Vecuronium Drug Information

Vecuronium bromide for injection is indicated as an adjunct to general anesthesia, to facilitate endotracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation.

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 respiration insufficiency or apnea. 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. Little or no increase in intensity of blockade or duration of action with vecuronium bromide is noted from the use of thiobarbiturates, narcotic analgesics, nitrous oxide, or droperidol. See OVERDOSAGE for discussion of other drugs used in anesthetic practice which also cause respiratory depression.

Prolonged to profound extensions of paralysis and/or muscle weakness as well as muscle atrophy have been reported after long-term use to support mechanical ventilation in the intensive care unit (see PRECAUTIONS, Long Term Use in I.C.U. ). The administration of vecuronium bromide has been associated with rare instances of hypersensitivity reactions (bronchospasm, hypotension and/or tachycardia, sometimes associated with acute urticaria or erythema); (see also CLINICAL PHARMACOLOGY ). There have been postmarketing reports of severe allergic reactions (anaphylactic and anaphylactoid reactions) associated with use of neuromuscular blocking agents, including VECURONIUM BROMIDE. These reactions, in some cases, have been life-threatening and fatal. Because these reactions were reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency (See WARNINGS and PRECAUTIONS ).

Drug Interactions Prior administration of succinylcholine may enhance the neuromuscular blocking effect of vecuronium and its duration of action. If succinylcholine is used before vecuronium, the administration of vecuronium should be delayed until the succinylcholine effect shows signs of wearing off. With succinylcholine as the intubating agent, initial doses of 0.04 to 0.06 mg/kg of vecuronium may be administered to produce complete neuromuscular block with clinical duration of action of 25 to 30 minutes (see CLINICAL PHARMACOLOGY ). The use of vecuronium before succinylcholine, in order to attenuate some of the side effects of succinylcholine, has not been sufficiently studied.

Other nondepolarizing neuromuscular blocking agents (pancuronium, d-tubocurarine, metocurine, and gallamine) act in the same fashion as does vecuronium, therefore, these drugs and vecuronium, may manifest an additive effect when used together. There are insufficient data to support concomitant use of vecuronium and other competitive muscle relaxants in the same patient. Inhalational Anesthetics: Use of volatile inhalational anesthetics such as enflurane, isoflurane, and halothane with vecuronium will enhance neuromuscular blockade.

Potentiation is most prominent with use of enflurane and isoflurane. With the above agents the initial dose of vecuronium may be the same as the balanced anesthesia unless the inhalational anesthetic has been administered for a sufficient time at a sufficient dose to have reached clinical equilibrium (see CLINICAL PHARMACOLOGY ). Antibiotics: Parenteral/intraperitoneal administration of high doses of certain antibiotics may intensify or produce neuromuscular block on their own. The following antibiotics have been associated with various degrees of paralysis: aminoglycosides (such as neomycin, streptomycin, kanamycin, gentamicin, and dihydrostreptomycin); tetracyclines; bacitracin; polymyxin B; colistin; and sodium colistimethate.

If these or other newly introduced antibiotics are used in conjunction with vecuronium, unexpected prolongation of neuromuscular block should be considered a possibility. Thiopental: Reconstituted vecuronium, which has an acid pH, should not be mixed with alkaline solutions (e.g., barbiturate solutions such as thiopental) in the same syringe or administered simultaneously during intravenous infusion through the same needle or through the same intravenous line (see DOSAGE AND ADMINISTRATION-COMPATIBILITY ). Other: Experience concerning injection of quinidine during recovery from use of other muscle relaxants suggests that recurrent paralysis may occur. This possibility must also be considered for vecuronium.

Vecuronium induced neuromuscular blockade has been counteracted by alkalosis and enhanced by acidosis in experimental animals (cat). 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. Magnesium salts, administered for the management of toxemia of pregnancy may enhance the neuromuscular blockade.

Drug/Laboratory Test Interactions: None known.

Pregnancy Teratogenic Effects Animal reproduction studies have not been conducted with vecuronium. It is also not known whether vecuronium can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Vecuronium should be given to a pregnant woman only if clearly needed.

Pediatric Use Infants under 1 year of age but older than 7 weeks also tested under halothane anesthesia, are moderately more sensitive to vecuronium on a mg/kg basis than adults and take about 1½ times as long to recover. See DOSAGE AND ADMINSTRATION: Use in Pediatrics subsection for recommendations for use in pediatric patients 7 weeks to 16 years of age. The safety and effectiveness of vecuronium in pediatric patients less than 7 weeks of age have not been established.

Vecuronium bromide is contraindicated in patients known to have a hypersensitivity to it.

The possibility of iatrogenic overdosage can be minimized by carefully monitoring muscle twitch response to peripheral nerve stimulation. Excessive doses of vecuronium produce enhanced pharmacological effects. Residual neuromuscular blockade beyond the time period needed may occur with vecuronium as with other neuromuscular blockers.

This may be manifested by skeletal muscle weakness, decreased respiratory reserve, low tidal volume, or apnea. A peripheral nerve stimulator may be used to assess the degree of residual neuromuscular blockade from other causes of decreased respiratory reserve. Respiratory depression may be due either wholly or in part to other drugs used during the conduct of general anesthesia such as narcotics, thiobarbiturates and other central nervous system depressants.

Under such circumstances the primary treatment is maintenance of a patent airway and manual or mechanical ventilation until complete recovery of normal respiration is assured. Pyridostigmine, neostigmine, or edrophonium, in conjunction with atropine or glycopyrrolate will usually antagonize the skeletal muscle relaxant action of vecuronium. Satisfactory reversal can be judged by adequacy of skeletal muscle tone and by adequacy of respiration.

A peripheral nerve stimulator may also be used to monitor restoration of twitch height. Failure of prompt reversal (within 30 minutes) may occur in the presence of extreme debilitation, carcinomatosis, and with concomitant use of certain broad spectrum antibiotics, or anesthetic agents and other drugs which enhance neuromuscular blockade or cause respiratory depression of their own. Under such circumstances the management is the same as that of prolonged neuromuscular blockade.

Ventilation must be supported by artificial means until the patient has resumed control of his respiration. Prior to the use of reversal agents, reference should be made to the specific package insert of the reversal agent. The effects of hemodialysis and peritoneal dialysis on plasma levels of vecuronium and its metabolite are unknown.