Norcuron 10 Mg Powder For Solution For Injection
Bar prints 100mm @ 100%
|
— |
«£► MSD ARTWORK |
|
— |
Item No.: 39765 |
|
E |
Revision Date & No.: 120315-1 |
|
= |
Pharma Code: 625 |
|
Schawk Job No.: 465793A01 | |
|
E |
Black Technical Info Profile |
|
E |
SCHAWK! |* nr- n/ C 0/, |
|
95% 3/0 ^^^^Proprietary |
39765/120315-1
Norcuron®
10 mg
I lOrganonl
powder for solution for injection
Information for the doctor
1 Name of the medicinal product
Norcuron® 10 mg, powder for solution for injection
2 Qualitative and quantitative composition
Norcuron 10 mg
1 vial contains 10 mg vecuronium bromide, which corresponds to 2 mg vecuronium bromide per ml.
For the full list of excipients, see section 6.1.
3 Pharmaceutical form
Powder for solution for injection.
4 Clinical particulars
4.1 Therapeutic indications
Norcuron is indicated as an adjunct to general anaesthesia to facilitate tracheal intubation and to provide skeletal muscle relaxation during surgery in adults, neonates, infants, children and adolescents.
4.2 Posology and method of administration Posology
As with other neuromuscular blocking agents, Norcuron should only be administered by, or under supervision of, experienced clinicians who are familiar with the action and use of these drugs.
As with all other neuromuscular blocking agents, the dosage of Norcuron should be individualised in each patient. The anaesthetic method used, the expected duration of surgery, the possible interaction with other drugs that are administered before or during anaesthesia and the condition of the patient should be taken into account when determining the dose.
The use of an appropriate neuromuscular monitoring technique is recommended to monitor neuromuscular block and recovery.
Inhalational anaesthetics potentiate the neuromuscular blocking effects of Norcuron. This potentiation however, becomes clinically relevant in the course of anaesthesia, when the volatile agents have reached the tissue concentrations required for this interaction. Consequently, adjustments with Norcuron should be made by administering smaller maintenance doses at less frequent intervals or by using lower infusion rates of Norcuron during long lasting procedures (longer than 1 hour) under inhalational anaesthesia (see section 4.5).
Adults
In adult patients the following dosage recommendations may serve as a general guideline for tracheal intubation and muscle relaxation for short to long lasting surgical procedures.
Tracheal intubation:
The standard intubating dose during routine anaesthesia is 80 to 100 micrograms vecuronium bromide per kg body weight, after which adequate intubation conditions are established within 90 to 120 seconds in nearly all patients.
Dosages of Norcuron for surgical procedures after intubation with suxamethonium:
Recommended doses: 30 to 50 micrograms vecuronium bromide per kg body weight.
If suxamethonium is used for intubation, the administration of Norcuron should be delayed until the patient has clinically recovered from the neuromuscular block induced by suxamethonium.
Maintenance dosing:
The recommended maintenance dose is 20 to 30 micrograms vecuronium bromide per kg body weight.
These maintenance doses should best be given when twitch height has recovered to 25% of control twitch height.
Dose requirements for administration of Norcuron by continuous infusion:
If Norcuron is administered by continuous infusion, it is recommended to give a loading dose first (see 'Tracheal Intubation') and, when neuromuscular block starts to recover, to start administration of Norcuron by infusion.
The infusion rate should be adjusted to maintain twitch response at 10% of control twitch height or to maintain 1 to 2 responses to train of four stimulation.
In adults, the infusion rate required to maintain neuromuscular block at this level, ranges from 0.8 to 1.4 micrograms vecuronium bromide/kg/min. For neonates and infants see below. Repeat monitoring of neuromuscular block is recommended since infusion rate requirements vary from patient to patient and with the anaesthetic method used.
Elderly patients
The same intubation and maintenance doses as for younger adults (80 - 100 micrograms/kg and 20 -30 micrograms/kg, respectively) can be used. However, the duration of action is prolonged in elderly compared to younger subjects due to changes in pharmacokinetic mechanisms. The onset time in elderly is similar to younger adults.
Overweight and obese patients
When used in overweight or obese patients (defined as patients with a body weight of 30% or more above ideal body weight), doses should be reduced taking into account an ideal body weight.
Higher doses
Should there be reason for selection of larger doses in individual patients, initial doses ranging from 150 micrograms up to 300 micrograms vecuronium bromide per kg body weight have been administered during surgery both under halothane and neurolept anaesthesia without adverse cardiovascular effects being noted as long as ventilation is properly maintained. The use of these high dosages of Norcuron pharmacodynamically decreases the onset time and increases the duration of action. In caesarean section (see also section 4.6) and neonatal surgery the dose should not exceed 100 micrograms/kg.
Paediatric population Adolescents (12 - 17 years).
Although there is very little information on dosage in adolescents, it is advised to use the same dose as in adults, based on the physiological development at this age.
Children (2 - 11 years).
Dose requirements in children are higher than for adults and neonates (see 'Paediatric patients' in section 5.1). However, the same intubation and maintenance doses as for adults (80 - 100 micrograms/kg and 20-30 micrograms/kg, respectively) are usually sufficient. Since the duration of action is shorter in children, maintenance doses are required more frequently.
Neonates (0 - 27 days) and infants (28 days - 23 months).
Because of the possible variations of the sensitivity of the neuromuscular junction, especially in neonates and probably in infants up to 4 months of age, an initial test dose of 10 - 20 micrograms vecuronium bromide per kg body weight followed by incremental doses until 90 to 95% depression of twitch response is achieved is recommended. In neonatal surgery the dose should not exceed 100 micrograms/kg. Dose requirements in older infants (5-23 months) are the same as in adults. However, since the onset time of Norcuron in these patients is considerably shorter than in adults and children, the use of high intubating doses in general is not required for early development of good intubating conditions.
Since the duration of action and recovery time with Norcuron is longer in neonates and infants than in children and adults, maintenance doses are required less frequently (see 'Paediatric patients' in section 5.1).
Preterm newborn infants
There are insufficient data to support dose recommendations for the use of vecuronium bromide in preterm newborn infants.
Continuous infusion in paediatric patients
There are insufficient data concerning continuous infusion of Vecuronium in paediatric patients, therefore, no dosing recommendations can be made.
Method of Administration
Norcuron should be administered following reconstitution with water. For instructions on the reconstitution of the medicinal product before administration, see section 6.6. Norcuron is administered.intravenously either as a bolus injection or as a continuous infusion (see also section 6.6).
4.3 Contraindications
Hypersensitivity to vecuronium or the bromide ion or to any of the excipients listed in section 6.1.
4.4 Special warnings and precautions for use
Monitoring respiratory function during recovery
Since Norcuron causes paralysis of the respiratory muscles, ventilatory support is mandatory for patients treated with this drug until adequate spontaneous respiration is restored.
Residual neuromuscular blockade
As with other neuromuscular blocking agents, residual neuromuscular blockade has been reported for Norcuron. In order to prevent complications resulting from residual neuromuscular blockade, it is recommended to extubate only after the patient has recovered sufficiently from neuromuscular block. Other factors which could cause residual neuromuscular blockade after extubation in the post-operative phase (such as drug interactions or patient condition) should also be considered.
If not used as part of standard clinical practice, the use of a reversal agent should be considered, especially in those cases where residual neuromuscular blockade is more likely to occur.
Drug hypersensitivity reactions
High rates of cross-sensitivity between neuromuscular blocking agents have been reported. Therefore, where possible, before administering Norcuron, hypersensitivity to other neuromuscular blocking agents should be excluded. Norcuron should only be used when absolutely essential in susceptible patients. Patients who experience a hypersensitivity reaction under general anaesthesia should be tested subsequently for hypersensitivity to other neuromuscular blockers.
Vagal reactions
Since Norcuron has no cardiovascular effects within the clinical dosage range, it does not attenuate bradycardia that may occur due to the use of some types of anaesthetics and opiates or due to vagal reflexes during surgery. Therefore, reassessment of the use and/or dosage of vagolytic drugs such as atropine for premedication or at induction of anaesthesia, may be of value for surgical procedures during which vagal reactions are more likely to occur (e.g. surgical procedures where anaesthetic drugs with known vagal stimulatory effects are used, opthalmic, abdominal or anorectal surgery, etc.).
Use in the internsive care unit (ICU)
In general, following long term use of neuromuscular blocking agents in the ICU, prolonged paralysis and/or skeletal muscle weakness has been noted. In order to help preclude possible prolongation of neuromuscular block and/or overdosage it is strongly recommended that neuromuscular transmission is monitored throughout the use of neuromuscular blocking agents. In addition, patients should receive adequate analgesia and sedation. Furthermore, muscle relaxants should be titrated to effect in the individual patients by or under supervision of experienced clinicians who are familiar with their actions and with appropriate neuromuscular monitoring techniques.
Myopathy after long term administration of non-depolarising neuromuscular blocking agents in the ICU in combination with corticosteroid therapy has been reported frequently. Therefore, for patients receiving both neuromuscular blocking agents and corticosteroids, the period of use of the neuromuscular blocking agent should be limited as much as possible.
The following conditions may influence the pharmacokinetics and/or pharmacodynamics of Norcuron:
Hepatic and/or biliary tract disease and renal failure Because vecuronium is excreted in bile and in urine, Norcuron should be used with caution in patients with clinically significant hepatic and/or biliary diseases and/or renal failure. In these patient groups prolongation of action has been observed, especially when high doses of vecuronium (200 micrograms/kg bodyweight) were administered in patients with hepatic disease.
Prolonged circulation time
Conditions associated with prolonged circulation time such as cardiovascular disease, old age, oedematous state resulting in an increased volume of distribution, may contribute to an increase in the onset time of neuromuscular block. The duration of action may also be prolonged due to a reduced plasma clearance.
Neuromuscular disease
As with other neuromuscular blocking agents, Norcuron should be used with extreme caution in patients with neuromuscular disease or after poliomyelitis since the response to neuromuscular blocking agents may be considerably altered in these cases. The magnitude and direction of this alteration may vary widely. In patients with myasthenia gravis or the myasthenic (Eaton Lambert) syndrome, small doses of Norcuron may have profound effects and Norcuron should be titrated to the response.
Hypothermia
In operations under hypothermia, the neuromuscular blocking effect of Norcuron is increased and the duration is prolonged.
Obesity
Like other neuromuscular blocking agents, Norcuron may exhibit a prolonged duration and a prolonged spontaneous recovery in obese patients, when the administered doses are calculated on actual body weight.
Burns
Patients with burns are known to develop resistance to non-depolarising agents. It is recommended that the dose is titrated to response.
Other conditions which may increase the effects of Norcuron are:
Hypokalaemia (e.g. after severe vomiting, diarrhoea, and diuretic therapy), hypermagnesaemia, hypocalcaemia (after massive transfusions), hypoproteinaemia, dehydration, acidosis, hypercapnoea, cachexia. Severe electrolyte disturbances, altered blood pH or dehydration should therefore be corrected when possible.
Based on preclinical findings, Norcuron may cause a reduction in the partial thromboplastin time and the prothrombin time, like pancuronium bromide, d-tubocurarine or other non-depolarising neuromuscular blocking agents.
4.5 Interaction with other medicinal products and other forms of interaction The following drugs have been shown to influence the magnitude and/or duration of action of non-depolarising neuromuscular blocking agents:
Effect of other drugs on Norcuron Increased effect:
Halogenated volatile anaesthetics potentiate the neuromuscular block of Norcuron. The effect only becomes apparent with maintenance dosing (see also section 4.2). Reversal of the block with anticholinesterase inhibitors could also be inhibited.
After intubation with suxamethonium (see section 4.2).
Long-term concomitant use of corticosteroids and Norcuron in the ICU may result in prolonged duration of neuromuscular block or myopathy (see also section 4.4 and 4.8).
Other drugs:
• antibiotics: aminoglycoside, lincosamide and polypeptide antibiotics, acylamino-penicillin antibiotics.
• diuretics, quinidine, magnesium salts, calcium channel blocking agents, lithium salts, cimetidine, lidocaine and acute administration of phenytoin or ^-blocking agents.
Recurarisation has been reported after post-operative administration of: aminoglycoside, lincosamide, polypeptide and acylamino-penicillin antibiotics, quinidine and magnesium salts (see section 4.4).
Decreased effect:
Prior chronic administration of phenytoin or carbamazepine Calcium chloride, potassium chloride Variable effect:
Administration of other non-depolarising neuromuscular blocking agents in combination with Norcuron may produce attenuation or potentiation of the neuromuscular block, depending on the order of administration and the neuromuscular blocking agent used.
Suxamethonium given after the administration of Norcuron may produce potentiation or attenuation of the neuromuscular blocking effect of Norcuron.
Effect of Norcuron on other drugs
Effect of Norcuron on lidocaine
Norcuron combined with lidocaine may result in a quicker onset of action of lidocaine.
4.6 Fertility, pregnancy and lactation
Fertility
Animal studies do not indicate an effect on fertility.
Pregnancy
There are insufficient data on the use of Norcuron during animal or human pregnancy to assess potential harm to the foetus. Norcuron should be given to a pregnant woman only when the attending physician decides that the benefits outweigh the risks.
Note: Reversal of Norcuron-induced neuromuscular block may be inhibited or unsatisfactory in patients receiving magnesium sulfate for toxaemia of pregnancy because magnesium salts enhance neuromuscular block. Therefore, in patients receiving magnesium sulfate, the dosage of Norcuron should be reduced and be carefully titrated to twitch response.
Caesarean section
Studies with Norcuron, administered in doses up to 100 micrograms/kg, have shown its safety for use in caesarean section. In caesarean section the dose should not exceed 100 micrograms/kg.
In several clinical studies Norcuron did not affect Apgar score, foetal muscle tonus or cardiorespiratory adaptation. From umbilical cord blood sampling it is apparent that only very little placental transfer of Norcuron occurs which did not lead to the observation of any clinical adverse effect in the new-born.
Breast-feeding
It is unknown whether vecuronium bromide is excreted in human breast milk. The excretion of vecuronium bromide in milk has not been studied in animals. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with vecuronium bromide should be made taking into account the benefit of breast-feeding to the child and the benefit of vecuronium bromide therapy to the woman.
4.7 Effects on ability to drive and use machines
Since Norcuron is used as an adjunct to general anaesthesia, the usual precautionary measures after a general anaesthesia should be taken for ambulatory patients.
Norcuron®
10.....mg.............
powder for solution for injection
lOrganonl
Information for the patient
Norcuron 10 mg, powder for solution for injection
Vecuronium bromide
Read all of this leaflet carefully before you are given this medicine because it contains important information for you.
■ Keep this leaflet. You may need to read it again.
■ If you have any further questions, ask your anaesthetist or other doctor.
■ If you get any side effects, talk to your anaesthetist or other doctor. This includes any possible side effects not listed in this leaflet. See
11. What Norcuron is and what it is used for
Norcuron contains the active ingredient vecuronium bromide. Norcuron is one of a group of drugs called muscle relaxants.
Muscle relaxants are used during an operation as part of a general anaesthetic. When you have an operation your muscles must be completely relaxed. This makes it easier for the surgeon to perform the operation. Norcuron is used as a muscle relaxant in adults, in children and adolescents (2 -17 years) and in newborn babies and infants (0 days - 23 months).
Normally, your nerves send messages called impulses to your muscles. Norcuron acts by blocking these impulses so that your muscles relax. Because your breathing muscles also relax, you will need help to breathe (artificial ventilation) during and after your operation until you can breathe on your own again.
During the operation your anaesthetist will keep a check on the effect of the muscle relaxant, and if necessary will give you some more. At the end of surgery, the effects of the drug are allowed to wear off and you will start breathing on your own. Sometimes the anaesthetist will give you another drug to help speed this up.
|
MSD PROFILE | ||
|
Profile: Profile Revision: Profile Revision Date: Dimensions (mm): |
BS 12_335 01 250512 361 x 435.5 | |
|
Over Sticker |
Varnish Free |
Text Free |
|
Pharma Code |
Braille Grid |
Tamper Evident |
|
Profile |
Perforation |
Fold |
section 4.
What is in this leaflet
1. What Norcuron is and what it is used for
2. What you need to know before Norcuron is given
3. How Norcuron is given
4. Possible side effects
5. How Norcuron is stored
6. Contents of the pack and other information
12. What you need to know before Norcuron is given
A Do not take Norcuron:
■ if you are allergic to vecuronium, the bromide ion or any of the other ingredients of this medicine (listed in section 6).
^Tell your anaesthetist or other doctor if this applies to you.
Warnings and precautions
Talk to your anaesthetist or other doctor before receiving this medicine:
■ if you are allergic to muscle relaxants ■ if you have had kidney, heart, liver or gall bladder disease ■ if you have had diseases affecting nerves and muscles ■ if you have fluid retention (oedema).
^Tell your anaesthetist or other doctor if any of these applies to you.
Some conditions may influence the effects of Norcuron -for example:
■ low calcium levels in the blood ■ low potassium levels in the blood ■ high magnesium levels in the blood ■ low levels of protein in the blood ■ too much acid in the blood ■ too much carbon dioxide in the blood
■ loss of too much water from the body, for example by being sick, diarrhoea or sweating (dehydration)
■ over-breathing leading to too little carbon dioxide in the blood (alkalosis)
■ general ill-health ■ burns
■ being very overweight (obesity)
■ very low body temperature (hypothermia).
If you have any of these conditions, your anaesthetist will take this into account when deciding the correct dose of Norcuron for you.
Other medicines and Norcuron
Tell your anaesthetist or other doctor if you are taking, have recently taken or might take any other medicines. This includes medicines or herbal products that you have bought without a prescription. Norcuron may affect other medicines or be affected by them.
Medicines which increase the effect of Norcuron:
■ certain medicines used to make you sleep during surgery (anaesthetics)
■ certain medicines which are used to treat bacterial infections (antibiotics)
■ certain medicines for heart disease or high blood pressure (water tablets, calcium channel blockers, beta-blockers and quinidine)
■ certain anti-inflammatory medicines (corticosteroids)
■ medicines for manic depressive illness (bipolar disorder)
■ medicines which cause increased volume of urine (diuretics)
■ laxatives containing magnesium salts
■ local anaesthetics (lidocaine)
■ acute use of medicines for epilepsy (phenytoin)
■ the medicine called cimetidine, used to treat stomach ulcers, heartburn or acid reflux.
Medicines which decrease the effect of Norcuron:
■ chronic use of medicines for epilepsy (phenytoin and carbamazepine)
■ calcium chloride and potassium chloride.
In addition, you may be given other medicines before or during surgery which can alter the effects of Norcuron. These include certain anaesthetics, other muscle relaxants, medicines such as phenytoin and medicines which reverse the effects of Norcuron. Norcuron may make certain anaesthetics work more quickly.
Turn over w
|
MSD ARTWORK | ||
|
o = O _E |
Item NO.: 39765 Revision Date & No.: 120315-1 Pharma Code: 625 Schawk Job No.: 465793A01 | |
|
<§> — E = E E O —= o = r— _— |
Black | |
|
</) JO —= *0 — a -e <0 —= CO = |
Technical Info Profile | |
|
SCHAWK! 99 95% 5% | ||
|
Proprietary |
39765/120315-1
4.8 Undesirable effects
Adverse reactions are rare (<1/1000). The most commonly occurring adverse reactions include changes in vital signs and prolonged neuromuscular block. The most frequently reported adverse reaction during post-marketing surveillance is 'anaphylactic and anaphylactoid reactions' and associated symptoms (reporting frequency <1/100 000). See also the explanations below the table.
Tabulated list of adverse reactions
|
MedDRA SOC |
Preferred term1 | |
|
Uncommon/rare (<1/100, >1/10 000) |
Very rare (<1/10 000) | |
|
Immune system disorders |
Hypersensitivity Anaphylactic reaction Anaphylactoid reaction Anaphylactic shock Anaphylactoid shock | |
|
Nervous system disorders |
Flaccid paralysis | |
|
Cardiac disorders |
Tachycardia | |
|
Vascular disorders |
Hypotension |
Circulatory collapse and shock Flushing |
|
Respiratory, thoracic and mediastinal disorders |
Bronchospasm | |
|
Skin and subcutaneous tissue disorders |
Angioneurotic edema Urticaria Rash Erythematous rash | |
|
Musculoskeletal and connective tissue disorders |
Muscular weakness2 Steroid myopathy2 | |
|
General disorders and administration |
Drug ineffective Decreased drug effect/ therapeutic response Increased drug effect/ therapeutic response |
Face oedema Injection site pain Injection site reaction |
|
site conditions | ||
|
Injury, poisoning and procedural complications |
Prolonged neuromuscular block Delayed recovery from anaesthesia |
Airway complication of anaesthesia |
MedDRA version 8.0
1 Frequencies are estimates derived from post-marketing surveillance reports and data from the general literature.
2 after long-term use in the ICU
Description of selected adverse reactions Prolonged Neuromuscular block
The most frequent adverse reaction to nondepolarising blocking agents as a class consists of an extension of the drug's pharmacological action beyond the time period needed. This may vary from skeletal muscle weakness to profound and prolonged skeletal muscle paralysis resulting in respiratory insufficiency or apnea. A few cases of myopathy have been reported after Norcuron was used in the ICU in combination with corticosteroids (see section 4.4).
Anaphylactic reactions
Although very rare, severe anaphylactic reactions to neuromuscular blocking agents, including Norcuron, have been reported. Anaphylactic/ anaphylactoid reactions usually comprise of several signs or symptoms e.g. bronchospasm, cardiovascular changes (e.g. hypotension, tachycardia, circulatory collapse - shock), and cutaneous changes (e.g. angioedema, urticaria). These reactions have, in some cases, been fatal. Due to the possible severity of these reactions, one should always assume they may occur and take the necessary precautions.
Histamine release andhistaminoidreactions Since neuromuscular blocking agents are known to be capable of inducing histamine release both locally at the site of injection and systemically, the possible occurrence of itching and erythematous reactions at the site of injection and/or generalised histaminoid (anaphylactoid) reactions (see also under anaphylactic reactions above) should always be taken into consideration when administering these drugs.
Experimental studies with intradermal injection of Norcuron have demonstrated that this drug has only a weak capacity for inducing local histamine release. Controlled studies in man failed to demonstrate any
■St-------------------------------------------------------------------------------------------
Your anaesthetist will take this into account when deciding the correct dose of Norcuron for you.
Pregnancy and breast-feeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your anaesthetist or other doctor for advice before taking this medicine. Your anaesthetist may still give you Norcuron, but you need to discuss it first. Norcuron may be given to you if you are having a Caesarean section.
Driving and using machines
A Do not drive or use machines until advised it is safe to do so. Because Norcuron is given as part of a general anaesthetic, you may feel tired, weak or dizzy for some time afterwards. Your anaesthetist will be able to advise you on how long the effects are likely to last.
significant rise in plasma histamine levels after intravenous administration of Norcuron. Nevertheless, such cases have rarely been reported during large scale use of Norcuron.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
4.9 Overdose
In the event of overdosage and prolonged neuromuscular block, the patient should continue to receive ventilatory support and sedation. In this situation there are two options for the reversal of neuromuscular block: (1) Sugammadex can be used for reversal of intense (profound) and deep block. The dose of Sugammadex to be administered depends on the level of neuromuscular block. The use of Sugammadex for the purposes of reversal of vercuronium-induced blockade is recommended for use only in the adult population. (2) An acetylcholinesterase inhibitor (e.g. neostigmine, edrophonium, pyridostigmine) can be used once spontaneous recovery starts and should be administered in adequate doses. When administration of an acetylcholinesterase inhibiting agent fails to reverse the neuromuscular effects of Norcuron, ventilation must be continued until spontaneous breathing is restored. Repeated dosage of an acetylcholinesterase inhibitor can be dangerous.
5 Pharmacological properties 5.1 Pharmacodynamic properties
Pharmacotherapeutic group: muscle relaxants, peripherally acting agents,
ATC code: MO3A C03.
Mechanism of action
Norcuron (vecuronium bromide) is a non-depolarising neuromuscular blocking agent, chemically designated as the aminosteroid 1-(3a, 17p-diacetoxy-2p piperidino-5a -androstan-16p-yl)-1 methylpiperidinium bromide.
Norcuron blocks the transmission process between the motor nerve-ending and striated muscle by binding competitively with acetylcholine to the nicotinic receptors located in the motor end-plate region of striated muscle.
Unlike depolarising neuromuscular blocking agents, such as suxamethonium, Norcuron does not cause muscle fasciculations.
Pharmacodynamic effects
Within the clinical dosage range, vecuronium does not block the sympathetic nicotininic receptors, and thus exerts no ganglion blocking activity. In addition, in this dose range vecuronium does not block the parasympathetic muscarinic receptors, and thus exerts no vagolytic activity.
Tracheal intubation
Within 90 to 120 seconds following intravenous administration of a dose of 80 to 100 micrograms vecuronium bromide per kg body weight, good to excellent conditions for endotracheal intubation occur and within 3 to 4 minutes following administration of these dosages, general muscle paralysis adequate for any type of surgery is established. The duration of action to 25% recovery of control twitch height (clinical duration) with this dose is 24 to 60 minutes. The time to 95% recovery of control twitch height following this dose is approximately 60 to 80 minutes. With higher dosages of Norcuron, onset time to maximal block is shortened and duration of action is prolonged.
Continuous intravenous infusion
When Norcuron is administered by continuous intravenous infusion, a steady state neuromuscular block of 90% can be maintained at a constant rate of drug delivery and without clinically significant prolongation of the recovery time from neuromuscular block at termination of the infusion.
Norcuron has no cumulative effects if maintenance doses are administered at 25% recovery of control twitch height. Several maintenance doses can therefore be given in succession.
These properties allow the use of Norcuron in short, medium and long lasting surgical procedures.
Reversal of neuromuscular block
Administration of acetylcholinesterase inhibitors, such as neostigmine, pyridostigmine or edrophonium, antagonises the action of Norcuron.
Paediatric population Neonates and infants
In neonates and infants the ED95 dose of vecuronium bromide under balanced anaesthesia was found to be approximately the same (approx. 47 micrograms/kg body weight) as in adults.
The onset time of Norcuron in neonates and infants is considerably shorter as compared to children and adults, probably due to the shorter circulation time and larger cardiac output. Also, a greater sensitivity of the neuromuscular junction to the action of neuromuscular blocking agents in these patients may account for a more rapid onset of action.
The duration of action and recovery time with Norcuron is longer in neonates and infants than in adults. Maintenance doses of Norcuron should therefore be less frequently administered.
Children
In children the ED95 dose of vecuronium bromide under balanced anaesthesia was found to be higher than in adults (81 vs 43 micrograms/kg bodyweight, respectively).
In comparison to adults, the duration of action and recovery time with Norcuron in children are in general approximately 30% and 20-30% shorter respectively.
Similar to adults, cumulative effects with repeat maintenance doses of approximately one quarter of the initial dose and administered at 25% recovery of control twitch height are not observed in paediatric patients.
5.2 Pharmacokinetic properties Distribution
After intravenous administration of 100-150 micrograms/kg vecuronium, the distribution half-life of vecuronium amounts to 1.2-1.4 minutes.
Vecuronium is mainly distributed in the extracellular fluid compartment. At steady state, the volume of distribution is 0.18-0.51 l.kg-1 in adult patients.
The plasma clearance of vecuronium amounts to 3.0-6.4 ml.kg-1.min-1 and its plasma elimination half-life is 36-117 minutes.
Biotransformation
The extent of metabolism of vecuronium is relatively low. In humans, a 3-hydroxy derivative having approximately 50% less neuromuscular blocking potency than vecuronium is formed in the liver. In patients not suffering from renal or hepatic failure, the plasma concentration of this derivative is below detection limit, and does not contribute to the neuromuscular block occurring after administration of Norcuron. Elimination
Biliary excretion is the main elimination route. It is estimated that within 24 hours after intravenous administration of Norcuron, 40 to 60% of the dose administered is excreted into the bile as monoquaternary compounds. Approximately 95% of these monoquaternary compounds is unchanged vecuronium and less than 5% is 3-hydroxy vecuronium. Prolonged duration of action has been observed in patients with liver disease and/or biliary tract disease, probably as a result of decreased clearance leading to an increased elimination half-life.
Renal elimination is relatively low. The amount of monoquaternary compounds excreted in the urine collected by intravesical catheter for 24 hours following Norcuron administration is 20-30% of the dose administered. In patients with renal failure, the duration of action may be prolonged. This is probably the result of an increased sensitivity to vecuronium, but it could also be the result of a reduced plasma clearance.
Paediatric population
There are limited pharmacokinetic data for vecuronium in the paediatric population. After intravenous administration, vecuronium plasma clearance is similar across neonates, infants and children (2.8-9.0 ml.kg-1.min-1) and not different from the clearance in adults. Volume of distribution at steady state (Vdss), in infants is similar to the one in adult patients (0.29-0.43 l/kg), whereas it is slightly smaller in children (0.13 - 0.32 l/kg).
5.3 Preclinical safety data
Vecuronium bromide showed no genotoxic, embryotoxic or teratogenic potential. Single and repeated dose toxicity studies in rats, dogs and cats revealed no special hazard for humans.
6 Pharmaceutical particulars
6.1 List of excipients
Norcuron is supplied as a freeze dried powder containing:
• Citric acid monohydrate (E330)
• Disodium hydrogen phosphate dihydrate (E339)
• Mannitol (E421)
• Sodium hydroxide (E524) (for pH correction)
• Phosphoric acid (E338) (for pH correction)
No preservative has been added.
6.2 Incompatibilities
As is the case for many other drugs, incompatibility has been documented for Norcuron when added to thiopental. This medicinal product must not be mixed with other medicinal products in the same syringe or bag except those mentioned in section 6.6. If Norcuron is administered via the same infusion line that is also used for other drugs, it is important that this infusion line is adequately flushed (e.g. with 0.9% sodium chloride) between administration of Norcuron and drugs for which incompatibility with Norcuron has been demonstrated or for which compatibility with Norcuron has not been established.
6.3 Shelf life 2 years.
Norcuron can be kept until the expiry date indicated on the packaging, provided it is stored under the prescribed conditions.
Chemical and physical in-use (i.e. following reconstitution) stability has been demonstrated for 24 hours at 15 to 25°C.
From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless reconstitution/dilution (etc.) has taken place in controlled and validated aseptic conditions.
The date mentioned after “EXP.” on the label of the vial is the expiry date up to which Norcuron may be used.
6.4 Special precautions for storage
Do not store above 25°C. Keep vials in the outer carton in order to protect from light.
For storage conditions after reconstitution of the medicinal product, see section 6.3.
Do not use Norcuron when the solution after reconstitution contains particles or is not clear.
6.5 Nature and contents of containers
Packaging of 10 vials each containing 10 mg vecuronium bromide.
Vials are made of type I glass. In correspondence please quote Lot number.
6.6 Special precautions for disposal and other handling Reconstitution:
Norcuron 10 mg
Addition of 5ml water for injections results in an isotonic solution of pH 4 containing 2 mg vecuronium bromide per ml. (2 mg/ml).
Alternatively, in order to obtain a solution with a lower concentration Norcuron 10 mg may be reconstituted with a volume up to 10 ml of the following infusion fluids:
• 5% glucose injection fluid
• 0.9% sodium chloride injection fluid
• Lactated Ringer's solution
• Lactated Ringer's injection and 5% glucose
• Glucose 5% and 0.9% sodium chloride injection
• Water for injections
Compatibilities
When Norcuron is reconstituted with water for injections, the resultant solution can be mixed with the following infusion fluids, packed in PVC or glass, to a dilution up to 40 mg/litre:
• 0.9% NaCl solution
• 5% glucose solution
• Ringer's solution
• Ringer's glucose
The above-mentioned reconstituted solution can also be injected in to the line of a running infusion of the following fluids:
• Lactated Ringer's solution
• Lactated Ringer's solution and 5% glucose
• Glucose 5% and 0.9% sodium chloride solution
• Haemaccel
• Dextran-40 5% in 0.9% sodium chloride solution
• Water for injections
Compatibility studies with other infusion fluids have not been performed.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7 Marketing authorisation holder
N V Organon, Kloosterstraat 6, PO Box 20, 5340 BH, Oss, The Netherlands
8 Marketing authorisation number(s)
PL 05003/0044
9 Date of first authorisation/renewal of the authorisation
Date of first authorisation: 04 Oct 1991 Date of latest renewal: 04 Aug 2000
10 Date of revision of the text
January 2015
SPC.NOR.15.UK.4195.IB-UV84
O MSD PROFILE
| 3. How Norcuron is given
The dose
Norcuron can be used in adults, adolescents and children of all ages, including infants and newborns. Your anaesthetist will work out the dose of Norcuron you need based on:
■ the type of anaesthetic
■ the expected length of the operation
■ other drugs you are taking
■ your state of health
■ your age
You will be given Norcuron for your surgical procedure. The normal dose is 80 - 100 micrograms per kg body weight and the effect will last 24 - 60 minutes. During the procedure it will be checked whether Norcuron is still working. You may be given additional doses if they are needed.
Route of administration
Norcuron will be given to you by your anaesthetist. Norcuron is given intravenously (into a vein), either as single injections or as a continuous infusion (a drip).
If more Norcuron is given to you than recommended
As your anaesthetist will be monitoring your condition carefully it is unlikely that you will be given too much Norcuron. However if this happens, your anaesthetist will keep you breathing artificially (on a ventilator) until you can breathe on your own. It is possible to counteract the effects of (too much) Norcuron and speed-up your recovery by giving you a drug that reverses the effet of Norcuron. You will be kept asleep while this takes place.
If you have any further questions on the use of this medicine, ask your anaesthetist or other doctor.
Like all medicines, this medicine can cause side effects, although not everybody gets them. If these side effects occur while you are under anaesthetic, they will be seen and treated by your anaesthetist.
Uncommon side effects (may affect up to 1 in 100 people)
■ the drug is too effective, or not effective enough
■ the drug works for longer than expected
■ lowering of blood pressure
■ increase in heart rate.
Very rare side effects (may affect less than 1 in 10,000 people)
■ allergic (hypersensitivity) reactions (such as difficulty in breathing, collapse of the circulation and shock)
■ wheezing of the chest
■ muscle weakness
■ swelling, a rash or redness of the skin
■ pain near the site of injection.
If any of the side effects gets serious
Or if you notice any side effects not listed in this leaflet:
^Tell your anaesthetist or other doctor.
Reporting of side effects
If you get any side effects, talk to your anaesthetist or other doctor. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard. By reporting side effects you can help provide more information on the safety of this medicine.
Profile: BS 12_335
Profile Revision: 01
Profile Revision Date: 250512
Dimensions (mm): 361 x 435.5
| 5. How Norcuron is stored
The hospital will keep Norcuron according to the correct storage conditions.
What Norcuron contains
The active substance of Norcuron is vecuronium bromide 10 mg per vial. It is dissolved before use, to make a solution.
The other ingredients are:
■ citric acid monohydrate (E330)
■ disodium hydrogen phosphate dihydrate (E339)
■ mannitol (E421)
■ sodium hydroxide (E524)
■ phosphoric acid (E338)
What Norcuron looks like and contents of the pack
Norcuron is a white powder, for solution for injection.
There are 10 vials of Norcuron per pack.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder: N.V. Organon, Kloosterstraat 6, PO Box 20, 5340 BH Oss, The Netherlands.
Manufacturer: NV Organon, Kloosterstraat 6, PO Box 20, 5340 BH Oss,
The Netherlands.
Problems reading this leaflet?
To listen to or request a copy of this leaflet in Braille, large print or audio, please call, free of charge: 0800 198 5000 (UK only). Please be ready to give the following information:
Product name: Norcuron Reference Number: PL 05003/0044
This is a service provided by the Royal National Institute of the Blind This leaflet was last revised in January 2015.
PIL.NOR.15.UK.4196.IB-UV84
forganonl
Over Sticker Varnish Free Text Free
Pharma Code Braille Grid Tamper Evident
Profile Perforation Fold