What are the contraindications for lorazepam (Ativan)?

Contraindications for Lorazepam

Lorazepam is absolutely contraindicated in patients with hypersensitivity to benzodiazepines or any formulation components, and in those with acute narrow-angle glaucoma. 1

Absolute Contraindications

• Hypersensitivity to benzodiazepines or any components of the lorazepam formulation 1
• Acute narrow-angle glaucoma 1

Critical Clinical Situations Requiring Extreme Caution (Relative Contraindications)

Severe Pulmonary Insufficiency

• Baseline respiratory insufficiency significantly increases risk of benzodiazepine-induced respiratory depression, particularly when lorazepam is combined with opioids or other CNS depressants 2, 3
• Respiratory depression is dose-dependent and more pronounced with concurrent sedative or opioid administration 3
• Use lower doses (0.25–0.5 mg) in patients with COPD or when co-administered with antipsychotics 2

Severe Liver Disease

• All benzodiazepines are metabolized by the liver, and lorazepam clearance is significantly reduced in patients with hepatic dysfunction 2, 3
• Delayed emergence from sedation occurs with hepatic impairment due to prolonged elimination half-life 3
• Benzodiazepines should be used with extreme caution in severe liver disease 2

Myasthenia Gravis

• Benzodiazepines should be avoided in patients with myasthenia gravis (unless using in imminently dying patient) 2

Cardiovascular Instability

• Patients with cardiovascular instability are at high risk for benzodiazepine-induced systemic hypotension, especially when lorazepam is administered with other cardiopulmonary depressants 3
• Hemodynamically unstable patients should avoid loading doses entirely 3

Renal Failure

• The elimination half-life and duration of clinical effect are increased in patients with renal failure 3
• Prolonged effects occur with renal dysfunction, requiring dose adjustments 3

Elderly Patients

• Elderly patients are significantly more sensitive to sedative effects of benzodiazepines 3
• Benzodiazepine clearance decreases with age 3
• Benzodiazepines should be avoided in older patients with cognitive impairment due to documented decreased cognitive performance 3
• Use lower doses (0.25–0.5 mg) in older or frail patients 2

Critical Safety Concern: Propylene Glycol Toxicity

• Parenteral lorazepam contains propylene glycol, which can cause metabolic acidosis and acute kidney injury in ICU patients 3
• Total daily IV doses as low as 1 mg/kg can cause propylene glycol toxicity (not just high-dose continuous infusions) 3
• Monitor serum osmol gap: values >10-12 mOsm/L indicate significant propylene glycol accumulation 3

Dangerous Drug Interactions

Concurrent Use with Olanzapine

• Fatalities have been reported with concurrent use of benzodiazepines with high-dose olanzapine 2
• Risk of oversedation and respiratory depression when combining with benzodiazepines 2

Opioid Co-Administration

• Extreme caution with opioid co-administration due to synergistic respiratory depression and hypotension 3

Cytochrome P450 Inhibitors

• Avoid concurrent use with medications that inhibit cytochrome P450 enzyme systems or glucuronide conjugation, as this reduces benzodiazepine clearance 3

Common Clinical Pitfalls

• Paradoxical agitation occurs in approximately 10% of patients treated with benzodiazepines 3
• Lorazepam may cause delirium, drowsiness, and paradoxical agitation 2
• Tolerance develops with long-term administration, requiring higher doses to achieve the same effect 3
• Cognitive impairment is associated with long-term use 3
• Marked rebound insomnia and anxiety occur following drug withdrawal, with peak withdrawal sleep disturbance several times greater than peak sleep improvement during drug administration 4, 5
• Episodes of memory impairment and confusion can occur 4
• Increased risk of falls in all patients, particularly elderly 2