DALMANE CAPSULES 30MG

1. Name Of The Medicinal Product

Dalmane 30 mg Capsules

2. Qualitative And Quantitative Composition

ICN

Capsules with black cap and opaque grey body with 30 printed in red on both cap and body, containing 32.8 mg flurazepam monohydrochloride (equivalent to 30 mg flurazepam).

3. Pharmaceutical Form

Dalmane capsules 30 mg.

4. Clinical Particulars

4.1 Therapeutic Indications

Short-term treatment of insomnia when it is severe, disabling or subjecting the individual to extreme distress. Dalmane is helpful in overcoming difficulties in getting to sleep and also in the problem of frequent nocturnal awakenings. Its properties make it particularly indicated where the total duration of sleep is less than adequate.

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

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

4.2 Posology And Method Of Administration

Adults

The dosage of Dalmane should be determined on an individual basis taking into account the severity of the insomnia and the patient's response to treatment. Dosage is important in determining the duration of effect and the occurrence of residual effects. For most patients the optimum dose is 15 mg – this will ensure a full night's sleep with minimal residual effects on wakening. Patients with severe insomnia may require 30 mg but residual effects on awakening, associated with an anxiolytic effect, are more frequent at this dose.

Elderly

Elderly or debilitated patients: the elderly or patients with impaired renal and/or hepatic function will be particularly susceptible to the adverse effects of Dalmane. The initial dose should not exceed 15 mg. If organic brain changes are present, the dosage of Dalmane should not exceed 15 mg in these patients.

In patients with chronic pulmonary insufficiency and in patients which chronic renal or hepatic disease, dosage may need to be reduced.

Children

Dalmane is contra-indicated for use in children.

Treatment should, if possible, be on an intermittent basis.

Treatment should be as short as possible and should be started with the lowest recommended dose. The maximum dose should not be exceeded. Generally the duration of treatment varies from a few days to two weeks with a maximum of four weeks, including the tapering off process. Patients who have taken benzodiazepines for a prolonged time may require a longer period during which doses are reduced. Specialist help may be appropriate. Little is known regarding the efficacy or safety of benzodiazepines in long-term use.

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. Long-term chronic use is not recommended.

The product should be taken just before going to bed.

Dalmane capsules are for oral administration.

4.3 Contraindications

Patients with known sensitivity to benzodiazepines; acute pulmonary insufficiency; respiratory depression; phobic or obsessional states; chronic psychosis; myasthenia gravis; sleep apnoea syndrome; severe hepatic insufficiency; use in children.

Use of this drug is contra-indicated in patients with a known hypersensitivity to benzodiazepines and any of the excipients. Hypersensitivity reactions with the benzodiazepines including rash, angioedema and hypotension have been reported on rare occasions in susceptible patients.

4.4 Special Warnings And Precautions For Use

In patients with chronic pulmonary insufficiency, and in patients with chronic renal or hepatic disease, dosage may need to be reduced.

Dalmane should not be used alone to treat depression or anxiety associated with depression, since suicide may be precipitated in such patients.

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

If the patient is awoken during the period of maximum drug activity, recall may be impaired.

Use of benzodiazepines may lead to the development of physical and psychological dependence. The dependence potential of the benzodiazepines is low, particularly when limited to short-term use, but this increases when high doses are used, especially when given over long periods. This is particularly so in patients with a history of alcoholism or drug abuse or in patients with marked personality disorders. Regular monitoring in such patients is essential, routine repeat prescriptions should be avoided and treatment should be withdrawn gradually. Symptoms such as depression, nervousness, extreme anxiety, tension, restlessness, confusion, mood changes, rebound insomnia, irritability, sweating, diarrhoea, headaches and muscle pain have been reported following abrupt cessation of treatment in patients receiving even normal therapeutic doses for short periods of time.

In severe cases the following symptoms may occur: derealisation, depersonalisation, hyperacusis, numbness and tingling of the extremities, hypersensitivity to light, noise and physical contact and hallucinations or epileptic seizures. In rare instances, withdrawal following excessive dosages may produce confusional states, psychotic manifestations and convulsions. Abuse of the benzodiazepines has been reported.

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

Abnormal psychological reactions to benzodiazepines have been reported. Rare behavioural 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. Extreme caution should therefore be used in prescribing benzodiazepines to patients with personality disorders. If any of these reactions occur, use of the drug should be discontinued. These reactions may be quite severe and are more likely to occur in children and the elderly.

Benzodiazepines may induce anterograde amnesia. The condition usually occurs 1

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Enhancement of the central depressive effect may occur if benzodiazepines are combined with centrally-acting drugs such as neuroleptics, tranquilisers, antidepressants, hypnotics, analgesics, enhancement of the euphoria may also occur leading to an increase in psychological dependence. The elderly require special supervision.

When Dalmane is used in conjunction with anti-epileptic drugs, side-effects and toxicity may be more evident, particularly with hydantoins or barbiturates or combinations including them. This requires extra care in adjusting dosage in the initial stages of treatment.

Known inhibitors of hepatic enzymes, eg cimetidine, have been shown to reduce the clearance of benzodiazepines and may potentiate their action and known inducers of hepatic enzymes, eg rifampicin, may increase the clearance of benzodiazepines.

Concommitant intake with alcohol should be avoided. The sedative effect may be enhanced when the product is used in combination with alcohol. This adversely affects the ability to drive or use machines.

4.6 Pregnancy And Lactation

There is no evidence as to drug safety in human pregnancy, nor is there evidence from animal work that it is free from hazard. Do not use during pregnancy, especially during the first and last trimesters, unless there are compelling reasons.

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.

Administration of benzodiazepines in the last trimester of pregnancy or during labour has been reported to produce irregularities in the foetal heart rate, and hypotonia, poor sucking and hypothermia and moderate respiratory depression in the neonate.

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 of developing withdrawal symptoms in the postnatal period.

No data regarding the passage of flurazepam into breast milk are available. However, in common with other benzodiazepines, its passage into breast milk might be expected. If possible, the use of Dalmane in mothers who are breast-feeding should be avoided.

4.7 Effects On Ability To Drive And Use Machines

Patients should be advised that, like all medicaments of this type, Dalmane might modify patients' performance at skilled tasks (driving, operating machinery, etc) to a varying degree depending upon dosage, administration, and sleep pattern and individual susceptibility. Patients should further be advised that alcohol may intensify any impairment, and should, therefore, be avoided during treatment.

4.8 Undesirable Effects

Common adverse effects include drowsiness during the day, numbed emotions, reduced alertness, confusion, fatigue, headache, dizziness, muscle weakness, ataxia and double vision. These phenomena are dose-related and are likely to be uncommon with the recommended dosage; they occur predominantly at the start of therapy and usually disappear with repeated administration. The elderly are particularly sensitive to the effects of centrally-depressant drugs.

Other adverse effects are rare and include vertigo, hypotension, gastro-intestinal upsets, skin rashes, visual disturbances, changes in libido, and urinary retention. Isolated cases of blood dyscrasias and jaundice have also been reported.

Occasionally patients treated with Dalmane experience a bitter after-taste.

4.9 Overdose

When taken alone in overdosage Dalmane presents few problems in management and 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 might have been taken.

Following overdose with oral benzodiazepines, vomiting should be induced if the patient is conscious or gastric lavage undertaken with the airway protected if the patient is unconscious. If there is no advantage in emptying the stomach, activated charcoal should be given to reduce absorption.

Special attention should be paid to respiratory and cardiovascular functions in intensive care. Overdose 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 and lethargy; in more serious cases, symptoms may include ataxia, hypotonia, hypotension, respiratory depression, rarely coma and very rarely death.

The value of dialysis has not been determined. Anexate is a specific IV antidote for use in emergency situations. Patients requiring such intervention should be monitored closely in hospital (see separate prescribing information).

If excitation occurs, barbiturates should not be used.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Dalmane is a benzodiazepine drug with hypnotic properties.

5.2 Pharmacokinetic Properties

The pharmacokinetic properties of Dalmane make it particularly indicated for patients whose total duration of sleep is less than adequate. The dosage of the drug is important in balancing the duration of effect with the occurrence of residual effects. On repeated dosing there is accumulation of an active metabolite, desalkylflurazepam, with steady state levels being reached within 2 to 3 weeks. Psychomotor studies have demonstrated, however, that a dose of 15 mg given for 7 consecutive nights did not significantly affect performance on the morning after final administration. However, impairment of performance was recorded on the morning after final administration of 30 mg for 7 consecutive nights. This latter dose is associated with daytime anxiolytic effects.

5.3 Preclinical Safety Data

Not applicable.

6. Pharmaceutical Particulars

6.1 List Of Excipients

30 mg capsules contain the following excipients: lactose, talc purified, magnesium stearate, black iron oxide E172, titanium dioxide E171 and yellow iron oxide E172.

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

Amber glass bottles and plastic adept containers - 5 years.

PVDC blister packs - 3 years.

Polythene bags in tins and small HDPE bottles - 2 years.

White securitainers - 1 year.

6.4 Special Precautions For Storage

Dalmane capsules should be stored in a dry place with a recommended maximum storage temperature of 25ºC.

6.5 Nature And Contents Of Container

PVDC blister packs, amber glass bottles, polythene bags in tins, plastic adept containers, white securitainers and small HDPE bottles, containing 30 capsules.

6.6 Special Precautions For Disposal And Other Handling

None.

7. Marketing Authorisation Holder

Meda Pharmaceuticals Ltd

Skyway House

Parsonage Road

Takeley

Bishop's Stortford

CM22 6PU

United Kingdom

8. Marketing Authorisation Number(S)

PL 15142/0017

9. Date Of First Authorisation/Renewal Of The Authorisation

3rd May 1999

10. Date Of Revision Of The Text

June 2009