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Adult Dosage

Dosage: 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 a peripheral nerve stimulator is recommended to monitor neuromuscular blockade and recovery.

The following dosages may serve as general guidelines for initial and maintenance intravenous bolus dose requirements of Norcuron to assure appropriate muscle relaxation throughout short, medium and long lasting surgical procedures under balanced anaesthesia, with and without the use of Norcuron for facilitation of endotracheal intubation.

Adults and children (see also use in paediatrics)

Intubating dose: 80 to 100 micrograms vecuronium bromide per kg body weight.

Dosages of Norcuron for surgical procedures after intubation with succinylcholine: 30 to 50 micrograms vecuronium bromide per kg body weight.

If succinylcholine is used for intubation, the administration of Norcuron should be delayed until the patient has clinically recovered from the neuromuscular block induced by succinylcholine.

Maintenance dose: 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.

Notes:

In obese patients, these doses should be reduced taking into account a lean body mass.

Since inhalational anaesthetics potentiate the action of Norcuron (see interactions), doses of Norcuron in general should be reduced during surgical procedures where these anaesthetics are used.

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 and neonatal surgery the dose should not exceed 100 micrograms/kg.

Neonates and infants up to one year of age

Because of the possible variations of the sensitivity of the neuromuscular junction, especially in neonates (up to 4 weeks) and probably in infants (up to 4 months of age), it is recommended that an initial test dose of 10 to 20 micrograms vecuronium bromide per kg body weight followed by incremental doses until 90 to 95% depression of twitch response is achieved. Dose requirements in infants of 5 months to 1 year of age 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 could be lower and are required less frequently. 

Dose requirements for administration of Norcuron by continuous infusion

If Norcuron is administered by continuous infusion, it is recommended that a bolus dose of ED₉₀ or 2xED₉₀ (40-100 micrograms per kg) is administered first and, when neuromuscular block starts to recover, administration of Norcuron by infusion is commenced. The infusion rate should be adjusted to maintain twitch response at 10% of control twitch height. 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 above. Repeated monitoring of neuromuscular block is essential since infusion rate requirements vary from patient to patient and with the anaesthetic method used.

Administration: Norcuron should be administered intravenously.

Contra Indications

Former anaphylactic reactions to vecuronium or the bromide ion

Special Precautions

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.

Since Norcuron causes relaxation of the respiratory muscles, mechanical ventilation until spontaneous respiration is restored, is necessary for patients treated with this drug.

Anaphylactic reactions to neuromuscular blocking agents in general have been reported. Although these are very rarely seen with Norcuron, precautions for treating such reactions if they would occur should always be taken. This is particularly important in the case of previous anaphylactic reactions to neuromuscular blocking agents, since allergic cross-reactivity to neuromuscular blocking agents has been reported.

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.).

Presently there are insufficient data to give recommendations for the use of Norcuron in the Intensive Care Unit. As with other muscle relaxants prolonged neuromuscular block following long term use of Norcuron in seriously ill patients in the Intensive Care Unit has been reported. It is essential that during continuous neuromuscular block patients receive adequate analgesia and sedation and that neuromuscular transmission is monitored throughout; furthermore, muscle relaxants should be administered in carefully adjusted doses, sufficient for the maintenance of less than complete block by or under the supervision of experienced clinicians who are familiar with its actions with appropriate neuromuscular monitoring techniques.

The following disease states may influence the pharmacokinetics and/or pharmacodynamics of Norcuron:

Hepatic and/or biliary tract disease

Despite the fact that Norcuron is excreted mainly via the bile, in general only moderate changes of the course of neuromuscular block induced by Norcuron are found in patients with hepatic and/or biliary tract diseases. In addition, these changes are dose dependent. With a dose of 100 micrograms vecuronium bromide per kg body weight, a slight, statistically not significant prolongation of the onset time and decrease of the duration of action were found as compared to normal patients. At doses of 150 and 200 micrograms vecuronium bromide per kg body weight, the prolongation of the onset time was even less pronounced (150 micrograms/kg) or absent (200 micrograms/kg), and no alterations of the duration of action were found in the 150 micrograms/kg group, while significant increases in the duration of action and in the recovery time were observed in the 200 micrograms/kg group.

Renal failure

Only limited changes of pharmacodynamic parameters were reported with Norcuron when administered to patients with renal failure.

As with other non-depolarising neuromuscular blocking agents, a limited degree of resistance to the action of Norcuron may occur in patients with renal failure. A slight, clinically not relevant, prolongation of onset time and recovery time may occur when Norcuron is administered to patients with renal failure.

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.

Neuromuscular disease

As with other neuromuscular blocking agents, Norcuron should be used with extreme caution in cases of neuromuscular disease or after poliomyelitis since the response to neuromuscular blocking agents may be considerably altered in these patients. 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 prolonged.

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.

Like pancuronium bromide, d-tubocurarine or other non-depolarising neuromuscular blocking agents, Norcuron may cause a reduction in the partial thromboplastin time and the prothrombin time.

Interactions

The following drugs have shown to influence the magnitude and/or duration of action of non-depolarising neuromuscular blocking agents:

Increased effect:

Anaesthetics:

• halothane, ether, enflurane, isoflurane, methoxyflurane, cycloproprane, propofol

• High doses of thiopental, methohexital, ketamine, fentanyl, gammahydroxybutyrate, etomidate

*Other non-depolarising neuromuscular blocking agents.

*Prior administration of succinylcholine (1 mg/kg).

*Other drugs:

• antibiotics:

aminoglycoside and polypeptide antibiotics, acylaminopenicillin antibiotics, high doses of metronidazole

• diuretics, β-adrenergic blocking agents, thiamine, MAO inhibiting agents, quinidine, protamine, α-adrenergic blocking agents, magnesium salts.

Decreased effect:

• neostigmine, edrophonium, pyridostigmine, aminopyridine derivatives.

• prior chronic administration of corticosteroids, phenytoin or carbamazepine

• noradrenaline, azathioprine (only transient and limited effect), theophylline, CaCl₂

Variable effect:

• depolarising muscle relaxants, e.g. succinylcholine, given after the administration of Norcuron may produce potentiation or attenuation of the neuromuscular blocking effect of Norcuron.

Adverse Reactions

The following adverse drug reactions to vecuronium bromide have been reported during post marketing surveillance and are very rare i.e. they occur with a frequency of less than 1 per 10,000:

Prolonged Neuromuscular block

The most frequent adverse reaction to nondepolarizing 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

Anaphylactic and histaminoid reactions

Anaphylactic reactions

Although very rare, severe anaphylactic reactions to neuromuscular blocking agents, including Norcuron, have been reported. Examples of anaphylactic/anaphylactoid reactions are: bronchospasm, cardiovascular changes (e.g. hypotension, tachycardia, circulatory collapse – shock), and cutaneous changes (e.g. angioedema, urticaria). These reactions have, in some cases, been fatal. Due to the possible severity of these reactions, one should always assume they may occur and take the necessary precautions.

Histamine release and histaminoid reactions

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 significant rise in plasma histamine levels after intravenous administration of Norcuron. Nevertheless, such cases have rarely been reported during large scale use of Norcuron.

Myopathy

Although very rare, myopathy following prolonged use of muscle relaxants in conjuction with high doses of steroids has been reported in patients in the Intensive Care Unit.

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