Introduction ⬇
AHFS Class:
Generic Name(s):
Associated Monographs
Lorazepam is a benzodiazepine. The drug has anticonvulsant, anxiolytic, and sedative properties.283,435
Uses ⬆ ⬇
Anxiety Disorders 
Lorazepam is used for the management of anxiety disorders or for the short-term relief of symptoms of anxiety or anxiety associated with depressive symptoms.283,547 The efficacy of lorazepam for long-term use (i.e., longer than 4 months) has not been evaluated.283,547 The need for continued therapy with the drug should be periodically reassessed.283,547
Preoperative Sedation, Anxiolysis, and Amnesia
Lorazepam injection is used for preoperative sedation, anxiolysis, and anterograde amnesia.435 Administration of lorazepam is especially useful in patients with preoperative anxiety who prefer diminished recall of events associated with the day of surgery.
Status Epilepticus
Lorazepam injection is used for the treatment of status epilepticus.435,543,545,546
Efficacy of IV lorazepam was established in 2 multicenter controlled trials in patients (mostly 18-65 years of age) with tonic-clonic status epilepticus, simple partial and complex partial status epilepticus, or absence status.435 The first study was a double-blind, randomized, active-control study that compared lorazepam 2 mg (with an additional 2-mg IV dose given if necessary) with diazepam 5 mg (with an additional 5-mg IV dose given if necessary).435 In this study, 80 or 57% of patients receiving lorazepam or diazepam, respectively, were considered responders, defined as the percentage of patients in whom seizures were terminated within 10 minutes after administration of the drug and who continued to be seizure-free for at least an additional 30 minutes.435 When an additional dose of study drug was administered to nonresponders, the overall response rate increased to 93% with lorazepam and 86% with diazepam.435 The second study was a double-blind, dose comparison trial; in this study, 61, 57, and 76% of patients receiving 1, 2, and 4 mg of lorazepam, respectively, were responders (as defined above).435
Clinical Perspective
Benzodiazepines are considered the initial drugs of choice for the management of status epilepticus because of their rapid onset of action, demonstrated efficacy, safety, and tolerability.545,563,756,757,758,759,761,762,763,764,765,766,767,771
Status epilepticus is a medical emergency that must be treated promptly to reduce substantial morbidity and mortality.545,763,764,766,767 Initial treatment should include standard critical care and supportive therapy (e.g., blood pressure and respiratory support, oxygen, IV access, identification and correction of underlying causes), followed by administration of a benzodiazepine.545,763,765,766 Although IV lorazepam is generally preferred because of its longer duration of action, studies generally have not identified any substantial differences between IV lorazepam, IV diazepam, and IM midazolam in terms of seizure cessation, and experts consider these therapies to be equivalent first-line options.545,763,764,765,766,767,768,769 Selection of an appropriate benzodiazepine should be individualized based on local availability, route of administration, pharmacokinetics, cost, and other factors (e.g., treatment setting).545,756,757,758,759,760,761,762,763,764,765,766,767,769 To achieve a rapid therapeutic effect, IV administration of a benzodiazepine is preferred; however, administration via other routes (e.g., IM, rectal, intranasal, buccal) may be considered when IV administration is not possible (e.g., in the prehospital setting).543,545,546,547,763,764,765,766,768,769 If seizures continue after initial therapy with a benzodiazepine, a second-line anticonvulsant agent (e.g., IV fosphenytoin or phenytoin, IV valproate sodium, IV levetiracetam, IV phenobarbital) should be administered.757,759,760,762,763,765,766 If refractory status epilepticus occurs, continuous IV infusion of anticonvulsants, IV barbiturates, or general anesthetics may be necessary.757,758,759,760,761,765,766
Early treatment with benzodiazepines in the prehospital setting can improve outcomes in patients with status epilepticus.563,768 Results of a placebo-controlled study in adults with out-of-hospital status epilepticus indicated that IV administration of benzodiazepines by paramedics was safe and effective in the management of this condition.563 Findings from this study indicated that both IV lorazepam and IV diazepam were more effective than placebo in controlling status epilepticus by the time of patient arrival in the emergency department.563 Because the need to establish IV access may delay administration of an IV benzodiazepine in the prehospital environment, use of other less invasive routes of administration may decrease the time to active treatment.763,765,768 Results of a randomized controlled study (RAMPART) indicate that IM administration of midazolam by paramedics in the prehospital setting may improve outcomes in patients with status epilepticus; in this study, 73% of patients who received IM midazolam achieved seizure resolution at the time of arrival in the emergency department compared with 63% of those who received IV lorazepam.763,765,768
Sedation in Critical Care Settings
Lorazepam, administered by intermittent injection or continuous IV infusion, has been used for sedation of intubated and mechanically ventilated adults and children in critical care settings† (e.g., intensive care unit [ICU]).565,800,801,819
Clinical Perspective
Sedative agents are administered in critically ill patients to reduce agitation and anxiety and increase tolerance to invasive procedures (e.g., mechanical ventilation).800,801 The provision of adequate analgesia and other measures to ensure patient comfort is recommended before sedatives are administered.800,801 Sedative agents should be titrated to the desired level of sedation; in most cases, a light rather than deep level of sedation is recommended in critically ill, mechanically ventilated adults because of improved clinical outcomes that have been demonstrated (e.g., shortened duration of mechanical ventilation and reduced ICU length of stay).800,801 The depth and quality of sedation should be assessed using a validated and reliable assessment tool (e.g., Richmond Agitation-Sedation Scale [RASS], Sedation-Agitation Scale [SAS]).801 Common sedative agents used in the ICU include benzodiazepines (e.g., midazolam, lorazepam), propofol, and dexmedetomidine.800,801,817 These agents appear to be similarly effective in providing adequate sedation in critically ill, mechanically ventilated adults.800,801 However, modest benefits in terms of other clinical outcomes (e.g., reduced duration of mechanical ventilation, shorter time to extubation, reduced risk of delirium) have been observed with the nonbenzodiazepine sedatives (dexmedetomidine and propofol) compared with benzodiazepines.800,801,817,818,819,820
Comparative studies have demonstrated a shorter time to light sedation and shorter time to extubation with propofol compared with benzodiazepines, and a shorter time to extubation and reduced risk of delirium with dexmedetomidine compared with benzodiazepines.800,818,819 In most of these studies, benzodiazepines were administered as a continuous IV infusion rather than as intermittent IV injections.800 Because of the apparent advantages and an overall favorable benefit-to-risk profile, experts state that nonbenzodiazepine sedatives (dexmedetomidine or propofol) may be preferred to benzodiazepines (midazolam or lorazepam) in mechanically ventilated, critically ill adults.800,801 This recommendation should be considered in the context of the specific clinical situation since benzodiazepines may still be preferred in certain situations (e.g., patients with anxiety, seizures, or alcohol or benzodiazepine withdrawal).801 When selecting an appropriate sedative agent, the patient's individual sedation goals should be considered in addition to specific drug-related (e.g., pharmacology, pharmacokinetics, adverse effects, availability, cost) and patient-related (e.g., comorbid conditions) factors.800,801
Because of its greater potency and slower clearance, emergence from short-term sedation with lorazepam may be longer than with midazolam; however, comparative studies have suggested that midazolam is associated with greater variability and a longer time to awakening than lorazepam when used for prolonged sedation.801
Schizophrenia
Benzodiazepines have been used for augmentation of antipsychotic therapy or adjunctive therapy in patients with schizophrenia†.529
The American Psychiatric Association (APA) suggests that a benzodiazepine may be used for the treatment of akathisia associated with antipsychotic therapy; however, the potential benefits of benzodiazepine therapy should be weighed against the potential adverse effects (e.g., somnolence, cognitive difficulties, problems with coordination, risk of misuse or development of a sedative use disorder, respiratory depression if used in high doses and particularly in combination with alcohol, other sedating medications, or opioids).529 Benzodiazepines (e.g., lorazepam) also have been used for augmentation treatment of catatonia.529
Cancer Chemotherapy-induced Nausea and Vomiting
Lorazepam also has been used in the management of nausea and vomiting associated with emetogenic cancer chemotherapy†.492,493,494,495,496,497,498,499,500,501,502,503,504 The American Society of Clinical Oncology (ASCO) guidelines on antiemetic therapy state that lorazepam is a useful adjunct to antiemetic drugs, but is not recommended as a single-agent antiemetic.630
Delirium
Lorazepam also has been used in the management of delirium.† 533,535,536,537 Although there is little evidence to support the use of benzodiazepines alone for general cases of delirium, there may be certain types of delirium for which benzodiazepines may be useful (e.g., delirium related to alcohol or benzodiazepine withdrawal).533 If a benzodiazepine is used for the treatment of delirium, specific agents with a short duration and no active metabolites (e.g., lorazepam) are preferred.533
Drug-induced Cardiovascular Emergencies
Lorazepam has been used adjunctively in the management of certain drug-induced cardiovascular emergencies† and cocaine-induced acute coronary syndrome†.696
Dosage and Administration ⬆ ⬇
Administration
Lorazepam is administered orally, IM, or by IV injection or IV infusion.283,435,547 The drug should not be administered by intra-arterial injection since arteriospasm can occur, which may cause gangrene and possibly require amputation. 435
Oral Administration
Lorazepam is administered orally as tablets or oral solution.283,547
Lorazepam oral concentrate solution should be mixed with a liquid (e.g., water, juices, carbonated or soda-like beverages) or semi-solid food (e.g., applesauce, pudding) just before administration using only the calibrated dropper provided by the manufacturer.547
Parenteral Administration
IM administration:IM injections of lorazepam are administered as undiluted solutions; IM injections should be administered deep into the muscle mass.435
IV injection: For direct IV administration, lorazepam injection must be diluted with an equal volume of compatible diluent, such as sterile water for injection, 0.9% sodium chloride injection, or 5% dextrose injection.435 Following dilution, the solution should be mixed thoroughly by gently inverting the container repeatedly until a homogenous solution is obtained; the solution should not be shaken vigorously.435 Solutions of lorazepam injection should not be used if they appear discolored or contain a precipitate.435 Following dilution, lorazepam may be injected directly into a vein or into the tubing of an existing IV infusion.435 Injections should be administered slowly at a rate not exceeding 2 mg/minute.435 Direct IV injection with the drug should be made with repeated aspiration to ensure that none of the drug is injected intra-arterially and that perivascular extravasation does not occur.435 Equipment necessary to maintain a patent airway and to support respiration and ventilation should be immediately available prior to administration of IV lorazepam.435 Vital signs should be monitored during IV infusion of the drug.435
IV infusion: A standard concentration of 1 mg/mL has been recommended (see Standardize 4 Safety section below).250
Standardize 4 Safety
Standardized concentrations for IV lorazepam have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care. Multidisciplinary expert panels were convened to determine recommended standard concentrations. Because recommendations from the S4S panels may differ from the manufacturer's prescribing information, caution is advised when using concentrations that differ from labeling, particularly when using rate information from the label. For additional information on S4S (including updates that may be available), see [Web].250
Table 1: Standardize 4 Safety Continuous IV Infusion Standard Concentration for Lorazepam250
Patient Population | Concentration Standard | Dosing Units |
|---|
Adults | 1 mg/mL | mg/hour |
Dosage
Dosage of lorazepam must be individualized, and the smallest effective dosage should be used (especially in geriatric or debilitated patients, in those with low serum albumin, and in patients currently receiving other CNS depressants) to avoid oversedation.
Anxiety Disorders
The usual initial adult oral dosage of lorazepam for the symptomatic treatment of anxiety is 2-3 mg daily, divided in 2 or 3 doses; dosage should be adjusted if necessary and as tolerated.283,547 In geriatric or debilitated patients, lorazepam therapy should be initiated with 1-2 mg daily, divided in 2 or 3 doses; dosage should be adjusted if necessary and as tolerated. Dosage may range from 1-10 mg daily (usually 2-6 mg) in divided doses, with the largest single dose given at bedtime.283,547 For insomnia caused by anxiety or transient situational stress in adults, 2-4 mg of lorazepam is given as a single daily dose, usually at bedtime.283,547 In patients who have received prolonged (e.g., for several months) lorazepam therapy, abrupt discontinuance of the drug should be avoided since manifestations of withdrawal can be precipitated; if the drug is to be discontinued in such patients, it is recommended that dosage be gradually tapered.
Preoperative Sedation, Anxiolysis, and Amnesia
For preoperative IM use in adults, the usual dose of lorazepam is 0.05 mg/kg administered by deep IM injection at least 2 hours prior to surgery.435 The IM dose should be individualized, but should not exceed 4 mg.435
Alternatively, lorazepam may be administered IV for preoperative use.435 For preoperative IV use, the usual initial dose of lorazepam for sedation and relief of anxiety is 0.044 mg/kg (or up to 2 mg total, whichever is smaller) administered 15-20 minutes prior to surgery; this dose is sufficient for sedating most adults and generally should not be exceeded in patients older than 50 years of age.435 For those patients in whom increased lack of recall about perioperative events is considered beneficial, lorazepam doses up to 0.05 mg/kg (maximum total dose of 4 mg) may be administered IV.435
Status Epilepticus
For the management of status epilepticus, the usual dose of lorazepam in adults is 4 mg by slow IV injection (rate of 2 mg/minute); if seizures continue or recur after a 10- to 15-minute period of observation, an additional 4-mg dose of the drug may be administered.435 The manufacturer states that experience with administration of additional doses of lorazepam is limited. 435 IM administration of lorazepam is not recommended for the treatment of status epilepticus because therapeutic plasma concentrations of the drug are not achieved as rapidly as with IV administration of the drug.435 However lorazepam may be given IM if IV access is not available.435
For the management of status epilepticus in children†, IV doses of 0.05-0.1 mg/kg have been used. 543,546,767
Sedation in Critical Care Settings
Dosage of sedative agents should be titrated to the desired level of sedation; in most cases, a light rather than deep level of sedation is recommended in critically ill mechanically ventilated adults because of improved clinical outcomes that have been demonstrated (e.g., shortened duration of mechanical ventilation, reduced ICU length of stay).800,801 The depth and quality of sedation should be assessed frequently using a validated and reliable assessment tool (e.g., Richmond Agitation-Sedation Scale [RASS], Sedation-Agitation Scale [SAS]).801
If lorazepam is used for sedation in intubated and mechanically ventilated adults in critical care settings†, some experts recommend an IV loading dose of 0.02-0.04 mg/kg (not to exceed 2 mg); the loading dose should be followed by intermittent injections of 0.02-0.06 mg/kg every 2-6 hours as needed or a continuous IV infusion at a rate of 0.01-0.1 mg/kg per hour (not to exceed 10 mg/hour).801 The infusion rate should be titrated to the lowest effective dosage to provide the desired level of sedation.564 Frequent assessment of the patient's sedation requirements and tapering of the infusion rate may prevent prolonged sedative effects.564
Although there is limited information available on the use of lorazepam for sedation in intubated and mechanically ventilated children in critical care settings†, some clinicians have suggested lorazepam dosages of 0.025-0.05 mg/kg (maximum initial dose of 2 mg) given as intermittent IV infusions every 2-4 hours in children 2 months of age or older.565 Alternatively, in these pediatric patients, lorazepam may be administered by a continuous IV infusion, at a rate of 0.025 mg/kg per hour (up to 2 mg/hour) which may be titrated as necessary or supplemented with rapid (“bolus”) injections of the drug to provide the desired level of sedation.565 Because of wide interpatient variations in dosage requirements and low hepatic metabolic function, the initial lorazepam dose should be reduced by 50% in infants younger than 2 months of age.565
Cancer Chemotherapy-induced Nausea and Vomiting
For the management of nausea and vomiting associated with emetogenic cancer chemotherapy†, including that associated with cisplatin, adults have received 2.5 mg of lorazepam orally the evening before and just after initiation of chemotherapy.496 Alternatively,496 adults have received 1.5 mg/m2 (usually up to a maximum dose of 3 mg) of lorazepam administered IV (usually over 5 minutes) 45 minutes before initiation of chemotherapy.
Delirium
For the management of delirium† in combination with haloperidol, combined therapy can be initiated in adults with an IV haloperidol dose of 3 mg followed immediately with an IV lorazepam dose of 0.5-1 mg.533 Dosage of the drugs should then be adjusted according to patient response and tolerance.533 ECG should be determined at baseline and periodically because of the risk of QT prolongation with haloperidol therapy.533 (See Uses: Delirium and also see Dosage: IV Dosage in Haloperidol 28:16.08.32.)
Dosage in Renal and Hepatic Impairment
The manufacturer states that a dosage adjustment is not required in patients with impaired renal function for single doses of lorazepam injection; however, caution should be exercised with administration of multiple doses of lorazepam injection over a short period of time.435
Since the pharmacokinetics of parenteral lorazepam do not appear to be altered in patients with hepatic impairment, dosage adjustment is not necessary in such patients.435 However, because oral lorazepam may exacerbate hepatic encephalopathy, dosage of oral lorazepam should be adjusted carefully in patients with severe hepatic insufficiency and lower than recommended dosages may be sufficient in these patients.283
Cautions ⬆ ⬇
Adverse effects reported with lorazepam are similar to those reported with other benzodiazepines.283 Changes in vital signs (e.g., respiratory rate, blood pressure) are the most frequent adverse effects associated with parenteral lorazepam administration.435 For further information on adverse effects reported with benzodiazepines, see Cautions in the Benzodiazepines General Statement 28:24.08. Flumazenil, a benzodiazepine antagonist, can be used in hospitalized patients as an adjunct, not a substitute for, proper management of lorazepam overdose.435
Precautions and Contraindications
Lorazepam shares the toxic potentials of the benzodiazepines, and the usual precautions of benzodiazepine administration should be observed. (See Cautions in the Benzodiazepines General Statement 28:24.08.)
A boxed warning has been included in the prescribing information for all benzodiazepines describing the risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions associated with all drugs in this class.900 Abuse and misuse can result in overdose or death, especially when benzodiazepines are combined with other medicines, such as opioid pain relievers, alcohol, or illicit drugs.900 Frequent follow-up with patients receiving benzodiazepines is important.900 Reassess patients regularly to manage their medical conditions and any withdrawal symptoms.900 Clinicians should assess a patient's risk of abuse, misuse, and addiction. Standardized screening tools are available ([Web]).900 To reduce the risk of acute withdrawal reactions, use a gradual dose taper when reducing the dosage or discontinuing benzodiazepines.900 Take precautions when benzodiazepines are used in combination with opioid addiction medications.900
Drugs that affect the CNS (e.g., phenothiazines, barbiturates, antidepressants, alcohol, scopolamine, monoamine oxidase inhibitors) may have additive CNS effects when used concomitantly with, or during the period of recovery from, lorazepam. Such combinations, or IV lorazepam used alone in higher than recommended doses, can produce excessive sedation which may result in partial airway obstruction. The manufacturer warns that scopolamine does not provide additional benefit when used concomitantly with lorazepam, but may increase sedation, hallucinations, and irrational behavior.
Concomitant use of benzodiazepines, including lorazepam, and opiate agonists or opiate partial agonists may result in profound sedation, respiratory depression, coma, and death.700,701,703,705,706,707 Patients receiving lorazepam and/or their caregivers should be apprised of the risks associated with concomitant therapeutic or illicit use of benzodiazepines and opiates.700,703 For further information on potential interactions with opiates, see Opiate Agonists and Opiate Partial Agonists under Drug Interactions: CNS Agents, in the Benzodiazepines General Statement 28:24.08.
When lorazepam is administered IV prior to regional or local anesthesia, especially at doses greater than 0.05 mg/kg or when opiate agonists or partial agonists are used concomitantly with recommended lorazepam doses, excessive sedation or drowsiness may occur; these effects may possibly interfere with patient cooperation in determining levels of anesthesia.
Lorazepam should be administered IV only in settings in which continuous monitoring of respiratory and cardiac function (i.e., pulse oximetry) is possible.435 Safety and efficacy of lorazepam may vary according to the dose administered and clinical status of the patient.435 Since lorazepam is capable of producing several levels of CNS depression—from mild to deep sedation, facilities, age- and size-appropriate equipment for bag/mask/valve ventilation and intubation, drugs, and skilled personnel necessary for ventilation and intubation, administration of oxygen, assisted or controlled respiration, airway management, and cardiovascular support should be immediately available whenever this drug is administered.435,566,567 Monitoring of vital signs also should continue during the recovery period.435,566,567 Lorazepam injection should be administered with extreme caution to geriatric or debilitated patients, and to patients with compromised pulmonary function (decreased reserve), since underventilation and/or hypoxic cardiac arrest may occur. For deeply sedated pediatric patients, a dedicated individual other than the clinician performing the procedure should monitor the patient throughout the procedure.566,567
Lorazepam should only be used for the treatment of status epilepticus by clinicians experienced in the comprehensive management of the disease.435 Since these patients may be at increased risk of respiratory depression associated with administration of IV lorazepam, they require careful monitoring of respiratory rate and maintenance of an adequate, patent airway.435 Ventilatory support also may be needed in some patients.435 Because of the prolonged duration of action of lorazepam, it should be considered that the sedative effects of the drug (especially after multiple doses) may increase the impairment of consciousness observed in the postictal state.435
The manufacturer warns that there is no evidence to date to support the use of lorazepam injection in patients with coma, shock, or acute alcohol intoxication. The manufacturer warns that there are insufficient data to support the use of lorazepam injection for outpatient endoscopic procedures; when these procedures are conducted in inpatients, adequate recovery room observation time is necessary and pharyngeal reflex activity should be minimized prior to the procedure by administering adequate topical or regional anesthesia.435
Adverse effects associated with propylene glycol (e.g., lactic acidosis, hyperosmolality, hypotension) or polyethylene glycol (e.g., acute tubular necrosis) may occur in patients receiving lorazepam injection.435 Manifestations of toxicity are more likely to occur in patients with renal impairment and those receiving higher than recommended dosages, although total daily IV doses as low as 1 mg/kg also have been reported to cause propylene glycol toxicity.435,801
Lorazepam injection is not recommended for use in patients with hepatic and/or renal failure, since the drug is most likely conjugated in the liver and since conjugated lorazepam is excreted via the kidneys. However, this does not preclude use of the drug in patients with mild to moderate hepatic or renal disease; in these patients, the lowest possible effective dose of lorazepam injection should be administered since the effects of the drug may be prolonged. The manufacturer states that administration of oral lorazepam may exacerbate hepatic encephalopathy and, therefore, the drug should be used with caution in patients with severe hepatic insufficiency and/or encephalopathy.283 Dosage of lorazepam should be adjusted carefully in patients with severe hepatic insufficiency; lower than recommended dosages may be sufficient in these patients.283 Because of the possibility of suicide in depressed patients, oral lorazepam should not be used in such patients without adequate antidepressant therapy.283,547
Patients should be informed of the pharmacologic effects of lorazepam (e.g., sedation, relief of anxiety, lack of recall) and the duration of these effects (8 hours or longer) so that they may adequately perceive the risks and benefits of use of lorazepam injection. Patients should be warned that lorazepam injection may impair their ability to perform activities requiring mental alertness or physical coordination (e.g., operating machinery, driving a motor vehicle) for 24-48 hours following administration of the drug. Impaired performance may persist for longer periods in geriatric patients, in patients using other drugs concomitantly, and as a result of the stress of surgery or general condition of the patient. Patients also should be warned that premature ambulation (within 8 hours of receiving lorazepam injection) may result in injury from falling. Patients also should be warned that concomitant use of lorazepam with sedatives, opiate analgesics (opiate agonists or partial agonists), or tranquilizers may increase the extent and duration of impaired performance, may cause excessive sedation, and, rarely, may interfere with recall and recognition of events on the day of surgery and the following day. Patients should be advised to abstain from consumption of alcoholic beverages for 24-48 hours following administration of lorazepam injection.
Lorazepam is contraindicated in patients with known hypersensitivity to benzodiazepines or any ingredients in the formulation (i.e., polyethylene glycol, propylene glycol, or benzyl alcohol) and in patients with acute angle-closure glaucoma or sleep apnea syndrome.283,435 Lorazepam injection also is contraindicated in patients with severe respiratory insufficiency, except in those requiring relief of anxiety and/or diminished recall of events while being mechanically ventilated.435 In addition, the injection is contraindicated in premature infants because the formulation contains benzyl alcohol.435
Pediatric Precautions
Safety and efficacy of lorazepam tablets and oral concentrate solution in children younger than 12 years of age have not been established.283
Safety and efficacy of lorazepam injection in pediatric patients younger than 18 years of age have not been established.435
In several open label studies conducted in pediatric patients (neonates as young as a few hours up to adolescents 18 years of age), paradoxical excitation, characterized by tremors, agitation, euphoria, logorrhea, and brief episodes of visual hallucinations, was reported in 10-30% of children younger than 8 years of age.435 Seizures and myoclonus have been reported in pediatric patients (especially in very low birth-weight neonates) receiving lorazepam injection.435 Brief tonic-clonic seizures were reported in pediatric patients who received lorazepam for the management of atypical petit mal status epilepticus.435
FDA warns that repeated or prolonged use of general anesthetics and sedation drugs, including lorazepam, in children younger than 3 years of age or during the third trimester of pregnancy may affect brain development.750,753 Animal studies in multiple species, including nonhuman primates, have demonstrated that use for longer than 3 hours of anesthetic and sedation drugs that block N -methyl-d-aspartic acid (NMDA) receptors and/or potentiate γ-aminobutyric acid (GABA) activity leads to widespread neuronal and oligodendrocyte cell loss and alterations in synaptic morphology and neurogenesis in the brain, resulting in long-term deficits in cognition and behavior.750,751,752,753 Across animal species, vulnerability to these neurodevelopmental changes occurs during the period of rapid brain growth or synaptogenesis; this period is thought to correlate with the third trimester of pregnancy through the first year of life in humans, but may extend to approximately 3 years of age.750 The clinical relevance of these animal findings to humans is not known.750 While some published evidence suggests that similar deficits in cognition and behavior may occur in children following repeated or prolonged exposure to anesthesia early in life, other studies have found no association between pediatric anesthesia exposure and long-term adverse neurodevelopmental outcomes.750,752 Most studies to date have had substantial limitations, and it is not clear whether the adverse neurodevelopmental outcomes observed in children were related to the drug or to other factors (e.g., surgery, underlying illness).750 There is some clinical evidence that a single, relatively brief exposure to general anesthesia in generally healthy children is unlikely to cause clinically detectable deficits in global cognitive function or serious behavioral disorders;750,751,752 however, further research is needed to fully characterize the effects of exposure to general anesthetics in early life, particularly for prolonged or repeated exposures and in more vulnerable populations (e.g., less healthy children).750
Anesthetic and sedation drugs are an essential component of care for children and pregnant women who require surgery or other procedures that cannot be delayed;750,753 no specific general anesthetic or sedation drug has been shown to be less likely to cause neurocognitive deficits than any other such drug.750 Pending further accumulation of data in humans from well-designed studies, decisions regarding the timing of elective procedures requiring anesthesia should take into consideration both the benefits of the procedure and the potential risks.750 When procedures requiring the use of general anesthetics or sedation drugs are considered for young children or pregnant women, clinicians should discuss with the patient, parent, or caregiver the benefits, risks (including potential risk of adverse neurodevelopmental effects), and appropriate timing and duration of the procedure.750,753 FDA states that procedures that are considered medically necessary should not be delayed or avoided.750,753
Lorazepam injection contains benzyl alcohol, polyethylene glycol, and propylene glycol and some pediatric patients (particularly premature and low-birth weight infants or those receiving high doses of the injection) may be susceptible to adverse effects associated with these ingredients.435 Although a causal relationship has not been established, administration of injections preserved with benzyl alcohol has been associated with toxicity in neonates.435,584,585,586,587,588,589,590 Toxicity appears to have resulted from administration of large amounts (i.e., 100-400 mg/kg daily) of benzyl alcohol in these neonates.584,585,586,587,588,589,590 Exposure to such excessive amounts of benzyl alcohol has been associated with CNS depression, metabolic acidosis, gasping respirations, gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse.435 Although use of drugs preserved with benzyl alcohol should be avoided in neonates whenever possible,584,586 the American Academy of Pediatrics (AAP) states that the presence of small amounts of the preservative in a commercially available injection should not proscribe its use when indicated in neonates.584
In pediatric patients, propylene glycol present in high doses of lorazepam injections, has been associated with adverse effects, including CNS toxicity, seizures, intraventricular hemorrhage, unresponsiveness, tachypnea, tachycardia, and diaphoresis.435
Geriatric Precautions
Clinical trials of lorazepam did not include sufficient numbers of patients ≥65 years of age to determine whether they respond differently than younger adults.283,435 However, unless enhanced suppression of recall is desired, patients >50 years of age generally should not be given an initial parenteral lorazepam dose greater than 2 mg since excessive and prolonged sedation may occur.435
No age-related differences in the pharmacokinetics of lorazepam have been identified; however, because of greater sensitivity and increased frequency of impaired hepatic or renal function in geriatric patients, the manufacturer suggests that patients in this age group receive initial dosages of the drug in the lower end of the usual range.283,435 Geriatric patients should be warned that lorazepam injection may cause excessive sedation for 6-8 hours or longer after surgery.435
Pregnancy, Fertility, and Lactation
Pregnancy
Lorazepam may cause fetal toxicity when administered to pregnant women. An increased risk of congenital malformations associated with use of anxiolytic agents (i.e., chlordiazepoxide, diazepam, and/or meprobamate) during the first trimester of pregnancy has been suggested by several human studies. In humans, lorazepam and its glucuronide have been shown to cross the placenta (as determined from samples of umbilical cord blood). The drug has also been shown to cause various adverse fetal effects during reproduction studies in animals. Lorazepam injection should not be used during pregnancy. In addition, the manufacturer does not recommend preoperative use of the injection for obstetric procedures (e.g., cesarean section) or during labor and delivery, since safety of the injection has not been established in such procedures. Oral or injectable lorazepam should be used during pregnancy only in life-threatening situations or severe disease (e.g., status epilepticus) for which safer drugs cannot be used or are ineffective. The possibility that a woman of childbearing potential may be pregnant at the time lorazepam is initiated should be considered.283,435 When lorazepam is administered during pregnancy or if the patient becomes pregnant while receiving the drug, the patient should be advised of the potential hazard to the fetus and about the desirability of discontinuing lorazepam.283
Based on animal data, repeated or prolonged use of general anesthetics and sedation drugs, including lorazepam, during the third trimester of pregnancy may result in adverse neurodevelopmental effects in the fetus.750,753 The clinical relevance of these animal findings to humans is not known; the potential risk of adverse neurodevelopmental effects should be considered and discussed with pregnant women undergoing procedures requiring general anesthetics and sedation drugs.750 (See Cautions: Pediatric Precautions.)
Fertility
It is not known whether lorazepam affects fertility in humans. No evidence of impaired fertility was observed in rats following oral administration of lorazepam doses of 20 mg/kg. At doses of 40 mg/kg or more, there was evidence of fetal resorption and increased fetal loss in rabbits.
Lactation
Lorazepam is distributed into milk. The potential exists that lorazepam can cause sedation or other adverse effects in nursing infants.435 The manufacturer of oral lorazepam states that the drug should not be administered to nursing women unless the potential benefits to the woman outweigh the possible risk to the infant.283 Nursing infants receiving oral lorazepam should be monitored for adverse effects (e.g., sedation, irritability).283 The manufacturer of lorazepam injection states that the drug should not be administered to nursing women because of possible adverse effects (e.g., sedation).435
Other Information ⬆ ⬇
Chemistry and Stability
Chemistry
Lorazepam is a benzodiazepine.
Stability
Lorazepam oral concentrate solution and lorazepam injection should be stored at 2-8°C and protected from light.435,547 Lorazepam tablets should be stored in well-closed containers at 25°C, but may be exposed to temperatures of 15-30°C.283
The manufacturer states that lorazepam injection should be diluted prior to IV administration with an equal volume of compatible diluent, including 0.9% sodium chloride injection or 5% dextrose injection.435 Solutions of lorazepam should not be used if they are discolored or contain a precipitate.435
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Preparations ⬆ ⬇
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Lorazepam is subject to control under the Federal Controlled Substances Act of 1970 as a schedule IV (C-IV) drug.
LORazepam
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|
Oral | For solution, concentrate | 2 mg/mL* | LORazepam Solution Concentrate (C-IV) | |
| Tablets | 0.5 mg* | Ativan® (C-IV) | Valeant |
| | | LORazepam Tablets ( C-IV ) | |
| | 1 mg* | Ativan® (C-IV; scored) | Valeant |
| | | LORazepam Tablets ( C-IV ) | |
| | 2 mg* | Ativan® (C-IV; scored) | Valeant |
| | | LORazepam Tablets ( C-IV ) | |
Parenteral | Injection | 2 mg/mL* | Ativan® (C-IV) | West-Ward |
| | | LORazepam Injection (C-IV) | |
| | 4 mg/mL* | Ativan® (C-IV) | West-Ward |
| | | LORazepam Injection ( C-IV ) | |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Copyright ⬆ ⬇
AHFS® Drug Information. © Copyright, 1959-2024, Selected Revisions June 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
† Use is not currently included in the labeling approved by the US Food and Drug Administration.
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