Esmeron50 mg/5 ml

Rocuronium is indicated - As an adjunct to general anesthesia to facilitate tracheal intubation during routine induction, and during rapid sequence induction when suxamethonium is contraindicated To provide skeletal muscle relaxation during surgery As an adjunct in the intensive care unit (ICU) to facilitate intubation and mechanical ventilation

Non depolarizing muscle relaxants

Rocuronium acts by competing for cholinergic receptors at the motor end-plate. This action is antagonized by acetylcholinesterase inhibitors, such as neostigmine and edrophonium. Rocuronium acts by competitively binding to nicotinic cholinergic receptors. The binding of vecuronium decreases the opportunity for acetylcholine to bind to the nicotinic receptor at the postjunctional membrane of the myoneural junction. As a result, depolarization is prevented, calcium ions are not released and muscle contraction does not occur. Evidence also suggests that nondepolarizing agents can affect ACh release. It has been hypothesized that nondepolarzing agents bind to postjunctional ("curare") receptors and may therefore interfere with the sodium and potassium flux, which is responsible for depolarization and repolarization of the membranes involved in muscle contraction.

Dosage: Like other neuromuscular blocking agents, Rocuronium should only be administered by, or under supervision of, experienced clinicians who are familiar with the action and use of these agents. The dosage of Rocuronium 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 medicines 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 anesthetics do potentiate the neuromuscular blocking effects of Rocuronium. 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 Rocuronium should be made by administering smaller maintenance doses at less frequent intervals or by using lower infusion rates of Rocuronium during long lasting procedures (longer than 1 hour) under inhalational anesthesia. In adult patients the following dosage recommendations may 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. Surgical Procedures: Tracheal Intubation: The standard intubating dose during routine anesthesia is 0.6mg Esmeron 50 mg/5 ml per kg body weight, after which adequate intubation conditions are established within 60 seconds in nearly all patients. A dose of 1.0mg Esmeron 50 mg/5 ml per kg body weight is recommended for facilitating tracheal intubation conditions during rapid sequence induction of anesthesia, after which adequate intubation conditions are also established within 60 seconds in nearly all patients. If a dose of 0.6mg Esmeron 50 mg/5 ml per kg body weight is used for rapid sequence induction of anesthesia, it is recommended to intubate the patient 90 seconds after administration of Esmeron 50 mg/5 ml. In patients undergoing Caesarean section it is recommended to only use a dose of 0.6mg Esmeron 50 mg/5 ml per kg body weight, since a 1.0mg/kg dose has not been investigated in this patient group. Maintenance Dosing: The recommended maintenance dose is 0.15mg Esmeron 50 mg/5 ml per kg body weight; in the case of long-term inhalational anesthesia this should be reduced to 0.075-0.1mg Esmeron 50 mg/5 ml per kg body weight. The maintenance doses should best be given when twitch height has recovered to 25% of control twitch height, or when 2-3 responses to train of four stimulation are present. Continuous Infusion: If Esmeron 50 mg/5 ml is administered by continuous infusion, it is recommended to give a loading dose of 0.6mg Esmeron 50 mg/5 ml 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 0.3-0.6mg/kg/hr and under inhalational anesthesia the infusion rate ranges from 0.3-0.4mg/kg/hr. Continuous monitoring of neuromuscular block is recommended since infusion rate requirements vary from patient to patient and with the anaesthetic method used. Dosing in Paediatric Patients: Children (1-14 years) and infants (1-12 months) under halothane anesthesia manifest similar sensitivity to Esmeron 50 mg/5 ml as adults. Onset of action is faster in infants and children than in adults. Clinical duration is shorter in children than in adults. For continuous infusion in paediatrics, the infusion rates, with exception of children, are the same as for adults. For children higher infusion rates might be necessary. 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. There are insufficient data to support dose recommendations for the use of Esmeron 50 mg/5 ml in neonates (0-1 month). The experience with Esmeron 50 mg/5 ml in rapid sequence induction in paediatric patients is limited. Esmeron 50 mg/5 ml is therefore not recommended for facilitating tracheal intubation conditions during rapid sequence induction in paediatric patients. 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 0.6mg Esmeron 50 mg/5 ml per kg body weight. A dose of 0.6mg 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 0.075-0.1mg Esmeron 50 mg/5 ml per kg body weight, and the recommended infusion rate is 0.3-0.4mg/kg/hr. 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 ideal body weight. Intensive Care Procedures (Tracheal Intubation): For tracheal intubation, the same doses should be used as described above under surgical procedures. Maintenance Dosing: The use of an initial loading dose of 0.6mg Esmeron 50 mg/5 ml 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 0.3-0.6mg/kg/hr 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 0.2-0.5mg/kg/hr 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. Special Populations: Esmeron 50 mg/5 ml is not recommended for the facilitation of mechanical ventilation in the intensive care in paediatric and geriatric patients due to a lack of data on safety and efficacy.

Dosage: Like other neuromuscular blocking agents, Rocuronium should only be administered by, or under supervision of, experienced clinicians who are familiar with the action and use of these agents. The dosage of Rocuronium 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 medicines 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 anesthetics do potentiate the neuromuscular blocking effects of Rocuronium. 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 Rocuronium should be made by administering smaller maintenance doses at less frequent intervals or by using lower infusion rates of Rocuronium during long lasting procedures (longer than 1 hour) under inhalational anesthesia. In adult patients the following dosage recommendations may 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. Surgical Procedures: Tracheal Intubation: The standard intubating dose during routine anesthesia is 0.6mg Esmeron 50 mg/5 ml per kg body weight, after which adequate intubation conditions are established within 60 seconds in nearly all patients. A dose of 1.0mg Esmeron 50 mg/5 ml per kg body weight is recommended for facilitating tracheal intubation conditions during rapid sequence induction of anesthesia, after which adequate intubation conditions are also established within 60 seconds in nearly all patients. If a dose of 0.6mg Esmeron 50 mg/5 ml per kg body weight is used for rapid sequence induction of anesthesia, it is recommended to intubate the patient 90 seconds after administration of Esmeron 50 mg/5 ml. In patients undergoing Caesarean section it is recommended to only use a dose of 0.6mg Esmeron 50 mg/5 ml per kg body weight, since a 1.0mg/kg dose has not been investigated in this patient group. Maintenance Dosing: The recommended maintenance dose is 0.15mg Esmeron 50 mg/5 ml per kg body weight; in the case of long-term inhalational anesthesia this should be reduced to 0.075-0.1mg Esmeron 50 mg/5 ml per kg body weight. The maintenance doses should best be given when twitch height has recovered to 25% of control twitch height, or when 2-3 responses to train of four stimulation are present. Continuous Infusion: If Esmeron 50 mg/5 ml is administered by continuous infusion, it is recommended to give a loading dose of 0.6mg Esmeron 50 mg/5 ml 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 0.3-0.6mg/kg/hr and under inhalational anesthesia the infusion rate ranges from 0.3-0.4mg/kg/hr. Continuous monitoring of neuromuscular block is recommended since infusion rate requirements vary from patient to patient and with the anaesthetic method used. Dosing in Paediatric Patients: Children (1-14 years) and infants (1-12 months) under halothane anesthesia manifest similar sensitivity to Esmeron 50 mg/5 ml as adults. Onset of action is faster in infants and children than in adults. Clinical duration is shorter in children than in adults. For continuous infusion in paediatrics, the infusion rates, with exception of children, are the same as for adults. For children higher infusion rates might be necessary. 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. There are insufficient data to support dose recommendations for the use of Esmeron 50 mg/5 ml in neonates (0-1 month). The experience with Esmeron 50 mg/5 ml in rapid sequence induction in paediatric patients is limited. Esmeron 50 mg/5 ml is therefore not recommended for facilitating tracheal intubation conditions during rapid sequence induction in paediatric patients. 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 0.6mg Esmeron 50 mg/5 ml per kg body weight. A dose of 0.6mg 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 0.075-0.1mg Esmeron 50 mg/5 ml per kg body weight, and the recommended infusion rate is 0.3-0.4mg/kg/hr. 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 ideal body weight. Intensive Care Procedures (Tracheal Intubation): For tracheal intubation, the same doses should be used as described above under surgical procedures. Maintenance Dosing: The use of an initial loading dose of 0.6mg Esmeron 50 mg/5 ml 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 0.3-0.6mg/kg/hr 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 0.2-0.5mg/kg/hr 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. Special Populations: Esmeron 50 mg/5 ml is not recommended for the facilitation of mechanical ventilation in the intensive care in paediatric and geriatric patients due to a lack of data on safety and efficacy.

The following agents have been shown to influence the magnitude and/or duration of action of non-depolarizing neuromuscular blocking agents: Effect of other agents on Esmeron 50 mg/5 ml- Increased Effect: Halogenated volatile anesthetics potentiate the neuromuscular block of Esmeron 50 mg/5 ml. The effect only becomes apparent with maintenance dosing. Reversal of the block with anti-cholinesterase inhibitors could also be inhibited. Long-term concomitant use of corticosteroids and Esmeron 50 mg/5 ml in the ICU may result in prolonged duration of neuromuscular block or myopathy.Other drugs:  Antibiotics: aminoglycoside, lincosamide and polypeptide antibiotics, acylamino-penicillin antibiotics.  Diuretics, quinidine and its isomer quinine, magnesium salts, calcium channel blocking agents, lithium salts, local anaesthetics (lidocaine i.v., bupivacaine epidural) and acute administration of phenytoin  Recurarization has been reported after post-operative administration of: aminoglycoside, lincosamide, polypeptide and acylamino-penicillin antibiotics, quinidine, quinine and magnesium. Decreased Effect: Prior chronic administration of phenytoin or carbamazepine. Protease inhibitors (gabexate, ulinastatin) Variable Effect: Administration of other non-depolarizing neuromuscular blocking agents in combination with Esmeron 50 mg/5 ml 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 Esmeron 50 mg/5 ml may produce potentiation or attenuation of the neuromuscular blocking effect of Esmeron 50 mg/5 ml. Effect of Esmeron 50 mg/5 ml on other drugs: Esmeron 50 mg/5 ml combined with lidocaine may result in a quicker onset of action of lidocaine.

Hypersensitivity to Rocuronium or to the Bromide ion or to any of the excipients.

In clinical trials, the most common adverse reactions (2%) are transient hypotension and hypertension. Other are: Anaphylaxis  Residual paralysis  Myopathy  Increased pulmonary vascular resistance Although very rare, severe anaphylactic reactions to neuromuscular blocking agents, including Esmeron 50 mg/5 ml, 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. Since neuromuscular blocking agents are known to be capable of inducing histamine release both locally at the site of injection and systemically, the possible occurrence of itching and erythematosus reactions at the site of injection and/or generalized histaminoid (anaphylactoid) reactions (see also under Anaphylactic Reactions above) should always be taken into consideration when administering these agents. In clinical studies only a slight increase in mean plasma histamine levels has been observed following rapid bolus administration of 0.3 0.9mg/kg Esmeron 50 mg/5 ml.Prolonged neuromuscular block: The most frequent adverse reaction to nondepolarizing 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: Myopathy has been reported after the use of various neuromuscular blocking agents in the ICU in combination with corticosteroids.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. In clinical studies, pain on injection has been noted in 16% of the patients who underwent rapid sequence induction of anesthesia with propofol and in less than 0.5% of the patients who underwent rapid sequence induction of anesthesia with fentanyl and thiopental.

Pregnancy: For Esmeron 50 mg/5 ml, 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 Esmeron 50 mg/5 ml to pregnant women.Caesarean section: In patients undergoing Caesarean section, Esmeron 50 mg/5 ml 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. Esmeron 50 mg/5 ml, administered in doses of 0.6mg/kg, has been shown to be safe in parturient undergoing Caesarean section. Esmeron 50 mg/5 ml does not affect Apgar score, foetal muscle tone nor cardio-respiratory adaptation. From umbilical cord blood sampling it is apparent that only limited placental transfer of Esmeron 50 mg/5 ml occurs which does not lead to the observation of clinical adverse effects in the newborn.Lactation: It is unknown whether Esmeron 50 mg/5 ml is excreted in human breast milk. Animal studies have shown insignificant levels of Esmeron 50 mg/5 ml in breast milk. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. Esmeron 50 mg/5 ml should be given to lactating women only when the attending physician decides that the benefits outweigh the risks.

Instructions for use/handling: Compatibility studies with the following infusion fluids have been performed. In nominal concentrations of 0.5mg/mL and 2.0mg/mL, Esmeron 50 mg/5 ml has been shown to be compatible with: 0.9% NaCl, 5% dextrose, 5% dextrose in saline, sterile water for injections, Lactated Ringers and Haemaccel. Administration should be commenced immediately after mixing, and should be completed within 24 hours. Unused solutions should be discarded.For use/handling: If Esmeron 50 mg/5 ml is administered via the same infusion line that is also used for other medicines, it is important that this infusion line is adequately flushed (e.g. with 0.9% NaCl) between administration of Esmeron 50 mg/5 ml and medicines for which incompatibility with Esmeron 50 mg/5 ml has been demonstrated or for which compatibility with Esmeron 50 mg/5 ml has not been established.

In the event of overdosage and prolonged neuromuscular block, the patient should continue to receive ventilatory support and sedation. In this situation there are two options for the reversal of neuromuscular block: Sugammadex can be used for reversal of intense (profound) and deep block. The dose of sugammadex to be administered depends of the level of neuromuscular block. An acetylcholinesterase inhibitor (e.g. neostigmine, edrophonium, pyridostigmine), with appropriate vagolytic (e.g atropine) can be used at reappearance of T2 or at the first signs of clinical recovery and should be administered in adequate doses. When administration of an acetylcholinesterase inhibiting agent fails to reverse the neuromuscular effects of Esmeron 50 mg/5 ml, ventilation must be continued until spontaneous breathing is restored. Repeated dosage of an acetylcholinesterase inhibitor can be dangerous.

Esmeron 50 mg/5 ml should be stored in the refrigerator at 2-8° C and not be frozen.

Non depolarizing muscle relaxants

Rocuronium acts by competing for cholinergic receptors at the motor end-plate. This action is antagonized by acetylcholinesterase inhibitors, such as neostigmine and edrophonium. Rocuronium acts by competitively binding to nicotinic cholinergic receptors. The binding of vecuronium decreases the opportunity for acetylcholine to bind to the nicotinic receptor at the postjunctional membrane of the myoneural junction. As a result, depolarization is prevented, calcium ions are not released and muscle contraction does not occur. Evidence also suggests that nondepolarizing agents can affect ACh release. It has been hypothesized that nondepolarzing agents bind to postjunctional ("curare") receptors and may therefore interfere with the sodium and potassium flux, which is responsible for depolarization and repolarization of the membranes involved in muscle contraction.

Pregnancy: For Esmeron 50 mg/5 ml, 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 Esmeron 50 mg/5 ml to pregnant women.Caesarean section: In patients undergoing Caesarean section, Esmeron 50 mg/5 ml 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. Esmeron 50 mg/5 ml, administered in doses of 0.6mg/kg, has been shown to be safe in parturient undergoing Caesarean section. Esmeron 50 mg/5 ml does not affect Apgar score, foetal muscle tone nor cardio-respiratory adaptation. From umbilical cord blood sampling it is apparent that only limited placental transfer of Esmeron 50 mg/5 ml occurs which does not lead to the observation of clinical adverse effects in the newborn.Lactation: It is unknown whether Esmeron 50 mg/5 ml is excreted in human breast milk. Animal studies have shown insignificant levels of Esmeron 50 mg/5 ml in breast milk. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. Esmeron 50 mg/5 ml should be given to lactating women only when the attending physician decides that the benefits outweigh the risks.