Lorazepam

# Lorazepam ## Overview - **Classification**: Benzodiazepine, Anxiolytic, Sedative-hypnotic, Anticonvulsant - **Mechanism**: Enhances the inhibitory effect of Gamma-aminobutyric acid (GABA) at the GABA-A receptor, leading to increased chloride ion influx, neuronal hyperpolarization, and decreased neuronal excitability. ## Primary Indications 1. **Anxiety Disorders** - Short-term relief of anxiety symptoms or anxiety associated with depressive symptoms. 2. **Insomnia** - Short-term treatment of insomnia due to anxiety or transient situational stress. 3. **Status Epilepticus** - Acute treatment of convulsive status epilepticus (IV route). 4. **Premedication** - Sedation, anxiolysis, and anterograde amnesia before surgical or diagnostic procedures. 5. **Chemotherapy-Induced Nausea and Vomiting (CINV)** - Adjunct for acute or anticipatory CINV. ## Adult Dosing ### Standard Dosing **Anxiety** - **Dose**: Oral **0.5 mg - 2 mg** - **Frequency**: 2-3 times daily - **Route**: Oral - **Duration**: Short-term, usually 2-4 weeks; assess need for continued use. **Insomnia** - **Dose**: Oral **0.5 mg - 2 mg** - **Frequency**: Once at bedtime - **Route**: Oral **Status Epilepticus** - **Dose**: IV **4 mg** (initial dose) - **Frequency**: May repeat once after 10-15 minutes if seizures persist - **Route**: Intravenous (IV), administered slowly over 2-5 minutes - **Maximum Dose**: **8 mg** total for a single episode **Preprocedural Sedation** - **Dose**: IV **2-4 mg** or **0.05 mg/kg** (whichever is less) - **Frequency**: Single dose - **Route**: IV, 30-45 minutes before procedure; IM **0.05 mg/kg** up to **4 mg**, 2 hours before procedure. - **Maximum Dose**: **4 mg** per dose. **Chemotherapy-Induced Nausea and Vomiting (CINV) Adjunct** - **Dose**: Oral/IV **0.5 mg - 2 mg** - **Frequency**: Every 4-6 hours PRN - **Route**: Oral or IV ### Dose Adjustments - **Renal Impairment**: No specific dose adjustment generally needed. Use with caution; start low, titrate slowly. - **Hepatic Impairment**: Reduce initial dose by **50%** and monitor closely. Lorazepam undergoes glucuronidation, which is less affected by liver dysfunction than oxidative metabolism. - **Elderly Patients**: Start with the **lowest effective dose** (e.g., **0.5 mg** initially). Increased risk of sedation, dizziness, falls, and paradoxical reactions. Titrate very slowly. ## Pediatric Dosing ### Neonates (0-28 days) - **Status Epilepticus**: Use with extreme caution, not preferred. If used, IV **0.05 mg/kg**. - **Frequency**: Single dose - **Maximum**: **2 mg** per dose - **Special Notes**: Propylene glycol toxicity risk with IV formulation; careful monitoring is essential. Alternatives are preferred. ### Infants (1-12 months) - **Status Epilepticus**: IV **0.05-0.1 mg/kg** over 2-5 minutes. - **Frequency**: May repeat once after 10-15 minutes. - **Maximum**: **4 mg** per dose; total max **0.2 mg/kg** or **8 mg**. ### Children (1-12 years) - **Status Epilepticus**: IV **0.05-0.1 mg/kg** over 2-5 minutes. - **Frequency**: May repeat once after 10-15 minutes. - **Maximum**: **4 mg** per dose; total max **0.2 mg/kg** or **8 mg**. - **Anxiety/Sedation (Oral)**: **0.05 mg/kg/dose** (max **2 mg**) once or divided daily. Not for long-term use. ### Adolescents (13-18 years) - **Dose**: Initiate with the lower end of adult dosing, e.g., Oral **0.5-1 mg**. - **Maximum**: Follow adult maximum doses, up to **10 mg/day** for anxiety. - **Special Notes**: Consider lowest effective dose due to potential for greater sensitivity. ## Safety Information ### Contraindications - **Absolute**: Hypersensitivity to benzodiazepines or any component of the formulation. - **Absolute**: Acute narrow-angle glaucoma. - **Absolute**: Severe respiratory insufficiency or sleep apnea (for oral). - **Absolute**: Myasthenia gravis (due to muscle relaxant properties). - **Absolute**: Co-administration with opioids (due to risk of profound sedation, respiratory depression, coma, and death). ### Common Adverse Effects - **Very Common (>10%)**: Sedation, drowsiness, fatigue, weakness. - **Common (1-10%)**: Dizziness, ataxia, blurred vision, unsteadiness, confusion, disorientation, slurred speech. - **Serious but Rare**: Respiratory depression, paradoxical reactions (excitement, aggression), anterograde amnesia, dependence, withdrawal seizures (upon abrupt discontinuation). ### Key Drug Interactions - **CNS Depressants (e.g., opioids, alcohol, barbiturates, antidepressants, antihistamines)**: Potentiates sedative and respiratory depressant effects. Avoid concomitant use or use lowest possible doses with careful monitoring. - **Valproic Acid / Probenecid**: May inhibit lorazepam metabolism, increasing its serum levels and effects. Reduce lorazepam dose by **50%** when co-administered. - **Theophylline**: May decrease the sedative effects of lorazepam. ## Monitoring & Follow-up - **Before Treatment**: Assess baseline mental status, respiratory status, and fall risk. - **During Treatment**: - Monitor sedation level, respiratory rate, blood pressure (especially with IV administration). - Observe for paradoxical reactions (agitation, aggression). - Assess for signs of tolerance or dependence with prolonged use. - **Clinical Signs**: Look for excessive drowsiness, slurred speech, ataxia, confusion, and respiratory depression. ## Clinical Pearls - 💡 **IV Lorazepam Administration**: Must be diluted with an equal volume of compatible diluent (NS, D5W, SWFI) immediately prior to IV use. Administer slowly (not > **2 mg/minute** for adults) to avoid adverse effects related to propylene glycol (e.g., metabolic acidosis, renal dysfunction). - 💡 **Abrupt Discontinuation**: Avoid abrupt discontinuation after prolonged use, especially at high doses, to prevent severe withdrawal symptoms (seizures, psychosis). Taper slowly. - 💡 **Antidote**: Flumazenil is a benzodiazepine receptor antagonist, but its use carries a risk of inducing acute withdrawal seizures, especially in chronic users. Use with extreme caution. - 💡 **Amnesia**: May cause anterograde amnesia, particularly at higher doses, making it useful for procedural sedation. Counsel patients accordingly. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.