Oxazepam

Approved Indications:

• Generalized Anxiety Disorder (GAD):
  Relief of anxiety symptoms, especially when associated with depression.
• Alcohol Withdrawal Syndrome:
  Management of acute symptoms such as agitation, tremor, and anxiety during alcohol detoxification.
• Short-term Treatment of Anxiety:
  Used for situational or transient anxiety, typically limited to 2–4 weeks.

Clinically Accepted Off-label Uses:

• Insomnia (short-term use): Especially in patients with comorbid anxiety.
• Agitation in Acute Psychiatric Conditions: As a sedative adjunct.
• Muscle Spasms: In tension-related cases involving anxiety.

Route: Oral
Administration Advice: Administer with or without food. Avoid alcohol and CNS depressants.

Adults:

• Anxiety:
  10–30 mg, 3–4 times daily; maximum: 120 mg/day in divided doses
• Alcohol Withdrawal:
  15–30 mg, 3–4 times daily; taper based on clinical response and duration of withdrawal symptoms

Elderly or Debilitated Patients:

• Start at 10 mg 2–3 times daily, titrate cautiously to avoid excessive sedation and falls

Pediatric Use:

• Not routinely recommended.
  If used (age ≥6 years): 0.02–0.07 mg/kg/dose, given 3–4 times daily, with close monitoring

Hepatic Impairment:

• Preferred in mild to moderate hepatic dysfunction due to conjugation metabolism (non-CYP dependent)
• Use with caution in severe hepatic impairment

Renal Impairment:

• Generally safe; no major adjustment required
• Monitor for increased sedation in reduced clearance

Oxazepam is a short-to-intermediate acting benzodiazepine that potentiates the effect of gamma-aminobutyric acid (GABA) by binding to the GABA-A receptor complex. This action increases chloride ion influx into neurons, causing hyperpolarization and reduced neuronal excitability, which results in anxiolytic, sedative, muscle relaxant, and anticonvulsant effects. Unlike other benzodiazepines, oxazepam is an active metabolite and is metabolized via direct glucuronidation, making it safer in patients with liver impairment.

• Absorption: Well absorbed orally
• Onset of Action: ~30–60 minutes
• Peak Plasma Concentration: 2–3 hours post-dose
• Bioavailability: Approximately 90%
• Distribution: Widely distributed; ~99% protein-bound
• Metabolism: Hepatic conjugation via glucuronidation (no active metabolites)
• Half-life: 5–15 hours (longer in elderly)
• Excretion: Renal (primarily as glucuronide conjugates)

• Pregnancy: FDA Category D
• Positive evidence of fetal risk (e.g., congenital malformations, withdrawal symptoms, neonatal CNS depression)
• Should only be used when potential benefit outweighs fetal risk
• Lactation:
• Excreted in breast milk in small amounts
• May cause sedation, feeding difficulties, or respiratory depression in infants
• Use is not recommended during breastfeeding unless absolutely necessary

• Class: Anxiolytic
• Subclass: Benzodiazepine (short-to-intermediate acting)
• Metabolism Type: Direct glucuronidation (ideal in liver-compromised patients)

• Hypersensitivity to oxazepam or other benzodiazepines
• Acute narrow-angle glaucoma
• Severe respiratory insufficiency (e.g., severe COPD, sleep apnea)
• Myasthenia gravis
• Severe hepatic impairment
• History of substance abuse (relative contraindication due to dependency risk)

• Dependence and Abuse:
• Risk increases with prolonged use, high doses, or in patients with addiction history
• Withdrawal Symptoms:
• Abrupt discontinuation may lead to rebound anxiety, seizures, agitation, or insomnia
• CNS Depression:
• Additive sedation with alcohol, opioids, or other CNS depressants
• Paradoxical Reactions:
• Rare but serious (e.g., aggression, hallucinations), especially in the elderly
• Cognitive Impairment:
• May cause drowsiness, confusion, and slowed reaction time
• Driving or Operating Machinery:
• Strongly discouraged due to sedative effects
• Tapering Required:
• Gradual dose reduction recommended even after short-term use

Common:

• Drowsiness
• Dizziness
• Fatigue
• Blurred vision
• Headache
• Nausea

Less Common:

• Confusion
• Irritability
• Ataxia
• Dry mouth
• Gastrointestinal upset

Serious (Rare):

• Respiratory depression
• Paradoxical agitation
• Anterograde amnesia
• Stevens-Johnson Syndrome (extremely rare)
• Hypotension

• Alcohol & Opioids:
• Increased risk of sedation, respiratory depression, coma, or death
• CNS Depressants (e.g., barbiturates, antihistamines):
• Additive sedative effect
• Oral Contraceptives:
• May slightly reduce clearance (not clinically significant)
• Antacids:
• May delay absorption slightly (no dosage adjustment required)
• No CYP450 Interactions:
• Advantageous in polypharmacy; oxazepam is not affected by enzyme inhibitors or inducers

• FDA & EMA Black Box Warnings (2020–2023):
• Benzodiazepines carry risk of abuse, misuse, addiction, physical dependence, and withdrawal
• Beers Criteria (2023):
• Oxazepam is included on the list of potentially inappropriate medications for the elderly due to fall risk and cognitive impairment
• Revised Guidance on Discontinuation:
• Emphasis on slow tapering even after short durations of use to avoid withdrawal symptoms
• Preferred in Liver Dysfunction:
• Due to simple metabolism, oxazepam remains one of the benzodiazepines of choice in patients with hepatic impairment

• Temperature: Store at 20°C to 25°C (68°F to 77°F)
• Humidity: Keep in a dry place, away from moisture
• Light Protection: Store away from direct sunlight
• Container: Keep in tightly closed original packaging
• Disposal: As a controlled substance, dispose of unused tablets through a pharmacy take-back program or follow local regulations