Active ingredients: Rocuronium bromide
Esmeron 10 mg / ml solution for injection for intravenous use
Why is Esmeron used? What is it for?
It is a medicine that contains rocuronium bromide an active substance that belongs to a class of medicines called muscle relaxants (medicines that make certain types of muscles relax).
Esmeron is indicated under general anesthesia to facilitate endotracheal intubation (during surgery, a tube is inserted into the trachea to facilitate artificial respiration and to obtain relaxation of certain types of muscles.Artificial respiration replaces natural respiration when this is no longer performed spontaneously) in adult and pediatric patients (from term infants to adolescents, aged 0 to less than 18 years). Furthermore, in adults the use of Esmeron is also indicated in intensive care units (ICU) to facilitate endotracheal intubation.
Contraindications When Esmeron should not be used
Do not use Esmeron if you are allergic to rocuronium bromide, bromide ions or any of the other ingredients of this medicine (listed in section 6).
Precautions for use What you need to know before taking Esmeron
At the end of the procedure, the anesthetist will let the effect of Esmeron subside and you will be able to breathe on your own.
Talk to your doctor or nurse before you are given this medicine
- if you are allergic to any muscle relaxant medicine
- if you have kidney, liver or biliary tract disease (which are used to carry bile)
- if you have heart disease or a disease affecting blood circulation
- if one or more areas of your body are swollen from fluid accumulation (for example in the ankles)
- if you have had neuromuscular diseases (diseases affecting both the nerves and the muscles they control), poliomyelitis (inflammation of the spinal cord caused by a virus that causes a form of paralysis), myasthenia gravis (a disease characterized by lack of strength in the muscles) , Eaton-Lambert syndrome (disease characterized by lack of muscle strength, impotence, styspsis and the formation of small blisters on the hands and feet)
- if you have ever had episodes of too low body temperature during anesthesia (hypothermia)
- if you are overweight - if you have burns
- if you have a low level of calcium in the blood (hypocalcaemia)
- if you have a low level of potassium in the blood (hypokalaemia)
- if you have a high level of magnesium in your blood (hypermagnesemia)
- if you have a low level of protein in the blood (hypoproteinaemia)
- if you have dehydration (the amount of water that is lost is greater than that which is consumed)
- if you have an increase in the amount of acids in your blood (acidosis)
- if you have an increase in the amount of carbon dioxide in your blood (hypercapnia)
- if you have excessive weight loss (cachexia).
If you have any of the conditions described above, your doctor will take them into account when determining the right dose of Esmeron for you.
Children and adolescents
Esmeron can be used in children (term infants and adolescents) however the anesthetist should review the medical history.
Interactions Which drugs or foods can modify the effect of Esmeron
Tell your doctor or nurse if you are taking, have recently taken or might take any other medicines. The following medicines have an influence on the effect and / or duration of action of Esmeron.
Medicines that increase the effect of Esmeron:
- inhaled anesthetics such as halothane, ether, enflurane, methoxyflurane, and cyclopropane
- suxamethonium, a muscle relaxant medicine
- corticosteroids (anti-inflammatory medicines). Long-term concomitant use of corticosteroids and Esmeron in intensive care units may induce myopathy (muscle disease) or prolongation of the muscle relaxation effect (see sections 2 and 4).
- high doses of some types of anesthetics such as thiopental, metoesital, ketamine, fentanyl, gamma-hydroxy-butyrate, ethomidate, and propofol
- other muscle relaxants
- other medicines:
- antibiotics (used to treat infections), such as aminoglycosides, lincosamides, polypeptides and acylaminopenicillins, tetracyclines, high doses of metronidazole
- diuretics (used to increase the amount of urine produced)
- thiamine (important for cell functions)
- medicines for depression called mono amino oxidase inhibitors (MAOIs)
- quinidine (used to treat heart disease and to regulate high blood pressure)
- quinine (medicine used to treat fever, pain and malaria)
- protamine (medicine used to treat bleeding)
- adrenergic blocking medicines, calcium channel blockers (medicines used to regulate high blood pressure)
- magnesium salts (laxatives)
- lithium salts (antidepressants)
- some anesthetics for local use (lidocaine, bupivacaine).
Medicines that decrease the effect of Esmeron:
- neostigmine, edrophonium (used to reactivate muscle function), previous chronic administration of corticosteroids
- antiepileptic medicines (phenytoin or carbamazepine)
- norepinephrine which is also used to increase muscle tone (the state of mild and persistent muscle contraction, present in normal conditions), azathioprine (medicine used in immune system alterations that give rise to direct responses against components of your body)
- theophylline (medicine used in the treatment of asthma)
- calcium chloride, potassium chloride
- protease inhibitors (medicines that fight HIV viruses).
Variable effect
- Administration of muscle relaxants in combination with Esmeron may decrease or increase muscle blockage depending on the order in which they are administered and the type of muscle relaxant used.
- Administration of suxamethonium after that of Esmeron can enhance or weaken muscle relaxation.
- The combination of Esmeron and lidocaine may influence the effect of lidocaine. No interaction studies (studies with medicines affecting the effect and duration of action of this medicine) have been conducted. The interactions of Esmeron with other medicines reported for adults (see "Other medicines and Esmeron") and the warnings and precautions listed above (see "Warnings and precautions"), should also be considered for children and adolescents.
Warnings It is important to know that:
Pregnancy, breastfeeding and fertility
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before being given this medicine.
There are no clinical trial data on the use of rocuronium bromide in pregnancy or in women of childbearing potential.
Caution is needed when prescribing Esmeron to pregnant women.
It is not known whether Esmeron is excreted in human milk.
Esmeron should only be given to women who are breastfeeding if the treating doctor considers that the benefits outweigh the risks.
Caesarean section
In patients undergoing caesarean section, Esmeron can be used during anesthesia.
The doctor will assess the best dose based on the patient's condition.
Driving and using machines
Do not use potentially dangerous machinery and do not drive before 24 hours have elapsed after complete recovery of muscle activity. Esmeron contains sodium This medicine contains less than 1 mmol (23 mg) sodium per 5 ml and per 10 ml ie, it is practically " sodium-free ".
Dosage and method of use How to use Esmeron: Dosage
This medicine will be given to you by an anesthetist or an experienced doctor who knows how Esmeron works and how to use it.
As with other muscle relaxants, the dosage of Esmeron must be established on a case-by-case basis, based on several factors such as: the type of anesthesia and the expected duration of the operation, the method of sedation (a state in which the patient does not completely lose consciousness) and the expected duration of artificial respiration, possible interaction with other medicinal products and the patient's condition.
Esmeron will be given to you as an intravenous bolus (single injection) or as a continuous infusion.
Use in children and adolescents
For infants (0-27 days), infants (28 days-2 months), toddlers (3-23 months), children (2-11 years) and adolescents (12-17 years) the recommended dose for endotracheal intubation during anesthesia and the maintenance dose (dose necessary to maintain the therapeutic effect) are similar to those recommended for adults.
However, the duration of action of the single dose for endotracheal intubation will be longer in neonates and infants than in children.
Overdose What to do if you have taken too much Esmeron
If you use more Esmeron than you should
Your anesthetist will closely monitor you when you are under the effects of Esmeron, so it is unlikely that you will be given too much Esmeron. However, if this happens, the relaxation of your muscles may increase. In this case, the anesthetist may give you medicines to cancel this effect and will ensure that the anesthesia and artificial respiration are continued until you are able to breathe on your own again.
If you have any further questions on the use of this medicine, ask your doctor or nurse.
Side Effects What are the side effects of Esmeron
Like all medicines, this medicine can cause side effects, although not everybody gets them.
The most commonly observed side effects include pain and / or reactions at the injection site and prolonged muscle blockage.
The most frequently reported serious side effects are allergic reactions (anaphylactic and anaphylactoid reactions).
Below is detailed information on side effects:
Uncommon (may affect up to 1 in 100 people) / Rare (may affect up to 1 in 1,000 people):
- tachycardia (increased heart rate)
- hypotension (low blood pressure)
- drug ineffectiveness, decreased therapeutic response, increased therapeutic response, injection site pain, injection site allergic reactions
- neuromuscular block (blocking the transmission of impulses from the nerve to the muscle) prolonged, delayed awakening from anesthesia
Very rare (may affect up to 1 in 10,000 people)
- hypersensitivity, allergic reactions (anaphylactic reaction, anaphylactic shock, anaphylactoid shock)
- flaccid paralysis (loss of normal muscle tone)
- circulatory collapse and shock (insufficient blood circulation throughout the body with a noticeable lowering of blood pressure), hot flashes
- bronchospasm (difficulty in breathing due to narrowing of the bronchi)
- angioneurotic edema (swelling of the skin, mucosa and submucosal tissues, of allergic origin), urticaria, dermatitis, erythematous rash (allergic skin reactions)
- muscle weakness, steroid myopathy (a pathological condition affecting the skeletal muscles caused by corticosteroid medicines)
- face edema (swelling of the face)
- breathing problems during anesthesia
Additional side effects in children
An "analysis of 11 clinical studies conducted in pediatric patients (n = 704) treated with rocuronium bromide (up to 1 mg / kg) found, as an undesirable effect to the drug, tachycardia which occurs with a frequency of 1" , 4%.
Reporting of side effects
If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at: www.agenziafarmaco.gov.it/ it / responsible. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label after EXP. The expiry date refers to the last day of that month.
The expiry date indicated refers to the product in intact packaging, correctly stored.
Do not use this medicine if you notice visible signs of deterioration.
After opening the vial, the solution is chemically stable for 24 hours at room temperature.
Since Esmeron does not contain preservatives, it is recommended not to use the remaining solution.
Esmeron must be stored in the dark and at a temperature between 2 ° and 8 ° C.
Esmeron can be stored at 8 ° to 30 ° C for 3 months before its expiration.
Deadline "> Other information
What Esmeron contains
Active ingredient: rocuronium bromide. 1 ml of Esmeron contains 10 mg of rocuronium bromide.
The other ingredients are: sodium acetate, sodium chloride, acetic acid and water for injections.
Description of what Esmeron looks like and contents of the pack
Solution for injection for intravenous use.
Packs
- 12 vials of 5 ml of 10 mg / ml solution;
- 10 vials of 5 ml of 10 mg / ml solution;
- 10 vials of 10 ml of 10 mg / ml solution.
Not all pack sizes may be marketed.
Deadline "> Information for healthcare professionals
The following information is intended for healthcare professionals only:
Warnings and Precautions
Since Esmeron causes paralysis of the respiratory muscles, artificial ventilation is essential for patients treated with this medicine until spontaneous breathing is restored. As with all muscle relaxants, it is important to anticipate any difficulties with intubation, especially if the drug is used as part of a rapid sequence induction technique.
In case of intubation difficulties characterized by the clinical need for immediate reversal of neuromuscular block induced by rocuronium, the use of sugammadex should be considered.
Cases of residual recurarization have been reported with Esmeron as with other muscle relaxants. In order to avoid the complications deriving from a "possible residual curarization, it is recommended to extubate the patient only after he has sufficiently recovered from the neuromuscular block. Geriatric patients (aged 65 years and over) may present an increased risk of residual neuromuscular block. Other factors should also be considered (eg drug interactions or patient condition) that could cause residual recurarization after postoperative extubation. If not already part of normal clinical practice, consider the use of antagonizing agents (such as sugammadex or acetylcholinesterase inhibitors), especially where residual curarization is more likely to occur.
Anaphylactic reactions may occur following the administration of muscle relaxants. Necessary precautions should always be taken to treat such reactions. Particularly in the case of previous anaphylactic reactions to muscle relaxants, special precautions should be taken as cases of cross allergy to muscle relaxants have been reported.
In general, prolonged paralysis and / or weakness of skeletal muscles have been observed following long-term administration of muscle relaxants in the intensive care unit. In order to avoid possible prolongation of neuromuscular block and / or overdose, monitoring of neuromuscular transmission is recommended during administration of muscle relaxants. Patients should also receive adequate analgesia and sedation. The dose of muscle relaxants should then be titrated to individual response by or under the supervision of an experienced physician who is familiar with the action of such medicinal products and appropriate neuromuscular monitoring techniques.
The onset of myopathy has been regularly reported following long-term administration of other non-depolarising muscle relaxants in the intensive care unit in combination with corticosteroid therapy.
Therefore, in patients treated with corticosteroids and muscle relaxants, the period of use of the latter should be limited as much as possible. If suxamethonium is used for intubation, administration of Esmeron should be postponed until the patient has clinically recovered from suxamethonium-induced neuromuscular blockade.
The pharmacokinetic and / or pharmacodynamic properties of Esmeron can be affected by the following conditions:
Diseases of the liver and / or biliary tract and renal insufficiency
Since rocuronium is excreted in the urine and bile, it should be used with caution in patients with clinically significant hepatic and / or biliary disease and / or with renal insufficiency. In these patients, prolongation of the action of rocuronium bromide was observed with doses from 0.6 mg / kg body weight.
Extended circulation time
Conditions associated with prolonged circulation time such as cardiovascular disease, old age and oedematous state which lead to an increase in the volume of distribution, may contribute to a prolongation of the latency time. Duration of action may also be prolonged due to reduced plasma clearance.
Neuromuscular diseases
Like other muscle relaxants, Esmeron should be used with extreme caution in patients with neuromuscular disease or after poliomyelitis, as the response to muscle relaxants can be considerably impaired in these cases.
The amplitude and orientation of this alteration can vary greatly. Since in patients with myasthenia gravis or myasthenic syndrome (Eaton-Lambert), administration of small doses of Esmeron can produce a profound effect, the medicinal product should be titrated according to the response obtained.
Hypothermia
During surgery in hypothermic conditions, the neuromuscular blocking effect induced by Esmeron increases in intensity and duration.
Obesity
Like other muscle relaxant medicinal products, Esmeron may induce prolongation of the duration of action and spontaneous recovery time in obese patients when the administered doses are calculated on the basis of actual body weight.
Burns
Since burn patients may develop resistance to nondepolarizing muscle relaxants, titration based on observed response is recommended.
Conditions that can increase the effects of Esmeron
Hypokalaemia (e.g. after severe vomiting, diarrhea and diuretic therapy), hypermagnesemia, hypocalcemia (after massive transfusions), hypoproteinemia, dehydration, acidosis, hypercapnia, cachexia. It is therefore necessary to correct, if possible, serious states of electrolyte imbalance, alteration of blood pH or dehydration.
Other medicines and Esmeron
The following medicinal products have an "influence" on the intensity and / or duration of action of non-depolarising muscle relaxants.
Effect of other medicinal products on Esmeron
Increased effect
- Anesthetics: Halothane, ether, enflurane, methoxyflurane, cyclopropane. Volatile halogenated anesthetics potentiate Esmeron-induced neuromuscular blockade. The effect becomes evident only with maintenance doses. It is also possible that the antagonizing action of the blockade of acetylcholinesterase inhibitors is inhibited.
- After intubation with suxamethonium.
- Long-term concomitant use of corticosteroids and Esmeron in intensive care units may lead to myopathy or prolongation of the duration of neuromuscular block.
- High doses of thiopental, methoesital, ketamine, fentanyl, gamma hydroxybutyrate, ethomidate and propofol.
- Other non-depolarizing neuromuscular blocking agents.
- Other Medicines
- Antibiotics: aminoglycosides, lincosamides, polypeptides and acylaminopenicillins, tetracyclines, high doses of metronidazole.
- Diuretics, thiamine, MAO-inhibitory medicinal products, quinidine and its quinine isomer, protamine, adrenergic blocking medicinal products, magnesium salts, calcium channel blockers, lithium salts, local anesthetics (IV lidocaine, epidural bupivacaine) and acute administration of phenytoin and ß -blockers.
There have been reports of recurarisation following postoperative administration of quinidine, quinine, magnesium salts and the following antibiotics: aminoglycosides, lincosamides, polypeptides and acylaminopenicillins.
Decreased effect
- Neostigmine, edrophonium, pyridostigmine, aminopyridine derivatives.
- Previous 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
- The administration of other non-depolarizing muscle relaxants in combination with Esmeron may induce the attenuation or enhancement of neuromuscular block depending on the order in which they are administered and the type of muscle relaxant used.
- Subsequent administration of suxamethonium to Esmeron may result in the enhancement or attenuation of the neuromuscular blocking effect induced by Esmeron.
Effect of Esmeron on other medicinal products
The combination of Esmeron and lidocaine can induce a reduction in the latency time of lidocaine.
Pediatric patients
No formal interaction studies have been conducted. Interactions for adults and related warnings and precautions should also be considered for pediatric patients.
Pregnancy and breastfeeding
Pregnancy
No clinical data on exposure to rocuronium bromide in pregnancy are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal / fetal development, parturition or postnatal development.
Caution is needed when prescribing Esmeron to pregnant women.
Caesarean section
In patients undergoing caesarean section, Esmeron can be used as part of the rapid sequence induction technique, provided that intubation difficulties are not expected and that a sufficient dose of anesthetic is administered or after intubation after administration of suxamethonium. Esmeron, given in doses of 0.6 mg / kg body weight, has been shown to be safe in pregnant women undergoing caesarean section. Esmeron does not affect Apgar score, fetal muscle tone or cardiorespiratory adaptation. The umbilical cord blood test indicates that rocuronium bromide crosses the placenta only minimally without giving rise to any observable adverse clinical effects on the newborn.
Note 1: Doses of 1.0 mg / kg body weight have been studied in rapid sequence induction of anesthesia, but not in patients undergoing caesarean section. Therefore, in this category of patients it is recommended to use only a dose of 0.6 mg / kg body weight.
Note 2: The reversibility of neuromuscular block induced by muscle relaxants may be inhibited or unsatisfactory in patients treated with magnesium salts for toxemia gravidarum, since magnesium salts increase neuromuscular block. Therefore, the dose of Esmeron should be reduced and carefully adjusted in relation to the response to stimulation in these patients.
Feeding time
It is not known whether Esmeron is excreted in human milk. Animal studies have found insignificant concentrations of Esmeron in the mother's milk. Animal studies do not reveal direct or indirect harmful effects with respect to pregnancy, embryonal / fetal development, parturition or postnatal development.
Esmeron should only be given to women who are breastfeeding if the treating doctor believes that the benefits outweigh the risks.
Posology and method of administration
As with other muscle relaxants, the dosage of Esmeron must be determined on a case-by-case basis. In determining the dose, the type of anesthesia, 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 patient's condition should be considered.
The use of an appropriate neuromuscular monitoring technique is recommended to monitor neuromuscular block and recovery.
Inhalation anesthetics potentiate the effects of Esmeron-induced neuromuscular blockade.
However, this potentiation becomes clinically relevant during the course of anesthesia, when the volatile substances have reached the tissue concentrations necessary for this interaction. Consequently, dose adjustments with Esmeron should be made by administering smaller maintenance doses at less frequent intervals or by using lower infusion rates in case of long-term interventions (over 1 hour) under inhalation anesthesia.
In adults the following recommended doses can be used as a general guide for endotracheal intubation, for myorelaxation in short to long duration interventions and for use in intensive care units.
Surgical interventions
Endotracheal intubation
The standard dose for intubation during standard anesthesia is 0.6 mg / kg body weight of rocuronium bromide which in almost all patients is sufficient to establish suitable conditions for intubation within 60 seconds.
To facilitate endotracheal intubation during rapid sequence induction of anesthesia, a dose of 1.0 mg / kg body weight of rocuronium bromide is recommended, which in almost all patients is sufficient to establish conditions within 60 seconds. suitable for intubation. If rocuronium bromide is administered at a dose of 0.6 mg / kg body weight for the induction of rapid sequence anesthesia, it is recommended to wait 90 seconds before intubating the patient.
High doses
Should the administration of higher doses of rocuronium bromide be necessary in particular patients, it is good to know that initial doses up to 2 mg / kg of body weight were administered during the operation without any adverse cardiovascular effects being observed. The use of high dosages of rocuronium bromide reduces the onset time and extends the duration of action.
Maintenance doses
The recommended maintenance dose is 0.15 mg / kg body weight of rocuronium bromide; in case of long-term inhalation anesthesia, the dose should be reduced to 0.075-0.1 mg / kg body weight. Maintenance doses should be given when the amplitude of the stimulus response has returned to 25% of the control value, or when 2 or 3 train of four responses (TOF) are present.
Continuous infusion
If rocuronium bromide is administered as a continuous infusion, it is recommended to give a loading dose of 0.6 mg / kg body weight and, at the first signs of recovery from neuromuscular block, to start administration by infusion. The rate of infusion should be adjusted to maintain the amplitude of the neuromuscular response at 10% of the control value or to maintain 1 or 2 responses to TOF stimulation. In adults, the infusion rate required to maintain neuromuscular block at these levels ranges from 0.3 to 0.6 mg / kg body weight under intravenous anesthesia and from 0.3 to 0.4 mg / kg. of body weight in the case of inhalation anesthesia.
Continuous monitoring of neuromuscular block is recommended, as the rate of infusion varies from patient to patient and depending on the technique used for anesthesia.
Pediatric patients
For infants (0-27 days), infants (28 days-2 months), toddlers (3 months-23 months), children (2-11 years) and adolescents (12-17 years) the dose recommended for intubation during standard anesthesia and the maintenance dose are similar to those recommended for adults.
However, the duration of action of the single dose for intubation will be longer in neonates and infants than in children.
For continuous infusion in pediatrics, except in the case of children (2-11 years), the infusion rates are the same as those used for adults.
For children 2 to 11 years of age, higher infusion rates may be required.
In the case of children (2-11 years) it is therefore recommended to start with the same initial infusion rate used for adults and then to adjust it subsequently in order to maintain the amplitude of the neuromuscular response at 10% of the control value or to maintain 1 or 2 responses to TOF stimulation during surgery.
In pediatric patients, the experience with rocuronium bromide for the induction of rapid sequence anesthesia is limited. In this category of patients the use of rocuronium bromide is therefore recommended to facilitate endotracheal intubation during induction in quick sequence.
Geriatric patients and patients with liver and / or biliary tract disease and / or renal insufficiency
The standard dose for intubation of geriatric patients and those with hepatic and / or biliary disease and / or renal insufficiency during routine anesthesia is 0.6 mg / kg body weight of rocuronium bromide. In the case of rapid sequence induction of anesthesia in patients expected to have a prolonged duration of action, a dose of 0.6 mg / kg body weight should be considered. Regardless of the technique used for anesthesia, the recommended maintenance dose for this category of patients is 0.075-0.1 mg / kg body weight of rocuronium bromide, with an infusion rate of 0.3- 0.4 mg / kg of body weight.
Overweight and obese patients
When the medicine is used in overweight or obese patients (defined as patients with a body weight of 30% or more of the ideal body weight), the dosage should be reduced taking into account the ideal body weight.
Intensive Care Procedures
Endotracheal intubation
As regards endotracheal intubation, refer to the same doses indicated above for surgical interventions.
Maintenance dose
An initial loading dose of rocuronium bromide of 0.6 mg / kg body weight is recommended, followed by continuous infusion as soon as the amplitude of response returns to 10% or from the time of reappearance of 1 or 2 responses to TOF stimulation.
Dosage should always be titrated in relation to the effect observed in each individual patient. In adult patients, the recommended initial infusion rate for maintenance of neuromuscular block is 80-90% (presence of 1 or 2 responses to TOF stimulation). ) is 0.3-0.6 mg / kg body weight for the first hour of administration, and should then be reduced over the next 6-12 hours based on individual response. After this period, the individual dose required remains relatively constant in each patient.
From controlled clinical studies, a marked individual variability of the hourly rate of infusion emerged, which varies on average from 0.2 to 0.5 mg / kg of body weight depending on the nature and extent of organ failure (i ), concomitantly administered medicinal products and individual patient characteristics. To ensure optimal patient control, monitoring of neuromuscular transmission is strongly recommended. Administration for up to 7 days has been studied.
Special patient populations
Esmeron is not indicated to facilitate mechanical ventilation in the ICU in pediatric and geriatric patients, as there is a lack of safety and efficacy data.
Side effects
The most commonly observed adverse drug reactions include pain and / or injection site reactions, altered vital signs and prolonged muscle block.
The reports of serious adverse reactions most frequently received by the pharmacovigilance system concern anaphylactic and anaphylactoid reactions and their associated symptoms.
Anaphylaxis
Although very rare, severe anaphylactic reactions to muscle relaxants, including Esmeron, have been reported. Anaphylactic / anaphylactoid reactions are: bronchospasm, cardiovascular changes (eg hypotension, tachycardia, circulatory collapse - shock) and skin changes (eg angioedema, urticaria). These reactions have in some cases been fatal.
Given the possible severity of these reactions, the possibility of their occurrence must always be taken into account and all necessary precautions taken.
Since muscle relaxants can induce histamine release both locally at the injection site and systemically, when administering these medicinal products, the possible occurrence of itching and erythematous reactions at the injection site and / or generalized histaminoid (anaphylactoid) reactions (see also what has been said above about anaphylactic reactions).
In clinical studies, only a slight increase in mean plasma histamine values was observed following rapid bolus administration of 0.3-0.9 mg / kg body weight of rocuronium bromide.
Prolonged neuromuscular block
The most frequent adverse reaction of the class of non-depolarizing muscle relaxants is the prolongation of the pharmacological action of the compound beyond the necessary period of time. The effects can range from weakness of the skeletal muscles to a profound and prolonged paralysis of the same which can induce respiratory failure. or apnea.
Myopathy
Cases of myopathy have been reported following the use of various muscle relaxant medicinal products in the ICU in combination with corticosteroids (see "Precautions for use").
Local reactions at the injection site
During the induction of anesthesia in rapid sequence, pain at the injection site has been reported, especially in cases where the patient had not yet completely lost consciousness and in particular when propofol was used for the induction. In clinical studies, Injection site pain was seen in 16% of patients undergoing rapid sequence induction of anesthesia with propofol, and in less than 0.5% of patients undergoing rapid sequence induction of anesthesia with fentanyl and thiopental.
Overdose
In the event of overdose and prolonged neuromuscular block, the patient should remain on controlled ventilation and under sedation. In this situation there are two options for reversal of neuromuscular block: 1) in adults, sugammadex can be used for reversal of intense and deep block. The dose of sugammadex to be administered depends on the level of neuromuscular block; 2) an acetylcholinesterase inhibitor (neostigmine, edrophonium, pyridostigmine) or sugammadex can be used at the first signs of spontaneous recovery in adequate doses.
If administration of anticholinesterases fails to reverse the neuromuscular effects of Esmeron, ventilation should be continued until spontaneous breathing is resumed. Repeated administration of acetylcholinesterase inhibitors can be dangerous. In animal studies, severe depression of cardiovascular function, resulting in heart failure, was observed only after administration of a cumulative dose of 750 X ED90 (135 mg / kg body weight of rocuronium bromide).
Instructions for use and handling
Compatibility studies have been performed with the following infusion fluids. In nominal concentrations of 0.5 mg / ml and 2.0 mg / ml Esmeron was found to be compatible with:
- 0.9% NaCl
- 5% dextrose
- 5% dextrose in physiological solution
- Water for injections
- Lactated Ringer's solution
- Haemaccel.
The solutions must be used within 24 hours and immediately after mixing them.
Discard the unused solution.
Incompatibility
Physical incompatibility has been documented when Esmeron is added to solutions containing the following medicinal products: amphotericin, amoxicillin, azathioprine, cefazoline, cloxacillin, dexamethasone, diazepam, enoximone, erythromycin, famotidine, furosemide, hydrocortisone sodium succinate, insulin, metoesitalolone, metoesitalolone succinate, thiopental, trimethoprim and vancomycin. Esmeron is also incompatible with Intralipid.
Esmeron must never be mixed with medicinal products other than those listed in the "Instructions for use and handling" section. If Esmeron is administered in the same infusion line as other medicinal products it is important that the infusion line is adequately washed (for example with 0.9% NaCl) between the administration of Esmeron and that of medicinal products whose incompatibility with Esmeron has already been demonstrated or whose compatibility with Esmeron has not yet been established.
Do not throw any medicines via wastewater or household waste. This will help protect the environment.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT -
ESMERON 10 MG / ML SOLUTION FOR INJECTION FOR INTRAVENOUS USE
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -
1 ml of Esmeron contains 10 mg of rocuronium bromide.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM -
Solution for injection for intravenous use (pH 3.8-4.2).
04.0 CLINICAL INFORMATION -
04.1 Therapeutic indications -
Esmeron is indicated in adult and pediatric patients (from full-term neonates to adolescents [0 to skeletal muscle during surgery. In adults, Esmeron is also indicated to facilitate endotracheal intubation during rapid sequence induction and as an adjuvant. in the Intensive Care Unit (ICU) to facilitate intubation and mechanical ventilation.
04.2 Posology and method of administration -
As with other muscle relaxants, the administration of Esmeron should only be practiced or supervised by an experienced doctor who is familiar with the action and how to use these medicines.
As with other muscle relaxants, the dosage of Esmeron must be determined on a case-by-case basis. In determining the dose, the type of anesthesia, 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 patient's condition should be considered.
The use of an appropriate neuromuscular monitoring technique is recommended to assess neuromuscular block and recovery.
Inhalation anesthetics potentiate the neuromuscular blocking effect induced by Esmeron.
However, this potentiation becomes clinically relevant during the course of anesthesia, when the volatile substances have reached the tissue concentrations necessary for this interaction. Consequently, dose adjustments with Esmeron should be made by administering smaller maintenance doses at less frequent intervals or by using lower infusion rates in case of long-term interventions (over 1 hour) under inhalation anesthesia (see section 4.5).
In adults, the following recommended doses can be used as a general guide for endotracheal intubation, for myorelaxation in short to long duration interventions and for use in ICUs.
Surgical interventions
Endotracheal intubation
The standard dose for intubation during standard anesthesia is 0.6 mg / kg body weight of rocuronium bromide which in almost all patients is sufficient to establish suitable conditions for intubation within 60 seconds. to facilitate endotracheal intubation during the induction of anesthesia in rapid sequence, a dose of 1.0 mg / kg body weight of rocuronium bromide is recommended, which in almost all patients is sufficient to establish suitable conditions within 60 seconds for intubation. If rocuronium bromide at a dose of 0.6 mg / kg body weight is administered for the induction of rapid sequence anesthesia, it is recommended to wait 90 seconds before intubating the patient.
For the use of rocuronium bromide during the induction of rapid sequence anesthesia in patients undergoing caesarean section, see section 4.6.
High doses
Should the administration of higher doses of rocuronium bromide be necessary in particular patients, it is good to know that initial doses up to 2 mg / kg of body weight were administered during the operation without any adverse cardiovascular effects being observed. The use of high dosages of rocuronium bromide reduces the latency time and prolongs the duration of action (see paragraph 5.1).
Maintenance doses
The recommended maintenance dose is 0.15 mg / kg body weight of rocuronium bromide; in case of long-term inhalation anesthesia, the dose should be reduced to 0.075-0.1 mg / kg body weight. Maintenance doses should be administered when the amplitude of the response to neuromuscular stimulation has returned to 25% of the control value, or when 2 or 3 responses to train of four stimulation (TOF) are present.
Continuous infusion:
If rocuronium bromide is administered as a continuous infusion, it is recommended to give a loading dose of 0.6 mg / kg body weight and, at the first signs of recovery from neuromuscular block, to start administration by infusion. The rate of infusion should be adjusted to maintain the magnitude of the neuromuscular response at 10% of the control value or to maintain 1 or 2 responses to TOF stimulation. In adults, the rate of infusion necessary to maintain neuromuscular block at these levels, it ranges from 0.3 to 0.6 mg / kg of body weight. h-1 in the case of intravenous anesthesia and from 0.3 to 0.4 mg / kg of body weight. h-1 in the case of anesthesia inhalation.
Continuous monitoring of neuromuscular block is recommended, as the rate of infusion varies from patient to patient and depending on the technique used for anesthesia.
Pediatric population
For infants (0-27 days), infants (28 days-2 months), toddlers (3-23 months), children (2-11 years) and adolescents (12-17 years) the recommended dose for intubation during standard anesthesia and the maintenance dose are similar to those recommended for adults.
However, the duration of action of the single dose for intubation will be longer in neonates and infants than in children (see section 5.1).
For continuous infusion in pediatrics, except in the case of children (2-11 years), the infusion rates are the same as those used for adults. For children 2 to 11 years of age, higher infusion rates may be required.
In the case of children (2-11 years) it is therefore recommended to start with the same initial infusion rate used for adults and then to adjust it subsequently in order to maintain the amplitude of the neuromuscular response at 10% of the control value or to maintain 1 or 2 responses to TOF stimulation during surgery.
In pediatric patients, the experience with rocuronium bromide for the induction of rapid sequence anesthesia is limited. In this category of patients, therefore, the use of rocuronium bromide is not recommended to facilitate endotracheal intubation during induction in quick sequence.
Geriatric patients and patients with liver and / or biliary tract disease and / or renal insufficiency
The standard dose for intubation of geriatric patients and those with hepatic and / or biliary disease and / or renal insufficiency during routine anesthesia is 0.6 mg / kg body weight of rocuronium bromide. In the case of rapid sequence induction of anesthesia in patients expected to have a prolonged duration of action, a dose of 0.6 mg / kg body weight should be considered. Regardless of the technique used for anesthesia, the recommended maintenance dose for this category of patients is 0.075-0.1 mg / kg body weight of rocuronium bromide, with an infusion rate of 0.3-0. , 4 mg / kg body weight h-1 (see Continuous infusion) (See also section 4.4).
Overweight and obese patients
When the medicine is used in overweight or obese patients (defined as patients with a body weight of more than 30% above ideal), the dosage should be reduced taking into account the ideal body weight.
Intensive Care Procedures
Endotracheal intubation
As regards endotracheal intubation, refer to the same doses indicated above for surgical interventions.
Maintenance doses
An initial loading dose of rocuronium bromide of 0.6 mg / kg body weight is recommended, followed by continuous infusion as soon as the amplitude of response returns to 10% or from the time of reappearance of 1 or 2 responses to TOF stimulation. Dosage should always be titrated in relation to the effect observed in each individual patient. In adult patients, the recommended initial infusion rate for maintenance of neuromuscular block is 80-90% (presence of 1 or 2 responses to TOF stimulation). ) is 0.3-0.6 mg / kg body weight. h-1 for the first hour of administration, and should then be reduced over the next 6-12 hours based on individual response. After this period, the individual dose required remains relatively constant in each individual patient.
From controlled clinical trials a marked individual variability of the hourly rate of infusion has emerged, which varies on average from 0.2 to 0.5 mg / kg of body weight. H-1 depending on the nature and extent of the "insufficiency d" organ (s), concomitantly administered medicinal products and individual patient characteristics. Monitoring of neuromuscular transmission is strongly recommended to ensure optimal patient control. Administration for up to 7 days has been studied.
Special patient populations
Esmeron is not indicated to facilitate mechanical ventilation in the ICU in pediatric and geriatric patients, as there is a lack of data on safety and efficacy.
Method of administration
Esmeron is administered intravenously either as a bolus or as a continuous infusion (see section 6.6).
04.3 Contraindications -
Hypersensitivity to rocuronium, bromide ions or to any of the excipients listed in section 6.1.
04.4 Special warnings and appropriate precautions for use -
Since Esmeron causes paralysis of the respiratory muscles, artificial respiration is essential for patients treated with this medicine until spontaneous respiration is restored. As with all muscle relaxants, it is important to anticipate any intubation difficulties, especially if the drug is used as part of a rapid sequence induction technique. In case of intubation difficulties characterized by clinical need for immediate reversal of the induced neuromuscular block from rocuronium, the use of sugammadex should be considered.
Cases of residual curarization have been reported with Esmeron as with other muscle relaxants. In order to avoid the complications deriving from a "possible residual curarization, it is recommended to extubate the patient only after he has sufficiently recovered from the neuromuscular block. Geriatric patients (aged 65 years and over) may present an increased risk of residual neuromuscular block.
It is also necessary to consider other factors (for example, any drug interactions or the patient's condition) that can cause residual curarization after extubation in the postoperative phase. If not already part of normal clinical practice, consider use antagonizing agents (such as sugammadex or acetylcholinesterase inhibitors), especially where residual curarization is more likely to occur.
Anaphylactic reactions may occur following the administration of muscle relaxants. Necessary precautions should always be taken to treat such reactions. Particularly in the case of previous anaphylactic reactions to muscle relaxants, special precautions should be taken as cases of cross allergy to muscle relaxants have been reported.
In general, prolonged paralysis and / or weakness of skeletal muscles have been observed following long-term administration of muscle relaxants in the ICU. In order to avoid possible prolongation of neuromuscular block and / or overdose, monitoring of neuromuscular transmission is recommended during administration of muscle relaxants. Patients should also receive adequate analgesia and sedation. The dose of muscle relaxants should then be titrated to individual response by or under the supervision of an experienced physician who is familiar with the action of such medicinal products and appropriate neuromuscular monitoring techniques.
The onset of myopathy has been regularly reported following long-term administration of other non-depolarising muscle relaxants in the ICU, in association with corticosteroid therapy. Therefore, in patients treated with corticosteroids and muscle relaxants, it should be limited as much as possible. the period of use of the latter.
If suxamethonium is used for intubation, administration of Esmeron should be postponed until the patient has clinically recovered from suxamethonium-induced neuromuscular blockade.
The pharmacokinetic and / or pharmacological properties of Esmeron can be affected by the following conditions:
Diseases of the liver and / or biliary tract and renal insufficiency
Since rocuronium is excreted in the urine and bile, it should be used with caution in patients with clinically significant hepatic and / or biliary disease and / or with renal insufficiency. Prolongation of the action of rocuronium bromide was observed in these patients with doses of 0.6 mg / kg body weight.
Extended circulation time
Conditions associated with prolonged circulation time such as cardiovascular disease, old age and oedematous state which lead to an increase in the volume of distribution, may contribute to a prolongation of the latency time. Duration of action may also be prolonged due to reduced plasma clearance.
Neuromuscular diseases
Like other muscle relaxants, Esmeron should be used with extreme caution in patients with neuromuscular disease or after poliomyelitis, as the response to muscle relaxants can be considerably impaired in these cases. The amplitude and orientation of this alteration can vary greatly. Since in patients with myasthenia gravis or myasthenic syndrome (Eaton-Lambert), administration of small doses of Esmeron can produce a profound effect, the medicinal product should be titrated according to the response obtained.
Hypothermia
During surgery in hypothermic conditions, the neuromuscular blocking effect induced by Esmeron increases in intensity and duration.
Obesity
Like other muscle relaxant medicinal products, Esmeron may induce prolongation of the duration of action and spontaneous recovery time in obese patients when the administered doses are calculated on the basis of actual body weight.
Burns
Since burn patients may develop resistance to nondepolarizing muscle relaxants, titration based on observed response is recommended.
Conditions that can increase the effects of Esmeron
Hypokalaemia (e.g. after severe vomiting, diarrhea and diuretic therapy), hypermagnesemia, hypocalcemia (after massive transfusions), hypoproteinemia, dehydration, acidosis, hypercapnia, cachexia.
It is therefore necessary to correct, if possible, serious states of electrolyte imbalance, alteration of blood pH or dehydration.
Important information about some of the ingredients of Esmeron:
This medicinal product contains less than 1 mmol (23 mg) sodium per 5 ml and per 10 ml ie, it is essentially "sodium free".
04.5 Interactions with other medicinal products and other forms of interaction -
The following medicinal products have been shown to have an "influence on the intensity and / or duration of action of non-depolarising muscle relaxant medicinal products:
Effect of other medicinal products on Esmeron
Enhancement of the effect
• Anesthetics: halothane, ether, enflurane, methoxyflurane, cyclopropane.
Volatile halogenated anesthetics potentiate Esmeron-induced muscle block. The effect becomes evident only with maintenance doses (see section 4.2). It is also possible that the antagonizing action of the blockade of acetylcholinesterase inhibitors is inhibited.
• After intubation with suxamethonium (see section 4.4).
• Long-term concomitant use of corticosteroids and Esmeron in the ICU may induce myopathy or prolongation of the duration of neuromuscular block (see sections 4.4 and 4.8).
• High doses of thiopental, metoesital, ketamine, fentanyl, gamma-hydroxy-butyrate, etomidate and propofol.
• Other nondepolarizing neuromuscular blocking agents.
• Other medicines
- Antibiotics: aminoglycosides, lincosamides, polypeptides, acylaminopenicillins. Tetracyclines, high doses of metonidazole.
- Diuretics, thiamine, MAO-inhibitory medicinal products, quinidine and its isomer quinine, protamine, adrenergic blocking medicinal products, magnesium salts, calcium channel blockers, lithium salts, local anesthetics (IV lidocaine, epidural bupivacaine) and acute administration of phenytoin and β-blockers.
There have been reports of recurarisation following post-operative administration of quinidine, quinine, magnesium salts and the following antibiotics: aminoglycosides, lincosamides, polypeptides and acylaminopenicillins (see section 4.4).
Decreased effect
• Neostigmine, edrophonium, pyridostigmine, aminopyridine derivatives.
• Previous 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-depolarising muscle relaxants in combination with Esmeron may induce the attenuation or enhancement of neuromuscular block, depending on the order in which they are administered and the type of muscle relaxant used.
• Subsequent administration of suxamethonium to Esmeron may result in the enhancement or attenuation of the neuromuscular blocking effect induced by Esmeron.
Effect of Esmeron on other medicinal products
The combination of Esmeron and lidocaine can induce a reduction in the latency time of lidocaine.
Pediatric population
No formal interaction studies have been conducted. The interactions for adults and the relevant special warnings and precautions for use listed above (see section 4.4) should also be considered for pediatric patients.
04.6 Pregnancy and breastfeeding -
Pregnancy
No clinical data on exposure to rocuronium bromide in pregnancy are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal / fetal development, parturition or postnatal development. Caution is required when prescribing Esmeron to pregnant women.
Caesarean section
In patients undergoing caesarean section, Esmeron can be used as part of the rapid sequence induction technique, provided that no intubation difficulties are anticipated and that a sufficient dose of anesthetic is administered or after intubation after administration of suxamethonium. .
Esmeron, given in doses of 0.6 mg / kg body weight, has been shown to be safe in pregnant women undergoing caesarean section. Esmeron does not affect Apgar score, fetal muscle tone or "cardiorespiratory adaptation. Cord blood test indicates that rocuronium bromide crosses the placenta only minimally without giving rise to any observable adverse clinical effects on the patient." newborn.
Note 1: Doses of 1.0 mg / kg body weight have been studied in rapid sequence induction of anesthesia, but not in patients undergoing caesarean section. Therefore, in this category of patients it is recommended to use only a dose of 0.6 mg / kg body weight.
Note 2: The reversibility of neuromuscular block induced by muscle relaxants may be inhibited or unsatisfactory in patients treated with magnesium salts for toxaemia gravidarum, since magnesium salts increase neuromuscular block. Therefore, the dose of Esmeron should be reduced and carefully adjusted in relation to the response to stimulation in these patients.
Feeding time
It is not known whether Esmeron is excreted in human milk. Animal studies have found insignificant concentrations of Esmeron in the mother's milk. Animal studies do not reveal direct or indirect harmful effects with respect to pregnancy, embryonal / fetal development, parturition or postnatal development.
Esmeron should only be given to women who are breastfeeding if the treating doctor believes that the benefits outweigh the risks.
04.7 Effects on ability to drive and use machines -
Since Esmeron is used as an adjunct to general anesthesia, the same precautions should be observed for outpatient patients as after general anesthesia.
04.8 Undesirable effects -
The most commonly observed adverse drug reactions include pain and / or injection site reactions, changes in vital signs and prolonged muscle block. The reports of serious adverse reactions most frequently received by the pharmacovigilance system concern "anaphylactic and anaphylactoid reactions" and associated symptoms. See also the explanations given below the table.
¹ The reported frequencies are the result of estimates obtained from the reports collected by the pharmacovigilance system and from the data in the literature.
² Since the data collected through the pharmacovigilance system does not allow to derive precise incidence values, the frequency of reports has been divided into two categories instead of five.
³ After long-term use in intensive care.
Anaphylaxis
Although very rare, severe anaphylactic reactions to muscle relaxants, including Esmeron, have been reported. Anaphylactic / anaphylactoid reactions are: bronchospasm, cardiovascular changes (eg hypotension, tachycardia, circulatory collapse, shock) and skin changes (eg angioedema, urticaria). These reactions have in some cases been fatal.
Given the possible severity of these reactions, the possibility of their occurrence must always be taken into account and all necessary precautions taken.
Since muscle relaxants can induce histamine release both locally at the injection site and systemically, when administering these medicinal products, the possible occurrence of itching and erythematous reactions at the injection site and / or generalized histaminoid (anaphylactoid) reactions (see also what has been said above about anaphylactic reactions).
In clinical studies, only a slight increase in mean plasma histamine values was observed following rapid bolus administration of 0.3-0.9 mg / kg body weight of rocuronium bromide.
Prolonged neuromuscular block
The most frequent adverse reaction of the class of non-depolarizing muscle relaxants is the prolongation of the pharmacological action of the compound beyond the necessary period of time. The effects can range from weakness of the skeletal muscles to a profound and prolonged paralysis of the same which can induce respiratory failure. or apnea.
Myopathy
Cases of myopathy have been reported following the use of various muscle relaxant medicinal products in the ICU in combination with corticosteroids (see section 4.4).
Local reactions at the injection site
During the induction of anesthesia in rapid sequence, pain at the injection site has been reported, especially in cases where the patient had not yet completely lost consciousness and in particular when propofol was used for the induction. In clinical studies, Injection site pain was seen in 16% of patients undergoing rapid sequence induction of anesthesia with propofol, and in less than 0.5% of patients undergoing rapid sequence induction of anesthesia with fentanyl and thiopental.
Pediatric population
A meta-analysis of 11 clinical trials with pediatric patients (n = 704) treated with rocuronium bromide (up to 1 mg / kg) found tachycardia, identified as an undesirable effect to the drug, with a frequency of 1.4%.
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose -
In the event of overdose and prolonged neuromuscular block, the patient should remain on controlled ventilation and under sedation. In this situation there are two options for reversal of neuromuscular block: 1) in adults, sugammadex can be used for reversal of intense and deep block. The dose of sugammadex to be administered depends on the level of neuromuscular block; 2) an acetylcholinesterase inhibitor (neostigmine, edrophonium, pyridostigmine) or sugammadex can be used at the first signs of spontaneous recovery in adequate doses.
If administration of anticholinesterases fails to reverse the neuromuscular effects of Esmeron, ventilation should be continued until spontaneous breathing is resumed. Repeated administration of acetylcholinesterase inhibitors can be dangerous.
In animal studies, severe depression of cardiovascular function, resulting in heart failure, was observed only after administration of a cumulative dose of 750 X ED90 (135 mg / kg body weight of rocuronium bromide). ).
05.0 PHARMACOLOGICAL PROPERTIES -
05.1 "Pharmacodynamic properties -
Pharmacotherapeutic category: muscle relaxants with peripheral action.
ATC code: M03AC09.
Mechanism of action
Esmeron (rocuronium bromide) is a non-depolarising muscle relaxant with intermediate action and rapid latency, with all the pharmacological effects characteristic of this class of medicines (curariforms). It acts by competition with acetylcholine on nicotinic receptors located on the endplate of the striated muscle.
Its action is antagonized by acetylcholinesterase inhibitors such as neostigmine, edrophonium and pyridostigmine.
Pharmacodynamic effects
The ED90 (dose required to depress the thumb response to ulnar nerve stimulation by 90%) under intravenous anesthesia is approximately 0.3 mg / kg body weight of rocuronium bromide. The ED95 in infants is lower than that in adults and children (0.25, 0.35 and 0.40 mg / kg body weight, respectively).
Clinical duration (time to spontaneous recovery of 25% of the control response) is 30-40 minutes with 0.6 mg / kg body weight of rocuronium bromide. The total duration (time elapsed until spontaneous recovery of 90% of the control response) is 50 minutes. The mean time to spontaneous recovery from 25 to 75% of response (recovery index) is 14 minutes after bolus administration of 0.6 mg / kg body weight of rocuronium bromide.
With lower dosages, equal to 0.3-0.45 mg / kg body weight (1-1½ x ED90), the latency time increases while the duration of action decreases. With high doses, equal to 2 mg / kg of body weight, the clinical duration is 110 minutes.
Intubation during routine anesthesia
Within 60 seconds of intravenous administration of a dose of 0.6 mg / kg body weight of rocuronium bromide (2 x ED90 under intravenous anesthesia), adequate conditions for intubation can be achieved in almost all patients, conditions that in "80% of cases are judged to be excellent. Within 2 minutes, complete muscle paralysis is established, suitable for any type of surgery.
After administration of 0.45 mg / kg body weight of rocuronium bromide, it takes 90 seconds to achieve acceptable conditions for intubation.
Rapid sequence induction
During the induction of anesthesia in rapid sequence, 1.0 mg / kg body weight of rocuronium bromide allows to obtain within 60 seconds the conditions suitable for intubation in 93% and 96% of patients respectively anesthetized with propofol. or fentanyl / thiopental. In 70% of these patients the conditions are evaluated as excellent. With this dosage the clinical duration is approximately 1 hour, after which the muscle block can be safely reversed. A dose equal to 0.6 mg / kg body weight of rocuronium bromide allows to obtain within 60 seconds the conditions suitable for intubation in 81% and 75% of patients anesthetized respectively with propofol or fentanyl / thiopental by means of the rapid sequence induction technique.
Pediatric population
The mean time to onset in infants, young children and children at the 0.6 mg / kg body weight dose used for intubation is slightly shorter than in adults. Comparison between pediatric patient groups found that the onset time in infants and adolescents (1.0 minutes) is slightly longer than in infants, toddlers and children (0.4, 0.6 and 0.8 minutes respectively). In children, the duration of relaxation and recovery time tend to be shorter than in the infant and adult. When comparing pediatric patient groups, it found that the mean time to reappearance of T3 was prolonged in neonates and infants (56.7 and 60.7 minutes, respectively) compared to toddlers, children and adolescents (45.4 , 37.6 and 42.9, respectively).
Mean (SD) time to onset and clinical duration following administration of an initial intubation dose * of 0.6 mg / kg rocuronium during sevoflurane / nitrous oxide and isoflurane / nitrous oxide anesthesia (maintenance) in the PP group (pediatric patients)
* Dose of rocuronium administered within 5 seconds.
** Calculated from the end of administration of the rocuronium intubation dose
Geriatric patients and patients with hepatic and / or biliary diseases and / or with renal dysfunction
The duration of action of maintenance doses of 0.15 mg / kg body weight of rocuronium bromide may be slightly longer under anesthesia with enflurane and isoflurane in geriatric patients and in those with liver and / or renal disease (approximately 20 minutes) compared to patients with no functional impairment of excretory organs undergoing intravenous anesthesia (approximately 13 minutes) (see section 4.2). No accumulation effects (progressive increase in duration of action) were observed following administration of repeated doses. maintenance recommended.
Intensive Care Unit
Following the continuous infusion into the ICU, the time it takes to return to a TOF ratio equal to 0.7 depends on the level of block at the end of the infusion. After continuous infusion for 20 hours or more, the median value (interval) of the time between the reappearance of the T2 response to TOF stimulation and the return to a TOF ratio of 0.7 is approximately 1.5 (1-5) hours in patients who do not present with multiple organ failure and 4 hours (1-25) in patients with multiple organ failure.
Cardiovascular surgery
Minimal and clinically insignificant changes in the most common cardiovascular parameters were observed in patients undergoing cardiovascular surgery during the latency time of a maximum block induced by the administration of 0.6-0.9 mg / kg body weight of Esmeron. , i.e. an increase of up to 9% in heart rate and up to 16% in mean arterial pressure compared to control values.
Reversibility of muscle relaxation
The action of rocuronium can be antagonized both with the administration of sugammadex and with acetylcholinesterase inhibitors (neostigmine, pyridostigmine or edrophonium). Sugammadex can be administered by routine inversion (at a value of 1-2 post tetanus count until T2 reappearance) or by immediate inversion (3 minutes after administration of rocuronium bromide).
Acetylcholinesterase inhibitors can be administered at the reappearance of the T2 response or at the first signs of clinical recovery.
05.2 "Pharmacokinetic properties -
Following intravenous administration of a single bolus dose of rocuronium bromide, the trend in plasma concentration over time follows three exponential phases. In the normal adult, the mean elimination half-life (95% CI) is 73. (66-80) minutes, the (apparent) volume of distribution under steady-state conditions at 203 (193-214) ml.kg-1 and the plasma clearance at 3.7 (3.5-3.9) ml.kg -1.min-1.
In controlled studies, a reduction in plasma clearance was observed in geriatric patients and in those with renal dysfunction, but this reduction did not reach a statistically significant level in most studies. In patients with liver disease, the mean elimination half-life is prolonged by 30 minutes while the mean plasma clearance is reduced by 1 ml.kg-1.min-1.
Pediatric population
The pharmacokinetic properties of rocuronium bromide in pediatric patients (n = 146) aged 0-17 years were evaluated by population analysis of the pharmacokinetic data from two clinical studies with anesthesia under sevoflurane (induction) and isoflurane / oxide nitrous (maintenance). All pharmacokinetic parameters were shown to be linearly proportional to body weight as indicated by a similar clearance (l.h-1.kg-1). The volume of distribution (l.kg-1) and the elimination half-life (h) decrease with age (years). Pharmacokinetic parameters for pediatric subjects for each age group are shown in the table below:
Estimated pharmacokinetic parameters (mean [SD]) of rocuronium bromide in typical pediatric patients during sevoflurane and nitrous oxide (induction) and isoflurane / nitrous oxide (maintenance anesthesia)
Intensive Care Unit
When the medicinal product is administered as a continuous infusion to facilitate mechanical ventilation for 20 hours or more, there is an increase in the mean elimination half-life and the mean (apparent) volume of distribution at steady state. considerable individual variability, related to the nature and extent of organ (or multi-organ) failure and to individual patient characteristics. A mean (± SD) elimination half-life of 21 was observed in patients with multi-organ failure, 5 (± 3.3) hours, a steady-state (apparent) volume of distribution of 1.5 (± 0.8) 1.kg-1, and a plasma clearance of 2.1 (± 0.8) mL. kg-1.min-1.
Rocuronium is excreted through the urine and bile. Urinary excretion is approximately 40% over 12-24 hours. After injection of a radiolabelled dose of rocuronium bromide, excretion occurs on average 47% in the urine and 43% in the faeces after 9 days. Approximately 50% is found in unchanged form.
05.3 Preclinical safety data -
Effects in non-clinical studies were observed only at exposures considered significantly in excess of the maximum human exposure, which suggests little clinical relevance.
There are no animal models capable of correctly reproducing the usually very complex picture of a patient admitted to intensive care. The safety data of Esmeron used to facilitate mechanical ventilation in ICUs are therefore largely based on the results obtained in clinical studies.
06.0 PHARMACEUTICAL INFORMATION -
06.1 Excipients -
Sodium acetate (pH regulator)
Sodium chloride
Acetic acid (pH regulator)
Water for injections
06.2 Incompatibility "-
Physical incompatibility has been documented when Esmeron is added to solutions containing the following medicinal products: amphotericin, amoxicillin, azathioprine, cefazoline, cloxacillin, dexamethasone, diazepam, enoximone, erythromycin, famotidine, furosemide, hydrocortisone sodium succinate, insulin, metoesitalolone, metoesitalolone succinate, thiopental, trimethoprim and vancomycin. Esmeron is also incompatible with Intralipid.
Esmeron must never be mixed with other medicinal products except those mentioned in section 6.6.
If Esmeron is administered in the same infusion line as other medicinal products it is important that the infusion line is adequately flushed (e.g. with 0.9% NaCl) between administration of Esmeron and medicinal products whose incompatibility with Esmeron has already been demonstrated or whose compatibility with Esmeron has not yet been established.
06.3 Period of validity "-
Esmeron has a shelf life of 3 years in unopened, properly stored packaging (see section 6.4). The expiry date is that indicated on the package and on the vial label.
After opening the vial, the solution is chemically stable for 24 hours at room temperature.
Since Esmeron does not contain preservatives, it is recommended that the unused solution be discarded.
06.4 Special precautions for storage -
Esmeron must be stored at 2-8 ° C and in the dark.
Esmeron can be stored at 8 ° to 30 ° C for 3 months before its expiration.
06.5 Nature of the immediate packaging and contents of the package -
Pack size of 12 vials containing 50 mg of rocuronium bromide each.
Pack of 10 vials containing 50 mg of rocuronium bromide each.
Pack size of 10 vials containing 100 mg of rocuronium bromide each.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling -
Compatibility studies have been performed with the following infusion fluids. In nominal concentrations of 0.5 mg / ml and 2.0 mg / ml Esmeron was found to be compatible with: 0.9% NaCl, 5% Dextrose, 5% Dextrose in physiological solution, Water for injections, Lactated Ringer and Haemaccel.
The solutions must be used within 24 hours and immediately after mixing them.
Discard the unused solution.
07.0 HOLDER OF THE "MARKETING AUTHORIZATION" -
N.V. ORGANON, Kloosterstraat 6, 5349 AB Oss (The Netherlands)
Representative in Italy
MSD Italia S.r.l.
Via Vitorchiano, 151
00189 Rome
08.0 MARKETING AUTHORIZATION NUMBER -
ESMERON 10 mg / ml Solution for injection for intravenous use - 12 vials of 5 ml
A.I.C. N ° 029209032
ESMERON 10 mg / ml Solution for injection for intravenous use - 10 vials of 5 ml
A.I.C. N ° 029209057
ESMERON 10 mg / ml Solution for injection for intravenous use - 10 vials of 10 ml
A.I.C. N ° 029209044
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION -
Date of first authorization: November 29, 1995 (A.I.C. Decree no. 833/1995)
Date of most recent renewal: December 31, 2010
10.0 DATE OF REVISION OF THE TEXT -
January 2015
