Zyvec

Uses

Zyvec Bromide is used for an adjunct to general anaesthesia to facilitate tracheal intubation and to provide skeletal muscle relaxation during surgery.

Zyvec is also used to associated treatment for these conditions: General Anesthesia, Facilitation of small bowel intubation therapy, Smooth muscle relaxation prior to radiological procedures

How Zyvec works

Zyvec is a bisquaternary nitrogen compound that acts by competitively binding to nicotinic cholinergic receptors. The binding of vecuronium decreases the opportunity for acetylcholine to bind to the nicotinic receptor at the postjunctional membrane of the myoneural junction. As a result, depolarization is prevented, calcium ions are not released and muscle contraction does not occur.

Dosage

Zyvec dosage

Like other neuromuscular blocking agents, Zyvec should only be administered by, or under supervision of, experienced clinicians who are familiar with the action and use of these agents.

Like with other neuromuscular blocking agents, the dosage of Zyvec should be individualised in each patient. The anaesthetic method used, the expected duration of surgery, the possible interaction with other medicines 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 do potentiate the neuromuscular blocking effects of Zyvec. 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 Zyvec should be made by administering smaller maintenance doses at less frequent intervals or by using lower infusion rates of Zyvec during long lasting procedures (longer than 1 hour) under inhalational anaesthesia.

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 0.08 to 0.1 mg vecuronium bromide per kg body weight, after which adequate intubation conditions are established within 90 to 120 seconds in nearly all patients.

Dosages of Zyvec for surgical procedures after intubation with suxamethonium:

Recommended doses:

• 0.03 to 0.05 mg vecuronium bromide per kg body weight.
• If suxamethonium is used for intubation, the administration of Zyvec should be delayed until the patient has clinically recovered from the neuromuscular block induced by suxamethonium.

Maintenance dosing:

• The recommended maintenance dose is 0.02 to 0.03 mg 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 Zyvec by continuous infusion.
• If Zyvec 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 Zyvec 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 µg 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.

Dosing in elderly patients:

• The same intubation and maintenance doses as for younger adults (0.08-0.1 mg/kg and 0.02-0.03 mg/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.
• In caesarean section and neonatal surgery the dose should not exceed 0.1 mg/kg.

Dosing in paediatric patients:

Because of the possible variation of the sensitivity of the neuromuscular junction, especially in neonates (up to 4 weeks) and probably in infants up to 4 months of age, an initial test dose of 0.01 to 0.02 mg 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 0.1 mg/kg. Dose requirements in neonates and infants (1-12 months) are the same as in adults. However, since the onset time of Zyvec 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 Zyvec is longer in neonates and infants than in children and adults, maintenance doses are required less frequently.

Dose requirements in children (2-10 years) are higher. However, the same intubation and maintenance doses as for adults (0.08-0.1 mg/kg and 0.02-0.03 mg/kg, respectively) 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.Dosing in overweight and obese patientsWhen 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 0.15 mg up to 0.30 mg 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 Zyvec pharmacodynamically decreases the onset time and increases the duration of action.

Zyvec should be administered following reconstitution. Zyvec is administered intravenously either as a bolus injection or as a continuous infusion

Addition of 5 mL 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, Zyvec 10 mg may be reconstituted with a volume up to 10 ml respectively 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

Side Effects

Side effects are rare (<1/1000). The most commonly occurring side effects include changes in vital signs and prolonged neuromuscular block. The most frequently reported side effects during post-marketing surveillance is 'anaphylactic and anaphylactoid reactions' and associated symptoms (reporting frequency <1/100,000).

Precaution

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

As with other neuromuscular blocking agents, residual curarization has been reported for Zyvec. In order to prevent complications resulting from residual curarization, it is recommended to extubate only after the patient has recovered sufficiently from neuromuscular block. Other factors which could cause residual curarization after extubation in the post-operative phase (such as medicine 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 curarization is more likely to occur. Anaphylactic reactions can occur following the administration of neuromuscular blocking agents. Precautions for treating such reactions should always be taken. Particularly in the case of previous anaphylactic reactions to muscle relaxants, special precautions should be taken since allergic cross-reactivity to muscle relaxants has been reported.

Since Zyvec 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 medicines 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 medicines with known vagal stimulatory effects are used, ophthalmic, 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 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-depolarizing 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.

Interaction

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

Effect of Other Agents on Zyvec:

Increased Effect:

• Halogenated volatile anaesthetics potentiate the neuromuscular block of Zyvec. The effect only becomes apparent with maintenance dosing (see also Dosage and Administration). Reversal of the block with anticholinesterase inhibitors could also be inhibited.
• After intubation with suxamethonium
• Long-term concomitant use of corticosteroids and Zyvec in the ICU may result in prolonged duration of neuromuscular block or myopathy.

Other medicines:

• antibiotics: aminoglycoside, lincosamide and polypeptide antibiotics, acylaminopenicillin antibiotics,
• diuretics, quinidine, magnesium salts, calcium channel blocking agents, lithium salts, cimetidine, lidocaine 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

Decreased Effect

(possible higher dose requirements):

• prior chronic administration of phenytoin or carbamazepine
• Variable Effect
• Administration of other non-depolarizing neuromuscular blocking agents in combination with Zyvec 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 Zyvec may produce potentiation or attenuation of the neuromuscular blocking effect of Zyvec.

Effect of Zyvec on other agents:

Effect of Zyvec on lidocaine: Zyvec combined with lidocaine may result in a quicker onset of action of lidocaine.

Food Interaction

Zyvec Drug Interaction

Moderate: etomidate, lorazepam, diltiazem, furosemide, methylprednisolone, midazolamUnknown: aspirin, charcoal, epinephrine, ipratropium, glucose, hydromorphone, ipratropium, norepinephrine, naloxone, acetaminophen, procaine penicillin, valproic acid, phytonadione, ondansetron

Zyvec Disease Interaction

Major: liver disease, paresis, pulmonary impair

Half Life

51–80 minutes

Elimination Route

Fecal (40-75%) and renal (30% as unchanged drug and metabolites)

Pregnancy & Breastfeeding use

There are insufficient data on the use of Zyvec during animal or human pregnancy to assess potential harm to the foetus. Zyvec should be given to a pregnant woman only when the attending physician decides that the benefits outweigh the risks.

Caesarean section: Studies with Zyvec, administered in doses up to 0.1mg/kg, have shown its safety for use in caesarean section. In caesarean section the dose should not exceed 0.1mg/kg. In several clinical studies Zyvec 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 Zyvec occurs which did not lead to the observation of any clinical adverse effect in the newborn.

Reversal of a Zyvec 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 Zyvec should be reduced and be carefully titrated to twitch response.

Lactation: There are no human data on the use of Zyvec during lactation. Zyvec should be given to lactating women only when the attending physician decides that the benefits outweigh the risks.

Acute Overdose

In the event of overdosage and prolonged neuromuscular block, the patient should continue to receive ventilatory support and sedation. Upon start of spontaneous recovery an acetylcholinesterase inhibitor (e.g. neostigmine, edrophonium, pyridostigmine) should be administered in adequate doses.

When administration of an acetylcholinesterase-inhibiting agent fails to reverse the neuromuscular effects of Zyvec, ventilation must be continued until spontaneous breathing is restored. Repeated dosage of an acetylcholinesterase inhibitor can be dangerous.

Storage Condition

Store between 20-25° C. Protect from light.

Innovators Monograph

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