| Oxazepam | |
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| Identifiers | |
| CAS number | 604-75-1 |
| PubChem | 4616, 921299 (R), 667436 (S) |
| ChemSpider | 4455 , 804298 |
| UNII | 6GOW6DWN2A |
| EC number | 210-076-9 |
| DrugBank | DB00842 |
| KEGG | D00464 |
| MeSH | Oxazepam |
| ChEBI | CHEBI:7823 |
| ChEMBL | CHEMBL568 |
| RTECS number | DF1400000 |
| ATC code | N05 |
| Jmol-3D images | Image 1 |
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| Properties | |
| Molecular formula | C15H11ClN2O2 |
| Molar mass | 286.71 g mol−1 |
| Exact mass | 286.050905313 g mol-1 |
| Melting point |
205-206 °C, 478-479 K, 401-403 °F |
| Solubility in water | 179 mg L-1 |
| log P | 2.216 |
| Acidity (pKa) | 10.939 |
| Basicity (pKb) | 3.058 |
| Pharmacology | |
| Bioavailability | 95.5% |
| Routes of administration |
Oral |
| Metabolism | Hepatic |
| Elimination half-life |
5-15 h |
| Excretion | Renal |
| Legal status | Prescription Only (S4)(AU) |
| Hazards | |
| GHS pictograms | |
| GHS signal word | WARNING |
| GHS hazard statements | H351 |
| GHS precautionary statements | P281 |
| EU classification | Xn |
| R-phrases | R40 |
| S-phrases | S36/37 |
| (verify) (what is: /?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) |
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| Infobox references | |
Oxazepam[1] (marketed in English speaking countries under the following brand names Alepam, Medopam, Murelax, Noripam, Opamox, Ox-Pam, Purata, Serax and Serepax, as Vaben in Israel, and as Sobril and Oxascand in Sweden), is a drug which is a short to intermediate acting 3-hydroxy benzodiazepine derivative.[2][3] Oxazepam is a benzodiazepine used extensively since the 1960s for the treatment of anxiety and insomnia and in the control of symptoms of alcohol withdrawal. It is a metabolite of diazepam, prazepam and temazepam.[4] Oxazepam has moderate amnesic, anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties compared to other benzodiazepines.[5]
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It is an intermediate acting benzodiazepine with a slow onset of action,[6] so it is usually prescribed to individuals who have trouble staying asleep, rather than falling asleep. It is commonly prescribed for anxiety disorders with associated tension, irritability, and agitation. It is also prescribed for drug and alcohol withdrawal, and for anxiety associated with depression. Physicians may use Oxazepam outside its approved indications to treat social phobia, posttraumatic stress disorder, insomnia, premenstrual syndrome, and other conditions.[7]
In the United Kingdom, oxazepam is available generically in the form of 10 mg, 15 mg and 30 mg tablets. In Finland, oxazepam is available generically in the form of 15 mg, 30 mg and 50 mg tablets. In France, oxazepam is available in the form of 10 mg and 50 mg tablets. In Australia, oxazepam is available in the form of 5 mg, 7.5 mg, 10 mg, 15 mg and 30 mg tablets.
Oxazepam along with diazepam, nitrazepam and temazepam, were the four benzodiazepines listed on the pharmaceutical benefits scheme and represented 82% of the benzodiazepine prescriptions in Australia in 1990-1991.[8]
The side effects of oxazepam are similar in nature to those of other benzodiazepines and may include dizziness, drowsiness, headache, memory impairment, paradoxical excitement, retrograde amnesia, but does not affect transient global amnesia. Side effects due to rapid decrease in dose or abrupt withdrawal from oxazepam may include abdominal and muscle cramps, convulsions, depression, inability to fall asleep or stay asleep, sweating, tremors, or vomiting.[9]
Oxazepam is contraindicated in Myasthenia gravis, chronic obstructive pulmonary disease and limited pulmonary reserve, as well as severe hepatic disease.
Benzodiazepines require special precaution if used in the elderly, during pregnancy, in children, alcohol- or drug-dependent individuals and individuals with comorbid psychiatric disorders.[10] Benzodiazepines including oxazepam are lipophilic drugs and rapidly penetrate membranes and therefore rapidly cross over into the placenta with significant uptake of the drug. Use of benzodiazepines in late pregnancy especially high doses may result in floppy infant syndrome.[11]
Oxazepam when taken during late in pregnancy, the third trimester, causes a definite risk to the neonate including a severe benzodiazepine withdrawal syndrome in the neonate with symptoms including hypotonia, and reluctance to suck, to apnoeic spells, cyanosis, and impaired metabolic responses to cold stress. Floppy infant syndrome and sedation in the new born may also occur. Symptoms of floppy infant syndrome and the neonatal benzodiazepine withdrawal syndrome have been reported to persist from hours to months after birth.[12]
Oxazepam as with other benzodiazepine drugs can cause tolerance, physical dependence, addiction and what is known as the benzodiazepine withdrawal syndrome. Withdrawal from oxazepam or other benzodiazepines often leads to withdrawal symptoms which are similar to those seen during alcohol and barbiturate withdrawal. The higher the dose and the longer the drug is taken the greater the risk of experiencing unpleasant withdrawal symptoms. Withdrawal symptoms can however occur at standard dosages and also after short term use. Benzodiazepine treatment should be discontinued as soon as possible via a slow and gradual dose reduction regimen.[13]
Oxazepam is an intermediate acting benzodiazepine of the 3-hydroxy family. Oxazepam acts on benzodiazepine receptors resulting in increased effect of GABA to the GABAA receptor which results in inhibitory effects on the central nervous system.[14][15] The half-life of oxazepam is 4–15 hours.[16] Oxazepam has been shown to suppress cortisol levels.[17] Oxazepam is the most slowly absorbed benzodiazepine and has the slowest onset of action of all the common benzodiazepines according to one British study.[18]
Oxazepam is an active metabolite formed during the breakdown of diazepam, nordazepam, and certain similar drugs. Oxazepam may be safer than many other benzodiazepines in patients with impaired liver function because it does not require hepatic oxidation, but rather it is simply metabolized via glucuronidation. This means that oxazepam is less likely to accumulate and cause adverse reactions in the elderly or people with liver disease. Oxazepam is similar to lorazepam in this respect. (1) There is preferential storage of oxazepam in some organs including the heart of the neonate. Absorption by any administered route and the risk of accumulation is significantly increased in the neonate and it is recommended to withdraw oxazepam during pregnancy and breast feeding as oxazepam is excreted in breast milk.[19]
As oxazepam is an active metabolite of diazepam, there is likely an overlap in possible interactions with other drugs or food, with exception of the pharmacokinetic CYP450 interactions (e.g. with cimetidine). Take precautions, and follow closely the prescription of your doctor, when taking oxazepam (or other benozodiazepines) in combinations with antidepressant medication (SSRIs such as Prozac, Zoloft, and Paxil, or multiple reuptake inhibitors such as Wellbutrin, Cymbalta, or Effexor), potent painkillers (opioids, e.g. morphine, oxycodone or methadone). Concurrent use of these medicines (as well as other benzodiazepines) can interact in a way that is difficult to predict. Drinking alcohol when taking oxazepam is not recommended. Concomitant use of oxazepam and alcohol can lead to increased sedation, severe problems with coordination (ataxiae), decreased muscle tone and in severe cases or in predisposed patients even to life-threatening intoxications with respiratory depression, coma and collapse. Concomitant use of alcohol and oxazepam (as well as other benzodiazepines) also increases the risk of an addiction.
Oxazepam is generally less toxic in overdose than other benzodiazepines.[20] Important factors which effect the severity of a benzodiazepine overdose include the dose ingested, the age of the patient, health status prior to overdose. Benzodiazepine overdoses can be much more dangerous if there has been a coingestion of other CNS depressants such as opiates or alcohol. Symptoms of an oxazepam overdose include:[21][22][23]
Oxazepam is a drug with the potential for misuse. Drug misuse is defined as taking the drug to achieve a high, or continuing to take the drug in the long term against medical advice.[24] Benzodiazepines, including diazepam, oxazepam, nitrazepam, and flunitrazepam, accounted for the largest volume of forged drug prescriptions in Sweden 1982-1986. During this time, a total of 52% of drug forgeries were for benzodiazepines, suggesting benzodiazepines were a major prescription drug class of abuse.[25]
However, due to its slow rate of absorption (the slowest of all benzodiazepines) and its slow onset of action,[18] oxazepam has a relatively low potential for abuse compared to some other benzodiazepines like temazepam, flunitrazepam, or triazolam, which have a high potential for abuse that is similar to barbiturate abuse potential.[26]
Oxazepam is a Schedule IV drug under the Convention on Psychotropic Substances.[27]
6-Chloro-2-chloromethyl-4-phenylquinazolin-3-oxide undergoes treatment with sodium hydroxide, giving 7-chloro-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepin-2-on-4-oxide. This undergoes an acetoxylation reaction of the third position of the benzodiazepine ring, using acetic anhydride, and which reminiscents the Polonovski reaction, giving 7-chloro-1,3-dihydro-3-acetoxy-5-phenyl-2H-benzodiazepin-2-one. Subsequent hydrolysis of the product's acetyl group gives oxazepam.[28][29][30][31][32][33]
Oxazepam is listed as a possible carcinogen (Group 2b) by the IARC.
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