SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Temazepam Oral Solution BP

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 5 ml of Temazepam Oral Solution BP contains 10 mg Temazepam.

3 PHARMACEUTICAL FORM

A clear, green, lemon-mint flavoured elixir.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Temazepam Oral Solution BP is indicated for the short-term treatment (up to 4 weeks including any tapering off) of insomnia, when it is disabling or subjecting the individual to extreme distress, and for premedication before minor surgery or other procedures, especially when hospital admission is not essential.

4.2 Posology and method of administration

Insomnia:

Dosage and duration of therapy should be individualised. The lowest effective dose should be prescribed for the shortest time possible. Generally, the duration of treatment varies from a few days to 4 weeks including the tapering off process. Extension of the treatment period should not take place without re-evaluation of the need for continued therapy.

Since insomnia is often transient and intermittent, the prolonged administration of Temazepam Oral Solution BP is generally unnecessary and is not recommended.

Treatment in all patients should be withdrawn gradually to minimise possible withdrawal symptoms. ( See 4.4 Special warnings and precautions for use).

Dosage:

Adults:

10-20mg, but in severe or persistent insomnia, it may be increased up to 40mg. The solution should be taken up to 30 minutes before going to bed.

Elderly:

10mg. If this dose is not effective, it may be cautiously increased to 20mg.

Children:

The safety and efficacy of Temazepam Oral Solution BP in children less than 18 years of age has not been established and such use is not recommended.

Premedication:

Adults:

20-30mg taken 30-60 minutes prior to surgery or other procedures.

Elderly:

Elderly patients are likely to respond to smaller doses, possibly half the normal adult dose. Children:

The safety and efficacy of Temazepam Oral Solution BP in children less than 18 years of age has not been established and such use is not recommended.

Patients should be accompanied home when Temazepam Oral Solution BP has been used as a premedicant prior to surgery or other procedures on a day attendance basis.

4.3 Contraindications

Severe respiratory insufficiency Sleep apnoea syndrome

Hypersensitivity to benzodiazepines including Temazepam Oral Solution BP or its components.

Myasthenia gravis Severe hepatic failure

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).

Temazepam Oral Solution BP should not be given to children

4.4 Special warnings and precautions for use

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. Patients should be advised that since their tolerance for alcohol and other CNS depressants will be diminished in the presence of Temazepam Oral Solution BP, these substances should either be avoided or taken in reduced dosage.

Temazepam Oral Solution BP is not intended for the primary treatment of psychotic illness or depressive disorders, and should not be used alone to treat depressed patients with associated insomnia. The use of benzodiazepines may have a disinhibiting effect and may release suicidal tendencies in depressed patients. Therefore, large quantities of Temazepam Oral Solution BP should not be prescribed to these patients.

Pre-existing depression may emerge during benzodiazepine use.

The use of benzodiazepines may lead to physical and psychological dependence. The risk of dependence on Temazepam Oral Solution BP is low when used at the recommended dose and duration, but increases with higher doses and longer term use. The risk of dependence is further increased in patients with a history of alcoholism or drug abuse or in patients with significant personality disorders. Therefore, use in individuals with a history of alcoholism or drug abuse should be avoided.

Dependence may lead to withdrawal symptoms, especially if treatment is discontinued abruptly. Therefore, the drug should always be discontinued gradually.

Symptoms reported following discontinuation of benzodiazepines include headaches, muscle pain, anxiety, tension, depression, insomnia, restlessness, confusion, irritability, sweating, and the occurrence of "rebound" phenomena whereby the symptoms that led to treatment with benzodiazepines recur in an enhanced form. These symptoms may be difficult to distinguish from the original symptoms for which the drug was prescribed.

In severe cases the following symptoms may occur: derealisation; depersonalisation; hyperacusis; tinnitus; numbness and tingling of the extremities; hypersensitivity to light, noise, and physical contact; involuntary movements; vomiting; hallucinations; convulsions. Convulsions may be more common in patients with pre-existing seizure disorders or who are taking other drugs that lower the convulsive threshold such as antidepressants.

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 has been reported in poly-drug users.

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

Insomnia may be a symptom of several other disorders. The possibility should be considered that the complaint may be related to an underlying physical or psychiatric disorder for which there is more specific treatment.

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 patient response. Lower doses may be sufficient in these patients. The same precautions apply to elderly or debilitated patients and patients with chronic respiratory insufficiency.

As with all CNS-depressants, the use of benzodiazepines may precipitate encephalopathy in patients with severe hepatic insufficiency. Therefore, use in these patients is contraindicated.

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 when long-term therapy is clinically necessary.

Transient anterograde amnesia or memory impairment has been reported in association with the use of benzodiazepines. 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).

Paradoxical reactions have been occasionally reported during benzodiazepines use (see 4.8 Undesirable Effects). Such reactions may be more likely to occur in children and the elderly. Should these occur, use of the drug should be discontinued.

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.

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

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.

In animal studies, an increased perinatal mortality has been seen following concomitant administration of temazepam and diphenhydramine to rabbits in the later stages of gestation compared with rabbits that received either drug alone. In humans, one case of stillbirth at term has been reported, occurring 8 hours after a pregnant patient received temazepam and diphenhydramine. Although a causal relationship has not been established it is recommended that the use of temazepam be avoided in pregnant women receiving antihistamines.

4.6 Pregnancy and lactation

Benzodiazepines should not be used during pregnancy, especially during the first and last trimesters. Benzodiazepines may cause foetal damage when administered to pregnant women.

If the drug is prescribed to a woman of childbearing potential. she should be warned to contact her physician about stopping the drug if she intends to become, or suspects that she is pregnant.

There is a possibility that infants born to mothers who take benzodiazepines chronically during the latter stages of pregnancy may develop physical dependence. Infants of mothers who ingested benzodiazepines for several weeks or more preceding delivery have been reported to have withdrawal symptoms during the postnatal period. Symptoms such as hvpoactivity, hypotonia, hvpothermia, respiratory depression, apnoea, feeding problems, and impaired metabolic response to cold stress have been reported in neonates born of mothers who have received benzodiazepines during the late phase of pregnancy or at delivery.

It is recommended that the use of temazepam be avoided in pregnant women receiving antihistamines (See Interactions).

Benzodiazepines are found in breast milk. In common with other benzodiazepines, temazepam should not be prescribed for mothers who are breast-feeding.

4.7    EFFECTS ON ABILITY TO DRIVE AND USE MACHINES

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.

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

(See also 4.5 Interactions with other Medicaments and other forms of Interaction)

4.8    UNDESIRABLE EFFECTS

Adverse reactions, when they occur, are usually observed at the beginning of therapy and generally decrease in severity or disappear with continued use or upon decreasing the dose.

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 or rebound phenomena (See warnings and precautions). Psychotic dependence may occur. Abuse has been reported in polydrug users.

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

In the management of overdosage with any drug, it should be borne in mind that multiple agents may have been taken.

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, and lethargy. In more serious cases, and especially when other CNS-depressant drugs or alcohol are ingested, symptoms may include ataxia, hypotension, hypotonia, respiratory depression, coma, and very rarely, death.

If ingestion was recent, induced vomiting and or gastric lavage should be undertaken, followed by general supportive care, monitoring of vital signs and close observation of the patient. If there is no advantage in emptying the stomach, activated charcoal may be effective in reducing absorption. Hypotension, though unlikely. may be controlled with noradrenaline. Temazepam is poorly dialysable.

The benzodiazepine antagonist, flumazenil may be useful in hospitalised patients for the management of benzodiazepine overdosage. Flumazenil product information should be consulted prior to use.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Temazepam is a benzodiazepine; it has anxiolytic, sedative and hypnotic characteristics as well as possible muscle relaxant and anticonvulsant characteristics.

5.2 Pharmacokinetic properties

Temazepam is well absorbed and rapidly excreted. Peak plasma levels are usually reached in 20 to 50 minutes. Temazepam has a plasma half life of about ten hours (range 5-15 hours). It is largely metabolised by a simple one-step process to a pharmacologically inert glucuronide. There are no major active metabolites and little risk of accumulation. Clinical studies have shown minimised effects on REM sleep patterns and on psychomotor performance on the day after treatment with Temazepam Oral Solution BP.

5.3 Preclinical safety data

No additional information of relevance to the prescriber.

List of excipients

Povidone 25; Polyethylene glycol 400; Ethanol Absolute; Glycerol; Sodium Phosphate, anhydrous; Citric acid; Chlorophyll; Sorbitol Solution 70%; Peppermint oil; Lemon flavour; Glycerol.

Incompatibilities

None stated.

MARKETING AUTHORISATION HOLDER

Focus Pharmaceuticals Ltd Capital House,

85 King William Street,

London EC4N 7BL,

United Kingdom.

MARKETING AUTHORISATION NUMBER(S)

PL 20046/0054

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 01/06/1999/ 16/01/2004

10 DATE OF REVISION OF THE TEXT

13/06/2016