Oxazepam - Drug Monograph

Introduction

Oxazepam is an intermediate-acting benzodiazepine medication primarily used for the management of anxiety disorders, alcohol withdrawal symptoms, and anxiety associated with depression. As a Schedule IV controlled substance, it represents an important therapeutic option in the benzodiazepine class with a distinct pharmacokinetic profile that offers certain clinical advantages over longer-acting alternatives.

Mechanism of Action

Oxazepam exerts its therapeutic effects by enhancing the activity of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. It binds to specific sites on the GABA-A receptor complex, facilitating the opening of chloride channels and resulting in neuronal hyperpolarization. This action increases GABAergic inhibition throughout the CNS, producing anxiolytic, sedative, hypnotic, anticonvulsant, and muscle relaxant effects. Unlike some benzodiazepines, oxazepam does not require hepatic oxidation for activation, as it is already in its active form.

Indications

• FDA-approved:

- Management of anxiety disorders - Short-term relief of anxiety symptoms - Anxiety associated with depression - Alcohol withdrawal symptoms

• Off-label uses (evidence-supported):

- Insomnia (short-term management) - Agitation in elderly patients (with caution) - Adjunctive treatment for muscle spasms

Dosage and Administration

• Anxiety: 10-15 mg orally 3-4 times daily
• Alcohol withdrawal: 15-30 mg orally 3-4 times daily
• Elderly/debilitated patients: Initial dose of 10 mg 3 times daily

• Hepatic impairment: Reduce dose by 50% or avoid use
• Renal impairment: Use with caution; consider dose reduction
• Geriatric patients: Start with lowest possible dose (5-10 mg daily)
• Pediatric patients: Safety and efficacy not established

• Oral administration with or without food
• Tablets should be swallowed whole
• Titrate dose gradually to minimize adverse effects
• Short-term use recommended (2-4 weeks)

Pharmacokinetics

• Absorption: Well absorbed from GI tract; bioavailability ~90%
• Distribution: Protein binding 86-99%; Vd ~1.0 L/kg
• Metabolism: Hepatic conjugation via glucuronidation (phase II metabolism)
• Elimination: Half-life 5-15 hours; primarily renal excretion (as glucuronide conjugate)
• Onset of action: 45-90 minutes
• Duration of action: 6-8 hours

Contraindications

• Hypersensitivity to oxazepam or other benzodiazepines
• Acute narrow-angle glaucoma
• Severe respiratory depression
• Severe hepatic impairment
• Myasthenia gravis
• Sleep apnea syndrome
• Pregnancy (especially first trimester)
• Breastfeeding

Warnings and Precautions

• Risk of dependence, abuse, and withdrawal
• Concomitant use with opioids may result in profound sedation, respiratory depression, coma, and death

• Elderly patients at increased risk of falls and cognitive impairment
• Potential for paradoxical reactions (agitation, aggression)
• Impaired coordination and judgment
• Depression and suicidal ideation
• Withdrawal symptoms upon discontinuation (taper gradually)
• Risk of next-day impairment
• Respiratory depression in patients with pulmonary disease

Drug Interactions

• Opioids: Increased CNS depression (avoid combination)
• Alcohol: Additive CNS depression
• Other CNS depressants: Enhanced sedative effects
• Flumazenil: Antagonizes effects of oxazepam

• CYP3A4 inhibitors/inducers: Minimal effect (oxazepam undergoes glucuronidation)
• Oral contraceptives: May decrease oxazepam clearance
• Proton pump inhibitors: Potential increased absorption

• Antipsychotics, antidepressants: Additive CNS effects
• Anticonvulsants: Potential altered seizure threshold
• Digoxin: Possible increased digoxin levels

Adverse Effects

• Drowsiness (15-30%)
• Dizziness (5-15%)
• Headache (5-10%)
• Fatigue (5-10%)
• Blurred vision (3-5%)

• Confusion
• Ataxia
• Memory impairment
• Nausea
• Dry mouth

• Respiratory depression
• Dependence and withdrawal syndrome
• Paradoxical reactions (agitation, aggression)
• Suicidal ideation
• Severe dermatological reactions
• Blood dyscrasias
• Hepatic dysfunction

Monitoring Parameters

• Comprehensive medical history
• Mental status examination
• Liver function tests
• Renal function assessment
• Respiratory status
• Fall risk assessment (especially elderly)

• Therapeutic response and symptom control
• Signs of excessive sedation
• Cognitive function
• Respiratory rate (especially with concomitant opioid use)
• Signs of dependence or misuse
• Withdrawal symptoms during taper
• Adverse effects

• Periodic reassessment of continued need
• Liver function (if long-term use)
• Cognitive assessment
• Fall risk reevaluation

Patient Education

• Take exactly as prescribed; do not increase dose without medical advice
• Avoid alcohol and other CNS depressants
• Do not operate machinery or drive until effects are known
• Report any thoughts of self-harm or worsening depression
• Do not stop abruptly; taper gradually under medical supervision
• Store securely to prevent misuse by others
• Use effective contraception; notify provider if pregnancy occurs

• Potential for dependence with long-term use
• Risk of next-day impairment
• Importance of regular follow-up appointments
• Alternative non-pharmacological strategies for anxiety management
• Proper disposal of unused medication

References

1. FDA Prescribing Information: Oxazepam Tablets 2. American Psychiatric Association. (2010). Practice Guideline for the Treatment of Patients with Anxiety Disorders. 3. Ashton, H. (2005). The diagnosis and management of benzodiazepine dependence. Current Opinion in Psychiatry, 18(3), 249-255. 4. Lader, M. (2011). Benzodiazepines revisited—will we ever learn? Addiction, 106(12), 2086-2109. 5. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 13th Edition 6. Lexicomp Online, Lexi-Drugs®. Oxazepam monograph. 7. Clinical Pharmacology [database online]. Oxazepam monograph. 8. World Health Organization. (2019). Guidelines for the Management of Alcohol Withdrawal.