Class: Benzodiazepines
VA Class: CN302
CAS Number: 846-49-1
Brands: Ativan

Introduction

Benzodiazepine; anticonvulsant, anxiolytic, and sedative.^{a b c d}

Uses for Lorazepam

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Anxiety Disorders

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

Preoperative Sedation, Anxiolysis, and Anterograde Amnesia

Preoperatively, to produce sedation, relieve anxiety, and provide anterograde amnesia.^{a d}

Status Epilepticus

A drug of choice in the management of status epilepticus.^a

Sedation in Critical-care Settings

Sedation† of intubated and mechanically ventilated patients in a critical care setting. Other agents with more rapid onset (e.g., diazepam, midazolam) preferred for rapid sedation of acute agitated patients.

Schizophrenia

Has been used in management of schizophrenia; may be helpful for management of anxiety, agitation, and sleep disturbances that are often present during the acute phase of schizophrenia in patients receiving antipsychotic therapy.

May be helpful in patients experiencing akathisia† while receiving antipsychotic drugs (e.g., for management of schizophrenia).

Also has been used for treatment of acute catatonic reactions†, whether associated with schizophrenia or other conditions.

Cancer Chemotherapy-induced Nausea and Vomiting

Alone or as adjunctive therapy for the management of nausea and vomiting† associated with emetogenic cancer chemotherapy (including cisplatin).

Delirium

Management of delirium† alone or in combination with an antipsychotic agent (e.g., haloperidol).

Drug-induced Cardiovascular Emergencies

Adjunct in the management of certain drug-induced cardiovascular emergencies† (e.g., drug-induced hemodynamically significant tachycardia†, hypertensive emergency†, acute coronary syndrome†, or acute anticholinergic syndrome†) when standard emergency cardiovascular care (ECC) guidelines may not be optimal or appropriate. Adjunct in the initial treatment of cocaine-induced acute coronary syndrome†.

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 continuous infusion.^{a b c d} Avoid intra-arterial injection (arteriospasm may cause gangrene, possibly requiring amputation).^{a d}

Oral Administration

Dilute dose of oral concentrate solution in 30 mL or more of diluent (e.g., water, juice, carbonated or soda-like beverages) or mix with semi-solid foods (e.g., applesauce, pudding) just prior to administration.^a

IM Administration

Administer undiluted injection deeply into a large muscle mass. IM administration is not usually recommended, but may be used if IV access is not available.

IV Administration

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

Direct 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.^{a d} If pain occurs during the injection, immediately stop the injection and determine whether intra-arterial injection or extravasation has occurred.^d

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

Dilution

For administration as a direct injection, dilute 2-mg/mL injection with an equal volume of compatible diluent (e.g., sterile water for injection, 0.9% sodium chloride injection, or 5% dextrose injection) immediately prior to IV administration.^{a d}

For administration as a continuous infusion, dilute the 2-mg/mL injection in a glass container to a concentration of ≤1 mg/mL with a compatible IV fluid. (See Solution Compatibility under Stability.)

Alternatively, 2-mg/mL injection may be administered undiluted as an infusion using a patient-controlled analgesia (PCA) device.

Rate of Administration

Administer by direct injection into a vein or the tubing of a free-flowing compatible IV infusion at a rate ≤2 mg/minute.^a (See Solution Compatibility under Stability.)

Dosage

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Pediatric Patients

Status Epilepticus†

IV

Initially, 0.05–0.1 mg/kg.

Sedation in Critical-care Settings†

IV

Children ≤12 years of age: Dosages of 0.025–0.05 mg/kg (up to 2 mg as initial dose) every 2–4 hours have been used. Alternatively, 0.025 mg/kg per hour (up to 2 mg/hour) as a continuous infusion; titrate infusion rate as necessary or supplement with rapid injections of the drug to provide the desired level of sedation. Children <2 months of age: Reduce initial dose by 50% because of wide interpatient variations in dosage requirements and low hepatic metabolic function.

Children >12 years of age: 0.02–0.06 mg/kg given every 2–6 hours. Alternatively, 0.01–0.1 mg/kg per hour as a continuous infusion; titrate infusion rate to the lowest dosage that provides desired level of sedation.

Adults

Anxiety

Oral

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

For insomnia caused by anxiety, 2–4 mg as a single daily dose at bedtime.^{a c}

Preoperative Sedation, Anxiolysis, and Anterograde Amnesia

IM

0.05 mg/kg (up to 4 mg) at least 2 hours prior to surgery.^{a d}

IV

Initially, 0.044 mg/kg (up to 2 mg) 15–20 minutes prior to surgery; do not routinely exceed this dosage in patients >50 years of age.^{a d} For amnesic effects, doses up to 0.05 mg/kg (maximum 4 mg) may be administered.^{a d}

Status Epilepticus

IV

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

Sedation in Critical-care Settings†

IV

0.02–0.06 mg/kg given every 2–6 hours.

Alternatively, 0.01–0.1 mg/kg per hour as a continuous infusion; titrate infusion rate to the lowest dosage that provides desired level of sedation.

Cancer Chemotherapy-induced Nausea and Vomiting†

Oral

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

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.

Prescribing Limits

Adults

Preoperative Sedation, Anxiolysis, and Anterograde Amnesia

IM

4 mg.^{a d}

IV

2 mg for sedation and relief of anxiety.^{a d} For amnesic effects, 4 mg;^{a d} 3 mg for management of chemotherapy-induced nausea and vomiting.^a

Special Populations

Hepatic Impairment

Dosage adjustments are not required for parenteral administration.

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.

Renal Impairment

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

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.

Anxiety Disorders

Oral

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

Preoperative Sedation, Anxiolysis, and Anterograde Amnesia

IM or IV

Patients >50 years of age generally should not receive initial dose >2 mg unless enhanced suppression of recall is desired.^{a d} Excessive and prolonged sedation may occur.

Cautions for Lorazepam

Contraindications

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

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

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

• Injection contraindicated in patients with sleep apnea.

• Injection contraindicated in patients with severe respiratory insufficiency, except in those patients receiving mechanical ventilation requiring relief of anxiety and/or diminished recall of events.

Warnings/Precautions

Warnings

Respiratory and Cardiovascular Effects

Use oral lorazepam with caution in patients with compromised respiratory function (e.g., chronic pulmonary insufficiency, sleep apnea).^{b c}

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

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

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

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.^d

Status Epilepticus

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

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

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.

CNS Effects

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

Concurrent use of other CNS depressants may cause additive or potentiated CNS depression.^{a b c d} (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 >0.5 mg/kg or when opiate agonists or partial agonists are used concomitantly with recommended lorazepam doses.^{a d}

Psychiatric Indications

Do not use in patients with depressive neuroses or psychotic reactions in which anxiety is not prominent.^{a c}

Abuse Potential

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

Withdrawal

Symptoms of withdrawal (similar to barbiturates or alcohol) may occur if discontinued abruptly.^{a c} Symptoms may be relieved by tapering the dosage.^{a c}

Endoscopic Procedures

Insufficient data to support use for outpatient endoscopic procedures; when used for inpatient endoscopic procedures, adequate recovery room observations required.^d

General Precautions

Suicide

Possibility of suicide in depressed patients; prescribe drug in the smallest feasible quantity.^{b c}

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.^{b c} Discontinue drug if such reactions occur.^{b c}

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. More likely to occur in patients with renal impairment.

Specific Populations

Pregnancy

Category D.^d

Lactation

Distributed into milk.^d

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

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

Pediatric Use

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

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

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

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

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 benzyl alcohol, polyethylene glycol, and propylene glycol. Large amounts of benzyl alcohol (i.e., 100–400 mg/kg daily) have been associated with toxicity in neonates; each mL of lorazepam injection contains 2 mg of benzyl alcohol.^d (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. Possibility of greater sensitivity to the drug (e.g., respiratory or CNS depression) in some geriatric individuals.^d

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. (See Geriatric Patients under Dosage and Administration.)

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

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

Hepatic Impairment

Lorazepam injection is not recommended for use in patients with hepatic failure; may be used in patients with mild to moderately severe hepatic disease.^d (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.

Renal Impairment

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

Common Adverse Effects

With oral therapy, sedation, dizziness, weakness, unsteadiness.^c

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

Interactions for Lorazepam

Specific Drugs

Lorazepam Pharmacokinetics

Absorption

Bioavailability

Readily absorbed from the GI tract following oral administration; absolute bioavailability is 90%.^c

Completely and rapidly absorbed following IM administration.^d

Peak plasma concentrations are attained in approximately 2 hours following oral administration^c and within 3 hours following IM administration.^d

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.^{b d}

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

Plasma Protein Binding

Approximately 85–91%.^{b c d}

Elimination

Metabolism

Extensively metabolized in the liver to inactive metabolites.^{c d}

Elimination Route

Excreted principally in urine as metabolites.^{c d}

Half-life

10–20 hours.^{b c d}

Special Populations

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

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

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

Stability

Storage

Oral

Tablets

Tight containers at 20–25°C.^c

Concentrate Solution

2–8°C; protect from light.^a

Parenteral

Injection

2–8°C; protect from light.^d

Compatibility

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

Parenteral

Solution Compatibility^HID

Drug Compatibility

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.

Advice to Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

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

• 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.^{c d}

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

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

• Importance of informing clinicians about any concomitant illnesses (e.g., depression, respiratory disorders).^c

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

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

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

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

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