Consumer medicine information

Vecuronium Sun

Vecuronium bromide

BRAND INFORMATION

Brand name

Vecuronium Sun

Active ingredient

Vecuronium bromide

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Vecuronium Sun.

What is in this leaflet

This leaflet is a summary of some of the information about the drug Vecuronium SUN

It does not contain all the available information.

It does not take the place of talking to your doctor.

All medicines have risks and benefits. Your doctor has weighed the risks of you having Vecuronium SUN against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor.

Keep this leaflet. You may need to read it again.

What Vecuronium SUN is used for

Vecuronium SUN is one of a group of medicines called muscle relaxants. Muscle relaxants are used during an operation as part of the general anaesthetic. When you have an operation, your muscles must be completely relaxed. This makes it easier for the surgeon to perform the operation.

Normally the nerves send messages to the muscles by impulses. Vecuronium SUN acts by blocking these impulses so the muscles are relaxed. Because the muscles needed for breathing also become relaxed you will need help with your breathing (artificial respiration) during and after your operation until you can breathe on your own. During the operation the effect of the muscle relaxants is constantly checked and if necessary some more drug is given. At the end of the operation the effects of Vecuronium SUN are allowed to wear off and you can start breathing on your own. Sometimes another drug is given to help speed this up. Vecuronium SUN can also be used in Intensive Care to keep your muscles relaxed.

Ask your doctor if you have any questions about this medicine.

Vecuronium SUN is not addictive.

Before you are given Vecuronium SUN

When you must not be given it

You must not be given Vecuronium SUN if you have an allergy to:

  • any medicine containing vecuronium bromide
  • any of the ingredients listed at the end of this leaflet

Some of the symptoms of an allergic reaction may include shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue or other parts of the body; rash, itching or hives on the skin.

Vecuronium SUN should not be given to a child under the age of one month. The safety of administration of Vecuronium SUN has not been established in children under the age of one month.

Before you are given it

If you are going to have an operation it is important that you discuss the following points with your doctor, since it can influence the way Vecuronium SUN is given to you.

Tell your doctor if you have or have had any medical conditions, especially the following:

  • an allergy to muscle relaxants
  • kidney disease
  • liver or gallbladder disease
  • a heart disease
  • diseases affecting nerves or muscles
  • oedema (local or generalised swelling due to fluid)

Certain medical conditions may affect how Vecuronium SUN works:

  • low potassium levels in the blood
  • high magnesium levels in the blood
  • low calcium levels in the blood
  • low levels of protein in the blood
  • dehydration
  • too much acid in the blood
  • too much carbon dioxide in the blood
  • general ill-health.
  • overweight
  • burns

If you are suffering from any of these conditions your doctor will take this into account when deciding the correct dose of Vecuronium SUN for you.

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you are pregnant or plan to become pregnant or you are breastfeeding. Your doctor will discuss the risks and benefits of using Vecuronium SUN if you are pregnant or breast-feeding.

If you have not told your doctor about any of the above, tell him/ her before you are given Vecuronium SUN.

Taking other medicines

Tell your doctor if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may be affected by Vecuronium SUN, or affect how well it works. These include:

  • anaesthetics, medicines to make you sleep during surgery
  • long term concurrent use of corticosteroids (antiinflammatory medicines) and Vecuronium SUN in the Intensive Care Unit
  • antibiotics
  • lithium, a medicine used to treat bipolar disorder
  • medicines used to treat heart disease or high blood pressure (quinidine, calcium channel blockers, beta-blockers and diuretics (fluid tablets))
  • quinine, medicine used to treat malaria
  • magnesium salts
  • lignocaine, a local anaesthetic
  • other muscle relaxants
  • phenytoin and carbamazepine, medicines used to treat epilepsy
  • cimetidine, a medicine used to treat reflux and stomach ulcers

You may need to use different amounts of your medicines or take different medicines. Your doctor will advise you.

If you are taking magnesium sulphate to treat toxaemia of pregnancy (preeclampsia), tell your doctor as the dose of Vecuronium SUN may need to be reduced.

Your doctor will have a complete list of medicines that may cause problems when used with Vecuronium SUN.

How Vecuronium SUN is given

Vecuronium SUN will be given by a doctor.

It will not be given to you until you are asleep from the anaesthetic. It will be injected into a vein before and/or during an operation. It will be given as a single injection or continuous infusion.

The usual dose is 0.1 mg Vecuronium bromide per kg body weight and the effect lasts 20-40 minutes. During the operation your doctor will check whether Vecuronium SUN is still working.

You may be given additional doses if they are needed.

Overdose

As Vecuronium SUN doses are carefully worked out and are given by a doctor experienced in its use, it is unlikely that you will be given too much Vecuronium SUN. However, if this does happen, your doctor will make sure that you continue breathing artificially until you can breathe on your own again. Your doctor may speed-up your recovery by giving you a drug that reverses the effects of Vecuronium SUN.

After having Vecuronium SUN

Things to be careful of

Your doctor will tell you when it is safe to drive and operate potentially dangerous machinery after you have been given Vecuronium SUN.

Side effects

Tell your doctor if you notice anything that is making you feel unwell.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Do not be alarmed by the following list for side effects. You may not experience any of them.

Ask your doctor to answer any questions you may have.

Tell your doctor if you notice the following and they worry you:

  • flushing
  • pain at injection site
  • irritation at injection site
  • red skin rash or itchy rash

Tell your doctor immediately if you notice any of the following:

  • fast heart beat
  • dizziness, light-headedness (low blood pressure)
  • muscle weakness or paralysis
  • aching muscles or weakness, not caused by exercise
  • wheezing, coughing
  • difficulty breathing
  • rapid, shallow breathing, cold, clammy skin, a rapid, weak pulse, dizziness, weakness and fainting
  • swelling of the face, lips, mouth, tongue or throat which may cause difficulty in swallowing or breathing
  • sudden signs of allergy such as rash, itching, hives on the skin, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or trouble breathing These are serious side effects. You may need urgent medical attention or hospitalisation.

Storage

Vecuronium SUN is stored in the hospital.

It must be kept below 25°C and protected from light.

Product description

What it looks like

A white powder, which is dissolved with sterile water for injection immediately before use.

Packs

Vecuronium SUN 10mg: Vials in packs of 1, 4, 10 and 20 without solvent.

The vial stopper is not made with natural rubber latex.

Ingredients

Vecuronium SUN contains 4 mg or 10 mg of vecuronium bromide as the active ingredient. It also contains:

  • citric acid
  • dibasic sodium phosphate
  • sodium hydroxide
  • phosphoric acid
  • mannitol

No preservative has been added.

Sponsor

Sun Pharma ANZ Pty Ltd.
Macquarie Park
Sydney NSW 2113
Australia

This leaflet was updated in June 2019.

Australian Registration Number: AUST R 223371

Published by MIMS December 2019

BRAND INFORMATION

Brand name

Vecuronium Sun

Active ingredient

Vecuronium bromide

Schedule

S4

 

1 Name of Medicine

Vecuronium bromide.

2 Qualitative and Quantitative Composition

Vecuronium Sun 10 mg: 10 mL vials each containing 10.0 mg sterile lyophilised vecuronium bromide.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Powder for injection.
It is an odourless, bitter tasting white to creamy white, microcrystalline powder. At 25°C (pH 3), its solubility is 16 mg/mL, and pKa is 8.97. Because vecuronium bromide hydrolyses rapidly in water, a ready-for-use aqueous solution form is not available.
Following reconstitution with solvent (Water for Injections) the resultant solution is isotonic and has a pH of 4.

4 Clinical Particulars

4.1 Therapeutic Indications

Vecuronium Sun is a skeletal muscle relaxant for use as an adjunct to general anaesthesia in adults and children for all surgical procedures.

4.2 Dose and Method of Administration

Vecuronium Sun should be administered in carefully adjusted dosage by or under the supervision of experienced clinicians who are familiar with the action and use of these drugs. The drug should not be administered unless facilities for intubation, artificial respiration, oxygen therapy, suction and reversal agents are immediately available.
To avoid microbial contamination, Vecuronium Sun should be used without delay once reconstituted and any residue should be discarded.

Reconstitution.

Vecuronium Sun 10 mg.

The contents of each vial should be dissolved in 5 mL water for injections.
After reconstitution, Vecuronium Sun is administered intravenously either as a bolus injection or as a continuous infusion.
When calculating the dose of neuromuscular blocking agents the following factors must be taken into account:
The anaesthetic technique used, potential interactions with the drugs used before and during anaesthesia, and the condition of the individual patient.
The use of an appropriate neuromuscular monitoring technique is recommended to monitor neuromuscular block and recovery.
Inhalation anaesthetics do potentiate the neuromuscular blocking effects of Vecuronium Sun. 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 Vecuronium Sun should be made by administering smaller maintenance doses at less frequent intervals or by using lower infusion rates of Vecuronium Sun during longer lasting procedures (longer than 1 hour) under inhalation anaesthesia (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Initial dose.

0.10 mg/kg provides good to excellent intubating conditions within 2.5 to 3 minutes.

Incremental doses.

0.02-0.04 mg/kg.
Skeletal muscle relaxation (to 25% recovery) lasts for 20-40 minutes after initial or incremental doses.
With suxamethonium as the intubating agent, initial doses of 0.04-0.06 mg/kg of Vecuronium Sun will produce complete neuromuscular block with a similar duration of clinical effect. If suxamethonium is used prior to Vecuronium Sun the administration of Vecuronium Sun should be delayed until the patient starts recovering from suxamethonium-induced neuromuscular blockade.
The effect of prior use of other non-depolarising neuromuscular blocking agents on the activity of Vecuronium Sun has not been studied.

Use by continuous infusion.

Infusion of Vecuronium Sun should be initiated only after early evidence of spontaneous recovery from the loading dose. The infusion of Vecuronium Sun should be individualised for each patient. The rate of administration 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 microgram vecuronium bromide per kg per min. For infants see "Dosage in children". Repeat monitoring of neuromuscular block is recommended since infusion rate requirements vary from patient to patient and with the anaesthetic method used.

Dosage in elderly patients.

The same intubation and maintenance doses as for younger adults 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.

Dosage in children.

Vecuronium Sun is not approved for use in neonates or premature babies. Therefore no dosing recommendation is made.
Infants under 1 year of age but older than 7 weeks are moderately more sensitive to Vecuronium Sun on a mg/kg basis than adults (also see Section 4.4 Special Warnings and Precautions for Use, Paediatric use). Since the onset time of Vecuronium Sun 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 Vecuronium Sun is longer in infants than in children and adults, maintenance doses are required less frequently.
Dose requirements for children (2-10 years) are higher (see Section 5.1 Pharmacodynamic Properties). However, the same intubation and maintenance doses as for adults are usually sufficient. Since the duration of action is shorter in children, maintenance doses are required more frequently.
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.

Dosage in 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 a reason for selection of larger doses in individual patients, initial doses ranging from 0.15 mg up to 0.4 mg vecuronium bromide per kg body weight have been administered for surgery both under halothane and neuroleptic anaesthesia without adverse cardiovascular effects being noted as long as ventilation is properly maintained. The use of these high dosages of Vecuronium Sun pharmacodynamically decreases the onset time and increases the duration of action.

Compatibility with infusions.

When Vecuronium Sun 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/L:
0.9% NaCl solution, 5% glucose solution, Ringer's solution, Ringer's solution 2.5% glucose.
When reconstituted with water for injections, Vecuronium Sun can also be injected into the line of a running infusion of the following fluids:
lactated Ringer's solution, lactated Ringer's solution and 5% glucose, 5% glucose and 0.9% NaCl solution, Haemaccel, Dextran-40 5% in 0.9% NaCl solution.
As is the case for many other drugs, Vecuronium Sun has been shown to be incompatible when added to thiopentone or thiopentone containing solutions.
Compatibility studies with other brands of these drugs or with other infusion fluids have not been performed.
If Vecuronium Sun 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% NaCl) between administration of Vecuronium Sun and drugs for which incompatibility with Vecuronium Sun has been demonstrated or for which compatibility with Vecuronium Sun has not been established.
Neither the reconstituted Vecuronium Sun in water for injections nor the solutions further diluted with the compatible infusion fluids contain any antimicrobial preservatives. To avoid microbial contamination hazards, the reconstituted or further diluted Vecuronium Sun injections should be used immediately after preparation and any residue discarded. Do not use Vecuronium Sun when the solution after reconstitution contains particles or is not clear.

4.3 Contraindications

Vecuronium Sun is contraindicated in patients known to be hypersensitive to any of its components including the bromide ion.

4.4 Special Warnings and Precautions for Use

Warning.

Since Vecuronium Sun causes paralysis of the respiratory muscles, ventilatory support is mandatory for patients treated with this drug until adequate spontaneous respiration is restored.

Precautions.

General.

Anaphylactic reactions.

Anaphylactic reactions can occur following the administration of neuromuscular blocking agents. Allergic cross-reactivity between muscle relaxants has been reported.

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 Section 4.8 Adverse Effects (Undesirable Effects)) should always be taken into consideration when administering these drugs. Experimental studies with intradermal injection of vecuronium bromide 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 levels after intravenous administration of vecuronium bromide. Such cases have been reported only rarely, despite the fact that vecuronium bromide is now widely used.

Cardiovascular effects.

Since vecuronium bromide has no cardiovascular effects within the clinical dose 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. The dosage or need for vagolytic drugs may thus be increased in such circumstances.
As with other neuromuscular blocking agents, residual curarization has been reported for vecuronium bromide. Factors which could cause residual curarization after extubation in the post-operative phase (such as drug interactions or patient condition) should also be considered. If not already used as part of usual clinical practice, the use of sugammadex or another reversal agent should be considered, especially in those cases where residual curarization is more likely to occur.

Use in neuromuscular syndromes.

Extreme caution should be exercised and very small doses used in patients with myasthenia gravis or myasthenic (Eaton-Lambert) syndrome. In such patients, an appropriate neuromuscular monitoring technique and use of a small test dose may be of value in monitoring the response to administration of muscle relaxants. In cases of neuromuscular disease or after poliomyelitis, similar caution should be exercised.

Altered circulation time.

Conditions associated with slower circulation time in cardiovascular disease, old age and oedematous states resulting in increased volume of distribution may contribute to a delay in onset time. The duration of action may also be prolonged due to a reduced plasma clearance. Therefore dosage should not be increased.

Disorders due to other treatments/conditions.

Conditions which may increase the neuromuscular blocking effects of vecuronium bromide are: hypokalaemia (e.g. after severe vomiting, diarrhoea, and diuretic therapy), hypermagnesaemia, hypocalcaemia (after massive transfusions), hypoproteinaemia, dehydration, acidosis, hypercapnia, cachexia.
Electrolyte imbalance and diseases which lead to electrolyte imbalance, such as adrenal cortical insufficiency, have been shown to alter neuromuscular blockade. Depending on the nature of the imbalance, either enhancement or inhibition may be expected.
Severe electrolyte disturbances, altered blood pH or dehydration, should therefore be corrected when possible, prior to administration of vecuronium bromide. Monitoring of neuromuscular block by nerve stimulator is useful in all severely ill patients.

Surgery under hypothermia.

In operations under hypothermia, the neuromuscular blocking effect of vecuronium bromide is increased and the duration is prolonged.

Obesity.

Like other neuromuscular blocking agents, vecuronium bromide may exhibit a prolonged duration of action 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.

C.N.S.

Vecuronium bromide has no known effect on consciousness, the pain threshold or cerebration. Administration must be accompanied by adequate anaesthesia or sedation.

I.C.U.

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 muscle relaxants. 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 the neuromuscular blocking agents and corticosteroids, the period of use of the neuromuscular blocking agent should be limited as much as possible.

Use in hepatic impairment and/or biliary tract disease and/or in renal impairment.

Since vecuronium is excreted in bile and urine, vecuronium bromide 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 (0.15 - 0.2 mg/kg bodyweight) were administered in patients with hepatic disease.

Use in the elderly.

No data available.

Paediatric use.

A variable, often prolonged, duration of action and potency has been observed in infants. Infants under 1 year of age but older than 7 weeks are moderately more sensitive to vecuronium bromide on a mg/kg basis than adults and take about 1½ times as long to recover (with or without halothane anaesthesia). Use of vecuronium bromide should therefore be avoided unless the expected benefits outweigh the potential risks (also see Section 4.1 Therapeutic Indications).

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

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 Vecuronium Sun.

Increased effect. Halogenated volatile anaesthetics potentiate the neuromuscular block of vecuronium bromide. The effect only becomes apparent with maintenance dosing (see Section 4.2 Dose and Method of Administration). With the presence of these volatile agents, reversal of the block with anticholinesterase inhibitors could also be inhibited.
After intubation with suxamethonium (see Section 4.2 Dose and Method of Administration).
Long-term concomitant use of corticosteroids and vecuronium bromide in the ICU may result in a prolonged duration of neuromuscular block or myopathy (see Section 4.4 Special Warnings and Precautions for Use; Section 4.8 Adverse Effects (Undesirable Effects)).

Other drugs.

Antibiotics: aminoglycoside, lincosamide and polypeptide antibiotics, acylamino-penicillin antibiotics;
diuretics, quinidine, magnesium salts, calcium channel blocking agents, lithium salts, cimetidine, lignocaine and acute administration of phenytoin or β-blocking agents.
Recurarization has been reported after post-operative administration of: aminoglycoside, lincosamide, polypeptide and acylamino-penicillin antibiotics, quinidine and magnesium salts (see Section 4.4 Special Warnings and Precautions for Use).
Decreased effect (possible higher dose requirements). Prior chronic administration of phenytoin or carbamazepine.
Variable effect. Administration of other non-depolarising neuromuscular blocking agents in combination with vecuronium bromide 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 a non-depolarising neuromuscular blocking agent may produce potentiation or attenuation of the neuromuscular blocking agent used.

Effect of Vecuronium Sun on other drugs.

Vecuronium bromide combined with lignocaine may result in a quicker onset of action of lignocaine.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No adverse effects on fertility or overall reproductive performance were observed in rats treated with intravenous vecuronium bromide at doses up to 15% of the clinical dose on a body surface area basis. Studies with vecuronium bromide alone or in combination with an anaesthetic agent, at doses comparable with clinical dosages, have not been conducted.
(Category C)
Vecuronium crosses the placenta but there have been no demonstrated adverse effects in the foetus or the newborn infant. In animal studies intravenous administration of vecuronium bromide to rats during the period of organogenesis at up to maternotoxic doses (about 15% of the recommended clinical dose, based on body surface area basis) was associated with slightly increased incidences of visceral abnormalities. Similar administration to rabbits at less than maternotoxic doses (about 0.5-2% of the recommended clinical dose, based on a body surface area) was also associated with increased incidences of visceral abnormalities.
There are insufficient data on the use of vecuronium bromide during animal or human pregnancy to assess potential harm to the foetus. Vecuronium bromide should be given to a pregnant woman only when the attending physician decides that the benefits outweigh the risks.

Note.

Reversal of vecuronium bromide-induced neuromuscular block may be unsatisfactory in patients receiving magnesium salts for the management of toxemia of pregnancy because magnesium salts enhance the neuromuscular blockade (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions). In patients, the dosage of vecuronium bromide should be reduced and carefully titrated to twitch response.

Caesarean section.

Studies with vecuronium bromide, administered in doses up to 0.1 mg/kg, have shown its safety for use in caesarean section.
In several clinical studies vecuronium bromide 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 bromide occurs, the amount being dependent on time from injection to delivery, and which did not lead to the observation of any clinical adverse effect in the new-born.
 There are no human data on the use of vecuronium bromide during lactation. A decrease in early postnatal survival was observed in rats at a maternal dose of about 15% of the clinical dose, based on body surface area. Vecuronium bromide should be given to lactating women only when the attending physician decides that the benefits outweigh the risks.

4.7 Effects on Ability to Drive and Use Machines

Since vecuronium bromide is used as an adjunct to general anaesthesia, the usual precautionary measures after general anaesthesia should be taken for ambulatory patients.

4.8 Adverse Effects (Undesirable Effects)

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). Please see Table 1.

Prolonged neuromuscular block.

With non-depolarising agents in general, the most frequent adverse reactions consist of an extension of the pharmacological action beyond the time period needed for surgery and anaesthesia or inadequate reversal of the neuromuscular blockade. 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 bromide was used in the ICU in combination with corticosteroids (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Inadequate reversal of the neuromuscular blockade is possible with vecuronium bromide as with all curariform drugs. These adverse reactions are managed by manual or mechanical ventilation until recovery is judged adequate (see Section 4.9 Overdose).

Anaphylactic reactions.

Although very rare, severe anaphylactic reactions to neuromuscular blocking agents, including vecuronium bromide, 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.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.9 Overdose

For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).
The possibility of iatrogenic overdosage can be minimised by carefully using an appropriate neuromuscular monitoring technique.

Clinical features.

The symptoms of overdosage with a non-depolarising muscle relaxant are those of prolonged paralysis, apnoea, low tidal volume, respiratory depression and/or persistent muscle weakness. Death may follow acute respiratory failure unless treated promptly.

Management.

1) Supportive measures.

Ventilatory support and sedation.

2) Reversal of neuromuscular blockade.

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. (2) An acetylcholinesterase inhibitor (e.g. pyridostigmine, neostigmine or edrophonium), with appropriate vagolytic (e.g. atropine) can be used at reappearance of T2 or at the first signs of clinical recovery and should be administered in adequate doses. Adequate reversal can be judged by the ability of the patient to lift his or her head for at least 5 seconds or preferably by the use of an appropriate neuromuscular monitoring technique. When administration of an acetylcholinesterase inhibiting agent fails to reverse the neuromuscular effects of Vecuronium Sun, ventilation must be continued until spontaneous breathing is restored. Overdosage of an acetylcholinesterase inhibitor can be dangerous.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Vecuronium bromide is a nondepolarising neuromuscular blocking agent possessing all of the characteristic pharmacological actions of this class of drugs (curariform). It acts by competing for cholinergic receptors at the motor end-plate. The antagonism to acetylcholine is inhibited and neuromuscular block is reversed by acetylcholinesterase inhibitors such as neostigmine, edrophonium and pyridostigmine. The neuromuscular block can also be reversed by sugammadex, a Selective Relaxant Binding Agent. The potency of vecuronium bromide is equal to or somewhat greater than that of pancuronium; the duration of neuromuscular blockade produced by vecuronium bromide is significantly shorter than that of pancuronium at initially equipotent doses with less cumulative effect. The time to onset of paralysis decreases and the duration of maximum effect increases with increasing vecuronium bromide doses. The use of an appropriate neuromuscular monitoring technique may be of benefit in assessing the degree of muscular relaxation.
An initial vecuronium bromide dose of 0.10 mg/kg generally produces first depression of twitch in approximately 1 minute, good or excellent intubation conditions within 2.5 to 3 minutes and maximum neuromuscular blockade within 3 to 5 minutes of injection in most patients. Because of the minimal tendency for cumulation, frequent maintenance doses can be given in succession. Vecuronium bromide is suitable for both short and prolonged operations.
At the clinical dosage, vecuronium bromide has no vagolytic or ganglion blocking actions and histamine release is not expected to be clinically significant. Therefore side-effects on the cardiovascular and pulmonary systems are not to be expected. It does not counteract those haemodynamic changes or known side effects produced by or associated with anaesthetic agents and the likelihood of reflex bradycardia may thus be increased. It has no known effect on consciousness, the pain threshold or cerebration.
The action of vecuronium bromide can be antagonised either by sugammadex or by acetylcholinesterase inhibitors, such as neostigmine, pyridostigmine or edrophonium, in appropriate dosage. Sugammadex can be given for routine reversal at 1-2 post-tetanic counts to reappearance of T2. Acetylcholinesterase inhibitors can be administered at reappearance of T2 or at the first signs of clinical recovery.
Paediatric patients.

Infants.

The ED95 dose of vecuronium bromide under nitrous oxide in oxygen anaesthesia was found to be approximately the same (approx. 47 microgram/kg body weight) as in adults. The onset of time is considerably shorter in infants as compared to children and adults, probably due to the shorter circulation time and relatively large cardiac output. Also, 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 vecuronium bromide is longer in infants than in adults. Maintenance doses of vecuronium bromide should therefore be less frequently administered (see Section 4.4 Special Warnings and Precautions for Use, Paediatric use; Section 4.2 Dose and Method of Administration).

Children.

The ED95 dose of vecuronium bromide under nitrous oxide in oxygen anaesthesia was found to be higher than in adults (0.081 vs 0.043 mg/kg body weight, respectively). In comparison to adults, the duration of action and recovery time with vecuronium bromide 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 control twitch height are not observed in paediatric patients.

Clinical trials.

Not applicable.

5.2 Pharmacokinetic Properties

Absorption and distribution.

After intravenous administration of 0.1-0.15 mg/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 0.16-0.51 L.kg-1 in adult patients.
The plasma clearance of vecuronium amounts to 3.0-5.6 mL.kg-1.min-1 and its plasma elimination half-life is 36-117 minutes.

Metabolism.

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 low, and does not contribute to the neuromuscular block occurring after administration of vecuronium bromide.

Excretion.

Biliary excretion is the main elimination route. It is estimated that within 24 hours after intravenous administration of vecuronium bromide, 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 vecuronium bromide 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 a reduced plasma clearance.

5.3 Preclinical Safety Data

Genotoxicity.

Vecuronium was not genotoxic in a series of assays for gene mutation (Salmonella typhimurium), chromosomal damage (rat micronucleus assay) or DNA damage.

Carcinogenicity.

Carcinogenicity studies with vecuronium have not been conducted.

6 Pharmaceutical Particulars

6.1 List of Excipients

Citric acid, dibasic sodium phosphate, sodium hydroxide and/or phosphoric acid to buffer and adjust the pH and mannitol to make isotonic.

6.2 Incompatibilities

See Section 4.2 Dose and Method of Administration, Compatibility with infusions.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C and protected from light.

6.5 Nature and Contents of Container

Vecuronium Sun 10 mg is packed in 10 mL colorless tubular glass vial with 20 mm grey bromobutyl rubber stopper sealed with 20 mm red flip off aluminum seal printed with 'Paralyzing Agent' in black. Each vial contains 10.0 mg sterile lyophilised vecuronium bromide.
The vial stopper is not made with natural rubber latex.
Single component: Boxes of 1, 4, 10 and 20 vials (without solvent).

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical Name: 1-[3α,17β-diacetoxy-2β- (piperidin-1-yl)-5α-androstan- 16β-yl]-1-methylpiperidinium bromide.
Non-proprietary Name: vecuronium bromide.
Laboratory Code: Org NC 45.

Chemical structure.


CAS number.

50700-72-6.
Mol. Formula: C34H57BrN2O4. Mol. Weight: 637.73.
Vecuronium bromide is a monoquaternary steroid derivative homologous with pancuronium bromide.
It is an odourless, bitter tasting white to creamy white, microcrystalline powder. At 25°C (pH 3), its solubility is 16 mg/mL, and pKa is 8.97. Because vecuronium bromide hydrolyses rapidly in water, a ready-for-use aqueous solution form is not available.
Following reconstitution with solvent (Water for Injections) the resultant solution is isotonic and has a pH of 4. Vecuronium Sun is available in 10 mL vials containing 10 mg of vecuronium bromide.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes