Incompatibility. See under Atracurium for details regarding the incompatibility of neuromuscular blockers.
Adverse Effects, Treatment, and Precautions
As for competitive neuromuscular blockers in general (see Atracurium). Mivacurium chloride has no significant vagal or ganglion blocking activity at recommended doses. It may induce histamine release especially when given in large doses rapidly. Mivacurium should be used with caution, if at all, in patients with plasma cholinesterase deficiency, since its duration of action will be prolonged in such patients.
In common with other competitive muscle relaxants patients with burns may develop resistance to mivacurium and require increased doses (see under Atracurium). However, as these patients may also have reduced plasma cholinesterase activity dosage requirements could also be reduced. Licensed product information recommends that such patients should be given a test dose of 15 to 20 micrograms/kg with subsequent dosage adjustments being guided by monitoring of the block.
Neuromuscular blockade was successfully achieved with mivacurium in an obese elderly patient with myasthenia gravis requiring surgery. Only about half the usual dose was required and even then recovery was delayed. See Atracurium for a discussion of the use of competitive neuromuscular blockers in patients with neuromuscular disorders.
Plasma cholinesterase deficiency
There have been reports of prolonged neuromuscular block produced by mivacurium in patients with plasma cholinesterase deficiency. Time to full recovery varied; one patient required up to 8 hours.
Mivacurium might be unsuitable for neuromuscular blockade of a limb which has been isolated with a tourniquet in order to provide a bloodless field for surgery. It is largely inactivated by the enzymatic action of plasma cholinesterase and would therefore continue to degrade locally leading to a loss of blockade in the limb, which could not be corrected by further doses unless the tourniquet was deflated.
However, as for other competitive neuromuscular blockers, the use of mivacurium to supplement regional anaesthesia has produced prolonged muscle weakness well beyond cuff deflation. This suggests that mivacurium is not broken down in the ischaemic limb and that recovery is not dependent on plasma concentrations of mivacurium. See also Local Anaesthetics, under Interactions of Atracurium, for a report of symptoms suggestive of local anaesthetic toxicity when prilocaine and mivacurium were used together.
For interactions associated with competitive neuromuscular blockers, see Atracurium.
Metoclopramide, an inhibitor of plasma cholinesterase, was found to significantly prolong the duration of action of mivacurium in patients undergoing surgery, although in this study only marginal inhibition of plasma cholinesterase by metoclopramide occurred.
Mivacurium is a mixture of 3 stereoisomers, 2 of which (cis-trans and trans-trans) are considered to account for most of the neuromuscular blocking effect. All 3 isomers are inactivated by plasma cholinesterase. Renal and hepatic mechanisms are involved in their elimination with excretion in urine and bile.
Uses and Administration
Mivacurium chloride is a benzylisoquinolinium competitive neuromuscular blocker (see Atracurium).
On intravenous injection muscle relaxation occurs within 1.5 to 2.5 minutes, depending on the dose with a duration of action of about 10 to 20 minutes. It is used for endotracheal intubation and to provide muscle relaxation in general anaesthesia for surgical procedures (see Anaesthesia) and to aid controlled ventilation (see Intensive Care).
Doses of neuromuscular blockers need to be carefully titrated for individual patients according to response, and may vary with the procedure, the other drugs given, and the state of the patient; monitoring of the degree of block is recommended in order to reduce the risk of overdosage. Mivacurium is given as the chloride although doses are expressed in terms of mivacurium base. The initial dose by intravenous injection is 70 to 250 micrograms/kg. Doses up to 150 micrograms/kg may be given over 5 to 15 seconds but higher doses should be given over 30 seconds.
In patients with asthma or cardiovascular disease, or those who are sensitive to falls in arterial blood pressure, it should be given over 60 seconds. To give a dose of 250 micrograms/kg for tracheal intubation, an injection of 150 micrograms/kg may be followed 30 seconds later by an injection of 100 micrograms/kg. Maintenance doses of 100 micrograms/kg may be given at intervals of 15 minutes. In children aged 2 to 6 months an initial dose of 150 micrograms/kg has been given; in children aged 7 months to 12 years, an initial dose of 200 micrograms/kg has been given. A maintenance dose of 100 micrograms/kg may be given every 6 to 9 minutes for children aged 2 months to 12 years.
Mivacurium chloride may also be given by continuous intravenous infusion for maintenance of block. For adults the initial rate is 8 to 10 micrograms/kg per minute adjusted every 3 minutes if necessary by increments of 1 microgram/kg per minute to a usual rate of 6 to 7 micrograms/kg per minute; in children aged 2 months to 12 years the usual dose is 11 to 14 micrograms/kg per minute.
Reduced doses may be required in the elderly and in patients with hepatic or renal impairment (see below).
Mivacurium has a shorter duration of action than most other competitive neuromuscular blockers. Studies suggest that it is a useful alternative to suxamethonium for the production of neuromuscular block of short duration and has the advantage that its block can be reversed with an anticholinesterase. For a discussion of the choice of anticholinesterase for reversal of neuromuscular block produced by short-acting blockers such as mivacurium, see under Neostigmine. Although its onset of action may be accelerated by giving a priming dose, mivacurium has a slower onset than suxamethonium and so may not be a suitable alternative when rapid intubation is required. For a general review of neuromuscular blockers, see Anaesthesia.
Administration in the elderly
In a study comparing the effects of mivacurium in elderly and young adults, the duration of neuromuscular effects was prolonged in elderly patients by about 30%. The mean infusion requirement in elderly patients was 3.67 micrograms/kg per minute compared with 5.5 micrograms/kg per minute in young adults.
Licensed product information states that elderly patients may require decreased infusion rates or smaller or less frequent maintenance bolus doses.
Administration in hepatic or renal impairment
The pharmacokinetics of mivacurium have been studied in patients with renal or hepatic impairment. The duration of relaxation produced by mivacurium was about 1.5 times greater than normal in patients with end-stage renal disease and up to about 3 times greater than normal in patients with end-stage liver disease. Reduced plasma-cholinesterase activity in the patients with hepatic impairment may have played an important part in this effect. Although an anticholinesterase such as neostigmine hastens recovery by only a few minutes in healthy subjects, its use may be indicated in patients in whom recovery is delayed.
Licensed product information recommends that in patients with end-stage renal or liver disease, the dose should be adjusted according to individual clinical response.
Austria: Mivacron; Novacrium;
Brazil: Mivacrorr ;
Canada: Mivacron ;
Czech Republic: Mivacron;
Hong Kong; Mivacron;
Israel: Mivacron ;
The Netherlands: Mivacron;
New Zealand: Mivacron;
South Africa: Mivacron;
United Kingdom (UK): Mivacron;
United States of America (US and USA): Mivacron.