Oxazepam

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with 60-70% ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with 60-70% ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with a combination filter cartridge, i.e. organic vapor/acid gas/HEPA (specific for organic vapors, HCl, acid gas, SO2 and a high efficiency particulate filter). (NTP, 1992)

Induced vomiting and/or gastric lavage should be undertaken, followed by general supportive care, monitoring of vital signs, and close observation of the patient. Hypotension, though unlikely, usually may be controlled with norepinephrine bitartrate Injection. The value of dialysis has not been adequately determined for oxazepam. The benzodiazepine antagonist flumazenil may be used In hospitalized patients as an adjunct to, not as a substitute for, proper management of benzodiazepine overdose. (L1712)

Concurrent use with benzodiazepines may, in theory, competitively inhibit hepatic glucuronidation and decrease the clearance of zidovudine; the toxicity of zidovudine potentially could be increased. /Benzodiazepines/

Concurrent use /of probenecid/ may impair glucuronide conjugation of lorazepam, oxazepam, or temazepam, resulting in increased effects and possibly excessive sedation.

When a benzodiazepine is used with an opioid analgesic, the dosage of the opioid analgesic should be reduced by at least one third and administered in small increments. /Benzodiazepines/

Concurrent use with benzodiazepines may decrease the therapeutic effects of levodopa. /Benzodiazepines/

For more Interactions (Complete) data for OXAZEPAM (10 total), please visit the HSDB record page.

Oxazepam, like other benzodiazepines, is rarely associated with serum ALT or alkaline phosphatase elevations, and clinically apparent liver injury from oxazepam is extremely rare, if it occurs at all. Despite its availability for more than 50 years, there have been no case reports of symptomatic, acute liver injury from oxazepam. Nevertheless, the possibility of liver dysfunction and jaundice are mentioned in the product label for oxazepam. Isolated single cases of clinically apparent liver injury have been reported with other benzodiazepines including alprazolam, chlordiazepoxide, clonazepam, diazepam, flurazepam, lorazepam, and triazolam. The clinical pattern of acute liver injury from benzodiazepines is typically cholestatic and mild-to-moderate in severity with a latency of 1 to 6 months. Fever and rash are uncommon as is autoantibody formation.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 390(SRC), determined from a log Kow of 2.24(2) and a regression-derived equation(3), indicates that oxazepam is expected to have moderate mobility in soil(SRC). Volatilization of oxazepam from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 5.5X10-10 atm-cu m/mole(SRC), determined using a fragment constant estimation method(4). Oxazepam is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.2X10-12 mm Hg(SRC), determined from a fragment constant method(5). Estimated pKa values of 1.55 (-C=N-) and 10.9 (-OH)(6) indicate that oxazepam will exist in its neutral form under environmentally relevant pH's (pH 5-9)(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 390(SRC), determined from a log Kow of 2.24(2) and a regression-derived equation(3), indicates that oxazepam is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 5.5X10-10 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). Estimated pKa values of 1.55 (-C=N-) and 10.9 (-OH)(5) indicate that oxazepam will exist in its neutral form under environmentally relevant pH's (pH 5-9)(SRC). According to a classification scheme(6), an estimated BCF of 11(SRC), from its log Kow(2) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Oxazepam is not expected to undergo hydrolysis in the environment due to the lack of hydrolyzable functional groups(8).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), oxazepam, which has an estimated vapor pressure of 4.2X10-12 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase oxazepam may be removed from the air by wet and dry deposition(SRC). Oxazepam does not absorb light with wavelengths >290 nm(3), and is not expected to be susceptible to direct photolysis by sunlight(SRC).

Common adverse effects associated with benzodiazepines such as oxazepam may include sedation, fatigue, depression, confusion, memory impairment, dizziness, ataxia, slurred speech, hyper-excitability, nervousness, and weakness. Less frequently encountered adverse effects may involve hypotension, hallucinations, mania, dry mouth, hypersalivation, edema, leukopenia, decreased libido, incontinence, rash, menstrual irregularities, jaundice, and diplopia. Severe adverse effects of oxazepam include respiratory depression and neonatal abstinence syndrome. Anterograde amnesia also has correlations with benzodiazepine use.

Well absorbed from the gastrointestinal tract following oral administration however is absorbed at a slower rate compared to other benzodiazepines like diazepam or flurazepam. Time to peak concentration = 2-4 hours. Onset of action is slow, > 3 hours, following oral administration.

Signs and Symptoms of Overdose

Similar to other benzodiazepines, oxazepam exerts its anxiolytic effects by potentiating the effect of gamma-aminobutyric acid (GABA) on GABA-A receptors through a cooperative mechanism of action. GABA receptors are ionotropic chloride-linked channel receptors that produce inhibitory postsynaptic potentials. When activated by GABA, the GABA receptor/chloride ionophore complex undergoes a conformational change that allows the passage of chloride ions through the channel. Benzodiazepines are believed to exert their effect by increasing the effect of GABA at its receptor. Benzodiazepine binding increases chloride conductance in the presence of GABA by increasing the frequency at which the channel opens. In contrast, barbiturates increase chloride conductance in the presence of GABA by prolonging the time in which the channel remains open. There are 18 subtypes of the GABA receptor subunits. The α₂ subunit of the α₂β₃γ₂ receptor complex is thought to mediate anxiolytic effects while the α₁ subunit of the α₁β₂γ₂ receptor complex is thought to mediate sedative, anticonvulsant and anterograde amnesia effects.

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical. [http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=604-75-1]

The Koc of oxazepam is estimated as 390(SRC), using a log Kow of 2.24(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that oxazepam is expected to have moderate mobility in soil.

/SIGNS AND SYMPTOMS/ Benzodiazepines are sedating drugs, which do not usually cause either profound CNS or respiratory depression or any nonsedative effects. Death may occur before hospital arrival due to sedation (particularly if combined with other CNS depressants), but the course of patients reaching hospital is generally uncomplicated. The clinical effects of benzodiazepine poisoning are due entirely to CNS depression. Severe poisoning may occasionally develop hypothermia, bradycardia, and hypotension. Respiratory and CNS depression may lead to aspiration pneumonia. However, deep coma (GCS less than 8) is unusual. Most patients are stuporous or still responsive to painful stimuli unless they have coingested other sedating drugs. Ataxia and nystagmus are common in nontolerant patients, but if pronounced, the possibility of concomitant drug over dose should be raised (i.e., anticonvulsant). /Benzodiazepines/

/SIGNS AND SYMPTOMS/ Signs and symptoms of overdose include somnolence, confusion, coma, hypoactive reflexes, dyspnea, labored breathing, hypotension, bradycardia, slurred speech, and unsteady gait or impaired coordination.

/SIGNS AND SYMPTOMS/ In addition to effects associated with psychological and physical dependence and withdrawal phenomena, chronic oxazepam administration has been associated in very rare cases with jaundice (both hepatocellular and cholestatic), nausea, skin rashes, lowering of blood pressure and, in isolated cases, with the enhancement of parkinsonism or arthritic symptoms.

/CASE REPORTS/ A 75 year-old comatous patient was admitted after ingestion of 200 mg oxazepam. Skin blisters, attributed to oxazepam toxicity, appeared on the left forearm the following day and regressed spontaneously nine days later.

For more Human Toxicity Excerpts (Complete) data for OXAZEPAM (6 total), please visit the HSDB record page.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl oxazepam, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Schedule IV shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. ... (c) Depressants. Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation which contains any quantity of the following substances, including its salts, isomers, and salts of isomers whenever the existence of such salts, isomers, and salts of isomers is possible within the specific chemical designation. Oxazepam is included on this list. DEA Controlled Substances Code Number: 2835.

MEDICATION: anxiolytic

Use (kg) in Switzerland (2009): >250

used extensively since the 1960s for the treatment of anxiety and insomnia and in the control of symptoms of alcohol withdrawal. [Wikipedia]

2-Amino-5-chlorobenzophenone is acylated with chloroacetyl chloride & the product is refluxed with sodium iodide to form the iodoacetamido compound. Reaction of one with hydroxylamine effects dehydration & dehydrohalogenation to form the benzodiazepine derivative. Treatment of two with acetic anhydride causes rearrangement to oxazepam which is simultaneously esterified to acetate. Saponification liberates oxazepam.

Information available in 2004 indicated that Oxazepam was used in the manufacture of pharmaceutical preparations in the following countries: Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, Colombia, Czech Republic, Denmark, Finland, France, Germany, Greece, Ireland, Israel, Italy, Mexico, New Zealand, Norway, Poland, Romania, Singapore, Spain, Sweden, Switzerland, Thailand, United Kingdom, USA (1,2)