LORazepam (Lexi-Drugs)

ALERT: US Boxed Warning
  Risks from concomitant use with opioids:
Drug Shortages

One or more forms of this drug may be in short supply or unavailable. Refer to the following for additional information:

ASHP: http://www.ashp.org/menu/DrugShortages

FDA: https://www.accessdata.fda.gov/scripts/drugshortages/dsp_ActiveIngredientDetails.cfm?AI=Lorazepam Injection, USP&st=c&tab=tabs-1

Pronunciation

(lor A ze pam)

Brand Names: US

Ativan; LORazepam Intensol

Brand Names: Canada

APO-LORazepam; Ativan; DOM-LORazepam; NTP-LORazepam [DSC]; PHL-LORazepam [DSC]; PMS-LORazepam; PRO-LORazepam; TEVA-LORazepam

Dosing: Adult

Anxiety disorder: Oral: Initial: 2 to 3 mg daily in 2 to 3 divided doses; usual dose: 2 to 6 mg daily in divided doses; however, daily dose may vary from 1 to 10 mg/day

Insomnia due to anxiety or stress: Oral:

<65 years: 0.5 to 2 mg at bedtime (Winkelman 2015)

≥65 years: 0.5 to 1 mg at bedtime (Winkelman 2015)

Note: The manufacturer recommends higher dosing (ie, 2 to 4 mg at bedtime); however, generally, it is a safer approach to employ the above recommended doses.

Premedication for anesthesia:

IM: 0.05 mg/kg administered 2 hours before surgery (maximum dose: 4 mg)

IV: 0.044 mg/kg administered 15 to 20 minutes before surgery (usual dose: 2 mg; maximum dose: 4 mg). Note: Doses >2 mg should generally not be exceeded in patients >50 years.

Sublingual tablet [Canadian product]: 0.05 mg/kg 1 to 2 hours before surgery (maximum dose: 4 mg)

Status epilepticus: IV:

American Epilepsy Society and Neurocritical Care Society recommendations: 0.1 mg/kg (maximum dose: 4 mg) given at a maximum rate of 2 mg/minute; may repeat in 5 to 10 minutes (AES [Glauser 2016]; NCS [Brophy 2012]). Note: Dilute dose 1:1 with saline.

Manufacturer’s labeling: 4 mg given slowly (2 mg/minute); may repeat in 10 to 15 minutes. May be given IM, but IV preferred.

Agitation in the ICU patient (off-label use): IV: Loading dose: 0.02 to 0.04 mg/kg (maximum single dose: 2 mg); Maintenance: 0.02 to 0.06 mg/kg every 2 to 6 hours as needed or0.01 to 0.1 mg/kg/hour; maximum dose: ≤10 mg/hour (Barr 2013)

Alcohol withdrawal delirium (off-label use) (Mayo-Smith 2004):

IV: 1 to 4 mg every 5 to 15 minutes until calm, then every hour as needed to maintain light somnolence

IM: 1 to 4 mg every 30 to 60 minutes until calm, then every hour as needed to maintain light somnolence

Alcohol withdrawal syndrome (off-label use): Note: Symptom-triggered regimens preferred over fixed-dose regimens; lower doses and shorter durations of treatment are needed (Soyka 2017).

Symptom-triggered regimen: Oral, IM, IV: 2 to 4 mg every 1 hour as needed; dose determined by a validated severity assessment scale (Mayo-Smith 1997)

Fixed-dose regimen: Oral, IM, IV: 2 mg every 6 hours for 4 doses, then 1 mg every 6 hours for 8 additional doses (Mayo-Smith 1997)

Chemotherapy-associated nausea and vomiting (off-label use): Breakthrough nausea/vomiting or as adjunct to standard antiemetics: Oral, IV, Sublingual (off-label route): 0.5 to 2 mg every 6 hours as needed (Lohr 2008)

Psychogenic catatonia (off-label use):

IM, Sublingual (off-label route): 1 to 2 mg; repeat dose in 3 hours then again in another 3 hours if initial and subsequent doses, respectively, are ineffective (Rosebush 1990, Rosebush 2010).

or

Oral, IM, IV: Initial: 1 mg; may repeat in 5 minutes if necessary. If initial challenge is unsuccessful, may increase dose up to 4 to 8 mg per day; may continue treatment for up to 5 days (Bush 1996).

Rapid tranquilization of the agitated patient (off-label use): Oral, IM, IV: 1 to 3 mg administered every 30 to 60 minutes; may be administered with an antipsychotic (eg, haloperidol) (Allen 2005; Battaglia 2005; De Fruyt 2004; Wilson 2012). Note: When administering IM, may consider a lower initial dose (eg, 0.5 mg) (Allen 2005).

Dosage adjustment for lorazepam with concomitant medications: Probenecid or valproic acid: Reduce lorazepam dose by 50%

Dosing: Geriatric

Refer also to adult dosing. Dose selection should generally be on the low end of the dosage range (initial dose not to exceed 2 mg).

Anxiety disorder: Oral: Initial: 1 to 2 mg daily in divided doses

Dosing: Renal Impairment: Adult

Oral: No dosage adjustment necessary (Aronoff 2007).

Parenteral:

Mild-to-moderate impairment: No dosage adjustment necessary for acute doses; use repeated doses with caution; may increase the risk of propylene glycol toxicity. Monitor closely if using for prolonged periods of time or at high doses.

Severe impairment or failure: Use is not recommended.

Dosing: Hepatic Impairment: Adult

Oral:

Mild-to-moderate impairment: No dosage adjustment necessary.

Severe impairment and/or encephalopathy: Use with caution; may require lower doses.

Parenteral:

Mild-to-moderate impairment: No dosage adjustment necessary; use with caution.

Severe impairment or failure: Use is not recommended.

Dosing: Pediatric

Chemotherapy-induced nausea and vomiting, anticipatory: Limited data available: Infants, Children, and Adolescents: Oral: 0.04 to 0.08 mg/kg/dose; maximum dose: 2 mg/dose; administer a dose the night before chemotherapy and again the next day prior to chemotherapy administration (Dupuis 2014)

Chemotherapy-associated nausea and vomiting, breakthrough: Limited data available: Children and Adolescents: IV: 0.025 to 0.05 mg/kg/dose every 6 hours as needed; maximum dose: 2 mg/dose (Dupuis 2003)

Anxiety, acute:

Infants and Children <12 years: Limited data available: Oral, IV: Usual: 0.05 mg/kg/dose (maximum dose: 2 mg/dose) every 4 to 8 hours; range: 0.02 to 0.1 mg/kg/dose (Kliegman 2007)

Children ≥12 years and Adolescents: Oral: 0.25 to 2 mg/dose 2 or 3 times daily; maximum dose: 2 mg/dose (Kliegman 2011)

Insomnia due to anxiety or stress: Children ≥12 years and Adolescents: Oral: Usual: 2 mg at bedtime; maximum: 4 mg/dose

Sedation (preprocedure): Limited data available: Children and Adolescents: Oral: Usual: 0.05 mg/kg; range reported in literature: 0.02 to 0.09 mg/kg (Burtles 1983; Henry 1991; Mundeleer 1980; Peters 1982). Note: In adults, the maximum dose is 4 mg/dose.

Status epilepticus: Limited data available: Infants, Children, and Adolescents:

IV: 0.05 to 0.1 mg/kg (maximum: 4 mg/dose) slow IV over 2 to 5 minutes; may repeat in 5 to 15 minutes if needed (AAP [Hegenbarth 2008]; NCS [Brophy 2012]; Kliegman 2007); usual total maximum dose: 8 mg (Crawford 1987; NICE 2012). Note: May be administered IM if IV not possible (AAP [Hegenbarth 2008]).

Intranasal: Note: Reserve for patients without IV access: 0.1 mg/kg/dose; maximum dose: 4 mg/dose (Ahmad 2006; Arya 2011; Kliegman 2011)

Dosing adjustment for lorazepam with concomitant medications: Children ≥12 years and Adolescents: Probenecid or valproic acid: Reduce lorazepam dose by 50%

Dosing: Renal Impairment: Pediatric

Oral: Children ≥12 years and Adolescents: There are no dosage adjustments provided in the manufacturer’s labeling; however, some clinicians recommend no dosage adjustments are necessary (Aronoff 2007).

IV:

Mild to moderate impairment: No dosage adjustment necessary for acute doses; use repeated doses with caution; may increase the risk of propylene glycol toxicity. Monitor closely if using for prolonged periods of time or at high doses.

Severe impairment or failure: Use is not recommended.

Dosing: Hepatic Impairment: Pediatric

Children ≥12 years and Adolescents: No dosage adjustment necessary. For severe hepatic disease, use with caution; benzodiazepines may worsen hepatic encephalopathy.

Use: Labeled Indications

Anxiety (oral): Management of anxiety disorders, short-term (≤4 months) relief of anxiety symptoms, or anxiety associated with depressive symptoms, or anxiety/stress-associated insomnia.

Anesthesia premedication (parenteral): Anesthesia premedication in adults to relieve anxiety or to produce amnesia (diminish recall) or sedation.

Anesthesia premedication (sublingual) [Canadian product]: Anesthesia premedication to relieve anxiety prior to surgical procedures.

Status epilepticus (parenteral): Treatment of status epilepticus.

Use: Off-Label: Adult

  Agitation in the ICU patientLevel of Evidence [G]

Based on the American Society of Critical Care Medicine guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit (ICU), intravenous lorazepam may be given for the management of agitation in these patients; however, in mechanically-ventilated patients, nonbenzodiazepine sedation may be preferred due to suggested increases in duration of mechanical ventilation, ICU length of stay, and incidence of delirium with benzodiazepines.

  Alcohol withdrawal deliriumLevel of Evidence [G]

Based on the World Federation of Societies of Biological Psychiatry guidelines for biological treatment of substance use and related disorders and American Society of Addiction Medicine guidelines for the management of alcohol withdrawal delirium, lorazepam has been recommended for the management of this condition Ref.

  Alcohol withdrawal syndromeLevel of Evidence [G]

Based on the World Federation of Societies of Biological Psychiatry guidelines for biological treatment of substance use and related disorders and American Society of Addiction Medicine guidelines for the treatment of alcohol withdrawal syndrome, lorazepam given for alcohol withdrawal is effective and recommended in the management of this condition Ref.

  Chemotherapy-associated nausea and vomiting (adjunct or breakthrough)Level of Evidence [G]

Based on the American Society of Clinical Oncology antiemetic guidelines for chemotherapy associated nausea and vomiting, lorazepam may be given as an adjunct for the management of chemotherapy-associated nausea and vomiting (as an adjunct to other antiemetic medications, not as a single agent) and for management of breakthrough episodes that occur despite optimal prophylaxis in patients who have already received olanzapine.

  Psychogenic catatoniaLevel of Evidence [C]

Data from a limited number of patients in a small number of studies suggest that lorazepam may be beneficial for the treatment of psychogenic catatonia Ref; clinical experience also suggests the utility of lorazepam in managing psychogenic catatonia Ref. Additional data may be necessary to further define the role of lorazepam in this condition.

  Rapid tranquilization of the agitated patientLevel of Evidence [G]

Based on the Expert Consensus Guidelines on the Treatment of Behavioral Emergencies, lorazepam may be given to rapidly tranquilize the agitated patient Ref. Based on the American Association for Emergency Psychiatry Project BETA Psychopharmacology Workgroup, benzodiazepines are recommended as first-line for agitation due to alcohol or benzodiazepine withdrawal or intoxication due to a CNS stimulant (eg, amphetamines) and second-line for agitation associated with psychosis in patients with known psychiatric disorders Ref.

Clinical experience also suggests the utility of lorazepam in managing the agitated patient Ref.

Level of Evidence Definitions
  Level of Evidence Scale
Clinical Practice Guidelines

Critical Care:

“Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit,” January 2013

Oncology: Antiemetics:

American Society of Clinical Oncology Clinical Practice Guideline Update, 2017

National Comprehensive Cancer Network (NCCN), Clinical Practice Guidelines in Oncology™, Antiemesis

Pediatric Oncology Group of Ontario, Guideline for the Prevention and Treatment of Anticipatory Nausea and Vomiting Due to Chemotherapy in Pediatric Cancer Patients, 2014

Psychiatry:

American Psychiatric Association (APA), “Practice Guideline for the Treatment of Patients with Panic Disorder,” January 2009

Status Epilepticus:

American Epilepsy Society Guidelines, “Treatment of Convulsive Status Epilepticus in Children and Adults,” January 2016

Substance Use Disorders:

Department of Veteran Affairs, Department of Defense, “VA/DoD Clinical Practice Guideline for Management of Substance Use Disorders (SUD),” August 2009

World Federation of Societies of Biological Psychiatry, “WFSBP guidelines for the biological treatment of substance use and related disorders, Part 1: Alcoholism, first revision” 2017

Administration: IM

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

Administration: IV

IV injection: Dilute prior to use (according to the manufacturer). Do not exceed 2 mg/minute or 0.05 mg/kg over 2 to 5 minutes. Monitor IV site during administration. Avoid intra-arterial administration. Avoid extravasation.

Administration: Oral

Lorazepam oral concentrate: Use only the provided calibrated dropper to withdraw the prescribed dose. Mix the dose with liquid (eg, water, juice, soda, soda-like beverage) or semisolid food (eg, applesauce, pudding), and stir for a few seconds to blend completely. The prepared mixture should be administered immediately.

Sublingual tablet [Canadian product]: Place under tongue; patient should not swallow for at least 2 minutes.

Administration: Pediatric

Oral: May administer with food to decrease GI distress; dilute oral solution in water, juice, soda, or semisolid food (eg, applesauce, pudding).

Intranasal: Administer undiluted (injectable formulation) into one nostril using a needleless syringe or nasal atomizer (Ahmad 2006; Anya 2011)

Parenteral:

IV: Dilute prior to administration. Do not exceed 2 mg/minute or 0.05 mg/kg over 2 to 5 minutes; administer IV using repeated aspiration with slow IV injection, to make sure the injection is not intra-arterial and that perivascular extravasation has not occurred.

IM: Administer undiluted by deep injection into muscle mass

Storage/Stability

Parenteral: Intact vials should be refrigerated (room temperature storage information may be available; contact product manufacturer to obtain current recommendations). Protect from light. Parenteral admixture in D5W, LR, or NS is stable at room temperature (25°C) for 24 hours (consult parenteral admixture resource for additional detail).

Oral concentrate: Store at colder room temperature or refrigerate at 2°C to 8°C (36°F to 46°F). Discard open bottle after 90 days.

Oral tablet: Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).

Sublingual tablet [Canadian product]: Store at 15°C to 25°C (59°F to 77°F). Protect from light.

Preparation for Administration: Adult

IV injection: According to the manufacturer, dilute IV dose prior to use with an equal volume of compatible diluent (D5W, NS, SWFI).

Infusion: Precipitation may occur upon dilution when preparing an infusion. Use 2 mg/mL injectable vial to prepare; there may be decreased stability when using 4 mg/mL vial. Dilute to ≤1 mg/mL with a compatible diluent in a non-PVC (eg, polyolefin, glass) container (consult parenteral admixture resource for additional detailed recommendations). Can also be administered undiluted (up to 4 mg/mL) via infusion into a central vein or into a peripheral vein with a running compatible maintenance IV solution (Johnson 2002).

IM: Administer undiluted.

Preparation for Administration: Pediatric

Parenteral: IV: Dilute dose prior to use with an equal volume of compatible diluent (D5W, NS, SWFI).

Neonates: Since both concentrations of the injection contain 2% benzyl alcohol, some experts recommend using the 4 mg/mL product for dilution with preservative free SWFI to make a 0.4 mg/mL dilution (in order to decrease the amount of benzyl alcohol delivered to the neonate); however, the stability of this dilution has not been studied.

Compatibility

See Trissel’s IV Compatibility Database

Extemporaneously Prepared

Note: Commercial oral solution is available (2 mg/mL)

Two different 1 mg/mL oral suspensions may be made from different generic lorazepam tablets (Mylan Pharmaceuticals or Watson Laboratories), sterile water, Ora-Sweet, and Ora-Plus.

Mylan tablets: Place one-hundred-eighty 2 mg tablets in a 12-ounce amber glass bottle; add 144 mL of sterile water to disperse the tablets; shake until slurry is formed. Add 108 mL Ora-Plus in incremental proportions; then add a quantity of Ora-Sweet sufficient to make 360 mL. Label “shake well” and “refrigerate”. Stable for 91 days when stored in amber glass prescription bottles at room temperature or refrigerated (preferred).

Watson tablets: Place one-hundred-eighty 2 mg tablets in a 12-ounce amber glass bottle; add 48 mL sterile water to disperse the tablets; shake until slurry is formed. Add 156 mL of Ora-Plus in incremental proportions; then add a quantity of Ora-Sweet sufficient to make 360 mL. Label “shake well” and “refrigerate”. Store in amber glass prescription bottles. Stable for 63 days at room temperature or 91 days refrigerated.

Lee ME, Lugo RA, Rusho WJ, et al, “Chemical Stability of Extemporaneously Prepared Lorazepam Suspension at Two Temperatures,” J Pediatr Pharmacol Ther, 2004, 9(4):254-58.

Medication Patient Education with HCAHPS Considerations

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience fatigue, headache, or injection site irritation. Have patient report immediately to prescriber signs of depression (suicidal ideation, anxiety, emotional instability, or illogical thinking), hallucinations, behavioral changes, change in balance, confusion, memory impairment, severe loss of strength and energy, severe dizziness, passing out, vision changes, muscle weakness, dark urine, jaundice, difficulty breathing, slow breathing, or shallow breathing (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Medication Safety Issues
  Sound-alike/look-alike issues:
  High alert medication:
  Geriatric Patients: High-Risk Medication:
  Administration issues:
Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Ativan: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/017794s044lbl.pdf

Contraindications

Hypersensitivity to lorazepam, any component of the formulation, or other benzodiazepines (cross-sensitivity with other benzodiazepines may exist); acute narrow-angle glaucoma; severe respiratory insufficiency (except during mechanical ventilation)

Parenteral: Additional contraindications: Hypersensitivity to polyethylene glycol, propylene glycol, or benzyl alcohol; sleep apnea; intra-arterial injection; use in premature infants

Canadian labeling: Additional contraindications (not in the US labeling): Myasthenia gravis

Warnings/Precautions

Concerns related to adverse effects:

• Anterograde amnesia: Benzodiazepines have been associated with anterograde amnesia (Nelson 1999).

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

• Paradoxical reactions: Paradoxical reactions, including hyperactive or aggressive behavior, have been reported with benzodiazepines; risk may be increased in adolescent/pediatric patients, geriatric patients, or patients with a history of alcohol use disorder or psychiatric/personality disorders (Mancuso 2004).

• 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:

• Drug abuse: Risk of dependence increases in patients with a history of alcohol or drug abuse and those with significant personality disorders; use with caution in these patients. Tolerance, psychological and physical dependence may also occur with higher dosages and prolonged use. The risk of dependence is decreased with short-term treatment (2 to 4 weeks); evaluate the need for continued treatment prior to extending therapy duration.

• 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. Parenteral use is not recommended in patients with hepatic failure.

• Psychiatric disorders: Preexisting depression may emerge or worsen during therapy. Not recommended for use in primary depressive or psychotic disorders. Should not be used in patients at risk for suicide without adequate antidepressant treatment.

• Renal impairment: Use with caution in patients with renal impairment. Parenteral use is not recommended in patients with renal failure.

• Respiratory disease: Use with caution in patients with respiratory disease, including COPD or sleep apnea. Benzodiazepines may cause significant respiratory depression.

Concurrent drug therapy issues:

• Concomitant use with opioids: [US Boxed Warning]: Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation. 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.

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Debilitated patients: Use with caution in debilitated patients; initial doses should be at the lower end of dosing range.

• Elderly patients: Elderly patients may be at an increased risk of death with use; risk has been found highest within the first 4 months of use in elderly 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).

• Pediatrics: In pediatric and neonatal patients <3 years, the repeated or lengthy exposure to sedatives or anesthetics during surgery/procedures may have detrimental effects on the child’s brain development and may contribute to various cognitive and behavioral problems. Epidemiological studies have reported various cognitive and behavioral problems including neurodevelopmental delay (and related diagnoses), learning disabilities, and ADHD. Clinical data suggest that single, relatively short exposures are not likely to have similar negative effects. Further studies are needed to fully characterize findings and ensure that these findings are not related to underlying conditions or the procedure itself. No specific anesthetic/sedative has been found to be safer. For elective procedures, risk vs benefits should be evaluated and discussed with parents/caregivers/patients; critical surgeries should not be delayed (FDA 2016).

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.

• Propylene glycol: Parenteral formulation may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures and respiratory depression; use caution (AAP 1997; Zar 2007). See manufacturer’s labeling. May consider using enteral delivery of lorazepam tablets to decrease the risk of propylene glycol toxicity (Lugo 1999).

Other warnings/precautions:

• 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.

• Hypnotic: Appropriate use: As a hypnotic, should be used only after evaluation of potential causes of sleep disturbance. Failure of sleep disturbance to resolve after 7 to 10 days may indicate psychiatric or medical illness. A worsening of insomnia or the emergence of new abnormalities of thought or behavior may represent unrecognized psychiatric or medical illness and requires immediate and careful evaluation.

• 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 anticonvulsant 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.

• Withdrawal: Rebound or withdrawal symptoms may occur following abrupt discontinuation or large decreases in dose. Use caution when reducing dose or withdrawing therapy; decrease slowly and monitor for withdrawal symptoms. Flumazenil may cause acute withdrawal in patients receiving long-term benzodiazepine therapy.

Geriatric Considerations

If a benzodiazepine is indicated, lorazepam may be a preferred agent to use in elderly patients because it is relatively short-acting with an inactive metabolite .

Refer to Medication Safety Issues for Beers Criteria information.

Warnings: Additional Pediatric Considerations

In pediatric and neonatal patients <3 years of age and patients in third trimester of pregnancy (ie, times of rapid brain growth and synaptogenesis), the repeated or lengthy exposure to sedatives or anesthetics during surgery/procedures may have detrimental effects on the child’s or fetus’ brain development and may contribute to various cognitive and behavioral problems; the FDA is requiring warnings be included in the manufacturer’s labeling for all general anesthetic/sedative drugs. Multiple animal species studies have shown adverse effects on brain maturation; in juvenile animals, drugs that potentiate GABA activity and/or block NMDA receptors for >3 hours demonstrated widespread neuronal and oligodendrocyte cell loss along with alteration in synaptic morphology and neurogenesis. Epidemiological studies in humans have reported various cognitive and behavioral problems including neurodevelopmental delay (and related diagnoses), learning disabilities, and ADHD. Human clinical data suggest that single, relatively short exposures are not likely to have similar negative effects. Further studies are needed to fully characterize findings and ensure that these findings are not related to underlying conditions or the procedure itself. No specific anesthetic/sedative has been found to be safer. For elective procedures, risk vs benefits should be evaluated and discussed with parents/caregivers/patients; critical surgeries should not be delayed (FDA 2016).

Use with caution in neonates, especially in preterm infants; several cases of neurotoxicity and myoclonus (rhythmic myoclonic jerking) have been reported. Paradoxical reactions, including hyperactive or aggressive behavior, have been reported with benzodiazepines, particularly in pediatric/adolescent or psychiatric patients; discontinue drug if this occurs.

Some dosage forms may contain propylene glycol; in neonates large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).

Pregnancy Considerations

Lorazepam and its metabolite cross the human placenta. Teratogenic effects in humans have been observed with some benzodiazepines (including lorazepam); however, additional studies are needed. The incidence of premature birth and low birth weights may be increased following maternal use of benzodiazepines; hypoglycemia and respiratory problems in the neonate may occur following exposure late in pregnancy. Neonatal withdrawal symptoms may occur within days to weeks after birth and “floppy infant syndrome” (which also includes withdrawal symptoms) have been reported with some benzodiazepines (including lorazepam). Elimination of lorazepam in the newborn infant is slow; following in utero exposure, term infants may excrete lorazepam for up to 8 days (Bergman 1992; Iqbal 2002; Wikner 2007).

Breast-Feeding Considerations

Lorazepam is present in breast milk.

The relative infant dose (RID) of lorazepam is 2.4% to 4.7% when calculated using the highest breast milk concentration located following benzodiazepine monotherapy with lorazepam and compared to an infant therapeutic dose of 0.15 to 0.3 mg/kg/day (0.05 mg/kg/dose every 4 to 8 hours). In general, breastfeeding is considered acceptable when the RID is <10% (Anderson 2016; Ito 2000); however, some sources note breastfeeding should only be considered if the RID is <5% for psychotropic agents (Larsen 2015). Using the highest total milk concentration (12 mcg/L free lorazepam plus 35 mcg/L conjugated lorazepam), the estimated the daily infant dose via breast milk is 7.05 mcg/kg/day. These milk concentrations were obtained following maternal administration of oral lorazepam 2.5 mg twice daily for the first five days postpartum; the mother had begun treatment with lorazepam prior to delivery (route, dose, and duration not specified) (Whitelaw 1981). Higher milk concentrations were observed in one mother who received both oral lorazepam and lormetazepam, which is partially metabolized to lorazepam (Lemmer 2007).

In general, sedation, lethargy, irritability, poor weight gain, and apnea have been reported in breastfed infants exposed to benzodiazepines; however, these adverse effects were not observed in breastfed infants exposed to lorazepam (Kelly 2012). The manufacturer warns of the potential for sedation, irritability, and impaired suckling in the infant. Monitor breastfed infants for drowsiness (WHO 2002).

Although the manufacturer recommends that lorazepam should not be administered to breastfeeding women unless the expected benefit to the woman outweighs the potential risk to the infant, short-acting benzodiazepines, including lorazepam, are considered compatible with breastfeeding (Kelly 2012; WHO 2002). When possible, limit exposure to single doses (WHO 2002).

Briggs’ Drugs in Pregnancy & Lactation
Adverse Reactions

>10%:

Central nervous system: Drowsiness, sedation

Local: Pain at injection site (IM: 1% to 17%; IV: 2%)

Miscellaneous: Paradoxical reaction

1% to 10%:

Cardiovascular: Hypotension (≤2%)

Central nervous system: Dizziness (7%), unsteadiness (3%), hallucinations (1%), coma (≤1%), confusion (≤1%), delirium (≤1%), depression (≤1%), excessive crying (≤1%), headache (≤1%), restlessness (≤1%), stupor (≤1%)

Local: Erythema at injection site (2%)

Neuromuscular & skeletal: Asthenia (≤4%)

Respiratory: Respiratory failure (2%), apnea (1%), hypoventilation (≤1%)

Frequency not defined:

Central 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

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: Anaphylactoid reaction, anaphylaxis, hypersensitivity reaction

Ophthalmic: Visual disturbance

Respiratory: Exacerbation of chronic obstructive pulmonary disease), respiratory depression

<1%, postmarketing, and/or case reports: Abnormal gait, abnormal hepatic function tests, abnormality in thinking, acidosis, agitation, amnesia, ataxia, blurred vision, bradycardia, cardiac arrhythmia, cardiac failure, cerebral edema, chills, cystitis, diplopia, disorder of hemostatic components of blood, gastrointestinal hemorrhage, hearing loss, heart block, hepatotoxicity, hypertension, hyperventilation, increased serum alkaline phosphatase, infection, injection site reaction, myoclonus, nausea, nervousness, neuroleptic malignant syndrome, paralysis, pericardial effusion, pheochromocytoma (aggravation), pneumothorax, propylene glycol toxicity (IV), pulmonary edema, pulmonary hemorrhage, pulmonary hypertension, seizure, sialorrhea, tachycardia, thrombocytopenia, tremor, urinary incontinence, ventricular arrhythmia, vomiting

Allergy and Idiosyncratic Reactions
Toxicology
Metabolism/Transport Effects

None known.

Drug Interactions 

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Risk X: Avoid combination

Benznidazole: May enhance the adverse/toxic effect of Products Containing Propylene Glycol. Risk X: Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Risk D: Consider therapy modification

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants.Risk D: Consider therapy modification

Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

CloZAPine: Benzodiazepines may enhance the adverse/toxic effect of CloZAPine. Management: Consider decreasing the dose of (or possibly discontinuing) benzodiazepines prior to initiating clozapine. Risk D: Consider therapy modification

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Risk C: Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk D: Consider therapy modification

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Risk D: Consider therapy modification

Fosphenytoin: Benzodiazepines may increase the serum concentration of Fosphenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy.Risk C: Monitor therapy

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.Risk D: Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk C: Monitor therapy

Loxapine: May enhance the adverse/toxic effect of LORazepam. Specifically, prolonged stupor, respiratory depression, and/or hypotension. Risk C: Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Melatonin: May enhance the sedative effect of Benzodiazepines. Risk C: Monitor therapy

Methadone: Benzodiazepines may enhance the CNS depressant effect of Methadone. Management: Clinicians should generally avoid concurrent use of methadone and benzodiazepines when possible; any combined use should be undertaken with extra caution. Risk D: Consider therapy modification

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification

MetroNIDAZOLE (Systemic): May enhance the adverse/toxic effect of Products Containing Propylene Glycol. A disulfiram-like reaction may occur. Risk X: Avoid combination

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Risk C: Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

OLANZapine: May enhance the adverse/toxic effect of Benzodiazepines. Management: Avoid concomitant use of parenteral benzodiazepines and IM olanzapine due to risks of additive adverse events (e.g., cardiorespiratory depression). Olanzapine prescribing information provides no specific recommendations regarding oral administration. Risk X: Avoid combination

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.Risk D: Consider therapy modification

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Risk D: Consider therapy modification

Phenytoin: Benzodiazepines may increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy. Risk C: Monitor therapy

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy

Probenecid: May increase the serum concentration of LORazepam. Risk D: Consider therapy modification

Pyrimethamine: LORazepam may enhance the hepatotoxic effect of Pyrimethamine. Risk C: Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy

Sodium Oxybate: Benzodiazepines may enhance the CNS depressant effect of Sodium Oxybate. Risk X: Avoid combination

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Teduglutide: May increase the serum concentration of Benzodiazepines. Risk C: Monitor therapy

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination

Theophylline Derivatives: May diminish the therapeutic effect of Benzodiazepines. Risk D: Consider therapy modification

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Valproate Products: May increase the serum concentration of LORazepam. Risk D: Consider therapy modification

Yohimbine: May diminish the therapeutic effect of Antianxiety Agents. Risk C: Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification

Monitoring Parameters

Respiratory and cardiovascular status, blood pressure, heart rate, symptoms of anxiety

Long-term therapy: CBC, liver function tests, LDH

High-dose or continuous IV use or IV use in patients with renal impairment: Clinical signs of propylene glycol toxicity, serum creatinine, BUN, serum lactate, osmolal gap; Note: An osmolal gap of ≥10 was predictive of elevated propylene glycol concentrations; values of ≥12 suggest propylene glycol toxicity (Barnes 2006; Yahwak 2008)

Critically-ill patients: Monitor depth of sedation with either the Richmond Agitation-Sedation Scale (RASS) or Sedation-Agitation Scale (SAS) (Barr 2013)

Advanced Practitioners Physical Assessment/Monitoring

Monitor blood pressure, heart rate, and respiratory function. Assess depth of sedation in critically-ill -patents. Obtain CBC and liver function tests in patients on high-dose or long term therapy. With prolonged parenteral use assess for signs of propylene glycol toxicity (serum creatinine, BUN, serum lactate, osmol gap). Assess for history of addiction; long-term use can result in dependence, abuse, or tolerance; periodically evaluate need for continued use. Assess fall risk prior to prescribing. Assess for improvement in anxiety.

Nursing Physical Assessment/Monitoring

Check ordered labs and report abnormalities. Monitor vital signs. Monitor depth of sedation in critically-ill patients. Monitor for signs and symptoms of withdrawal or aggressive or hyperactive behavior.

Controlled Substance

C-IV

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Concentrate, Oral:

LORazepam Intensol: 2 mg/mL (30 mL) [alcohol free, dye free, sugar free; unflavored flavor]

Generic: 2 mg/mL (30 mL)

Solution, Injection:

Ativan: 2 mg/mL (1 mL, 10 mL); 4 mg/mL (1 mL, 10 mL) [contains benzyl alcohol, polyethylene glycol, propylene glycol]

Generic: 2 mg/mL (1 mL, 10 mL); 4 mg/mL (1 mL, 10 mL)

Tablet, Oral:

Ativan: 0.5 mg

Ativan: 1 mg, 2 mg [scored]

Generic: 0.5 mg, 1 mg, 2 mg

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Injection:

Generic: 2 mg/mL (1ml); 4 mg/mL (1ml)

Tablet, Oral:

Ativan: 0.5 mg, 1 mg, 2 mg

Generic: 0.5 mg, 1 mg, 2 mg

Tablet Sublingual, Sublingual:

Ativan: 0.5 mg [contains FD&C BLUE #1 ALUMINUM LAKE, FD&C YELLOW #10 ALUMINUM LAKE, FD&C YELLOW #6 ALUMINUM LAKE]

Ativan: 1 mg

Ativan: 2 mg [contains FD&C BLUE #2 ALUMINUM LAKE]

Generic: 0.5 mg, 1 mg, 2 mg

Anatomic Therapeutic Chemical (ATC) Classification
  • N05BA06
Generic Available (US)

Yes

Pricing: US

Concentrate (LORazepam Intensol Oral)

2 mg/mL (per mL): $1.60

Concentrate (LORazepam Oral)

2 mg/mL (per mL): $1.33 – $1.60

Solution (Ativan Injection)

2 mg/mL (per mL): $2.28

4 mg/mL (per mL): $3.17

Solution (LORazepam Injection)

2 mg/mL (per mL): $0.62 – $4.06

4 mg/mL (per mL): $2.05 – $3.92

Tablets (Ativan Oral)

0.5 mg (per each): $29.66

1 mg (per each): $39.62

2 mg (per each): $63.14

Tablets (LORazepam Oral)

0.5 mg (per each): $0.07 – $0.70

1 mg (per each): $0.07 – $0.91

2 mg (per each): $0.09 – $1.32

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer’s AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

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.

Pharmacodynamics/Kinetics

Onset of action:

Anticonvulsant: IV: Within 10 minutes

Hypnosis: IM: 20 to 30 minutes

Sedation: IV: Within 2 to 3 minutes (Greenblatt 1983)

Duration: Anesthesia premedication: Adults: IM, IV: ~6 to 8 hours

Absorption: IM: Rapid and complete absorption; Oral: Readily absorbed

Distribution: IV: Vd:

Neonates: 0.76 ± 0.37 L/kg (range: 0.14 to 1.3 L/kg) (McDermott 1992)

Pediatric patients (Chamberlain 2012):

5 months to < 3 years: 1.62 L/kg (range: 0.67 to 3.4 L/kg)

3 to <13 years: 1.5 L/kg (range: 0.49 to 3 L/kg)

13 to <18 years: 1.27 L/kg (range: 1 to 1.54 L/kg)

Adults: 1.3 L/kg

Protein binding: ~91%

Metabolism: Hepatic; rapidly conjugated to lorazepam glucuronide (inactive)

Bioavailability: Oral: 90%

Half-life elimination:

Full-term neonates: IV: 40.2 ± 16.5 hours; range: 18 to 73 hours (McDermott 1992)

Pediatric patients (Chamberlain 2012): IV:

5 months to <3 years: 15.8 hours (range: 5.9 to 28.4 hours)

3 to <13 years: 16.9 hours (range: 7.5 to 40.6 hours)

13 to <18 years: 17.8 hours (range: 8.2 to 42 hours)

Adults: Oral: ~12 hours; IV: ~14 hours; IM: ~13 to 18 hours (Greenblatt 1983); End-stage renal disease (ESRD): ~18 hours

Time to peak: IM: ≤3 hours; Oral: ~2 hours; Sublingual tablet [Canadian product]: 1 hour

Excretion: Urine (~88%; predominantly as inactive metabolites); feces (~7%)

Dental Use

Short-term relief of anxiety prior to dental appointment

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Dental Health Professional Considerations

An adult companion should accompany the patient to and from dental office.

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation) (see Dental Health Professional Considerations)

Effects on Bleeding

No information available to require special precautions

Dental Usual Dosing

Anxiety and sedation: Adults: Oral: 1 to 10 mg/day in 2 to 3 divided doses; usual dose: 2 to 6 mg/day in divided doses

Preoperative: Adults:

IM: 0.05 mg/kg administered 2 hours before surgery (maximum: 4 mg/dose)

IV: 0.044 mg/kg 15 to 20 minutes before surgery (usual maximum: 2 mg/dose)

Preprocedural anxiety: Adults: Oral: 1 to 2 mg 1 hour before procedure

FDA Approval Date
July 25, 1980
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Jennum P, Baandrup L, Ibsen R, et al. Increased all-cause mortality with use of psychotropic medication in dementia patients and controls: A population-based register study. Eur Neuropsychopharmacol. 2015;25(11):1906-1913. doi: 10.1016/j.euroneuro.2015.08.014.[PubMed 26342397]

Johnson TJ, Voss G. Continuous infusion of undiluted lorazepam injection. Am J Health Syst Pharm. 2002;59(1):78-79.[PubMed 11813472]

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Kelly LE, Poon S, Madadi P, Koren G. Neonatal benzodiazepines exposure during breastfeeding. J Pediatr. 2012;161(3):448-451.[PubMed 22504099]

Lapierre YD and Labelle A, “Manic-Like Reaction Induced by Lorazepam Withdrawal,” Can J Psychiatry, 1987, 32(8):697-8.[PubMed 3690487]

Larsen ER, Damkier P, Pedersen LH, et al. Use of psychotropic drugs during pregnancy and breast-feeding. Acta Psychiatr Scand Suppl. 2015;(445):1-28.[PubMed 26344706]

Laszlo J, Clark RA, Hanson DC, et al, “Lorazepam in Cancer Patients Treated With Cisplatin: A Drug Having Antiemetic, Amnesic, and Anxiolytic Effects,” J Clin Oncol, 1985, 3(6):864-9.[PubMed 4040158]

Lee DS, Wong HA, and Knoppert DC, “Myoclonus Associated With Lorazepam Therapy in Very-Low-Birth-Weight Infants,” Biol Neonate, 1994, 66(6):311-5.[PubMed 7727612]

Lee ME, Lugo RA, Rusho WJ, et al, “Chemical Stability of Extemporaneously Prepared Lorazepam Suspension at Two Temperatures,” J Pediatr Pharmacol Ther, 2004, 9(4):254-8.[PubMed 23118704]

Lee SA, Lee JK, Heo K, “Coma Probably Induced by Lorazepam-Valproate Interaction,” Seizure, 2002, 11(2):124-5.[PubMed 11945099]

Lemmer P, Schneider S, Mühe A, Wennig R. Quantification of lorazepam and lormetazepam in human breast milk using GC-MS in the negative chemical ionization mode. J Anal Toxicol. 2007;31(4):224-226.[PubMed 17555647]

Lheureux P and Askenasi R, “Specific Treatment of Benzodiazepine Overdose,” Hum Toxicol, 1988, 7(2):165-70.[PubMed 3132418]

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Lugo RA, Chester EA, Cash J, et al, “A Cost Analysis of Enterally Administered Lorazepam in the Pediatric Intensive Care Unit,” Crit Care Med, 1999, 27(2):417-21.[PubMed 10075070]

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Mancuso CE, Tanzi MG, Gabay M. Paradoxical reactions to benzodiazepines: literature review and treatment options. Pharmacotherapy. 2004;24(9):1177-1185.[PubMed 15460178]

Manno EM, “New Management Strategies in the Treatment of Status Epilepticus,” Mayo Clin Proc, 2003, 78(4):508-18.[PubMed 12683704]

Marshall JD, Farrar HC, and Kearns GL, “Diarrhea Associated With Enteral Benzodiazepine Solutions,” J Pediatr, 1995, 126(4):657-9.[PubMed 7699551]

Mayo-Smith MF, “Pharmacological Management of Alcohol Withdrawal. A Meta-analysis and Evidence-Based Practice Guideline. American Society of Addiction Medicine Working Group on Pharmacological Management of Alcohol Withdrawal,” JAMA, 1997, 278(2):144-51[PubMed 9214531]

Mayo-Smith MF, Beecher LH, Fischer TL, et al. Management of Alcohol Withdrawal Delirium. An Evidence-Based Practice Guideline [published correction appears in Arch Intern Med. 2004;164(18):2068]. Arch Intern Med. 2004;164(13):1405-1412.[PubMed 15249349]

McDermott CA, Kowalczyk AL, Schnitzler ER, et al, “Pharmacokinetics of Lorazepam in Critically Ill Neonates With Seizures,” J Pediatr, 1992, 120(3):479-83.[PubMed 1538303]

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Brand Names: International

Abinol (CL); Ansilor (PT); Anta (TH); Anxiar (RO); Anxira (TH); Anzepam (TW); Aplacasse (AR); Aripax (GR); Ativan (AE, AU, BB, BF, BJ, CI, CO, ET, GB, GH, GM, GN, IE, IN, JO, KE, KR, KW, LR, MA, ML, MR, MT, MU, MW, MX, NE, NG, NZ, PE, PH, PK, SA, SC, SD, SG, SL, SN, TN, TW, TZ, UG, UY, VE, VN, ZA, ZM, ZW); Bonatranquan (DE); Control (IT); Donix (ES); Emotival (AR); Larpose (IN, LK); Laubeel (DE); Lauracalm (LU); Lonza (TH); Lopa (BD); Lopam (TW); Lora (CN); Lorabenz (DK); Lorafen (LV, PL); Loram (HR); Lorans (AE, CY, EG, IQ, IR, IT, JO, KW, LB, LT, LY, MT, MY, OM, SA, SY, YE); Loranxil (HU); Loravan (KR); Lorax (BR); Loraxen (BD); Lorazep (TH); Lorazepam-Efeka (LU); Lorazepam-Eurogenerics (LU); Lorazin (TW); Lorenin (PT); Loridem (LU); Lorivan (IL, MT, TR); Lorsilan (HR); Lozam (CR, DO, GT, HN, NI, PA, SV); Lozicum (BD, HK); Merlit (AT, RU); Merlopam (ID); Nervistop L (AR); Neuropam (TW); Novhepar (GR); Orfidal (ES); Renaquil (ID); Rilex (HU); Sedatival (AR); Sidenar (AR); Silence (HK, TW); Stapam (TW); Tavor (BG, CZ, DE, GR, IT, TR); Temesta (AT, BE, CH, DK, FI, FR, LU, NL, SE); Titus (AE, BF, BJ, CI, CY, EG, ET, GH, GM, GN, GR, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZM, ZW); Tranqipam (ZA); Trapax (AR, PY); Trapex (BD, IN); Vigiten (LU)

Lorazepam (Patient Education – Adult Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(lor A ze pam)

Brand Names: US

Ativan; LORazepam Intensol

Brand Names: Canada

Ativan

Warning
  • This drug is a benzodiazepine. The use of a benzodiazepine drug along with opioid drugs has led to very bad side effects. Side effects that have happened include slowed or trouble breathing and death. Opioid drugs include drugs like codeine, oxycodone, and morphine. Opioid drugs are used to treat pain and some are used to treat cough. Talk with the doctor.
  • If you are taking this drug with an opioid drug, get medical help right away if you feel very sleepy or dizzy; if you have slow, shallow, or trouble breathing; or if you pass out. Caregivers or others need to get medical help right away if the patient does not respond, does not answer or react like normal, or will not wake up.
What is this drug used for?
  • It is used to treat anxiety.
  • It is used to treat seizures.
  • It is used to ease anxiety before surgery.
  • It may be given to you for other reasons. Talk with the doctor.
What do I need to tell my doctor BEFORE I take this drug?
  • If you have an allergy to lorazepam or any other part of this drug.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have any of these health problems: Glaucoma, low mood (depression), or certain mental problems.
  • If you have sleep apnea.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.
What are some things I need to know or do while I take this drug?
  • All products:
  • Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists.
  • Talk with your doctor before you use other drugs and natural products that slow your actions.
  • Have your blood work checked if you are on this drug for a long time. Talk with your doctor.
  • This drug may be habit-forming with long-term use.
  • Do not take this drug for longer than you were told by your doctor.
  • If you have been taking this drug on a regular basis and you stop it all of a sudden, you may have signs of withdrawal. Do not stop taking this drug all of a sudden without calling your doctor. Tell your doctor if you have any bad effects.
  • If you are 65 or older, use this drug with care. You could have more side effects.
  • Use with care in children. Talk with the doctor.
  • This drug may cause harm to the unborn baby if you take it while you are pregnant. If you are pregnant or you get pregnant while taking this drug, call your doctor right away.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.
  • All oral products:
  • Avoid driving and doing other tasks or actions that call for you to be alert until you see how this drug affects you.
  • Avoid drinking alcohol while taking this drug.
  • Injection:
  • Avoid driving and doing other tasks or actions that call for alertness for 1 to 2 full days after getting this drug and until the effects of this drug have worn off.
  • Do not try to get out of bed without help for at least 8 hours after you use this drug. You may fall and hurt yourself.
  • Avoid drinking alcohol for 1 to 2 full days after getting this drug.
  • Some products have benzyl alcohol. Do not give a product that has benzyl alcohol in it to a newborn or infant. Talk with the doctor to see if this product has benzyl alcohol in it.
  • For a procedure:
  • Studies in young animals and children have shown that frequent or long-term use of anesthesia drugs or drugs used for sleep in children younger than 3 years of age may lead to long-term brain problems. This may also happen in unborn babies if the mother uses this drug during the third trimester of pregnancy. Talk with the doctor.
What are some side effects that I need to call my doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of low mood (depression), thoughts of killing yourself, nervousness, emotional ups and downs, thinking that is not normal, anxiety, or lack of interest in life.
  • Hallucinations (seeing or hearing things that are not there).
  • Change in how you act.
  • Change in balance.
  • Feeling confused.
  • Memory problems or loss.
  • Feeling very tired or weak.
  • Very bad dizziness or passing out.
  • Change in eyesight.
  • Muscle weakness.
  • Dark urine or yellow skin or eyes.
  • This drug may cause very bad and sometimes deadly breathing problems. Call your doctor right away if you have slow, shallow, or trouble breathing.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
  • All products:
  • Feeling sleepy.
  • Dizziness.
  • Headache.
  • Feeling tired or weak.
  • Injection:
  • Irritation where the shot is given.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best taken?
  • Use this drug as ordered by your doctor. Read all information given to you. Follow all instructions closely.
  • All oral products:
  • Take with or without food. Take with food if it causes an upset stomach.
  • Liquid (solution):
  • Use the dropper that comes with this drug to measure the drug.
  • Mix the liquid with water, juice, soda, applesauce, or pudding before taking it.
  • Swallow the mixture right away. Do not store for use at a later time.
  • Under the tongue (sublingual) tablet:
  • Place tablet under the tongue and let dissolve.
  • Do not swallow for at least 2 minutes after using this drug.
  • Injection:
  • It is given as a shot into a muscle or vein.
What do I do if I miss a dose?
  • All oral products:
  • If you take this drug on a regular basis, take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.
  • Many times this drug is taken on an as needed basis. Do not take more often than told by the doctor.
  • Injection:
  • Call your doctor to find out what to do.
How do I store and/or throw out this drug?
  • Tablets and under the tongue (sublingual) tablets:
  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Liquid (solution):
  • Store in a refrigerator. Do not freeze.
  • Throw away any part not used after 3 months.
  • All oral products:
  • Protect from light.
  • Injection:
  • If you need to store this drug at home, talk with your doctor, nurse, or pharmacist about how to store it.
  • All products:
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else’s drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.
Lorazepam (Patient Education – Pediatric Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(lor A ze pam)

Brand Names: US

Ativan; LORazepam Intensol

Brand Names: Canada

Ativan

Warning
  • This drug is a benzodiazepine. The use of a benzodiazepine drug along with opioid drugs has led to very bad side effects. Side effects that have happened include slowed or trouble breathing and death. Opioid drugs include drugs like codeine, oxycodone, and morphine. Opioid drugs are used to treat pain and some are used to treat cough. Talk with the doctor.
  • If your child is taking this drug with an opioid drug, get medical help right away if your child feels very sleepy or dizzy; if your child has slow, shallow, or trouble breathing; or if your child passes out. Get medical help right away if your child does not respond, does not answer or react like normal, or will not wake up.
What is this drug used for?
  • It is used to treat anxiety.
  • It is used to treat upset stomach and throwing up.
  • It is used to treat seizures.
  • It is used to calm a child before care.
  • It may be given to your child for other reasons. Talk with the doctor.
What do I need to tell the doctor BEFORE my child takes this drug?
  • If your child has an allergy to this drug or any part of this drug.
  • If your child is allergic to any drugs like this one or any other drugs, foods, or other substances. Tell the doctor about the allergy and what signs your child had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If your child has any of these health problems: Glaucoma, low mood (depression), or certain mental problems.
  • If your child has sleep apnea, talk with the doctor.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell the doctor and pharmacist about all of your child’s drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for your child to take this drug with all of his/her drugs and health problems. Do not start, stop, or change the dose of any drug your child takes without checking with the doctor.
What are some things I need to know or do while my child takes this drug?
  • All products:
  • Tell all of your child’s health care providers that your child is taking this drug. This includes your child’s doctors, nurses, pharmacists, and dentists.
  • Alcohol may interact with this drug. Be sure your child does not drink alcohol.
  • Talk with the doctor before giving your child other drugs and natural products that may slow your child’s actions.
  • Have your child’s blood work checked if he/she is on this drug for a long time. Talk with your child’s doctor.
  • This drug may be habit-forming with long-term use.
  • Do not have your child use longer than you have been told by your child’s doctor.
  • If your child has been taking this drug on a regular basis and stops taking it all of a sudden, your child may have signs of withdrawal. Do not stop giving this drug all of a sudden without calling the doctor. Tell the doctor if your child has any bad effects.
  • Use with care in children. Talk with the doctor.
  • If your child is pregnant or breast-feeding a baby:
  • This drug may cause harm to the unborn baby if your child takes it during pregnancy. If your child is pregnant or gets pregnant while taking this drug, call the doctor right away.
  • Tell the doctor if your child is breast-feeding a baby. You will need to talk about any risks to the baby.
  • All oral products:
  • Have your child avoid tasks or actions that call for alertness until you see how this drug affects your child. These are things like riding a bike, playing sports, or using items such as scissors, lawnmowers, electric scooters, toy cars, or motorized vehicles.
  • Injection:
  • Have your child avoid tasks or actions that call for alertness for 1 to 2 full days after your child gets this drug and until the effects of this drug have worn off. These include things like riding a bike, playing sports, or using items such as scissors, lawnmowers, electric scooters, toy cars, or motorized vehicles.
  • Do not let your child get out of bed without help for at least 8 hours after your child uses this drug. Your child may fall and hurt him/herself.
  • Some products have benzyl alcohol. Do not give a product that has benzyl alcohol in it to a newborn or infant. Talk with the doctor to see if this product has benzyl alcohol in it.
  • For a procedure:
  • Studies in young animals and children have shown that frequent or long-term use of anesthesia drugs or drugs used for sleep in children younger than 3 years of age may lead to long-term brain problems. This may also happen in unborn babies if the mother uses this drug during the third trimester of pregnancy. Talk with the doctor.
What are some side effects that I need to call my child’s doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your child’s doctor or get medical help right away if your child has any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of low mood (depression), thoughts of killing yourself, nervousness, emotional ups and downs, thinking that is not normal, anxiety, or lack of interest in life.
  • Hallucinations (seeing or hearing things that are not there).
  • Change in how you act.
  • Change in balance.
  • Feeling confused.
  • Memory problems or loss.
  • Feeling very tired or weak.
  • Very bad dizziness or passing out.
  • Change in eyesight.
  • Muscle weakness.
  • Dark urine or yellow skin or eyes.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your child’s doctor or get medical help if any of these side effects or any other side effects bother your child or do not go away:
  • All products:
  • Feeling sleepy.
  • Dizziness.
  • Headache.
  • Feeling tired or weak.
  • Injection:
  • Irritation where the shot is given.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your child’s doctor. Call your child’s doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best given?
  • Give this drug as ordered by your child’s doctor. Read all information given to you. Follow all instructions closely.
  • All oral products:
  • Give this drug with or without food. Give with food if it causes an upset stomach.
  • Liquid (solution):
  • Use the dropper that comes with this drug to measure the drug.
  • Mix the liquid with water, juice, soda, applesauce, or pudding before giving it to your child.
  • Give the mixture right away. Do not store for use at a later time.
  • Under the tongue (sublingual) tablet:
  • Place under your child’s tongue and let dissolve all the way before swallowing. Do not let your child chew, suck, or swallow the tablet.
  • Do not let your child swallow for at least 2 minutes after using this drug.
  • Injection:
  • It is given as a shot into a muscle or vein.
What do I do if my child misses a dose?
  • All oral products:
  • If your child takes this drug on a regular basis, give a missed dose as soon as you think about it.
  • Give a missed dose as soon as you think about it.
  • If it is close to the time for your child’s next dose, skip the missed dose and go back to your child’s normal time.
  • Do not give 2 doses at the same time or extra doses.
  • Many times this drug is given on an as needed basis. Do not give to your child more often than told by the doctor.
  • Injection:
  • Call your child’s doctor to find out what to do.
How do I store and/or throw out this drug?
  • Tablets and under the tongue (sublingual) tablets:
  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Liquid (solution):
  • Store in a refrigerator. Do not freeze.
  • Throw away any part not used after 3 months.
  • All oral products:
  • Protect from light.
  • Injection:
  • If you need to store this drug at home, talk with your child’s doctor, nurse, or pharmacist about how to store it.
  • All products:
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your child’s symptoms or health problems do not get better or if they become worse, call your child’s doctor.
  • Do not share your child’s drug with others and do not give anyone else’s drug to your child.
  • Keep a list of all your child’s drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your child’s doctor.
  • Talk with your child’s doctor before giving your child any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your child’s doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.