NOTE: This drug is discontinued in the US.

Description: Mivacurium is a short-acting, nondepolarizing, neuromuscular blocking agent. Mivacurium is used to cause skeletal muscle relaxation as an adjunct to general anesthesia or for endotracheal intubation. Mivacurium antagonizes the action of acetylcholine by competitively binding to cholinergic receptors on the motor endplate. Compared to atracurium, another nondepolarizing agent, mivacurium has a similar onset of action, but is shorter acting. Like succinylcholine, an ultra-short acting depolarizing agent, mivacurium is metabolized by plasma cholinesterase and may have a prolonged duration of action in patients with pseudocholinesterase deficiency. The pharmacodynamic effects of mivacurium are dose-dependent. Mivacurium has mild to moderate histamine releasing properties, which increase with the dose and rate of IV administration. Like other neuromuscular blockers, significant variation in patient sensitivity and dosage requirements exist for mivacurium, requiring careful patient selection, dosage titration and monitoring. Mivacurium was approved by the FDA in 1992 and significant revisions were made to the safety labeling in 1998. Abbott discontinued the manufacturer of Mivacron® in 2006, secondary to business reasons; no other manufacturer currently supplies mivacurium injection in the U.S.

Mechanism of Action: Mivacurium is a bezylisoquinoline nondepolarizing agent which competitively binds to nicotinic receptors on the motor end-plate to antagonize the action of acetylcholine, resulting in blockade of neuromuscular transmission. Blockade of neuromuscular transmission is antagonized by acetylcholinesterase inhibitors, such as neostigmine or edrophonium. Unlike depolarizing agents such as succinylcholine, mivacurium does not stimulate cholinergic receptors. Skeletal muscle relaxation proceeds in a predictable order, starting with muscles associated with fine movements, e.g., eyes, face, and neck. These effects are followed by muscle relaxation of the limbs, chest, and abdomen and, finally, the diaphragm. Larger doses increase the risk of developing respiratory depression due to relaxation of the intercostal muscles and diaphragm. Muscle tone returns in the reverse order.

Mivacurium does not affect cardiac muscarinic receptors like pancuronium nor block ganglionic nicotinic receptors like d-tubocurarine; thereby minimizing the risk of tachycardia and hypotension. However, mivacurium does have the potential for substantial histamine release. At recommended doses, mivacurium has no significant hemodynamic effects. Increased dose, rapid rate of IV administration, or failure to individualize dosage for patient conditions may increase the risk of histamine-related adverse effects such as hypotension, tachycardia and bronchospasm. Elevations of plasma histamine levels correlate with decreased blood pressure. Like succinylcholine, patients with reduced plasma cholinesterase due to disease or medications (e.g. pseudocholinesterase deficiency) have exaggerated sensitivity to mivacurium, evidenced by prolonged neuromuscular blockade.

Pharmacokinetics: Mivacurium is administered intravenously. The onset of action is about 3—6 minutes and duration lasts approximately 15—30 minutes; although substantial variability exists depending on dosage and patient characteristics. Mivacurium is a mixture of three stereoisomers, with 92—96% occurring as the trans-trans and cis-trans diesters which are equipotent in blocking neuromuscular transmission. The cis-cis diester produces minimal (< 5%) neuromuscular blocking activity in humans. Like other nondepolarizing neuromuscular blockers, mivacurium is hydrophilic, has a small volume of distribution and is distributed primarily to extracellular fluids. Protein binding of mivacurium has not been evaluated due to rapid hydrolysis in plasma. Like succinylcholine, mivacurium is rapidly metabolized by plasma cholinesterase; however the resulting metabolites are inactive. Unchanged mivacurium is not significantly eliminated via the renal or biliary route. The mean elimination half-lives for the clinically significant trans-trans and cis-trans stereoisomers are 2.0 and 1.8 minutes, respectively, in adults receiving opioid/nitrous oxide/oxygen anesthesia. The low volume of distribution, short half-life and high clearance of the two potent stereoisomers of mivacurium account for its short duration of action.

Patients with hepatic dysfunction have significantly increased elimination half-lives and reduced plasma clearance of the two most potent stereoisomers of mivacurium; requiring dosage adjustment. Renal impairment or failure did not alter the pharmacokinetics of the two more potent stereoisomers of mivacurium; however, did prolong the half-lives of the cis-cis isomer and the inactive metabolites of mivacurium. The mivacurium infusion rates required to maintain suppression of neuromuscular transmission were unchanged in this study. Mivacurium infusion rates do not need to be adjusted in renal dysfunction; however, the duration of block may be longer in some patients.

At recommended mivacurium doses, the time to maximum neuromuscular blockade is similar to intermediate-acting agents (e.g. atracurium), but longer than the ultra-short-acting agent, succinylcholine. The clinical duration of action of mivacurium is one-third to one-half that of the intermediate-acting agents and 2 to 2.5 times that of succinylcholine. The time to maximum peak and clinical duration are dose-dependent. The average dose required to produce 95% suppression of muscular response to ulnar nerve stimulation (ED95) for mivacurium in adults receiving opioid/nitrous oxide/oxygen anesthesia is approximately 0.07 mg/kg. In children (2 to 12 years), mivacurium has a higher ED95, faster onset, and shorter duration of action than observed for adults. Higher mg/kg doses are required in children and recovery time is faster following reversal.

Drug Information Provided by
Gold Standard, Inc. � 2007