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| Pronunciation | /ɒkˈsæzɪpæm/ ok-SAZ-i-pam |
| Trade names | Serax, Alepam, Serepax, others |
| Addiction liability | Low–moderate |
| Routes of administration | By mouth |
| Drug class | Benzodiazepine |
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| Pharmacokinetic data | |
| Bioavailability | 92.8% |
| Metabolism | Hepatic (glucuronidation) |
| Onset of action | 30 - 120 minutes |
| Eliminationhalf-life | 6–9 hours[3][4][5] |
| Duration of action | 6 - 12 hours |
| Excretion | Renal |
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| ECHA InfoCard | 100.009.161 |
| Chemical and physical data | |
| Formula | C15H11ClN2O2 |
| Molar mass | 286.71 g·mol−1 |
| 3D model (JSmol) | |
| Melting point | 205 to 206 °C (401 to 403 °F) |
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Oxazepam is a short-to-intermediate-actingbenzodiazepine.[7][8] Oxazepam is used for the treatment ofanxiety,[9][10]insomnia, and to control symptoms ofalcohol withdrawal syndrome.
It is a metabolite ofdiazepam,prazepam, andtemazepam,[11] and has moderateamnesic,anxiolytic,anticonvulsant,hypnotic,sedative, andskeletal muscle relaxant properties compared to other benzodiazepines.[12]
It was patented in 1962 and approved for medical use in 1964.[13]
Oxazepam is an intermediate-acting benzodiazepine with a slow onset of action,[14] 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 alcoholwithdrawal, and for anxiety associated withdepression. Oxazepam is sometimes prescribedoff-label to treatsocial phobia,post-traumatic stress disorder,insomnia,premenstrual syndrome, and other conditions.[15]
The side effects of oxazepam are similar to those of other benzodiazepines, and may include dizziness, drowsiness, headache, memory impairment,paradoxical excitement, andanterograde amnesia, but does not affecttransient global amnesia.[citation needed] Withdrawal effects due to rapid decreases in dosage or abrupt discontinuation of oxazepam may include abdominal and musclecramps,seizures,depression,insomnia,sweating,tremors, ornausea andvomiting.[16]
In September 2020, the U.S.Food and Drug Administration (FDA) required theboxed warning be updated for all benzodiazepine medicines to describe the risks of abuse, misuse,addiction,physical dependence, and withdrawal reactions consistently across all the medicines in the class.[17]
Oxazepam, as with other benzodiazepine drugs, can causetolerance,physical dependence,addiction, andbenzodiazepine withdrawal syndrome. Withdrawal from oxazepam or other benzodiazepines often leads to withdrawal symptoms which are similar to those seen during alcohol andbarbiturate withdrawal. The higher the dose and the longer the drug is taken, the greater the risk of experiencing unpleasant withdrawal symptoms. Withdrawal symptoms can occur, though, at standard dosages and also after short-term use. Benzodiazepine treatment should be discontinued as soon as possible by a slow and gradual dose reduction regimen.[18]
Oxazepam is contraindicated inmyasthenia gravis,chronic obstructive pulmonary disease, and limited pulmonary reserve, as well as severehepatic disease.
Benzodiazepines require special precautions if used in the elderly, during pregnancy, in children, alcohol- or drug-dependent individuals, and individuals withcomorbidpsychiatric disorders.[19] Benzodiazepines including oxazepam are lipophilic drugs and rapidly penetrate membranes, so rapidly crosses over into the placenta with significant uptake of the drug. Use of benzodiazepines in late pregnancy, especially high doses, may result infloppy infant syndrome.[20]
Oxazepam, when taken during thethird trimester, causes a definite risk to theneonate, including a severebenzodiazepine withdrawal syndrome includinghypotonia, reluctance to suck,apnoeic spells,cyanosis, and impairedmetabolic responses to cold stress. Floppy infant syndrome and sedation in the newborn 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.[21]
As oxazepam is an active metabolite of diazepam, an overlap in possible interactions is likely with other drugs or food, with exception of the pharmacokineticCYP450 interactions (e.g. withcimetidine). Precautions and following the prescription are required when taking oxazepam (or other benzodiazepines) in combinations withantidepressants oropioids. Concurrent use of these medications can interact in a way that is difficult to predict. Drinkingalcohol when taking oxazepam is not recommended. Concomitant use of oxazepam and alcohol can lead to increasedsedation, memory impairment,ataxia, decreased muscle tone, and, in severe cases or in predisposed patients,respiratory depression andcoma.
Oxazepam is generally less toxic in overdose than other benzodiazepines.[22] Important factors which affect the severity of a benzodiazepine overdose include the dose ingested, the age of the patient, and health status prior to overdose. Benzodiazepine overdoses can be much more dangerous if a coingestion of otherCNS depressants such as opiates or alcohol has occurred. Symptoms of an oxazepam overdose include:[23][24][25]
Oxazepam is an intermediate-acting benzodiazepine of the 3-hydroxy family; it acts onbenzodiazepine receptors, resulting in increased effect ofGABA to the GABAA receptor which results in inhibitory effects on thecentral nervous system.[26][27] Thehalf-life of oxazepam is between 6 and 9 hours.[5][4][28] It has been shown to suppresscortisol levels.[29] Oxazepam is the most slowly absorbed and has the slowest onset of action of all the common benzodiazepines according to one British study.[30]
Oxazepam is an active metabolite formed during the breakdown ofdiazepam,nordazepam, and certain similar drugs. It 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 byglucuronidation, so oxazepam is less likely to accumulate and cause adverse reactions in the elderly or people with liver disease. Oxazepam is similar tolorazepam in this respect.[31]Preferential storage of oxazepam occurs 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 withdrawal of oxazepam during pregnancy and breast feeding is recommended, as oxazepam is excreted in breast milk.[32]
Two milligrams of oxazepam equates to 1 mg of diazepam according to the benzodiazepine equivalency converter, therefore 20 mg of oxazepam according to BZD equivalency equates to 10 mg of diazepam and 15 mg oxazepam to 7.5 mg diazepam (rounded up to 8 mg of diazepam).[33] Some BZD equivalency converters use 3 to 1 (oxazepam to diazepam), 1 to 3 (diazepam to oxazepam) as the ratio (3:1 and 1:3), so 15 mg of oxazepam would equate to 5 mg of diazepam.[34]
Oxazepam exists as aracemic mixture.[35] Early attempts to isolateenantiomers were unsuccessful; the correspondingacetate has been isolated as a single enantiomer. Given the different rates ofepimerization that occur at different pH levels, it was determined that there would be no therapeutic benefit to the administration of a single enantiomer over the racemic mixture.[36]
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.[37]It is in several countries the benzodiazepine of choice for novice users, due to a low chance of accumulation and a relatively slow absorption speed.[38]
Oxazepam has the potential for misuse, defined as taking the drug to achieve a high, or continuing to take the drug in the long term against medical advice.[39] Benzodiazepines, including diazepam, oxazepam, nitrazepam, and flunitrazepam, accounted for the largest volume of forged drug prescriptions in Sweden from 1982 to 1986. During this time, a total of 52% of drug forgeries were for benzodiazepines, suggesting they were a major prescription drug class of abuse.[40]
However, due to its slow rate of absorption and its slow onset of action,[30] oxazepam has a relatively low potential for abuse compared to some other benzodiazepines, such as temazepam, flunitrazepam, ortriazolam. This is similar to the varied potential for abuse between different drugs of thebarbiturate class.[41]
Oxazepam is aSchedule IV drug under theConvention on Psychotropic Substances.[42]
Oxazepam is marketed under many brand names worldwide, including: Alepam, Alepan, Anoxa, Anxiolit, Comedormir, durazepam, Murelax, Nozepam, Oksazepam, Opamox, Ox-Pam, Oxa-CT, Oxabenz, Oxamin, Oxapam, Oxapax, Oxascand, Oxaze, Oxazepam, Oxazépam, Oxazin, Oxepam, Praxiten, Purata, Selars, Serax, Serepax, Seresta, Séresta, Serpax, Sobril, Tazepam, Vaben, and Youfei.[43]
It is also marketed in combination withhyoscine as Novalona and in combination withalanine as Pausafrent T.[43]
InScrabble, "Oxazepam" is considered the third-highest scoring word, scoring 392 points when played in the ideal spot.[44]
In 2013, a laboratory study which exposedEuropean perch to oxazepam concentrations equivalent to those present inEuropean rivers (1.8 μg/L) found that they exhibited increased activity, reduced sociality, and higher feeding rate.[45] In 2016, a follow-up study which exposedsalmonsmolt to oxazepam for seven days before letting them migrate observed increased intensity of migratory behaviour compared to controls.[46] A 2019 study associated this faster, bolder behaviour in exposed smolt to increased mortality due to a higher likelihood of beingpredated on.[47]
On the other hand, a 2018 study from the same authors, which kept 480 European perch and 12northern pikes in 12 ponds over 70 days, half of them control and half spiked with oxazepam, found no significant difference in either perch growth or mortality. However, it suggested that the latter could be explained by the exposed perch and pike being equally hampered by oxazepam, rather than the lack of an overall effect.[48] Lastly, a 2021 study built on these results by comparing two whole lakes filled with perch and pikes - one control while the other was exposed to oxazepam 11 days into experiment, at concentrations between 11 and 24 μg/L, which is 200 times greater than the reported concentrations in the European rivers. Even so, there were no measurable effects on pike behaviour after the addition of oxazepam, while the effects on perch behaviour were found to be negligible. The authors concluded that the effects previously attributed to oxazepam were instead likely caused by a combination of fish being stressed by human handling and small aquaria, followed by being exposed to a novel environment.[49]
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