Mivacron Special Precautions

In common with all the other neuromuscular blocking agents MIVACRON paralyses the respiratory muscles as well as other skeletal muscles but has no effect on consciousness. MIVACRON should be administered only by or under the close supervision of an experienced anaesthetist with adequate facilities for endotracheal intubation and artificial ventilation.
Prolonged and intensified neuromuscular blockade following MIVACRON may occur secondary to reduced plasma cholinesterase activity in the following states or pathological conditions: physiological variation as in pregnancy and the puerperium (see Use in Pregnancy and Lactation); genetically determined abnormalities of plasma cholinesterase (see as follows and Contraindications); severe generalised tetanus, tuberculosis and other severe or chronic infections; chronic debilitating disease, malignancy, chronic anaemia and malnutrition; myxoedema and collagen diseases; decompensated heart disease; peptic ulcer; burns (see as follows); end-stage hepatic failure, (see Dosage & Administration); acute, chronic or end-stage renal failure (see Dosage & Administration); iatrogenic: following plasma exchange, plasmapheresis, cardiopulmonary bypass, and as a result of concomitant drug therapy (see Interactions).
In common with suxamethonium/succinylcholine, patients homozygous for the atypical plasma cholinesterase gene (1 in 2500 patients) are extremely sensitive to the neuromuscular blocking effect of MIVACRON. In three such adult patients, a small dose of MIVACRON 0.03 mg/kg (approximately the ED_10-20 in genotypically normal patients), produced complete neuromuscular block for 26 to 128 minutes.
In patients heterozygous for the atypical plasma cholinesterase gene, the clinically effective duration of block of MIVACRON 0.15 mg/kg is approximately 10 minutes longer than in control patients.
Once spontaneous recovery had begun, neuromuscular block in these patients was antagonised with conventional doses of neostigmine.
Patients with burns may develop resistance to non-depolarising neuromuscular blocking agents and require increased doses. However, such patients may also have reduced plasma cholinesterase activity, requiring dose reduction. Consequently, burn patients should be given a test dose of 0.015 to 0.020 mg/kg MIVACRON followed by appropriate dosing guided by monitoring of block with a nerve stimulator.
Caution should be exercised in administering MIVACRON to patients with a history suggestive of an increased sensitivity to the effects of histamine, e.g. asthma.
If MIVACRON is used in this group of patients it should be administered over 60 seconds.
Caution should also be exercised when administering MIVACRON to patients who have shown hypersensitivity to other neuromuscular blocking agents since a high rate of cross-sensitivity (greater than 50%) between neuromuscular blocking agents has been reported.
MIVACRON should be administered over a period of 60 seconds to patients who may be unusually sensitive to falls in arterial blood pressure, for example those who are hypovolaemic.
In adults, doses of MIVACRON of greater than or equal to 0.2 mg/kg (greater than or equal to 3x ED₉₅) have been associated with histamine release when administered by rapid bolus injection. However, the slower administration of the 0.2 mg/kg MIVACRON dose and the divided administration of the 0.25 mg/kg MIVACRON dose (see Dosage & Administration) minimise the cardiovascular effects of these doses.
Cardiovascular safety did not appear to be compromised in children given a rapid bolus dose of 0.2 mg/kg in clinical studies.
MIVACRON does not have significant vagal or ganglion blocking properties in the recommended dosage range. Recommended doses of MIVACRON consequently have no clinically significant effects on heart rate and will not counteract the bradycardia produced by many anaesthetic agents or by vagal stimulation during surgery.
In common with other non-depolarising neuromuscular blocking agents, increased sensitivity to MIVACRON can be expected in patients with myasthenia gravis, other forms of neuromuscular disease and cachectic patients. Severe acid-base or electrolyte abnormalities may increase or reduce sensitivity to MIVACRON.
MIVACRON solution is acidic (approximately pH 4.5) and should not be mixed in the same syringe or administered simultaneously through the same needle with highly alkaline solutions (e.g. barbiturate solutions). It has been shown to be compatible with some commonly used peri-operative drugs supplied as acidic solutions, e.g. fentanyl, alfentanil, sufentanil, droperidol and midazolam. Where other anaesthetic agents are administered through the same indwelling needle or cannula as used for MIVACRON, and compatibility has not been demonstrated, it is recommended that each drug is flushed through with physiological saline.
Studies in malignant hyperthermia-susceptible pigs indicated that MIVACRON does not trigger this syndrome. MIVACRON has not been studied in malignant hyperthermia-susceptible patients.
Reversal of neuromuscular block: as with other neuromuscular blocking agents, evidence of spontaneous recovery should be observed prior to administration of reversal agent (e.g. neostigmine). The use of a peripheral nerve stimulator to evaluate recovery prior to and following reversal of neuromuscular block is strongly recommended.
No data are available on the long-term use of MIVACRON injection in patients undergoing mechanical ventilation in the intensive care unit.
Effects on Ability to Drive and Use Machines: This precaution is not relevant to the use of MIVACRON. MIVACRON will always be used in combination with a general anaesthetic and therefore the usual precautions relating to performance of tasks following general anaesthesia apply.