Vecuronium Bromide

Pronunciation

Class: Neuromuscular Blocking Agents
VA Class: MS200
Chemical Name: 1-[(2β,3α,5α,16β,17β)-3,17-bis(acetyloxy)-2-(1-piperidinyl) androstan-16-yl]-1-methylpiperidinium bromide
Molecular Formula: C34H57N2O4•Br
CAS Number: 50700-72-6
Brands: Norcuron

Warning(s)

  • Should be administered only by individuals experienced in the use of neuromuscular blocking agents.1

Introduction

Nondepolarizing neuromuscular blocking agent.1 3 4 5

Uses for Vecuronium Bromide

Skeletal Muscle Relaxation

Production of skeletal muscle relaxation during surgery after general anesthesia has been induced.1

Facilitation of endotracheal intubation;1 15 16 30 39 40 41 46 54 63 68 71 77 80 113 117 124 129 131 142 however, succinylcholine generally is preferred in emergency situations where rapid intubation is required.110 111 112 141 145 A single dose should not be used in place of succinylcholine for rapid sequence induction of anesthesia (“crash intubation”).141

Slideshow: View Frightful (But Dead Serious) Drug Side Effects

Treatment to increase pulmonary compliance during assisted or controlled respiration after general anesthesia has been induced.1

Has been used for facilitation of mechanical ventilation in intensive care setting.1 186 187 188 189 190 191 192 193

Vecuronium Bromide Dosage and Administration

General

  • Adjust dosage carefully according to individual requirements and response.1 2

  • Assess neuromuscular blockade and recovery in patients undergoing anesthesia; a peripheral nerve stimulator is recommended to accurately monitor the degree of muscle relaxation and to minimize the possibility of overdosage.1

  • To avoid patient distress, administer only after unconsciousness has been induced.141

Facilitation of Endotracheal Intubation

  • Endotracheal intubation for nonemergency surgical procedures generally can be performed within 2.5–3 minutes following administration of 0.08- to 0.1-mg/kg dose.1 61 75 (See Onset and also Duration under Pharmacokinetics.)

Maintenance of Neuromuscular Blockade

  • Repeated administration of maintenance doses appears to have little, if any, cumulative effect on duration of neuromuscular blockade.1 16 17 40 51 62 71 72 80 93 143

  • Rate of spontaneous recovery from neuromuscular blockade following discontinuance of maintenance infusion usually is comparable to that following administration of a single IV injection.1

  • Close monitoring recommended to avoid excessive dosage when continuous infusion is employed.30 33 39 113

Reversal of Neuromuscular Blockade

  • To reverse neuromuscular blockade, administer a cholinesterase inhibitor (e.g., neostigmine, pyridostigmine, edrophonium), usually in conjunction with an antimuscarinic (e.g., atropine, glycopyrrolate) to block adverse muscarinic effects of the cholinesterase inhibitor.1 2 11 16 17 18 19 28 39 40 41 43 44 45 46 47 88 137 143

Administration

Administer IV only;1 do not administer IM.144

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer initial (intubating) dose by rapid IV injection;1 administer maintenance dosage for prolonged surgical procedures by intermittent IV injection or continuous IV infusion.1

Consult specialized references for specific procedures and techniques of administration.HID

Do not mix in the same syringe or administer through the same needle as an alkaline solution.1

Reconstitution

Reconstitute vial containing 10 or 20 mg of vecuronium bromide with 10 or 20 mL of bacteriostatic water for injection, respectively, to provide a solution containing 1 mg/mL.1 2 Use within 5 days.1

When reconstituted with other compatible solutions (see Solution Compatibility under Stability), use within 24 hours and discard unused portions.1

Dilution

For continuous IV infusion, dilute the reconstituted solution to the desired concentration (usually 0.1 or 0.2 mg/mL) in a compatible IV solution (see Solution Compatibility under Stability).1 2 30 80 113 Use within 24 hours.1

Dosage

Available as vecuronium bromide; dosage expressed in terms of the salt.1

Pediatric Patients

Skeletal Muscle Relaxation
Initial (Intubating) Dosage
IV

Children 7 weeks to 1 year of age may receive dosages recommended for adults.27 148 (See Adults under Dosage and Administration.)

Children 1–9 years of age may require slightly higher initial doses than adults.1 2 27 28 (See Adults under Dosage and Administration.)

Children >10 years of age should receive dosages recommended for adults.1 2 (See Adults under Dosage and Administration.)

Maintenance Dosage
Intermittent IV Injection

Children 7 weeks to 1 year of age may receive doses recommended for adults; however, less frequent administration may be necessary.27 148 (See Adults under Dosage and Administration and also see Pediatric Use under Cautions.)

Children 1–9 years of age may require more frequent doses than adults.1 2 28 (See Adults under Dosage and Administration.)

Children >10 years of age should receive dosages recommended for adults.1 2 (See Adults under Dosage and Administration.)

Continuous IV Infusion

Dosage recommendations not established; administration by continuous IV infusion not adequately studied.1

Adults

Skeletal Muscle Relaxation
Initial (Intubating) Dosage
IV

0.08–0.1 mg/kg.1 2 (See Onset and also Duration under Pharmacokinetics.)

Reduce initial dosage by about 15% (i.e., to 0.06–0.085 mg/kg) when administered >5 minutes after administration of enflurane, isoflurane, or halothane has been initiated or after steady-state anesthesia has been achieved.1 2 See Interactions: Specific Drugs.

If larger initial dose is required, 0.15–0.28 mg/kg has been administered in patients undergoing halothane anesthesia with minimal adverse cardiovascular effects as long as ventilation was adequately maintained.1 2

If administering following succinylcholine, reduce dosage to 0.05–0.06 mg/kg with balanced anesthesia or 0.04–0.06 mg/kg with inhalation anesthesia.1 2

Maintenance Dosage
Intermittent IV Injection

0.01–0.015 mg/kg, administered as necessary, in patients receiving balanced anesthesia.1 2

0.008–0.012 mg/kg, administered as necessary, in patients receiving inhalation anesthesia.144 Increase dose (i.e., to >0.01–0.015 mg/kg) if longer intervals between doses are desirable.1

Administer first maintenance dose generally 25–45 minutes after the initial dose in patients undergoing balanced or inhalation anesthesia.1 2

Administer repeat maintenance doses at relatively regular intervals (i.e., from 12–15 minutes in patients undergoing balanced anesthesia or at slightly longer intervals in those undergoing enflurane or isoflurane anesthesia).1 2

Continuous IV Infusion

Initially, 1 mcg/kg per minute.1 Adjust infusion rate to maintain 90% neuromuscular blockade; 0.8–1.2 mcg/kg per minute usually maintains continuous neuromuscular blockade in most patients.1 39

Initiate continuous IV infusion only after early spontaneous recovery from initial IV dose is evident (approximately 20–40 minutes after rapid IV administration of initial dose1 30 33 39 76 80 113 118 ).1 Required infusion rates decrease progressively and become relatively constant within 30–50 minutes.30 39 113

May need to reduce infusion rate by about 25–60% approximately 45–60 minutes following initial IV dose if steady-state anesthesia has been induced with enflurane or isoflurane.1 Reduction in infusion rate may not be necessary if steady-state anesthesia has been induced with halothane.1

Special Populations

Hepatic Impairment

Data currently insufficient for specific dosage recommendations.1 Some clinicians suggest usual initial dose;141 151 others suggest a reduced initial dose.141 Adjust maintenance dosing (probably with reduced doses) carefully according to patient’s response.141 151 (See Hepatic Impairment under Cautions.)

Renal Impairment

Usual initial and maintenance doses recommended for patients with renal failure who are optimally prepared with dialysis prior to surgery; monitor carefully to determine interval between doses.141 149 (See Renal Impairment under Cautions.)

Manufacturer recommends consideration of decreased initial dose if emergency surgery is necessary in patients with severe renal failure (i.e., Clcr <10 mL/minute) who are not optimally prepared with dialysis;1 2 however, most clinicians believe that usual initial dose may be given.141 Adjust maintenance doses carefully according to patient’s response.141

Geriatric Patients

Dosage necessary to maintain steady-state neuromuscular blockade30 32 33 may be decreased.

Burn Patients

Substantially increased doses may be required due to development of resistance.175 (See Burn Patients under Cautions.)

Intensive Care Setting

Dosage recommendations not established for prolonged, continuous IV infusions during mechanical ventilation in intensive care settings.1 (See Intensive Care Setting under Cautions.)

Patients with Neuromuscular Disease

Administer small test dose (e.g., 0.005–0.02 mg/kg)141 144 and monitor response.1 (See Neuromuscular Disease under Cautions.)

Other Populations

Patients in whom substantial histamine release would be particularly hazardous (e.g., patients with clinically important cardiovascular disease) or patients with any history suggesting a greater risk of histamine release (e.g., a history of severe anaphylactoid reactions or asthma): Administer slowly over 1–2 minutes or longer; discontinue administration if any signs of histamine release occur.141 144 (See Hypersensitivity Reactions under Cautions.)

Cautions for Vecuronium Bromide

Contraindications

  • Known hypersensitivity to vecuronium bromide or any ingredient in the formulation.144

Warnings/Precautions

Warnings

Respiratory Effects

Potential for severely compromised respiratory function and respiratory paralysis.1 110 111 127 128

Should be used only by individuals experienced in the use of neuromuscular blocking agents and in the maintenance of an adequate airway and respiratory support.1 2 Facilities and personnel necessary for intubation, administration of oxygen, and assisted or controlled respiration should be immediately available.1

IV cholinesterase inhibitor (e.g., neostigmine, pyridostigmine, edrophonium) should be readily available.1 18 19 39 40 41 44 88 (See Reversal of Neuromuscular Blockade under Dosage and Administration.)

Use with caution in patients with pulmonary impairment or respiratory depression.b

Neuromuscular Disease

Possible exaggerated neuromuscular blockade in patients with neuromuscular disease (e.g., myasthenia gravis, Eaton-Lambert syndrome).1

Administer small test dose; monitor response carefully with a peripheral nerve stimulator.1 141 144

Sensitivity Reactions

Hypersensitivity Reactions

Histamine-like hypersensitivity reactions (e.g., bronchospasm, flushing, redness, hypotension, and tachycardia) are not likely to occur.1 12 18 48 143

General Precautions

Burn Patients

Resistance to therapy can develop in burn patients,169 170 172 173 174 175 particularly those with burns over 25–30% or more of body surface area.175

Resistance becomes apparent ≥1 week after the burn,169 170 171 172 173 174 175 peaks ≥2 weeks after the burn,170 171 172 174 persists for several months or longer,170 172 and decreases gradually with healing.169 170 172 174

Consider possible need for substantially increased doses.175

Cardiovascular Effects

Exhibits minimal cardiovascular effects;1 3 5 6 19 143 therefore, will not counteract the bradycardia induced by many anesthesia agents1 21 59 (e.g., high-dose fentanyl)122 143 or by vagal stimulation.141

Intensive Care Setting

Possible prolonged paralysis and/or muscle weakness and atrophy.1

Continuous monitoring of neuromuscular transmission recommended during neuromuscular blocking agent therapy in intensive care setting.1 Do not administer additional doses before there is a definite response to nerve stimulation tests.1 If no response is elicited, discontinue administration until response returns.1

Impaired Circulation

Possible delayed onset of action and delayed maximum effect in patients with impaired circulation or in those with cardiovascular disease or edema (vecuronium volume of distribution may be increased).1 2 141 Larger-than-usual initial doses are not recommended; caution advised when administering a subsequent dose before the maximum effect of the initial dose is attained.141

Electrolyte Disturbances

Possible prolonged paralysis in patients with electrolyte disturbances (e.g., increased plasma magnesium concentrations) or acid-base imbalances.186 187 189 190

Carefully monitor the degree of neuromuscular blockade with a peripheral nerve stimulator in patients with severe electrolyte disturbances (i.e., hypermagnesemia, hypokalemia, hypocalcemia)141 or diseases that result in electrolyte disturbances (e.g., adrenocortical insufficiency).141

Malignant Hyperthermia

Malignant hyperthermia is rarely associated with use of neuromuscular blocking agents and/or potent inhalation anesthetics.b Insufficient data to determine whether vecuronium is capable of initiating the development of this condition.1

Be vigilant for possible development of malignant hyperthermia and prepared for its management in any patient undergoing general anesthesia.168

Carcinomatosis

Carefully monitor the degree of neuromuscular blockade with a peripheral nerve stimulator.1

Obesity

Use with caution in severely obese patients; maintenance of adequate airway and ventilation support prior to, during, and following administration of neuromuscular blocking agents may require particular care.1

Debilitated Patients

Carefully monitor the degree of neuromuscular blockade with a peripheral nerve stimulator in patients with severe debilitation.1

Specific Populations

Pregnancy

Category C.1

Lactation

Not known whether vecuronium is distributed into milk.1 141 Caution advised if used in nursing women.1 141

Pediatric Use

Safety and efficacy not established in children <7 weeks of age.1 144

Has been used safely and effectively in children >7 weeks of age who were undergoing surgery.27 28 Children 7 weeks–1 year of age may be more sensitive than adults to the neuromuscular blocking effects and generally require 50% longer to recover from neuromuscular blockade.1 2 27 148

Vecuronium bromide that has been reconstituted with bacteriostatic water for injection containing benzyl alcohol should not be used in neonates.1 163 164 165 166 167

Geriatric Use

Possible increased time to onset of neuromuscular blockade31 and decreased rate of recovery compared with younger adults.30 32 33

Hepatic Impairment

Prolonged duration of and rate of recovery from neuromuscular blockade.1 38 79 90

Use with caution; careful monitoring with a peripheral nerve stimulator recommended.1

Renal Impairment

Onset and duration of and rate of recovery from neuromuscular blockade not substantially altered by renal dysfunction;1 74 84 149 however, possible prolonged duration of blockade in patients with severe renal impairment who have not undergone dialysis prior to surgery.1 2 Careful monitoring with a peripheral nerve stimulator recommended to avoid inadvertent overdosage; consider reduced initial dose.1

Common Adverse Effects

Skeletal muscle weakness.1

Interactions for Vecuronium Bromide

Specific Drugs

Drug

Interaction

Comments

Acylaminopenicillins (e.g., mezlocillin, piperacillin)

Prolonged neuromuscular blockade158 159

Use with caution158 159

Anesthetics, general (enflurane, halothane, isoflurane)

Increased potency and prolonged duration of neuromuscular blockade1 2 3 13 14 18 23 73 89 129 143

Reduced vecuronium dosage may be required1 2 14 23 89 (See Dosage under Dosage and Administration)

Anti-infective agents (aminoglycosides, bacitracin, clindamycin, lincomycin, polymyxins, tetracyclines)

Possible prolonged duration of neuromuscular blockade1 2 3 13 18 156

Calcium-channel blocking agents (e.g., verapamil)

Possible prolonged duration of neuromuscular blockade43

Dantrolene

Possible prolonged duration of neuromuscular blockade157

Magnesium salts

Increased neuromuscular blockade;1 141 154 155 reversal may be impeded1 141 155

Use with caution; reduce dosage as necessary1 141 154 155

Neuromuscular blocking agents, nondepolarizing

Possible increased neuromuscular blockade1

Concomitant administration not recommended1

Quinidine

Possible recurrence of paralysis1

Succinylcholine

Possible increased potency and prolonged duration of neuromuscular blockade1 2 3 21 33 62 124 131 132

Administer vecuronium in reduced dosage after effects of succinylcholine begin to dissipate1

Vecuronium Bromide Pharmacokinetics

Absorption

Bioavailability

Poorly absorbed from the GI tract.b

Onset

Time to maximum neuromuscular blockade decreases as the dose increases.1 2 17 18 26 46 69 70 87

Following IV administration of 0.08–0.1 mg/kg, neuromuscular blockade begins within 1 minute and is maximal at 3–5 minutes.1 2

Duration

Duration of neuromuscular blockade increases as the dose increases.1 2 17 47 70 80 87

Duration of clinically sufficient neuromuscular blockade induced by initial dose of 0.08–0.1 mg/kg under balanced or halothane anesthesia is about 25–30 or 30–40 minutes, respectively.2

Spontaneous recovery to about 25% of baseline generally occurs within 25–40 minutes under balanced anesthesia and is usually 95% complete 45–65 minutes after administration.1

The time necessary for 25–75% recovery from neuromuscular blockade following doses of 0.08–0.1 mg/kg under balanced or halothane anesthesia is about 15–25 minutes;1 144 recovery time following initial doses appears to be dose dependent.17 141

Special Populations

Hepatic dysfunction (i.e., cirrhosis, cholestasis) may prolong duration of and rate of recovery from neuromuscular blockade.1 38 79 90

In patients with severe renal impairment who have not undergone dialysis prior to surgery, duration of neuromuscular blockade may be prolonged.1 2

In geriatric patients, increased time of onset31 and decreased rate of recovery from neuromuscular blockade.30 32 33

In patients undergoing cardiopulmonary bypass surgery under induced hypothermia, duration of neuromuscular blockade may be prolonged.152

Distribution

Extent

Appears to rapidly distribute into extracellular space.2 100 Undergoes rapid and extensive hepatic extraction.116 Crosses the placenta minimally;94 95 96 97 not known whether distributed into milk.144

Plasma Protein Binding

Approximately 60–90%.1 2 57 99

Special Populations

In children <1 year of age, volume of distribution is increased.148 In geriatric patients, volume of distribution may be decreased.100 In patients with renal failure, volume of distribution may be slightly increased.74 84 104

Elimination

Metabolism

Metabolic fate not fully characterized in humans.1 2 3 106 116 143 In vitro, vecuronium undergoes spontaneous deacetylation to form hydroxy derivatives.9

Elimination Route

Excreted principally in feces via biliary elimination;1 38 79 90 143 also excreted in urine.1 2 106 116

Half-life

Biphasic;1 3 18 26 38 84 94 95 98 104 terminal elimination half-life averages 65–75 minutes.1

Special Populations

In patients with cirrhosis, half-life averages 84 minutes.38

In patients with renal failure, half-life not substantially altered;84 104 potential for high plasma concentrations of 3-desacetyl vecuronium (neuromuscular blocking activity is ≥50% of that of vecuronium).186 187 189 190 84 104

During late pregnancy, half-life decreases to about 35–40 minutes.1 2 94 95

Stability

Storage

Parenteral

Powder for Injection

15–30°C; protect from light.1 2

Following reconstitution with bacteriostatic water for injection containing benzyl alcohol, 2–8°C or room temperature (<30°C) for 5 days.1

Following reconstitution with sterile water for injection or other compatible solution (see Solution Compatibility under Stability), 2–8°C for 24 hours.1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Unstable in the presence of bases.10 11

Solution CompatibilityHID

Compatible

Dextrose 5% in sodium chloride 0.9%

Dextrose 5% in water

Ringer's injection, lactated

Sodium chloride 0.9%

Drug Compatibility
Admixture CompatibilityHID

Compatible

Ciprofloxacin

Y-Site CompatibilityHID

Compatible

Alprostadil

Aminophylline

Amiodarone HCl

Cefazolin sodium

Cefuroxime sodium

Co-trimoxazole

Dexmedetomidine HCl

Diltiazem HCl

Dobutamine HCl

Dopamine HCl

Epinephrine HCl

Esmolol HCl

Fenoldopam mesylate

Fentanyl citrate

Fluconazole

Gentamicin sulfate

Heparin sodium

Hetastarch in lactated electrolyte injection (Hextend)

Hydrocortisone sodium succinate

Hydromorphone HCl

Isoproterenol HCl

Labetalol HCl

Linezolid

Lorazepam

Midazolam HCl

Milrinone lactate

Morphine sulfate

Nicardipine HCl

Nitroglycerin

Norepinephrine bitartrate

Palonosetron HCl

Propofol

Ranitidine HCl

Sodium nitroprusside

Vancomycin HCl

Incompatible

Amphotericin B cholesteryl sulfate complex

Diazepam

Etomidate

Furosemide

Micafungin sodium

Actions

  • Produces skeletal muscle relaxation by causing a decreased response to acetylcholine (ACh) at the myoneural (neuromuscular) junction of skeletal muscle.b

  • Exhibits high affinity for ACh receptor sites and competitively blocks access of ACh to motor end-plate of myoneural junction; may affect ACh release.b

  • Blocks the effects of both the small quantities of ACh that maintain muscle tone and the large quantities of ACh that produce voluntary skeletal muscle contraction; does not alter the resting electrical potential of the motor end-plate or cause muscular contractions.b

  • Exhibits minimal cardiovascular effects.1 3 5 6 19 145

  • Appears to have little histamine-releasing activity.1 4 12 18 19 48 49 50 52 143 147 A less potent stimulator of histamine release than atracurium or pancuronium.52 147

Advice to Patients

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., cardiovascular disease, neuromuscular disease).1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Vecuronium Bromide

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV use only

10 mg*

Vecuronium Bromide for Injection

20 mg*

Vecuronium Bromide for Injection

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions September 6, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

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5. Miller RD. Is atracurium an ideal neuromuscular blocking drug? Anesth Analg (Cleveland). 1982; 61:721-2. Editorial. (IDIS 157359)

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8. Booij LHDJ, Vree TB, Crul JF. Org-NC45: a new steroidal non-depolarizing muscle relaxant. Pharm Weekbl Sci Ed. 1982; 1-4. (IDIS 145892)

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32. d’Hollander A, Barvais L, Massaut J et al. Vecuronium in geriatric patients. In: Agoston S, Bowman WC, Miller RD, Viby-Mogensen J, eds. Clinical experiences with Norcuron (Org NC 45, vecuronium bromide). Amsterdam: Excerpta Medica; 1983:171-4.

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34. Crul JF. General discussion. In: Agoston S, Bowman WC, Miller RD, Viby-Mogensen J, eds. Clinical experiences with Norcuron (Org NC 45, vecuronium bromide). Amsterdam: Excerpta Medica; 1983:196-8.

35. Brandom BW, Rudd GD, Cook DR. Clinical pharmacology of atracurium in paediatric patients. Br J Anaesth. 1983; 55(Suppl 1):117-21S.

36. Funk DI, Crul JF, vd Pol FM. Effects of changes in acid-base balance on neuromuscular blockade produced by Org-NC 45. Acta Anaesthesiol Scand. 1980; 24:119-24. [PubMed 6104411]

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39. Newton DEF. Vecuronium—continuous infusion in general clinical practice. In: Agoston S, Bowman WC, Miller RD, Viby-Mogensen J, eds. Clinical experiences with Norcuron (Org NC 45, vecuronium bromide). Amsterdam: Excerpta Medica; 1983:109-14.

40. Clarke RSJ. Intubating conditions and neuromuscular effects following administration of vecuronium bromide. Comparison with suxamethonium chloride and pancuronium bromide. In: Agoston S, ed. Clinical experiences with Norcuron (Org NC 45, vecuronium bromide). Amsterdam: Excerpta Medica; 1983:60-8.

41. Thomas B, Rolly G, Huylenbroek G et al. Clinical use of vecuronium bromide in balanced anesthesia. Comparison with pancuronium bromide. In: Agoston S, ed. Clinical experiences with Norcuron(Org NC 45, vecuronium bromide). Amsterdam: Excerpta Media; 1983:76-84.

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b. AHFS Drug Information 2004. McEvoy GK, ed. Neuromuscular blocking agents general statement. Bethesda, MD: American Society of Health-System Pharmacists; 2004:1303-6.

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