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Pronunciation
(oks A ze pam)
Generic Available (U.S.)
Yes: Capsule
Controlled Substance
C-IV
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Use: Labeled Indications
Treatment of anxiety; management of ethanol withdrawal
Use: Unlabeled/Investigational
Anticonvulsant in management of simple partial seizures; hypnotic
Pregnancy Considerations
Oxazepam crosses the placenta. Teratogenic effects have been observed with some benzodiazepines; however, additional studies are needed. The incidence of premature birth and low birth weights may be increased following maternal use of benzodiazepines; hypoglycemia and respiratory problems in the neonate may occur following exposure late in pregnancy. Neonatal withdrawal symptoms may occur within days to weeks after birth and “floppy infant syndrome” (which also includes withdrawal symptoms) have been reported with some benzodiazepines.
Breast-Feeding Considerations
Drowsiness, lethargy, or weight loss in nursing infants have been observed in case reports following maternal use of some benzodiazepines.
Contraindications
Hypersensitivity to oxazepam or any component of the formulation (cross-sensitivity with other benzodiazepines may exist); narrow-angle glaucoma (not in product labeling, however, benzodiazepines are contraindicated); not indicated for use in the treatment of psychosis; pregnancy
Warnings/Precautions
Concerns related to adverse effects:
• Anterograde amnesia: Benzodiazepines have been associated with anterograde amnesia.
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Hypotension: May cause hypotension (rare); use with caution in patients with cardiovascular or cerebrovascular disease, or in patients who would not tolerate transient decreases in blood pressure.
• Paradoxical reactions: Paradoxical reactions, including hyperactive or aggressive behavior, have been reported with benzodiazepines, particularly in adolescent/pediatric or psychiatric patients.
Disease-related concerns:
• Depression: Use caution in patients with depression, particularly if suicidal risk may be present.
• Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Impaired gag reflex: Use with caution in patients with an impaired gag reflex.
• Renal impairment: Use with caution in patients with renal impairment.
• Respiratory disease: Use with caution in patients with respiratory disease.
Concurrent drug therapy issues:
• CNS depressants/psychoactive medications: Use with caution in patients receiving other CNS depressants or psychoactive medication; effects with other sedative drugs or ethanol may be potentiated.
Special populations:
• Debilitated patients: Use with caution in debilitated patients.
• Elderly: Due to increased sensitivity in this age group, smaller doses of benzodiazepines may be safer and as effective. Avoid using doses >60 mg daily of oxazepam (Beers Criteria).
• Fall risk: Use with extreme caution in patients who are at risk of falls; benzodiazepines have been associated with falls and traumatic injury.
• Pediatrics: Safety and efficacy in established in pediatric patients <6 years of age; dose has not been established between 6-12 years of age.
Dosage form specific issues:
• Tartrazine: Serax® 15 mg tablet contains tartrazine.
Other warnings/precautions:
• Appropriate use: Does not have analgesic, antidepressant, or antipsychotic properties.
• Withdrawal: Rebound or withdrawal symptoms may occur following abrupt discontinuation or large decreases in dose. Use caution when reducing dose or withdrawing therapy; decrease slowly and monitor for withdrawal symptoms. Flumazenil may cause withdrawal in patients receiving long-term benzodiazepine therapy.
Adverse Reactions
Frequency not defined.
Cardiovascular: Syncope (rare), edema
Central nervous system: Drowsiness, ataxia, dizziness, vertigo, memory impairment, headache, paradoxical reactions (excitement, stimulation of effect), lethargy, amnesia, euphoria
Dermatologic: Rash
Endocrine & metabolic: Decreased libido, menstrual irregularities
Genitourinary: Incontinence
Hematologic: Leukopenia, blood dyscrasias
Hepatic: Jaundice
Neuromuscular & skeletal: Dysarthria, tremor, reflex slowing
Ocular: Blurred vision, diplopia
Miscellaneous: Drug dependence
Drug Interactions
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
CloZAPine: Benzodiazepines may enhance the adverse/toxic effect of CloZAPine. Risk D: Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Exceptions: Levocabastine (Nasal). Risk C: Monitor therapy
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
Fosphenytoin: Benzodiazepines may increase the serum concentration of Fosphenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy. Risk C: Monitor therapy
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: For patients being treated with hydroxyzine, a reduction in the dose of any other CNS depressants that are to be used in combination is recommended. With concurrent use, monitor patients closely for excessive response to the combination. Risk D: Consider therapy modification
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification
OLANZapine: May enhance the adverse/toxic effect of Benzodiazepines. Management: Avoid concomitant use of parenteral benzodiazepines and IM olanzapine due to risks of additive adverse events (e.g., cardiorespiratory depression). Olanzapine prescribing information provides no specific recommendations regarding oral administration. Risk X: Avoid combination
Phenytoin: Benzodiazepines may increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy
Theophylline Derivatives: May diminish the therapeutic effect of Benzodiazepines. Risk D: Consider therapy modification
Yohimbine: May diminish the therapeutic effect of Antianxiety Agents. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: May increase CNS depression; monitor for increased effects with coadministration. Caution patients about effects.
Herb/Nutraceutical: Avoid valerian, St John's wort, kava kava, gotu kola (may increase CNS depression).
Mechanism of Action
Binds to stereospecific benzodiazepine receptors on the postsynaptic GABA neuron at several sites within the central nervous system, including the limbic system, reticular formation. Enhancement of the inhibitory effect of GABA on neuronal excitability results by increased neuronal membrane permeability to chloride ions. This shift in chloride ions results in hyperpolarization (a less excitable state) and stabilization.
Pharmacodynamics/Kinetics
Absorption: Almost complete
Protein binding: 86% to 99%
Metabolism: Hepatic to inactive compounds (primarily as glucuronides)
Half-life elimination: 2.8-5.7 hours
Time to peak, serum: 2-4 hours
Excretion: Urine (as unchanged drug [50%] and metabolites)
Dosage
Oral:
Adults:
Anxiety: 10-30 mg 3-4 times/day
Ethanol withdrawal: 15-30 mg 3-4 times/day
Hypnotic: 15-30 mg
Elderly: Oral: Anxiety: 10 mg 2-3 times/day; increase gradually as needed to a total of 30-45 mg/day. Dose titration should be slow to evaluate sensitivity.
Hemodialysis: Not dialyzable (0% to 5%)
Administration: Oral
Administer orally in divided doses.
Monitoring Parameters
Respiratory and cardiovascular status
Reference Range
Therapeutic: 0.2-1.4 mcg/mL (SI: 0.7-4.9 μmol/L)
Patient Education
Drug may cause physical and/or psychological dependence. Do not use alcohol. Maintain adequate hydration unless instructed to restrict fluid intake. You may experience drowsiness, lightheadedness, impaired coordination, dizziness, blurred vision, nausea, vomiting, dry mouth, or constipation. Report persistent CNS effects (eg, confusion, depression, suicide ideation, increased sedation, excitation, headache, agitation, insomnia or nightmares, dizziness, fatigue, impaired coordination, changes in personality, or changes in cognition) or worsening of condition.
Geriatric Considerations
Because of its relatively short half-life and its lack of active metabolites, oxazepam is recommended for use in the elderly when a benzodiazepine is indicated.
This medication is considered to be potentially inappropriate in this patient population (Beers Criteria severity: High).
Additional Information
Not intended for management of anxieties and minor distresses associated with everyday life. Treatment longer than 4 months should be re-evaluated to determine the patient's need for the drug. Abrupt discontinuation after sustained use (generally >10 days) may cause withdrawal symptoms.
Anesthesia and Critical Care Concerns/Other Considerations
Not intended for management of anxieties and minor distresses associated with everyday life; treatment >4 months should be re-evaluated to determine the patient's need for the drug. Chronic use of this agent may increase the perioperative benzodiazepine dose needed to achieve desired effect. Abrupt discontinuation after sustained use (generally >10 days) may cause withdrawal symptoms.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation).
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Comment
In 2007, the FDA requested that all manufacturers of sedative-hypnotic drug products revise labeling to include a greater emphasis on the risks of adverse effects. These risks include severe allergic reactions (anaphylaxis, angioedema) and complex sleep-related behaviors, which may include sleep-driving (driving while not fully awake and with no memory of the event), making phone calls, and preparing and eating food while asleep.
There are two subtypes of GABA receptors (GABA-A and GABA-B) and three different benzodiazepine receptors (Bz1, Bz2, and Bz3). Benzodiazepine receptors and effects appear to be linked to the GABA-A receptors. Benzodiazepines do not bind to GABA-B receptors. The role of GABA-B receptors is unclear. Benzodiazepines have no specificity for benzodiazepine receptor subtypes.
Oxazepam is a short half-life benzodiazepine. Duration of action after a single dose is determined by redistribution rather than metabolism. Tolerance develops to the sedative, hypnotic, and anticonvulsant effects. It does not develop to the anxiolytic or skeletal muscle relaxing effects. Psychological and physical dependence may occur with prolonged use of benzodiazepines. The onset of withdrawal symptoms is usually seen on the first day without drug and lasts 5-7 days in patients receiving short half-life benzodiazepines, whereas, the onset occurs after 5 days with a duration of 10-14 days after abrupt discontinuance of long half-life benzodiazepines. Risk factors for abuse include personal or family history of substance abuse and personality disorder. Oxazepam undergoes phase II metabolism and, therefore, is less likely to be affected in patients with hepatic dysfunction.
Nursing: Physical Assessment/Monitoring
Assess for history of addiction; long-term use can result in dependence, abuse, or tolerance; periodically evaluate need for continued use. For inpatient use, institute safety measures to prevent falls. Monitor for oversedation, dizziness, confusion, or ataxia which may impair physical and mental capabilities. Taper dosage slowly when discontinuing.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, oral: 10 mg, 15 mg, 30 mg
Serax®: 10 mg, 15 mg, 30 mg
Tablet, oral:
Serax®: 15 mg [contains tartrazine]
Pricing: U.S. (www.drugstore.com)
Capsules (Oxazepam)
10 mg (30): $17.99
15 mg (30): $21.99
30 mg (30): $35.99
References
American Academy of Pediatrics Committee on Drugs, "Transfer of Drugs and Other Chemicals Into Human Milk,” Pediatrics, 2001, 108(3):776-89.
Bergman U, Rosa FW, Baum C, et al, "Effects of Exposure to Benzodiazepine During Fetal Life," Lancet, 1992, 340(8821):694-6.
Hicks R, Dysken MW, Davis JM, et al, “The Pharmacokinetics of Psychotropic Medication in the Elderly: A Review,” J Clin Psychiatry, 1981, 42(10):374-85.
Iqbal MM, Sobhan T, Ryals T, et al, "Effects of Commonly Used Benzodiazepines on the Fetus, the Neonate, and the Nursing Infant," Psychiatr Serv, 2002, 53(1):39-49.
Kangas L, Erkkola R, Kanto J, et al, "Transfer of Free and Conjugated Oxazepam Across the Human Placenta," Eur J Clin Pharmacol, 1980, 17(4):301-4.
Mokhlesi B, Leikin JB, Murray P, et al, “Adult Toxicology in Critical Care: Part II: Specific Poisonings,” Chest, 2003, 123(3):897-922.
Moshkowitz M, Pines A, Finkelstein A, et al, “Skin Blisters as a Manifestation of Oxazepam Toxicity,” J Toxicol Clin Toxicol, 1990, 28(3):383-6.
Wikner BN, Stiller CO, Bergman U, et al, "Use of Benzodiazepines and Benzodiazepine Receptor Agonists During Pregnancy: Neonatal Outcome and Congenital Malformations," Pharmacoepidemiol Drug Saf, 2007, 16(11):1203-10.
Zileli MS, Teletar F, Deniz S, et al, “Oxazepam Intoxication Simulating Nonketo-Acidotic Diabetic Coma,” JAMA, 1971, 215(12):1986.
International Brand Names
Lexi-Comp.com
Last full review/revision May 2011
Content last modified May 2011
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