We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we'll assume that you are happy to receive all cookies on the medicines.ie website. Find out more

Roche Products (Ireland) Ltd

3004 Lake Drive, Citywest, Naas Road, Dublin 24,
Telephone: +353 1 469 0700
Fax: +353 1 469 0791
Medical Information e-mail: ireland.druginfo@roche.com
Summary of Product Characteristics last updated on medicines.ie: 24/07/2014
SPC Lexotan Tablets 1.5mg and 3mg

When a pharmaceutical company changes an SPC or PIL, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.

Updated on 24/07/2014 and displayed until Current
Reasons for adding or updating:
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 3 - Pharmaceutical form
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 4.8 - Undesirable effects
  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 4.9 - Overdose
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 10 - Date of revision of the text
Date of revision of text on the SPC:   22-Jul-2014
Legal Category:   Product subject to medical prescription which may not be renewed (A)

Free-text change information supplied by the pharmaceutical company

Underlined Text = new text
Struck Through Text = deleted text

            [ … ]

 

2.         QUALITATIVE AND QUANTITATIVE COMPOSITION

 

            [ … ]

 

Excipient(s) with known effect:

For thea full list of excipients, see section 6.1.

 

 

3.         PHARMACEUTICAL FORM

 

[ … ]

 

The tablets can be divided into equal halvesdoses.

 

 

4.2       Posology and method of administration

 

[ … ]

 

Children

Lexotan should is not befor used in children less than 12 years of age.

 

4.3       Contra-indications

 

Myasthenia gravis

Hypersensitivity to benzodiazepines

Severe respiratory insufficiency

Sleep apnoea syndrome

Severe hepatic insufficiency (benzodiazepines are not indicated to treat patients with severe hepatic insufficiency as they may cause encephalopathy)

 

                                    Bromazepam must not be administered to patients with known hypersensitivity to the active substance or to any of the excipients listed in section 6.1, benzodiazepines, severe respiratory insufficiency, severe hepatic insufficiency (benzodiazepines are not indicated to treat patients with severe hepatic insufficiency as they may cause encephalopathy), myasthenia gravis or sleep apnea syndrome.

 

4.4       Special warnings and precautions for use

 

Amnesia

It should be borne in mind that bBenzodiazepines may induce anterograde amnesia.  The condition occurs most often several hours after ingesting the product and therefore to reduce the risk patients should ensure that they will be able to have an uninterrupted sleep of several hours.Anterograde amnesia may occur using higher therapeutic dosages (documented at 6mg), the risk increasing at higher dosages.  Amnestic effects may be associated with inappropriate behaviour (see also sectionalso 4.8 Undesirable Effects).  The condition occurs most often several hours after ingesting the product and therefore to reduce the risk patients should ensure that they will be able to have an uninterrupted sleep of 7 – 8 hours (see section 4.8).

 

Psychiatric and “paradoxical” reactions

Reactions like restlessness, agitation, irritability, aggressiveness, delusion, rages, nightmares, hallucinations, psychoses, inappropriate behaviour and other adverse behavioural effects are known to occur when using benzodiazepines.  Should this occur, use of the medicinal productdrug should be discontinued.

 

They are more likely to occur in children and the elderly.

 

Duration of treatment

The duration of treatment should be as short as possible (see section 4.2).  The overall duration of treatment generallyand should not exceed eight to twelve not be more than 8 – 12 weeks, including a tapering off process.  Extension beyond these periods should not take place without re-evaluation of the situation.

 

It may be useful to inform the patient when treatment is started that it will be of limited duration and to explain precisely how the dosage will be progressively decreased.  Moreover it is important that the patient should be aware of the possibility of rebound phenomena, thereby minimising anxiety over such symptoms should they occur while the medicinal product is being discontinued.

 

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.  When benzodiazepines with a long duration of action are being used it is important to warn against changing to a benzodiazepine with a short duration of action, as withdrawal symptoms may develop.

 

General precautions

Concomitant use of alcohol / CNS depressants:

The concomitant use of bromazepamLexotan with alcohol or/and CNS depressants should be avoided. Such concomitant use has the potential to increase the clinical effects of bromazepamLexotan possibly including severe sedation, clinically relevant respiratory and/or cardio-vascular depression (see section 4.5).

 

Medical history of alcohol or drug abuse:

Lexotan should be used with extreme caution in patients with a medical history of alcohol or drug abuse.

 

The Patients patient should be checked regularly at the start of treatment in order to minimise the dosage and/or the frequency of administration and to prevent overdose due to accumulation.

 

Tolerance

Some loss of efficacy to the effects of benzodiazepinesLexotan may develop after repeated use for a few weeks.

 

Specific patient groups

Benzodiazepines should not be given to children without careful assessment of the need to do so; the duration of treatment must be kept to a minimum.

 

  Elderly should be given a reduced dose (see section 4.2). Due to the myorelaxant effect of benzodiazepines, the risk of falls and consequently of hip fractures in elderly patients is increased.

 

 A lower dose is also recommended for patients with chronic respiratory insufficiency due to the risk of respiratory depression.

 

  Benzodiazepines are not indicated to treat patients with severe hepatic insufficiency as they may precipitate encephalopathy.

 

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

 

Benzodiazepines should not be used alone to treat depression or anxiety associated with depression (suicide may be precipitated in such patients). Therefore, bromazepam should be used with caution and the prescription size should be limited in patients with signs and symptoms of a depressive disorder or suicidal tendencies.

 

Benzodiazepines should be used with extreme caution in patients with a history of alcohol or drug abuse (see section 4.5 Interation with other medicinal products and other forms of interactions).  

 

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

 

Dependence

Use of benzodiazepines and benzodiazepine-like agents may lead to the development of physical and psychic dependence upon these products, (see section 4.8).  The risk of dependence increases with dose and duration of treatment; it is also greater in patients with a medical history of alcohol and/or drug abuse.

 

Once physical dependence has developed, abrupt termination of treatment will be accompanied by withdrawal symptoms.  These may consist of headaches, diarrhoea, muscle pain, extreme anxiety, tension, restlessness, confusion and irritability.  In severe cases the following symptoms may occur: derealisation, depersonalisation, hyperacusis, numbness and tingling of the extremities, hypersensitivity to light, noise and physical contact, hallucinations or epileptic seizures, (see section 4.8).

 

Rebound insomnia and anxiety: a transient syndrome whereby the symptoms that led to treatment with a benzodiazepine recur in an enhanced form, may occur on withdrawal of treatment.  It may be accompanied by other reactions including mood changes, anxiety or sleep disturbances and restlessness.  Since the risk of withdrawal phenomena/rebound phenomena is greater after abrupt discontinuation of treatment, it is recommended that the dosage is decreased gradually.

                       

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

 

4.5       Interaction with other medicinal products and other forms of interaction

 

Pharmacodynamic Drug-Drug Interaction (DDI)

Benzodiazepines produce an additive effect when co-administered with alcohol or other CNS depressants. Concomitant intake with alcohol is not recommended.

 

Bromazepam 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 antipsychotics (neuroleptics), anxiolytics/sedatives, some antidepressant agents, opioids, anticonvulsants, sedative H1-antihistamines.

 

Special care should be made with drugs depressing respiratory function such as opioids (analgesics, antitussives, substitutive treatments), notably in elderly people.

 

Enhanced effects on sedation, respiration and hemodynamics may occur when Lexotan is co-administered with any centrally acting depressants including alcohol.

 

Alcohol should be avoided in patients receiving Lexotan (see section 4.4).

 

(See section 4.9) Overdose for warnings of other central nervous system depressants, including alcohol.

 

In the case of narcotic analgesics, enhancement of the euphoria may also occur leading to an increase in psychic drug dependence.

 

Pharmacokinetic Drug-Drug Interaction (DDI)

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

 

                                    Pharmacokinetic interactions can occur when bromazepam is administered along with drugs that inhibit the hepatic enzyme CYP3A4 by increasing the plasma levels of bromazepam. To a lesser degree this also applies to benzodiazepines that are metabolized only by conjugation.

 

                                    The co-administration of bromazepam with strong CYP3A4 inhibitors (for example azole antifungals, protease inhibitors or some macrolides) should be made with caution and a substantial dose reduction considered.  In the case of narcotic analgesics enhancement of euphoria may also occur, leading to an increase in psychic drug dependence.

 

Co-administration of cimetidine may prolong the elimination half-life of bromazepam.

 

 

4.6       Fertility, Pregnancy and lactation

 

                        Pregnancy

Although no specific clinical data are available for bromazepam, a large amount of data based on cohort studies indicate that first trimester exposure to benzodiazepine is not associated with an increase in the risk of major malformation.  However, some early case-control epidemiological studies have found an increased risk of oral clefts.  The data indicated that the risk of having an infant with an oral cleft after maternal benzodiazepine exposure is less than 2/1000 compared with an expected rate for such defects of approximately 1/1000 in the general population.

 

                                    Benzodiazepine treatment at high dose, during the second and/or the third trimester of pregnancy, has revealed a decrease of foetal active movements and a variability of foetal cardiac rhythm.

 

                                    When treatment has to be administered for medical reasons during the last part of pregnancy, even at low doses, floppy infant syndrome such as axial hypotonia, sucking troubles leading to a poor weight gain may be observed.  These signs are reversible but they may last from 1 up to 3 weeks, according to the half-life of the product.  At high doses, respiratory depression or apnea and hypothermia in newborn may appear.  Moreover, neonatal withdrawal symptoms with hyperexitability, agitation and tremor may be observed a few days after birth, even if no floppy infant syndrome is observed.

 

                                    Taking into account these data, the use of bromazepam during pregnancy may be considered, if therapeutic indications and posology are strictly respected.

Benzodiazepines should only be used during pregnancy or lactation if considered essential by the physician.

 

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 bromazepam treatment is necessary during the last part of pregnancy, high doses should be avoided and withdrawal symptoms and/or floppy infant syndrome should be monitored in newborn.

 

                                    Since bromazepam is transferred to breast milk, breast feeding is not recommended during treatment.

 

Animal studies with benzodiazepines have shown minor effects on the foetus while a few studies have reported a late behavioural disturbance in offspring exposed in utero.

 

                        Breast-feeding

Since bromazepam is transferred to breast milk, breast feeding is not recommended during treatment.

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, 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 post-natal 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

 

Sedation, amnesia, impaired concentration and impaired muscular function may adversely affect the ability to drive or to use machines.  If insufficient sleep duration occurs, the likelihood of impaired alertness may be increased (see section also section 4.5 Interactions) with other medicaments and other forms of interaction).  Patients should further be advised that alcohol may intensify any impairment, and should, therefore, be avoided during treatment.This effect is increased if the patient has taken alcohol.

 

4.8       Undesirable effects

 

Lexotan is well tolerated in therapeutic doses.  The following undesirable effects may occur:

 

Psychiatric Disorders:

Confusional state, emotional disorder.  These phenomena occur predominantly at the start of therapy and usually disappear with repeated administration. Libido disorders have been reported occasionally.

 

Depression: Pre-existing depression may be unmasked during benzodiazepine use.

 

Paradoxical reactions such as restlessness, agitation, irritability, aggression, delusion, anger, nightmares, hallucinations, psychosis, inappropriate behaviour and other adverse behavioural effects are known to occur with benzodiazepines or benzodiazepine-like agents (see section 4.4).  Should this occur, the use of the drug should be discontinued.  They are more likely to occur in children and elderly patients than in other patients.

 

Dependence: Chronic use (even therapeutic doses) may lead to the development of physical and psychic drug dependence: discontinuation of therapy may result in withdrawal or rebound phenomena (see section 4.4).

Abuse of benzodiazepines has been reported.

 

Nervous System Disorder: Drowsiness, headache, dizziness, decreased alertness, ataxia.  These phenomena occur predominantly at the start of therapy and usually disappear with repeated administration.  Anterograde amnesia may occur using therapeutic dosages, the risk increasing at higher dosages.  Amnestic effects may be associated with inappropriate behaviour.

 

Eye Disorders: Diplopia, this phenomenon occurs predominantly at the start of therapy and usually disappears with repeated administration.

 

Gastrointestinal Disorders: Gastrointestinal disorders have been reported occasionally.

 

Skin and Subcutaneous Tissue Disorders: Skin reactions have been reported occasionally.

 

Musculoskeletal and Connective Tissue Disorders: Muscle weakness, this phenomenon occurs predominantly at the start of therapy and usually disappears with repeated administration.

 

General Disorders and Administration Site Conditions: Fatigue, this phenomenon occurs predominantly at the start of therapy and usually disappears with repeated administration.

 

Injury, Poisoning and Procedural Complications: There have been reports of falls and fractures in benzodiazepine users. The risk is increased in those taking concomitant sedatives (including alcoholic beverages) and in the elderly.

 

Respiratory Disorders: Respiratory depression.

 

Cardiac Disorders: Cardiac failure including cardiac arrest.

 

The following undesirable effects have been reported during treatment with bromazepam with the following frequencies:

Very common: ³1/10;

Common ³1/100 to <1/10;

Uncommon ³1/1,000 to <1/100

Rare (³1/10,000 to <1/1,000)

Very rare (<1/10,000)

Not known (cannot be estimated from the available data)

 

MedDRA System Organ Class

 

Undesirable effects

Immune System Disorders

 

frequency not known

Hypersensitivity, anaphylactic shock, angioedema

Psychiatric Disorders

 

frequency not known

Confusional state*, emotional disorder*, libido disorders, drug dependence**, drug abuse**, withdrawal syndrome** 

Depression

Paradoxical reactions such as restlessness, agitation, irritability, aggression, delusion, anger, nightmares, hallucinations, psychosis, inappropriate behaviour**

Anterograde amnesia**, memory impairment

Nervous System Disorders

 

frequency not known

Somnolence*, headache*, dizziness*, decreased alertness*, ataxia*

Eye Disorders

 

frequency not known

Diplopia*

Cardiac Disorders

 

 frequency not known

Cardiac failure including cardiac arrest

Respiratory, Thoracic and Mediastinal Disorders

 

frequency not known

Respiratory depression

Gastrointestinal Disorders

 

frequency not known

Nausea*, vomiting*, constipation

Skin and Subcutaneous Tissue Disorders

 

 

frequency not known

Rash, pruritus, urticaria

 

Musculoskeletal and Connective Tissue  Disorders

 

frequency not known

Muscle weakness*

Renal and Urinary disorders

 

frequency not known

Urinary retention

General Disorders and Administration Site Conditions

 

 

frequency not known

Fatigue*

Injury, Poisoning and Procedural Complications

 

 

frequency not known

Falls, fractures***

 

* These phenomena occur predominantly at the start of therapy and usually disappear with repeated administration

 

** see 4.4 Warnings and Precautions

 

*** The risk of falls and fractures is increased in those taking concomitant sedatives (including alcoholic beverages) and in the elderly.

 

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 to IMBHPRA Pharmacovigilance, Earlsfort Terrace, IRL-Dublin 2.  Tel: +353 1 6764971, Fax: +353 1 6762517, Website: www.imbhpra.ie, e-mail: imbpharmacovigilance@imb.iemedsafety@hpra.ie.

 

 

4.9       Overdose

 

Symptoms

Benzodiazepines commonly cause drowsiness, ataxia, dysarthria and nystagmus. Overdose of bromazepam Lexotan is seldom life-threatening if the drug is taken alone, but may lead to slurred speech areflexia, apnea, hypotension, cardiorespiratory depression and coma.  Coma, if it occurs, usually lasts a few hours but it may be more protracted and cyclical, particularly in elderly patients. Benzodiazepine respiratory depressant effects are more serious in patients with respiratory disease.

 

[ … ]

 

 

5.1       Pharmacodynamic properties

 

Pharmacotheapeutic group: Anxiolytic, ATC code: N05BA08.

 

Bromazepam is a pyridylbenzodiazepine compound with anxiolytic properties.

 

5.2       Pharmacokinetic properties

 

[ … ]

 

Pharmacokinetics in special populations

The elimination half-life may be prolonged in elderly patients (see section 4.2 Posology and method of administration).

 

                        [ … ]

 

10.         DATE OF  REVISION OF THE TEXT

 

16 August 201322 July 2014

                                                                                                                       

 

              [ … ]

 

Updated on 30/08/2013 and displayed until 24/07/2014
Reasons for adding or updating:
  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 10 - Date of revision of the text
Date of revision of text on the SPC:   16-Aug-2013
Legal Category:   Product subject to medical prescription which may not be renewed (A)

Free-text change information supplied by the pharmaceutical company



Underlined text = new text

Strike throught text = deleted text                                                                          

 

 

4.8                   Undesirable effects

 

[ … ]

 

Injury, Poisoning and Procedural Complications: There have been reports of falls and fractures in benzodiazepine users. The risk is increased in those taking concomitant sedatives (including alcoholic beverages) and in the elderly.An increased risk for falls and fractures has been reported in elderly benzodiazepine users.

 

[ … ]

 

 

10.       DATE OF  REVISION OF THE TEXT

 

November 201016 August 2013
Updated on 10/12/2010 and displayed until 30/08/2013
Reasons for adding or updating:
  • Change to section 3 - Pharmaceutical form
Date of revision of text on the SPC:   19-Nov-2010
Legal Category:   Product subject to medical prescription which may not be renewed (A)

Free-text change information supplied by the pharmaceutical company



Underlined text has been added:

3                 PHARMACEUTICAL FORM

 

Lexotan 1.5 mg Tablets:

Tablet

            Off-white to slightly yellow, cylindrical, biplane tablets scored on one side and marked Roche 1.5 on reverse.

 

            Lexotan 3 mg Tablets:

Tablet

Pale red, slightly speckled, cylindrical, biplane tablets scored on one side and marked Roche 3 on reverse.

 

The tablets can be divided into equal halves.

Updated on 04/01/2010 and displayed until 10/12/2010
Reasons for adding or updating:
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose
  • Change to section 10 - Date of revision of the text
Date of revision of text on the SPC:   25-Nov-2009
Legal Category:   Product subject to medical prescription which may be renewed (B)

Free-text change information supplied by the pharmaceutical company

Underlined text = new text
Struck through text = deleted text

4.2       Posology and method of administration

 

The patient should be checked regularly at the start of treatment in order to minimise the dosage and/or the frequency of administration to prevent overdose due to accumulation.

 

Elderly and/or debilitated patients

Elderly patients require lower doses because of individual variations in sensitivity and pharmacokinetics; doses should not exceed half those normally recommended (see section 5.2 Pharmacokinetics in special populations).

 

 

4.4       Special warnings and precautions for use

 

General precautions

Concomitant use of alcohol / CNS depressants:

The concomitant use of Lexotan with alcohol or/and CNS depressants should be avoided. Such concomitant use has the potential to increase the clinical effects of Lexotan possibly including severe sedation, clinically relevant respiratory and/or cardio-vascular depression (see section 4.5).

 

Medical history of alcohol or drug abuse:

Lexotan should be used with extreme caution in patients with a medical history of alcohol or drug abuse.

 

Patients should be checked regularly at the start of treatment in order to minimize the dosage and/or the frequency of administration and to prevent overdose due to accumulation.

 

Tolerance

Some loss of efficacy to the effects of Lexotan benzodiazepines may develop after repeated use for a few weeks.

 

Dependence

Use of benzodiazepines and benzodiazepine-like agents may lead to the development of physical and psychic dependence upon these products, (see section 4.8).  The risk of dependence increases with dose and duration of treatment; it is also greater in patients with a medical history of alcohol and/or drug abuse.

 

Amnesia

It should be borne in mind that bBenzodiazepines may induce anterograde amnesia.  Anterograde amnesia may occur using higher therapeutic dosages (documented at 6mg), the risk increasing at higher dosages.  Amnestic effects may be associated with inappropriate behaviour.  The condition occurs most often several hours after ingesting the product and therefore to reduce the risk patients should ensure that they will be able to have an uninterrupted sleep of 7 – 8 hours (see section 4.8).

 

Benzodiazepines should not be used alone to treat depression or anxiety associated with depression (suicide may be precipitated in such patients).    Patients with known or presumed dependence on alcohol, medicines or drugs should not take benzodiazepines, except in rare situations under medical supervision.

 

4.5       Interaction with other medicinal products and other forms of interaction

 

Pharmacokinetic Drug-Drug Interaction (DDI)

Not recommended:     Concomitant intake with alcohol.

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

 

Take into account:     Combinations with CNS depressants

Enhancement of the central depressive effect may occur in cases of concomitant use with antipsychotics (neuroleptics), hypnotics, anxiolytics/sedatives, antidepressant agents, narcotic analgesics, anti-epileptic drugs, anaesthetics and sedative antihistamines.

 

In the case of narcotic analgesics, enhancement of the euphoria may also occur leading to an increase in psychic dependence.

 

Pharmacodynamic Drug-Drug Interaction (DDI)

Enhanced effects on sedation, respiration and hemodynamics may occur when Lexotan is co-administered with any centrally acting depressants including alcohol.

 

Alcohol should be avoided in patients receiving Lexotan (see section 4.4).

 

(See section 4.9) Overdose for warnings of other central nervous system depressants, including alcohol.

 

In the case of narcotic analgesics, enhancement of the euphoria may also occur leading to an increase in psychic drug dependence.

 

4.8       Undesirable effects

 

Drowsiness (when the product is used as a hypnotic it should be stated explicitly, drowsiness during the day), numbed emotions, reduced alertness, confusion, fatigue, headache, dizziness, muscle weakness, ataxia or double vision.  These phenomena occur predominantly at the start of therapy and usually disappear with repeated administration.

 

Other side-effects like gastrointestinal disturbances, changes in libido or skin reactions have been reported occasionally.

 

Amnesia

Anterograde amnesia may occur using therapeutic dosages, the risk increasing at higher dosages.  Amnestic effects may be associated with inappropriate behaviour (see section 4.4 Special warnings and special precautions for use).

 

Depression

Pre-existing depression may be unmasked during benzodiazepine use.

 

Psychiatric and “paradoxical” reactions

Reactions like restlessness, agitation, irritability, aggressiveness, delusion, rages, nightmares, hallucinations, psychoses, inappropriate behaviour and other adverse behavioural effects are known to occur when using benzodiazepines or benzodiazepine-like agents, see section 4.4 Special warnings and special precautions for use.  They may be quite severe with this product.  Should this occur, the use of the drug should be discontinued.  They are more likely to occur in children and the elderly than in other patients.

 

Dependence

Use (even at therapeutic doses) may lead to the development of physical dependence:  discontinuation of the therapy may result in withdrawal or rebound phenomena (see section 4.4 Special warnings and special precautions for use).  Psychic dependence may occur.  Abuse of benzodiazepines has been reported.

 

Lexotan is well tolerated in therapeutic doses.  The following undesirable effects may occur:

 

Psychiatric Disorders:

Confusional state, emotional disorder.  These phenomena occur predominantly at the start of therapy and usually disappear with repeated administration. Libido disorders have been reported occasionally.

 

Depression: Pre-existing depression may be unmasked during benzodiazepine use.

 

Paradoxical reactions such as restlessness, agitation, irritability, aggression, delusion, anger, nightmares, hallucinations, psychosis, inappropriate behaviour and other adverse behavioural effects are known to occur with benzodiazepines or benzodiazepine-like agents (see section 4.4).  Should this occur, the use of the drug should be discontinued.  They are more likely to occur in children and elderly patients than in other patients.

 

Dependence: Chronic use (even therapeutic doses) may lead to the development of physical and psychic drug dependence: discontinuation of therapy may result in withdrawal or rebound phenomena (see section 4.4)

Abuse of benzodiazepines has been reported.

 

Nervous System Disorder: Drowsiness, headache, dizziness, decreased alertness, ataxia.  These phenomena occur predominantly at the start of therapy and usually disappear with repeated administration.  Anterograde amnesia may occur using therapeutic dosages, the risk increasing at higher dosages.  Amnestic effects may be associated with inappropriate behaviour.

 

Eye Disorders: Diplopia, this phenomenon occurs predominantly at the start of therapy and usually disappears with repeated administration.

 

Gastrointestinal Disorders: Gastrointestinal disorders have been reported occasionally.

 

Skin and Subcutaneous Tissue Disorders: Skin reactions have been reported occasionally.

 

Musculoskeletal and Connective Tissue Disorders: Muscle weakness, this phenomenon occurs predominantly at the start of therapy and usually disappears with repeated administration.

 

General Disorders and Administration Site Conditions: Fatigue, this phenomenon occurs predominantly at the start of therapy and usually disappears with repeated administration.

 

Injury, Poisoning and Procedural Complications: An increased risk for falls and fractures has been reported in elderly benzodiazepine users.

 

Respiratory Disorders: Respiratory depression.

 

Cardiac Disorders: Cardiac failure including cardiac arrest.

 

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. Overdose of Lexotan is seldom life-threatening if the drug is taken alone, but may lead to areflexia, apnea, hypotension, cardiorespiratory depression and coma.  Coma, if it occurs, usually lasts only a few hours but it may be more protracted and cyclical, particularly in elderly patients. Benzodiazepine respiratory depressant effects are more serious in patients with respiratory disease.

 

If CNS depression is severe consider the use of flumazenil (Anexate®), a benzodiazepine antagonist. This should only be administered under closely monitored conditions. It has a short half-life (about an hour), therefore patients administered flumazenil will require monitoring after its effects have worn off. Flumazenil is contraindicated to be used with extreme caution in the presence of drugs that reduce seizure threshold (e.g. tricyclic antidepressants). Refer to the prescribing information for flumazenil (Anexate®), for further information on the correct use of this drug.

 

 

 

10.       DATE OF  REVISION OF THE TEXT

 

April 2007November 2009

                                                                                                                       

 

Updated on 02/12/2009 and displayed until 04/01/2010
Reasons for adding or updating:
  • Change to section 3 - Pharmaceutical form
Date of revision of text on the SPC:   25-Nov-2009
Legal Category:   Product subject to medical prescription which may be renewed (B)

Free-text change information supplied by the pharmaceutical company

The colour of the 3 mg tablets have changed from pink to pale red, slightly speckled
Updated on 08/06/2007 and displayed until 02/12/2009
Reasons for adding or updating:
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.9 - Overdose
  • Change to section 5.3 - Preclinical safety data
  • Change to section 6.1 - List of excipients
Date of revision of text on the SPC:   04/2007
Legal Category:   prescription only

Free-text change information supplied by the pharmaceutical company

Text underlined has been added, text with strike through deleted:

 

QUALITATIVE AND QUANTITATIVE COMPOSITION

 

Lexotan 1.5mg Tablets:

Each tablet contains 1.5mg bromazepam

            Excipients: Also contains 96.1mg lactose monohydrate

 

Lexotan 3mg Tablets:

Each tablet contains 3mg bromazepam

Excipients: Also contains 94.3mg lactose monohydrate

 

For a full list of excipients, see section 6.1.

 

Overdose

 

As with other benzodiazepines, overdose 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 have been taken.

 

Following overdose with any medicinal product, 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.  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 and lethargy.  In most cases it is sufficient to monitor the vital functions and await recovery.  Higher doses, especially in combination with other centrally acting drugs, can result in ataxia, hypotonia, hypotension, respiratory depression, rarely coma and very rarely death.

 

Flumazenil may be useful as an antidote.  Patients requiring such intervention should be monitored closely in hospital (see separate prescribing information). Flumazenil is not recommended in patients with epilepsy who have been treated with benzodiazepines.  Antagonism in such patients may produce seizures.

 

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, if it occurs, usually lasts only a few hours but it may be more protracted and cyclical, particularly in elderly patients. Benzodiazepine respiratory depressant effects are more serious in patients with respiratory disease.

 

Benzodiazepines increase the effects of other central nervous system depressants, including alcohol.

 

Treatment

Monitor the patient’s vital signs and institute supportive measures as indicated by the patient’s clinical state. In particular, patients may require symptomatic treatment for cardiorespiratory effects or central nervous system effects.

 

Further absorption should be prevented using an appropriate method e.g. treatment within 1-2 hours with activated charcoal. If activated charcoal is used airway protection is imperative for drowsy patients. In case of mixed ingestion gastric lavage may be considered, however not as a routine measure

 

If CNS depression is severe consider the use of flumazenil (Anexate®), a benzodiazepine antagonist. This should only be administered under closely monitored conditions. It has a short half-life (about an hour), therefore patients administered flumazenil will require monitoring after its effects have worn off. Flumazenil is contraindicated in the presence of drugs that reduce seizure threshold (e.g. tricyclic antidepressants). Refer to the prescribing information for flumazenil (Anexate®), for further information on the correct use of this drug.

 

Preclinical safety data

 

There is no further information from the preclinical testing which could be of relevance to the prescriber which has not been included in other sections of the Summary of Product Characteristics.

 

Carcinogenicity

Carcinogenicity studies conducted in rats did not reveal any evidence of a carcinogenic potential for bromazepam.

 

Mutagenicity

Bromazepam was not genotoxic in in-vitro and in-vivo tests.

 

Impairment of Fertility

Daily oral administration of bromazepam did not have any affect on the fertility and general reproductive performance of rats.

 

Teratogenicity

Increases in foetal mortality, an increase in the stillbirth rate and a reduction in pup survival have been observed when bromazepam was given to pregnant rats. In studies on embryotoxicity/teratogenicity no teratogenic effect was detected up to a dosage of 125 mg/kg/day.

Following per os administration with doses of up to 50 mg/kg/day to pregnant rabbits a reduction in maternal weight gain, a reduction in foetal weight and an increase in the incidence of resorptions have been observed.

 

Other

Chronic toxicity

No deviations from normal were observed in long-term toxicology studies except for an increase in liver weight. Histopathological examination revealed centrolobular hepatocellular hypertrophy which was considered to be indicative of enzyme induction by bromazepam. Adverse effects observed after high doses were slight to moderate sedation, ataxia, isolated brief convulsive seizures, occasional elevation in serum alkaline phosphatase and a borderline increase in SGPT (ALT).

 

List of excipients

 

Lexotan 1.5mg Tablets:

Microcrystalline cellulose

Lactose monohydrate

Magnesium stearate

Talc

 

Lexotan 3mg Tablets:

Microcrystalline cellulose

Lactose monohydrate

Magnesium stearate

Talc

Erythrosine aluminium lake (E127).

 

DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION

 

Date of first authorisation:          31 October 1980/

 

Date of last renewal:                 31 October 2005

 

 

DATE OF (PARTIAL) REVISION OF THE TEXT

 

March 2006April 2007

 

Updated on 21/04/2006 and displayed until 08/06/2007
Reasons for adding or updating:
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 10 - Date of revision of the text
Updated on 13/12/2005 and displayed until 21/04/2006
Reasons for adding or updating:
  • Change to section 7 - Marketing authorisation holder
  • Change to section 10 - Date of revision of the text
Updated on 10/10/2005 and displayed until 13/12/2005
Reasons for adding or updating:
  • Change to section 10 - Date of revision of the text
  • Change to section 7 - Marketing authorisation holder
Updated on 20/05/2005 and displayed until 10/10/2005
Reasons for adding or updating:
  • New SPC for medicines.ie

Document Links

 
  View all medicines
from this company
View Document
Bookmark and Share

Active Ingredients

 
   Bromazepam