Oxazepam

Usage

• Oxazepam is prescribed for the short-term relief (2-4 weeks) of anxiety symptoms, including anxiety associated with depression, alcohol withdrawal symptoms (tremulousness, agitation), and tension, irritability, and agitation in older adults. It is not recommended for children under 6 years of age.
• Pharmacological classification: Benzodiazepine, Anxiolytic, Sedative-Hypnotic.
• Mechanism of Action: Oxazepam enhances the effect of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) by binding to the benzodiazepine site on the GABA_A receptor complex. This binding increases the frequency of chloride channel opening, leading to neuronal hyperpolarization and reduced neuronal excitability.

Alternate Names

• Generic Name: Oxazepam
• Brand Names: Serax, Alepam, Murelax, Ox-Pam, Pasaden, Praxiten, Serepax, Seresta, Zapex

How It Works

• Pharmacodynamics: Oxazepam’s anxiolytic, sedative, and anticonvulsant effects are mediated through its enhancement of GABAergic neurotransmission, resulting in decreased central nervous system activity.
• Pharmacokinetics:
  • Absorption: Oxazepam is well-absorbed after oral administration.
  • Metabolism: Oxazepam is metabolized in the liver primarily by glucuronidation, forming inactive oxazepam glucuronide. It does not undergo extensive CYP450 metabolism.
  • Elimination: Oxazepam glucuronide is excreted primarily in the urine. It has an elimination half-life of approximately 4-15 hours, which may be prolonged in elderly patients and those with hepatic impairment.
• Mode of Action: Oxazepam binds allosterically to the benzodiazepine site on the GABA_A receptor complex, increasing the affinity of GABA for its binding site. This leads to increased chloride influx and neuronal hyperpolarization, inhibiting neuronal firing.
• Elimination pathways: Primarily renal excretion as oxazepam glucuronide. Minimal CYP450 enzyme involvement.

Dosage

Standard Dosage

Adults:

• Anxiety: 10-15 mg orally 3-4 times daily for mild to moderate anxiety; 15-30 mg orally 3-4 times daily for severe anxiety. Maximum dose generally should not exceed 60 mg/day for elderly or debilitated patients.
• Alcohol withdrawal: 15-30 mg orally 3-4 times daily.
• Insomnia associated with anxiety: 15-25 mg orally 1 hour before bedtime; may increase to a maximum of 50 mg if necessary.

Children:

• Not recommended for children under 6 years of age.
• 6-12 years: Dosage not clearly established; use with caution if necessary. Dose needs to be determined by a doctor.
• Over 12 years: 10-15 mg orally 3-4 times a day (mild to moderate anxiety); 15-30 mg orally 3-4 times a day (severe anxiety).

Special Cases:

• Elderly Patients: Initial dose 10 mg orally three times daily, increasing cautiously to 15 mg three or four times daily if needed and tolerated. Use the smallest effective dose to avoid oversedation.
• Patients with Renal Impairment: No specific dosage adjustments are typically required due to minimal renal excretion of the unchanged drug.
• Patients with Hepatic Dysfunction: No specific dosage adjustments are typically required, but caution is advised. Start with lower doses and titrate cautiously.
• Patients with Comorbid Conditions: Careful consideration is required in patients with respiratory disorders, depression, or substance use disorders.

Clinical Use Cases

Oxazepam is not typically recommended for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Other benzodiazepines like midazolam or lorazepam are generally preferred in these settings.

Dosage Adjustments

Dose adjustments may be necessary based on patient response and tolerance. Lower doses are recommended for elderly or debilitated patients.

Side Effects

Common Side Effects:

Drowsiness, dizziness, lightheadedness, fatigue, headache, impaired coordination, dry mouth.

Rare but Serious Side Effects:

Confusion, amnesia, paradoxical excitement (increased agitation, aggression, hallucinations), respiratory depression (especially with concomitant opioid use), allergic reactions.

Long-Term Effects:

Cognitive impairment, dependence, withdrawal symptoms upon discontinuation.

Adverse Drug Reactions (ADR):

Severe allergic reactions (anaphylaxis), respiratory depression requiring ventilatory support, paradoxical reactions requiring discontinuation of therapy.

Contraindications

• Hypersensitivity to oxazepam or other benzodiazepines.
• Acute angle-closure glaucoma (although the clinical rationale for this has been questioned).
• Severe respiratory insufficiency.
• Severe hepatic impairment.
• Myasthenia gravis.
• Sleep apnea.

Drug Interactions

• CNS depressants: Alcohol, opioids, barbiturates, antihistamines, and other sedatives can potentiate CNS depression.
• CYP450 Inhibitors/Inducers: Oxazepam is primarily glucuronidated, so CYP450 interactions are less significant compared to other benzodiazepines. However, some interactions may still occur.
• Other: Sodium oxybate, clozapine, digoxin, kava, orlistat.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: D (Use only if potential benefit outweighs risk; there is positive evidence of human fetal risk). Oxazepam can cross the placenta and may cause fetal harm, including floppy infant syndrome and withdrawal symptoms in newborns. Avoid use during pregnancy, especially during the first trimester.
• Breastfeeding: Oxazepam is excreted in breast milk, but levels are generally low. Monitor the infant for sedation, poor feeding, and weight gain. If oxazepam use is necessary during breastfeeding, consider using the lowest effective dose for the shortest duration possible.

Drug Profile Summary

• Mechanism of Action: Enhances GABAergic neurotransmission.
• Side Effects: Drowsiness, dizziness, confusion, respiratory depression.
• Contraindications: Hypersensitivity, acute angle-closure glaucoma, severe respiratory/hepatic impairment, myasthenia gravis.
• Drug Interactions: CNS depressants, some CYP450 interactions.
• Pregnancy & Breastfeeding: Avoid use if possible due to potential fetal risks and excretion in breast milk.
• Dosage: See detailed dosage section above.
• Monitoring Parameters: Respiratory rate, mental status, level of sedation.

Popular Combinations (Generally not recommended unless carefully considered by a physician)

Precautions

• Pre-screening for allergies, respiratory or hepatic disorders, and substance use disorders.
• Avoid abrupt discontinuation; taper dose gradually to minimize withdrawal symptoms.
• Caution in elderly, children, and patients with renal or hepatic impairment.
• Avoid alcohol and other CNS depressants.
• Advise patients about potential for impaired cognitive and motor function; restrict driving and operating machinery.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Oxazepam?

A: See detailed dosage guidelines above. It varies depending on indication, age, and patient-specific factors.

Q2: What are the common side effects of Oxazepam?

A: Common side effects include drowsiness, dizziness, lightheadedness, fatigue, headache, impaired coordination, and dry mouth.

Q3: Can Oxazepam be used during pregnancy?

A: Oxazepam should be avoided during pregnancy, especially in the first trimester, due to the potential risk of fetal harm. Consult a healthcare professional before using oxazepam during pregnancy.

Q4: How is Oxazepam metabolized?

A: Oxazepam is primarily metabolized via glucuronidation in the liver, forming inactive oxazepam glucuronide. It does not undergo extensive CYP450 metabolism.

Q5: What are the contraindications for Oxazepam?

A: Contraindications include hypersensitivity to oxazepam or other benzodiazepines, acute angle-closure glaucoma, severe respiratory insufficiency, severe hepatic impairment, and myasthenia gravis.

Q6: Does Oxazepam interact with other medications?

A: Yes, oxazepam can interact with other medications, particularly CNS depressants like alcohol, opioids, and other sedatives. Consult a healthcare professional for specific drug interaction guidance.

Q7: What are the signs of Oxazepam overdose?

A: Oxazepam overdose can manifest as profound sedation, respiratory depression, coma, and potentially death. Seek immediate medical attention if overdose is suspected.

Q8: Can Oxazepam be used for long-term anxiety management?

A: Oxazepam is generally recommended for short-term use (2-4 weeks) due to the risk of dependence and tolerance. Long-term use should be carefully considered and monitored by a healthcare professional.

Q9: What should patients be advised regarding activities requiring alertness while taking Oxazepam?

A: Patients should be cautioned against driving, operating machinery, or engaging in activities requiring alertness while taking oxazepam, as it can impair cognitive and motor function.