Mivacurium parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Injection solutions of mivacurium.
Drugs List
Therapeutic Indications
Uses
Neuromuscular blockade to facilitate intubation during surgery
Dosage
The neuromuscular block achieved with mivacurium may be reversed with anticholinesterase agents. However, because the spontaneous recovery time following mivacurium administration is rapid, a reversal may not be required, as it shortens recovery time by only 5 to 6 minutes.
Neuromuscular function should be monitored throughout the use of mivacurium in order to establish individual dose requirements.
Adults
Intravenous injection
The mean dose required to produce 95% suppression of the adductor pollicis single twitch response to ulnar stimulations is 0.07mg/kg in adults receiving narcotic analgesia.
The recommended bolus dose range for healthy adults is 0.07mg/kg to 0.25mg/kg. The duration of blockade is related to the dose as follows:
A dose of 0.07mg/kg provides clinically effective block for approximately 13 minutes.
A dose of 0.15mg/kg provides clinically effective block for approximately 16 minutes.
A dose of 0.2mg/kg provides clinically effective block for approximately 20 minutes.
A dose of 0.25mg/kg provides clinically effective block for approximately 23 minutes.
Doses of up to 0.15mg/kg may be given over 5 to 15 seconds. Higher doses should be given over 30 seconds to minimise the risk of adverse cardiovascular effects.
The following dose regimes are recommended for tracheal intubation:
EITHER
0.2mg/kg administered over 30 seconds provides good to excellent conditions for tracheal intubation within 2 to 2.5 minutes.
OR
0.15mg/kg administered over 5 to 15 seconds, followed 30 seconds later, by 0.1mg/kg provides good to excellent conditions for tracheal intubation within 1.5 to 2 minutes of administration of the first dose.
With mivacurium, significant train-of-four fade is not seen during onset. It is often possible to intubate the trachea before complete abolition of the train-of-four response of the adductor pollicis muscle has occurred.
Full block may be prolonged with maintenance doses of mivacurium. Doses of 0.1mg/kg administered during narcotic anaesthesia provides approximately 15 additional minutes of clinically effective block. Successive supplementary doses do not cause an accumulation of neuromuscular blocking effect.
Concurrent isoflurane/enflurane anaesthesia
The neuromuscular blocking action of mivacurium is potentiated by isoflurane or enflurane. If isoflurane or enflurane are used for anaesthesia, the initial mivacurium dose should be reduced by up to 25%.
Concurrent halothane anaesthesia
Halothane appears to have only a minimum potentiating effect on mivacurium and dose reduction of mivacurium is probably not necessary.
Recovery
Once spontaneous recovery begins, it is completed in approximately 15 minutes and is independent of the dose administered.
Intravenous infusion
Continuous infusion of mivacurium may be used to maintain neuromuscular block. Following evidence of spontaneous recovery from the initial mivacurium dose, an infusion rate of 8 to 10micrograms/kg/minute is recommended.
The initial infusion rate should be adjusted according to the patient's response to peripheral nerve stimulation and clinical criteria. If necessary, the infusion rate may be adjusted in increments of 1microgram/kg/minute. In general, an infusion rate should be maintained for at least 3 minutes before the rate is changed.
On average, an infusion rate of 6 to 7micrograms/kg/minute will maintain neuromuscular block within the range of 89% to 99% for extended periods in adults receiving narcotic anaesthesia.
Concurrent isoflurane/enflurane anaesthesia
The mivacurium infusion rate may be reduced by up to 40%.
Concurrent sevoflurane anaesthesia
The mivacurium infusion rate should be reduced by up to 50%.
Concurrent halothane anaesthesia
Smaller reductions in infusion rate may be required.
Recovery
Spontaneous recovery following mivacurium infusion is independent of the duration of infusion and comparable to the recovery rates reported for single injections.
Continuous infusion of mivacurium has not been associated with the development of tachyphylaxis or cumulative neuromuscular blockade.
Elderly
In elderly patients receiving single bolus doses of mivacurium, the onset time, duration of action and recovery rate may be prolonged by 20% to 30% compared to younger patients.
Elderly patients may require decreased infusion rates or smaller or less frequent maintenance bolus doses.
Children
Children aged 12 to 18 years (See Dosage; Adult)
Children aged 2 months to 12 years
Mivacurium has a faster onset, a shorter clinically effective duration of action and a more rapid spontaneous recovery rate in this age group than those seen for adults.
The mean dose required to produce 95% suppression of the adductor pollicis single twitch response to ulnar stimulations is approximately 0.07mg/kg in infants aged 2 to 6 months and approximately 0.1mg/kg in children aged 7 months to 12 years.
Cardiovascular safety did not appear to be compromised in children given a rapid bolus dose of 0.2 mg/kg in clinical studies.
Tracheal intubation
Recommended initial doses are as follows:
Children aged 7 months to 12 years
0.2mg/kg provides maximum neuromuscular block 1.7 minutes after administration. The duration of clinically effective block is 9 minutes.
Children aged 2 to 6 months
0.15mg/kg provides maximum neuromuscular block 1.4 minutes after administration. The duration of clinically effective block is 9 minutes.
As maximum block is usually obtained within 2 minutes following administration, tracheal intubation should be possible within this time.
Children generally require more frequent maintenance doses and higher infusion rates than required in adults.
The suggested maintenance dose in children aged between 2 months and 12 years is 0.1mg/kg (injection). This provides a duration of clinically effective block of 6 to 9 minutes after administration.
The manufacturer suggests if mivacurium is administered by intravenous infusion, the average infusion rate required to maintain 89% to 99% neuromuscular block is 11 to 14micrograms/kg/minute.
Alternative sources suggest a maintenance infusion of 8 to 10micrograms/kg/minute titrated in 1microgram/kg/minute increments every 3 minutes to the usual dose of 11 to 14micrograms/kg/minute.
Concurrent sevoflurane anaesthesia
The mivacurium infusion rate should be reduced by up to 70% when administered with sevoflurane in children.
Once spontaneous recovery is underway in children, it is complete in approximately 10 minutes.
Patients with Renal Impairment
Dosage should be adjusted to individual clinical response in these patients.
In end-stage renal failure patients, the clinically effective duration of block produced by 0.15 mg/kg is approximately 1.5 times longer than in patients with normal renal function.
The Renal Drug Handbook suggest the following amendments for patients with renal impairment:
A glomerular filtration rate of 10ml/minute to 50ml/minute: Initially 50% of normal dose and adjust to response. Slower infusion rate may be required.
A glomerular filtration rate of below 10ml/minute: Initially 50% of normal dose and adjust to response. Slower infusion rate may be required. There may be a shorter time to maximum neuromuscular block and a slower spontaneous recovery may be experienced.
Patients with Hepatic Impairment
Dosage should be adjusted to individual clinical response in these patients.
End-stage hepatic failure
The clinically effective duration of block produced by 0.15mg/kg is approximately 3 times longer than in patients with normal hepatic function. This is due to the reduced plasma cholinesterase activity seen in these patients.
Additional Dosage Information
Patients with clinically significant cardiovascular disease
The initial dose of mivacurium should be administered over at least 60 seconds. This administration time has minimal haemodynamic effects to patients undergoing cardiac surgery.
Patients with increased sensitivity to the effects of histamine
The dose should be administered over 60 seconds.
Patients who are sensitive to falls in arterial blood pressure
The dose should be administered over 60 seconds.
Patients with reduced plasma cholinesterase activity
Mivacurium is metabolised by plasma cholinesterase. The activity of plasma cholinesterase may be reduced in the presence of genetic abnormalities in plasma cholinesterase (e.g. patients who are heterozygous or homozygous for the atypical plasma cholinesterase gene), in various pathological conditions, and by the administration of certain drugs.
There is a possibility of prolonged neuromuscular block following mivacurium administration in these patients. Mild reductions (within 20% of the lower limit of normal) are not associated with clinically significant effects on duration of block.
In patients who are heterozygous for the atypical plasma cholinesterase gene, the clinically effective duration of block following the administration of 0.15mg/kg of mivacurium is approximately 10 minutes longer than in control patients.
Patients with burns
Resistance to mivacurium may develop in patients with burns and therefore these patients may require increased doses. However, these patients may also have reduced plasma cholinesterase activity, which may require dose reduction. Burn patients should therefore be given a test dose of 0.015mg/kg to 0.02mg/kg mivacurium followed by an appropriate dose as determined by the monitoring of block with a nerve stimulator.
Patients with obesity
In patients weighing 30% or more above their ideal bodyweight for their height, the initial dose of mivacurium should be based on the ideal body weight of the patient and not actual body weight.
Contraindications
Children under 2 months
Homozygotes for the atypical plasma cholinesterase gene
Precautions and Warnings
Burns
Cachexia
Elderly
Obesity
Plasma cholinesterase deficiency
Asthma
Breastfeeding
Hypovolaemia
Myasthenia gravis
Neuromuscular disorder
Pregnancy
Renal impairment
Severe cardiovascular disorder
Severe electrolyte imbalance
Severe hepatic impairment
Histamine release may occur, particularly with rapid injection
Anticholinesterase should be immediately available to reverse blockade
Ventilation should be controlled by anaesthetist
Incompatible with sodium bicarbonate and other alkaline substances
To be administered by anaesthetist or a doctor trained in intensive care
Ventilatory support facilities must be immediately available
Monitor neuromuscular block & recovery using a peripheral nerve stimulator
Burns patients may require dose modification
In obese patients dosing should be based on ideal weight
Respiration must be assisted in all patients as mivacurium paralyses the respiratory muscles. Before leaving the theatre following anaesthesia, is it essential to ensure that the patient is breathing spontaneously, deeply and regularly.
Prolonged and intensified neuromuscular blockade following mivacurium may occur secondary to reduced plasma cholinesterase activity in the following:
Physiological variation (such as during pregnancy and the puerperium)
Genetically determined abnormalities in plasma cholinesterase
Severe or chronic infections including generalised tetanus and tuberculosis
Chronic debilitating disease, malignancy, chronic anaemia and malnutrition
Myxoedema and collagen diseases
Decompensated heart disease
Peptic ulcer
Iatrogenic: following plasma exchange, plasmapheresis, cardiopulmonary bypass, and as a result of concomitant drug therapy
Burns
Pregnancy and Lactation
Pregnancy
Use mivacurium with caution in pregnancy, only when the expected clinical benefit to the mother outweighs any potential risk to the foetus, otherwise mivacurium should not be used in pregnancy.
Plasma cholinesterase levels decrease during pregnancy which consequently affects the metabolism of mivacurium. Mivacurium has been used to maintain neuromuscular block during Caesarean section, but adjustments to the infusion rate are required due to the reduced levels of plasma cholinesterase.
Patients pre-treated with magnesium sulfate undergoing Caesarean section may require a further reduction in infusion rate. This is due to the potentiating effects of magnesium.
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Lactation
Use mivacurium with caution in breastfeeding.
It is not known if mivacurium is excreted in human milk. Discontinue breastfeeding during treatment with mivacurium.
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Side Effects
Anaphylactic reaction
Anaphylactoid reaction
Bronchospasm
Erythema
Flushing
Hypotension
Tachycardia
Urticaria
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: September 2016
Reference Sources
Summary of Product Characteristics: Mivacron Injection 2 mg/ml. GlaxoSmithKline UK. Revised September 2016.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 20 September 2017
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