Lormetazepam Tablets 1mg
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Lormetazepam Tablets 1mg.
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 1 mg of Lormetazepam.
Excipient(s): Contains 98.8 mg Lactose (anhydrous)
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Tablet.
White, round, flat bevel edged tablet, approximately 7 mm in diameter, marked LT breakline 1 on one side with “G” on the reverse
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Lormetazepam Tablets are indicated for the short term (up to 4 weeks) treatment of insomnia, when it is severe, disabling or subjecting the individual to extreme distress.
As with all benzodiazepines, doctors should be aware that long-term use may lead to dependency and withdrawal symptoms in certain patients.
4.2 Posology and method of administration
For oral administration.
In all cases the lowest effective dose necessary to control symptoms should be used (up to four weeks). Treatment should, if possible, be intermittent. Lormetazepam should not be used for long term chronic treatment.
Adults: The usual dosage is 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 is not recommended for use in children.
All patients taking Lormetazepam should be carefully monitored and routine repeat prescriptions avoided. Treatment in all patients should be withdrawn gradually with careful monitoring and reassessment to minimise possible withdrawal symptoms. Patients who have taken benzodiazepines for a long time may require a longer period during which doses are reduced.
For patients with mild to moderate chronic respiratory insufficiency or hepatic insufficiency a dose reduction should be considered.
4.3 Contraindications
Hypersensitivity to benzodiazepines or to any of the excipients listed in section 6.1.
Lormetazepam is contra-indicated in patients with
- Myasthenia gravis
- Severe respiratory insufficiency (e.g. severe chronic obstructive pulmonary disease)
- Sleep apnea syndrome
- Acute intoxication with alcohol, hypnotics, analgesics or psychotropic drugs (neuroleptics, antidepressants, lithium)
4.4 Special warnings and precautions for use
Duration of treatment
The duration of treatment should be as short as possible. Generally it varies from a few days to two weeks with a maximum of four weeks, including gradual reduction of dose.
The patient should be informed when treatment is started that it will be of limited duration and it should be precisely explained how the dosage will be progressively decreased.
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 situation.
For more information concerning patients under 18 years of age, see section 4.2 ‘Posology and method of administration’.
Tolerance
Some loss of efficacy to the hypnotic effects of Lormetazepam may develop after repeated use for a few weeks.
Dependence
Use of Lormetazepam and other benzodiazepines may lead to the development of physical and psychic dependence upon these products. Abuse of benzodiazepines has been reported. The risk of dependence increases with dose and duration of treatment; it is also greater in patients with a history of alcohol or drug abuse. Therefore, Lormetazepam should be used with extreme caution in patients with a history of alcohol or drug abuse.
Once physical dependence has developed, abrupt termination of treatment will be accompanied by withdrawal reactions. These may consist of extreme anxiety, tension, restlessness, confusion, irritability, headaches and muscle pain. In severe cases the following symptoms may occur: derealization, depersonalization, hallucinations, paresthesia of the limbs, sensory disturbance to light, noise and physical contact, hyperacusis and epileptic seizures.
There are indications that, in the case of benzodiazepines with a short duration of action, withdrawal phenomena can become manifest within the dosage interval, especially when the dosage is high. This is unlikely to happen with Lormetazepam because its elimination half-life is about 10 hours.
However, switching to Lormetazepam after long and/or high-dose use of a benzodiazepine with a significantly longer duration of action may result in the development of withdrawal symptoms.
Rebound insomnia, a transient syndrome whereby the insomnia that led to treatment with a benzodiazepine recurs in enhanced form, may occur on withdrawal of treatment.
Since the risk of withdrawal phenomena/rebound phenomena is greater after abrupt discontinuation of treatment, it is recommended that the dosage is gradually decreased. The patient should be made aware of the possibility of rebound phenomena thereby minimizing anxiety over such symptoms, should they occur while Lormetazepam is being discontinued.
Amnesia
Lormetazepam may induce anterograde amnesia. The condition occurs most often in the first few hours after ingesting the product. In order to reduce the risk of anterograde amnesia patients should ensure that sufficient uninterrupted sleep of 7 - 8 hours is possible.
Psychiatric and paradoxical reactions
Reactions like restlessness, agitation, irritability, aggressiveness, delusion, rages, nightmares, hallucinations, psychoses, inappropriate, abnormal behavior and other adverse behavior disorders 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 children and the elderly, as well as in patients with organic brain syndrome.
Lormetazepam is not recommended for the primary treatment of psychotic illness. It should not be used alone for the treatment of sleep disorder associated with depression.
Pre-existing depression may be unmasked during benzodiazepine use, including Lormetazepam Suicide may be precipitated in such patients. Lormetazepam should be used with caution in these patients with depression.
Specific patient groups Pediatric patients
For insomnia, Lormetazepam should not be given to patients under 18 years of age without careful assessment of the need to do so; the duration of treatment must be kept to a minimum (see section 4.2 ‘Posology and method of administration’).
Elderly
Benzodiazepines, including Lormetazepam may be associated with an increased risk of falling due to adverse effects including ataxia, muscle weakness, dizziness, somnolence/sleepiness, fatigue, and therefore it is recommended to treat particularly elderly patients with caution.
Elderly should be given a reduced dose (see section 4.2 ‘Posology and method of administration - Short term treatment of insomnia).
Patients with spinal and cerebellar ataxia
Lormetazepam should be administered with caution to patients with spinal and cerebellar ataxia.
Patients with chronic respiratory insufficiency
A lower dose is also recommended for patients with chronic respiratory insufficiency due to the risk of respiratory depression (see also section 4.3 ‘Contraindications’).
Patients with hepatic insufficiency
There are limited pharmacokinetic data concerning single dosing of Lormetazepam in patients with mild to moderate hepatic insufficiency. The reduced plasma clearance in these patients leads to an average 2-fold increase of maximum concentration and systemic exposure (AUC). However, no pharmacokinetic data from clinical trials are available regarding repeated dosing of Lormetazepam in this patient population.
It is recommended to treat patients with severe hepatic insufficiency with caution, as benzodiazepines may precipitate encephalopathy.
Patients with severe renal insufficiency
Lormetazepam should be administered with caution to patients with severe renal insufficiency.
Alcohol
Lormetazepam oral drops, solution contains small amounts of ethanol (alcohol), less than 100 mg per ml (1 ml corresponds to 25 drops). This may be harmful for those suffering from alcoholism. To be taken into account in pregnant or breast-feeding women, children and high-risk groups such as patients with liver disease, or epilepsy.
Excipients
This medicinal product contains lactose-anhydrous. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
4.5 Interaction with other medicinal products and other forms of interaction
Benzodiazepines produce an additive effect when co-administered with alcohol or other CNS depressants.
Concomitant intake with alcohol is not recommended. Special care should be made with drugs depressing respiratory function such as opioids (analgesics, antitussives, substitutive treatments), notably in the elderly people.
Lormetazepam should be used with caution when combined with other CNS depressants. Enhancement of the central depressive effect may occur in case of concomitant use with anaesthetics, antipsychotics (neuroleptics), anxiolytics/sedatives, some antidepressant agents, opioids, anticonvulsants, sedative H1-antihistamines.
Interactions of benzodiazepines and other drug classes (beta-blocking agents, cardiac glycosides, methylxantines, oral contraceptives and several antibiotics) have been reported. Patients using beta-blocking agents, cardiac glycosides, methylxantines, oral contraceptives and antibiotics concomitantly should be treated with caution, especially at the beginning of the treatment with lormetazepam.
4.6 Fertility, pregnancy and lactation
As a precaution, Lormetazepam should not be used during pregnancy, delivery and lactation.
Women of childbearing potential
If Lormetazepam is prescribed to a woman of childbearing potential, she should be warned to contact her physician regarding discontinuation of Lormetazepam if she intends to become or suspects that she is pregnant.
Pregnancy
If, for compelling medical reasons, Lormetazepam is administered during the late phase of pregnancy, or during labor and delivery, effects on the neonate, such as hypothermia, hypotonia, moderate respiratory depression and sucking difficulties can be expected due to the pharmacological action of the compound.
Moreover, infants born to mothers who took Lormetazepam or other benzodiazepines chronically during the late phase of pregnancy may have developed physical dependence and may be at some risk of developing withdrawal symptoms in the postnatal period.
Lactation
Since small amounts of the drug may enter the breast-milk, Lormetazepam should not be administered to breastfeeding mothers.
4.7 Effects on ability to drive and use machines
Lormetazepam has major influence on the ability to drive and use machines, as it causes sedation, amnesia, impaired concentration and impaired muscular function. If insufficient sleep duration 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
4.8 Undesirable effects
Summary of safety profile
At the beginning of the treatment, somnolence during the day, emotional disorder, depressed consciousness, confusion, fatigue, headache, dizziness, muscular weakness, ataxia or double vision may occur; these reactions usually disappear with repeated administration.
The most frequently observed adverse drug reactions (ADRs) in patients receiving Lormetazepam are headache, sedation, and anxiety.
The most serious adverse drug reactions (ADRs) in patients receiving Lormetazepam are angioedema, completed suicide or suicide attempt in association with unmasking of pre-existing depression.
Tabulated list of adverse reactions
The adverse drug reactions observed with Lormetazepam are represented in the table below. They are classified according to System Organ Class. The most appropriate MedDRA terminology is used to describe a certain reaction and its synonyms and related conditions.
Adverse drug reactions from clinical trials (in 852 patients; administered dose: 0.5 mg to 3 mg lormetazepam) are classified according to their frequencies.
The ADRs identified only during post marketing surveillance, and for which a frequency could not be estimated, are listed under “not known”.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Table 1: Adverse drug reactions reported in clinical trials or during post-marketing surveillance in patients treated with Lormetazepam
|
System Organ Class (MedDRA) |
Very common (>1/10) |
Common (>1/100 to <1/10) |
Not known (cannot be estimated from the available data) |
|
Immune system disorders |
Angioedema * |
|
System Organ Class (MedDRA) |
Very common (>1/10) |
Common (>1/100 to <1/10) |
Not known (cannot be estimated from the available data) |
|
Psychiatric disorders |
Anxiety Libido decreased |
Completed suicide (unmasking of pre-existing depression)* Suicide attempt (unmasking of pre-existing depression)* Acute psychosis§ Hallucination^ Dependence^ Depression (unmasking of preexisting depression/ Delusion§ Withdrawal syndrome (rebound insomnia) § Agitation§ Aggression§ Irritability§ Restlessness§ Anger § Nightmare§ Abnormal behavior§ Emotional disorder | |
|
Nervous system disorders |
Headache |
Dizziness§ Sedation Somnolence^ Disturbance in attention Amnesia§ Visual impairment Speech disorder Dysgeusia Bradyphrenia |
Confusional state Depressed level of consciousness Ataxia§ Muscular weakness§ |
|
Cardiac disorders |
Tachycardia |
|
System Organ Class (MedDRA) |
Very common (>1/10) |
Common (>1/100 to <1/10) |
Not known (cannot be estimated from the available data) |
|
Gastrointestinal disorders |
Vomiting Nausea Abdominal pain upper Constipation Dry mouth | ||
|
Skin and subcutaneous tissue disorders |
Pruritus |
Urticaria Rash | |
|
Renal and urinary disorders |
Micturition disorder | ||
|
General disorders and administration site conditions |
Asthenia Hyperhidrosis |
Fatigue§ | |
|
Injury, poisoning, and procedural complications |
Fall |
* life-threatening and/or fatal cases have been reported § see section ‘Special warnings and precautions for use’
Description of selected adverse reactions Dependence
Use of Lormetazepam and other benzodiazepines may lead to the development of physical and psychic dependence upon these products.
Once physical dependence has developed, abrupt termination of treatment will be accompanied by withdrawal reactions. These may consist of extreme anxiety, tension, restlessness, confusion, irritability, headaches and muscle pain. In severe cases the following symptoms may occur: derealization, depersonalization, hallucinations, paresthesia of the limbs, sensory disturbance to light, noise and physical contact, hyperacusis and epileptic seizures.
For more information concerning dependence / withdrawal phenomena see section ‘Special warnings and special precautions for use’.
Psychiatric disorders
Rebound insomnia may occur on withdrawal of treatment.
Psychiatric and paradoxical reactions: Reactions like restlessness, agitation, irritability, aggressiveness, delusion, rages, nightmares, hallucinations, psychoses, inappropriate abnormal behavior and other adverse behavior disorders are known to occur when using Lormetazepam
Pre-existing depression may be unmasked during benzodiazepine use, including Lormetazepam. Suicide may be precipitated in such patients. Lormetazepam should be used with caution in these patients with depression.
Nervous system disorders
Amnesia: Lormetazepam may induce anterograde amnesia.
4.9 Overdose
As with other benzodiazepines, overdose of Lormetazepam 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 may have been taken and that respiratory depression, rarely coma and very rarely death may occur. Special attention must be paid to respiratory and cardiovascular functions in intensive care.
Symptoms
The symptoms of mild lormetazepam intoxication are drowsiness, tiredness, ataxic symptoms, disturbed vision.
Oral intake of higher doses may result in deep sleep ranging to unconsciousness, respiratory depression, hypotension.
Therapy
Patients with milder symptoms of intoxication should be allowed to sleep them off under observation. On oral intake of larger amounts, vomiting should be induced within one hour 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.
Flumazenil may be useful as an antidote.
For further information concerning the safe use of flumazenil please refer to the SmPC for products containing flumazenil.
PHARMACOLOGICAL PROPERTIES
5
5.1 Pharmacodynamic properties
Lormetazepam is a benzodiazepine derivative with general properties similar to those of diazepam. It has been used as a hypnotic in the short-term management of insomnia in usual doses of 0.5 to 1.5mg at night.
5.2 Pharmacokinetic properties
Lormetazepam is rapidly absorbed from the gastro-intestinal tract and metabolised to the inactive glucuronide. The terminal half-life is reported to be about 12 hours.
5.3 Preclinical safety data
There are no preclinical safety data of relevance to the prescriber which are additional to that already included in other sections of the SPC.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Lactose anhydrous
Dibasic calcium phosphate anhydrous
Crospovidone
Purified talc
Magnesium stearate
6.2 Incompatibilities
None known
6.3 Shelf life
36 months
6.4 Special precautions for storage
Store in a dry place below 25°C.
6.5 Nature and contents of container
Polypropylene containers with polyethylene caps (with optional use of polyethylene ullage filler) or HDPE containers with polyethylene snap closures in packs of 5, 7,10, 14, 15, 20, 21, 25, 28, 30, 50, 56, 60, 84, 90, 100, 112, 120, 168, 180, 250 and 500 tablets.
6.6 Special precautions for disposal
No special requirements.
7 MARKETING AUTHORISATION HOLDER
Generics [UK] Limited T/A Mylan Station Close Potters Bar Hertfordshire EN6 1TL
8. MARKETING AUTHORISATION NUMBER
PL 04569/0177
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date MA granted: 16th February 1987 Last renewal date: 25th September 1998
10 DATE OF REVISION OF THE TEXT
14/01/2016