OXAZEPAM

Chemistry - A benzodiazepine, oxazepam occurs as a creamy white to pale yellow powder. It ispractically insoluble in water.

Storage, Stability, Compatibility

Store oxazepam capsules and tablets at room temperature inwell-closed containers.

Pharmacology - OXAZEPAM

The subcortical levels (primarily limbic, thalamic, and hypothalamic) of the CNSare depressed by oxazepam and other benzodiazepines thus producing the anxiolytic, sedative, skeletal muscle relaxant and anticonvulsant effects seen. The exact mechanism of action isunknown, but postulated mechanisms include: antagonism of serotonin, increased release of and/orfacilitation of gamma-aminobutyric acid (GABA) activity, and diminished release or turnover ofacetylcholine in the CNS. Benzodiazepine specific receptors have been located in the mammalianbrain, kidney, liver, lung, and heart. In all species studied, receptors are lacking in the white matter.

Uses, Indications

Oxazepam is used most frequently in small animal medicine as an appetitestimulant in cats and dogs. It may also be useful as an oral anxiolytic agent for adjunctive therapyof anxiety-related disorders.

Pharmacokinetics - OXAZEPAM

Oxazepam is absorbed from the GI tract, but it is one the more slowly absorbed oral benzodiazepines. Oxazepam. like other benzodiazepines is widely distributed; it ishighly bound to plasma proteins (97% in humans). While not confirmed, oxazepam may cross theplacenta and enter maternal milk. Oxazepam is principally conjugated in the liver via glucuronidation to an inactive metabolite. Serum half-life in humans range from 3-21 hours.

Contraindications, Precautions, Reproductive Safety

Oxazepam is contraindicated in patientswho are hypersensitive to it or other benzodiazepines or have acute narrow angle glaucoma.
Benzodiazepines have been reported to exacerbate myasthenia gravis. While oxazepam is lesssusceptible to accumulation than many other benzodiazepines in patients with hepatic dysfunction, itshould be used with caution nonetheless. Rarely, oxazepam has reportedly precipitated tonic-clonicseizures, it should be used with caution in susceptible patients.
Safe use during pregnancy has not been established; teratogenic effects of similar benzodiazepineshave been noted in rabbits and rats. It is not known if the drug enters maternal milk.

Adverse Effects, Warnings

The most prevalent adverse effects seen with oxazepam in smallanimals is sedation and occasionally, ataxia. These may be transient and dosage adjustment may berequired to alleviate. For more information on less likely occurring adverse effects with benzodiazepines, see the diazepam monograph.
Overdosage, Acute Toxicity - When used alone, oxazepam overdoses are generally limited tosignificant CNS depression (confusion, coma, decreased reflexes, etc.). Treatment of significantoverdoses consist of standard protocols for removing and/or binding the drug in the gut if takenorally, and supportive systemic measures. The use of analeptic agents (CNS stimulants such ascaffeine, amphetamines, etc) are generally not recommended.

Drug Interactions

Metabolism of oxazepam may be decreased and excessive sedation may occurif given with the following drugs: cimetidine, erythromycin, isoniazid, ketoconazole, propranolol, & valproic acid. This interaction is less likely to occur with oxazepam, than other benzodiazepines (e.g., diazepam) because oxazepam undergoes glucuronide conjugation.
Probenecid however, may impair the glucuronide conjugation of oxazepam.
If administered with other CNS depressant agents (barbiturates, narcotics, anesthetics, etc.) additive CNS depressant effects may occur.Laboratory Considerations - Benzodiazepines may decrease the thyroidal uptake of I123 or I131.