(lor A ze pam)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
LORazepam Intensol: 2 mg/mL (30 mL) [alcohol free, dye free, sugar free; unflavored flavor]
Generic: 2 mg/mL (30 mL)
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)
Ativan: 0.5 mg, 1 mg [DSC]
Ativan: 1 mg [scored]
Ativan: 2 mg [DSC]
Ativan: 2 mg [scored]
Generic: 0.5 mg, 1 mg, 2 mg
Brand Names: U.S.
- LORazepam Intensol
- Anticonvulsant, Benzodiazepine
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.
IM: Rapid and complete absorption; Oral: Readily absorbed
IV: Vd: Crosses the blood brain barrier
Neonates: 0.76 ± 0.37 L/kg (range: 0.14 to 1.3 L/kg) (McDermott 1992)
Pediatric patients (Chamberlain 2012): Crosses the blood brain barrier
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
Hepatic; rapidly conjugated to inactive compounds
Urine (~88%; predominantly as inactive metabolites); feces (~7%)
Onset of Action
Anticonvulsant: IV: Within 10 minutes
Hypnosis: IM: 20 to 30 minutes
Sedation: IV: Within 2 to 3 minutes (Greenblatt 1983)
Time to Peak
IM: ≤3 hours; Oral: ~2 hours; Sublingual tablet [Canadian product]: 1 hour
Duration of Action
Anesthesia premedication: Adults: IM, IV: ~6 to 8 hours
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 1981); End-stage renal disease (ESRD): ~18 hours
~85% to 93%; free fraction may be significantly higher in elderly (Greenblatt, 1981)
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 to relieve anxiety or to produce amnesia (diminish recall) or sedation
Anesthesia premedication (sublingual): Canadian labeling: Anesthesia premedication to relieve anxiety prior to surgical procedures
Status epilepticus (parenteral): Treatment of status epilepticus
Agitation in the ICU patient (IV); alcohol withdrawal delirium; alcohol withdrawal syndrome; chemotherapy-associated nausea and vomiting (either as an adjunct to standard antiemetics or for breakthrough or anticipatory nausea/vomiting); partial complex seizures (refractory); psychogenic catatonia; rapid tranquilization of the agitated patient; status epilepticus (in pediatrics)
Hypersensitivity to lorazepam, any component of the formulation, or other benzodiazepines (cross-sensitivity with other benzodiazepines may exist); acute narrow-angle glaucoma; sleep apnea (parenteral); intra-arterial injection of parenteral formulation; severe respiratory insufficiency (except during mechanical ventilation)
Canadian labeling: Additional contraindications (not in the US labeling): Myasthenia gravis
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 or 0.01 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) (Mayo-Smith, 1997):
Oral, IM, IV (fixed-dose regimen): 2 mg every 6 hours for 4 doses, then 1 mg every 6 hours for 8 additional doses
Oral, IM, IV (symptom-triggered regimen): 2 to 4 mg every 1 hour as needed; dose determined by a validated severity assessment scale
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)
Partial complex seizures, refractory (off-label use): Oral: 1 mg twice daily; increase biweekly in increments of 1 mg twice daily until seizures stop or side effects occur (Walker, 1984); however, additional data may be necessary to further define the role of lorazepam in this condition
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); however, additional data may be necessary to further define the role of lorazepam in this condition
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); however, additional data may be necessary to further define the role of lorazepam in this condition
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%
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:
US labeling: Initial: 1 to 2 mg daily in divided doses
Canadian labeling: Initial: 0.5 mg daily; titrate cautiously as tolerated
Premedication for anesthesia: IM, IV: Canadian labeling: Reduce the initial dose by approximately 50% and adjust as needed and tolerated; IV dose should generally not exceed 2 mg in patients >50 years.
Chemotherapy-associated nausea and vomiting (off-label use):
Anticipatory nausea/vomiting (prevention and treatment): Infants ≥1 month, Children, and Adolescents: Oral: 0.04 to 0.08 mg/kg/dose (maximum dose: 2 mg) once at bedtime the evening prior to chemotherapy and once the next day before chemotherapy (Dupuis 2014)
Breakthrough nausea/vomiting: Children ≥2 years and Adolescents: IV: 0.025 to 0.05 mg/kg/dose (maximum dose: 2 mg) every 6 hours as needed (Dupuis 2003); however, additional data may be necessary to further define the role of lorazepam in children for chemotherapy-associated nausea and vomiting
Status epilepticus: Infants, Children, and Adolescents (off-label use):
Neurocritical Care Society recommendation: IV: 0.1 mg/kg (maximum dose: 4 mg) given at a maximum rate of 2 mg/minute; may repeat in 5 to 10 minutes (NCS [Brophy 2012]). Note: Dilute dose 1:1 with saline.
American Academy of Pediatrics recommendation: IV, IM: 0.05 to 0.1 mg/kg (maximum dose: 4 mg); may repeat dose every 10 to 15 minutes if seizure continues (AAP [Hegenbarth 2008])
Dosage adjustment for lorazepam with concomitant medications: Probenecid or valproic acid: Reduce lorazepam dose by 50%
Dosing: Renal Impairment
Oral: No dosage adjustment necessary (Aronoff 2007).
IM, IV: Risk of propylene glycol toxicity. Monitor closely if using for prolonged periods of time or at high doses.
Mild-to-moderate disease: Use with caution.
Severe disease or failure: Use is not recommended.
Dosing: Hepatic Impairment
Mild-to-moderate disease: No dose adjustment necessary.
Severe insufficiency and/or encephalopathy: Use with caution; may require lower doses.
Mild-to-moderate disease: Use with caution.
Severe disease or failure: Use is not recommended.
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.
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.
IM: Should be administered (undiluted) deep into the muscle mass.
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.
Continuous IV infusion (off-label administration mode; Barr 2013) solutions should have an in-line filter and the solution should be checked frequently for possible precipitation (Grillo 1996).
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.
See Trissel’s IV Compatibility Database
Parenteral: Intact vials should be refrigerated (room temperature storage information may be available; contact product manufacturer to obtain current recommendations). Protect from light. Do not use discolored or precipitate-containing solutions. 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.
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy
Analgesics (Opioid): CNS Depressants may enhance the CNS depressant effect of Analgesics (Opioid). Management: Avoid concomitant use of opioid analgesics 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. Consider therapy modification
Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
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. Consider therapy modification
Cannabis: May enhance the CNS depressant effect of CNS Depressants. 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. Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. 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. Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. 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. Monitor therapy
Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. 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. 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. Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Loxapine: May enhance the adverse/toxic effect of LORazepam. Specifically, prolonged stupor, respiratory depression, and/or hypotension. Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Methadone: Benzodiazepines may enhance the CNS depressant effect of Methadone. Avoid combination
Methotrimeprazine: May enhance the CNS depressant effect of CNS Depressants. CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. 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. Consider therapy modification
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy
Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Monitor therapy
Nabilone: May enhance the CNS depressant effect of CNS Depressants. 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. Avoid combination
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. 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. Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. 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. 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. Monitor therapy
Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Monitor therapy
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy
Probenecid: May increase the serum concentration of LORazepam. Consider therapy modification
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. 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. Monitor therapy
Sodium Oxybate: Benzodiazepines may enhance the CNS depressant effect of Sodium Oxybate. 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. 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. Consider therapy modification
Teduglutide: May increase the serum concentration of Benzodiazepines. Monitor therapy
Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination
Theophylline Derivatives: May diminish the therapeutic effect of Benzodiazepines. Consider therapy modification
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Valproate Products: May increase the serum concentration of LORazepam. Consider therapy modification
Yohimbine: May diminish the therapeutic effect of Antianxiety Agents. 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. Consider therapy modification
Frequency not always defined.
Cardiovascular: Hypotension (≤2%)
Central nervous system: Sedation (≤16%), dizziness (≤7%), drowsiness (2% to 4%), unsteadiness (3%), headache (1%), coma (≤1%), stupor (≤1%), aggressive behavior, agitation, akathisia, amnesia, anxiety, central nervous system stimulation, disinhibition, disorientation, dysarthria, euphoria, excitement, extrapyramidal reaction, fatigue, hostility, hypothermia, irritability, mania, memory impairment, outbursts of anger, psychosis, seizures, sleep apnea (exacerbation), sleep disturbances, slurred speech, suicidal behavior, suicidal ideation, vertigo
Dermatologic: Alopecia, skin rash
Gastrointestinal: Changes in appetite, constipation
Endocrine & metabolic: Change in libido, hyponatremia, SIADH
Genitourinary: Impotence, orgasm disturbance
Hematologic & oncologic: Agranulocytosis, pancytopenia, thrombocytopenia
Hepatic: Increased serum alkaline phosphatase, increased serum bilirubin, increased serum transaminases, jaundice
Hypersensitivity: Anaphylaxis, anaphylactoid reaction, hypersensitivity reaction
Local: Pain at injection site (IM: 1% to 17%; IV: ≤2%), erythema at injection site (≤2%)
Neuromuscular & skeletal: Weakness (≤4%)
Ophthalmic: Visual disturbances (including diplopia and blurred vision)
Respiratory: Respiratory failure (1% to 2%), apnea (1%), hypoventilation (≤1%), exacerbation of obstructive pulmonary disease, nasal congestion, respiratory depression, worsening of sleep apnea
<1% (Limited to important or life-threatening): Abnormal gait, abnormal hepatic function tests, abnormality in thinking, acidosis, cardiac arrhythmia, ataxia, blood coagulation disorder, bradycardia, cardiac arrest, cardiac failure, cerebral edema, confusion, convulsions, cystitis, decreased mental acuity, delirium, depression, drug dependence (with prolonged use), drug toxicity (polyethylene glycol or propylene glycol poisoning [prolonged IV infusion]), excessive crying, gastrointestinal hemorrhage, hallucinations, hearing loss, heart block, hematologic abnormality, hepatotoxicity, hypertension, hyperventilation, hyporeflexia, infection, injection site reaction, myoclonus, neuroleptic malignant syndrome, paralysis, pericardial effusion, pheochromocytoma (aggravation), pneumothorax, pulmonary edema, pulmonary hemorrhage, pulmonary hypertension, seizure, tachycardia, urinary incontinence, ventricular arrhythmia, withdrawal syndrome
Concerns related to adverse effects:
• Anterograde amnesia: Benzodiazepines have been associated with anterograde amnesia.
• 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, particularly in adolescent/pediatric or psychiatric patients.
• 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.
• Impaired gag reflex: Use with caution in patients with an impaired gag reflex.
• 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.
• 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.
• Debilitated patients: Use with caution in debilitated patients; initial doses should be at the lower end of dosing range.
• Fall risk: Use with extreme caution in patients who are at risk of falls; benzodiazepines have been associated with falls and traumatic injury.
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 contains polyethylene glycol. May be associated with toxicity in high-dose and/or longer-term therapy.
• Propylene glycol: Parenteral formulation contains propylene glycol (PG). May be associated with dose-related toxicity and can occur ≥48 hours after initiation of lorazepam. Limited data suggest increased risk of PG accumulation at doses of ≥6 mg/hour for 48 hours or more (Nelson 2008). Monitor for signs of toxicity which may include acute renal failure, lactic acidosis, and/or osmol gap. May consider using enteral delivery of lorazepam tablets to decrease the risk of PG toxicity (Lugo 1999).
• 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.
Respiratory and cardiovascular status, blood pressure, heart rate, symptoms of anxiety
CBC, liver function tests; clinical signs of propylene glycol toxicity (for continuous high-dose and/or long duration intravenous use) including serum creatinine, BUN, serum lactate, osmol gap); Note: An osmol 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)
Pregnancy Risk Factor
Teratogenic effects have been observed in some animal reproduction studies. 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).
• 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.
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