MIVACRON INJECTION 10 MG/5 ML [SIN07624P]

Product Info

MIVACRON INJECTION 10 MG/5 ML

[SIN07624P]

Indication

Indications

MIVACRON is a highly selective, short-acting, non-depolarising neuromuscular blocking agent with a fast recovery profile.

MIVACRON is used as an adjunct to general anaesthesia to relax skeletal muscles and to facilitate tracheal intubation and mechanical ventilation.

The injection formulation contains no antimicrobial preservative and is intended for single patient use.

Dosing

Dosage and Administration

In common with all neuromuscular blocking agents, monitoring of neuromuscular function is recommended during the use of MIVACRON in order to individualise dosage requirements.

With MIVACRON, 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.

Populations

• Adults

MIVACRON is administered by intravenous (i.v.) injection. The mean dose required to produce 95% suppression of the adductor pollicis single twitch response to ulnar nerve stimulation (ED₉₅) is 0.07 mg/kg (range 0.06 to 0.09) in adults receiving narcotic anaesthesia.

The following dose regimens are recommended for tracheal intubation:

I. A dose of 0.2 mg/kg, administered over 30 seconds, produces good to excellent conditions for tracheal intubation within 2.0 to 2.5 minutes.

II. A dose of 0.25 mg/kg, administered as a divided dose (0.15 mg/kg followed 30 seconds later by 0.1 mg/kg), produces good to excellent conditions for tracheal intubation within 1.5 to 2.0 minutes of completion of administration of the first dose portion.

The recommended bolus dose range for healthy adults is 0.07 to 0.25 mg/kg. The duration of neuromuscular block is related to the dose. Doses of 0.07, 0.15, 0.20 and 0.25 mg/kg produce clinically effective block for approximately 13, 16, 20 and 23 minutes, respectively. Doses of up to 0.15 mg/kg may be administered over 5 to 15 seconds. Higher doses should be administered over 30 seconds in order to minimise the possibility of occurrence of cardiovascular effects.

Full block can be prolonged with maintenance doses of MIVACRON. Doses of 0.1 mg/kg administered during narcotic anaesthesia each provide approximately 15 minutes of additional clinically effective block.

Successive supplementary doses do not give rise to accumulation of neuromuscular blocking effect.

The neuromuscular blocking action of MIVACRON is potentiated by isoflurane or enflurane anaesthesia. If steady-state anaesthesia with isoflurane or enflurane has been established, the recommended initial dose of MIVACRON should be reduced by up to 25%.

Halothane appears to have only a minimal potentiating effect on MIVACRON and dose reduction is probably not necessary.

Once spontaneous recovery is underway, it is complete in approximately 15 minutes and is independent of the dose administered.

The neuromuscular block produced by MIVACRON can be rapidly reversed with standard doses of anticholinesterase agents. However, because spontaneous recovery after MIVACRON is rapid, reversal may not be routinely required since it shortens recovery time by only 5 to 6 minutes.

Use by infusion (Injection formulation only):

Continuous infusion of MIVACRON may be used to maintain neuromuscular block. Upon early evidence of spontaneous recovery from an initial MIVACRON dose, an infusion rate of 8 to 10 micrograms/kg/min (0.5 to 0.6 mg/kg/h) is recommended.

The initial infusion rate should be adjusted according to the patient's response to peripheral nerve stimulation and clinical criteria.

Adjustments of the infusion rate should be made in increments of approximately 1 microgram/kg/min (0.06 mg/kg/h). In general a given rate should be maintained for at least 3 minutes before a rate change is made.

On average, an infusion rate of 6 to 7 micrograms/kg/min will maintain neuromuscular block within the range of 89% to 99% for extended periods in adults receiving narcotic anaesthesia. During steady-state isoflurane or enflurane anaesthesia, reduction in the infusion rate by up to 40% should be considered. A study has shown that the MIVACRON infusion rate requirement should be reduced by up to 50% with sevoflurane. With halothane, smaller reductions in infusion rate may be required.

Spontaneous recovery after infusion of MIVACRON is independent of the duration of infusion and comparable to recovery reported for single doses.

Continuous infusion of MIVACRON has not been associated with the development of tachyphylaxis or cumulative neuromuscular blockade.

MIVACRON injection (2 mg/ml) may be used undiluted for infusion. It is compatible with the following infusion fluids:

• sodium chloride i.v. infusion (0.9% w/v)

• glucose i.v. infusion (5% w/v)

• sodium chloride (0.18% w/v) and glucose (4% w/v) i.v. infusion

• Lactated Ringer's injection, United States Pharmacopoeia (USP).

When diluted with the listed infusion solutions in the proportion of 1 plus 3 (i.e. to give 0.5 mg/ml) MIVACRON injection has been shown to be chemically and physically stable for at least 48 hours at 30°C. However, since the product contains no antimicrobial preservative, dilution should be carried out immediately prior to use, administration should commence as soon as possible thereafter and any remaining solution should be discarded.

• Children aged 2 to 12 years

MIVACRON has a higher ED₉₅ (approximately 0.1 mg/kg), faster onset, shorter clinically effective duration of action and more rapid spontaneous recovery in children aged 2 to 12 years, than in adults.

The recommended bolus dose range for children aged 2 to 12 years is 0.1 to 0.2 mg/kg. When administered during stable narcotic or halothane anaesthesia, a dose of 0.1 and 0.2 mg/kg produces clinically effective block for an average of 7 minutes and 10 minutes respectively.

A MIVACRON dose of 0.2 mg/kg is recommended for tracheal intubation. Maximum block is usually achieved within 2 minutes following administration of this dose and intubation should be possible within this time.

Maintenance doses are generally required more frequently in children than in adults. Available data suggest that a maintenance dose of 0.1 mg/kg will give approximately 6 to 7 minutes of additional clinically effective block.

Children generally require higher infusion rates than adults. During halothane anaesthesia, the mean infusion rate required to maintain 89 to 99% neuromuscular block averages 10 to 15 mcg/kg/min (0.6 to 1.0 mg/kg/hr).

The neuromuscular blocking action of mivacurium is potentiated by inhalational agents. A study has shown that the mivacurium infusion rate requirement should be reduced by up to 70% with sevoflurane in children aged 2–12 years.

Once spontaneous recovery is underway, it is complete in approximately 10 minutes.

• Children under two years of age

No dose recommendations for neonates and infants under two years of age can be made until further information becomes available.

• Elderly

In elderly patients receiving single bolus doses of MIVACRON, the onset time, duration of action and recovery rate may be extended relative to younger patients by 20 to 30%. Elderly patients may also require smaller or less frequent maintenance bolus doses.

Use by infusion (Injection formulation only):

Elderly patients may also require decreased infusion rates.

• Patients with cardiovascular disease

In patients with clinically significant cardiovascular disease, the initial dose of MIVACRON should be administered over 60 seconds.

MIVACRON has been administered in this way with minimal haemodynamic effects to patients undergoing cardiac surgery.

• Patients with reduced renal function

In patients with end-stage renal failure, the clinically effective duration of block produced by 0.15 mg/kg MIVACRON is approximately 1.5 times longer than in patients with normal renal function. Subsequently, dosage should be adjusted according to individual clinical response.

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 Warnings and Precautions – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

• Patients with reduced hepatic function

In patients with end-stage hepatic failure, the clinically effective duration of block produced by 0.15 mg/kg MIVACRON is approximately three times longer than in patients with normal hepatic function. This prolongation is related to the markedly reduced plasma cholinesterase activity seen in these patients.

Subsequently, dosage should be adjusted according to individual clinical response.

• Patients with reduced plasma cholinesterase activity

MIVACRON 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), and in various pathologic conditions (see Warnings and Precautions – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information) and by administration of certain drugs (see Interactions – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). 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 Contraindications and Warnings and Precautions for information about homozygous and heterozygous patients – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

• Obese patients

In obese patients (those weighing 30% or more above their ideal body weight for height), the initial dose of MIVACRON should be based upon ideal body weight and not actual body weight.

Contraindications

Contraindications

• MIVACRON is contraindicated in patients known to be homozygous for the atypical plasma cholinesterase gene (see Warnings and Precautions – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

• MIVACRON should not be administered to patients known to have a hypersensitivity to mivacurium or excipients.