Temazepam 10mg / 5ml Oral Solution

1. Name Of The Medicinal Product

Temazepam 10mg/5ml Oral Solution

2. Qualitative And Quantitative Composition

Temazepam BP 10mg/5ml

3. Pharmaceutical Form

An elixir containing 10mg Temazepam BP per 5ml for oral administration.

4. Clinical Particulars

4.1 Therapeutic Indications

Temazepam is indicated for the short term treatment of sleep disturbances, considered severe or disabling or where insomnia is subjecting the individual to extreme distress. This product is especially useful in those patients for whom particularly rapid onset of hypnotic action is required and for whom the persistence of hypnotic effect after rising would be undesirable.

Temazepam is particularly suitable for patients with transient sleep disorders in whom re-establishment of normal sleep patterns is expected following the resolution of precipitating factors.

It is also indicated for pre-medication for minor surgical and investigative procedures, especially in the case of outpatients.

4.2 Posology And Method Of Administration

For oral administration only.

Adults:

Insomnia: Each 5ml dose of Temazepam Elixir is equivalent to 10mg Temazepam. The usual dose is 5 - 15ml orally on retiring; a dose of 10ml will be found to be satisfactory for most patients. This may be increased to 15 - 20ml (30 - 40mg Temazepam) in patients who do not respond to the lower dose. Lower doses may be adequate for some patients, as for the elderly.

Pre- medication

10 - 20ml from half an hour to one hour prior to surgery or investigative procedures.

Elderly:

Elderly patients or those suffering from cerebral vascular changes such as arteriosclerosis are likely to respond to smaller doses. Half the normal dose, 2.5 to 7.5ml (5 - 15mg) may be sufficient for a therapeutic response.

Children:

Insomnia: Not recommended

Pre-medication:

1mg (0.5ml)/Kg one hour prior to surgery or investigative procedures.

Treatment should if possible be intermittent. The lowest dose which can control symptoms should be used. It should not be continued beyond 4 weeks.

Long term chronic use is not recommended.

Treatment should always be tapered off gradually. Patients who have taken benzodiazepines for a long time may require a longer period during which doses are reduced.

4.3 Contraindications

Myasthenia gravis

Known hypersensitivity to Benzodiazepines.

Severe respiratory insufficiency.

Sleep apnoea syndrome.

Severe hepatic insufficiency.

Phobic or obsessional state; chronic psychosis

Mild anxiety states

Acute narrow angle glaucoma

As monotherapy in patients with depression or those with anxiety and depression (suicide may be precipitated in these patients)

4.4 Special Warnings And Precautions For Use

Doses of 30mg and above are more likely to cause hangover effects to persist into the following day than lower doses, particularly in patients unused to hypnotics and in the elderly. As with all compounds which have an effect on the CNS, patients should be advised not to consume alcohol whilst taking temazepam.

An underlying cause for insomnia should be sought before deciding upon the use of benzodiazepines for symptomatic relief.

Temazepam should be given with caution to patients with chronic pulmonary insufficiency, or those with renal or hepatic dysfunction.

Where Temazepam is used as a medication before surgical or investigative procedures, the patients should be accompanied home.

Tolerance: Some loss of efficacy to the hypnotic effects of short acting benzodiazepines may develop after repeated use for a few weeks

Psychiatric and 'paradoxical' reactions: 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 product should be discontinued. These reactions are more likely to occur in the elderly.

Benzodiazepines are not recommended for the primary treatment of psychotic illness.

Dependence potential and withdrawal symptoms: In general, the dependence potential of benzodiazepines is low, but this increases when high dosage is used, especially when given over long periods. This is particularly so in patients with a history of alcoholism, drug abuse or in patients with marked personality disorders. Regular monitoring of treatment in such patients is essential and routine repeat prescriptions should be avoided.

Treatment in all patients should be withdrawn gradually as symptoms such as depression, nervousness, rebound insomnia, irritability, sweating, headaches, dizziness, impaired concentration, tinnitus, loss of appetite, tremor, perceptual disturbances, nausea, vomiting, abdominal cramps, palpitations, mild systolic hypertension, tachycardia, orthostatic hypotension, photophobia, hyperacusis, muscle pain, extreme anxiety, tension, restlessness, confusion and diarrhoea have been reported following abrupt cessation of treatment with benzodiazepines in patients receiving even normal therapeutic doses for short periods of time. Abrupt withdrawal following excessive dosage may produce confusion, toxic psychosis, convulsions, derealisation, depersonalisation, tingling of extremities, hypersensitivity to light, noise and physical contact, hallucinations, epileptic seizures or a condition resembling delirium tremens. Broken sleep with vivid dreams may persist for some weeks after withdrawal.

Benzodiazepines should be used with extreme caution in patients with a history of alcohol or drug abuse.

In cases of loss or bereavement, psychological adjustment may be inhibited by benzodiazepines.

Extreme caution should be used in prescribing benzodiazepines in patients with personality disorders.

Excipient Warnings

This product contains sorbitol. Patients with rare hereditary problems of fructose intolerance should not take this medicine.

This product contains 10%v/v ethanol, i.e. up to 395mg per dose equivalent to 10ml of beer or 4ml of wine per dose. It is harmful for those suffering from alcoholism. It should be taken into account in high-risk groups such as patients with liver disease or epilepsy. It may modify or increase the effect of other medicines.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

The concurrent use of other CNS depressants such as general anaesthetics, antipsychotics, monoamine oxidase inhibitors, anxiolytics/sedatives, sedative antihistamines, anti-depressants and hypnotics, lofexidine and nabilone should be avoided as it will result in an enhancement of the central depressive effect. In the case of narcotic analgesics enhancement of the euphoria may also occur leading to an increase in psychotic dependence.

Alcohol - Concomitant intake is not recommended.

The sedative effects may be enhanced when the product is used in combination with alcohol. This affects the ability to drive or use machines.

Antiepileptic drugs– plasma phenytoin concentrations may be increased or decreased by temazepam. Phenytoin levels may need monitoring during temazepam withdrawal. Side effects may be more evident with hydantoins or barbiturates.

Antihypertensives– enhanced hypotensive effects. Enhances sedative effect with alpha blockers or moxonidine.

Antivirals– concurrent use of zidovudine with benzodiazepines may decrease zidovudine clearance. Ritonavir may inhibit benzodiazepine hepatic metabolism

Clozapine– reports of cardiorespiratory collapse. Also increase in hypersalivation with both drugs.

Disulfiram– inhibits the metabolism of benzodiazepines and enhances sedative effect. May cause temazepam toxicity.

Dopaminergics– concurrent use with benzodiazepines may decrease the therapeutic effects of levodopa.

Muscle relaxants– Baclofen and Tizanidine – enhanced sedative effect.

4.6 Pregnancy And Lactation

Insufficient data are available on temazepam to assess its safety during pregnancy and lactation. If the product is prescribed to a woman of child bearing age, she should be warned to contact her physician about stopping the product if she intends to become, or suspects that she is, pregnant. If for compelling medical reasons, temazepam is administered during the late phase of pregnancy, or during labour, effects on the neonate, such as hypothermia, hypotonia, and moderate respiratory depression, can be expected due to the pharmacological action of the product. Moreover, infants born to mothers who took benzodiazepines chronically during the later stages of pregnancy may have developed physical dependence and may be at some risk of developing withdrawal symptoms in the postnatal period.

Since benzodiazepines are found in breast milk, temazepam should not be administered 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 Interactions).

4.8 Undesirable Effects

Anterograde amnesia may occur using therapeutic dosages, the risk increasing at higher dosages. Amnesia may be associated with inappropriate behaviour. In cases of loss or bereavement, psychological adjustment may be inhibited by benzodiazepines.

Common adverse effects of benzodiazepines include drowsiness, sedation, blurring of vision, unsteadiness, numbed emotions, reduced alertness, dizziness, muscle weakness, ataxia, fatigue, respiratory depression or slurred speech. These phenomena occur predominantly at the start of therapy and usually disappear thereafter. These symptoms are likely to be potentiated by alcohol. The elderly are more liable to experience such effects.

Abnormal psychological reaction to benzodiazepines has been reported.

Rare behavioural adverse effects include paradoxical aggressive outbursts, excitement, confusion, restlessness, agitation, irritability, delusion, rages, nightmares, hallucinations, psychoses, inappropriate behaviour and the uncovering of depression with suicidal tendencies. Should this occur, use of the product should be discontinued. Extreme caution should therefore be used in prescribing benzodiazepines in patients with personality disorders. These reactions are more likely to occur in the elderly.

Other adverse effects, including hypotension, gastro-intestinal and visual disturbances, skin rashes, urinary retention, headache, vertigo, changes in libido, dry mouth, restless sleep, dysarthria, tremor, hypersalivation, hypersensitivity, incontinence, blood dyscrasias and jaundice have been reported occasionally.

Dependence: Use (even at therapeutic doses) may lead to the development of physical dependence: Discontinuation of therapy may result in withdrawal of rebound phenomena (See warnings and precautions). Psychotic dependence may occur. Abuse has been reported in polydrug users.

4.9 Overdose

Symptoms

Benzodiazepines commonly cause drowsiness, ataxia, dysarthria, mental confusion and nystagmus. Coma, hypotension, hypotonia and respiratory depression occasionally occur but are seldom serious if these drugs are taken alone. Coma usually lasts only a few hours but in elderly people it may be more protracted and cyclical. Benzodiazepine respiratory depressant effects are more serious in patients with severe chronic respiratory disease. Benzodiazepines potentiate the effects of other central nervous system depressants, including alcohol.

Management

Consider activated charcoal in adults or children who have taken more than 1mg/kg within 1 hour, provided they are not too drowsy. The benefit of gastric decontamination is uncertain. Gastric lavage is unnecessary if these drugs have been taken alone. The value of dialysis has not been determined for temazepam. Patients who are asymptomatic at four hours are unlikely to develop symptoms. Institute supportive measures as indicated by the patient's clinical state. If CNS depression is severe consider the use of flumazenil (Anexate), a benzodiazepine antagonist. This should rarely be required. It has a short half-life (about an hour) and should NOT TO BE USED IN MIXED OVERDOSE OR AS A "DIAGNOSTIC" TEST. It is contraindicated in the presence of drugs that reduce seizure threshold (e.g. tricyclic antidepressants).

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Temazepam has a similar pharmacological action to Oxazepam and Diazepam, that is central nervous system sedation, anxiolysis and muscle relaxation. Animal studies show anticonvulsant activity. These effects are likely to be due to potentiation of gamma-aminobutyric acid (GABA) although other neurotransmitters may also be affected. Evidence suggests a close molecular association between the sites and action for GABA and the benzodiazepines.

5.2 Pharmacokinetic Properties

Reported elimination half-life values for Temazepam after night time administration in young volunteers vary from 5.3 - 11.5 hours. There is, however, an approximately 30% increase in the half-life of Temazepam when taken in the morning. The mean elimination half-life values in young volunteers after morning administration vary from 8.3 - 13.6 hours. In the elderly the half-life may be longer with a mean value of about 15 hours. The half-life in elderly women may be longer than in elderly men.

5.3 Preclinical Safety Data

None

6. Pharmaceutical Particulars

6.1 List Of Excipients

Ethanol

Propylene Glycol

Peppermint Oil

Caramel E150

Trometamol

Citric Acid Monohydrate

Patent Blue V E131

Glycerol

Sorbitol Solution 70%

Purified Water

6.2 Incompatibilities

None known

6.3 Shelf Life

24 months

After opening 3 months

6.4 Special Precautions For Storage

Store between 4°C and 25°C and protect from light.

6.5 Nature And Contents Of Container

100ml, 150ml, 200ml, 300ml, 450ml and 500ml amber glass bottles. Aluminium, wadded, roll-on pilfer proof closures or HDPE, EPE wadded, tamper evident child resistant closures or HDPE, EPE wadded, tamper evident closures.

6.6 Special Precautions For Disposal And Other Handling

Keep out of the reach of children.

Administrative Data

7. Marketing Authorisation Holder

Rosemont Pharmaceuticals Ltd

Rosemont House

Yorkdale Industrial Park

Braithwaite Street

Leeds

LS11 9XE

8. Marketing Authorisation Number(S)

PL 00427/0089

9. Date Of First Authorisation/Renewal Of The Authorisation

26.9.95

10. Date Of Revision Of The Text

13 Jan 2010