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Mivacurium

Pronunciation

(mye va KYOO ree um)

Index Terms

  • BWB1090U
  • Mivacron
  • Mivacronreg

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Mivacron: 10 mg/5 mL (5 mL); 20 mg/10 mL (10 mL)

Brand Names: U.S.

  • Mivacron

Pharmacologic Category

  • Neuromuscular Blocker Agent, Nondepolarizing

Pharmacology

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.

Distribution

Vd (mean):147 to 274 mL/kg

Metabolism

Enzymatic hydrolysis via plasma cholinesterase, inactive metabolites

Excretion

Urine (~7% as unchanged drug; Cook 1992) and bile

Onset of Action

Neuromuscular blockade: IV (dose dependent): 1.5 to 3 minutes; Elderly: 1.5 minutes slower; Children 2 to 12 years of age: Faster than adults

Peak: IV (dose dependent): 2.3 to 4.9 minutes

Duration of Action

Short due to rapid hydrolysis by plasma cholinesterases; clinically effective block may last for 15 to 20 minutes; spontaneous recovery may be 95% complete in 21 to 34 minutes (dose dependent); duration shorter in children and 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.

Half-Life Elimination

~2 minutes

Special Populations: Renal Function Impairment

Duration is ~1.5 times longer in patients with ESRD.

Special Populations: Hepatic Function Impairment

Duration is ~3 times longer in patients with end-stage hepatic disease.

Special Populations: Elderly

Onset and recovery rate may be slower and duration may be longer.

Special Populations: Children

Onset and recovery rate are faster and duration is shorter in children 2 to 12 years.

Use: Labeled Indications

Neuromuscular blockade: Adjunct to general anesthesia, to facilitate tracheal intubation, and to provide skeletal muscle relaxation during surgery or mechanical ventilation

Contraindications

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.

Dosing: Adult

Neuromuscular blockade: IV: Dose to effect; doses must be individualized due to interpatient variability.

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).

Dosage adjustment for concomitant inhalational anesthetics at steady state: Consider reduction of mivacurium continuous infusion rate by ≤35% to 40% or a reduction of bolus dose by ≤25% with concomitant isoflurane or enflurane at steady state; greater reductions may be necessary with higher concentrations of isoflurane or enflurane. Consider small reduction of mivacurium dosage with concomitant halothane administration.

Dosing: Geriatric

Refer to adult dosing; may require decreased infusion rates or smaller or less frequent maintenance bolus doses

Dosing: Pediatric

Neuromuscular blockade: IV: Dose to effect; doses must be individualized due to interpatient variability.

Children 2 to 12 years:

Intermittent bolus: 0.2 mg/kg over 5 to 15 seconds.

Continuous infusion: 14 mcg/kg/minute (0.84 mg/kg/hour).

Children >12 and Adolescents: Refer to adult dosing.

Dosage adjustment for concomitant inhalational anesthetics: Refer to adult dosing.

Dosing: Renal Impairment

Mild to severe impairment: IV: Initial bolus: 0.15 mg/kg; subsequent dosing is based on clinical response.

Dosing: Hepatic Impairment

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).

Dosing: Obesity

Dose obese patients (weight ≥30% more than IBW) based on IBW.

Reconstitution

May prepare an infusion solution (final concentrations: 0.5 mg/mL) by admixing with an appropriate diluent (eg, NS, D5W, D5NS, LR, D5LR). Do not mix with alkaline solutions having a pH >8.5 (eg, barbiturates).

Administration

IV: For IV administration only. May administer as IV bolus and/or continuous infusion.

Storage

Store intact vials at 25°C (77°F);.excursions permitted between 15°C and 30°C (59°F and 86°F). Do not freeze. Mivacurium diluted to 0.5 mg/mL in D5W, D5NS, NS, LR, or D5LR in PVC bags is stable at 5°C to 25°C (41°F to 77°F) for up to 24 hours. Discard unused portion.

Drug Interactions

AbobotulinumtoxinA: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Acetylcholinesterase Inhibitors: May diminish the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Amifampridine: May diminish the therapeutic effect of Neuromuscular-Blocking Agents. Neuromuscular-Blocking Agents may diminish the therapeutic effect of Amifampridine. Monitor therapy

Aminoglycosides: May enhance the respiratory depressant effect of Neuromuscular-Blocking Agents. Monitor therapy

Bacitracin (Systemic): May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Calcium Channel Blockers: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Capreomycin: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

CarBAMazepine: May decrease the serum concentration of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Cardiac Glycosides: Neuromuscular-Blocking Agents may enhance the arrhythmogenic effect of Cardiac Glycosides. Monitor therapy

Clindamycin (Topical): May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Colistimethate: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. 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. Consider therapy modification

Cyclophosphamide: May increase the serum concentration of Mivacurium. Monitor therapy

CycloSPORINE (Systemic): May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Echothiophate Iodide: May increase the serum concentration of Mivacurium. Monitor therapy

Estrogen Derivatives: May increase the serum concentration of Mivacurium. 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). Monitor therapy

Inhalational Anesthetics: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

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. 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. Monitor therapy

Lincosamide Antibiotics: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Lithium: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Local Anesthetics: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Exceptions: Benzocaine; Benzydamine; Cocaine; Dibucaine; Dyclonine; Ethyl Chloride; Hexylresorcinol; Lidocaine (Ophthalmic); Lidocaine (Topical); Pramoxine; Proparacaine; Tetracaine (Ophthalmic); Tetracaine (Topical). 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. Monitor therapy

Magnesium Salts: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Minocycline: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

OnabotulinumtoxinA: Neuromuscular-Blocking Agents may enhance the neuromuscular-blocking effect of OnabotulinumtoxinA. Monitor therapy

Phenelzine: May increase the serum concentration of Mivacurium. Monitor therapy

Pholcodine: May enhance the adverse/toxic effect of Neuromuscular-Blocking Agents. Specifically, anaphylaxis has been reported. Monitor therapy

Polymyxin B: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Consider therapy modification

Procainamide: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

QuiNIDine: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

QuiNINE: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Avoid combination

RimabotulinumtoxinB: Neuromuscular-Blocking Agents may enhance the neuromuscular-blocking effect of RimabotulinumtoxinB. Monitor therapy

Sertraline: May increase the serum concentration of Mivacurium. Monitor therapy

Spironolactone: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Tetracycline Derivatives: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Trimebutine: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Vancomycin: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Adverse Reactions

>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

Warnings/Precautions

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.

• Bradycardia: Does not counteract bradycardia produced by anesthetics/vagal stimulation.

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 which may antagonize neuromuscular blockade: Acid-base and/or electrolyte abnormalities, 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 which 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 which may potentiate neuromuscular blockade: Acid-base and/or electrolyte abnormalities, cachexia, carcinomatosis, debilitation, neuromuscular diseases, Eaton-Lambert syndrome, myasthenia gravis, and myasthenic syndrome 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.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

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.

• 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.

• 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.

• Obesity: Use with caution in obese patients (weight ≥30% than their ideal body weight [IBW]); determine initial dose using the patient’s IBW.

Other warnings/precautions:

• Appropriate use: Maintenance of an adequate airway and respiratory support is critical. Does not relieve pain or produce sedation; use should include appropriate anesthesia, pain control, and sedation. Use of a peripheral nerve stimulator to monitor drug effects is recommended.

• Experienced personnel: Should be administered by adequately trained individuals familiar with its use.

Monitoring Parameters

Vital signs (heart rate, blood pressure, respiratory rate); degree of muscle relaxation (via peripheral nerve stimulator and presence of spontaneous movement). In the ICU setting, prolonged paralysis and generalized myopathy, following discontinuation of agent, may be minimized by appropriately monitoring degree of blockade.

Pregnancy Risk Factor

C

Pregnancy Considerations

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).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience flushing (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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