Oxazepam 30 Mg Tablets
1
NAME OF THE MEDICINAL PRODUCT
Oxazepam 30 mg tablets 2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 30 mg of oxazepam.
Excipient with known effect:
Lactose - 85 mg
For the full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM Tablet.
Orange tablet marked “OM” break line “30” on one side and “G” on the other.
4. CLINICAL PARTICULARS
4.1. Therapeutic Indications
Oxazepam tablets are indicated for the short-term relief (2-4 weeks) only of anxiety that is severe, disabling or subjecting the individual to unacceptable distress, occurring alone or in association with insomnia or short term psychosomatic, organic or psychotic illness.
The use of Oxazepam to treat short-term ‘mild’ anxiety is considered to be inappropriate and unsuitable.
4.2 Posology and method of administration
For oral administration only.
Adults
Severe anxiety: The recommended dosage is 15-30mg three or four times daily.
Insomnia associated with anxiety:
Most patients need a dose of 15-25mg but some patients may need up to 50mg. The dose should be taken one hour before retiring.
Elderly patients and those who are particularly sensitive to benzodiazepines The recommended dosage is 10-20mg three or four times daily.
Children
Oxazepam is not recommended for the treatment of anxiety or insomnia in children.
For patients with impaired liver and/or renal function, lower doses may be sufficient.
Treatment of anxiety should not be continued beyond 8-12 weeks including a tapering off period.
Treatment of insomnia should be as short as possible. Generally, the duration of treatment varies from a few days to two weeks with a maximum, including tapering off process of four weeks.
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 for the shortest possible time. The maximum dose should not be exceeded. In certain cases extension beyond the maximum treatment period may be necessary; if so, it should not take place without re-evaluation of the patient’s status with special expertise.
All patients taking oxazepam should be carefully monitored and routine repeat prescriptions should be avoided.
Patients who have taken benzodiazepines for a long time may require a longer period during which doses are reduced. Long-term chronic use is not recommended.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Myasthenia gravis, hypersensitivity to benzodiazepines, phobic or obsessional states, chronic psychosis, respiratory depression, acute pulmonary insufficiency, sleep apnoea syndrome, severe hepatic insufficiency.
4.4 Special warnings and precautions for use
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. Therefore, benzodiazepines should be used with extreme caution in patients with a history of alcohol or drug abuse.
Once physical dependence has developed, abrupt discontinuation of benzodiazepines may be associated with physiological and psychological symptoms of withdrawal including depression, anxiety, headache, muscle pain, insomnia, tension, restlessness, irritability and sweating. Other symptoms such as persistent tinnitus, involuntary movements, paraesthesia, perceptual changes, confusion, convulsions, abdominal and muscle cramps and vomiting may be characteristic of benzodiazepine withdrawal syndrome. In severe cases the following symptoms may occur: derealisation, depersonalisation, hyperacusis, numbness and tingling of the extremities, hypersensitivity to light, noise and physical contact, hallucinations or epileptic seizures.
Rebound insomnia and anxiety: a transient syndrome whereby the symptoms that led to treatment with a benzodiazepine recur in 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 dosage be decreased gradually.
The duration of treatment should be as short as possible (see also 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 a 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 it will be of limited duration and 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 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.
Reactions like restlessness, agitation, irritability, aggressiveness, delusion, rages, nightmares, hallucinations, psychoses, inappropriate behaviour and other adverse behavioural 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 elderly.
Benzodiazepines may induce anterograde amnesia. The condition occurs most often several hours after ingesting the product and therefore to reduce the risk to patients should ensure that they will be able to have an uninterrupted sleep of 7-8 hours.
In cases of loss or bereavement, psychological adjustment may be inhibited by benzodiazepines. Disinhibiting effects may be manifested in various ways. Suicide may be precipitated in patients who are depressed and aggressive behaviour toward self and others may be precipitated. Extreme caution should therefore be used in prescribing benzodiazepines in patients with personality disorders.
Benzodiazepines should not be used alone to treat depression or anxiety associated with depression. Benzodiazepines are not recommended for the primary treatment of psychotic illness.
A lower dose is 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.
Benzodiazepines are not indicated to treat patients with renal impairment, muscle weakness or porphyria.
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)
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
Concomitant intake with alcohol is not recommended. The sedative effect may be enhanced when the product is used in combination with alcohol. This affects the ability to drive or use machines.
Take into account the combination of benzodiazepines with central nervous system (CNS) depressants. Enhancement of the central depressive effect may occur in cases of concomitant use with antipsychotics (neuroleptics), hypnotics, anxiolytics/sedatives, antidepressant agents, narcotic analgesics, anaesthetics and sedating antihistamines, lofexidine, nabilone and tizanidine. In the case of narcotic analgesics enhancement of the euphoria may also occur leading to an increase in psychic dependence.
Compounds which inhibit certain hepatic enzymes (particularly cytochrome P450) may enhance the activity of benzodiazepines.
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).
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).
4.6 Fertility, pregnancy and lactation
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 late 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.
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, impaired concentration and impaired muscular function may adversely affect the ability to drive or to use machines. If insufficient sleep duration occurs, the likelihood of impaired alertness may be increased (see also section 4.5). As with all patients on CNS depressant drugs,
patients should be warned not to drive or operate machinery until it is known that they do not become drowsy or dizzy from Oxazepam.
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
• 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
4.8 Undesirable effects
Drowsiness during the day, numbed emotions, reduced alertness, confusion, fatigue, vertigo, headache, syncope, dizziness, muscle weakness, ataxia or double vision: These phenomena occur predominantly at the start of therapy and usually disappear with repeated administration. Occasionally hypotension has occurred. Blurred vision, disorientation, dreams and fever have also occurred. Other side effects like gastro-intestinal disturbances, nausea, changes in libido, skin reactions (morbilliform, urticarial and macropapular), lethargy, oedema, slurred speech, tremor, blood dyscrasias, leukopenia, jaundice, increased liver enzymes, salivation changes, dysarthria, incontinence and urinary retention have been reported occasionally. Mild excitatory effects with stimulation of affect have sometimes been reported in psychiatric patients these reactions usually appear in the first two weeks of therapy.
Anterograde amnesia may occur using therapeutic doses, the risk increasing at high dosages. Amnesic effects may be associated with inappropriate behaviour.
Pre-existing depression with suicidal tendencies may be unmasked during benzodiazepine use.
Reactions like restlessness, agitation, irritability, aggressiveness, delusion, rages, nightmares, hallucinations, psychoses, inappropriate behaviour and other adverse behavioural effects are known to occur when using benzodiazepines. They may be quite severe and are more likely to occur in children and older people.
Use (even at therapeutic doses) may lead to the development of physical dependence: Discontinuation of the therapy may result in withdrawal or rebound phenomenon (see also section 4.4). Psychic dependence may occur. Abuse has been reported.
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 given 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 patients clinical state. The patient is likely to sleep and therefore a clear airway should be maintained.
Overdosage 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, dysarthria, nystagmus and lethargy, in more serious cases, symptoms may include ataxia, hypotonia, hypotension, respiratory depression, rarely coma and very rarely death.
Flumazenil, 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: Benzodiazepine derivatives, ATC code: N05BA04
Oxazepam is a benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant and amnesic properties. Its actions are mediated by enhancement of the activity of aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain.
5.2 Pharmacokinetic properties
Oxazepam is well absorbed from the gastrointestinal tract and reaches peak plasma concentrations in about 1 - 5 hours. Oxazepam is extensively bound to plasma proteins and has been reported to have a half-life ranging from about 6 to 20 hours. It is the ultimate pharmacologically active metabolite of diazepam and is itself largely metabolised to the inactive glucuronide which is excreted in the urine. Oxazepam has a volume of distribution of 0.4-2.3 L.kg-1.
Oxazepam crosses the placental barrier and is excreted in breast milk; lethargy and weight loss may occur in breast fed infants.
5.3 Preclinical safety data
There are no preclinical safety data of relevance to the prescriber, which are additional to those already included in other sections of the SmPC.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Lactose Hydrous 200,
Maize Starch,
Isopropyl Alcohol, Povidone K30,
Magnesium Stearate Sodium Starch Glycollate,
Quinoline yellow (E104) Erythrosine (E127)
6.2. Incompatibilities
None
6.3. Shelf Life
3 years
6.4 Special precautions for storage
Store in the original package. Protect from light. Store in a cool dry place.
6.5 Nature and contents of container
Polyethylene container with polyethylene tamper evident caps, fitted with a general polyethylene ullage filler in packs of 100, 250, 500 and 1000 tablets.
6.6 Special precautions for disposal
None.
7 MARKETING AUTHORISATION HOLDER
Generics [UK] Ltd t/a Mylan Station Close Potters Bar Herts EN6 1TL
8. MARKETING AUTHORISATION NUMBER
PL 04569/0104
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of first authorisation: 28th April 1986 Date of latest renewal: 31st January 2003
10 DATE OF REVISION OF THE TEXT
24/06/2014