Active ingredients: Rocuronium (Rocuronium bromide)
Rocuronium Hospira 10 mg / ml solution for injection / infusion
Why is Rocuronium used - Generic drug? What is it for?
Rocuronium Hospira is part of a group of drugs called muscle relaxants. Normally the nerves send messages to the muscles by means of impulses. Rocuronium Hospira works by blocking these impulses so that the muscles relax. When undergoing surgery, the muscles must be completely relaxed. This allows the surgeon to perform the surgery more easily.
In adults and children during general anesthesia Rocuronium Hospira can be used to facilitate the insertion of a tube into the windpipe for artificial ventilation (mechanically assisted breathing) and to ensure that the muscles are relaxed during the procedure.
If you are an adult your doctor may use this medicine as an adjunct to the intensive care unit (ICU) (eg to make it easier to insert a tube into your windpipe while you are receiving mechanical assisted breathing). It could also be treated with this medicine in emergencies when the tube needs to be quickly inserted into the trachea.
Contraindications When Rocuronium should not be used - Generic drug
Do not use Rocuronium Hospira
- if you are allergic to rocuronium bromide, bromide ion or any of the other ingredients of this medicine.
Precautions for use What you need to know before taking Rocuronium - Generic drug
Talk to your doctor or anesthetist before using Rocuronium Hospira:
- if you are allergic to any muscle relaxant
- if you have kidney, heart, liver or biliary disease
- if you have heart disease or disease affecting blood circulation
- if you have suffered from a disease of the nerves and muscles such as polio, myasthenia gravis or Eaton-Lambert syndrome
- if you have fluid retention (edema)
- if you have been told that you have a low level of calcium (hypocalcaemia), potassium (hypokalaemia) or protein (hypoproteinemia) in your blood
- if you have been told that you have a high level of magnesium (hypermagnesemia) or carbon dioxide (hypercapnia) in your blood
- if you have lost a lot of water from your body, for example when you were sick, you have suffered from diarrhea, sweating
- if you are overweight (obese)
- if you are elderly
- if your body temperature is too low (hypothermia)
- if you have burns
- if you have an increased amount of acids in your blood (acidosis) • if you have excessive weight loss and poor physical condition (cachexia).
Children and geriatric patients
Rocuronium Hospira can be used in children (infants and adolescents) and in geriatric patients however, the anesthetist should evaluate the medical history.
Interactions Which drugs or foods can modify the effect of Rocuronium - Generic drug
Tell your doctor or anesthetist if you are taking, have recently taken or might take any other medicines which include both herbal products and non-prescription medicines. Rocuronium Hospira can affect other medicines or be affected by them, in particular: • some anti-inflammatory medicines (corticosteroids) when used for a long time together with Rocuronium Hospira, for example during intensive care
- some antibiotics
- some medicines to treat heart disease or high blood pressure (diuretics, calcium channel blockers, beta-blockers, alpha blockers) and quinidine, magnesium salts that can be used as laxatives or in some heart diseases such as pre -eclampsia
- lithium used in depressive illnesses (bipolar disorders)
- some medicines to treat epilepsy
- calcium chloride and potassium chloride (medicines that change the levels of potassium or calcium in the blood)
- some protease inhibitors known as gabexate and ulinastatin (can be used to treat various viral infections or clinical conditions such as pancreatitis)
- azathioprine (used for the prevention of transplant rejection and the treatment of autoimmune diseases)
- theophylline (used to treat asthma)
- medicines used to treat myasthenia gravis (neostigmine, edrophonium, pyridostigmine)
- aminopyridine derivatives (medicines used in Eaton-Lambert syndrome)
- quinine (used to treat malaria or nocturnal leg cramps)
Note that you may be given other medicines during the procedure which may affect the effects of Rocuronium Hospira. These include some anesthetics, other muscle relaxants, medicines such as phenytoin and medicines that reverse the effect of Rocuronium Hospira. Rocuronium Hospira may make some anesthetics work faster. Your anesthetist will take this into account when determining the correct dose of Rocuronium Hospira for you.
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 or anesthetist for advice before using this medicine.
There are very limited data on the use of Rocuronium Hospira during pregnancy or lactation in humans and there are no data on breastfeeding women. Rocuronium Hospira should only be given to pregnant and lactating women when the doctor decides that the benefits outweigh the risks. Rocuronium Hospira can be given during a caesarean section. There are no data on the effects of this medicine on fertility.
Driving and using machines
Rocuronium Hospira has a strong influence on the ability to drive and use machines.
Therefore, it is not recommended to drive a car or operate machinery during the first 24 hours after recovering from the effects of this medicine. Your doctor will tell you when you can start driving and using machines again. You should always be accompanied home by a responsible adult after your treatment.
Rocuronium Hospira contains sodium
Each milliliter (ml) of Rocuronium Hospira contains 1.56 mg of sodium. This medicinal product contains less than 1 mmol sodium (23 mg) per dose, making it essentially 'sodium-free'.
Dose, Method and Time of Administration How to use Rocuronium - Generic drug: Posology
Dose
The anesthetist will calculate the required dose of Rocuronium Hospira according to:
- the type of anesthetic
- the expected duration of the intervention
- other medicines you are taking
- of his state of health.
The normal dose is 0.6 mg per kg of body weight and the effect lasts for 30-40 minutes.
How Rocuronium Hospira is given
Rocuronium Hospira will be given to you by the anesthetist. Rocuronium Hospira is given intravenously (into a vein) either as single injections or by continuous infusion (drip).
Overdose What to do if you have taken an overdose of Rocuronium - Generic drug
Your anesthetist will closely monitor you when you are under the effects of Rocuronium Hospira, so it is unlikely that you will be given too much Rocuronium Hospira. However, if this happens, the anesthetist will ensure that the anesthesia and artificial ventilation are continued. until she is able to breathe on her own again, and she will be kept asleep while all of this happens.
If you have any further questions on the use of this medicine, ask your doctor or anesthetist.
Side Effects What are the side effects of Rocuronium - Generic drug
Like all medicines, this medicine can cause side effects, although not everybody gets them. If these side effects occur while you are anesthetized, they will be treated by the anesthetist
If any side effect becomes serious, talk to your doctor or anesthetist.
The following side effects have been reported at the frequency given below:
Uncommon (≥1 / 1,000 to <1/100); Very rare (<1 / 10,000);
Uncommon side effects (may affect up to 1 in 100 people)
- the medicine is either too effective or not effective enough
- the medicine has a longer duration of action than expected
- reduces blood pressure
- increases heart rate
- pain near the injection site.
Very rare side effects (may affect less than 1 in 10,000 people)
- allergic reactions (such as difficulty in breathing, circulatory collapse and shock)
- chest wheezing
- muscle weakness
- swelling, rash or redness of the skin
- problems with the airways
If you get any side effects, talk to your doctor or anesthetist. 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.it/it/responsabili. ".
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.
After first opening: As Rocuronium Hospira does not contain preservatives, use the solution immediately after opening the vial. After dilution with infusion fluids the chemical and physical stability in use of the diluted medicinal product has been demonstrated for 72 hours at 30 ° C.
From a microbiological point of view, the diluted medicinal product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 ° C to 8 ° C.
Store in the refrigerator (between 2 ° C and 8 ° C). Rocuronium Hospira can be stored outside the refrigerator at a maximum temperature of 30oC for a maximum period of 12 weeks. The medicine should not be put back in the refrigerator if stored out of the refrigerator. The retention period must not exceed the stability period.
Do not use this medicine after the expiry date which is stated on the label and on the carton after "EXP".
Do not use Rocuronium Hospira if you notice that the solution is not clear and has visible particles.
Rocuronium Hospira must not be disposed of in household waste or wastewater. This will help protect the environment.
Other Information
What Rocuronium Hospira contains
- The active ingredient is rocuronium bromide.
- each milliliter (ml) contains 10 mg of rocuronium bromide.
- each 5ml vial contains 50 mg of rocuronium bromide.
- each 10ml vial contains 100 mg of rocuronium bromide.
- the other ingredients are anhydrous sodium acetate, sodium chloride, glacial acetic acid, sodium hydroxide and water for injections.
- Each 5 ml vial of Rocuronium Hospira contains 7.8 mg of sodium.
- Each 10 ml vial of Rocuronium Hospira contains 15.6 mg of sodium.
What Rocuronium Hospira looks like and contents of the pack
Rocuronium Hospira is a colorless to yellow-orange solution for injection.
It is available in 50 mg vials (10 vials per pack) or 100 mg vials (10 vials per pack) of rocuronium bromide.
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
ROCURONIUM HOSPIRA 10 MG / ML SOLUTION FOR INJECTION / FOR INFUSION
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each ml of Rocuronium Hospira contains 10 mg of rocuronium bromide.
Each 5 ml vial contains 50 mg of rocuronium bromide
Each 10 ml vial contains 100 mg of rocuronium bromide.
Excipient with known effect:
Each 5 ml vial of Rocuronium Hospira contains 7.8 mg of sodium.
Each 10 ml vial of Rocuronium Hospira contains 15.6 mg of sodium.
For the full list of excipients, see section 6.1
03.0 PHARMACEUTICAL FORM
Solution for injection / infusion
Clear, colorless to yellow-orange solution
pH of the solution between 3.8 and 4.2
Osmolarity: 256-312 mOsmol / kg
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Rocuronium Hospira is indicated in adult and pediatric patients (term neonates to adolescents [0 to skeletal muscle during surgery.
In adults Rocuronium Hospira is also indicated to facilitate endotracheal intubation during rapid sequence induction and as an adjunct in intensive care units (ICU) to facilitate intubation and short-term mechanical ventilation (see also sections 4.2 and 5.1).
04.2 Posology and method of administration
Dosage
As with other muscle relaxants, the administration of Rocuronium Hospira should only be practiced or supervised by an experienced physician who is familiar with the action and methods of use of these drugs.
As with other muscle relaxants, the dosage of Rocuronium Hospira must be established for each patient. 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 drugs 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.
Surgical interventions
Inhalation anesthetics potentiate the neuromuscular blocking effect induced by Rocuronium Hospira.
This enhancement 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 Rocuronium Hospira should be made by administering smaller maintenance doses at less frequent intervals or by using speed. less infusion in case of long-term interventions (over 1 hour) under inhalation anesthesia (see section 4.5).
Adults
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.
Endotracheal intubation
The standard dose for intubation during standard anesthesia is 0.6 mg / kg of body weight of Rocuronium Hospira 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 Hospira is recommended, which in almost all patients is sufficient to establish the conditions suitable for the If Rocuronium Hospira 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.
For the use of Rocuronium Hospira during the induction of rapid sequence anesthesia in patients undergoing caesarean section, see section 4.6.
Maintenance doses
The recommended maintenance dose of Rocuronium Hospira is 0.15 mg / kg of body weight; 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 Hospira is administered as a continuous infusion, it is recommended to give a loading dose of 0.6 mg / kg body weight of Rocuronium Hospira 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 / h in the case of intravenous anesthesia and from 0.3 to 0.4 mg / kg / h 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.
As the dose is individual, monitoring is therefore essential. The above doses are to be intended as a guide.
Pediatric patients
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.
Experience with rocuronium for the induction of rapid sequence anesthesia in pediatric patients is limited.
The use of Rocuronium Hospira to facilitate endotracheal intubation during rapid sequence induction is therefore not recommended in this category of patients.
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 Hospira. 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 between 0.075-0.1 mg / kg body weight of Rocuronium Hospira, with an infusion rate ranging between 0.3-0. 4 mg / kg / h (see also section Continuous infusion).
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 Hospira 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 between 0.3-0.6 mg / kg / h for the first hour of administration, and should then be reduced over the next 6-12 hours based on individual response. Thereafter, the individual dose required remains relatively constant.
Clinical studies have shown a marked individual variability of the infusion rate, which varies on average from 0.2 to 0.5 mg / kg / h depending on the nature and extent of organ (s) failure. administered concomitantly and of 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
Rocuronium Hospira is not recommended 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
Rocuronium Hospira 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 Rocuronium Hospira 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 Rocuronium Hospira 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. It is also necessary to consider other factors (eg. Possible drug interactions or the patient's condition). able to cause a residual curarization after extubation in the postoperative phase. 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.
It is essential to ensure that the patient breathes spontaneously, deeply and regularly before leaving him alone after anesthesia.
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 strongly 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 Rocuronium Hospira should be postponed until the patient has clinically recovered from suxamethonium-induced neuromuscular blockade.
The pharmacokinetic and / or pharmacological properties of Rocuronium Hospira may 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, Rocuronium Hospira should be used with extreme caution in patients with neuromuscular disease or after poliomyelitis, as the response to muscle relaxants may 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 Rocuronium Hospira 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 Rocuronium Hospira increases in intensity and duration.
Obesity
Like other muscle relaxant medicinal products, Rocuronium Hospira 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.
Patients undergoing caesarean section
Reversal of muscle relaxant-induced neuromuscular blockade may be inhibited or unsatisfactory in patients taking magnesium salts for toxaemia in pregnancy, as magnesium salts potentiate neuromuscular blockade. Therefore, rocuronium dosage should be decreased in these patients and given to scalar doses based on the stimulatory muscle response.
Conditions that may increase the effects of Rocuronium Hospira
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.
Each ml contains 1.56 mg of sodium. This medicinal product contains less than 1 mmol sodium (23 mg) per dose, 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 Rocuronium Hospira
Enhancement of the effect
• Volatile halogenated anesthetics (eg halothane, enflurane, methoxyflurane)
potentiate the muscle block induced by Rocuronium Hospira. 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).
• High doses of thiopental, metoesital, ketamine, fentanyl, gamma-hydroxy-butyrate, etomidate and propofol
• Other nondepolarizing neuromuscular blocking agents.
• Concomitant long-term use of corticosteroids and Rocuronium Hospira in the ICU may induce myopathy or prolongation of the duration of neuromuscular block (see sections 4.4 and 4.8).
Other drugs
- Antibiotics: aminoglycosides, lincosamides (e.g. lincomycin and clindamycin) polypeptide antibiotics, acylaminopenicillin antibiotics, tetracyclines, high doses of metronidazole.
- Diuretics, quinidine and its quinine isomer, magnesium salts, calcium channel blocking agents, lithium salts, local anesthetics (i.v. lidocaine, epidural bupivacaine) and acute administration of phenytoin and? -Blockers.
There have been reports of recurarisation following postoperative administration of: aminoglycosides, lincosamides, polypeptide and acylaminopenicillin antibiotics, quinidine, quinine and magnesium salts (see section 4.4).
Decreased effect
• Previous chronic administration of phenytoin or carbamazepine
• Protease inhibitors (gabexate, ulinastatin)
• Calcium chloride, potassium chloride
• Noradrenaline, azathioprine (only transient and limited effect), theophylline
• Neostigmine, edrophonium, pyridostigmine, aminopyridine derivatives.
Variable effect
• The administration of other non-depolarising muscle relaxants in combination with Rocuronium Hospira may induce the attenuation or enhancement of the blockade.
neuromuscular, depending on the order in which they are administered and the type of muscle relaxant used.
• Administration of suxamethonium subsequent to that of Rocuronium Hospira may result in potentiation or attenuation of the neuromuscular blocking effect induced by Rocuronium Hospira.
Effect of Rocuronium Hospira on other medicinal products
The combination of Rocuronium Hospira and lidocaine may induce a reduction in the latency time of lidocaine.
Pediatric patients
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 Rocuronium Hospira. to pregnant women.
Caesarean section
In patients undergoing caesarean section, Rocuronium Hospira can be used as part of the rapid sequence induction technique, provided that no intubation difficulties are expected and a sufficient dose of anesthetic is administered or after facilitated intubation with suxamethonium. .
Rocuronium Hospira, given in doses of 0.6 mg / kg body weight, has been shown to be safe in pregnant women undergoing caesarean section. Rocuronium Hospira 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. of the newborn.
Note 1: Doses of 1.0 mg / kg body weight have been studied in the induction of rapid sequence 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 Rocuronium Hospira should be reduced and carefully adjusted in relation to the response to stimulation in these patients.
Feeding time
It is not known whether Rocuronium Hospira is excreted in human milk. Animal studies have found insignificant concentrations of Rocuronium Hospira in the mother's milk.
Rocuronium Hospira should only be given to women who are breastfeeding if the doctor considers that the benefits outweigh the risks.
Fertility
There are no data on the effects of rocuronium bromide on fertility.
04.7 Effects on ability to drive and use machines
Rocuronium affects the ability to drive or use machines. It is not recommended to use potentially dangerous machinery or to drive an automobile within the first 24 hours of fully recovering from the neuromuscular blocking action of rocuronium bromide.
Since Rocuronium Hospira 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 frequency of undesirable effects is classified into the following categories:
Uncommon / rare (≥ 1 / 10,000 to
Not known (cannot be estimated from the available data)
The frequencies are estimates obtained from post-marketing surveillance reports from the general literature.
Post-marketing surveillance data fails to generate accurate incidence data. For this reason, reporting frequency has been divided into three categories rather than five.
Adverse drug reactions most commonly observed post-marketing include anaphylactic and anaphylactoid reactions and related symptoms. See also explanations at the bottom of the table.
a After long-term use in intensive care.
Myopathy
Cases of myopathy have been reported following the use of various muscle relaxant medicinal products in the ICU in combination with corticosteroids (see sections 4.4 and 4.5).
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.
Class effects
Anaphylactic reactions
Although very rare, severe anaphylactic reactions to muscle relaxants, including Rocuronium Hospira, 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 should always be considered and all necessary precautions taken (see section 4.4).
Increases in histamine levels
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 histamine (anaphylactoid) reactions such as bronchospasm and cardiovascular changes eg hypotension and tachycardia.Rash, exanthema, urticaria, bronchospasm and hypotension have been reported very rarely in patients treated with rocuronium bromide.
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.
Pediatric patients
A meta-analysis of 11 clinical trials with pediatric patients (n = 704) treated with rocuronium (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. There are two options for reversing the neuromuscular block:
1) In adults, sugammadex can be used for the reversal of marked, intense (deep) block. A dosage of 16 mg / kg body weight is recommended. After administration of sugammadex the patient should be carefully monitored for controlled return neuromuscular function;
2) an acetylcholinesterase inhibitor (eg. Neostigmine, edrophonium, pyridostigmine) can be used at the first signs of spontaneous recovery in adequate doses.
If administration of anticholinesterases fails to antagonize the neuromuscular effects of Rocuronium Hospira, ventilation should be continued until spontaneous respiration 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 group (ATC code): muscle relaxants, agents with peripheral action.
ATC code: M03AC09.
Mechanism of action
Rocuronium Hospira is a non-depolarising neuromuscular blocker with intermediate action and short latency, which possesses all the pharmacological characteristics of this class of drugs (curariforms). It acts by competition on the nicotinic receptors for acetylcholine located on the driving plate.
This 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, respectively).
The clinical duration (time to spontaneous recovery of 25% of the control response) is 30-40 minutes with 0.6 mg / kg 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 the response (recovery index) is 14 minutes after bolus administration of 0.6 mg / kg of rocuronium bromide.
With lower dosages, equal to 0.3-0.45 mg / kg body weight (1-1.5 x ED90), the latency time increases while the duration of action decreases. With high doses, equal to 2 mg / kg 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 which 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 patients
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 insufficiency
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 or kidney disease (approximately 20 minutes). compared to patients without functional impairment of excretory organs undergoing intravenous anesthesia (approximately 13 minutes). No accumulation effects (progressive increase in duration of action) were observed following administration of repeated recommended maintenance doses.
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 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 Rocuronium Hospira. cardiovascular, 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 my 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 may be at the reappearance of the T2 response or at the first signs of clinical recovery.
05.2 Pharmacokinetic properties
Distribution and disposal
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 and the plasma clearance at 3.7 (3.5-3.9) ml / kg / min.
When administered as a continuous infusion, to facilitate mechanical ventilation over a period of 20 hours or more, the mean elimination half-life and mean (apparent) volume of distribution at steady state are increased. In controlled clinical trials it is There was a high degree of variability between patients, related to the nature and extent of (multiple) organ failure and to individual patient characteristics. A mean (+ SD) elimination half-life of 21.5 (+3.3) hours, an (apparent) volume of distribution at steady state of 1.5 (+0) was observed in patients with multiple organ failure. , 8) l / kg-1 and a plasma clearance of 2.1 (+0.8) ml / kg / min.
Rocuronium is excreted in the urine and bile. Urine excretion reaches about 40% within 12-24 hours. After injection of a radiolabelled dose of rocuronium bromide, excretion of the radiolabelled medium averages 47% in the urine and 43% in the faeces after 9 days. About 50% is recovered as rocuronium bromide.
Biotransformation
No metabolites were found in plasma.
Pediatric population
The apparent volume of distribution in infants (3-12 months) is greater than in older children (1-8 years) as well as in adults. In children 3 to 8 years of age, clearance is greater and the elimination half-life is approximately 20 minutes shorter than in adults and children less than 3 years of age.
The pharmacokinetics of rocuronium bromide in pediatric patients (n = 146) aged 0 to 17 years were determined by population analysis of overall pharmacokinetic data obtained in two clinical studies under anesthesia with sevoflurane (induction) and isoflurane / nitrous oxide (maintenance). All pharmacokinetic parameters were linearly proportional to body weight, as evidenced by a similar clearance (l / kg / h). Volume of distribution (l / kg) and elimination half-life (h) decreased with age (years). The pharmacokinetic parameters of typical pediatric patients in each age group are summarized below:
Estimated pharmacokinetic (PK) parameters (mean [SD]) of rocuronium bromide in typical pediatric patients during sevoflurane and nitrous oxide (induction) and isoflurane / nitrous oxide (maintenance anesthesia)
Geriatric patients and patients with hepatic and / or biliary tract diseases and / or with renal insufficiency
In controlled studies, plasma clearance in elderly patients and in patients with renal insufficiency was reduced, however in most studies without reaching the limits of statistical significance. In patients with hepatic insufficiency, the mean elimination half-life extended by 30 minutes and the mean plasma clearance was reduced by 1 ml / kg / min.
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 Rocuronium Hospira 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 anhydrous (E262)
• Sodium chloride
• Glacial acetic acid (to correct the pH) (E260)
• Sodium hydroxide (to correct pH) (E524)
• Water for injections
06.2 Incompatibility
Physical incompatibility has been documented when Rocuronium Hospira is added to solutions containing the following medicinal products: amphotericin, amoxicillin, azathioprine, cefazolin, cloxacillin, dexamethasone, diazepam, enoximone, erythromycin, famotidine, furosemide, hydrocortisone sodium succedolone, metnisolone, prednisolone, insulin sodium succinate, thiopental, trimethoprim and vancomycin. Rocuronium Hospira is also incompatible with Intralipid.
Rocuronium Hospira must never be mixed with medicinal products other than those listed in section 6.6.
If Rocuronium Hospira is administered in the same infusion line used for other medicinal products it is important that the infusion line is adequately flushed (e.g. with 0.9% NaCl) between administration of Rocuronium Hospira and medicinal products whose incompatibility with Rocuronium Hospira has already been demonstrated or whose compatibility with Rocuronium Hospira has not yet been established.
06.3 Period of validity
Sealed vial: 3 years.
After first opening: As Rocuronium Hospira does not contain preservatives, use the solution immediately after opening the vial.
After dilution: After dilution with infusion fluids (see section 6.6) the chemical and physical in-use stability of the diluted medicinal product (see section 6.6) has been demonstrated for 72 hours at 30 ° C.
From a microbiological point of view, the diluted medicinal product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 ° C to 8 ° C, unless dilution has taken place under conditions of controlled and validated asepsis.
06.4 Special precautions for storage
Store in the refrigerator (between 2 ° C and 8 ° C).
Rocuronium Hospira can be stored outside the refrigerator at a maximum temperature of 30oC for a maximum period of 12 weeks. The medicine should not be put back in the refrigerator if stored out of the refrigerator. The retention period must not exceed the stability period.
06.5 Nature of the immediate packaging and contents of the package
Rocuronium Hospira 50mg / 5ml (10mg / ml)
5 ml glass vial (type I) with chlorobutyl rubber stopper and aluminum flip-off cap. The vial stopper rubber does not contain latex.
Each 50 mg vial contains 5 ml of solution.
Rocuronium Hospira 100mg / 10ml (10mg / ml)
10 ml glass vial (type I) with chlorobutyl rubber stopper and aluminum flip-off cap. The vial stopper rubber does not contain latex.
Each 100 mg vial contains 10 ml of solution.
Each pack contains 10 vials.
06.6 Instructions for use and handling
The solution should be visually inspected prior to use. Only clear solutions practically free of particles should be used.
Compatibility with the following infusion fluids has been demonstrated.
Rocuronium Hospira in nominal concentrations of 0.5 mg / ml and 2.0 mg / ml is compatible with:
0.9% NaCl, 5% glucose, 5% glucose in 0.9% NaCl, water for injections in Lactated Ringer's solution.
Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
Hospira Italia S.r.l.
Via Orazio, 20/22
80122 Naples
08.0 MARKETING AUTHORIZATION NUMBER
042535017 "10 mg / ml solution for injection or infusion" 10 glass vials of 5 ml
042535029 "10 mg / ml solution for injection or infusion" 10 glass vials of 10 ml
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 09/2014
10.0 DATE OF REVISION OF THE TEXT
09/2014
