Is Ativan (lorazepam) safe?

Is Ativan (Lorazepam) Safe?

Lorazepam is safe when used appropriately for short-term treatment (up to 4 months) in carefully selected patients, but carries significant risks including respiratory depression when combined with opioids, propylene glycol toxicity with IV formulations, physical dependence, cognitive impairment, and severe withdrawal reactions—making it contraindicated in patients with severe respiratory insufficiency, severe liver disease, and myasthenia gravis. 1

Critical Safety Concerns

Life-Threatening Drug Interactions

• Combining lorazepam with opioids can cause fatal respiratory depression, coma, and death 1
• The FDA mandates a black box warning for concomitant use with opioids due to synergistic respiratory depression 1
• Extreme caution is required with concurrent use of alcohol, barbiturates, antipsychotics, or other CNS depressants, which significantly worsen sedation and respiratory depression 1
• Fatalities have been reported when benzodiazepines are combined with high-dose olanzapine 2

Absolute Contraindications

• Severe pulmonary insufficiency (COPD, sleep apnea) due to dose-dependent respiratory depression 2, 1
• Severe liver disease, as lorazepam clearance is significantly reduced in hepatic dysfunction and can worsen hepatic encephalopathy 2, 1
• Myasthenia gravis, except in imminently dying patients 2
• Known allergy to lorazepam or other benzodiazepines 1

Propylene Glycol Toxicity (IV Formulation)

• Parenteral lorazepam contains propylene glycol, which can cause metabolic acidosis and acute kidney injury 2
• Toxicity can occur with total daily IV doses as low as 1 mg/kg, not just high-dose continuous infusions 2
• Monitor serum osmol gap: values >10-12 mOsm/L indicate significant propylene glycol accumulation 2

High-Risk Populations Requiring Dose Reduction

Elderly Patients

• Elderly patients have significantly increased sensitivity to benzodiazepines due to decreased clearance 3, 1
• The American Academy of Family Physicians recommends initiating treatment with doses approximately 50% lower than those for young adults 3
• Initial dosage should not exceed 2 mg in elderly or debilitated patients 1
• Higher risk of falls, cognitive decline, and paradoxical agitation in elderly patients 4, 3

Renal Insufficiency

• The elimination half-life and duration of clinical effect are increased in patients with renal failure 3, 2
• Patients with renal insufficiency require careful monitoring and dose adjustments 3

Hepatic Impairment

• For patients with advanced liver disease, the initial dose should be reduced to 0.25 mg orally 2-3 times daily 4
• Delayed emergence from sedation occurs due to prolonged elimination half-life 2

Respiratory Compromise

• Use lower doses (0.25-0.5 mg) in patients with COPD 2
• Baseline respiratory insufficiency significantly increases risk of benzodiazepine-induced respiratory depression 2

Addiction and Dependence Risks

Abuse Potential

• Lorazepam is a Schedule IV controlled substance with risk of abuse, misuse, and addiction even at prescribed doses 1
• Regular use can lead to tolerance, addiction, depression, and cognitive impairment 4
• Serious side effects from abuse include delirium, paranoia, suicidal thoughts, seizures, and difficulty breathing 1

Physical Dependence and Withdrawal

• Abrupt discontinuation can cause life-threatening withdrawal reactions including seizures, severe mental changes, and suicidal thoughts 1
• Protracted withdrawal syndrome can last weeks to more than 12 months with symptoms including anxiety, cognitive impairment, depression, insomnia, paresthesias, and tinnitus 1
• Withdrawal symptoms include rebound insomnia that can be several times worse than baseline sleep disturbance 5, 6
• Rebound anxiety occurs during withdrawal, with subjective daytime anxiety increasing above baseline levels 5, 6

Common Adverse Effects

Central Nervous System

• Most common side effects include sedation, dizziness, weakness, and unsteadiness 1
• Approximately 10% of patients experience paradoxical agitation 4, 2
• Anterograde amnesia is a reliable effect, particularly useful in anesthesia settings but problematic in other contexts 7, 6
• Episodes of memory impairment and confusion can occur 5
• Pre-existing depression may emerge or worsen during benzodiazepine use 1

Cardiovascular

• Patients with cardiovascular instability are at high risk for benzodiazepine-induced systemic hypotension, especially when combined with other cardiopulmonary depressants 2
• Hemodynamically unstable patients should avoid loading doses entirely 2

Appropriate Clinical Use

Approved Indications and Duration

• FDA-approved for treating anxiety disorders and short-term relief of anxiety symptoms or anxiety with depression 1
• Safety and effectiveness beyond 4 months of use is not established 1
• Safety and effectiveness in children less than 12 years of age is not established 1

Pediatric Emergency Use

• For status epilepticus in children: 0.1-0.3 mg/kg IV every 5-10 minutes (maximum 10 mg per dose) administered over approximately 2 minutes 8
• For pediatric status epilepticus: 0.05-0.10 mg/kg IV over 2 minutes (maximum single dose 5 mg) 4
• Lorazepam may be preferred over diazepam for status epilepticus due to prolonged duration of anticonvulsant activity 8

Adjunctive Use in Oncology

• The National Comprehensive Cancer Network recommends 0.25-0.5 mg orally three times daily for anticipatory nausea/vomiting in oncology patients 4
• For delirium/agitation in oncology: 1 mg subcutaneously or IV (maximum 2 mg), with reduced doses for elderly, frail, or COPD patients 4
• Lorazepam is useful as an adjunct to antiemetic drugs but not recommended as a single-agent antiemetic 8

Pregnancy and Breastfeeding

• Lorazepam may harm the unborn baby; risk-benefit discussion required 1
• Lorazepam passes into breast milk and may harm the baby; breastfeeding is not recommended while taking lorazepam 1

Clinical Monitoring Requirements

Laboratory Monitoring

• Some patients develop leukopenia and elevated LDH 1
• Periodic blood counts and liver function tests are recommended for patients on long-term therapy 1
• Monitor serum osmol gap for propylene glycol toxicity with IV formulations 2

Clinical Monitoring

• Elderly or debilitated patients should be monitored frequently with careful dosage adjustment according to patient response 1
• Monitor for signs of respiratory depression, especially when combined with opioids or other CNS depressants 1
• Watch for paradoxical reactions, which may be more likely in children and elderly; discontinue if these occur 1

Key Clinical Pitfalls to Avoid

• Never abruptly discontinue lorazepam—taper slowly to prevent life-threatening withdrawal 1
• Never combine with opioids without close supervision—risk of fatal respiratory depression 1
• Do not use in patients with severe respiratory disease—risk of respiratory arrest 2, 1
• Avoid long-term use beyond 4 months—efficacy and safety not established 1
• Do not use in outpatient settings or patients with expected hospital stay <72 hours due to prolonged duration of action 7
• Recognize that tolerance develops with long-term use, requiring higher doses for the same effect 2