Rocuronium Bromide 50 Mg/5 Ml Solution

ROCURONIUM BROMIDE INJECTION, 50 mg/5 mL RBC is indicated as an adjunct to general anaesthesia to facilitate tracheal intubation during routine and rapid sequence induction, and to provide skeletal muscle relaxation during surgery. ROCURONIUM BROMIDE INJECTION, 50 mg/5 mL RBC is also indicated as an adjunct in the Intensive Care Unit to facilitate intubation and mechanical ventilation for up to 3 days in adults 18 to 65 years.

Dosage: ROCURONIUM BROMIDE INJECTION, 50 mg/5 mL RBC should only be administered by, or under supervision of, experienced doctors who are familiar with the action and use of these medicines. The dosage 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 medication that is administered concomitantly, and the condition of the patient should be considered when determining the dose. The use of an appropriate neuromuscular monitoring technique is recommended for the evaluation of neuromuscular block and recovery. Inhalational anaesthetics potentiate the neuromuscular blocking effects of ROCURONIUM BROMIDE INJECTION, 50 mg/5 mL RBC. Potentiation, however, becomes clinically relevant during anaesthesia, when the volatile agents have reached the tissue concentrations required for this interaction. Consequently, adjustments with ROCURONIUM BROMIDE INJECTION, 50 mg/5 mL RBC should be made by administering smaller maintenance doses at less frequent intervals or by using lower infusion rates of ROCURONIUM BROMIDE INJECTION, 50 mg/5 mL RBC during long lasting procedures (longer than 1 hour) under inhalational anaesthesia (see u201csection 4.5u201d). Risk of Medication Errors: Accidental administration of neuromuscular blocking agents may result in serious adverse events, including fatal outcomes. Store ROCURONIUM BROMIDE INJECTION, 50 mg/5 mL RBC with the cap and ferrule intact and in a manner that minimizes the possibility of selecting the wrong product (see u201csection 4.4u201d). In adult patients the following dosage recommendations serve as a general guideline for tracheal intubation and muscle relaxation for short to long lasting surgical procedures and for use in the Intensive Care Unit.

Hypersensitivity to rocuronium or to the bromide ion or to any of the excipients. There is insufficient data to support recommendations for the use of ROCURONIUM BROMIDE INJECTION 50 mg/5 mL RBC in neonates (0 to 1 month). ROCURONIUM BROMIDE INJECTION 50 mg/5 mL RBC is not recommended for the facilitation of mechanical ventilation in the intensive care in paediatric and elderly patients due to a lack of data on safety and efficacy. Safety in pregnancy and lactation has not been demonstrated (see u201csection 4.6u201d).

Since ROCURONIUM BROMIDE INJECTION 50 mg/5 mL RBC causes paralysis of the respiratory muscles, ventilatory support is mandatory for patients treated with this medicine 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 neuromuscular blockade has been reported for ROCURONIUM BROMIDE INJECTION 50 mg/5 mL RBC. To prevent complications resulting from residual neuromuscular blockade, it is recommended to extubate only after the patient has recovered sufficiently from neuromuscular block. Elderly patients (65 years or older) may be at increased risk for residual neuromuscular block. Other factors which could cause residual neuromuscular blockade 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 (such as sugammadex or cetylcholinesterase inhibitors) should be considered, especially in those cases where residual neuromuscular blockade is more likely to occur. High rates of cross-sensitivity between neuromuscular blocking agents have been reported. Therefore, where possible, before administering ROCURONIUM BROMIDE INJECTION 50 mg/5 mL RBC, hypersensitivity to other neuromuscular blocking agents should be excluded. ROCURONIUM BROMIDE INJECTION 50 mg/5 mL RBC should only be used when absolutely essential in susceptible patients. Patients who experience a hypersensitivity reaction under general anaesthesia should be tested subsequently for hypersensitivity to other neuromuscular blockers. Rocuronium may increase the heart rate. 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 block and/or overdosage 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, neuromuscular blocking agents 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. Myopathy after long-term administration of other non-depolarising 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. If suxamethonium is used for intubation, the administration of ROCURONIUM BROMIDE INJECTION 50 mg/5 mL RBC should be delayed until the patient has clinically recovered from the neuromuscular block induced by suxamethonium. Because rocuronium bromide is always used with other medicines and because of the risk of malignant hyperthermia during anesthesia, even in the absence of known triggering factors, physicians should be aware of the early symptoms, confirmatory diagnosis, and treatment of malignant hyperthermia prior to the start of anesthesia. Animal studies have shown that rocuronium bromide is not a triggering factor for malignant hyperthermia. Rare cases of malignant hyperthermia with ROCURONIUM BROMIDE INJECTION 50 mg/5 mL RBC have been observed thru post-marketing surveillance; however, the causal association has not been proven. The following conditions may influence the pharmacokinetics and/or pharmacodynamics of ROCURONIUM BROMIDE INJECTION 50 mg/5 mL RBC: Hepatic and/or biliary tract disease and renal failure. Because rocuronium is excreted in urine and bile, 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 action has been observed with doses of 0.6 mg/kg rocuronium bromide. 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. The duration of action may also be prolonged due to a reduced plasma clearance. Neuromuscular disease. Like other neuromuscular blocking agents, ROCURONIUM BROMIDE INJECTION 50 mg/5 mL RBC 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 INJECTION 50 mg/5 mL RBC may have profound effects and ROCURONIUM BROMIDE INJECTION 50 mg/5 mL RBC should be titrated to the response. Hypothermia. In surgery under hypothermic conditions, the neuromuscular blocking effect of ROCURONIUM BROMIDE INJECTION 50 mg/5 mL RBC is increased and the duration prolonged. Obesity. Like other neuromuscular blocking agents, ROCURONIUM BROMIDE INJECTION 50 mg/5 mL RBC 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-depolarising neuromuscular blocking agents. It is recommended that the dose is titrated to response. Conditions which may increase the effects of ROCURONIUM BROMIDE INJECTION 50 mg/5 mL RBC. Hypokalaemia (e.g., after severe vomiting, diarrhoea, and diuretic therapy), hypermagnesaemia, hypocalcaemia (after massive transfusions), hypoproteinaemia, dehydration, acidosis, hypercapnia, cachexia. Severe electrolyte disturbances altered blood pH or dehydration should therefore be corrected when possible. Excipients with known effect. Sodium. This medicine contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially 'sodium-free'.

The following medicines have been shown to influence the magnitude and/or duration of action of non-depolarising neuromuscular blocking agents. Effect of other medicines on ROCURONIUM BROMIDE INJECTION 50 mg/5 mL RBC. Increased effect: u2022 Halogenated volatile anaesthetics potentiate the neuromuscular block of ROCURONIUM BROMIDE INJECTION 50 mg/5 mL RBC. The effect only becomes apparent with maintenance dosing (see section 4.2). Reversal of the block with acetylcholinesterase inhibitors could also be inhibited. u2022 After intubation with suxamethonium (see section 4.4). u2022 Long-term concomitant use of corticosteroids and ROCURONIUM BROMIDE INJECTION 50 mg/5 mL RBC in the ICU may result in prolonged duration of neuromuscular block or myopathy (see sections 4.4 and 4.8). Other medicines: u2022 Antibiotics: aminoglycoside, lincosamide and polypeptide antibiotics, acylamino-penicillin antibiotics. u2022 Diuretics, quinidine and its isomer quinine, magnesium salts, calcium channel blocking agents, lithium salts, local anaesthetics (lidocaine (lignocaine) i.v, bupivacaine epidural) and acute administration of phenytoin or B-blocking agents. Recurarisation has been reported after post-operative administration of aminoglycoside, lincosamide, polypeptide and acylamino-penicillin antibiotics, quinidine, quinine and magnesium salts (see section 4.4). Decreased effect: u2022 Prior chronic administration of phenytoin or carbamazepine. u2022 Calcium chloride, potassium chloride. u2022 Protease inhibitors (gabexate, ulinastatin). Variable effect: u2022 Administration of other non-depolarising neuromuscular blocking agents in combination with ROCURONIUM BROMIDE INJECTION 50 mg/5 mL RBC may produce attenuation or potentiation of the neuromuscular block, depending on the order of administration and the neuromuscular blocking agent used. u2022 Suxamethonium given after the administration of ROCURONIUM BROMIDE INJECTION 50 mg/5 mL RBC may produce potentiation or attenuation of the neuromuscular blocking effect of ROCURONIUM BROMIDE INJECTION 50 mg/5 mL RBC. Effect of ROCURONIUM BROMIDE INJECTION 50 mg/5 mL RBC on other medicines. ROCURONIUM BROMIDE INJECTION 50 mg/5 mL RBC combined with lidocaine (lignocaine) may result in a quicker onset of action of lidocaine (lignocaine). Paediatric population. No formal interaction studies have been performed. The above-mentioned interactions for adults (see section 4.4) should be considered for paediatric 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. Safety in pregnancy has not yet been demonstrated. Caesarean section. In patients undergoing Caesarean section, ROCURONIUM BROMIDE INJECTION 50 mg/5 mL RBC can be used as part of a rapid sequence induction technique, provided no intubation difficulties are anticipated and a sufficient dose of anaesthetic agent is administered or following suxamethonium facilitated intubation. However, ROCURONIUM BROMIDE INJECTION 50 mg/5 mL RBC, administered in doses of 0,6 mg/kg may not produce adequate conditions for intubation until 90 seconds after administration. This dose has been shown to be safe in parturient undergoing Caesarean section. ROCURONIUM BROMIDE INJECTION 50 mg/5 mL RBC does not affect Apgar score, foetal muscle tone or 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. Note 1: doses of 1,0 mg/kg have been investigated during rapid sequence induction of anaesthesia, but not in Caesarean 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 INJECTION 50 mg/5 mL RBC 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. Insignificant levels of rocuronium bromide were found in the milk of lactating rats. There are no human data on the use of ROCURONIUM BROMIDE INJECTION 50 mg/5 mL RBC during lactation. Safety in breastfeeding has not been established.

Since ROCURONIUM BROMIDE INJECTION 50 mg/5 mL RBC is used as an adjunct to general anaesthesia, the usual precautionary measures after a general anaesthesia should be taken for ambulatory patients.

{Frequency to change to Frequent, Less frequent and Frequency unknown}. Adverse reactions frequency is defined using the following convention: Frequent - Very common (u22641/10); common (u22641/100 to <1/10); Less frequent - uncommon (u22641/1,000 to <1/100); rare (u22641/10,000 to<1/1,000); very rare (<1/10,000); Frequency not known - (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 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.

SYSTEM ORGAN CLASS Immune system disorders Hypersensitivity Anaphylactic reaction Anaphylactoid reaction Anaphylactic shock Anaphylactoid shock Less frequent Nervous system disorders Flaccid paralysis Less frequent Cardiac disorders Tachycardia Less frequent Kounis syndrome Frequency not known Vascular disorders Hypotension Frequent Circulatory collapse and shock Flushing Less frequent Respiratory, Thoracic, and mediastinal disorders: Bronchospasm Less frequent Skin and subcutaneous tissue disorders Angioneurotic oedema Urticaria Rash Erythematous rash Less frequent Musculoskeletal and connective tissue disorders Muscular weakness Steroid myopathy Less frequent General disorders and administration site conditions: Medicine ineffective Medicine effect/ therapeutic response decreased Medicine effect/ therapeutic response increased Injection site pain Injection site reaction Malignant hypothermia Frequent Face oedema Less frequent Injury, poisoning, and procedural complications Prolonged neuromuscular block Delayed recovery from anaesthesia Frequent Airway complication of anesthesia Less frequent Anaphylaxis Although very rare, severe anaphylactic reactions to neuromuscular blocking agents, including ROCURONIUM BROMIDE INJECTION 50 mg/5 mL RBC, 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 they may occur and take the necessary precautions.

In the event of overdosage and prolonged neuromuscular block, the patient should continue to receive ventilatory support and sedation. At the start of spontaneous recovery an acetylcholinesterase inhibitor (e.g., neostigmine, edrophonium, pyridostigmine) should be administered in adequate doses. When administration of an acetylcholinesterase inhibiting agent fails to reverse the neuromuscular effects of ROCURONIUM BROMIDE INJECTION 50 mg/5 mL RBC, 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 ED 90 (135 mg/kg rocuronium bromide) was administered. Further treatment is symptomatic and supportive.