OXAZEPAM
|
DESCRIPCION Oxazepam is an oral benzodiazepine used for the management of symptoms associated with anxiety disorders and for short-term amelioration of the symptoms of anxiety or anxiety associated with depression. Oxazepam is often preferable to chlordiazepoxide, flurazepam, and prazepam in treating anxiety or insomnia, particularly in the elderly or in patients with liver disease, because oxazepam has a relatively short half-life and does not generate active metabolites. Oxazepam was approved by the FDA in 1965 Mecanismo de acción: Benzodiazepines act at the level of the limbic, thalamic, and hypothalamic regions of the CNS and can produce any level of CNS depression required including sedation, hypnosis, skeletal muscle relaxation, and anticonvulsant activity. Recent evidence indicates that benzodiazepines exert their effects through enhancement of the gamma-aminobutyric acid (GABA)-benzodiazepine receptor complex. GABA is an inhibitory neurotransmitter that exerts its effects at specific receptor subtypes designated GABA-A and GABA-B. GABA-A is the primary receptor subtype in the CNS and is thought to be involved in the actions of anxiolytics and sedatives. Specific benzodiazepine receptor subtypes are thought to be coupled to GABA-A receptors. Three types of BNZ receptors are located in the CNS and other tissues; the BNZ1 receptors are located in the cerebellum and cerebral cortex, the BNZ2 receptors in the cerebral cortex and spinal cord, and the BNZ3 receptors in peripheral tissues. Activation of the BNZ1 receptor is thought to mediate sleep while the BNZ2 receptor affects muscle relaxation, anticonvulsant activity, motor coordination, and memory. Benzodiazepines bind nonspecifically to BNZ1 and BNZ2 which ultimately enhances the effects of GABA. Unlike barbiturates which augment GABA responses by increasing the length of time that chloride channels are open, benzodiazepines enhance the effects of GABA by increasing GABA affinity for the GABA receptor. Binding of GABA to the site opens the chloride channel resulting in a hyperpolarized cell membrane that prevents further excitation of the cell. Benzodiazepines alleviate insomnia by decreasing the latency to sleep and increasing sleep continuity and total sleep time through their effects on GABA. Pharmacokinetics: Oxazepam is administered orally and is rapidly absorbed. The onset of action occurs within 60—120 minutes. The drug is widely distributed and is approximately 85%—95% protein-bound. This benzodiazepine may cross the placenta or distribute into breast milk (see Contraindications). The half-life of oxazepam is 5—15 hours. Metabolism occurs in the liver by direct conjugation with glucuronic acid to produce inactive metabolites. Subsequently, the metabolites are excreted in the urine. Indications...Dosage For the treatment of anxiety: •for treatment of mild to moderate anxiety: Oral dosage: Adults and adolescents: 10—15 mg PO 3—4 times per day. Elderly and debilitated patients: Initially, 10 mg PO three times daily; increase with caution up to 15 mg three times daily or four times daily if needed and tolerated. In general, elderly patients tolerate typical adult dosages of oxazepam. Federal OBRA guidelines recommend daily dose not exceed 60 mg/day PO, unless higher doses are needed for maintenance of the resident's functional status. Avoid any single dose > 30 mg PO. Children age 6—12 years: An absolute dose has not been established for this age group; a dose of 1 mg/kg/day PO, administered in divided doses 3—4 times per day is a suggested average effective dose. Dosage should be carefully titrated from a low initial dosage. Children age < 6 years: Safe and effective use has not been established. •for treatment of severe anxiety and agitation associated with depression: Oral dosage: Adults: 10—30 mg PO 3—4 times per day. Elderly and debilitated patients: Initially, 10 mg PO three times daily; increase with caution up to 15 mg three times daily or four times daily if needed and tolerated. In general, elderly patients tolerate typical adult dosages of oxazepam. Federal OBRA guidelines recommend daily dose not exceed 60 mg/day PO, unless higher doses are needed for maintenance of the resident's functional status. Avoid any single dose > 30 mg PO. •for the short-term treatment of insomnia† related to transient, situational anxiety: Adults: 10—25 mg PO as a single dose given one hour before retiring. For treatment of acute ethanol withdrawal: Oral dosage: Adults: 15—30 mg PO three times daily or four times daily; the elderly may need a reduced initial dose. Patients with hepatic impairment: No specific dosage adjustment appears necessary. Oxazepam's elimination has not been shown to be significantly impaired in hepatic disease like hepatitis or cirrhosis compared to control patients. Oxazepam is metabolized by glucuronidation to inactive metabolites. Patients with renal impairment: It appears that no dosage adjustments are needed; adjust dosage according to patient response and tolerance. Oxazepam is not removed by hemodialysis. Oral Administration •May administer without regard to meals. Contraindications Some tablet preparations of oxazepam contain tartrazine dye that can cause allergic reactions or bronchial asthma in patients with tartrazine dye hypersensitivity. This reaction occurs more frequently in patients who are allergic to aspirin. Oxazepam can cause physical and psychological dependence, and should be used with extreme caution in patients with known, suspected, or a history of substance abuse. Abrupt discontinuation of oxazepam after prolonged use can cause seizures in susceptible patients. The severity of withdrawal symptoms may be associated with higher doses. Abrupt discontinuation of benzodiazepine therapy has been reported to cause withdrawal symptoms such as irritability, nervousness, and insomnia. Benzodiazepine withdrawal is more likely to occur following abrupt cessation after excessive or prolonged doses, but it can occur following the discontinuance of therapeutic doses administered for as few as 1—2 weeks. Benzodiazepine withdrawal also can be more intense if the benzodiazepine involved possesses a relatively short duration of action such as alprazolam or oxazepam. Abdominal cramps, confusion, depression, perceptual disturbances, sweating, nausea, vomiting, parasthesias, photophobia, hyperacusis, tachycardia, and trembling also occur during benzodiazepine withdrawal, but the incidence of these reactions is lower. Convulsions, hallucinations, delirium, and paranoia also can occur. Benzodiazepines should be withdrawn cautiously and slowly, using a very gradual dosage-tapering schedule. Oxazepam should be used with extreme caution in patients with respiratory depression, pulmonary disease such as severe COPD (chronic obstructive pulmonary disease), or sleep apnea because the drug can exacerbate ventilatory failure. Oxazepam should be used with extreme caution in patients with myasthenia gravis because the drug can exacerbate this condition. The administration of oxazepam can exacerbate acute intermittent porphyria, so the drug should be used with caution in patients with this condition. Oxazepam is occasionally beneficial for patients with major depression or psychosis. The drug should be administered cautiously to patients with suicidal ideation. Oxazepam is classified as pregnancy category D because it can cause harm to the fetus when administered to pregnant women. Positive evidence of human fetal risk exists based on investigational, marketing, or human studies, but the potential benefit to the mother may outweigh the potential risks to the fetus. Oxazepam might be distributed into breast milk, causing sedation, feeding difficulties, and weight loss in the nursing infant. The use of oxazepam during breast-feeding is generally not recommended. Oxazepam should be administered cautiously to patients with severe renal impairment because the elimination half-life of the drug can be prolonged, possibly resulting in toxicity. Patients with late stage Parkinson's disease may experience worsening of their psychosis or impaired cognition with administration of benzodiazepines. Benzodiazepines may also cause incoordination or paradoxical reactions that may worsen symptoms of Parkinson's disease. The clearance and/or elimination of many drugs are reduced in the elderly. Delayed elimination can either intensify or prolong the actions of adverse reactions of the drug. Benzodiazepines have been associated with falls in the elderly. The impairment of cognitive and motor function may be more marked in this patient group and lower initial dosage is recommended together with close monitoring (see Dosage). The safe and effective use of oxazepam in children under 6 years old has not been established and an absolute dose for children between 6—12 years has not been established. Children are generally more sensitive to the CNS effects of the benzodiazepines. Interactions Concomitant administration of oxazepam with CNS-depressant drugs, including opiate agonists, butorphanol, nalbuphine, pentazocine, phenothiazines, barbiturates, entacapone, ethanol, some H1-blockers (e.g., brompheniramine, carbinoxamine, cetirizine, chlorpheniramine, clemastine, cyproheptadine, dimenhydrinate, diphenhydramine, doxylamine, methdilazine, promethazine, trimeprazine), general anesthetics, tramadol, tricyclic antidepressants, or other anxiolytics, sedatives, and hypnotics, can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent. Oral contraceptives can decrease the effects of oxazepam because oral contraceptives enhance glucuronidation, thereby decreasing serum concentrations of concomitantly administered benzodiazepines that undergo glucuronidation. Patients receiving oral contraceptive therapy should be observed for evidence of decreased response to oxazepam. Probenecid may inhibit the hepatic metabolism of oxazepam although this interaction has been documented with other benzodiazepines and not oxazepam per se. Patients receiving benzodiazepines should be monitored for signs of an exaggerated response if probenecid is used concomitantly. Flumazenil and benzodiazepines are pharmacological opposites. Flumazenil is specifically used to reverse the actions of benzodiazepines. Clinicians should note that the duration of action for some benzodiazepines may be much longer than that of flumazenil and repeat doses of flumazenil may be necessary. It appears prudent to recommend caution when oxazepam is prescribed in conjunction with melatonin. In animal studies, melatonin has been shown to increase benzodiazepine binding to receptor sites, and this may result in clinically significant drug interactions. Case reports exist of concomitant benzodiazepine and melatonin use in humans; the cases resulted in lethargy, short-term amnestic responses, or prolonged benzodiazepine activity. These apparent interactions could have been the result of a pharmacokinetic or pharmacodynamic enhancement of benzodiazepine activity by melatonin. An interaction of kava kava, Piper methysticum with benzodiazepines has been reported in the medical literature. A single case report is noted of an acute, lethargic and disoriented state in a 54-year old male following the ingestion of alprazolam and kava kava for 3 consecutive days. After several hours, he gradually became more alert. The gentleman denied taking more than his normal prescribed dose of alprazolam or excessive doses of kava kava.[1839] The possibility of interactions at normal prescription dosages of benzodiazepines signals the need for patients to avoid concomitant administration of kava kava. Any substances that act on the CNS, including psychopharmacologic agents, may interact with valerian, Valeriana officinalis. These interactions are probably pharmacodynamic in nature, or result from additive mechanisms of action. The possibility of pharmacodynamic interactions at normal prescription dosages of anxiolytics, sedatives, and hypnotics signals the need for patients to avoid concomitant administration of valerian. Adverse Reactions Most of the adverse effects associated with oxazepam therapy are dose-dependent and CNS-related including headache, drowsiness, ataxia, dizziness, confusion, depression, syncope, fatigue, tremor, and vertigo. Daytime anxiety or wakefulness during the last third of the night may develop during several weeks of consistent nightly dosing with oxazepam. These effects are thought to be due to the development of tolerance, which leads to a deficiency of benzodiazepine binding sites. CNS stimulation can occur in as many as 10% of patients receiving benzodiazepines and is of particular significance in psychiatric patients and hyperactive children. This paradoxical effect is possibly due to disinhibition of previously inhibited responses. Symptoms of CNS stimulation include nightmares, talkativeness, excitement, mania, tremor, insomnia, anxiety, restlessness, euphoria, acute rage reactions, and hyperactivity. Benzodiazepine therapy usually should be discontinued if signs of CNS stimulation occur. Physiological dependence on oxazepam is evidenced by manifestation of withdrawal symptoms. Abrupt withdrawal of benzodiazepine therapy has been reported to cause withdrawal symptoms such as irritability, nervousness, and insomnia. Benzodiazepine withdrawal is more likely to occur following abrupt cessation of excessive or prolonged doses, but it can occur following the discontinuance of therapeutic doses administered for as few as 1—2 weeks. Abdominal cramps, confusion, depression, perceptual disturbances, sweating, nausea, vomiting, parasthesias, photophobia, hyperacusis, tachycardia, and trembling also occur during benzodiazepine withdrawal, but the incidence of these reactions is lower. Convulsions, hallucinations, delirium, and paranoia also can occur. Benzodiazepines should be withdrawn cautiously and slowly, using a very gradual dosage-tapering schedule. PRESENTACION El oxazepam no se comercializa en España como monofármaco SUXIDINA: Dimeticona, Enzimas amilolíticas lipolíticas proteolítica, Metoclopramida clorhidrato, Oxazepam succinato. REID |
|
REFERENCIAS
|
