SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Lormetazepam Tablets 0.5 mg or

Dormagen Tablets 0.5mg

2.    QUALITATIVE AND QUANTITATIVE COMPOSITION

Lormetazepam Tablets 0.5mg contain 0.5mg lormetazepam.

Lormetazepam (INN, BAN) is chemically defined as 7-chloro-5-(2-chlorophenyl)- 1,3-dihydro-3-hydroxy-1 -methyl-2H-1,4-benzodiazepin-2-one.

3. PHARMACEUTICAL FORM

Lormetazepam Tablets 0.5mg are round white tablets, 6.5mm in diameter with ‘GP036’ embossed on one side and plain on the other.

4.    CLINICAL PARTICULARS

4.1.    Therapeutic Indications

Lormetazepam is indicated for the short term treatment of insomnia when it is disabling or subjecting the individual to extreme distress.

4.2. Posology and Method of Administration

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 2 weeks, with a maximum of 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 lormetazepam is generally unnecessary and is not recommended.

Treatment in all patients should be withdrawn gradually to minimise possible withdrawal symptoms (see Special Warnings and Precautions for Use).

Dosage:

Adults: 0.5mg to 1.5mg before retiring.

Subsequently the initial dosage may be increased in individual cases if this proves necessary

Elderly: The lower adult dose is preferable for elderly patients

Children: Lormetazepam has not been evaluated for the treatment of children

4.3. Contra-Indications

Severe respiratory insufficiency.

Sleep apnoea syndrome.

Hypersensitivity to benzodiazepines including Lormetazepam Tablets or their components.

Myasthenia gravis.

Severe hepatic failure.

4.4 Special warnings and precautions for use

Patients should be advised that since their tolerance for other CNS depressants will be diminished in the presence of lormetazepam, these substances should either be avoided or taken in reduced dosage. Lormetazepam may enhance the sedative effects of alcohol. Since this affects the ability to drive or use machinery, alcohol should be avoided while taking lormetazepam.

Lormetazepam 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 lormetazepam 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 lormetazepam is low when used at the recommended dose and duration, but increased 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 (see 4.8 Undesirable effects). Therefore, the drug should always be discontinued gradually.

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 of 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.

Caution should be used in the treatment of patients with acute narrow-angle glaucoma.

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 a more specific treatment.

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 where repeated courses of treatment are considered clinically necessary.

Transient anterograde amnesia or memory impairment has been reported in association with the use of benzodiazepines. This condition, which may be associated with inappropriate behaviour, 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. Such reactions are more likely to occur in children and the elderly. Should these occur, use of the drug should be discontinued (see 4.8 Undesirable Effects).

Contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

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.

4.5 Interaction with other medicinal products and other forms of interaction

The benzodiazepines, including lormetazepam produce additive CNS depressant effects when co-administered with other medications which themselves produce CNS depression e.g., alcohol, barbiturates, antipsychotics, sedatives/hypnotics, anxiolytics, antidepressants, narcotic analgesics, sedative antihistamines, anticonvulsants, and anaesthetics.

Concomitant use of alcohol is not recommended. The sedative effects may be enhanced when lormetazepam is used in combination with alcohol. This will affect the ability to drive or use machines.

An enhancement of the euphoria induced by narcotic analgesics may occur with benzodiazepine use, leading to an increase in psychic dependence.

Compounds which inhibit certain hepatic enzymes (particularly cytochrome P450) may enhance the activity of benzodiazepines. To a lesser degree this also applies to benzodiazepines which are metabolised only by conjugation.

Administration of theophylline or aminophylline may reduce the sedative effects of benzodiazepines, including lormetazepam.

Enhanced hypotensive effects may occur when lormetazepam is given to patients treated with antihypertensive agents.

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 later 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 hypoactivity, hypotonia, hypothermia, 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.

Lactation: Since limited data indicates that a small proportion of parent drug and its conjugate is excreted in breast milk, lormetazepam should not be given to breast-feeding women. Sedation and inability to suckle have occurred in neonates of lactating mothers taking benzodiazepines.

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 (see also Interactions).

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

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.

Most frequently reported adverse reactions associated with benzodiazepines include daytime drowsiness, dizziness, muscle weakness and ataxia.

Adverse reactions are listed by frequency: common (>1/100, <1/10); uncommon (>1/1,000, <1/100), rare (>1/10,000, <1/1,000); very rare (<1/10,000).

Blood and lymphatic system disorders

Very rare: Thrombocytopenia, leucopenia, agranulocytosis, pancytopenia Immune system disorders

Very rare: Hypersensitivity including anaphylaxis/anaphylactoid reactions Endocrine disorders

Very rare: Inappropriate antidiuretic hormone secretion, hyponatraemia Psychiatric disorders

Rare: Confusion, depression and unmasking of depression, numbed emotions, disinhibition, euphoria, appetite changes, sleep disturbance, change in libido, decreased orgasm

Unknown: Dependence, Suicidal ideation/attempt

Paradoxical reactions such as restlessness, agitation, irritability, aggressiveness, delusion, rage, insomnia, nightmares, hallucinations, psychoses, sexual arousal, and inappropriate behaviour have been occasionally reported during use.

Nervous system

Very common: Daytime drowsiness, sedation Common: Dizziness, ataxia

Rare: headache, reduced alertness, dysarthria/slurred speech, transient anterograde amnesia or memory impairment

Very rare: Tremor, extrapyramidal reactions, Coma (see 4.9 Overdose)

Eye disorders

Rare: Visual disturbances (diplopia, blurred vision)

Vascular disorders

Rare: Hypotension (see 4.4 Special warnings and precautions).

Respiratory thoracic and mediastinal disorders

Rare: Apnoea, worsening of sleep apnoea, worsening of obstructive pulmonary disease.

Respiratory depression (see 4.9 Overdose)

Gastrointestinal disorders

Rare: Nausea, constipation, salivation changes

Hepatobiliary disorders

Rare: Abnormal liver function test values (increases in bilirubin, transaminases, alkaline phosphatase), jaundice

Skin and subcutaneous tissue disorders Rare: Rash, allergic dermatitis

Musculoskeletal disorders Common: Muscle weakness

Reproductive system and breast disorders Rare: Impotence

General disorders Common: Asthenia, fatigue Very rare: Hypothermia

Drug withdrawal symptoms (see 4.4 Special warnings and precautions) 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; hyperreflexia, tremor, nausea, vomiting; diarrhoea, abdominal cramps, loss of appetite, agitation, palpitations, tachycardia, panic attacks, vertigo, short-term    memory loss, hallucinations/delirium; catatonia;

hyperthermia, 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.

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. Special attention should be paid to respiratory and cardiovascular functions in intensive care. Hypotension, though unlikely, may be controlled with noradrenaline. Lormetazepam 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.

PHARMACOLOGICAL PROPERTIES

5.1. Pharmacodynamic Properties

Lormetazepam is a benzodiazepine with anxiolytic, muscle relaxant, sedative and hypnotic properties. Clinical studies have shown minimal effects on REM sleep and on psychomotor performance on the day after treatment with lormetazepam.

5.2. Pharmacokinetic Properties

Lormetazepam is rapidly absorbed from the gastrointestinal tract and is metabolised by a simple one-step process to a pharmacologically inactive glucuronide. There are no major metabolites and little risk of accumulation. Lormetazepam has a terminal phase half life of about 11 hours.

5.3. Pre-clinical Safety Data

Fertility in male and female rats was not adversely affected by oral lormetazepam.

6. PHARMACEUTICAL PARTICULARS 6.1. List of Excipients

Lactose, maize starch, polyvinylpyrrolidone and magnesium stearate.

6.2. Incompatibilities

None known.

6.3. Shelf Life

60 months.

Special Precautions for Storage

Store in a cool dry place.

6.5. Nature and Contents of Container

1.    PVC/aluminium foil blister packs: Pack sizes of 28, 30 or 100 tablets.

2.    Opaque polypropylene Securitainers: Pack sizes of 28, 30 or 100 tablets.

3.    Amber glass bottles: Pack sizes of 28, 30 or 100 tablets.

6.6 Special precautions for disposal

None stated.

7    MARKETING AUTHORISATION HOLDER

Genus Pharmaceuticals Holding Limited

T/A Genus Pharmaceuticals

Linthwaite

Huddersfield

HD75QH

UK

8.    MARKETING AUTHORISATION NUMBER

PL 17225/0012

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

10/03/2009

10 DATE OF REVISION OF THE TEXT

27/01/2015