WARNINGS Risks from Concomitant Use with Opioids: Concomitant use of benzodiazepines, including oxazepam, and opioids may result in profound sedation, respiratory depression, coma, and death.

Because of these risks, reserve concomitant prescribing of these drugs in patients for whom alternative treatment options are inadequate.

Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone.

If a decision is made to prescribe oxazepam concomitantly with opioids, prescribe the lowest effective dosages and minimum durations of concomitant use, and follow patients closely for signs and symptoms of respiratory depression and sedation.

In patients already receiving an opioid analgesic, prescribe a lower initial dose of oxazepam than indicated in the absence of an opioid and titrate based on clinical response.

If an opioid is initiated in a patient already taking oxazepam, prescribe a lower initial dose of the opioid and titrate based upon clinical response.

Advise both patients and caregivers about the risks of respiratory depression and sedation when oxazepam is used with opioids.

Advise patients not to drive or operate heavy machinery until the effects of concomitant use with the opioid have been determined (see PRECAUTIONS: Drug Interactions .

) Abuse, Misuse, and Addiction : The use of benzodiazepines, including Oxazepam, exposes users to the risks of abuse, misuse, and addiction, which can lead to overdose or death.

Abuse and misuse of benzodiazepines often (but not always) involve the use of doses greater than the maximum recommended dosage and commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes, including respiratory depression, overdose, or death ( see DRUG ABUSE AND DEPENDENCE: Abuse ) .

Before prescribing Oxazepam and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction (e.g., using a standardized screening tool).

Use of Oxazepam, particularly in patients at elevated risk, necessitates counseling about the risks and proper use of Oxazepam along with monitoring for signs and symptoms of abuse, misuse, and addiction.

Prescribe the lowest effective dosage; avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug.

If a substance use disorder is suspected, evaluate the patient and institute (or refer them for) early treatment, as appropriate.

Dependence and Withdrawal Reactions: To reduce the risk of withdrawal reactions, use a gradual taper to discontinue Oxazepam or reduce the dosage (a patient-specific plan should be used to taper the dose) (see DOSAGE AND ADMINISTRATION : Discontinuation or Dosage Reduction of Oxazepam).

Patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages, and those who have had longer durations of use.

Acute Withdrawal Reactions The continued use of benzodiazepines, including Oxazepam, may lead to clinically significant physical dependence.

Abrupt discontinuation or rapid dosage reduction of Oxazepam after continued use or administration of flumazenil (a benzodiazepine antagonist) may precipitate acute withdrawal reactions, which can be life threatening.

(e.g., seizures) (see DRUG ABUSE AND DEPENDENCE-Dependence ) .

Protracted Withdrawal Syndrome In some cases, benzodiazepine users have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months (see DRUG ABUSE AND DEPENDENCE-Dependence ).

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.

ADVERSE REACTIONS The necessity for discontinuation of therapy due to undesirable effects has been rare.

Transient, mild drowsiness is commonly seen in the first few days of therapy.

If it persists, the dosage should be reduced.

In few instances, dizziness, vertigo, headache, and rarely syncope have occurred either alone or together with drowsiness.

Mild paradoxical reactions, i.e., excitement, stimulation of affect, have been reported in psychiatric patients; these reactions may be secondary to relief of anxiety and usually appear in the first two weeks of therapy.

Other side effects occurring during oxazepam therapy include rare instances of minor diffuse skin rashes-morbilliform, urticarial, and maculopapular nausea, lethargy, edema, slurred speech, tremor and altered libido.

Such side effects have been infrequent and are generally controlled with reduction of dosage.

A case of an extensive fixed drug eruption also has been reported.

Although rare, leukopenia and hepatic dysfunction including jaundice have been reported during therapy.

Periodic blood counts and liver-function tests are advisable.

Ataxia with oxazepam has been reported in rare instances and does not appear to be specifically related to dose or age.

Although the following side reactions have not as yet been reported with oxazepam, they have occurred with related compounds (chlordiazepoxide and diazepam): paradoxical excitation with severe rage reactions, hallucinations, menstrual irregularities, change in EEG pattern, blood dyscrasias including agranulocytosis, blurred vision, diplopia, incontinence, stupor, disorientation, fever, and euphoria.

Transient amnesia or memory impairment has been reported in association with the use of benzodiazepines.