during routine anaesthesia is 0.6 mg rocuronium bromide per kg body weight, which results in adequate intubation conditions within 60 seconds in nearly all patients. A dose of 1.0 mg rocuronium bromide per kg body weight is recommended for facilitating tracheal intubation conditions during rapid sequence induction of anaesthesia, after which adequate intubation conditions are also established within 60 seconds in nearly all patients. If a dose of 0.6 mg rocuronium bromide per kg body weight is used for rapid sequence induction of anaesthesia, it is recommended to intubate the patient 90 seconds after administration of rocuronium bromide.
Maintenance dosage: The recommended maintenance dose is 0.15 mg rocuronium bromide per kg body weight. In case of long-term inhalational anaesthesia it should be reduced to 0.075 - 0.1 mg of rocuronium bromide per kg body weight.
The maintenance doses should best be given when twitch height has recovered to 25 % of control twitch height, or when 2 to 3 responses to train-of-four stimulation (TOF) are present.
Continuous infusion: If rocuronium bromide is administered by continuous infusion, it is recommended to give a loading dose of 0.6 mg rocuronium bromide per kg body weight and, when the 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 anaesthesia, the infusion rate required to maintain the neuromuscular block at this level ranges from 0.3 - 0.6 mg/kg/h. Under inhalational anaesthesia the infusion rate ranges from 0.3 - 0.4 mg/kg/h.
Continuous monitoring of the neuromuscular block is essential since infusion rate requirements vary from patient to patient and with the anaesthetic method used.
Dosage in pregnant patients: In patients undergoing Caesarean section, it is recommended to only use a dose of 0.6 mg rocuronium bromide per kg body weight, since a 1.0 mg/kg dose has not been investigated in this patient group.
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 should be reduced and be titrated to twitch response.
Paediatric population: For neonates (0-28 days), infants (28 days to ≤ 3 months), toddlers (> 3 months to ≤ 2 years), children (2-11 years), and adolescents (12 to ≤ 17 years) the recommended intubation dose during routine anaesthesia and maintenance dose are similar to those in adults. However, the duration of action of the single intubating dose will be longer in neonates and infants than in children.
For continuous infusion in pediatrics, the infusion rates, with exception of children, are the same as for adults. For children higher infusion rates might be necessary.
Thus, for children the same initial infusion rates as for adults are recommended and this should be adjusted to maintain twitch response at 10 % of control twitch height or to maintain 1 or 2 responses to train-of-four stimulation during the procedure.
The experience with rocuronium bromide in rapid sequence induction in paediatric patients is limited. Rocuronium bromide is therefore not recommended for facilitation tracheal intubation conditions during rapid sequence induction in paediatric patients.
Dosage 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 anaesthesia is 0.6 mg rocuronium bromide per kg body weight. A dose of 0.6 mg per kg body weight should be considered for rapid sequence induction of anaesthesia in patients in which a prolonged duration of action is expected however adequate conditions for intubation may not be established for 90 seconds after administration of rocuronium bromide. Regardless of the anaesthetic technique used, the recommended maintenance dose for these patients is 0.075 - 0.1 mg rocuronium bromide per kg body weight, and the recommended infusion rate is 0.3 - 0.4 mg/kg/h (see also Continuous infusion as previously mentioned).
Dosage 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.
Intensive care procedures: Tracheal intubation: For tracheal intubation, the same doses should be used as previously described under Surgical Procedures.
Administration: Rocuronium bromide is administered intravenously (i.v.) either as a bolus injection or as a continuous infusion (for further information see also Pharmaceutical precautions under Cautions for Usage).
In the event of overdose and prolonged neuromuscular block, the patient should continue to receive ventilatory support and sedation. There are two options for the reversal of neuromuscular block: (1) In adults, sugammadex can be used for reversal of intense (profound) and deep block. The dose of sugammadex to be administered depends on the level of neuromuscular block.
(2) An acetylcholinesterase inhibitor (e.g. neostigmine, edrophonium, pyridostigmine) or sugammadex can be used once spontaneous recovery starts and should be administered in adequate doses. When administration of an acetylcholinesterase inhibiting agent fails to reverse the neuromuscular effects of rocuronium bromide ventilation must be continued until spontaneous breathing is restored. Repeated dosage of an acetylcholinesterase inhibitor can be dangerous.
In animal studies, severe depression of cardiovascular function, ultimately leading to cardiac collapse, did not occur until a cumulative dose of 750 x ED90 (135 mg per kg body weight) was administered.
Rocuronium bromide is contra-indicated in patients with hypersensitivity to rocuronium bromide or to the bromide ion or to any of the excipients.
Rocuronium bromide should be administered only by an experienced staff familiar with the use of neuromuscular blocking agents. Adequate facilities and staff for endotracheal intubation and artificial ventilation have to be available for immediate use.
Since rocuronium bromide causes paralysis of the respiratory muscles, ventilatory support is mandatory for patients treated with this active substance until adequate spontaneous respiration is restored. As with all neuromuscular blocking agents, it is important to anticipate intubation difficulties, particularly when used as part of a rapid sequence induction technique.
As with other neuromuscular blocking agents, residual curarization has been reported for Rocuronium. In order to prevent complications resulting from residual curarization, it is recommended to extubate only after the patient has recovered sufficiently from neuromuscular block. Other factors which could cause residual curarization after extubation in the post-operative phase (such as drug interactions or patient condition) should also be considered. If not used as part of standard clinical practice, the use of a reversal agent should be considered, especially in those cases where residual curarization is more likely to occur.
It is essential to ensure that the patient is breathing spontaneously, deeply and regularly before leaving the theatre after anaesthesia.
Anaphylactic reactions (see previously mentioned) can occur after the administration of neuromuscular blocking agents. Precautions for treating such reactions should always be taken. Particularly in the case 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 higher than 0.9 mg rocuronium bromide per kg body weight may increase the heart rate; this effect could counteract the bradycardia produced by other anaesthetic agents or by vagal stimulation.
In general, following long term use of neuromuscular blocking agents in the ICU, prolonged paralysis and/or skeletal muscle weakness has been noted. In order to help preclude possible prolongation of neuromuscular blockage and/or overdose, it is strongly recommended that neuromuscular transmission is monitored throughout the use of neuromuscular blocking agents. In addition, patients should receive adequate analgesia and sedation. Furthermore, muscle relaxants should be titrated to the effect in the individual patient. This should be done by or under the supervision of experienced clinicians who are familiar with the effects and with appropriate neuromuscular monitoring techniques.
Because rocuronium bromide is always used with other agents and because of the possibility of the occurrence of malignant hyperthermia during anaesthesia, even in the absence of known triggering agents, clinicians should be familiar with the early signs, confirmatory diagnosis and treatment of malignant hyperthermia prior to the start of any anaesthesia. In animal studies it was shown that rocuronium bromide is not a triggering factor for malignant hyperthermia.
Myopathy after long term administration of other non-depolarizing neuromuscular blocking agents in the ICU in combination with corticosteroid therapy has been reported regularly. Therefore, for patients receiving both neuromuscular blocking agents and corticosteroids, the period of use of the neuromuscular blocking agent should be limited as much as possible.
Rocuronium should only be administered after full recovery from the neuromuscular blockade caused by suxamethonium.
The following conditions may influence the pharmacokinetics and/or pharmacodynamics of rocuronium bromide: Hepatic and/or biliary tract disease and renal failure: Rocuronium bromide is excreted in urine and bile. Therefore, it should be used with caution in patients with clinically significant hepatic and/or biliary diseases and/or renal failure. In these patient groups prolongation of the effect 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 diseases, old age and an oedematous state resulting in an increased volume of distribution, may contribute to a slower onset of the effect. The duration of action may also be prolonged due to a reduced plasma clearance.
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 the response.
Conditions which may increase the effects of rocuronium bromide: Hypokalaemia (e.g. after severe vomiting, diarrhoea or diuretic therapy), hypermagnesaemia, hypocalcaemia (after massive transfusions), hypoproteinaemia, dehydration, acidosis, hypercapnia and cachexia.
Severe electrolyte disturbances, altered blood pH or dehydration should therefore be corrected when possible.
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially 'sodium- free'.
Effects on ability to drive and use machines: Since rocuronium bromide is used as an adjunct to general anesthesia, the usual precautionary measures after a general anesthesia should be taken for ambulatory patients.
Pregnancy: For rocuronium bromide, no clinical data on exposed pregnancies are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development.
Caution should be exercised when prescribing rocuronium bromide to pregnant women.
Cesarean section: 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 suxamethonium facilitated intubation. Rocuronium bromide, administered in doses of 0.6 mg/kg, has been shown to be safe in parturients undergoing Cesarean section. Rocuronium bromide does not affect Apgar score, foetal muscle tone nor cardiorespiratory 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 infant.
Note 1: doses of 1.0 mg/kg have been investigated during rapid sequence induction of anaesthesia, but not in Cesarean section patients. Therefore, only a dose of 0.6 mg/kg is recommended in this patient group.
Note 2: 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.
Breast-feeding: It is unknown whether rocuronium bromide is excreted in human breast milk. Animal studies have shown insignificant levels of rocuronium bromide in breast milk.
Rocuronium bromide should be given to lactating women only when the attending physician decides that the benefits outweigh the risks.
The most commonly occurring adverse drug reactions include injection site pain/reaction, changes in vital signs and prolonged neuromuscular block. The most frequently reported serious adverse drug reactions during post-marketing surveillance is 'anaphylactic and anaphylactoid reactions' and associated symptoms. See also the explanations following the table. (See table.)
Click on icon to see table/diagram/image
Although very rare, severe anaphylactic reactions to neuromuscular blocking agents, including rocuronium bromide, have been reported. Anaphylactic/anaphylactoid reactions are: bronchospasm, cardiovascular changes (e.g. hypotension, tachycardia, circulatory collapse - shock), and cutaneous changes (e.g. angioedema, urticaria). 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.
Local injection site reactions:
During rapid sequence induction of anaesthesia, 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. In clinical studies, pain on injection has been noted in 16 % of the patients who underwent rapid sequence induction of anaesthesia with propofol and in less than 0.5 % of the patients who underwent rapid sequence induction of anaesthesia with fentanyl and thiopental.
Increased histamine level:
Since neuromuscular blocking agents are known to be capable of inducing histamine release both locally and systemically, the possible occurrence of itching and erythematous reaction at the site of injection and/or generalised histaminoid (anaphylactoid) reactions such as bronchospasm and cardiovascular changes e.g. hypotension and tachycardia should always be taken into consideration when administering these drugs. Rash, exanthema, urticaria, bronchospasm and hypotension have been reported very rarely in patients given rocuronium bromide.
In clinical studies only a slight increase in mean plasma histamine level has been observed following rapid bolus administration of 0.3 - 0.9 mg rocuronium bromide per kg body weight.
Prolonged neuromuscular block:
The most frequent adverse reaction to non-depolarizing blocking agents as a class consists of an extension of the agent's pharmacological action beyond the time period needed. This may vary from skeletal muscle weakness to profound and prolonged skeletal muscle paralysis resulting in respiratory insufficiency or apnoea.
Myopathy has been reported after the use of various neuromuscular blocking agents in the ICU in combination with corticosteroids (see Precautions).
A meta-analysis of 11 clinical studies in paediatric patients (n=704) with rocuronium bromide (up to 1 mg/kg) showed that tachycardia was identified as adverse drug reaction with a frequency of 1.4 %.
The following medicinal products have been shown to influence the magnitude and/or duration of the effect of non-depolarizing neuromuscular blocking agents: Increased effect: Halogenated volatile anaesthetics potentiate the neuromuscular block of rocuronium bromide. The effect only becomes apparent with maintenance dosing (see Dosage & Administration). Reversal of the block with acetylcholinesterase inhibitors could also be inhibited.
After intubation with suxamethonium (see Precautions).
High doses of: thiopental, methohexital, ketamine, fentanyl, gammahydroxybutyrate, etomidate and propofol.
Other non-depolarizing neuromuscular blocking agents.
Prior administration of suxamethonium (see Precautions).
Long term concomitant use of corticosteroids and Rocuronium in the ICU may result in prolonged duration of neuromuscular block or myopathy (see Precautions and Adverse Reactions).
Other medicinal products: Antibiotics: aminoglycosides, lincosamides (e.g. lincomycin and clindamycin), polypeptide antibiotics, acylamino-penicillin antibiotics, tetracyclines, high doses of metronidazole; Diuretics, thiamine, MAO inhibiting agents, quinidine and its isomer quinine, protamine, adrenergic blocking agents; Magnesium salts, calcium channel blocking agents, lithium salts, local anaesthetics (lidocaine i.v., bupivacaine epidural) and acute administration of phenytoin or β-blocking agents.
Recurarization has been reported after post-operative administration of: aminoglycoside, lincosamide, polypeptide and acylamino-penicillin antibiotics, quinidine, quinine and magnesium salts (see Precautions).
Decreased effect: Neostigmine, edrophonium, pyridostigmine, aminopyridine derivatives; Prior chronic administration of corticosteroids, phenytoin or carbamazepine; Noradrenaline, azathioprine (only transient and limited effect), theophylline, calcium chloride, potassium chloride; protease inhibitors (gabexate, ulinastatin).
Variable effect: Administration of other non-depolarizing neuromuscular blocking agents in combination with rocuronium bromide may produce attenuation or potentiation of the neuromuscular block, depending on the order of administration and the neuromuscular blocking agent used.
Suxamethonium given after the administration of rocuronium bromide may produce potentiation or attenuation of the neuromuscular blocking effect of rocuronium bromide.
Effect of rocuronium bromide on other medicinal products: Rocuronium bromide combined with lidocaine may result in a quicker onset of action of lidocaine.
Paediatric patients: No formal interaction studies have been performed. The previously mentioned interactions for adults and their special warnings and precautions for use (see Precautions) should also be taken into account for paediatric patients.
Pharmaceutical precautions: Any unused solutions should be discarded.
The solution is to be visually inspected prior to use. Only clear solutions practically free from particles should be used.
Rocuronium has shown to be compatible with: sodium chloride 9 mg/ml (0.9 %) and glucose 50 mg/ml (5 %) solution for infusion.
If rocuronium bromide is administered via the same infusion line with other medicinal products, it is important that the infusion line is adequately flushed (e.g. with sodium chloride 9 mg/ml (0.9 %) solution for infusion) between administration of rocuronium bromide and medicinal products for which incompatibility with rocuronium bromide has been demonstrated or for which compatibility with rocuronium bromide has not been established.
Any unused product or waste material should be disposed of in accordance with local requirements.
Incompatibilities: Physical incompatibility has been documented for rocuronium bromide when added to solutions containing the following active substances: amphotericin, amoxicillin, azathioprine, cefazolin, cloxacillin, dexamethasone, diazepam, enoximone, erythromycin, famotidine, furosemide, hydrocortisone sodium succinate, insulin, intralipid, methohexital, methylprednisolone, prednisolone sodium succinate, thiopental, trimethoprim and vancomycin.
This medicinal product must not be mixed with other medicinal products except those previously mentioned in Pharmaceutical precautions.
Store in a refrigerator (2 °C - 8 °C).
After dilution: Chemical and physical in-use stability of a 5.0 mg/ml and 0.1 mg/ml solution has been demonstrated for 24 hours at room temperature exposed to room light in glass, PE and PVC when diluted with sodium chloride 9 mg/ml (0.9 %) and glucose 50 mg/ml (5 %) solution for infusion, and in PP and PE when diluted with Ringer's Lactate solution for infusion.
From the microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8 °C, unless dilution has taken place in controlled and validated aseptic conditions.
M03AC09 - rocuronium bromide ; Belongs to the class of other quaternary ammonium-containing agents used as peripherally-acting muscle relaxants.
Soln for inj/infusion (vial) 50 mg/5 mL (clear, colourless to pale brownish-yellow solution) x 10's.