Oxazepam

Oxazepam is a short- to intermediate-acting benzodiazepine used for anxiety, short-term insomnia and alcohol withdrawal. It is conjugated directly by the liver and has no active metabolites, so it is a preferred benzodiazepine in liver disease and in older adults. Availability varies by region.

Classification. Benzodiazepine, short- to intermediate-acting.

Mechanism. Positive allosteric modulation of GABA-A receptors, which increases chloride channel opening and neuronal inhibition.

Pharmacokinetics. Slow oral absorption, peak in 2 to 3 hours. Glucuronidated to inactive metabolites. Half-life 4 to 15 hours. Approximate equivalence for switching: oxazepam 20 mg is about diazepam 10 mg.

All regimens are oral with no loading dose.

Anxiety, adults (short term).

• Start 10 to 15 mg three times daily.
• Titration: increase to 15 to 30 mg three or four times daily as needed.
• Usual 30 to 90 mg daily in divided doses. Maximum 120 mg daily.
• Duration: no longer than 2 to 4 weeks.

Insomnia, short term. 15 to 25 mg at night, up to 50 mg if required, for no more than 2 to 4 weeks.

Alcohol withdrawal, adults. 15 to 30 mg three or four times daily, reducing over 5 to 7 days; give thiamine to all patients.

Dose limits. Older adults: start 10 mg two or three times daily; maximum 30 mg daily. Liver impairment: no adjustment, but use lower doses in severe disease. Kidney impairment: start low.

Contraindications. Respiratory depression, severe sleep apnoea, acute pulmonary insufficiency, myasthenia gravis, severe liver impairment, acute narrow-angle glaucoma, hypersensitivity. Major warning of profound sedation and death with opioids; abuse and misuse; dependence and withdrawal.

Serious adverse effects. Respiratory depression, dependence and withdrawal seizures, paradoxical agitation, delirium in older adults, falls, anterograde amnesia.

Common adverse effects. Drowsiness, dizziness, ataxia, headache, confusion, memory impairment.

Interactions. Opioids, alcohol, gabapentinoids and other sedatives add respiratory depression. Few cytochrome interactions. Probenecid can raise levels. Clozapine with oxazepam can cause collapse.

Common prescribing errors. Prescribing for longer than 4 weeks; combining with opioids; abrupt stopping; using high doses in older adults.

Special groups.

• Pregnancy: avoid; floppy infant syndrome and neonatal withdrawal with late exposure.
• Breastfeeding: avoid repeated dosing; infant sedation reported.
• Children: not advised.
• Older adults: preferred benzodiazepine but start 10 mg; falls and delirium.
• Kidney impairment: start low.
• Liver impairment: preferred benzodiazepine; use lower doses in severe disease.

Formulations. Tablets 10 mg, 15 mg and 30 mg; capsules 10 mg, 15 mg and 30 mg in some regions. Give in divided doses, with the larger dose at night for insomnia.

Baseline. Alcohol and sedative use, respiratory status, liver and kidney function, history of dependence, pregnancy status, medicines list.

Monitoring. Review at 2 weeks and at the end of the planned course. In alcohol withdrawal, assess severity every 1 to 4 hours and withhold the dose if the patient is drowsy.

Stopping. After more than 2 to 4 weeks of use, reduce the dose by 5 to 10% every 1 to 2 weeks, more slowly at the lowest doses.

Referral and escalation. Refer to addiction or psychiatric services for dependence or withdrawal. Seizures, delirium or respiratory depression needs emergency care.