Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2016 Publisher: Sun Pharmaceutical Industries Europe B.V., Polarisavenue 87, 2132 JH Hoofddorp, The Netherlands
Hypersensitivity to the active substance, to bromide ion or to any of the excipients listed in section 6.1.
Since vecuronium causes paralysis of the respiratory muscles, ventilatory support is mandatory for patients treated with this drug until adequate spontaneous respiration is restored.
As with other neuromuscular blocking agents, residual neuromuscular blockade has been reported for vecuronium. 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.
High rates of cross-sensitivity between neuromuscular blocking agents have been reported. Therefore, where possible, before administering vecuronium, hypersensitivity to other neuromuscular blocking agents should be excluded. Vecuronium 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.
Since vecuronium 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.).
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 vecuronium
Because vecuronium is excreted in bile and in urine, vecuronium 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.
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.
As with other neuromuscular blocking agents, vecuronium 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 vecuronium may have profound effects and vecuronium should be titrated to the response.
In operations under hypothermia, the neuromuscular blocking effect of vecuronium is increased and the duration is prolonged.
Like other neuromuscular blocking agents, vecuronium may exhibit a prolonged duration and a prolonged spontaneous recovery in obese patients, when the administered doses are calculated on actual body weight.
Patients with burns are known to develop resistance to non-depolarising agents. It is recommended that the dose is titrated to response.
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, vecuronium 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.
The following drugs have been shown to influence the magnitude and/or duration of action of non-depolarising neuromuscular blocking agents.
Halogenated volatile anaesthetics potentiate the neuromuscular block of vecuronium. The effect only becomes apparent with maintenance dosing (see also section 4.2). Reversal of the block with cholinesterase inhibitors could also be inhibited.
After intubation with suxamethonium (see section 4.2).
Long-term concomitant use of corticosteroids and vecuronium in the ICU may result in prolonged duration of neuromuscular block or myopathy (see also section 4.4 and 4.8).
Other drugs:
Recurarisation has been reported after post-operative administration of:
Administration of other non-depolarising neuromuscular blocking agents in combination with vecuronium 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 vecuronium may produce potentiation or attenuation of the neuromuscular blocking effect of vecuronium.
Vecuronium combined with lidocaine may result in a quicker onset of action of lidocaine.
Animal studies do not indicate an effect on fertility.
There are insufficient data on the use of vecuronium during animal or human pregnancy to assess potential harm to the foetus. Vecuronium should be given to a pregnant woman only when the attending physician decides that the benefits outweigh the risks.
Reversal of vecuronium-induced neuromuscular block may be inhibited or unsatisfactory in patients receiving magnesium sulphate for toxaemia of pregnancy because magnesium salts enhance neuromuscular block. Therefore, in patients receiving magnesium sulphate, the dosage of vecuronium should be reduced and be carefully titrated to twitch response.
Studies with vecuronium, 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 vecuronium 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 vecuronium occurs which did not lead to the observation of any clinical adverse effect in the new-born.
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.
Since vecuronium is used as an adjunct to general anaesthesia, the usual precautionary measures after a general anaesthesia should be taken for ambulatory patients.
Adverse drug reactions (ADRs) are rare (<1/1000). The most commonly occurring ADRs include changes in vital signs and prolonged neuromuscular block. The most frequently reported ADR during post-marketing surveillance is ‘anaphylactic and anaphylactoid reactions’ and associated symptoms (reporting frequency <1/100 000). See also the explanations below the table 1.
Table 1:
Adverse reactions are ranked under headings of frequency, the most frequent first, using the following convention: uncommon/rare (<1/100, >1/10,000), very rare (<1/10,000).
Very rare: Hypersensitivity, Anaphylactic reaction, Anaphylactoid reaction, Anaphylactic shock, Anaphylactoid shock
Very rare: Flaccid paralysis
Uncommon/rare: Tachycardia
Uncommon/rare: Hypotension
Very rare: Circulatory collapse and shock, Flushing
Very rare: Bronchospasm
Very rare: Angioneurotic edema, Urticaria, Rash, Erythematous rash
Very rare: Muscular weakness1, Steroid myopathy1
Uncommon/rare: Drug ineffective, Decreased drug effect/therapeutic response, Increased drug effect/therapeutic response
Very rare: Face oedema, Injection site pain, Injection site reaction
Uncommon/rare: Prolonged neuromuscular block, Delayed recovery from anaesthesia
Very rare: Airway complication of anaesthesia
MedDRA version 8.0
Frequencies are estimates derived from post-marketing surveillance reports and data from the general literature.
1 after long-term use in the ICU
The most frequent adverse reaction to non-depolarising 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 apnoea. A few cases of myopathy have been reported after vecuronium was used in the ICU in combination with corticosteroids (see section 4.4).
Although very rare, severe anaphylactic reactions to neuromuscular blocking agents, including vecuronium, 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.
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 vecuronium have demonstrated that this drug has only a weak capacity for inducing local histamine release. Controlled studies in man failed to demonstrate any significant rise in plasma histamine levels after intravenous administration of vecuronium. Nevertheless, such cases have rarely been reported during large scale use of vecuronium.
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, website www.mhra.gov.uk/yellowcard.
As is the case for many other drugs, incompatibility has been documented for vecuronium when added to thiopental.
This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.
If vecuronium 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 vecuronium and drugs for which incompatibility with vecuronium has been demonstrated or for which compatibility with vecuronium has not been established.
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