Skip to Content

Oxazepam

Pronunciation

Class: Benzodiazepines
VA Class: CN302
Chemical Name: 7 chloro-1,3-dihydro-3-hydroxy-5-phenyl-2H-1,4-benzodiazepin-2-one
Molecular Formula: C15H11ClN2O2
CAS Number: 604-75-1

Warning(s)

Special Alerts:

[Posted 08/31/2016]

AUDIENCE: Pharmacy, Internal Medicine, Psychiatry, Neurology, Family Practice

ISSUE: FDA review has found that the growing combined use of opioid medicines with benzodiazepines or other drugs that depress the central nervous system (CNS) has resulted in serious side effects, including slowed or difficult breathing and deaths. Opioids are used to treat pain and cough; benzodiazepines are used to treat anxiety, insomnia, and seizures. In an effort to decrease the use of opioids and benzodiazepines, or opioids and other CNS depressants, together, FDA is adding Boxed Warnings, our strongest warnings, to the drug labeling of prescription opioid pain and prescription opioid cough medicines, and benzodiazepines. See the Drug Safety Communication, available at: , for a listing of all approved prescription opioid pain and cough medicines, and benzodiazepines and other CNS depressants.

FDA conducted and reviewed several studies showing that serious risks are associated with the combined use of opioids and benzodiazepines, other drugs that depress the CNS, or alcohol (see the FDA Drug Safety Communication, available at: , for a Data Summary). Based on these data, FDA is requiring several changes to reflect these risks in the opioid and benzodiazepine labeling, and new or revised patient Medication Guides. These changes include the new Boxed Warnings and revisions to the Warnings and Precautions, Drug Interactions, and Patient Counseling Information sections of the labeling.

FDA is continuing to evaluate the evidence regarding combined use of benzodiazepines or other CNS depressants with medication-assisted therapy (MAT) drugs used to treat opioid addiction and dependence. FDA is also evaluating whether labeling changes are needed for other CNS depressants, and will update the public when more information is available.

BACKGROUND: Opioids are powerful prescription medicines that can help manage pain when other treatments and medicines cannot be taken or are not able to provide enough pain relief. Benzodiazepines are a class of medicines that are widely used to treat conditions including anxiety, insomnia, and seizures.

RECOMMENDATION: Health care professionalsshould limit prescribing opioid pain medicines with benzodiazepines or other CNS depressants only to patients for whom alternative treatment options are inadequate. If these medicines are prescribed together, limit the dosages and duration of each drug to the minimum possible while achieving the desired clinical effect. Warn patients and caregivers about the risks of slowed or difficult breathing and/or sedation, and the associated signs and symptoms. Avoid prescribing prescription opioid cough medicines for patients taking benzodiazepines or other CNS depressants, including alcohol.

Patients taking opioids with benzodiazepines, other CNS depressant medicines, or alcohol, and caregivers of these patients, should seek medical attention immediately if they or someone they are caring for experiences symptoms of unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.

For more information visit the FDA website at: and .

Introduction

Benzodiazepine.a b c Anxiolytic, sedative.a b c

Uses for Oxazepam

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Alcohol Withdrawal

Relief of agitation and tremor and prevention or symptomatic relief of delirium tremens and hallucinations associated with acute alcohol withdrawal.a b c

Anxiety Disorders

Management of anxiety disorders and short-term relief of anxiety or anxiety associated with depressive symptoms.a b c

One of several preferred benzodiazepines in geriatric patients and patients with liver disease (because of its short elimination half-life and lack of active metabolites).b

Oxazepam Dosage and Administration

General

  • Use the smallest effective dosage (especially in geriatric or debilitated patients and in those with low serum albumin) to avoid oversedation.a b

  • In patients who have received prolonged (e.g., for several months) therapy, avoid abrupt discontinuance, since manifestations of withdrawal can be precipitated; gradually taper dosage.a b c

Anxiety

  • Periodically reassess the usefulness of the drug.a b c Efficacy beyond 4 months not systematically evaluated.a b c Administer for the shortest possible period of time; frequent dosage adjustments may be required.b

Administration

Oral Administration

Administer orally in divided doses, generally 3 or 4 times daily.a b c

Dosage

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Pediatric Patients

Anxiety Disorders
Oral

Children 6–12 years of age: Dosage not clearly established.a c

Adults

Alcohol Withdrawal
Oral

15–30 mg 3 or 4 times daily.a c

Anxiety Disorders
Oral

Mild to moderate anxiety: 10–15 mg 3 or 4 times daily.a c

Severe anxiety: 15–30 mg 3 or 4 times daily.a c

Special Populations

Hepatic Impairment

No specific dosage recommendations.c

Renal Impairment

No specific dosage recommendations.c

Geriatric Patients

Initially, 10 mg 3 times daily.a c Increase dosage to 15 mg 3 or 4 times daily if needed and tolerated.a c Use the smallest effective dosage to avoid oversedation.a b

Other Populations

Use the smallest effective dosage in debilitated patients and patients with low serum albumin concentrations to avoid oversedation.a b

Cautions for Oxazepam

Contraindications

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

  • Known hypersensitivity to oxazepam.c

  • Many manufacturers state that benzodiazepines are contraindicated in patients with acute angle-closure glaucoma but may be administered to patients with open-angle glaucoma who are receiving appropriate therapy; however, clinical rationale for this contraindication has been questioned.b

Warnings/Precautions

Warnings

CNS Effects

Performance of activities requiring mental alertness and physical coordination may be impaired.b c

Concurrent use of other CNS depressants may cause additive or potentiated CNS depression.b c (See Specific Drugs under Interactions.)

Psychiatric Indications

Avoid use in patients with depressive neuroses or psychotic reactions in which anxiety is not prominent.b c

Abuse Potential

Possible tolerance, psychologic dependence, and physical dependence following prolonged use.b c

Patients with a history of drug or alcohol dependence or abuse are at risk of habituation or dependence; use only with careful surveillance in such patients.c

Withdrawal Syndrome

Abrupt discontinuance may result in symptoms of withdrawal (similar to barbiturates).a b c Symptoms may be relieved by tapering the dosage.a b c

Fetal/Neonatal Morbidity

Retrospective studies suggest increased risk of congenital malformations in infants of mothers who received anxiolytics (chlordiazepoxide, diazepam, meprobamate) during the first trimester of pregnancy. b c Since use of anxiolytics is rarely urgent, their use during the first trimester almost always should be avoided.b c

General Precautions

Hypotension

Hypotension reported rarely.c Administer with caution to patients in whom a drop in BP might lead to cardiac complications, particularly geriatric patients.c

Suicide

Use with caution in depressed patients; potential for suicidal tendencies.b Prescribe and dispense drug in the smallest feasible quantity.b

Laboratory Testing

Monitor blood counts and liver function tests periodically during prolonged therapy.b c Leukopenia and hepatic dysfunction (including jaundice) reported rarely.c

Specific Populations

Pregnancy

Category D.d (See Fetal/Neonatal Morbidity under Cautions.)

Lactation

Many benzodiazepines are distributed into milk.b Not known whether oxazepam is distributed into milk.d Discontinue nursing or the drug.b

Pediatric Use

Safety and efficacy not established in children <6 years of age.a c

Dosage for children 6–12 years of age not clearly established.a c

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.c Possibility of greater sensitivity to the drug (e.g., sedation, hypotension, paradoxical excitation) in some geriatric individuals.c

Select initial dosage at the lower end of the usual range because of potential for greater sensitivity and age-related decreases in hepatic or renal function.c (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Use with caution.b

Renal Impairment

Use with caution.b

Common Adverse Effects

Drowsiness,b c dizziness,b c vertigo,b c headache.b c

Interactions for Oxazepam

Specific Drugs

Drug

Interaction

Comments

CNS depressants (e.g., alcohol, anticonvulsants)

Additive CNS effectb c

Use with caution to avoid overdosage;b c dosage reduction or discontinuance of CNS depressant may be necessaryc

Contraceptives, oral

Apparent increase in oxazepam metabolisme

Clinical importance not establishede

Oxazepam Pharmacokinetics

Absorption

Bioavailability

Readily absorbed from the GI tract,b with peak plasma concentration usually attained within about 3 hours.c

Distribution

Extent

Benzodiazepines are widely distributed into body tissues and cross the blood-brain barrier.b

Oxazepam crosses the placenta.b d

Benzodiazepines generally are distributed into milk.b Not known whether oxazepam is distributed into milk.d

Plasma Protein Binding

Benzodiazepines are highly bound to plasma proteins.b

Elimination

Metabolism

Conjugated with glucuronic acid in the liver to form a single, major inactive metabolite.b c

Elimination Route

Excreted principally in urine.b c

Half-life

8.2 hours (range: 3–21 hours).b c

Special Populations

Hepatic impairment: Pharmacokinetics not altered substantially in patients with cirrhosis.f

Geriatric patients >80 years of age: Half-life is prolonged.c Age <80 years does not appear to substantially alter pharmacokinetics.c

Benzodiazepines are not appreciably removed by hemodialysis.b

Stability

Storage

Oral

Capsules

Tight, light-resistant container at 20–25°C; protect from moisture.c

Actions

  • Effects appear to be mediated through the inhibitory neurotransmitter GABA; the site and mechanism of action within the CNS appear to involve a macromolecular complex (GABAA-receptor-chloride ionophore complex) that includes GABAA receptors, high-affinity benzodiazepine receptors, and chloride channels.

Advice to Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

  • Potential for drug to impair mental alertness or physical coordination; avoid driving or operating machinery until effects on individual are known.b c

  • Importance of informing clinicians of any behavioral or mental changes, memory impairment, tolerance, or dependence/withdrawal symptoms.b c

  • Importance of taking only as prescribed; do not increase dosage or duration of therapy or abruptly discontinue drug unless otherwise instructed by a clinician.b c

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and alcohol consumption.b c

  • Importance of informing clinicians about any concomitant illnesses, particularly depression.c

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.a b c

  • Importance of informing patients of other important precautionary information.b c (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Subject to control under the Federal Controlled Substances Act of 1970 as a schedule IV (C-IV) drug.a

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Oxazepam

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

10 mg*

Oxazepam Capsules ( C-IV)

Actavis, Sandoz, Teva

15 mg*

Oxazepam Capsules ( C-IV)

Actavis, Sandoz, Teva

30 mg*

Oxazepam Capsules ( C-IV)

Actavis, Sandoz, Teva

AHFS DI Essentials. © Copyright, 2016, American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814. Review Date: September 06, 2016.

References

a. AHFS drug information 2008. McEvoy GK, ed. Oxazepam. Bethesda, MD: American Society of Health-System Pharmacists; 2008:2599-60.

b. AHFS drug information 2008. McEvoy GK, ed. Benzodiazepines general statement. Bethesda, MD: American Society of Health-System Pharmacists; 2008:2571-80.

c. Sandoz. Oxazepam capsules prescribing information. Princeton, NJ; 2007 Nov.

d. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 7th ed. Baltimore, MD: Williams & Wilkins; 2005:1220.

e. AHFS drug information 2008. McEvoy GK, ed. Estrogen-progestin combinations. Bethesda, MD: American Society of Health-System Pharmacists; 2008:3128-43.

f. Bailey L, Ward M, Musa MN. Clinical pharmacokinetics of benzodiazepines. J Clin Pharmacol. 1994; 34:804-11. [PubMed 7962667]

Hide