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Anxiety Disorders

Lorazepam shares the actions of other benzodiazepines and is used for the management of anxiety disorders or for the short-term relief of symptoms of anxiety or anxiety associated with depressive symptoms. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic. The efficacy of lorazepam for long-term use (i.e., longer than 4 months) as an anxiolytic has not been evaluated. The need for continued therapy with the drug should be periodically reassessed.

Preoperative Sedation, Anxiolysis, and Anterograde Amnesia

Lorazepam injection is used preoperatively in adults to produce sedation, relieve anxiety, and provide anterograde amnesia. Administration of lorazepam injection is especially useful in patients with preoperative anxiety who prefer diminished recall of events associated with the day of surgery. Lorazepam injection may be used in conjunction with atropine sulfate, opiate analgesics, other parenterally administered analgesics, commonly used anesthetics, and skeletal muscle relaxants.

Status Epilepticus

Lorazepam is used IV for the management of status epilepticus and IV lorazepam or diazepam generally is considered the drug of choice for termination of this condition. The efficacy of IV lorazepam was established in 2 multicenter controlled trials in patients (mostly 18-65 years of age) with tonic-clonic status epilepticus, simple partial and complex partial status epilepticus, or absence status.

In a double-blind, randomized, active-control study in 58 patients with status epilepticus, efficacy of lorazepam (given as a 2-mg IV dose with an additional 2-mg IV dose if necessary) was compared with that of diazepam (given as a 5-mg IV dose with an additional 5-mg IV dose if necessary). In this study, 80 or 57% of patients receiving lorazepam or diazepam, respectively, were considered responders, defined as the percentage of patients in whom seizures were terminated within 10 minutes after administration of the drug and who continued to be seizure-free for at least an additional 30 minutes. When patients who did not respond to the initial doses of lorazepam or diazepam received an additional 2-4 mg of lorazepam or 5-10 mg of diazepam, respectively, the overall response rate increased to 93 or 86%, respectively. In addition, in another clinical study in adults with status epilepticus, 61, 57, and 76% of patients receiving 1, 2, and 4 mg of lorazepam, respectively, reportedly were responders (as defined above). Although IV diazepam has been used more extensively, some clinicians prefer IV lorazepam because of its more prolonged duration of effect. For continuing seizures, a long-acting anticonvulsant (e.g., IV phenytoin, IV fosphenytoin) can be added presumptively to IV benzodiazepine therapy for the management of status epilepticus.

Sedation in Critical-care Settings

Lorazepam, administered by an intermittent injection or continuous IV infusion, has been used for sedation of intubated and mechanically ventilated adults and children during treatment in a critical-care setting. Lorazepam has been shown to be as effective as midazolam or propofol in terms of the level of sedation and the time required to achieve adequate sedation, and usually, the number of daily dose adjustments. In one study, midazolam IV infusions required more frequent dosage adjustments to maintain the desired level of sedation than lorazepam. Some clinicians recommend the use of lorazepam in most patients that require prolonged sedation in a critical-care setting, while propofol or midazolam is the preferred drug for short-term sedation. Because of the lorazepam's slow onset of action, the drug is not effective for the treatment of acute agitation and midazolam or diazepam is preferred for rapid sedation of the acutely agitated patient.


Lorazepam also has been used in the management of schizophrenia and may be helpful for the management of anxiety, agitation, and sleep disturbances that are often present during the acute phase of schizophrenia in patients receiving antipsychotic therapy. In addition, the drug also has been used in patients who experience akathisia while receiving antipsychotic drugs and for the treatment of acute catatonic reactions, whether associated with schizophrenia or other conditions.

Cancer Chemotherapy-induced Nausea and Vomiting

Lorazepam also has been used alone, but usually in combination with other drugs, such as 5-HT3 receptor antagonists, and/or corticosteroids, for the management of nausea and vomiting associated with emetogenic cancer chemotherapy, including that associated with cisplatin.


Lorazepam also has been used in the management of delirium. Results of several open studies suggest that combined therapy with IV lorazepam and IV haloperidol was more effective than IV haloperidol alone, with a shorter duration of delirium during combined therapy and fewer extrapyramidal manifestations. If a benzodiazepine is used for the treatment of delirium, those with a short duration and no active metabolites (e.g., lorazepam) are preferred.

Drug-induced Cardiovascular Emergencies

Lorazepam has been used adjunctively in the management of certain drug-induced cardiovascular emergencies and cocaine-induced acute coronary syndrome.

Dosage and Administration


Lorazepam is administered orally or by IM or IV injection. The drug should not be administered by intra-arterial injection since arteriospasm can occur which may cause gangrene and possibly require amputation.

When lorazepam oral concentrate solution is used, the dose should be added to 30 mL or more of diluent (e.g., water, juices, carbonated or soda-like beverages) or to semi-solid foods (e.g., applesauce, pudding) just before administration.

IM injections of lorazepam, administered as undiluted solutions, should be made deeply into a large muscle mass.

Prior to IV administration, lorazepam injection must be diluted with an equal volume of compatible diluent, such as sterile water for injection, 0.9% sodium chloride injection, or 5% dextrose injection. To dilute a prefilled syringe (Tubex) containing lorazepam injection, extrude all of the air from the half-filled syringe, slowly aspirate an equal volume of diluent, pull back slightly on the plunger to provide space for mixing, and then immediately mix the contents thoroughly by gently inverting the syringe repeatedly until a homogenous solution results. The syringe should not be shaken vigorously since this will cause air entrapment. Alternatively, a dilution for IV administration may be prepared by withdrawing the desired dose from a vial of lorazepam injection into an empty syringe, and then following the procedure for mixing described for the prefilled syringe. Solutions of lorazepam injection should not be used if they appear discolored or contain a precipitate.

Following dilution of the drug, lorazepam may be injected directly into a vein or into the tubing of a free-flowing compatible IV infusion (e.g., 0.9% sodium chloride, 5% dextrose), at a rate of injection not exceeding 2 mg/minute. Direct IV injection with the drug should be made with repeated aspiration to ensure that none of the drug is injected intra-arterially and that perivascular extravasation does not occur.

Equipment necessary to maintain a patent airway and to support respiration and ventilation should be immediately available prior to administration of IV lorazepam. Vital signs should be monitored during IV infusion of the drug. When lorazepam has been used as a continuous IV infusion for sedation of intubated and mechanically ventilated patients, some clinicians have recommended that the 2-mg/mL injection be diluted in a glass container to a concentration of 1 mg/mL or less with a compatible IV fluid (e.g., 0.9% sodium chloride injection, 5% dextrose injection). Alternatively, the 2-mg/mL lorazepam injection may be administered undiluted as an infusion, using a patient-controlled analgesia (PCA) device.


Dosage of lorazepam must be individualized, and the smallest effective dosage should be used (especially in geriatric or debilitated patients, in those with low serum albumin, and in patients currently receiving other CNS depressants) to avoid oversedation.

Anxiety Disorders

The usual initial adult oral dosage of lorazepam for the symptomatic treatment of anxiety is 2-3 mg daily, divided in 2 or 3 doses. In geriatric or debilitated patients, lorazepam therapy should be initiated with 1-2 mg daily, divided in 2 or 3 doses. Dosage may range from 1-10 mg daily (usually 2-6 mg) in divided doses, with the largest single dose given at bedtime. For insomnia caused by anxiety in adults, 2-4 mg of lorazepam is given as a single daily dose, usually at bedtime. In patients who have received prolonged (e.g., for several months) lorazepam therapy, abrupt discontinuance of the drug should be avoided since manifestations of withdrawal can be precipitated; if the drug is to be discontinued in such patients, it is recommended that dosage be gradually tapered.

Preoperative Sedation, Anxiolysis, and Anterograde Amnesia

For preoperative IM use in adults, the usual dose of lorazepam is 0.05 mg/kg administered by deep IM injection at least 2 hours prior to surgery. The IM dose should be individualized, but should not exceed 4 mg. IM administration of lorazepam injection is not recommended in patients younger than 18 years of age.

Alternatively, lorazepam may be administered IV for preoperative use. For preoperative IV use, the usual initial dose of lorazepam for sedation and relief of anxiety is 0.044 mg/kg (up to 2 mg total) administered 15-20 minutes prior to surgery; this dose is sufficient for sedating most adults and generally should not be exceeded in patients older than 50 years of age. For those patients in whom increased lack of recall about perioperative events is considered beneficial, lorazepam doses up to 0.05 mg/kg (maximum total dose of 4 mg) may be administered IV.

Status Epilepticus

For the management of status epilepticus, the usual IV dosage of lorazepam for patients 18 years of age and older is 4 mg. If seizures continue or recur after a 10- to 15-minute period of observation, an additional 4-mg dose of the drug may be administered. The manufacturer states that experience with administration of additional doses of lorazepam is limited. IM administration of lorazepam is not recommended for the treatment of status epilepticus, because therapeutic plasma concentrations of the drug are not achieved as rapidly as with IV administration of the drug. However lorazepam may be given IM if IV access is not available.

For the management of status epilepticus in children, an IV dosage of 0.05-0.1 mg/kg may used.

Sedation in Critical-Care Settings

For sedation in intubated and mechanically ventilated adults and children older than 12 years of age during treatment in critical-care settings, intermittent lorazepam injections of 0.02-0.06 mg/kg may be given every 2-6 hours. When given as a continuous IV infusion, an infusion rate of 0.01-0.1 mg/kg per hour has been recommended. The infusion rate should be titrated to the lowest effective dosage to provide desired level of sedation. Frequent assessment of the patient's sedation requirements and tapering of the infusion rate may prevent prolonged sedative effects.

Although there is limited information available on the use of lorazepam for sedation in intubated and mechanically ventilated children during treatment in critical-care settings, some clinicians have suggested lorazepam dosages of 0.025-0.05 mg/kg (maximum initial dose of 2 mg) given as intermittent IV infusions every 2-4 hours in children 2 months of age and older. Alternatively, in these pediatric patients, lorazepam may be administered by a continuous IV infusion, at a rate of 0.025 mg/kg per hour (up to 2 mg/hour) which may be titrated as necessary or supplemented with rapid (''bolus'') injections of the drug to provide the desired level of sedation. Because of wide interpatient variations on dosage requirements and low hepatic metabolic function, the initial lorazepam dose should be reduced by 50% in infants younger than 2 months of age.

Cancer Chemotherapy-induced Nausea and Vomiting

For the management of nausea and vomiting associated with emetogenic cancer chemotherapy, including that associated with cisplatin, adults have received 2.5 mg of lorazepam orally the evening before and just after initiation of chemotherapy. Alternatively, adults have received 1.5 mg/m (usually up to a maximum dose of 3 mg) of lorazepam administered IV (usually over 5 minutes) 45 minutes before initiation of chemotherapy.


For the management of delirium in combination with haloperidol, combined therapy can be initiated in adults with an IV haloperidol dose of 3 mg followed immediately with an IV lorazepam dose of 0.5-1 mg. Dosage of the drugs should then be adjusted according to patient response and tolerance. ECG should be determined at baseline and periodically because of the risk of QT prolongation with haloperidol therapy. and also

Dosage in Renal and Hepatic Impairment

The manufacturer states that a dosage adjustment is not required in patients with impaired renal function for single doses of lorazepam injection; however, caution should be exercised with administration of multiple doses of lorazepam injection over a short period of time.

Since the pharmacokinetics of parenteral lorazepam do not appear to be altered in patients with hepatic impairment, dosage adjustment is not necessary in such patients. However, because oral lorazepam may exacerbate hepatic encephalopathy, dosage of oral lorazepam should be adjusted carefully in patients with severe hepatic insufficiency and lower than recommended dosages may be sufficient in these patients.


Adverse effects reported with lorazepam are similar to those reported with other benzodiazepines. Changes in vital signs (e.g., respiratory rate, blood pressure) are the most frequent adverse effects associated with parenteral lorazepam administration. For further discussion of the cautions, precautions, and contraindications associated with lorazepam, . Flumazenil, a benzodiazepine antagonist, can be used in hospitalized patients as an adjunct, not a substitute for, proper management of lorazepam overdose.

Precautions and Contraindications

Drugs that affect the CNS (e.g., phenothiazines, barbiturates, antidepressants, alcohol, scopolamine, monoamine oxidase inhibitors) may have additive CNS effects when used concomitantly with, or during the period of recovery from, lorazepam. Such combinations, or IV lorazepam used alone in higher than recommended doses, can produce excessive sedation which may result in partial airway obstruction. The manufacturer warns that scopolamine does not provide additional benefit when used concomitantly with lorazepam, but may increase sedation, hallucinations, and irrational behavior.

Concomitant use of benzodiazepines, including lorazepam, and opiate agonists or opiate partial agonists may result in profound sedation, respiratory depression, coma, and death. Patients receiving lorazepam and/or their caregivers should be apprised of the risks associated with concomitant therapeutic or illicit use of benzodiazepines and opiates.

When lorazepam is administered IV prior to regional or local anesthesia, especially at doses greater than 0.05 mg/kg or when opiate agonists or partial agonists are used concomitantly with recommended lorazepam doses, excessive sedation or drowsiness may occur; these effects may possibly interfere with patient cooperation in determining levels of anesthesia.

Lorazepam should be administered IV only in settings in which continuous monitoring of respiratory and cardiac function (i.e., pulse oximetry) is possible. Safety and efficacy of lorazepam may vary according to the dose administered and clinical status of the patient. Since lorazepam is capable of producing several levels of CNS depression--from mild to deep sedation, 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 whenever this drug is administered. Monitoring of vital signs also should continue during the recovery period. Lorazepam injection should be administered with extreme caution to geriatric or debilitated patients, and to patients with compromised pulmonary function (decreased reserve), since underventilation and/or hypoxic cardiac arrest may occur. For deeply sedated pediatric patients, a dedicated individual other than the clinician performing the procedure should monitor the patient throughout the procedure.

Lorazepam should only be used for the treatment of status epilepticus by clinicians experienced in the comprehensive management of the disease. Since these patients may be at increased risk of respiratory depression associated with administration of IV lorazepam, they require careful monitoring of respiratory rate and maintenance of an adequate, patent airway. Ventilatory support also may be needed in some patients. Because of the prolonged duration of action of lorazepam, it should be considered that the sedative effects of the drug (especially after multiple doses) may increase the impairment of consciousness observed in the postictal state.

The manufacturer warns that there is no evidence to date to support the use of lorazepam injection in patients with coma, shock, or acute alcohol intoxication. The manufacturer warns that there are insufficient data to support the use of lorazepam injection for outpatient endoscopic procedures; when these procedures are conducted in inpatients, adequate recovery room observations are necessary and pharyngeal reflex activity should be minimized prior to the procedure by administering adequate topical or regional anesthesia.

Adverse effects associated with propylene glycol (e.g., lactic acidosis, hyperosmolality, hypotension) or polyethylene glycol (e.g., acute tubular necrosis) may occur in patients receiving lorazepam injection at higher than recommended dosages. Manifestations of toxicity are more likely to occur in patients with renal impairment.

Lorazepam injection is not recommended for use in patients with hepatic and/or renal failure, since the drug is most likely conjugated in the liver and since conjugated lorazepam is excreted via the kidneys. However, this does not preclude use of the drug in patients with mild to moderately severe hepatic or renal disease; in these patients, the lowest possible effective dose of lorazepam injection should be administered since the effects of the drug may be prolonged. The manufacturer states that administration of oral lorazepam may exacerbate hepatic encephalopathy and, therefore, the drug should be used with caution in patients with severe hepatic insufficiency and/or encephalopathy. Dosage of lorazepam should be adjusted carefully in patients with severe hepatic insufficiency; lower than recommended dosages may be sufficient in these.

Patients should be informed of the pharmacologic effects of lorazepam (e.g., sedation, relief of anxiety, lack of recall) and the duration of these effects (8 hours or longer) so that they may adequately perceive the risks and benefits of use of lorazepam injection. Patients should be warned that lorazepam injection may impair their ability to perform activities requiring mental alertness or physical coordination (e.g., operating machinery, driving a motor vehicle) for 24-48 hours following administration of the drug. Impaired performance may persist for longer periods in geriatric patients, in patients using other drugs concomitantly, and as a result of the stress of surgery or general condition of the patient. Patients also should be warned that premature ambulation (within 8 hours of receiving lorazepam injection) may result in injury from falling. Patients also should be warned that concomitant use of lorazepam injection with sedatives, opiate analgesics (opiate agonists or partial agonists), or tranquilizers may increase the extent and duration of impaired performance, may cause excessive sedation, and, rarely, may interfere with recall and recognition of events on the day of surgery and the following day. Patients should be advised to abstain from consumption of alcoholic beverages for 24-48 hours following administration of lorazepam injection.

Lorazepam injection is contraindicated in patients with known hypersensitivity to benzodiazepines or any ingredients in the formulation (i.e., polyethylene glycol, propylene glycol, or benzyl alcohol) and in patients with acute angle-closure glaucoma or sleep apnea syndrome. The injection also is contraindicated in patients with severe respiratory insufficiency, except in those requiring relief of anxiety and/or diminished recall of events while being mechanically ventilated.

Pediatric Precautions

Safety and efficacy of lorazepam tablets and oral concentrate solution in children younger than 12 years of age have not been established. The safety of lorazepam injection in children younger than 18 years of age with status epilepticus has not been systematically evaluated. In several open label studies conducted in pediatric patients (neonates as young as a few hours up to adolescents 18 years of age), paradoxical excitation, characterized by tremors, agitation, euphoria, logorrhea, and brief episodes of visual hallucinations, was reported in 10-30% of children younger than 8 years of age. Brief tonic-clonic seizures were reported in pediatric patients who received lorazepam for the management of atypical petit mal status epilepticus.

The efficacy of lorazepam injection for preoperative sedation has not been established in children younger than 18 years of age. Seizures and myoclonus have been reported in pediatric patients (especially in low birth-weight neonates) receiving lorazepam injection.

FDA warns that repeated or prolonged use of general anesthetics and sedation drugs, including lorazepam, in children younger than 3 years of age or during the third trimester of pregnancy may affect brain development. Animal studies in multiple species, including nonhuman primates, have demonstrated that use for longer than 3 hours of anesthetic and sedation drugs that block N-methyl-d-aspartic acid (NMDA) receptors and/or potentiate γ-aminobutyric acid (GABA) activity leads to widespread neuronal and oligodendrocyte cell loss and alterations in synaptic morphology and neurogenesis in the brain, resulting in long-term deficits in cognition and behavior. Across animal species, vulnerability to these neurodevelopmental changes occurs during the period of rapid brain growth or synaptogenesis; this period is thought to correlate with the third trimester of pregnancy through the first year of life in humans, but may extend to approximately 3 years of age. The clinical relevance of these animal findings to humans is not known. While some published evidence suggests that similar deficits in cognition and behavior may occur in children following repeated or prolonged exposure to anesthesia early in life, other studies have found no association between pediatric anesthesia exposure and long-term adverse neurodevelopmental outcomes. Most studies to date have had substantial limitations, and it is not clear whether the adverse neurodevelopmental outcomes observed in children were related to the drug or to other factors (e.g., surgery, underlying illness). There is some clinical evidence 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; however, further research is needed to fully characterize the effects of exposure to general anesthetics in early life, particularly for prolonged or repeated exposures and in more vulnerable populations (e.g., less healthy children).

Anesthetic and sedation drugs are an essential component of care for children and pregnant women who require surgery or other procedures that cannot be delayed; no specific general anesthetic or sedation drug has been shown to be less likely to cause neurocognitive deficits than any other such drug. Pending further accumulation of data in humans from well-designed studies, decisions regarding the timing of elective procedures requiring anesthesia should take into consideration both the benefits of the procedure and the potential risks. When procedures requiring the use of general anesthetics or sedation drugs are considered for young children or pregnant women, clinicians should discuss with the patient, parent, or caregiver the benefits, risks (including potential risk of adverse neurodevelopmental effects), and appropriate timing and duration of the procedure. FDA states that procedures that are considered medically necessary should not be delayed or avoided.

Lorazepam injection contains benzyl alcohol, polyethylene glycol, and propylene glycol and some pediatric patients (premature and low-birth weight infants or those receiving high doses of the injection) may be susceptible to adverse effects associated with these ingredients. Although a causal relationship has not been established, administration of injections preserved with benzyl alcohol has been associated with toxicity in neonates. Toxicity appears to have resulted from administration of large amounts (i.e., 100-400 mg/kg daily) of benzyl alcohol in these neonates. Exposure to such excessive amounts of benzyl alcohol has been associated with CNS depression, metabolic acidosis, gasping respirations, gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. Although use of drugs preserved with benzyl alcohol should be avoided in neonates whenever possible, the American Academy of Pediatrics (AAP) states that the presence of small amounts of the preservative in a commercially available injection should not proscribe its use when indicated in neonates.

In pediatric patients, propylene glycol present in high doses of lorazepam injections, has been associated with adverse effects, including CNS toxicity, seizures, intraventricular hemorrhage, unresponsiveness, tachypnea, tachycardia, and diaphoresis.

Geriatric Precautions

Clinical trials of lorazepam did not include sufficient numbers of patients 65 years and older to determine whether they respond differently than younger adults. However, unless enhanced suppression of recall is desired, patients older than 50 years of age generally should not be given an initial parenteral lorazepam dose greater than 2 mg since excessive and prolonged sedation may occur.

No age-related differences in the pharmacokinetics of lorazepam have been identified; however, because of greater sensitivity and increased frequency of impaired hepatic or renal function in geriatric patients, the manufacturer suggests that patients in this age group receive initial dosages of the drug in the lower end of the usual range.(See Dosage and Administration: Dosage) Geriatric patients should be warned that lorazepam injection may cause excessive sedation for 6-8 hours or longer after surgery.

Mutagenicity and Carcinogenicity

Studies to determine the mutagenic potential of lorazepam have not been performed. No evidence of carcinogenicity was observed in rats or mice during an 18-month study using oral lorazepam.

Pregnancy, Fertility, and Lactation


Lorazepam may cause fetal toxicity when administered to pregnant women. An increased risk of congenital malformations associated with use of anxiolytic agents (i.e., chlordiazepoxide, diazepam, and/or meprobamate) during the first trimester of pregnancy has been suggested by several human studies. In humans, lorazepam and its glucuronide have been shown to cross the placenta (as determined from samples of umbilical cord blood). The drug has also been shown to cause various adverse fetal effects during reproduction studies in animals. Lorazepam injection should not be used during pregnancy. In addition, the manufacturer does not recommend preoperative use of the injection for obstetric procedures (e.g., cesarean section) or during labor and delivery, since safety of the injection has not been established in such procedures. Oral or injectable lorazepam should be used during pregnancy only in life-threatening situations or severe disease (e.g., status epilepticus) for which safer drugs cannot be used or are ineffective. The possibility that a woman of childbearing potential may be pregnant at the time lorazepam is initiated should be considered. When lorazepam is administered during pregnancy or if the patient becomes pregnant while receiving the drug, the patient should be advised of the potential hazard to the fetus and about the desirability of discontinuing lorazepam.

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. The clinical relevance of these animal findings to humans is not known; the potential risk of adverse neurodevelopmental effects should be considered and discussed with pregnant women undergoing procedures requiring general anesthetics and sedation drugs.(See Cautions: Pediatric Precautions.)


It is not known whether lorazepam affects fertility in humans. No evidence of impaired fertility was observed in rats following oral administration of lorazepam doses of 20 mg/kg. At doses of 40 mg/kg or more, there was evidence of fetal resorption and increased fetal loss in rabbits.


Lorazepam is distributed into milk; other benzodiazepines have been shown to distribute into milk. Because of the potential for sedation in nursing infants, a decision should be made to discontinue nursing or lorazepam, taking into account the importance of the drug to the woman. Oral lorazepam should not be administered to nursing women unless the potential benefits to the woman outweigh the possible risk to the infant. Nursing infants receiving oral lorazepam should be monitored for adverse effects (e.g., sedation, irritability). The manufacturer states that IV lorazepam injection should not be administered to nursing women, because of possible adverse effects (e.g., sedation).

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