Lozicum

Approved Indications:

• Anxiety Disorders: Management of generalized anxiety disorder (GAD) and short-term relief of anxiety symptoms.
• Insomnia Associated with Anxiety or Stress: Short-term treatment of sleep disturbances caused by anxiety or situational stress.
• Premedication for Anesthesia or Procedures: Used to relieve anxiety, induce sedation, and produce anterograde amnesia prior to surgery or diagnostic procedures.
• Status Epilepticus: First-line intravenous treatment for acute convulsive status epilepticus.
• Sedation in Intensive Care Units (ICU): For managing agitation or facilitating mechanical ventilation.

Clinically Accepted Off-Label Uses:

• Alcohol Withdrawal Syndrome: Adjunctive treatment for agitation, tremors, or seizures related to alcohol withdrawal.
• Chemotherapy-Induced Nausea and Vomiting (CINV): Used as an adjunct in combination with antiemetics to reduce anticipatory or breakthrough nausea.
• Acute Agitation in Psychiatric Disorders: Temporary management of agitation in schizophrenia or bipolar mania.

Adults:

• Anxiety:
• Oral: 1–3 mg per day in 2–3 divided doses.
• Usual range: 2–6 mg/day. Maximum: 10 mg/day.
• Insomnia Due to Anxiety:
• Oral: 2–4 mg at bedtime.
• Premedication:
• Oral: 2–4 mg the night before and/or 1–2 hours before the procedure.
• IM: 0.05 mg/kg (usual dose: 2 mg) 1 hour before procedure.
• IV: 0.044 mg/kg (max 2 mg) 15–20 minutes prior to procedure.
• Status Epilepticus:
• IV: 4 mg at a rate of 2 mg/min; may repeat once after 10–15 minutes if seizures persist.

Pediatrics (≥12 years):

• Short-term Anxiety Treatment: 0.05 mg/kg/dose orally 2–3 times daily; max 2–3 mg/day.
• Premedication:
• IM: 0.05 mg/kg (max 4 mg).
• IV: 0.044 mg/kg slowly over several minutes.

Geriatric Patients:

• Initiate at 0.25–0.5 mg orally 2–3 times daily.
• Use caution due to increased sensitivity and fall risk.

Renal Impairment:

• No specific dosage adjustment, but monitor closely.

Hepatic Impairment:

• Use with caution; consider lower doses and extended intervals due to decreased clearance.

Routes of Administration: Oral, intravenous (IV), intramuscular (IM)
Frequency: 2–3 times daily (oral); single or repeated IV doses as needed
Duration: Use for the shortest duration possible; reassess regularly

Lorazepam is a benzodiazepine that enhances the effect of gamma-aminobutyric acid (GABA), the brain’s main inhibitory neurotransmitter. It binds to specific benzodiazepine sites on the GABA-A receptor complex, increasing the opening frequency of chloride channels, leading to membrane hyperpolarization. This results in anxiolytic, sedative-hypnotic, anticonvulsant, and muscle-relaxant effects. Lorazepam also impairs short-term memory formation (anterograde amnesia), which is useful during medical procedures.

• Absorption: Rapid and complete oral absorption; peak plasma levels reached in approximately 2 hours.
• Bioavailability: Oral bioavailability ≈ 90%.
• Distribution: Highly lipophilic; 85–90% protein-bound.
• Metabolism: Metabolized in the liver via glucuronidation to inactive metabolites.
• Half-life: 10–20 hours (longer in elderly and those with liver impairment).
• Onset of Action:
• IV: 1–3 minutes
• IM: 15–30 minutes
• Oral: 30–60 minutes
• Elimination: Excreted renally as inactive glucuronide conjugates.

Pregnancy:

• Category D: Positive evidence of fetal risk, including congenital malformations (e.g., cleft palate), floppy infant syndrome, and neonatal withdrawal.
• Should only be used if the potential benefit outweighs the fetal risk.

Lactation:

• Lorazepam is excreted in breast milk.
• May cause sedation, poor feeding, or respiratory depression in nursing infants.
• Use with caution and monitor the infant for adverse effects.

• Class: Benzodiazepine
• Subclass: Intermediate-acting benzodiazepine with anxiolytic, sedative, anticonvulsant, and muscle-relaxant properties

• Hypersensitivity to lorazepam or other benzodiazepines
• Acute narrow-angle glaucoma
• Myasthenia gravis
• Severe respiratory insufficiency (except during mechanical ventilation)
• Sleep apnea syndrome
• Premature or neonatal infants (injectable formulations containing benzyl alcohol)

• CNS Depression: Risk of sedation, respiratory depression, coma, and death, especially when combined with opioids or alcohol.
• Dependency and Withdrawal: Long-term use can lead to physical and psychological dependence; abrupt discontinuation may cause withdrawal symptoms or seizures.
• Elderly: Higher risk of cognitive impairment, falls, and delirium.
• Paradoxical Reactions: Possible agitation, hallucinations, or aggression—particularly in children and older adults.
• Hepatic Impairment: Reduced metabolism may lead to drug accumulation and prolonged sedation.
• IV Administration: Requires close monitoring of respiratory and cardiovascular status.

Common:

• Drowsiness, sedation, dizziness, fatigue
• Weakness, unsteadiness
• Confusion, depression

Less Common:

• Headache, visual disturbances
• Nausea, dry mouth, constipation

Serious/Rare:

• Respiratory depression (especially with IV use or opioid co-administration)
• Hypotension, bradycardia (IV)
• Paradoxical agitation or aggression
• Seizures upon abrupt withdrawal (especially after prolonged use)

Onset: Within 30–60 minutes (oral), 1–3 minutes (IV)
Dose Dependence: CNS depression and respiratory effects increase with higher doses

• Opioids: Increased risk of profound sedation, respiratory depression, coma, and death
• Alcohol and Other CNS Depressants: Additive depressant effects
• Valproic Acid: Inhibits lorazepam metabolism, increasing plasma levels
• Probenecid: Reduces lorazepam clearance and increases effects
• Theophylline/Aminophylline: May antagonize sedative effects

Enzyme Involvement:

• Lorazepam is primarily metabolized by hepatic glucuronidation, not significantly involving CYP450 enzymes

• FDA Black Box Warning (Updated): Strong warning against co-administration with opioids due to risk of fatal respiratory depression.
• Beers Criteria (2023): Lorazepam is listed as potentially inappropriate for elderly patients due to fall and cognitive risks.
• Practice Guidelines: Recent psychiatric guidelines recommend limiting benzodiazepine use for anxiety to short-term treatment and preferring SSRIs or SNRIs for long-term management.

• Tablets: Store at controlled room temperature (15°C to 30°C). Protect from moisture and light. Keep in original container.
• Injectable Form: Store in a refrigerator at 2°C to 8°C. Protect from light. Do not freeze.
• Handling: Discard if solution becomes discolored or cloudy. Shake gently if needed before IV administration.