Lorazepam
Lorazepam is a intermediate-acting benzodiazepine indicated for the management of anxiety disorders and short-term relief of anxiety symptoms. It is also used for preoperative sedation and status epilepticus treatment. Its intermediate duration of action and reliable absorption make it a preferred benzodiazepine in many clinical situations.
Clinical Overview
Primary Clinical Applications
Lorazepam is effective for generalized anxiety disorder, panic disorder, and situational anxiety. It is also commonly used in hospital settings for acute agitation, alcohol withdrawal, and as preoperative medication. Its predictable pharmacokinetics make it suitable for both acute and short-term chronic use.
Mechanism and Onset
Lorazepam enhances GABA activity at benzodiazepine receptors, producing anxiolytic, sedative, and anticonvulsant effects. Oral absorption is reliable with onset in 1-2 hours, while IV administration provides immediate effects for emergency situations.
Clinical Advantages
Unlike some benzodiazepines, lorazepam is not significantly affected by hepatic impairment and has no active metabolites, making it safer in elderly patients and those with liver disease.
Key Clinical Points
No active metabolites
Lorazepam undergoes direct glucuronidation rather than oxidative metabolism, so it produces no active metabolites and does not accumulate the way diazepam or chlordiazepoxide do.
Safe in hepatic impairment
Because it bypasses the cytochrome P450 system, no dose adjustment is needed in liver disease. This makes it the benzodiazepine of choice in alcohol withdrawal complicated by hepatic dysfunction.
Intravenous route for status epilepticus
Reliable oral absorption with onset in one to two hours, and immediate effect intravenously, which is why it features in status epilepticus protocols alongside its anxiolytic uses.
Contraindicated in myasthenia gravis
Also contraindicated in acute narrow-angle glaucoma, sleep apnoea syndrome, and severe respiratory insufficiency. Carries the class boxed warning for dependence and opioid co-administration.
Start at 0.5 to 1 mg daily in older adults
Falls and cognitive impairment remain significant despite the favourable metabolic profile. Pregnancy Category D, and the drug enters breast milk.
Prescribing Information
Dosing & Administration
Anxiety Disorders – Adults:
- Initial: 2-3 mg daily in divided doses (0.5-1 mg 2-3 times daily)
- Range: 1-10 mg daily in divided doses
- Maximum: 10 mg daily
Elderly or Debilitated:
- Initial: 0.5-1 mg daily in divided doses
- Titrate slowly based on response and tolerance
Insomnia (short-term):
- Dose: 2-4 mg at bedtime
Preoperative Sedation:
- IM: 0.05 mg/kg (maximum 4 mg) 2 hours before surgery
- IV: 0.044 mg/kg (maximum 2 mg) 15-20 minutes before surgery
Indications
- Anxiety disorders
- Short-term relief of anxiety symptoms
- Anxiety associated with depression
- Preoperative sedation
- Status epilepticus (IV)
Contraindications
- Hypersensitivity to benzodiazepines
- Acute narrow-angle glaucoma
- Sleep apnea syndrome
- Severe respiratory insufficiency
- Myasthenia gravis
Warnings & Precautions
- Boxed Warning: Risk of abuse, misuse, dependence; respiratory depression when combined with opioids
- Physical and psychological dependence with prolonged use
- Withdrawal syndrome with abrupt discontinuation
- Cognitive impairment and falls risk in elderly
- Respiratory depression, especially with concurrent CNS depressants
Drug Interactions
- Opioids: Increased risk of respiratory depression and death
- CNS depressants: Enhanced sedation and respiratory depression
- Alcohol: Dangerous potentiation of effects
- Probenecid: May increase lorazepam levels
Adverse Reactions
Common (>10%):
- Sedation, dizziness, weakness, unsteadiness
Cognitive:
- Memory impairment, confusion, depression
Serious:
- Respiratory depression, paradoxical reactions, dependence
Special Populations
- Elderly: Start with 0.5-1 mg daily, increased fall risk
- Hepatic Impairment: No dose adjustment needed (not hepatically metabolized)
- Pregnancy: Category D – avoid in pregnancy
- Lactation: Enters breast milk, use caution
Frequently Asked Questions
What is Lorazepam used for?
Lorazepam is a intermediate-acting benzodiazepine indicated for the management of anxiety disorders and short-term relief of anxiety symptoms. It is also used for preoperative sedation and status epilepticus treatment. Its intermediate duration of action and reliable absorption make it a preferred benzodiazepine in many clinical situations.
What class of drug is Lorazepam?
Lorazepam is classified as: Benzodiazepine.
No active metabolites?
Lorazepam undergoes direct glucuronidation rather than oxidative metabolism, so it produces no active metabolites and does not accumulate the way diazepam or chlordiazepoxide do.
Safe in hepatic impairment?
Because it bypasses the cytochrome P450 system, no dose adjustment is needed in liver disease. This makes it the benzodiazepine of choice in alcohol withdrawal complicated by hepatic dysfunction.
Intravenous route for status epilepticus?
Reliable oral absorption with onset in one to two hours, and immediate effect intravenously, which is why it features in status epilepticus protocols alongside its anxiolytic uses.
Contraindicated in myasthenia gravis?
Also contraindicated in acute narrow-angle glaucoma, sleep apnoea syndrome, and severe respiratory insufficiency. Carries the class boxed warning for dependence and opioid co-administration.
Source: FDA prescribing information (DailyMed)