Diazepam Rectal Tubes (Sandoz Limited)

1. Name Of The Medicinal Product

Diazepam Rectal Tubes 5mg.

Diazepam Rectal Tubes 10mg.

2. Qualitative And Quantitative Composition

Diazepam Rectal Tubes 5mg:

Each rectal tube contains diazepam BP 5mg in 2.5ml of fluid.

Diazepam Rectal Tubes 10mg:

Each rectal tube contains diazepam BP 10mg in 2.5ml of fluid.

3. Pharmaceutical Form

Rectal tube.

4. Clinical Particulars

4.1 Therapeutic Indications

Diazepam has anticonvulsant, anxiolytic, sedative, muscle relaxant and amnesic properties.

It is indicated:

i. For the short-term relief (2 to 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;

ii. As a sedative and premedicant;

iii. As an anticonvulsant in the management of status epilepticus, febrile convulsions and poisoning;

iv. In the control of muscle spasms as in tetanus;

v. In the management of alcohol withdrawal symptoms;

The use of diazepam to treat short-term anxiety is inappropriate and

unsuitable. Diazepam should be used to treat insomnia only when it is

severe, disabling or subjecting the individual to extreme stress.

4.2 Posology And Method Of Administration

Tubes are for single use only.

The lowest dose that can control the symptoms should be used and treatment should not be continued beyond 4 weeks.

Adults and Children over 3 years: One 10mg tube. If a child is particularly small, then consideration should be given to reducing the dose to one 5mg tube and reducing the depth of insertion.

Children 1 to 3 years: One 5mg tube. Insert the tube to about half-nozzle length (approximately 2.5cm).

Children under 1: Not recommended.

Elderly and Debilitated Patients: The dosage should be half that recommended to adults.

For acute muscle spasm, acute anxiety or agitation use 10mg and repeat if necessary after 4 hours.

For sedative cover during dental or other surgical and medical procedures, give a dose dependent on patient's response using 0.2mg/kg body weight as a guide.

Doses should be repeated only on medical advice. Long-term chronic use is not recommended and treatment should always be tapered off gradually. When a benzodiazepine is used as a hypnotic, treatment should, if possible, be intermittent.

Method of administration: For rectal administration.

4.3 Contraindications

Patients with a known sensitivity to benzodiazepines; acute pulmonary insufficiency; respiratory depression.

4.4 Special Warnings And Precautions For Use

The lowest dose that can control the symptoms should be used and treatment should not be continued beyond 4 weeks. The risk of dependence increases when high dosages are attained, 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.

Treatment should always be tapered off gradually. Sudden cessation of treatment can result in symptoms such as depression, nervousness, rebound insomnia, irritability, sweating and diarrhoea even in patients receiving normal therapeutic doses for short periods of time. Abrupt withdrawal following high dosage may produce confusion, toxic psychosis, convulsions or a condition resembling delirium tremens.

Diazepam should not be used to treat chronic psychoses or phobic or obsessional states. Because diazepam-induced disinhibition may precipitate suicidal or aggressive behaviour, it should not be used alone to treat depression or anxiety related depression. Caution must be exercised when treating patients with personality disorders.

Elderly or debilitated patients may be more prone to adverse effects and care must be taken in patients with impaired liver or kidney function. Care is also required in patients with organic brain disease (particularly arteriosclerosis).

Diazepam should be avoided in cases of loss or bereavement as psychological adjustment may be inhibited by benzodiazepines.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Sedation, or respiratory or cardiovascular depression may be enhanced if diazepam is combined with centrally acting drugs such as anaesthetics, analgesics, antidepressants, hypnotics, neuroleptics and tranquillisers.

Concomitant intake with alcohol is not recommended since the sedative effect is increased.

Diazepam is primarily metabolised by hepatic microsomal oxidation and drugs which affect liver enzymes, such as cimetidine and phenobarbitone, may alter its pharmacokinetics.

Diazepam has been reported to be displaced from protein-binding sites by sodium valproate.

4.6 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

The side-effects of diazepam, such as sedation and impaired muscle function, may adversely affect the ability to drive or use machines. Insufficient sleep may also increase the likelihood of impaired alertness. (See also Interactions, Section 4.5.)

4.8 Undesirable Effects

Diazepam may cause drowsiness, sedation, blurring of vision, unsteadiness and ataxia. These may occur after a single as well as repeated doses and persist to the following day. Less common effects include vertigo, headache, confusion, slurred speech, visual disturbance, tremor, changes in libido, skin rashes and gastro-intestinal upset. Jaundice or blood dyscrasias have been reported rarely. High doses may be associated with respiratory depression or hypotension.

Abnormal psychological reactions to benzodiazepines have been reported. Rare behavioural adverse effects include paradoxical aggressive outbursts, excitement, confusion and the uncovering of depression with suicidal tendencies.

4.9 Overdose

Symptoms

Benzodiazepines commonly cause drowsiness, ataxia, dysarthria and nystagmus. Coma, hypotension 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 1 mg/kg within 1 hour, provided they are not too drowsy. Gastric lavage is unnecessary if these drugs have been taken alone. 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

Diazepam is a long-acting benzodiazepine tranquilliser with anticonvulsant, sedative, muscle relaxant and amnesic properties.

5.2 Pharmacokinetic Properties

Diazepam is well absorbed with peak blood levels being achieved 1 to 2 hours after administration.

5.3 Preclinical Safety Data

Not required.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Benzoic acid, absolute alcohol, propylene glycol, sodium benzoate, benzyl alcohol and water.

6.2 Incompatibilities

None known.

6.3 Shelf Life

24 months.

6.4 Special Precautions For Storage

Store in a cool dry place below 22°C.

6.5 Nature And Contents Of Container

Rectal tubes made from low density polyethylene.

Pack sizes: 2, 5, 10, 15 and 20.

6.6 Special Precautions For Disposal And Other Handling

For single use only.

7. Marketing Authorisation Holder

Sandoz Ltd

Woolmer Way

Bordon

Hampshire

GU35 9QE

8. Marketing Authorisation Number(S)

PL 4416/0027

PL 4416/0028

9. Date Of First Authorisation/Renewal Of The Authorisation

28 February 1983/9 March 1993

10. Date Of Revision Of The Text

6 July 2005