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Lorazepam
Noman Ghiasi; Raman Marwaha.

Author Information
Last Update: December 23, 2018.

Indications
Lorazepam is a benzodiazepine medication developed by DJ Richards. It went on the market in
the United States in 1977. Lorazepam is commonly used as the sedative and anxiolytic of choice
in the inpatient setting owing to its fast (1 to 3 minute) onset of action when administered
intravenously.[1] Lorazepam is also one of the few sedative-hypnotics with a relatively clean side
effect profile. Lorazepam is FDA approved for short-term (4 months) relief of anxiety symptoms
related to anxiety disorders, anxiety-associated insomnia, anesthesia premedication in adults to
relieve anxiety or to produce sedation/amnesia, and treatment of status epilepticus.[2] Off-label
(non-FDA-approved) uses for Lorazepam include rapid tranquilization of the agitated patient,
alcohol withdrawal delirium, alcohol withdrawal syndrome, insomnia, panic disorder, delirium,
chemotherapy-associated anticipatory nausea and vomiting (adjunct or breakthrough), as well as
psychogenic catatonia.[3]

Mechanism of Action
Lorazepam binds to benzodiazepine receptors on the postsynaptic GABA-A ligand-gated
chloride channel neuron at several sites within the central nervous system (CNS) and enhances
the inhibitory effects of GABA, which increases the conductance of chloride ions into the cell.
This shift in chloride ions results in hyperpolarization and stabilization of the cellular plasma
membrane.[4] Its inhibitory action in the amygdala helps with anxiety disorders while its
inhibitory action in the cerebral cortex helps in seizure disorders.

Administration
Lorazepam has an 85% bioavailability when taken by mouth and is metabolized in the liver by
glucuronidation using the CYP450 enzymes and has a half-life of 14 hours.[5] Lorazepam can be
administered orally, intravenously (IV), or intramuscularly (IM). The onset of its action is 1 to 3
minutes if administered IV and 15 to 30 minutes if administered IM. Lorazepam reaches its peak
plasma time in 2 hours if administered orally.

Anxiety disorder: Initial starting dose: 2 mg to 3 mg by mouth, can repeat dose 2 to 3 times per
day Maximum dosage 10 mg per day.[6]

Insomnia due to anxiety or stress: In patients less than 65 years of age: 0.5 to 2 mg at bedtime In
patients over 65 years age: 0.5 to 1 mg at bedtime.

Premedication for anesthesia: IM 0.05 mg/kg administered 2 hours prior to surgery (maximum
dose 4 mg); IV 0.044 mg/kg administered 15 to 20 minutes prior to surgery (maximum dose 4
mg). Note: In patients older than 50 years of age, maximum dosage is 2 mg.[7]

Status epilepticus: IV 0.1 mg/kg (maximum dose 4 mg), at a maximum rate of 2 mg per minute;
may repeat in 5 to 10 minutes Note: Must dilute dose with 1:1 saline.

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Agitation in the intensive care unit (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 per hour with a maximum dosing of less than 10 mg per hour.

Alcohol withdrawal delirium (off-label use: IV 1 to 4 mg every 5 to 15 minutes until the patient
is calm; Can repeat every hour as need; IM 1 to 4 mg every 30 to 60 minutes until the patient is
calm; Can repeat every hour as needed.[8]

Alcohol withdrawal syndrome (off-label use): Symptom-triggered regimen: Oral, IM, IV 2 mg to

4 mg per hour as needed; dose must be determined by the severity assessment scale. Fixed-dose
regimen: Oral, IM, IV 2 mg every 6 hours for 4 doses, followed by 1 mg every 6 hours for 8
additional doses. Note: Symptom-triggered regimen is preferred over the fixed-dose regimens;
lower doses and shorter duration of treatment are needed.

For chemotherapy-associated nausea and vomiting (off-label use): For breakthrough

nausea/vomiting or as an adjunct to standard antiemetics oral, IV, sublingual: 0.5 to 2 mg every 6
hours as needed.

For psychogenic catatonia (off-label use): IM 1 mg to 2 mg; can repeat dose in 3 hours then
again in another 3 hours if initial and subsequent doses are ineffective; Oral, IM, IV: Initially 1
mg and may repeat in 5 minutes if necessary. If the initial challenge is unsuccessful, may
increase the dose up to 4 to 8 mg per day and may continue treatment for up to 5 days.[9]

Adverse Effects
Like most benzodiazepines, adverse reactions to lorazepam include CNS and respiratory
depression, which are dose-dependent. More severe effects occur with high doses.[10]

Serious adverse effects of lorazepam include:

Respiratory depression

Respiratory failure

Seizures suicidality

Dependency and abuse

Tachycardia

Hypotension

Syncope

Blood dyscrasias

Jaundice

Paradoxical reaction; hyperactive and aggressive behavior

Gangrene (intra-arterial)

Withdrawal symptoms if abruptly discontinued after long-term use.

Cognitive deficits

Behavioral changes

Common adverse effects of lorazepam include:

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Sedation

Dizziness

Asthenia

Ataxia

Local injection site reaction

Respiratory depression

Hypoventilation with IV use

Hypotension

Fatigue

Amnesia

Confusion

Disinhibition

Irritability

Libido changes

Menstrual irregularities

Diplopia

Dysarthria

Appetite changes

Constipation

Incontinence

Urinary retention

Dystonia

AST and ALT elevation

Contraindications
Lorazepam is contraindicated in patients with an anaphylactic reaction to lorazepam, any
component of the formulation, other benzodiazepines (cross-sensitivity with other
benzodiazepines may exist), intra-arterial administration, use in neonates or infants, severe
respiratory impairment (except during mechanical ventilation), pregnancy (third trimester), and
acute narrow-angle glaucoma, severe respiratory insufficiency.[11] Additional contraindications
include Hypersensitivity to polyethylene glycol, propylene glycol, or benzyl alcohol, and sleep
apnea. It can cause “floppy infant syndrome” due to neonatal withdrawal.

Monitoring
Monitor respiratory and cardiovascular status, blood pressure, heart rate, and symptoms of
anxiety. With Long-term therapy, monitor CBC, liver function tests, and LDH. With high-dose or
continuous IV use or IV use in patients with renal impairment, monitor clinical signs of

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propylene glycol toxicity, serum creatinine, BUN, serum lactate, and osmolality gap. With
critically ill patients, monitor the depth of sedation. Lorazepam is a Schedule IV drug and
patients may develop dependence and tolerance with long-term use. It is recommended to use the
lowest possible effective dose for the shortest period. When stopping Lorazepam, it should be
tapered by 0.5 mg every 3 days to avoid withdrawal symptoms.[12]

Toxicity
Lorazepam can cause CNS and respiratory depression in overdose. It can lead to hypotension,
ataxia, confusion, coma and can be fatal. Concurrent use of benzodiazepines and opioids may
result in profound sedation, respiratory depression, coma, and death.[13] Concomitant
prescribing of benzodiazepines and opioids must be reserved for patients for whom alternative
treatment options are inadequate. Dosages and durations of Lorazepam must be limited to the
minimum required. Patients must be followed for signs and symptoms of respiratory depression.
Lorazepam, as with other benzodiazepines, is rarely associated with elevations in serum ALT,
and clinically apparent liver injury from lorazepam is extremely rare.[14] The clinical pattern of
acute liver injury from benzodiazepines is typically cholestatic. Flumazenil is used as an antidote
to benzodiazepine toxicity.[15] Flumazenil competes with benzodiazepines for binding at the
GABA/benzodiazepine receptor complex. Abrupt awakening can cause dysphoria, agitation, and
increased adverse effects.[16] If it is administered to patients who have received a
benzodiazepine chronically, abrupt interruption of benzodiazepine antagonism by flumazenil can
induce benzodiazepine withdrawal including seizures. Flumazenil has minimal effects on
benzodiazepine-induced respiratory depression, and suitable ventilatory support should be
available in treating acute benzodiazepine overdose.[17]

Enhancing Healthcare Team Outcomes

Lorazepam, like other benzodiazepine medications, is a highly addictive medication. Great care
must be taken when prescribing lorazepam at high doses or prolonged durations, particularly in
patients with a history of substance use disorder or concurrent opioid prescriptions. Managing
such patients requires an inter-professional team of healthcare professionals that include nurses,
pharmacists, and a number of specialist physicians to monitor for signs of abuse, diversion or
concomitant use with other prescription or non-prescription sedative medications. Prescribing
physicians must be vigilant in prescribing benzodiazepine such as lorazepam and make use of
State and Federal controlled substance monitoring and diversion databases to identify high-risk
patients with multiple and frequent prescriptions for benzodiazepines, opioids, muscle relaxants,
and other sedative-hypnotics.

Questions
To access free multiple choice questions on this topic, click here.

Figure

Lorazepam chemical structure. Contributed from the Public

Domain

References
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