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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
CNS depressants including alcohol and opioids increase sedation risk Abrupt discontinuation can cause withdrawal symptoms.
| Breastfeeding | Oxazepam is excreted into breast milk in low concentrations. M/P ratio is approximately 0.3. Reports of drowsiness and poor feeding in infants. Caution advised; monitor infant for sedation and feeding issues. |
| 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. |
■ 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 benzodiazepines","Narrow-angle glaucoma","Severe hepatic impairment","Myasthenia gravis","Pregnancy (especially first trimester)","Breastfeeding","Concurrent use with opioids (unless no alternatives)"]
| 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"] |
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| 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. |