Mivacron 2mg/ml Solution for Injection

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4.2       Posology and Method of Administration

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Prolonged and intensified neuromuscular blockade may also occur in patients with acute or chronic renal failure as a result of reduced levels of plasma cholinesterase (see section 4.4 Special Warnings and Special Precautions for Use)

Dose in patients with reduced plasma cholinesterase activity: 

Mivacurium is metabolised by plasma cholinesterase.  Plasma cholinesterase activity may be diminished in the presence of genetic abnormalities of plasma cholinesterase (e.g. patients heterozygous or homozygous for the atypical plasma cholinesterase gene), in various pathological conditions (see section 4.4 Special Warnings and Special Precautions for Use).  The possibility of prolonged neuromuscular block following administration of Mivacron must be considered in patients with reduced plasma cholinesterase activity.  Mild reductions (i.e. within 20% of the lower limit of the normal range) are not associated with clinically significant effects on duration.

(See section 4.3 Contraindications and section 4.4 Special Warnings and Special Precautions for Use, for information about homozygous and heterozygous patients).

4.4       Special Warnings and Special Precautions for Use

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 mivacurium may occur secondary to reduced plasma cholinesterase activity in the following states or pathological conditions:

         Physiological variation as in pregnancy and the puerperium (see section 4.6 Pregnancy and Lactation).

         Genetically determined abnormalities of plasma cholinesterase (see below and section 4.3 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 below)

         End-stage hepatic failure, (see section 4.2 Posology and Method of Administration)

         Acute, chronic or end-stage renal failure (see section 4.2 Posology and Method of Administration)

         Iatrogenic: following plasma exchange, plasmapheresis, cardiopulmonary bypass, and as a result of concomitant drug therapy (see Section 4.5 Interaction with Other Medicinal Products and Other Forms of Interaction).

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 mivacurium.  In three such adult patients, a small dose of 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 mivacurium 0.15 mg/kg is approximately 10 min longer than in control patients.

Once spontaneous recovery had begun, neuromuscular block in these patients was antagonized 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 mivacurium 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.

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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 0.015-0.020 mg/kg Mivacron followed by appropriate dosing guided by monitoring of block with a nerve stimulator.

4.7       Effects on Ability to Drive and Use Machines

This precaution is not relevant to the use of mivacurium.  Mivacurium will always be used in combination with a general anaesthetic and therefore the usual precautions relating to performance of tasks following general anaesthesia apply