Short-to-intermediate-acting benzodiazepine (based on half-life) (Griffin 2013). Binds to stereospecific benzodiazepine receptors on the postsynaptic GABA neuron at several sites within the central nervous system, including the limbic system, reticular formation. Enhancement of the inhibitory effect of GABA on neuronal excitability results by increased neuronal membrane permeability to chloride ions. This shift in chloride ions results in hyperpolarization (a less excitable state) and stabilization. Benzodiazepine receptors and effects appear to be linked to the GABA-A receptors. Benzodiazepines do not bind to GABA-B receptors.

Anxiety (oral):

Hypersensitivity to lorazepam, any component of the formulation, or other benzodiazepines (cross-sensitivity with other benzodiazepines may exist); acute narrow-angle glaucoma.

Dosing: Adult Note: Reduce dose or avoid use in patients receiving opioids or with significant chronic disease (eg, respiratory compromise). Avoid use in patients with a history of substance use, misuse of medications, or depression, except for acute or emergency situations (eg, acute agitation, status epilepticus) (Ref ). Akathisia, antipsychotic-induced Akathisia, antipsychotic-induced (alternative agent) (off-label use): Oral (immediate release): Initial: 0.5 to 1 mg twice daily; may increase dose based on response and tolerability up to 6 mg/day, in divided doses (Ref ). Anxiety Anxiety: Anxiety and agitation, acute/severe (monotherapy or adjunctive therapy): IM, IV, Oral (immediate release): 0.5 to 2 mg every 4 to 6 hours as needed up to 10 mg/day; adjust dose based on response and tolerability. In severely agitated inpatients, some experts recommend doses up to 4 mg and repeat IM or IV doses as frequently as 10 to 30 minutes; may give alone or in combination with an antipsychotic (Ref ). Anxiety disorders (adjunctive therapy or monotherapy) (alternative agent): Note: Generally used short-term for symptom relief until preferred therapy (eg, serotonin reuptake inhibitor) is effective (eg, 4 to 6 weeks followed by tapering). Long-term low-dose (eg, 0.5 mg/day) therapy may be considered in select patients, when preferred treatments are ineffective or poorly tolerated (Ref ). Use with caution in patients with comorbid posttraumatic stress disorder (PTSD); benzodiazepines may worsen PTSD symptoms (Ref ). Immediate release: Oral: Initial: 0.5 to 1 mg 2 to 3 times daily; although most patients will experience relief with this dose, may increase daily dose gradually based on response and tolerability in increments of 1 mg every 2 to 3 days up to 6 mg/day in 2 to 4 divided doses; some patients may require doses up to 10 mg/day for optimal response. Some experts recommend a lower initial dose of 0.5 to 1 mg once to twice daily (Ref ). Extended release 24-hour capsules: Oral: Initial: Determine stable daily dose using IR tablets in 3 divided doses. Maintenance: May convert to extended release at the total daily dose of immediate release; administer once daily in the morning. Note: For dosage adjustments, discontinue extended release and switch to immediate release. Advanced cancer and/or palliative care: IM, IV, Oral (immediate release): 0.25 to 2 mg every 3 to 6 hours as needed (Ref ). Note: The injectable solution may be administered rectally or subcutaneously, and the tablet and oral solution may be administered sublingually at the same doses when other routes are unavailable (Ref ). Performance- or phobia-related anxiety (monotherapy or adjunctive therapy): Note: Provide a test dose, at the same dose to be used for treatment, in advance of the stimulus to ensure tolerability (Ref ). Oral (immediate release): 0.5 to 2 mg once 30 to 60 minutes before the stimulus (Ref ). Procedural anxiety (premedication): Oral (immediate release), Sublingual (off-label use): 0.5 to 2 mg once 30 to 90 minutes before procedure; if needed due to incomplete response, may repeat the dose (usually at 50% of the initial dose) after 30 to 60 minutes (Ref ). IV: 1 to 4 mg or 0.02 to 0.04 mg/kg (maximum single dose: 4 mg) once 5 to 20 minutes before procedure; if needed based on incomplete response and/or duration of procedure, may repeat the dose (usually at 50% of the initial dose) after ≥5 minutes (Ref ). Catatonia Catatonia (off-label use): Diagnosis: Note: Partial, temporary relief of signs following administration is consistent with the diagnosis; a negative response does not rule out catatonia (Ref ). IV (preferred): 1 to 2 mg once; if no response in 5 to 10 minutes, repeat dose once (Ref ). IM, Oral (immediate release), Sublingual: 2 mg once; may administer up to 2 additional doses at 3-hour intervals if needed (Ref ). Treatment: Note: For patients with malignant catatonia, electroconvulsive therapy should begin immediately (Ref ). IM, IV, Oral (immediate release): Initial: 1 to 2 mg 3 times daily; IV preferred for initial dosing with switch to oral as patient improves. May increase dose based on response and tolerability in increments of 3 mg every 1 to 2 days to a usual dose of 6 to 21 mg/day. Doses up to 30 mg/day have been reported (Ref ). For patients at risk of cardiorespiratory compromise or oversedation, some experts recommend initiating with 0.5 mg 3 times daily (Ref ). Duration of treatment: Remission is usually achieved in 4 to 10 days; maintenance therapy at the effective dose is usually continued for 3 to 6 months to maintain recovery, although longer courses may be needed (Ref ). Chemotherapy-induced nausea and vomiting, prevention and treatment Chemotherapy-induced nausea and vomiting, prevention and treatment (adjunctive therapy) (off-label use): Anticipatory or breakthrough nausea/vomiting, as an adjunct to conventional antiemetics: Oral (immediate release), IV, Sublingual: 0.5 to 1 mg every 6 hours as needed; doses up to 2 mg have been described (Ref ). Intoxication Intoxication: Cocaine, methamphetamine, and other sympathomimetics (off-label use): Based on limited data: IV: 2 to 4 mg every 3 to 10 minutes as needed for agitation, sedation, seizures, hypertension, and tachycardia until desired symptom control achieved. Large cumulative doses may be required for some patients; monitor for respiratory depression and hypotension (Ref ). Note: Initiating treatment at 1 mg may be adequate in patients who are only mildly or moderately intoxicated, but doses should be repeated or increased as needed. Consider IM administration if IV access is not possible; however, effects will be delayed (Ref ). Mechanically ventilated patients in the ICU, sedation Mechanically ventilated patients in the ICU, sedation (alternative agent) (off-label use): Note: Used as part of a multimodal strategy. In general, nonbenzodiazepine sedation is preferred due to risk of prolonged sedation and delirium with continuous benzodiazepine use. Titrate to light level of sedation (eg, Richmond Agitation-Sedation Scale 0 to −2) or clinical effect (eg, ventilator dyssynchrony). Intermittent as-needed therapy is preferred to avoid drug accumulation and prolonged sedation associated with continuous infusions (Ref ). Continuous infusions are not recommended for use in most ICU patients due to propylene glycol (PG) accumulation and subsequent complications (osmol gap metabolic acidosis, kidney failure); monitor PG accumulation with osmol gap; nonbenzodiazepine or midazolam continuous infusions are generally preferred (Ref ). Intermittent (preferred): Non–weight-based dosing: IV: Initial dose: 1 to 4 mg; Maintenance: 1 to 4 mg every 2 to 6 hours as needed (Ref ). Weight-based dosing: IV: Initial dose: 0.02 to 0.04 mg/kg (maximum single dose: 4 mg); Maintenance: 0.02 to 0.06 mg/kg every 2 to 6 hours as needed (maximum single dose: 4 mg) (Ref ). Continuous infusion: IV: 0.5 to 10 mg/hour or 0.01 to 0.1 mg/kg/hour continuous infusion (maximum dose: 10 mg/hour) (Ref ). Neuroleptic malignant syndrome Neuroleptic malignant syndrome (adjunctive therapy) (off-label use): Note: Following withdrawal of causative agent while continuing supportive care, use for moderate to severe muscle rigidity with elevated creatine kinase. May also use for any patient experiencing agitation (Ref ). IM, IV: 0.5 to 2 mg every 4 to 6 hours until symptom resolution; use higher doses (eg, 1 to 2 mg) for management of muscle rigidity (Ref ). Seizures Seizures: Note: If IV access is not available, IM lorazepam is not recommended due to erratic absorption and a slow time to peak drug levels. May consider sublingual or subcutaneous lorazepam or IM midazolam (Ref ). Acute active seizures (non-status epilepticus) (off-label use): IV: 4 mg given at a maximum rate of 2 mg/minute; may repeat at 3 to 5 minutes if seizures continue (Ref ). Status epilepticus: IV: 4 mg given at a maximum rate of 2 mg/minute; may repeat at 3 to 5 minutes if seizures continue; a nonbenzodiazepine antiseizure agent should follow to prevent seizure recurrence, even if seizures have ceased (Ref ). Serotonin syndrome Serotonin syndrome (serotonin toxicity) (off-label use): IV: 2 to 4 mg IV every 8 to 10 minutes based upon patient response (Ref ). Substance withdrawal Substance withdrawal: Alcohol withdrawal syndrome (alternative agent) (off-label use): Note: Symptom-triggered regimens preferred over fixed-dose regimens. Dosage and frequency may vary based on institution-specific protocols. Although longer-acting benzodiazepines are preferred in general, shorter-acting benzodiazepines, including lorazepam, may be preferable in patients with impaired liver function. Some experts recommend avoiding IM administration due to variable absorption (Ref ). Symptom-triggered regimen: Oral (immediate release), IV: 2 to 4 mg as needed; dose and frequency determined by withdrawal symptom severity using a validated severity-assessment scale such as the Clinical Institute Withdrawal Assessment for Alcohol, revised scale (CIWA-Ar) (Ref ). Fixed-dose regimen: Oral (immediate release), IV: 1 to 4 mg every 4 to 6 hours for 1 day, then gradually taper dose over 3 to 4 days; additional doses may be considered based on withdrawal symptoms and validated assessment scale scores (eg, CIWA-Ar) (Ref ). Opioid withdrawal (autonomic instability and agitation) (adjunctive therapy) (alternative agent) (off-label use) : Based on limited data: IV: 1 to 2 mg every 10 minutes until hemodynamically stable and adequate sedation (Ref ). Vertigo, acute episodes Vertigo, acute episodes (alternative agent) (off-label use): Note: Reserve use for symptomatic relief of episodes lasting several hours to days (maximum duration: 3 days); chronic use may impede adaptation and recovery (Ref ). IM, IV, Oral (immediate release): 0.5 to 2 mg every 4 to 12 hours as needed for up to 48 to 72 hours (Ref ). Discontinuation of therapy: Unless safety concerns require a more rapid withdrawal, gradually taper to detect reemerging symptoms and minimize rebound and withdrawal symptoms in patients receiving therapy ≥4 weeks or as appropriate based on patient-specific factors (Ref ). Low or moderate dose, no concerns for benzodiazepine use disorder: Taper total daily dose by 20% to 25% every week based on response and tolerability (taper increments will be limited by available dosage forms) (Ref ). Extended or high-dose therapy, or suspected benzodiazepine use disorder: Taper total daily dose by approximately 25% every 1 to 2 weeks based on response, tolerability, and individual patient factors (taper increments will be limited by available dosage forms) (Ref ). Reduce dose more rapidly in the beginning, and slow the dose reduction as the taper progresses because earlier stages of withdrawal are easier to tolerate (Ref ). The optimal duration and taper increment will vary; up to 6 months may be necessary for some patients on higher doses, and a taper rate of 50% every week may be tolerated in some patients (Ref ). For benzodiazepines with half-lives significantly <24 hours, including lorazepam, consider substituting an equivalent dose of a long-acting benzodiazepine to allow for a more gradual reduction in drug serum concentrations (Ref ). Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

IM: Should be administered (undiluted) deep into the muscle mass.

1 to 2 hours

Adverse Reactions The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. >10%: Local: Pain at injection site (IM: 1% to 17%; IV: 2%) Nervous system: Drowsiness, sedated state 1% to 10%: Cardiovascular: Hypotension (≤2%) Local: Erythema at injection site (2%) Nervous system: Coma (≤1%), confusion (≤1%), delirium (≤1%), depression (≤1%), dizziness (7%), excessive crying (≤1%), hallucinations (1%), headache (≤1%), restlessness (≤1%), stupor (≤1%), unsteadiness (3%) Neuromuscular & skeletal: Asthenia (≤4%) Respiratory: Apnea (1%), hypoventilation (≤1%), respiratory failure (2%) <1%: Cardiovascular: Hypertension Endocrine & metabolic: Acidosis Gastrointestinal: Nausea, sialorrhea, vomiting Genitourinary: Cystitis Hematologic & oncologic: Thrombocytopenia Hepatic: Abnormal hepatic function tests, increased serum alkaline phosphatase Infection: Infection Local: Injection site reaction Nervous system: Abnormal gait, abnormality in thinking, agitation, ataxia, brain edema, chills, myoclonus, seizure Neuromuscular & skeletal: Tremor Otic: Hearing loss Respiratory: Hyperventilation Frequency not defined: Dermatologic: Alopecia, skin rash Endocrine & metabolic: Change in libido, hyponatremia, increased lactate dehydrogenase, SIADH Gastrointestinal: Changes in appetite, constipation Genitourinary: Impotence, orgasm disturbance Hematologic & oncologic: Agranulocytosis, leukopenia, pancytopenia Hepatic: Increased serum bilirubin, increased serum transaminases, jaundice Hypersensitivity: Anaphylaxis, hypersensitivity reaction Nervous system: Disinhibition, disorientation, drug dependence, dysarthria, dysautonomia, euphoria, extrapyramidal reaction, fatigue, hypothermia, memory impairment, sleep apnea (exacerbation), slurred speech, suicidal ideation, suicidal tendencies, vertigo, withdrawal syndrome Ophthalmic: Visual disturbance Respiratory: Exacerbation of chronic obstructive pulmonary disease, respiratory depression Miscellaneous: Paradoxical reaction (Mancuso 2004) Postmarketing: Cardiovascular: Bradycardia, cardiac arrhythmia, cardiac failure, heart block, pericardial effusion, prolonged QT interval on ECG (Ziegenbein 2004), tachycardia, ventricular arrhythmia Endocrine & metabolic: Pheochromocytoma (aggravation) Gastrointestinal: Gastrointestinal hemorrhage Genitourinary: Urinary incontinence Hematologic & oncologic: Disorder of hemostatic components of blood, pulmonary hemorrhage Hepatic: Hepatotoxicity Hypersensitivity: Fixed drug eruption (Agulló-García 2018) Nervous system: Aggressive behavior (Bond 1988, Pietras 2005), anterograde amnesia (Pandit 1976), nervousness, neuroleptic malignant syndrome, paralysis Ophthalmic: Blurred vision, diplopia (Lucca 2014) Respiratory: Pneumothorax, pulmonary edema, pulmonary hypertension Miscellaneous: Propylene glycol toxicity (IV) (Neale 2005)

Warnings/Precautions Concerns related to adverse effects: • Sleep-related activities: Hazardous sleep-related activities, such as sleep-driving, cooking and eating food, and making phone calls while asleep, have been noted with benzodiazepines (Dolder 2008). Disease-related concerns: • Depression: Avoid use in patients with depression because of concerns about worsening mood symptoms, particularly if suicidal risk may be present, except for acute or emergency situations (eg, acute agitation, status epilepticus) (Craske 2022). • Hepatic impairment: Use with caution in patients with hepatic impairment, insufficiency, and/or encephalopathy. Dose adjustment (lower doses) may be needed. May worsen hepatic encephalopathy. • Renal impairment: Use with caution in patients with renal impairment. • Respiratory disease: Reduce dose or avoid use in patients with respiratory disease, including chronic obstructive pulmonary disease or sleep apnea. Benzodiazepines may cause significant respiratory depression. Concurrent drug therapy issues: • Concomitant use with opioids: In patients already receiving an opioid analgesic, prescribe a lower initial dose of lorazepam than indicated in the absence of an opioid and titrate based on clinical response. If an opioid is initiated in a patient already taking lorazepam, prescribe a lower initial dose of the opioid and titrate based upon clinical response. • Flumazenil: Flumazenil may cause withdrawal in patients receiving long-term benzodiazepine therapy. Special populations: • Debilitated patients: Use with caution in debilitated patients; initial doses should be at the lower end of dosing range. • Older adult patients: Older adult patients may be at an increased risk of death with use; risk has been found highest within the first 4 months of use in older adult dementia patients (Jennum 2015; Saarelainen 2018). • Fall risk: Use with extreme caution in patients who are at risk of falls; benzodiazepines have been associated with falls and traumatic injury (Nelson 1999). Dosage form specific issues: • Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein-binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer's labeling. • Polyethylene glycol: Parenteral formulation may contain polyethylene glycol. May be associated with toxicity in high-dose and/or longer-term therapy. • Tartrazine: Some formulations may contain tartrazine (FD&C Yellow No. 5), which may cause allergic-type reactions (including bronchial asthma) in susceptible individuals, particularly those who also have aspirin sensitivity. Other warnings/precautions: • Abuse, misuse, and addiction: Counsel patients at increased risk on proper use and monitoring for signs and symptoms of abuse, misuse, and addiction. Institute early treatment or refer patients in whom substance use disorder is suspected. Limit dosages and durations to the minimum required. • Appropriate use: Does not have analgesic, antidepressant, or antipsychotic properties. Status epilepticus should not be treated with injectable benzodiazepines alone; requires close observation and management and possibly ventilatory support. When used as a component of preanesthesia, monitor for heavy sedation and airway obstruction; equipment necessary to maintain airway and ventilatory support should be available. • Tolerance: Lorazepam is a short half-life benzodiazepine. Duration of action after a single dose is determined by redistribution rather than metabolism. Tolerance develops to the sedative, hypnotic, and antiseizure effects. It does not develop to the anxiolytic effects (Vinkers 2012). Chronic use of this agent may increase the perioperative benzodiazepine dose needed to achieve desired effect.