|fdaLIADPed=This product is not indicated in pediatric patients under 6 years of age. Absolute dosage for pediatric patients 6 to 12 years of age is not established.
|fdaLIADPed=This product is not indicated in pediatric patients under 6 years of age. Absolute dosage for pediatric patients 6 to 12 years of age is not established.
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Oxazepam in pediatric patients.
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Oxazepam in pediatric patients.
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*15 mg — Each red opaque gelatin #4 capsule printed with[[File:Oxazepam capsule symbol.jpg|none|10px]]and 069 in black ink on both cap and body contains 15 mg of Oxazepam, USP. Capsules are supplied in bottles of 100 (NDC 0228-2069-10) and 500 (NDC 0228-2069-50).
*15 mg — Each red opaque gelatin #4 capsule printed with[[File:Oxazepam capsule symbol.jpg|none|10px]]and 069 in black ink on both cap and body contains 15 mg of Oxazepam, USP. Capsules are supplied in bottles of 100 (NDC 0228-2069-10) and 500 (NDC 0228-2069-50).
*30 mg — Each maroon opaque gelatin #4 capsule printed with[[File:Oxazepam capsule symbol.jpg|none|10px]] and 073 in blue ink on both cap and body contains 30 mg of Oxazepam, USP. Capsules are supplied in bottles of 100 (NDC 0228-2073-10).
*30 mg — Each maroon opaque gelatin #4 capsule printed with[[File:Oxazepam capsule symbol.jpg|none|10px]] and 073 in blue ink on both cap and body contains 30 mg of Oxazepam, USP. Capsules are supplied in bottles of 100 (NDC 0228-2073-10).
|storage=*Store at 25(C (77(F); excursions permitted to 15( to 30(C (59( to 86(F).
|storage=*Store at 25(C (77(F); excursions permitted to 15( to 30(C (59( to 86(F).
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Overview
Oxazepam is a Benzodiazepine that is FDA approved for the treatment of anxiety disorders and anxiety with alcohol withdrawal syndrome. Common adverse reactions include {{{adverseReactions}}}.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Anxiety
Because of the flexibility of this product and the range of emotional disturbances responsive to it, dosage should be individualized for maximum beneficial effects.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Oxazepam in adult patients.
This product is not indicated in pediatric patients under 6 years of age. Absolute dosage for pediatric patients 6 to 12 years of age is not established.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Oxazepam in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Oxazepam in pediatric patients.
Contraindications
History of previous hypersensitivity reaction to oxazepam.
Oxazepam is not indicated in psychoses.
Warnings
As with other CNS-acting drugs, patients should be cautioned against driving automobiles or operating dangerous machinery until it is known that they do not become drowsy or dizzy on oxazepam therapy.
Patients should be warned that the effects of alcohol or other CNS-depressant drugs may be additive to those of oxazepam, possibly requiring adjustment of dosage or elimination of such agents.
Consequently, after extended therapy, abrupt discontinuation should generally be avoided and a gradual dosage-tapering schedule followed.
Addiction-prone individuals (such as drug addicts or alcoholics) should be under careful surveillance when receiving oxazepam or other psychotropic agents because of the predisposition of such patients to habituation and dependence.
Adverse Reactions
Clinical Trials Experience
There is limited information regarding Oxazepam Clinical Trials Experience in the drug label.
Postmarketing Experience
There is limited information regarding Oxazepam Postmarketing Experience in the drug label.
Drug Interactions
There is limited information regarding Oxazepam Drug Interactions in the drug label.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Oxazepam in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Oxazepam in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Oxazepam during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Oxazepam in women who are nursing.
Pediatric Use
Safety and effectiveness in pediatric patients under 6 years of age have not been established. Absolute dosage for pediatric patients 6 to 12 years of age is not established.
Geriatic Use
Clinical studies of oxazepam were not adequate to determine whether subjects aged 65 and over respond differently than younger subjects.
Age (<80 years old) does not appear to have a clinically significant effect on oxazepam kinetics.
Clinical circumstances, some of which may be more common in the elderly, such as hepatic or renal impairment, should be considered.
Greater sensitivity of some older individuals to the effects of oxazepam (e.g., sedation, hypotension, paradoxical excitation) cannot be ruled out.
In general, dose selection for oxazepam for elderly patients should be cautious, usually starting at the lower end of the dosing range.
Gender
There is no FDA guidance on the use of Oxazepam with respect to specific gender populations.
Race
There is no FDA guidance on the use of Oxazepam with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Oxazepam in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Oxazepam in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Oxazepam in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Oxazepam in patients who are immunocompromised.
Administration and Monitoring
Administration
Oral
Monitoring
There is limited information regarding Oxazepam Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Oxazepam and IV administrations.
Overdosage
In the management of overdosage with any drug, it should be born in mind that multiple agents may have been taken.
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 benzodiazepineantagonistflumazenil may be used in hospitalized patients as an adjunct to, not as a substitute for, proper management of benzodiazepine overdose. The prescriber should be aware of a risk of seizure in association with flumazenil treatment, particularly in long-term benzodiazepine users and in cyclic antidepressant overdose. The complete flumazenil package insert including CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS should be consulted prior to use.
There is limited information regarding Oxazepam Mechanism of Action in the drug label.
Structure
Oxazepam is the first of a chemical series of compounds, the 3-hydroxybenzodiazepinones.
Oxazepam is 7 chloro-1,3-dihydro-3-hydroxy-5-phenyl-2H-1,4-benzodiazepin-2-one, and has the following structural formula:
Oxazepam is a white crystalline powder.
Pharmacodynamics
There is limited information regarding Oxazepam Pharmacodynamics in the drug label.
Pharmacokinetics
Pharmacokinetic testing in 12 volunteers demonstrated that a single 30 mg dose of a capsule, tablet or suspension will result in an equivalent extent of absorption.
For the capsule and tablet, peak plasma levels averaged 450 mg/mL and were observed to occur about 3 hours after dosing.
The mean elimination half-life for oxazepam was approximately 8.2 hours (range 5.7 to 10.9 hours).
This product has a single, major inactive metabolite in man, a glucuronide excreted in urine.
Age (<80 years old) does not appear to have a clinically significant effect on oxazepam kinetics.
A statistically significant increase in elimination half-life in the very elderly (>80 years of age) as compared to younger subjects has been reported, due to a 30% increase in volume of distribution, as well as a 50% reduction in unbound clearance ofoxazepam in the very elderly.
Nonclinical Toxicology
There is limited information regarding Oxazepam Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Oxazepam Clinical Studies in the drug label.
How Supplied
Oxazepam capsules are available as follows:
10 mg — Each pink opaque gelatin #4 capsule printed withand 067 in black ink on both cap and body contains 10 mg of Oxazepam, USP. Capsules are supplied in bottles of 100 (NDC 0228-2067-10) and 500 (NDC 0228-2067-50).
15 mg — Each red opaque gelatin #4 capsule printed withand 069 in black ink on both cap and body contains 15 mg of Oxazepam, USP. Capsules are supplied in bottles of 100 (NDC 0228-2069-10) and 500 (NDC 0228-2069-50).
30 mg — Each maroon opaque gelatin #4 capsule printed with and 073 in blue ink on both cap and body contains 30 mg of Oxazepam, USP. Capsules are supplied in bottles of 100 (NDC 0228-2073-10).
Storage
Store at 25(C (77(F); excursions permitted to 15( to 30(C (59( to 86(F).
Keep tightly closed.
Dispense in a tight, light-resistant container as defined in the USP.
Images
Drug Images
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Oxazepam is an intermediate acting benzodiazepine. Oxazepam acts on benzodiazepine receptors resulting in an enhancement of the binding of GABA to the GABAA receptor which results in inhibitory effects on the central nervous system.[1][2] The half life of oxazepam is 4-15 hours.[3] Oxazepam has been shown to suppress cortisol levels.[4]
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. Absorption by any administered route and the risk of accumulation is significantly increased in the neonate and there is clinical justification to recommend the withdrawal of oxazepam during pregnancy and breast feeding as oxazepam is excreted in breast milk.[5]
Indications
It is an intermediate acting benzodiazepine with a slow onset of action, 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. Also prescribed for sleepwalking before a neurologist is involved when the sleepwalker may be a problem or danger to themselves.
When tolerance and habituation occurs brain concentration of oxazepam increase according to degree of tolerance.[6]
Dependence
Oxazepam as with other benzodiazepine drugs can cause 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 regime.[7]
The Committee on the Review of Medicines
The Committee on the Review of Medicines (UK) carried out a review into benzodiazepines due to significant concerns of tolerance, drug dependence and benzodiazepine withdrawal problems and other adverse effects. The committee found that benzodiazepines do not have any antidepressant or analgesic properties and are therefore unsuitable treatments for conditions such as depression, tension headaches and dysmenorrhoea. Benzodiazepines are also not beneficial in the treatment of psychosis due to a lack of efficacy. The committee also recommended against benzodiazepines being used in the treatment of anxiety or insomnia in children. The committee was in agreement with the Institute of Medicine (USA) and the conclusions of a study carried out by the White House Office of Drug Policy and the National Institute on Drug Abuse (USA) that there was little evidence that long term use of benzodiazepine hypnotics were beneficial in the treatment of insomnia due to the development of tolerance. Benzodiazepines tended to lose their sleep promoting properties within 3 - 14 days of continuous use and in the treatment of anxiety the committee found that there was little convincing evidence that benzodiazepines retained efficacy in the treatment of anxiety after 4 months continuous use due to the development of tolerance. The committee found that the regular use of benzodiazepines caused the development of dependence characterised by tolerance to the therapeutic effects of benzodiazepines and the development of the benzodiazepine withdrawal syndrome including symptoms such as anxiety, apprehension, tremor, insomnia, nausea, and vomiting upon cessation of benzodiazepine use. Withdrawal symptoms tended to develop within 24 hours on the cessation of a short acting benzodiazepine and within 3 - 10 days after the cessation of a more short acting benzodiazepine. Withdrawal effects could occur after treatment lasting only 2 weeks at therapeutic dose levels however withdrawal effects tended to occur with habitual use beyond 2 weeks and were more likely the higher the dose. The withdrawal symptoms may appear to be similar to the original condition. The committee recommended that all benzodiazepine treatment be withdrawn gradually and recommended that benzodiazepine treatment be used only in carefully selected patients and that therapy be limited to short term use only. It was noted in the review that alcohol can potentiate the central nervous system depressant effects of benzodiazepines and should be avoided. The central nervous system depressant effects of benzodiazepines may make driving or operating machinery dangerous and the elderly are more prone to these adverse effects. In the neonate high single doses or repeated low doses have been reported to produce hypotonia, poor sucking, and hypothermia in the neonate and irregularities in the fetal heart. Benzodiazepines should be avoided in lactation. Withdrawal from benzodiazepines should be gradual as abrupt withdrawal from high doses of benzodiazepines may cause confusion, toxic psychosis, convulsions, or a condition resembling delirium tremens. Abrupt withdrawal from lower doses may cause depression, nervousness, rebound insomnia, irritability, sweating, and diarrhoea.[8]
Dosage
Mild/moderate anxiety - 10 to 15mg, 3 to 4 times daily
Severe anxiety - 15 to 30mg, 3 to 4 times daily
Symptoms related to alcohol withdrawal - 15 to 30mg, 3 to 4 times daily
Availability
In the United Kingdom, oxazepam is available generically in the form of 10mg, 15mg and 30mg tablets.
Side effects
The side effects of oxazepam are similar in nature to those of other benzodiazepines.
Side effects from oxazepam are common and include:
drowsiness,
dizziness,
tiredness,
weakness,
dry mouth,
diarrhea,
upset stomach,
changes in appetite,
heart palpitations,
anxiety,
trouble breathing,
shortness of breath,
angry outbursts,
trouble sleeping,
tremors
Template:Sect-stub
Internal tremors have been alleviated by using 15mg of oxazepam as required, usually approximately four hourly.
Interactions
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 potent painkillers (opioids, e.g. morphine, oxycodone or methadone). Avoid drinking alcoholic beverages when taking oxazepam; alcohol and oxazepam (as well as other benzodiazepines) are interacting in a way, that is difficult to pre-estimate, 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 coma and collapse.
Concomitant use of alcohol and oxazepam (as well as other benzodiazepines) also increases the risk of an addiction.
Benzodiazepines including oxazepam may inhibit the glucuronidation of morphine leading to increased levels of and prolongation of the effects of morphine.[9]
Special precautions
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.[10]
Pregnancy
There is inconclusive evidence that benzodiazepines including oxazepam if taken early in pregnancy may result in reduced IQ, neurodevelopmental problems, physical malformations in cardiac or facial structure as well as other malformations in some new borns. 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.[11]
Oxazepam is a drug which is very frequently involved in drug intoxication, including overdose.[12] Oxazepam overdose has been involved in fatal overdoses in an Australian study of drug related deaths. Benzodiazepines were found to be the sole cause of death in one third of cases.[13]
Benzodiazepines, including diazepam, oxazepam, nitrazepam, temazepam, and flunitrazepam account for the largest volume of forged drug prescriptions in Sweden, a total of 52% of drug forgeries being for benzodiazepines, suggesting benzodiazepines are a major prescription drug class of abuse.[14]
↑Christensen P (1992). "Benzodiazepine-induced sedation and cortisol suppression. A placebo-controlled comparison of oxazepam and nitrazepam in healthy male volunteers". Psychopharmacology. 106 (4): 511–6. PMID1349754. Unknown parameter |coauthors= ignored (help)
↑Olive G (1977). "Pharmacologic bases of use of benzodiazepines in peréinatal medicine". Arch Fr Pediatr. 34(1): 74–89. PMID851373. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
↑Chodera A (1984). "Pharmacokinetic aspects of habituation to benzodiazepines". Pol J Pharmacol Pharm. 36 (4): 353–60. PMID6152051. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
↑MacKinnon GL (1982). "Benzodiazepine withdrawal syndrome: a literature review and evaluation". The American journal of drug and alcohol abuse. 9 (1): 19–33. PMID6133446. Unknown parameter |coauthors= ignored (help)
↑Pacifici GM (1986). "Metabolic interaction between morphine and various benzodiazepines". Acta Pharmacol Toxicol (Copenh). 58 (4): 249–52. PMID2872767. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
↑Kanto JH. (1982). "Use of benzodiazepines during pregnancy, labour and lactation, with particular reference to pharmacokinetic considerations". Drugs. 23 (5): 354–80. PMID6124415. Unknown parameter |month= ignored (help)
↑McElhatton PR. (1994). "The effects of benzodiazepine use during pregnancy and lactation". Reprod Toxicol. 8 (6): 461–75. PMID7881198. Unknown parameter |month= ignored (help)
↑Zevzikovas A (2002). "[Analysis of benzodiazepine derivative mixture by gas-liquid chromatography]". Medicina (Kaunas). 38 (3): 316–20. PMID12474705. Unknown parameter |coauthors= ignored (help)
↑Drummer OH (1996). "Sudden death and benzodiazepines". Am J Forensic Med Pathol. 17 (4): 336–42. PMID8947361. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
↑Bergman U (1989). "Use of prescription forgeries in a drug abuse surveillance network". Eur J Clin Pharmacol. 36 (6): 621–3. PMID2776820. Unknown parameter |coauthors= ignored (help)
↑Mant A (1993). "Benzodiazepine utilisation in Australia: report from a new pharmacoepidemiological database". Aust J Public Health. 17 (4): 345–9. PMID7911332. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
