OXAZEPAM
Clinical safety rating: avoid
Positive evidence of fetus risks but benefits may outweigh risks in some cases
Binds to GABA-A receptor at benzodiazepine binding site, enhancing Cl- ion conductance and increasing inhibitory neurotransmission. Anxiolytic, sedative, hypnotic, anticonvulsant, and muscle relaxant effects.
| Metabolism | Hepatic via glucuronidation (UGT enzymes, primarily UGT2B15). Major metabolite: oxazepam glucuronide (inactive). Not metabolized by CYP450. |
| Excretion | Renal (primarily as glucuronide conjugates, with less than 1% unchanged); biliary/fecal excretion is minimal. |
| Half-life | Terminal elimination half-life is 5-15 hours (mean 8 hours); no active metabolites, thus accumulation is minimal even with repeated dosing. |
| Protein binding | 96-98% bound to albumin. |
| Volume of Distribution | 0.7-1.2 L/kg; indicates extensive tissue distribution. |
| Bioavailability | Oral: approximately 90% (well absorbed). |
| Onset of Action | Oral: 1-2 hours to peak effect; IM: slower and erratic absorption; IV: not approved. |
| Duration of Action | Duration is 6-12 hours; clinical effects may persist longer in elderly or hepatic impairment due to reduced clearance. |
| Molecular Weight | 286.7 |
10-30 mg orally 3-4 times daily; maximum 120 mg/day.
| Dosage form | CAPSULE |
| Renal impairment | GFR 10-50 mL/min: administer every 12-24 hours; GFR <10 mL/min: not recommended. |
| Liver impairment | Child-Pugh Class A: no adjustment; Class B: reduce dose by 50%; Class C: avoid use. |
| Pediatric use | Children 6-12 years: 0.5 mg/kg/day divided every 6-8 hours; not recommended under 6 years. |
| Geriatric use | Initial dose 5 mg 2-3 times daily; increase cautiously; maximum 60 mg/day. |
| 1st trimester | Avoid unless essential; may be associated with congenital malformations (limited data). |
| 2nd trimester | Use only if benefit outweighs risk; risk of hypotonia and respiratory depression in neonate. |
| 3rd trimester | Avoid; high risk of neonatal withdrawal syndrome and floppy infant syndrome. |
Clinical note
CNS depressants including alcohol and opioids increase sedation risk Abrupt discontinuation can cause withdrawal symptoms.
| Placental transfer | Oxazepam crosses the placenta; minimal data on degree, but similar benzodiazepines have significant transfer. |
| Breastfeeding | Oxazepam is excreted into breast milk in low amounts; however, accumulation is possible due to long half-life in neonates. Observe infant for sedation, poor feeding, and weight gain. Use alternative with shorter half-life if possible. |
■ FDA Black Box Warning
Concomitant use with opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for patients for whom alternative treatment options are inadequate.
| Common Effects | alcohol withdrawal |
| Serious Effects |
Hypersensitivity to oxazepam or any benzodiazepineSevere respiratory insufficiencyMyasthenia gravisSevere hepatic impairmentNarrow-angle glaucomaSleep apnea syndrome
| Precautions | Risk of sedation, respiratory depression, and dependence, Withdrawal reactions upon discontinuation, Use with caution in elderly (increased sensitivity), Hepatic impairment may require dose adjustment, May impair ability to drive or operate machinery, Risks of anterograde amnesia and paradoxical reactions |
| Food/Dietary |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Increased risk of oral clefts (odds ratio ~2.2) with benzodiazepine exposure. Third trimester: Risk of neonatal withdrawal syndrome (irritability, hypertonia, feeding difficulties) and floppy infant syndrome (hypotonia, lethargy, respiratory depression). Use only if benefit clearly outweighs risk. |
| Fetal Monitoring | Monitor maternal sedation, respiratory status, and blood pressure. In third trimester, assess fetal heart rate and movements. Neonates should be observed for signs of withdrawal or floppy infant syndrome for at least 48 hours postpartum. |
| Fertility Effects | No specific studies on human fertility. In animals, high doses caused decreased pregnancy rates. In men, benzodiazepines may rarely cause decreased libido or erectile dysfunction. Clinical relevance unclear. |
| Grapefruit and grapefruit juice do not interact with oxazepam. Avoid or limit alcohol intake. No specific food restrictions. |
| Clinical Pearls | Oxazepam is a benzodiazepine with intermediate onset and elimination half-life (5-15 hours), making it suitable for elderly patients due to reduced risk of accumulation. It undergoes glucuronidation only, no CYP450 metabolism, hence minimal drug-drug interactions. Useful in alcohol withdrawal and anxiety with hepatic impairment. Avoid in narrow-angle glaucoma and severe respiratory insufficiency. |
| Patient Advice | Do not drive or operate machinery until you know how oxazepam affects you, as it may cause drowsiness or dizziness. · Avoid alcohol and other CNS depressants while taking this medication, as it can increase sedation and risk of overdose. · Take exactly as prescribed. Do not increase dose or frequency without consulting your doctor, as dependence can develop. · Do not stop suddenly; gradual dose reduction is needed to avoid withdrawal symptoms like anxiety, insomnia, and seizures. · Inform your doctor if you are pregnant, planning to become pregnant, or breastfeeding, as oxazepam may harm the fetus or infant. |