Oxazepam Tablets Bp 30mg
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Oxazepam 30 mg Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 30mg of Oxazepam
Excipient with known effect: Each tablet contains 84.9 mg of lactose For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Tablet
Pink compressed FBE tablet with break line one side, or coded OXA 30 and break line one side, twin triangle logo on reverse
The score line is not intended for breaking the tablet
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Oxazepam is recommended for short term use of approximately 2-4 weeks.
As with all benzodiazepines, doctors should be aware that long term use may lead to dependence and withdrawal symptoms in certain patients.
Oxazepam is indicated for the short-term treatment of anxiety that is disabling or subjecting the individual to unacceptable distress, occurring alone or in association with psychosomatic, organic or psychotic illness.
4.2 Posology and method of administration
Posology
In all cases the dosage of Oxazepam should be titrated according to the needs of the individual patient and the lowest effective dose necessary to control symptoms should be used. Oxazepam should not be used for long term chronic treatment.
Adults
Severe Anxiety
30 - 60 mg three times daily. Less Severe Anxiety
30 mg three times daily and 30 mg at night.
Patients with severe sleep disturbance can be given 60 mg at night.
Elderly
Elderly patients may respond to lower doses and the lowest adult dose should be used initially.
All patients taking Oxazepam should be carefully monitored and routine repeat prescriptions should be avoided. Treatment in all patients should be withdrawn gradually with careful monitoring and reassessment to minimise possible withdrawal symptoms. Patients who have taken benzodiazepines for a long time may require a longer period during which doses are reduced. Should longer term therapy be necessary then intermittent treatment may be considered to minimise the risk of dependence. Treatment should not be continued beyond 4 weeks.
Paediatric population
Not recommended for children.
Method of administration
For oral administration.
4.3 Contraindications
(a) Hypersensitivity to benzodiazepines or to any excipients listed in section 6.1.
(b) To treat short-term ‘mild’ anxiety: their use here is inappropriate and unsuitable.
(c) Alone, to treat depression or anxiety associated with depression. Suicide may be precipitated in such patients.
(d) For phobic or obsessional states.
(e) For the treatment of chronic psychosis.
(f) In acute pulmonary insufficiency and where there is respiratory depression.
(g) In patients with myasthenia gravis.
(h) In patients with sleep apnoea syndrome.
(i) In severe hepatic insufficiency.
4.4 Special warnings and precautions for use
Dependence
Dependence (and therefore withdrawal symptoms) can occur with therapeutic doses given for short periods of time, as well as high doses or prolonged administration. Thus the lowest dose which can control symptoms should be used and long term chronic use is not recommended. When used as anxiolytics, benzodiazepams should not be continued beyond four 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.
Once physical dependence has developed, abrupt termination of treatment will be accompanied by withdrawal symptoms.
Whatever the indication, treatment should always be tapered off gradually to negate withdrawal symptoms. Patients who have taken benzodiazepines for a long time may require a longer period during which these doses are reduced. Possible withdrawal symptoms include extreme anxiety, tremor, confusion, insomnia, perceptual disorders, fits, depression, headaches, muscle pain, tension, restlessness, confusion and irritability, sweating, gastrointestinal and other somatic symptoms. These sometimes may be difficult to distinguish from the symptoms of the original illness. In severe cases the following symptoms may occur: derealisation, depersonalisation, hyperacusis, numbness and tingling of extremities, hypersensitivity to light, noise and physical contact, hallucinations or epileptic seizures. Withdrawal effects usually appear shortly after stopping a benzodiazepine with a short half life, or up to several days after stopping one with a long half life. Symptoms may continue for weeks or months.
Other symptoms such as persistent tinnitus, involuntary movements, paraesthesia, perceptual changes and confusion may be characteristic of benzodiazepine withdrawal syndrome.
The use of benzodiazepines may release suicidal tendencies in depressed patients. Oxazepam should not be used alone to treat depression or anxiety associated with depression. Other rarely reported behavioural effects of the benzodiazepines include paradoxical aggressive outbursts, excitement and confusion. Amnesia may occur and in cases of loss or bereavement psychological adjustment may be inhibited by benzodiazepines.
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. Since the risk of withdrawal phenomena/rebound phenomena is greater after abrupt discontinuation of treatment, it is recommended that the dosage is gradually decreased.
Psychiatric and paradoxical reaction
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.
Tolerance
Some loss of efficacy to the hypnotic effects of benzodiazepines may develop after repeated use for a few weeks.
Duration of treatment
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.
Amnesia
Benzodiazepines may induce anterograde amnesia. The condition occurs most often several hours after ingesting the product and therefore to reduce the risk patients should ensure that they will be able to have an uninterrupted sleep of 7-8 hours (see also section.4.8).
Specific patient groups
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). The elderly may also experience confusion and the dosage of Oxazepam should not exceed one-half the usual recommended adult dose. The use of benzodiazepines with other centrally acting drugs is likely to increase the sedative effects. This is especially so in the elderly.
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. Oxazepam is conjugated in the liver.
Benzodiazepines are not recommended for the primary treatment of psychotic illness or marked personality disorder.
Benzodiazepines should be used with extreme caution in patients with a history of alcohol or drug abuse.
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.
4.5 Interaction with other medicinal products and other forms of interaction
Not recommended
Alcohol
Concomitant intake with alcohol.
The sedative effects may be enhanced when the product is used in combination with alcohol. This effects the ability to drive or use machines.
Take into account
Combination with CNS depressants
Enhancement of other CNS depressant drugs such as antipsychotics (neuroleptics), narcotic analgesics (enhancement of the euphoria may also occur leading to an increase in psychic dependence), antidepressant, hypnotics, anxiolytics/sedatives, anaesthetics and sedative antihistamines, lofexidine, nabilone and tizanidine.
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.
4.6 Fertility, pregnancy and lactation
Pregnancy
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.
If, for compelling medical reasons, the product is administered during the latter phase of pregnancy, or during labour at high doses, effects on the neonate, such as hypothermia, hypotonia and moderate respiratory depression, can be expected, due to the pharmacological action of the compound.
Moreover, infants born to mothers who took benzodiazepines chronically during the latter stages of pregnancy may have developed physical dependence and may be at some risk for developing withdrawal symptoms in the postnatal period.
Breast-feeding
Since benzodiazepines are found in the breast milk, benzodiazepines should not be given to breast feeding mothers.
4.7 Effects on ability to drive and use machines
Sedation, amnesia 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: 1
4.8 Undesirable effects
Blood and lymphatic system disorders
Blood dyscrasias, leucopenia Psychiatric disorders
Mild drowsiness1, disorientation, dreams, nightmares, lethargy, amnesia (see below), mild excitatory effects with stimulation of effect2 3, numbed emotions, reduced alertness, restlessness, agitation, irritability, delusions, rages, psychoses, inappropriate behaviour, behavioural adverse effects include paradoxical aggressive outbursts, excitement, hallucinations, aggression, confusion, uncovering of depression with suicidal tendencies4.
These are more likely to occur in children and the elderly.
Nervous system disorders
Dizziness, light-headedness1, ataxia, vertigo, headache, syncope, slurred speech, tremor, dysarthria.
Eye disorders
Blurred vision, visual disturbances, double vision.
Vascular disorders
Hypotension, hypertension
Gastrointestinal disorders
Nausea, salivation changes, gastro-intestinal disturbances.
Hepatobiliary disorders
Increased liver enzymes, and 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.
*** Extreme caution should therefore be exercised in prescribing benzodiazepines to patients with personality disorders.
Amnesia
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).
Dependence
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.
Use (even at therapeutic doses) may lead to the development of physical dependence: discontinuation of the therapy may result in withdrawal of rebound phenomena (see section 4.4). Psychic dependence may occur. Abuse of benzodiazepines has been reported.
Withdrawal
As with all benzodiazepines, withdrawal may be associated with physiological and psychological symptoms including persistent tinnitus, involuntary movements, paraesthesia, perceptual changes, 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 of suspected adverse reactions
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.
4.9 Overdose
As with other benzodiazepines, overdose should not present a threat to life unless combined with other CNS depressants (including alcohol).
In the management of overdose with any medicinal product, it should be borne in mind that multiple agents may have been taken.
Following overdose with oral benzodiazepines, activated charcoal should be considered to reduce absorption. 50g for adults and 10-15g for children if they have taken more than 1mg/kg within 1 hour, provided they are not too drowsy.
Special attention should be paid to respiratory and cardiovascular functions in intensive care. Supportive measures are indicated depending on the patient’s clinical state. The patient is likely to sleep and therefore a clear airway should be maintained.
Overdose of benzodiazepines is usually manifested by degrees of central nervous system depression ranging from drowsiness to coma. In mild cases, symptoms include drowsiness, mental confusion, dysarthia, nystagmus and lethargy, in more serious cases, symptoms may include ataxia, hypotoniahypotension, respiratory depression and rarely coma, very rarely death.
Flumazenil (Anexate), a benzodiazepine antagonist, is available but should rarely be required. It has a short half-life (about an hour). Flumazenil is NOT TO BE USED IN MIXED OVERDOSE OR AS A "DIAGNOSTIC" TEST.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Oxazepam is a benzodiazepine tranquilliser. It is used in the short-term treatment of anxiety.
ATC Code: N05BA
5.2 Pharmacokinetic properties
Oxazepam is reported to be readily and completely absorbed from the gastro-intestinal tract, with a half life ranging from about 6 to 20 hours. It is the ultimate pharmacologically active metabolite of diazepam. Oxazepam is conjugated with glucuronic acid in the liver and excreted in urine as the pharmacologically inactive glucuronide.
Oxazepam is extensively bound to plasma proteins with a free fraction of 4-13% which is partly responsible for the large variation in the volume of distribution. Data are not available on the concentration of Oxazepam in the CSF or brain tissue in man. It is excreted in human milk in small amounts. It readily crosses the placental barrier and the concentration is higher in the foetus than in the mother.
5.3 Preclinical safety data
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Lactose Maize Starch
Pregelatinised Maize Starch Anstead Dispersed Pink (11150) Magnesium Stearate
6.2 Incompatibilities
None known.
6.3 Shelf life
3 years
6.4 Special precautions for storage
Store in a cool dry place. Store in the original container in order to protect from light.
6.5 Nature and contents of container
A polypropylene tubular container with a tamper-evident tear strip in pack sizes of: 7, 14, 21, 28, 30, 50, 56, 60, 84, 90, 100, 112, 120, 250, 500 and 1000 tablets or PVdC coated PVC/Aluminium blisters (60/m2 PVdC on 250p PVC/20p A1) in pack sizes of: 7, 14, 21, 28, 30, 50, 56, 60, 84, 90, 100, 112 and 120 tablets.
Not all pack sizes may be marketed
6.6 Special precautions for disposal and other handling
No special requirements for disposal.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
Tillomed Laboratories Limited
3 Howard Road
Eaton Socon
St Neots
Cambridgeshire
PE19 8ET
UK
8 MARKETING AUTHORISATION NUMBER(S)
PL 11311/0528
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
Date of first authorization: 22/10/1979 Date of latest renewal: 16/12/2008
10 DATE OF REVISION OF THE TEXT
22/06/2016
The medicine is likely to affect your ability to drive
• Do not drive until you know how the medicine affects you
• It is an offence to drive while under the influence of this medicine
• However, you would not be committing an offence (called ‘statutory defence’) if:
o The medicine has been prescribed to treat a medical or dental problem and
o You have taken it according to the instructions given by the prescriber and in the information provided with the medicine and o It was not affecting your ability to drive safely
Commonly seen in the first few days of therapy. If it becomes troublesome dosage should be reduced.
Reported in psychiatric patients and usually occur within the first few weeks of
therapy.