This information is intended for use by health professionals

1. Name of the medicinal product

Oxazepam 10 mg tablets

2. Qualitative and quantitative composition

Each tablet contains 10 mg of oxazepam.

Excipient with known effect:

Lactose monohydrate – 95 mg

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Tablet.

White tablet marked “OM” break line “10” 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

Posology

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 an extended withdrawal period during which doses are reduced. Long-term chronic use is not recommended.

Adults

Severe anxiety: The recommended dosage is 15-30 mg three or four times daily.

Insomnia associated with anxiety

Most patients need a dose of 15-25 mg but some patients may need up to 50 mg. The dose should be taken one hour before retiring.

Elderly patients and those who are particularly sensitive to benzodiazepines. The recommended dosage is 10-20 mg three or four times daily.

Children

Oxazepam is not recommended for the treatment of anxiety or insomnia in children.

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.

Method of administration

For oral administration only.

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

Tolerance

Some loss of efficacy to the hypnotic effects of benzodiazepines may develop after repeated use for a few weeks.

Dependence

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 extreme anxiety, headache, muscle pain, insomnia, tension, restlessness, confusion and irritability. 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.

Duration of treatment

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 re-evaluation 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.

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.

Psychiatric and paradoxical reaction

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.

Amnesia

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 (see section 4.8).

Specific patient groups

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 or marked personality disorder. Suicide may be precipitated in patients who are depressed and aggressive behaviour toward self and others may be precipitated.

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, 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.

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).

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

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 affect**, 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, gastrointestinal disturbances.

Hepatobiliary disorders

Increased liver enzymes, jaundice.

Skin and subcutaneous tissue disorders

Minor diffuse skin rashes (morbilliform, urticarial and macropapular).

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.

* 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.

Amnesia

Anterograde amnesia may occur using therapeutic dosages, the risk increasing at higher dosages.

Amnestic 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.

Withdrawal

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. Other symptoms such as depression, persistent tinnitus, involuntary movements, paraesthesia, perceptual changes, confusion, convulsions, abdominal and muscle cramps and vomiting may be characteristic of benzodiazepine withdrawal syndrome.

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, ataxia, dysarthria, nystagmus and lethargy, in more serious cases, symptoms may include 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 Monohydrate

Maize Starch

Isopropyl Alcohol

Povidone K30

Magnesium Stearate

Sodium Starch Glycollate

6.2 Incompatibilities

None

6.3 Shelf life

3 years

6.4 Special precautions for storage

Store below 25°C.

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.

PVC/PVdC/Aluminium blisters containing 28 tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

None.

7. Marketing authorisation holder

Generics [UK] Ltd t/a Mylan

Station Close

Potters Bar

Herts

EN6 1TL

UK

8. Marketing authorisation number(s)

PL 04569/0102

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

06/2017