Brand name: Ativan
Drug class: Benzodiazepines

Medically reviewed by Drugs.com on Jun 10, 2024. Written by ASHP.

Introduction

Benzodiazepine; anticonvulsant, anxiolytic, and sedative.^{283 435 a b}

Uses for Lorazepam

Anxiety Disorders

Management of anxiety disorders and short-term relief of anxiety or anxiety associated with depressive symptoms.^{283 547}

Preoperative Sedation, Anxiolysis, and Amnesia

Used preoperatively to produce sedation, anxiolysis, and anterograde amnesia.⁴³⁵

Particularly useful when relief of anxiety and diminished recall of events associated with the surgical procedure are desired.⁴³⁵

Status Epilepticus

Treatment of status epilepticus.^{435 543 545 546}

Benzodiazepines are considered initial drugs of choice for management of status epilepticus because of their rapid onset of action, demonstrated efficacy, safety, and tolerability.^{545 563 756 757 758 759 761 762 763 764 765 766 767 771} Evidence supports use of IV lorazepam, IV diazepam, or IM midazolam.^{545 763 764 765 766 767 768 769} Individualize choice of therapy based on local availability, route of administration, pharmacokinetics, cost, and other factors (e.g., treatment setting).^{545 756 757 758 759 760 761 762 763 764 765 766 767 769}

Sedation in Critical Care Settings

Has been used for sedation of intubated and mechanically ventilated patients in critical care settings^{† [off-label]} (e.g., ICU).^{565 800 801 819}

Nonbenzodiazepine sedatives (dexmedetomidine or propofol) are generally preferred to benzodiazepines in mechanically ventilated, critically ill adults because of some modest clinical benefits that have been demonstrated (e.g., reduced duration of mechanical ventilation, shorter time to extubation, reduced risk of delirium).^{800 801 817 818 819 820}

When selecting an appropriate sedative agent, consider patient's individual sedation goals in addition to specific drug-related (e.g., pharmacology, pharmacokinetics, adverse effects, availability, cost) and patient-related (e.g., comorbid conditions such as anxiety, seizures, or alcohol or benzodiazepine withdrawal) factors.^{800 801}

Schizophrenia

Benzodiazepines have been used for augmentation of antipsychotic therapy or adjunctive therapy in patients with schizophrenia^{† [off-label]}.⁵²⁹

The American Psychiatric Association (APA) suggests that a benzodiazepine may be used for the treatment of akathisia associated with antipsychotic therapy; however, potential benefits of benzodiazepine therapy should be weighed against potential adverse effects.⁵²⁹

Benzodiazepines (e.g., lorazepam) also have been used for augmentation treatment of catatonia.⁵²⁹

Cancer Chemotherapy-induced Nausea and Vomiting

Has been used in the management of nausea and vomiting^{† [off-label]} associated with emetogenic cancer chemotherapy.^{492 493 494 495 496 497 498 499 500 501 502 503 504}

The American Society of Clinical Oncology (ASCO) guidelines on antiemetic therapy state that lorazepam is a useful adjunct to antiemetic drugs, but is not recommended as a single-agent antiemetic.⁶³⁰

Delirium

Has been used in the management of delirium^{† [off-label]}.^{533 535 536 537}

Although there is little evidence to support use of benzodiazepines alone for general cases of delirium, these drugs may be useful for certain types of delirium (e.g., delirium related to alcohol or benzodiazepine withdrawal).⁵³³

Drug-induced Cardiovascular Emergencies

Adjunct in the management of certain drug-induced cardiovascular emergencies^{† [off-label]}.⁶⁹⁶ May be beneficial adjunctively in patients with cocaine-induced acute coronary syndrome^†.⁶⁹⁶

Lorazepam Dosage and Administration

General

• Use smallest effective dosage to avoid oversedation.^{a b}

• In patients who have received prolonged (e.g., for several months) therapy, avoid abrupt discontinuance, since manifestations of withdrawal can be precipitated; gradually taper dosage.^a

Administration

Administer orally, IM, or by IV injection or IV infusion.^{283 435 547 a} Avoid intra-arterial injection (arteriospasm may cause gangrene, possibly requiring amputation).⁴³⁵

Oral Administration

Mix oral concentrate solution with a liquid (e.g., water, juice, carbonated or soda-like beverage) or semi-solid food (e.g., applesauce, pudding).⁵⁴⁷ Use the calibrated dropper provided by manufacturer.⁵⁴⁷ Stir liquid or food mixture gently for a few seconds and then consume immediately; do not store mixture for future use.⁵⁴⁷

IM Administration

Administer undiluted and inject deep into the muscle mass.⁴³⁵ IM administration usually not recommended in the treatment of status epilepticus, but may be used if IV access not available.⁴³⁵

IV Administration

Administer by direct IV injection or into tubing of an existing IV infusion.^{435 a}

Equipment necessary to maintain a patent airway and to support respiration and ventilation should be immediately available prior to IV administration.⁴³⁵ Monitor vital signs during IV infusion of the drug.⁴³⁵

IV injection:For administration as a direct IV injection, dilute commercially available injection with an equal volume of compatible diluent (e.g., sterile water for injection, 0.9% sodium chloride injection, or 5% dextrose injection).⁴³⁵ Following dilution, mix solution thoroughly by gently inverting container repeatedly until a homogenous solution is obtained; do not shake vigorously.⁴³⁵ Administer IV injection slowly at a rate not exceeding 2 mg/minute.⁴³⁵ Direct IV injection should be made with repeated aspiration to ensure that none of the drug is injected intra-arterially and that perivascular extravasation does not occur.⁴³⁵ If pain occurs during injection, immediately stop administration and determine whether intra-arterial injection or extravasation has occurred.⁴³⁵

IV infusion: A standard concentration of 1 mg/mL has been recommended (see Standardize 4 Safety section below).²⁵⁰

Standardize 4 Safety

Standardized concentrations for IV lorazepam have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care. Because recommendations from the S4S panels may differ from the manufacturer’s prescribing information, caution is advised when using concentrations that differ from labeling, particularly when using rate information from the label. For additional information on S4S (including updates that may be available), see [Web].²⁵⁰

Dosage

Pediatric Patients

Status Epilepticus†

IV

Doses of 0.05–0.1 mg/kg have been used.^{543 546}

Sedation in Critical Care Settings†

IV

Children ≥2 months of age: Some clinicians have suggested intermittent IV infusions of 0.025–0.05 mg/kg (up to 2 mg as initial dose) every 2–4 hours.⁵⁶⁵ Alternatively, a continuous IV infusion at a rate of 0.025 mg/kg per hour (up to 2 mg/hour) has been given with supplemental injections as needed to provide the desired level of sedation.⁵⁶⁵ Reduce initial dose by 50% in children <2 months of age because of wide interpatient variations in dosage requirements and low hepatic metabolic function.⁵⁶⁵

Adults

Anxiety

Oral

Initially, 2–3 mg daily divided in 2 or 3 doses.^{283 547} Maintenance dosage of 1–10 mg daily (usually 2–6 mg) in divided doses, with the largest dose administered at bedtime.^{283 547} Increase dosage gradually if higher dosage is indicated; increase the evening dose before the daytime doses.^a

For insomnia caused by anxiety or transient situational stress, 2–4 mg as a single daily dose, usually at bedtime.^{283 547}

Preoperative Sedation, Anxiolysis, and Amnesia

IM

0.05 mg/kg (up to 4 mg) at least 2 hours prior to surgery.⁴³⁵

IV

Initially, 0.044 mg/kg (or total of 2 mg, whichever is smaller) 15–20 minutes prior to surgery; do not routinely exceed this dosage in patients >50 years of age.⁴³⁵ For amnestic effects, doses up to 0.05 mg/kg (maximum 4 mg) may be administered.⁴³⁵

Status Epilepticus

IV

Initially, 4 mg.⁴³⁵ If seizures continue or recur after a 10- to 15-minute observation period, administer an additional 4-mg dose.⁴³⁵ Manufacturer states that experience with administration of additional doses is limited.⁴³⁵

Sedation in Critical Care Settings†

IV

Some experts recommend loading dose of 0.02–0.04 mg/kg (up to 2 mg), followed by intermittent injections of 0.02–0.06 mg/kg every 2–6 hours as needed or a continuous IV infusion at a rate of 0.01–0.1 mg/kg per hour (not to exceed 10 mg/hour).⁸⁰¹

Cancer Chemotherapy-induced Nausea and Vomiting†

Oral

2.5 mg the evening before and just after initiation of chemotherapy.⁴⁹⁶

IV

1.5 mg/m² (up to 3 mg) over 5 minutes, given 45 minutes before administration of chemotherapy.^a

Delirium†

IV

0.5–1 mg, immediately following 3 mg of haloperidol.⁵³³

Prescribing Limits

Adults

Preoperative Sedation, Anxiolysis, and Amnesia

IM

Manufacturer recommends maximum dose of 4 mg.⁴³⁵

IV

Manufacturer states initial dose of up to 2 mg usually administered for sedation and relief of anxiety.⁴³⁵ Doses up to 4 mg may be administered for amnestic effects.⁴³⁵

Status Epilepticus

IV

Manufacturer states experience with doses beyond the usual (4 mg initially, followed by an additional 4-mg dose 10–15 minutes later if seizures continue or recur) very limited.⁴³⁵

Sedation in Critical Care Settings†

IV

Some experts recommend that IV loading doses not exceed 2 mg.⁸⁰¹

If a continuous IV infusion is used, some experts recommend that the infusion be administered no faster than 10 mg/hour.⁸⁰¹

Special Populations

Hepatic Impairment

Dosage adjustments not required for parenteral administration.⁴³⁵

Adjust oral dosage carefully in patients with severe hepatic insufficiency because oral therapy may exacerbate hepatic encephalopathy; lower than recommended dosages may be sufficient in these patients.²⁸³

Renal Impairment

Dosage adjustment not required for single doses of lorazepam injection; however, exercise caution with administration of multiple doses over a short period of time.⁴³⁵

Geriatric Patients

Cautious dosage selection recommended because of greater sensitivity and possible age-related decreases in hepatic or renal function; initiate therapy at the lower end of the usual range.^{283 435}

Anxiety Disorders

Oral: Initially, 1–2 mg daily divided in 2 or 3 doses.^a

Preoperative Sedation, Anxiolysis, and Amnesia

Patients >50 years of age generally should not receive initial IV dose >2 mg.⁴³⁵ Excessive and prolonged sedation may occur.⁴³⁵

Cautions for Lorazepam

Contraindications

• Known hypersensitivity to benzodiazepines or any ingredient in the formulation (e.g., benzyl alcohol, polyethylene glycol, or propylene glycol in the injection).^{283 435}

• Acute angle-closure glaucoma (but may be administered to patients with open-angle glaucoma who are receiving appropriate therapy);^{283 435} however, clinical rationale for this contraindication has been questioned.^b

• Injection also contraindicated in patients with sleep apnea, patients with severe respiratory insufficiency (except in those requiring relief of anxiety and/or diminished recall of events while receiving mechanical ventilation), and in premature infants (because the formulation contains benzyl alcohol).⁴³⁵

• Do not administer injection intra-arterially.⁴³⁵

Warnings/Precautions

Warnings

Concomitant Use with Opiates

Concomitant use of benzodiazepines, including lorazepam, and opiates may result in profound sedation, respiratory depression, coma, and death.^{700 701 703 705 706 707} (See Boxed Warning.) Substantial proportion of fatal opiate overdoses involve concurrent benzodiazepine use.^{700 701 705 706 707 711}

Reserve concomitant use of lorazepam and opiates for patients in whom alternative treatment options are inadequate.^{700 703} (See Specific Drugs under Interactions.)

Respiratory and Cardiovascular Effects

Use oral lorazepam with caution in patients with compromised respiratory function (e.g., COPD, sleep apnea).^{283 547 b}

Possible apnea, hypotension, bradycardia, or cardiac arrest with parenteral administration, particularly in geriatric or severely ill patients, in patients with limited pulmonary reserve or unstable cardiovascular status, or if the drug is administered IV too rapidly.^{b 566 567}

Concomitant use of other CNS depressants may increase the risk of apnea.^a

Administer IV only in settings in which continuous monitoring of respiratory and cardiac function (i.e., pulse oximetry) is possible.⁴³⁵ Monitoring of vital signs should continue during recovery period.^{435 566 567}

Facilities, age- and size-appropriate equipment for bag/mask/valve ventilation and intubation, drugs, and skilled personnel necessary for ventilation and intubation, administration of oxygen, assisted or controlled respiration, airway management, and cardiovascular support should be immediately available when lorazepam is administered IV.^{435 566 567}

Status Epilepticus

Should be used for the treatment of status epilepticus only by clinicians experienced in the comprehensive management of the disease.⁴³⁵

Careful monitoring of respiratory rate and maintenance of an adequate, patent airway is required; ventilatory support may be necessary.⁴³⁵

Because of the prolonged duration of action, sedative effects of lorazepam (especially after multiple doses) may increase impairment of consciousness observed in the postictal state.⁴³⁵

CNS Effects

Performance of activities requiring mental alertness and physical coordination (operating machinery, driving a motor vehicle) may be impaired.^{a b} Impairment may persist for 24–48 hours following parenteral administration.^{435 a} Premature ambulation may result in falls.⁴³⁵

Concurrent use of other CNS depressants may cause additive or potentiated CNS depression.^{283 547 a b} (See Concomitant Use with Opiates under Cautions and also see Specific Drugs under Interactions.)

May interfere with assessment of level of anesthesia when administered IV prior to regional or local anesthesia, especially when given at doses >0.05 mg/kg or when opiate agonists or partial agonists are used concomitantly with recommended lorazepam doses.^{435 a}

Psychiatric Indications

Do not use in patients with primary depressive disorder or psychosis.^{283 547 a}

Abuse Potential

Possible tolerance, psychologic dependence, and physical dependence following prolonged administration.^{283 b}

Patients with a history of drug or alcohol dependence or abuse are at risk of habituation or dependence; use only with careful surveillance in such patients.^{283 547 b}

Withdrawal

Symptoms of withdrawal (similar to barbiturates or alcohol) may occur if discontinued abruptly.^{283 547 a} Avoid abrupt discontinuance; gradually taper dosage following extended therapy.^{283 547 a}

Endoscopic Procedures

Insufficient data to support use for outpatient endoscopic procedures; when used for inpatient endoscopic procedures, adequate recovery room observation time required.⁴³⁵

General Precautions

Suicide

Possibility of suicide in depressed patients; do not use in such patients without adequate antidepressant therapy.^{283 547 b}

Paradoxical Reactions

Paradoxical reactions (e.g., anxiety, excitation, hostility, aggression, rage, sleep disturbances/insomnia, sexual arousal, hallucinations) may occur, particularly in children and geriatric patients.^{283 547 b} Discontinue drug if such reactions occur.^{283 547 b}

Propylene Glycol or Polyethylene Glycol Toxicity

Possible adverse effects associated with propylene glycol (e.g., lactic acidosis, hyperosmolality, hypotension) or polyethylene glycol (e.g., acute tubular necrosis) in patients receiving higher than recommended parenteral dosages.⁴³⁵ More likely to occur in patients with renal impairment.⁴³⁵

Specific Populations

Pregnancy

Category D.⁴³⁵

Based on animal data, repeated or prolonged use of general anesthetics and sedation drugs, including lorazepam, during the third trimester of pregnancy may result in adverse neurodevelopmental effects in the fetus.^{750 753} (See Pediatric Use under Cautions and also see Advice to Patients.)

Lactation

Distributed into milk.⁴³⁵

Administer orally to nursing women only if the potential benefits to the woman outweigh the possible risk to the infant.²⁸³ Monitor nursing infants for adverse effects (e.g., sedation, irritability).²⁸³

Do not administer lorazepam injection to nursing women because of possible adverse effects to the infant (e.g., sedation).⁴³⁵

Pediatric Use

Safety and efficacy of tablets and oral concentrate solution not established in children <12 years of age.²⁸³

Safety of the injection for treatment of status epilepticus or efficacy for preoperative sedation not established in children <18 years of age.⁴³⁵

Paradoxical excitation (e.g., tremors, agitation, euphoria, logorrhea, brief episodes of visual hallucinations) reported in 10–30% of children <8 years of age.⁴³⁵

Seizures and myoclonus reported in pediatric patients, especially low birth weight neonates, receiving lorazepam injection.⁴³⁵ Brief tonic-clonic seizures reported in children receiving lorazepam for the management of atypical petit mal status epilepticus.⁴³⁵

Repeated or prolonged use of general anesthetics and sedation drugs, including lorazepam, in children <3 years of age or during the third trimester of pregnancy may adversely affect neurodevelopment.^{750 753} In animals, use for >3 hours of anesthetic and sedation drugs that block N-methyl-d-aspartic acid (NMDA) receptors and/or potentiate GABA activity leads to widespread neuronal apoptosis in the brain and long-term deficits in cognition and behavior;^{750 751 752 753} clinical relevance to humans is unknown.⁷⁵⁰ Some evidence suggests similar deficits may occur in children following repeated or prolonged exposure to anesthesia early in life.^{750 752} Some evidence also indicates that a single, relatively brief exposure to general anesthesia in generally healthy children is unlikely to cause clinically detectable deficits in global cognitive function or serious behavioral disorders.^{750 751 752} Most studies to date have substantial limitations; further research needed to fully characterize effects, particularly for prolonged or repeated exposures and in more vulnerable populations (e.g., less healthy children).⁷⁵⁰ Consider benefits and potential risks when determining the timing of elective procedures requiring anesthesia.⁷⁵⁰ FDA states that medically necessary procedures should not be delayed or avoided.^{750 753} (See Advice to Patients.)

Some pediatric patients (premature and low-birth weight infants or those receiving high doses of lorazepam injection) may be susceptible to adverse effects associated with benzyl alcohol, polyethylene glycol, and propylene glycol.⁴³⁵ Large amounts of benzyl alcohol (i.e., 100–400 mg/kg daily) have been associated with toxicity in neonates.^{435 584 585 586 587 588 589 590} (See Propylene Glycol or Polyethylene Glycol Toxicity under Cautions.)

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.^{283 435} Possibility of greater sensitivity to the drug (e.g., respiratory or CNS depression. sedation) in some geriatric individuals.⁴³⁵

Select initial dosages at the lower end of the usual range because of potential for greater sensitivity and age-related decreases in hepatic or renal function.^{283 435} (See Geriatric Patients under Dosage and Administration.)

May cause excessive sedation for 6–8 hours or longer after surgery in this population.⁴³⁵

Possible paradoxical excitation (e.g., anxiety, excitation, hostility, aggression, rage, sleep disturbances/insomnia, sexual arousal, hallucinations).^{b 283}

Hepatic Impairment

Lorazepam injection is not recommended for use in patients with hepatic failure; use with caution in patients with mild to moderate hepatic disease.⁴³⁵ (See Hepatic Impairment under Dosage and Administration.)

Oral lorazepam may exacerbate hepatic encephalopathy; therefore, use with caution in patients with severe hepatic insufficiency and/or encephalopathy.²⁸³

Renal Impairment

Lorazepam injection is not recommended for use in patients with renal failure; use with caution in patients with mild to moderate renal disease.⁴³⁵ (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

With oral therapy, sedation, dizziness, weakness, unsteadiness.²⁸³

With parenteral therapy for the management of status epilepticus, hypotension, somnolence, respiratory failure; with parenteral therapy for preoperative use, excessive sleepiness, drowsiness.⁴³⁵

With IM injections, local effects (e.g., pain, sensation of burning, redness) observed at the injection site.⁴³⁵

Drug Interactions

Specific Drugs

Lorazepam Pharmacokinetics

Absorption

Bioavailability

Readily absorbed following oral administration; absolute bioavailability is 90%.²⁸³

Completely and rapidly absorbed following IM administration.⁴³⁵

Peak plasma concentrations are attained in approximately 2 hours following oral administration²⁸³ and within 3 hours following IM administration.⁴³⁵

Onset

After IV administration, the onset of anticonvulsant, anxiolytic, or sedative action occurs in 1–5 minutes.^b

After IM administration, the onset of action is 15–30 minutes.^b

Duration

After IV or IM administration, the duration of anticonvulsant, anxiolytic, or sedative action is 12–24 hours.^b

Distribution

Extent

Widely distributed into body tissues; crosses the blood-brain barrier.^{435 b}

Crosses the placenta and is distributed into milk.^{435 b}

Plasma Protein Binding

Approximately 85–91%.^{283 435 b}

Elimination

Metabolism

Extensively metabolized in the liver to inactive metabolites.^{283 435}

Elimination Route

Excreted principally in urine as metabolites.^{283 435}

Half-life

10–20 hours.^{283 435 b}

Special Populations

In neonates, clearance reduced by 80% compared with healthy adults.⁴³⁵

In geriatric patients or patients with hepatic cirrhosis, clearance not substantially altered.^{435 b}

In patients with renal impairment, clearance of lorazepam glucuronide is reduced, but total clearance of lorazepam is not altered following single IV dose.⁴³⁵

Stability

Storage

Oral

Tablets

Tight containers at 25°C (may be exposed to 15–30°C).²⁸³

Oral Concentrate Solution

2–8°C; protect from light.⁵⁴⁷

Parenteral

Injection

2–8°C; protect from light.⁴³⁵

Actions

• Effects appear to be mediated through the inhibitory neurotransmitter GABA; the site and mechanism of action within the CNS appear to involve a macromolecular complex (GABA_A-receptor-chloride ionophore complex) that includes GABA_A receptors, high-affinity benzodiazepine receptors, and chloride channels.^{320 358 359 360 361 362 363 364 365 366 367 368 369 370}

Advice to Patients

• Provide manufacturer's patient information (e.g., medication guide) to the patient each time oral lorazepam preparations (tablets, solution concentrate) are dispensed.^{283 547}

• Risk of potentially fatal additive effects (e.g., profound sedation, respiratory depression, coma) if used concomitantly with opiates either therapeutically or illicitly.^{700 703} Avoid concomitant use of opiate antitussives;^{700 704} also avoid concomitant use of opiate analgesics unless use is supervised by clinician.^{700 703}

• Potential for drug to impair mental alertness or physical coordination; avoid driving or operating machinery until effects on individual are known.^{283 435} Following parenteral dose, wait 24–48 hours or until drowsiness subsides before participating in such activities.⁴³⁵

• Importance of informing patients of the pharmacologic effects of lorazepam (e.g., sedation, relief of anxiety, lack of recall) and the duration of these effects (≥8 hours) so that they may understand the risks and benefits.⁴³⁵

• Importance of avoiding premature ambulation (within 8 hours of dose) in patients receiving parenteral lorazepam.^{a 435}

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.^{283 435} Importance of avoiding alcohol-containing beverages or products (for at least 24–48 hours after parenteral administration).^{435 b}

• When procedures requiring general anesthetics or sedation drugs, including lorazepam, are considered for young children or pregnant women, importance of discussing with the patient, parent, or caregiver the benefits, risks (including potential risk of adverse neurodevelopmental effects), and appropriate timing and duration of the procedure.^{750 753}

• Importance of informing clinicians about any concomitant illnesses (e.g., depression, respiratory disorders).^{283 435}

• Importance of taking only as prescribed; do not increase dosage or duration of therapy unless otherwise instructed by a clinician.²⁸³

• Importance of not abruptly discontinuing therapy; consult clinician about discontinuing use.²⁸³

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{283 435}

• Importance of informing patients of other important precautionary information. ^{283 435} (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

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

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Lorazepam is subject to control under the Federal Controlled Substances Act of 1970 as a schedule IV (C-IV) drug.

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

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