Note: Dose to effect; doses must be individualized due to interpatient variability. Ensure adequate pain control and sedation prior to and during administration of neuromuscular blockade to achieve deep sedation (SCCM [Murray 2016]).
Neuromuscular blockade for endotracheal intubation, surgery, or mechanical ventilation ( as adjunct to general anesthesia ): IV:
Intermittent bolus: Initial: 0.15 mg/kg over 5 to 15 seconds, or 0.2 mg/kg over 30 seconds, or 0.25 mg/kg in divided doses (0.15 mg/kg followed in 30 seconds by 0.1 mg/kg); maintenance: 0.1 mg/kg at ~15 minute intervals.
Burn patients: Administer test dose of 0.015 to 0.02 mg/kg, then follow with appropriate dosing and monitoring.
Cardiovascular disease (clinically significant) or increased sensitivity to release of histamine (eg, asthma): Initial: ≤0.15 mg/kg over 60 seconds.
Continuous infusion: Initial: 9 to 10 mcg/kg/minute (0.54 to 0.6 mg/kg/hour) upon evidence of spontaneous recovery from initial bolus dose. Usual infusion rate: 5 to 7 mcg/kg/minute under balanced anesthesia.
Note: If continuous infusion is initiated simultaneously with the initial dose, a lower initial infusion rate should be used (eg, 4 mcg/kg/minute).
Intensive care unit paralysis (eg, use for up to 48 hours in patients with early ARDS with PaO2/FiO2 <150, to facilitate mechanical ventilation, or for shivering from therapeutic hypothermia) (off-label dosing): IV: Initial bolus of 0.25 mg/kg, followed by 5 to 6 mcg/kg/minute (0.3 to 0.36 mg/kg/hour) (deBacker 2017)
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Mild to severe impairment: IV: Initial bolus: 0.15 mg/kg; subsequent dosing is based on clinical response.
Mild to severe impairment: IV: Initial bolus: 0.15 mg/kg; subsequent dosing is based on clinical response. Decrease infusion rates by as much as 50% (dependent on the degree of hepatic impairment).
(For additional information see "Mivacurium: Pediatric drug information")
Note: Titrate dose to effect; dose must be individualized due to interpatient variability. Obese patients (weighing ≥30% IBW) should be dosed on IBW.
Adjunct to surgical anesthesia (neuromuscular blockade): Note: Due to pharmacodynamics differences in pediatric patients than adults, children 2 to 12 years require a higher mg/kg dose and often more frequent repeat maintenance dosing or higher continuous infusion rates.
Children 2 to 12 years:
Intermittent IV bolus: 0.2 mg/kg over 5 to 15 seconds.
Continuous IV infusion: Usual dose: 14 mcg/kg/minute (0.84 mg/kg/hour); range: 5 to 31 mcg/kg/minute (0.3 to 1.86 mg/kg/hour); begin infusion upon evidence of spontaneous recovery from initial dose.
Adolescents:
Intermittent IV bolus: Initial: 0.15 mg/kg over 5 to 15 seconds, or 0.2 mg/kg over 30 seconds, or a total bolus of 0.25 mg/kg divided into 2 doses (0.15 mg/kg followed in 30 seconds by 0.1 mg/kg).
Maintenance: 0.1 mg/kg at ~15-minute intervals; begin upon evidence of spontaneous recovery from initial bolus.
Burn patients: Administer test dose of 0.015 to 0.02 mg/kg, then follow with appropriate dosing and monitoring.
Cardiovascular disease (clinically significant) or increased sensitivity to release of histamine (eg, asthma): Initial: ≤0.15 mg/kg over 60 seconds.
Continuous IV infusion: Initial: 9 to 10 mcg/kg/minute (0.54 to 0.6 mg/kg/hour); begin infusion upon evidence of spontaneous recovery from initial bolus dose. Usual infusion rate: 5 to 7 mcg/kg/minute (0.3 to 0.42 mg/kg/hour) under balanced anesthesia; range: 1 to 15 mcg/kg/minute (0.06 to 0.9 mg/kg/hour). Note: A lower initial infusion rate (eg, 4 mcg/kg/minute [0.24 mg/kg/hour]) should be used if started simultaneously with initial bolus.
ICU paralysis (eg, facilitate mechanical ventilation) in select adequately sedated patients: Limited data available in ages <2 years (Martin 1999):
Infants: IV: Initial bolus: 0.2 mg/kg, followed by continuous IV infusion of 10 mcg/kg/minute (0.6 mg/kg/hour).
Children: IV: Initial bolus: 0.2 mg/kg, followed by continuous IV infusion of 16 mcg/kg/minute (0.96 mg/kg/hour).
Adolescents: IV: Initial bolus: 0.2 mg/kg, followed by continuous IV infusion of 7 mcg/kg/minute (0.42 mg/kg/hour).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no pediatric specific recommendations; based on experience in adult patients, consider bolus dose adjustment; subsequent dosing based on clinical response and no adjustment of infusion rates is necessary.
There are no pediatric specific recommendations; based on experience in adult patients, consider bolus dose adjustment; subsequent dosing based on clinical response and consider dosing adjustment of infusion (dependent on the degree of hepatic impairment).
Refer to adult dosing; may require decreased infusion rates or smaller or less frequent maintenance bolus doses
Dose obese patients (weight ≥30% more than IBW) based on IBW.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Mivacron: 10 mg/5 mL (5 mL) [DSC]; 20 mg/10 mL (10 mL) [DSC]
IV: For IV administration only. May administer as IV bolus and/or continuous infusion.
Parenteral:
Intermittent IV bolus:
Children 2 to 12 years: Administer undiluted over 5 to 15 seconds
Adolescents: Administer undiluted over 5 to 30 seconds; the specific rate depends on dose to prevent hemodynamic effects
Continuous IV infusion: Further dilute and administer via an infusion pump; use infusion solutions within 24 hours of preparation
Neuromuscular blockade for endotracheal intubation, surgery, or mechanical ventilation: As an adjunct to general anesthesia to facilitate tracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation in adequately sedated ICU patients
Note: Neuromuscular blockade does not provide pain control, sedation, or amnestic effects. Appropriate analgesic and sedative mediations should be used before and during administration of neuromuscular blockade to achieve deep sedation.
Acute respiratory distress syndrome; Shivering due to therapeutic hypothermia following cardiac arrest
Mivacron may be confused with Mevacor
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
According to the 2020 to 2021 ISMP Targeted Medication Safety Best Practices for Hospitals, neuromuscular blockers should be segregated, sequestered, and differentiated from all other medication wherever they are stored. This includes:
Only storing in places within the hospital that they are routinely used.
Placing in sealed boxes or in rapid sequence intubation kits (preferred).
Limiting availability in automated dispensing cabinets to perioperative, labor and delivery, critical care, and emergency departments only.
Placing in separate lidded containers within the pharmacy refrigerator or other isolated pharmacy storage area.
Affixing an auxiliary label to clearly communicate respiratory paralysis will occur and ventilation required on all storage bins and/or automated dispensing pockets/drawers (exception anesthesia-prepared syringes) stating one of the following:
Warning: Causes Respiratory Arrest – Patient Must Be Ventilated
Warning: Paralyzing Agent – Causes Respiratory Arrest
Warning: Causes Respiratory Paralysis – Patient Must Be Ventilated
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Cardiovascular: Flushing (16% to 25%)
1% to 10%: Cardiovascular: Hypotension (<1% to 4%; dosage and time dependent)
<1%, postmarketing, and/or case reports: Anaphylactoid reaction, anaphylaxis, bradycardia, bronchospasm, cardiac arrhythmia, delayed recovery from neuromuscular block (prolonged effect), dizziness, drug tolerance (diminished effect), erythema, hypersensitivity reaction, hypoxemia, injection site reaction, muscle spasm, phlebitis, skin rash, tachycardia, urticaria, wheezing
Hypersensitivity to mivacurium or any component of the formulation
Documentation of allergenic cross-reactivity for neuromuscular blockers is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.
Concerns related to adverse effects:
• Anaphylaxis: Severe anaphylactic reactions have been reported (some life-threatening and fatal). Appropriate emergency treatment (including epinephrine 1 mg/mL) should be immediately available during use. Use caution in patients with previous anaphylactic reactions to other neuromuscular-blocking agents.
• Bradycardia: Does not counteract bradycardia produced by anesthetics/vagal stimulation.
• Neuromuscular cross-sensitivity: Cross-sensitivity with other neuromuscular-blocking agents may occur; use extreme caution in patients with previous anaphylactic reactions.
Disease-related concerns:
• Burn injury: Resistance may occur in burn patients (≥20% of total body surface area), usually several days after the injury, and may persist for several months after wound healing (Han 2009). These patients may require increased doses or patients may also have reduced plasma cholinesterase activity, requiring dose reduction.
• Cardiovascular disease: Use with caution in patients with clinically significant cardiovascular disease; reduce initial dosage and inject slowly (over 60 seconds). Carefully monitor hemodynamic status and maintain adequate hydration in these patients.
• Conditions that may antagonize neuromuscular blockade (decreased paralysis): Respiratory alkalosis, hypercalcemia, demyelinating lesions, peripheral neuropathies, denervation, and muscle trauma may result in antagonism of neuromuscular blockade (ACCM/SCCM/ASHP [Murray 2002]; Greenberg 2013; Miller 2010; Naguib 2002).
• Conditions that may diminish plasma cholinesterase activity: Plasma cholinesterase genetic abnormalities, malignant tumors, infections, anemia, decompensated heart disease, peptic ulcer, and myxedema may diminish plasma cholinesterase activity and result in prolonged neuromuscular blockade.
• Conditions that may potentiate neuromuscular blockade (increased paralysis): Electrolyte abnormalities (eg, severe hypocalcemia, severe hypokalemia, hypermagnesemia), neuromuscular diseases, metabolic acidosis, respiratory acidosis, Eaton-Lambert syndrome and myasthenia gravis may result in potentiation of neuromuscular blockade (Greenberg 2013; Miller 2010; Naguib 2002).
• Renal impairment: Use with caution in patients with renal impairment; prolonged neuromuscular block may occur. Reduced plasma cholinesterase activity may occur in patients with renal disease.
• Hepatic impairment: Use with caution in patients with hepatic impairment; prolonged neuromuscular block may occur. Markedly reduced plasma cholinesterase activity may occur in patients with chronic hepatic disease.
Special populations:
• Elderly: Use with caution in the elderly; effects and duration are more variable.
• Immobilized patients: Resistance may occur in patients who are immobilized.
• Homozygous for atypical plasma cholinesterase gene: Use with extreme caution if at all in patients homozygous for the atypical plasma cholinesterase gene; extremely sensitive to the neuromuscular blocking effect of mivacurium.
Other warnings/precautions:
• Appropriate use: Maintenance of an adequate airway and respiratory support is critical. All patients should receive eye care including liberal use of lubricating drops, gel, or ointment and eyelids should remain closed during continuous neuromuscular blockade to protect against damage to the cornea (ulceration and drying).
• Experienced personnel: Should be administered by adequately trained individuals familiar with its use.
• Histamine release: Use with caution in patients in whom substantial histamine release would be potentially hazardous (eg, asthma); reduce initial dosage and inject slowly (over 60 seconds). Carefully monitor hemodynamic status and maintain adequate hydration in these patients.
• Risk of medication errors: Accidental administration may be fatal. Confirm proper selection of intended product, store vial so the cap and ferrule are intact and the possibility of selecting the wrong product is minimized, and ensure that the intended dose is clearly labeled and communicated, when applicable.
In children 2 to 12 years, mivacurium produces minimal hemodynamic changes (MAP, HR) at usual doses; however, higher doses (>0.2 mg/kg) may produce transient decreases in MAP. In adults, the decreased MAP was observed 1 to 3 minutes postdose and associated with histamine release with resolution in an additional 1 to 3 minutes.
None known.
Acetylcholinesterase Inhibitors: May diminish the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy
Aminoglycosides: May enhance the therapeutic effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Bacitracin (Systemic): May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Botulinum Toxin-Containing Products: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Bromperidol: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Calcium Channel Blockers: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy
Capreomycin: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
CarBAMazepine: May decrease the serum concentration of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy
Cardiac Glycosides: Neuromuscular-Blocking Agents may enhance the arrhythmogenic effect of Cardiac Glycosides. Risk C: Monitor therapy
Clindamycin (Topical): May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Colistimethate: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Management: If possible, avoid concomitant use of these products. Monitor for deeper, prolonged neuromuscular-blocking effects (respiratory paralysis) in patients receiving concomitant neuromuscular-blocking agents and colistimethate. Risk D: Consider therapy modification
Corticosteroids (Systemic): Neuromuscular-Blocking Agents (Nondepolarizing) may enhance the adverse neuromuscular effect of Corticosteroids (Systemic). Increased muscle weakness, possibly progressing to polyneuropathies and myopathies, may occur. Management: If concomitant therapy is required, use the lowest dose for the shortest duration to limit the risk of myopathy or neuropathy. Monitor for new onset or worsening muscle weakness, reduction or loss of deep tendon reflexes, and peripheral sensory decriments Risk D: Consider therapy modification
Cyclophosphamide: May increase the serum concentration of Mivacurium. Risk C: Monitor therapy
CycloSPORINE (Systemic): May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Echothiophate Iodide: May increase the serum concentration of Mivacurium. Risk C: Monitor therapy
Estrogen Derivatives: May increase the serum concentration of Mivacurium. Risk C: Monitor therapy
Fosphenytoin-Phenytoin: May diminish the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Fosphenytoin-Phenytoin may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Fosphenytoin-Phenytoin may decrease the serum concentration of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy
Inhalational Anesthetics: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Management: When initiating a non-depolarizing neuromuscular blocking agent (NMBA) in a patient receiving an inhalational anesthetic, initial NMBA doses should be reduced 15% to 25% and doses of continuous infusions should be reduced 30% to 60%. Risk D: Consider therapy modification
Ketorolac (Nasal): May enhance the adverse/toxic effect of Neuromuscular-Blocking Agents (Nondepolarizing). Specifically, episodes of apnea have been reported in patients using this combination. Risk C: Monitor therapy
Ketorolac (Systemic): May enhance the adverse/toxic effect of Neuromuscular-Blocking Agents (Nondepolarizing). Specifically, episodes of apnea have been reported in patients using this combination. Risk C: Monitor therapy
Lincosamide Antibiotics: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Lithium: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Local Anesthetics: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Loop Diuretics: May diminish the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Loop Diuretics may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Magnesium Salts: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Metoclopramide: May enhance the neuromuscular-blocking effect of Mivacurium. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Phenelzine: May increase the serum concentration of Mivacurium. Risk C: Monitor therapy
Pholcodine: May enhance the adverse/toxic effect of Neuromuscular-Blocking Agents. Specifically, anaphylaxis has been reported. Risk C: Monitor therapy
Polymyxin B: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Management: If possible, avoid concomitant use of neuromuscular-blocking agents and polymyxin B. If concomitant use cannot be avoided, monitor for deeper, prolonged neuromuscular-blocking effects (eg, respiratory paralysis) in patients receiving this combination. Risk D: Consider therapy modification
Procainamide: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
QuiNIDine: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
QuiNINE: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk X: Avoid combination
Sertraline: May increase the serum concentration of Mivacurium. Risk C: Monitor therapy
Tetracyclines: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Thiazide and Thiazide-Like Diuretics: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy
Trimebutine: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy
Vancomycin: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Adverse events have not been observed in animal reproduction studies. Plasma cholinesterase concentrations are decreased in pregnancy; neuromuscular blockade may be prolonged and intensified. Use in cesarean section has been reported; adjustment of the dose may be necessary (Kim 1999).
It is not known if mivacurium is present in breast milk. Plasma cholinesterase concentrations are decreased immediately postpartum; neuromuscular blockade may be prolonged and intensified. The manufacturer recommends that caution be exercised when administering mivacurium to breastfeeding women.
Vital signs (heart rate, blood pressure, respiratory rate); degree of muscle paralysis (eg, presence of spontaneous movement, ventilator asynchrony, shivering, and consider use of a peripheral nerve stimulator with train of four monitoring along with clinical assessments)
Antagonizes acetylcholine by competitively binding to cholinergic sites on motor endplates in skeletal muscle. This inhibits contractile activity in skeletal muscle leading to muscle paralysis.
Onset of action: Neuromuscular blockade (dose dependent): IV: Adults: 1.5 to 3 minutes; Elderly: 1.5 minutes slower; Children 2 to 12 years of age: Faster than adults
Peak: Neuromuscular blockade (dose dependent): IV: Children 2 to 12 years of age: Median range: 1.6 to 2.8 minutes; Adults: Median range: 2.3 to 4.9 minutes
Duration of action: Short due to rapid hydrolysis by plasma cholinesterases; duration may be slightly longer in the elderly; may also be longer in patients with hepatic or renal impairment and patients with reduced plasma cholinesterase (pseudocholinesterase) activity; hypothermia may prolong the duration of action
Children: Clinically effective block may last 10 minutes (6 to 15 minutes) with 95% spontaneous recovery in 14 to 26 minutes
Adult: Clinically effective block may last for 15 to 20 minutes; spontaneous recovery may be 95% complete in 21 to 34 minutes (dose dependent)
Distribution: Vd (mean): 147 to 274 mL/kg
Metabolism: Enzymatic hydrolysis via plasma cholinesterase, inactive metabolites
Half-life elimination: ~2 minutes
Excretion: Urine (~7% as unchanged drug; Cook 1992) and bile
Renal function impairment: Duration is ~1.5 times longer in patients with ESRD.
Hepatic function impairment: Duration is ~3 times longer in patients with end-stage hepatic disease.
Pediatric: Onset and recovery rate are faster and duration is shorter in children 2 to 12 years of age. In children 2 to 12 years of age when used as adjunct to general anesthesia (nitrous oxide/oxygen/opioid), typical intermittent IV doses produced a maximum effect at a mean 1.9 minutes (range: 1.3 to 3.3 minutes) and a clinically effective blockade for a mean of 10 minutes (range: 6 to 15 minutes).
Geriatric: Onset and recovery rate may be slower and duration may be longer.
Solution (Mivacron Intravenous)
10 mg/5 mL (per mL): $5.49
20 mg/10 mL (per mL): $3.59
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