Mivacurium

SPC §4.2 (Mivacurium 2mg/ml injection). ED95 (mean dose producing 95% suppression of the adductor pollicis single twitch response) is 0.07 mg/kg (range 0.06 to 0.09) in adults receiving narcotic anaesthesia. Duration of block is dose related: 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. INJECTION SPEED: 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 cardiovascular effects. ANAESTHETIC INTERACTION: the neuromuscular blocking action is potentiated by isoflurane or enflurane — if steady-state anaesthesia with isoflurane or enflurane has been established, the recommended initial mivacurium dose should be reduced by up to 25% and the infusion rate reduced by up to 40%; with sevoflurane the infusion rate requirement should be reduced by up to 50%; halothane has only a minimal potentiating effect and dose reduction is probably not necessary (smaller infusion rate reductions may be required). RECOVERY/REVERSAL: once spontaneous recovery is underway it is complete in approximately 15 minutes and is independent of the dose administered; block can be reversed with standard doses of anticholinesterase agents, but because spontaneous recovery is rapid, reversal may not be routinely required as it shortens recovery time by only 5-6 minutes. Continuous infusion has not been associated with tachyphylaxis or cumulative neuromuscular blockade. ADMINISTRATION: mivacurium 2 mg/ml may be used undiluted for infusion; compatible with sodium chloride 0.9%, glucose 5%, sodium chloride 0.18% with glucose 4%, and Lactated Ringer's Injection USP — when diluted 1 plus 3 (to 0.5 mg/ml) it is chemically and physically stable for at least 48 hours at 30 degrees C, but as there is no antimicrobial preservative, dilution should be carried out immediately prior to use. SPECIAL POPULATIONS: ELDERLY — onset time, duration of action and recovery rate may be extended relative to younger patients by 20 to 30%; elderly patients may also require decreased infusion rates or smaller or less frequent maintenance bolus doses. CARDIOVASCULAR DISEASE — in patients with clinically significant cardiovascular disease the initial dose should be administered over 60 seconds. OBESITY — in obese patients (30% or more above ideal bodyweight for height) the initial dose should be based upon ideal bodyweight, not actual bodyweight. HEPATIC — in end-stage liver failure the clinically effective duration of block produced by 0.15 mg/kg is approximately three times longer than normal (markedly reduced plasma cholinesterase activity); adjust dosage according to individual clinical response. PLASMA CHOLINESTERASE — prolonged block must be considered in patients with reduced plasma cholinesterase activity; mild reductions (within 20% of the lower limit of normal) are not associated with clinically significant effects on duration. Patients homozygous for the atypical plasma cholinesterase gene are extremely sensitive (a dose of 0.03 mg/kg produced complete block for 26 to 128 minutes in three such adults) and mivacurium is contraindicated in them; in heterozygous patients the clinically effective duration of block from 0.15 mg/kg is approximately 10 minutes longer than in controls. BURNS — patients with burns should be given a test dose of 0.015-0.020 mg/kg mivacurium followed by appropriate dosing guided by monitoring of block with a nerve stimulator. HISTAMINE SENSITIVITY — caution in patients with a history suggestive of increased sensitivity to histamine (e.g. asthma); if used, administer over 60 seconds. Monitoring of neuromuscular function is recommended to individualise dosage requirements. Mivacurium paralyses the respiratory muscles as well as other skeletal muscles but has no effect on consciousness, and should be administered only by or under close supervision of an experienced anaesthetist with adequate facilities for endotracheal intubation and artificial ventilation. §4.5 was not retrieved in this bundle (the §4.4 text was truncated at the source-fetch limit).

TWO AGE BANDS — dosePerKg left null because the SPC gives different figures by age. INFANTS AND CHILDREN AGED 2 MONTHS - 12 YEARS. ED95: approximately 0.07 mg/kg in infants aged 2 to 6 months; approximately 0.1 mg/kg in infants and children aged 7 months to 12 years. Dose for tracheal intubation: 2-6 months — 0.15 mg/kg (time to maximum neuromuscular block 1.4 min, duration of clinically effective block 9 min; data obtained during halothane anaesthesia); 7 months - 12 years — 0.2 mg/kg (1.7 min, 9 min; data obtained during halothane or narcotic anaesthesia). Maintenance dose 2 months - 12 years: 0.1 mg/kg, duration of clinically effective block 6-9 minutes. Average infusion rate required to maintain 89-99% neuromuscular block, 2 months - 12 years: 11-14 micrograms/kg/min (0.7-0.9 mg/kg/hr). The neuromuscular blocking action is potentiated by inhalational agents — the 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. NEONATES AND INFANTS <2 MONTHS: safety and efficacy have not yet been established — 'no recommendation on posology can be made'. Paediatric patients homozygous for the atypical plasma cholinesterase gene are extremely sensitive to the neuromuscular blocking effect (§4.4). Verify against a children's formulary before prescribing.