Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2020 Publisher: Tillomed Laboratories Limited, 220 Butterfield, Great Marlings, Luton, LU2 8DL, UK
Patients should be advised that since their tolerance for alcohol and other CNS depressants will be diminished in the presence of oxazepam, these substances should either be avoided or taken in reduced dosage.
Some loss of efficacy to the hypnotic effects of benzodiazepines may develop after repeated use for a few weeks.
Use of benzodiazepines may lead to the development of physical and psychic dependence upon these products. The risk of dependence increases with dose and duration of treatment; it is also greater in patients with a history of alcohol or drug abuse, or in patients with significant personality disorders.
Dependence may lead to withdrawal symptoms (see section 4.8), especially if treatment is discontinued abruptly.
Rebound insomnia and anxiety: a transient syndrome whereby the symptoms that led to treatment with a benzodiazepine recur in an enhanced form, may occur on withdrawal of treatment. It may be accompanied by other reactions including mood changes, anxiety or sleep disturbances and restlessness.
It may be useful to inform the patient that treatment will be of limited duration and that it will be discontinued gradually.
The patient should also be made aware of the possibility of “rebound” phenomena to minimise anxiety should they occur.
Abuse of benzodiazepines has been reported.
Due to the potential adverse reactions including ataxia, muscle weakness, dizziness, drowsiness and fatigue (see section 4.8), Benzodiazepines may be associated with an increased risk of falling especially in elderly patients. As a result, caution should be exercised particularly when getting up at night. The elderly should receive a reduced dose (see section 4.2).
The duration of treatment should be as short as possible (see section 4.2) depending on the indication, but should not exceed 4 weeks for insomnia and eight to twelve weeks in case of anxiety, including tapering off process. Extension beyond these periods should not take place without reevaluation of the situation.
It may be useful to inform the patient when treatment is started that it will be of limited duration and to explain precisely how the dosage will be progressively decreased. Moreover it is important that the patient should be aware of the possibility of rebound phenomena, thereby minimising anxiety over such symptoms should they occur while the medicinal product is being discontinued.
There are indications that, in the case of benzodiazepines with a short duration of action, withdrawal phenomena can become manifest within the dosage interval, especially when the dosage is high.
When benzodiazepines with a long duration are being used it is important to warn against changing to a benzodiazepine with a short duration of action, as withdrawal symptoms may develop.
Concomitant use of oxazepam and opioids may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing of sedative medicines such as benzodiazepines or related drugs such as oxazepam with opioids should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe oxazepam concomitantly with opioids, the lowest effective dose should be used, and the duration of treatment should be as short as possible (see also general dose recommendation in section 4.2).
The patients should be followed closely for signs and symptoms of respiratory depression and sedation. In this respect, it is strongly recommended to inform patients and their caregivers (where applicable) to be aware of these symptoms (see section 4.5).
Benzodiazepines may induce anterograde amnesia. This condition usually occurs several hours after ingestion therefore patients should ensure that they will be able to have a period of uninterrupted sleep which is sufficient to allow dissipation of drug effect (e.g. 7-8 hours) wherever possible.
Reactions like restlessness, agitation, irritability, aggressiveness, delusion, rages, nightmares, hallucinations, psychoses, inappropriate behavior and other adverse behavioral effects are known to occur when using benzodiazepines. Should this occur, use of the medicinal product should be discontinued.
They are more likely to occur in children and the elderly.
Benzodiazepines should not be given to children without careful assessment of the need to do so; the duration of treatment must be kept to a minimum. Elderly should be given a reduced dose (see section 4.2). A lower dose is also recommended for patients with chronic respiratory insufficiency due to the risk of respiratory depression. Benzodiazepines are not indicated to treat patients with severe hepatic insufficiency as they may precipitate encephalopathy, renal impairment, muscle weakness or porphyria.
Benzodiazepines are not recommended for the primary treatment of psychotic illness or marked personality disorder.
Benzodiazepines should not be used alone to treat depression or anxiety associated with depression (suicide may be precipitated in such patients). Also, pre-existing depression may emerge during benzodiazepine use.
Benzodiazepines should be used with extreme caution in patients with a history of alcohol or drug abuse.
Caution should be used in the treatment of patients with acute narrow-angle glaucoma.
Patients with impaired renal or hepatic function should be monitored frequently and have their dosage adjusted carefully according to response. Lower doses may be sufficient in these patients. The same precautions apply to elderly or debilitated patients and patients with chronic respiratory insufficiency.
Some patients taking benzodiazepines have developed a blood dyscrasia, and some have had elevations in liver enzymes. Periodic haematologic and liver-function assessments are recommended where repeated courses of treatment are considered clinically necessary.
Although hypotension has occurred only rarely, benzodiazepines should be administered with caution to patients in whom a drop in blood pressure might lead to cardiovascular or cerebrovascular complications. This is particularly important in elderly patients.
Oxazepam tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
The following drug interactions with oxazepam should be considered:
Alcohol
Concomitant intake with alcohol is not recommended. The sedative effects may be enhanced when oxazepam is used in combination with alcohol. This effects the ability to drive or use machines.
Combination with CNS depressants
Enhancement of other CNS depressant drugs such as barbiturates, antipsychotics, narcotic analgesics (enhancement of euphoria may also occur, leading to an increase in psychic dependence), antidepressants, hypnotics, anticonvulsants, anaesthetics, sedative antihistamines, lofexidine, nabilone and tizanidine.
Opioids
The concomitant use of sedative medicines such as benzodiazepines or related drugs such as oxazepam with opioids increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect. The dosage and duration of concomitant use should be limited (see section 4.4).
Muscle Relaxants
When taken with muscle relaxants, the overall muscle-relaxing effect may be increased (accumulative) therefore caution is advised, especially in elderly patients and at higher doses (risk of falling, see Section 4.4).
Oestrogen containing contraceptives (concurrent use may cause a decrease in plasma levels of oxazepam).
Antibacterials (Rifampicin may increase the metabolism of oxazepam).
Antivirals (concurrent use of zidovudine with benzodiazepines may decrease Zidovudine clearance. Ritonavir may inhibit benzodiazepine hepatic metabolism). The clinical significance of these interactions has yet to be established.
Antiepileptic drugs (concurrent use of phenytoin may cause oxazepam serum levels to fall. Side effects may be more evident with hydantoins or barbiturates).
Antihypertensives (enhanced hypotensive effects. Enhances sedative effect with alpha blockers or moxonidine)
Dopaminergics (concurrent use with benzodiazepines may decrease the therapeutic effects of levodopa).
Baclofen (enhanced sedative effect).
Probenecid (may increase effects and possibility of excessive sedation).
Compounds which inhibit certain hepatic enzymes (particularly cytochrome P450) may enhance the activity of benzodiazepines. To a lesser degree this also applies to benzodiazepines that are metabolised only by conjugation.
If the product is prescribed to a woman of childbearing potential, she should be warned to contact her physician regarding discontinuance of the product if she intends to become or suspects that she is pregnant.
Benzodiazepines should not be used during pregnancy, especially during the first and last trimesters. Benzodiazepines may cause foetal damage when administered to pregnant women.
There is a possibility that infants born to mothers who took benzodiazepines chronically during the later stages of pregnancy may develop physical dependence. The infant may also develop withdrawal symptoms during the postnatal period such as hypoactivity, hypotonia, hypothermia, respiratory depression, apnoea, feeding problems, and impaired metabolic response to cold stress.
The concentration of oxazepam and its conjugate in human breast milk is approximately 10% of the plasma level. Therefore, oxazepam should not be administered to breast-feeding mothers.
Sedation, amnesia, dizziness and impaired muscular function may adversely affect the ability to drive or use machines. If insufficient sleep occurs, the likelihood of impaired alertness may be increased (see also section 4.5).
This medicine can impair cognitive function and can affect a patient’s ability to drive safely. This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988. When prescribing this medicine, patients should be told:
*The medicine is likely to affect your ability to drive
Blood and lymphatic system disorders: Blood dyscrasias, leucopenia
Psychiatric disorders: Mild drowsiness*, disorientation, dreams, †nightmares, lethargy, amnesia (see below), mild excitatory effects with stimulation of effect**, numbed emotions, reduced alertness, †restlessness, †agitation, †irritability, †delusions, †rages, †psychoses, †inappropriate behaviour, behavioural adverse effects including paradoxical †aggressive outbursts, excitement, †hallucinations, confusion, uncovering of depression with suicidal tendencies***.
† These are more likely to occur in children and the elderly.
Nervous system disorders: Dizziness, light-headedness*, ataxia, vertigo, headache, syncope, slurred speech, tremor, dysarthria.
Eye disorders: Blurred vision, double vision.
Vascular disorders: Hypotension.
Gastrointestinal disorders: Nausea, salivation changes, gastro-intestinal disturbances.
Hepatobiliary disorders: Increased liver enzymes, jaundice.
Skin and subcutaneous tissue disorders: Minor diffuse skin rashes (morbilliform, urticarial and maculopapular).
Musculoskeletal and connective tissue disorders: Muscle weakness.
Renal and urinary disorders: Incontinence, urinary retention.
Reproductive system and breast disorders: Altered libido.
General disorders and administration site conditions: Fever, oedema, fatigue.
Injury, poisoning and procedural complications: Fall.
* Commonly seen in the first few days of therapy. If this becomes troublesome dosage should be reduced.
** Reported in psychiatric patients and usually occur within the first few weeks of therapy.
*** Extreme caution should therefore be exercised in prescribing benzodiazepines to patients with personality disorders.
Anterograde amnesia may occur using therapeutic dosages, the risk increasing at higher dosages. Amnesic effects may be associated with inappropriate behaviour (see section 4.4).
When used at the appropriate recommended dosage for short term treatment of anxiety the dependence potential of oxazepam is low. However, the risk of dependence increases with higher doses and longer-term use and is further increased in patients with a history of alcoholism, drug abuse or in patients with marked personality disorders (see section 4.4).
As with all benzodiazepines, withdrawal may be associated with physiological and psychological symptoms including depression, persistent tinnitus, involuntary movements, paraesthesia, perceptual changes, confusion, convulsions, muscle cramps, abdominal cramps and vomiting.
Symptoms such as anxiety, depression, headache, insomnia, tension and sweating have been reported following abrupt discontinuation of benzodiazepines and these symptoms may be difficult to distinguish from the original symptoms of anxiety.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard.
None known.
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