Consumer medicine information

Lexotan [8710]

Bromazepam

BRAND INFORMATION

Brand name

Lexotan Tablets

Active ingredient

Bromazepam

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Lexotan [8710].

What is in this leaflet

This leaflet answers some common questions about Lexotan.

It does not contain all the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking Lexotan against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine.

You may need to read it again.

What Lexotan is used for

Lexotan contains the active ingredient bromazepam.

Lexotan belongs to a group of medicines called benzodiazepines which are thought to work by their action on brain chemicals.

Lexotan is used for anxiety, tension or agitation. Anxiety or tension associated with the normal stress of everyday life usually does not require treatment with medicines.

Your doctor, however, may have prescribed Lexotan for another purpose.

Ask your doctor if you have any questions why Lexotan has been prescribed for you.

In general, benzodiazepines such as Lexotan should be taken for short time periods only (for example 2 to 4 weeks). Continuous long-term use is not recommended unless advised by your doctor.

This medicine may be addictive.

This medicine is available only with a doctor's prescription.

Before you take Lexotan

Do not take Lexotan if:

  1. you have had an allergic reaction to Lexotan, other benzodiazepines or any ingredients listed at the end of this leaflet

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin
  1. you have severe and chronic lung disease
  2. you have severe liver disease
  3. you suffer from sleep apnoea (temporary stops in breathing when asleep)
  4. you have a muscle weakness disease known as myasthenia gravis
  5. the package is torn or shows signs of tampering
  6. the expiry date (EXP) printed on the pack has passed
  • If you take this medicine after the expiry date has passed, it may not work as well.

Do not give Lexotan to children.

Safety and effectiveness in children have not been established.

If you are not sure if you should be taking Lexotan, talk to your doctor.

Before you start to take it:

Your doctor must know about all the following before you start to take Lexotan.

Tell your doctor if:

  1. you are pregnant or plan to become pregnant

Lexotan is not recommended for use in pregnant women. Your doctor will discuss the risks and benefits of using Lexotan if you are pregnant or plan to become pregnant.

  1. you are breast-feeding or plan to breast-feed

Lexotan passes into breast milk and therefore there is a possibility that the breast-fed baby may be affected. Lexotan is not recommended for use whilst breast-feeding.

  1. you have any other health problems, especially the following:
  • liver, kidney or lung disease
  • high or low blood pressure
  • you suffer from depression, psychosis or schizophrenia
  • you suffer from fits or convulsions (epilepsy)
  • you have high pressure in the eye (glaucoma)
  • history of alcohol or drug abuse
  1. you drink alcohol regularly
  • Alcohol may increase the effects of Lexotan.
  1. you are lactose intolerant
  2. you are allergic to any other medicines, foods, dyes or preservatives.

If you have not told your doctor about any of the above, tell them before you start taking Lexotan.

Taking other medicines

Tell your doctor if you are taking any other medicines, including any that you have bought without a prescription from a pharmacy, supermarket or health food shop.

Some medicines may interfere with Lexotan. These medicines include:

  • other sleeping tablets, sedatives or tranquillisers
  • other medicines for anxiety
  • medicines used to treat certain mental and emotional conditions
  • medicines for depression such as fluvoxamine
  • medicines to control fits (epilepsy)
  • some medicines used to treat allergies and colds
  • pain relievers
  • muscle relaxants
  • anaesthetics
  • some medicines used to treat bacterial infections
  • some medicines used to treat HIV infection
  • some medicines used to treat heart conditions or high blood pressure
  • cimetidine - a medicine used to treat ulcers
  • disulfiram - a medicine used in the treatment of alcohol abuse

These medicines may be affected by Lexotan, or may affect how well Lexotan works. You may need to use different amounts of your medicine, or you may need to take different medicines. Your doctor will advise you.

Your doctor or pharmacist has more information on medicines to be careful with or avoid whilst taking Lexotan.

If you have not told your doctor about any of the above, tell them before you start taking Lexotan.

Ask your doctor or pharmacist if you are not sure about this list of medicines.

How to take Lexotan

Follow all directions given to you by your doctor or pharmacist carefully.

They may differ from the information contained in this leaflet.

If you do not understand the instructions on the box, ask your doctor or pharmacist for help.

How much to take

Take Lexotan exactly as your doctor has prescribed.

Your doctor will tell you how many tablets to take each day.

The dose varies from person to person depending on age and the condition being treated. The usual dose is between 6 to 12 mg daily. Elderly patients may need to take less.

How to take it

Swallow the tablets whole with a glass of water.

When to take it

Take the tablets as directed by your doctor. It should be taken on an empty stomach, 30 to 60 minutes before food.

How long to take it

Do not use Lexotan for longer than your doctor says.

Lexotan should be used for short periods only (for example 2 to 4 weeks). Continuous long-term use is not recommended unless advised by your doctor.

The use of benzodiazepines may lead to dependence on the medicine.

If you forget to take it

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to. Otherwise, take it as soon as you remember and then go back to taking it as you would normally.

Do not take a double a dose to make up for one you have missed.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering your dose, ask your pharmacist for some hints.

If you take too much (overdose)

If you think that you or anyone else may have taken too much Lexotan, immediately telephone your doctor or Poisons Information Centre (telephone 13 11 26) or go to Accident and Emergency at your nearest hospital. Do this even if there are no signs of discomfort or poisoning.

You may need urgent medical attention.

If you take too much Lexotan you may feel drowsy, confused, tired, dizzy, have difficulty breathing, feel weak or become unconscious.

Keep telephone numbers for these places handy.

If you are not sure what to do, contact your doctor or pharmacist.

While you are taking Lexotan

Things you must do

Tell all doctors, dentists and pharmacists who are treating you that you are taking Lexotan.

Do not take any other medicines whether they require a prescription or not without first telling your doctor.

Tell your doctor if you become pregnant while taking Lexotan.

Tell your doctor if, for any reason, you have not taken your medicine exactly as prescribed.

Otherwise, your doctor may think that it was not effective and change your treatment unnecessarily.

Tell your doctor if you feel the tablets are not helping your condition.

Be sure to keep all of your appointments with your doctor so that your progress can be checked.

Things you must not do

Do not drive or operate machinery until you know how Lexotan affects you.

Lexotan may cause drowsiness or dizziness in some people and therefore may affect alertness.

Make sure you know how you react to Lexotan before you drive a car, operate machinery, or do anything else that could be dangerous if you are drowsy, dizzy or not alert.

Even if you take Lexotan at night, you may still be drowsy or dizzy the next day.

Do not take Lexotan for a longer time than your doctor has prescribed.

Lexotan should be taken for short periods only (for example 2 to 4 weeks), unless advised otherwise by your doctor.

Do not change your dose without first checking with your doctor.

Do not stop taking Lexotan or lower the dose, without first checking with your doctor.

Stopping this medicine suddenly may cause some unwanted effects. Your doctor will explain how you should slowly reduce your dose of Lexotan before you can stop taking it completely.

Do not suddenly stop taking Lexotan if you suffer from epilepsy.

Suddenly stopping this medicine may make your epilepsy worse.

Do not give Lexotan to anyone else even if they have the same condition as you.

Do not use Lexotan to treat other complaints unless your doctor says to.

Things to be careful of

Be careful if you are elderly, unwell, drinking alcohol or taking other medicines.

Some people may experience side effects such as drowsiness, confusion, dizziness and unsteadiness, which may increase the risk of a fall.

Your doctor may suggest that you avoid alcohol or reduce the amount of alcohol you drink while you are taking Lexotan.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Lexotan.

Lexotan helps most people with anxiety but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

If you are over 65 years of age you may have an increased chance of getting side effects.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following and they worry you:

  • drowsiness, tiredness
  • dizziness
  • headache
  • unpleasant dreams
  • muscle weakness

These are the more common side effects of Lexotan.

Tell your doctor as soon as possible if you notice any of the following and they worry you:

  • blurred vision
  • rash
  • tremor
  • loss of appetite
  • dry mouth
  • slurred speech
  • loss of memory, inattentiveness, confusion, lack of concentration

Tell your doctor immediately if you notice any of the following:

  • sudden anxiety or excitation
  • seeing, feeling or hearing things that are not there
  • nightmares

These are serious side effects and you may need medical attention.

Tell your doctor immediately, or go to Accident and Emergency at your nearest hospital, if you notice any of the following:

  • shortness of breath or difficulty in breathing

These are serious side effects. You may need urgent medical attention. Serious side effects are rare.

This is not a complete list of all possible side effects. Others may occur in some people and there may be some side effects not yet known.

Tell your doctor if you notice anything else that is making you feel unwell, even if it is not on this list.

Ask your doctor or pharmacist if you don't understand anything on this list.

Do not be alarmed by this list of possible side effects.

You may not experience any of them.

After taking Lexotan

Storage

Keep your tablets in the blister pack until it is time to take them.

If you take the tablets out of the blister pack they may not keep well.

Keep Lexotan in a cool dry place where the temperature stays below 30°C.

Do not store it, or any other medicine, in a bathroom or near a sink.

Do not leave it in the car or on window sills.

Heat and dampness can destroy some medicines.

Keep Lexotan where young children cannot reach it.

A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking Lexotan, or the tablets have passed their expiry date, ask your pharmacist what to do with any tablets that are left over.

Product description

Availability

Lexotan comes in two tablet strengths, 3 mg and 6 mg. Both strengths are available in packs of 30.

What Lexotan looks like

Lexotan 3 mg tablets are pale red, slightly speckled, cylindrical, biplanar tablets marked with ROCHE/3 on one side and a simple break mark on the other side.

Lexotan 6 mg tablets are greenish-grey to greyish-green, slightly speckled, cylindrical, biplanar tablets marked with ROCHE/6 on one side and a simple break mark on the other side.

Ingredients

Active ingredient - bromazepam

  • each 3 mg tablet contains 3 mg bromazepam
  • each 6 mg tablet contains 6 mg bromazepam

Inactive ingredients -

3 mg and 6 mg tablets contain

  • lactose
  • microcrystalline cellulose (460)
  • talc (553)
  • magnesium stearate (470)

The 3 mg tablets also contain the colouring agent

  • iron oxide red CI 77491 (172(ii))

The 6 mg tablets also contain the colouring agents

  • indigotine CI 73015 (132)
  • iron oxide yellow, CI 77492 (172 (iii))

Lexotan tablets are gluten free.

Distributor

Lexotan is distributed by:

Roche Products Pty Limited
ABN 70 000 132 865
Level 8, 30-34 Hickson Road
Sydney NSW 2000
Medical enquiries: 1 800 233 950

Please check with your pharmacist for the latest Consumer Medicine Information.

Australian Registration Numbers

  • Lexotan 3 mg Tablets
    AUST R 52269
  • Lexotan 6 mg Tablets
    AUST R 52270

This leaflet was prepared on 28 February 2018

BRAND INFORMATION

Brand name

Lexotan Tablets

Active ingredient

Bromazepam

Schedule

S4

 

1 Name of Medicine

Bromazepam.

6.7 Physicochemical Properties

Bromazepam is a pale yellow, odourless, crystalline powder, with melting point 243-251°C. Its solubility is 0.1% in water at 25°C and 10% in dilute hydrochloric acid. Bromazepam differs from other benzodiazepines in the presence of bromine in position 7 and a pyridine ring in position 5, in place of a phenyl ring.
The chemical name for bromazepam is 7-bromo-1,3-dihydro-5-(2-pyridyl)-2H-1,4-benzodiazepin-2-one. The molecular formula is C14H10BrN3O and molecular weight is 316.16.

Chemical structure.


CAS number.

1812-30-2.

2 Qualitative and Quantitative Composition

Lexotan 3 mg tablets contain bromazepam 3mg.
Lexotan 6 mg tablets contain bromazepam 6 mg.

Excipients with known effect.

Lactose monohydrate.
For the full list of excipients, see Section 6.1.

3 Pharmaceutical Form

Tablets.
Lexotan 3 mg tablets are pale red, slightly speckled, cylindrical, biplanar tablets marked with ROCHE/3 on one side and a simple break mark on the other side.
Lexotan 6 mg tablets are greenish-grey to greyish-green, slightly speckled, cylindrical, biplanar tablets marked with ROCHE/6 on one side and a simple break mark on the other side.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: anxiolytic, ATC code: N05BA08.

Mechanism of action.

Bromazepam is a benzodiazepine with anxiolytic action.
At low doses, Lexotan selectively reduces tension and anxiety. At high doses, sedative and muscle relaxant properties appear.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Bromazepam, taken in the fasting state, is almost completely absorbed. Peak plasma levels of bromazepam are reached between 0.5-4 hours and may be maintained for up to 12 hours. The mean peak bromazepam level after a 12 mg oral dose is about 140 nanogram/mL. There is significant variation between subjects.
The absolute (versus IV solution) bioavailability of the tablet is 60%.
There is no information on the effect of food on absorption.

Distribution.

On average, 70% of bromazepam is bound to plasma proteins, which is considerably less than for diazepam and is attributed to the increased polarity of the molecule due to the presence of the pyridyl radical. The volume of distribution is about 50 L.

Metabolism.

Bromazepam undergoes extensive metabolism. The main metabolic pathway involves hydroxylation in position 3 with subsequent glucuronidation and cleavage of the heterocyclic ring with subsequent hydroxylation in the benzene ring and conjugation. Two metabolites predominate: 3-hydroxy-bromazepam and 2-(2-amino-5-bromo-3-hydroxybenzoyl) pyridine.

Excretion.

Less than 2% of a dose is excreted unchanged. The urinary recovery of intact bromazepam and the glucuronide conjugates of 3-hydroxy-bromazepam and 2-(2-amino-5-bromo-3-hydroxybenzoyl) pyridine is 2%, 27% and 40% of the administered dose.
Bromazepam has an elimination half-life of about 17 hours (range 11-22 h). The clearance is about 40 mL/min.

Pharmacokinetics in special populations.

Elderly.

The elimination half-life may be prolonged in elderly patients. The average reduction in clearance in elderly patients compared to young subjects is nearly 50%.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

4 Clinical Particulars

4.1 Therapeutic Indications

Symptomatic relief of tension, anxiety and agitation. Anxiety and tension associated with the stress of everyday life usually does not require treatment with an anxiolytic.

4.3 Contraindications

Lexotan is contraindicated in patients with: known hypersensitivity to benzodiazepines or any of the excipients; severe respiratory insufficiency including chronic obstructive airways disease with incipient respiratory failure; severe hepatic impairment as it may precipitate hepatic encephalopathy; sleep apnoea syndrome; myasthenia gravis.

4.4 Special Warnings and Precautions for Use

General.

Medical history of alcohol or drug abuse.

Patients with known or presumed dependence on alcohol or drugs should not take benzodiazepines unless under medical supervision.

Concomitant use of alcohol/CNS depressants.

Patients should be advised that their tolerance for alcohol and other CNS depressants will be diminished and concomitant use of Lexotan and alcohol 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 cardiovascular depression that could result in coma or death (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions; Section 4.9 Overdose).

Duration of treatment.

In general, benzodiazepines should be prescribed for short periods only (e.g. 2-4 weeks). Continuous long-term use of Lexotan is not recommended. There is evidence that tolerance develops to the sedative effects of benzodiazepines. After as little as one week of therapy, withdrawal symptoms can appear following the cessation of recommended doses (e.g. rebound insomnia following cessation of a hypnotic benzodiazepine).
Following the prolonged use of Lexotan at therapeutic doses, withdrawal from the medication should be gradual. An individualised withdrawal timetable needs to be planned for each patient in whom dependence is known or suspected. Periods from four weeks to four months have been suggested. As with other benzodiazepines, when treatment is suddenly withdrawn, a temporary increase in sleep disturbance can occur after use of Lexotan (see information on Dependence below).

Hypotension.

Although hypotension has occurred rarely, Lexotan should be administered with caution to patients in whom a drop in blood pressure might lead to cardiac or cerebral complications. This is particularly important in elderly patients.

Amnesia.

Transient amnesia or memory impairment has been reported in association with the use of benzodiazepines. Anterograde amnesia may occur at therapeutic dosages with the risk increasing at higher dosages. Amnesiac effects may be associated with inappropriate behaviour.

Myasthenia gravis.

Lexotan could increase the muscle weakness in myasthenia gravis and should not be used in patients with this condition (see Section 4.3 Contraindications).

Acute narrow angle glaucoma.

Caution should be used in the treatment of patients with acute narrow angle glaucoma because of atropine-like side effects.

Impaired renal/liver function and blood dyscrasias.

Patients with impaired renal or hepatic function should use benzodiazepine medication with caution and dosage reduction may be advisable. In rare instances, some patients taking benzodiazepines have developed blood dyscrasias, and some have had elevation of liver enzymes. As with other benzodiazepines, periodic blood counts and liver function tests are recommended.

Depression, psychosis and schizophrenia.

Lexotan is not recommended as primary therapy in patients with depression, anxiety and/or psychosis. In such conditions, psychiatric assessment and supervision are necessary if benzodiazepines are indicated. Benzodiazepines may increase depression in some patients and may contribute to deterioration in severely disturbed schizophrenics with confusion and withdrawal. Pre-existing depression may be unmasked during benzodiazepine use. Suicidal tendencies may be present or uncovered and protective measures may be required.

Psychiatric and 'paradoxical' reactions.

Paradoxical reactions such as restlessness, agitation, irritability, rages, hallucinations, aggressiveness, anxiety, delusion, anger, nightmares, psychoses, inappropriate behaviour and other adverse behavioural effects, acute rage, stimulation or excitement are known to occur with benzodiazepines. Should these occur, the use of the drug should be discontinued. They are more likely to occur in children and in the elderly.

Impaired respiratory function.

Lexotan should be used with extreme caution in patients with respiratory depression. In patients with chronic obstructive pulmonary disease, benzodiazepines can cause increased arterial carbon dioxide tension and decreased oxygen tension (see Section 4.3 Contraindications).

Epilepsy.

When Lexotan is administered to persons with convulsive disorders, an increase in the frequency and/or severity of grand mal seizures may occur, necessitating increased anticonvulsant medication. Abrupt withdrawal of benzodiazepines in persons with convulsive disorders may be associated with a temporary increase in the frequency and/or severity of seizures.

Hereditary problems.

As Lexotan contains lactose, patients with rare hereditary problems such as galactose intolerance, Lapp lactase deficiency or glucose/galactose malabsorption should not take this drug.

Abuse.

Caution must be exercised in administering Lexotan to individuals known to be addiction prone or those whose history suggests they may increase the dosage on their own initiative. It is desirable to limit repeat prescription without adequate medical supervision.

Dependence.

The use of benzodiazepines may lead to dependence, as defined by the presence of a withdrawal syndrome on discontinuation of the medicine. 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, Lexotan should be used with extreme caution in patients with a history of alcohol or drug abuse. Abuse has been reported more commonly in poly-drug abusers.
Tolerance, as defined by a need to increase the dose in order to achieve the same therapeutic effect, seldom occurs in patients receiving recommended doses under medical supervision. Tolerance to sedation may occur with benzodiazepines, especially in those with drug seeking behaviour.

Withdrawal.

Withdrawal symptoms similar in character to those noted with barbiturates and alcohol have occurred following abrupt discontinuation of benzodiazepines or changing to a benzodiazepine with a considerably shorter elimination half-life. These symptoms range from headaches, diarrhoea, muscle pain, insomnia, tension, restlessness, confusion, irritability, anxiety, dysphoria, palpitations, panic attacks, vertigo, myoclonus, akinesia, hypersensitivity to light, sound and touch, abnormal body sensations (e.g. feeling of motion, metallic taste), hyperacusis, numbness and tingling of the extremities, convulsions, depersonalisation, derealisation, delusional beliefs, hyper-reflexia and loss of short-term memory, to a major syndrome which may include convulsions, tremor, abdominal and muscle cramps, confusional state, delirium, hallucinations, hyperthermia, psychosis, vomiting and sweating (see Section 4.8 Adverse Effects (Undesirable Effects)). Such manifestations of withdrawal, especially the more serious ones, are more common in patients who have received excessive doses over a prolonged period. However, withdrawal symptoms have been reported following abrupt discontinuation of benzodiazepines taken continuously at therapeutic levels. Accordingly, Lexotan should be terminated by tapering the dose to minimise occurrence of withdrawal symptoms. Patients should be advised to consult with their physician before either increasing the dose or abruptly discontinuing the medication.
Rebound phenomena have been described in the context of benzodiazepine use. Rebound insomnia and anxiety mean an increase in the severity of these symptoms beyond pretreatment levels following cessation of benzodiazepines. Rebound phenomena in general possibly reflect re-emergence of pre-existing symptoms combined with withdrawal symptoms. Some patients prescribed benzodiazepines with very short half-lives (in the order of 2-4 h) may experience relatively mild rebound symptoms in between their regular doses. Withdrawal/rebound symptoms may follow high doses for relatively short periods.
The risk of withdrawal and rebound phenomena is greater after abrupt discontinuation of treatment.

Use in hepatic impairment.

Benzodiazepines may have a contributory role in precipitating episodes of hepatic encephalopathy in patients with severe hepatic impairment (see Section 4.3 Contraindications). Special caution should be exercised when administering Lexotan to patients with mild to moderate hepatic impairment.

Use in the elderly.

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.
Elderly or debilitated patients may be particularly susceptible to the sedative effects of benzodiazepines and associated giddiness, ataxia and confusion, which may increase the risk of a fall.
In a trial of 32 subjects, elderly people (aged 61 to 80 years) had significantly higher mean peak serum bromazepam concentrations, smaller volume of distribution, lower oral clearance, and increased serum free fraction compared to young people (aged 21 to 29 years). This association was statistically significant even when corrected for bodyweight. The average reduction in clearance in elderly patients compared to young patients was nearly 50%.
The pharmacological effects of benzodiazepines appear to be greater in elderly patients than in younger patients, even at similar plasma benzodiazepine concentrations, possibly because of age-related changes in drug-receptor interactions, post-receptor mechanisms and organ function. A reduction in dose for patients above 50 years is recommended.

Paediatric use.

Benzodiazepines may impair mental alertness in children. Bromazepam is not recommended for use in children due to insufficient evidence of safety and efficacy in this age group.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Pharmacokinetic drug-drug interaction.

Lexotan undergoes hepatic microsomal oxidation via the cytochrome P450 liver enzymes. Therefore, caution should be taken in patients taking medicines that inhibit the P450 liver enzymes (e.g. azole antifungals, macrolide antibiotics, HIV protease inhibitors, calcium channel blocking agents).
Lexotan undergoes oxidative metabolism and, consequently, may interact with disulfiram or cimetidine resulting in increased plasma levels of Lexotan. Patients should be observed closely for evidence of enhanced benzodiazepine response during concomitant treatment with either disulfiram or cimetidine; some patients may require a reduction in benzodiazepine dosage. Coadministration of cimetidine, a multi-CYP inhibitor, and possibly propranolol, may prolong the elimination half-life of bromazepam through a substantially reduced rate of clearance (with cimetidine the mean rate of clearance was reduced by 50%). In a trial of 18 healthy subjects there was no evidence of a drug interaction between bromazepam and oral contraceptives. Combined administration with fluvoxamine, an inhibitor of CYP1A2, results in significantly increased bromazepam exposure (AUC: 2.4-fold) and elimination half-life (1.9-fold).
In a trial of six healthy volunteers, bromazepam did not affect antipyrine metabolism, which is a surrogate marker for CYP1A2, CYP2B6, CYP2C and CYP3A activity.

Pharmacodynamic drug-drug interaction.

The benzodiazepines, including Lexotan, produce additive CNS depressant effects when coadministered with other medications which themselves produce CNS depression e.g. barbiturates, alcohol, sedatives, antidepressants, hypnotics, anxiolytics, phenothiazines and other antipsychotics, skeletal muscle relaxants, antihistamines, narcotic analgesics and anaesthetics (see Section 4.4 Special Warnings and Precautions for Use). Alcohol should be avoided in patients receiving Lexotan.
In the case of narcotic analgesics enhancement of euphoria may also occur, leading to an increase in psychic drug dependence.
The anticholinergic effects of atropine and similar medicines, antihistamines and antidepressants may be potentiated.
Interactions have been reported between some benzodiazepines and anticonvulsants, with changes in the serum concentration of the benzodiazepine or anticonvulsant. It is recommended that patients be observed for altered responses when benzodiazepines and anticonvulsants are prescribed together and that serum level monitoring of the anticonvulsant be performed more frequently.

Other interactions.

Minor EEG changes, usually low voltage fast activity, of no known clinical significance, have been reported with benzodiazepine administration.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category C)
Benzodiazepines cross the placenta and may cause hypotonia, reduced respiratory function and hypothermia in the newborn infant. Continuous treatment during pregnancy and administration of high doses in connection with delivery should be avoided. Withdrawal symptoms in newborn infants have been reported with this class of medicines.
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.
If Lexotan is prescribed to a woman of childbearing potential, she should be warned to contact her physician regarding discontinuing Lexotan if she intends to become or suspects that she is pregnant.
As benzodiazepines pass into breast milk, nursing mothers should not take Lexotan.

4.8 Adverse Effects (Undesirable Effects)

Most adverse effects encountered with Lexotan have been referable to the central nervous system.

Adverse events in clinical trials.

In clinical trials, in which the mean daily dose of Lexotan was 24 mg, the following adverse events were reported in ≥ 1% of patients treated with Lexotan (see Table 1).

Post-marketing adverse reactions.

Psychiatric disorders.

Confusional state, disorientation, emotional and mood disturbances, changes in libido, nervousness and depression have been reported.
Paradoxical reactions such as restlessness, agitation, irritability, aggressiveness, delusion, anger, nightmares, sleep disorders, hallucinations, psychosis, inappropriate behaviour, nervousness, anxiety, abnormal dreams, hyperactivity and other adverse behavioural effects are known to occur. They are more likely to occur in children and elderly patients than in other patients.

Dependence.

Chronic use (even at therapeutic doses) may lead to the development of physical and psychological drug dependence: discontinuation of therapy may result in withdrawal or rebound phenomena (see Section 4.4 Special Warnings and Precautions for Use).
Abuse of benzodiazepines is more common in poly-drug users.

Nervous system disorders.

Drowsiness and ataxia become less common with repeated administration. Headache, dizziness, decreased alertness, seizures, tremor, speech disorders and incontinence have been reported.
Anterograde amnesia may occur at therapeutic dosages with the risk increasing at higher dosages. Amnesic effects may be associated with inappropriate behaviour.

Eye disorders.

Diplopia and blurred vision have been reported.

Gastrointestinal disorders.

Gastrointestinal disorders, dry mouth, nausea and vomiting have been reported.

Metabolic and nutritional disorders.

Anorexia has been reported.

Skin and subcutaneous tissue disorders.

Skin reactions including pruritus and rash have been reported.

Musculoskeletal and connective tissue disorders.

Muscle weakness and muscle spasm have been reported.

General disorders and administration site conditions.

Fatigue.

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 has been reported.

Cardiac disorders.

Cardiac failure including cardiac arrest, hypotension, tachycardia and palpitations have been reported.

Investigations.

Instances of decreased haemoglobin and increased white cell counts have been reported.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

Dose.

As the effect of food on bromazepam absorption is unknown, doses should preferably be given on an empty stomach.
The maximum recommended dose is 60 mg daily.

Average dose for ambulatory patients.

3 mg two or three times daily. It is often an advantage to make the evening dose larger than other doses or when the total dose is low (e.g. 3 or 6 mg), to give the total dose in the evening.

Severe hospitalised cases.

6-12 mg two or three times daily.
These amounts are general recommendations and dosage should be individually determined. Treatment of outpatients should begin with low doses, gradually increasing to the optimum level. When treatment is ceased withdrawal should be gradual. The duration of treatment should be as short as possible.
Patients 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 of bromazepam.
The patient should be reassessed regularly and the need for continued treatment should be evaluated. The overall treatment should not be more than 2-4 weeks, followed by a tapering off process of up to 6-8 weeks (see Section 4.4 Special Warnings and Precautions for Use).

Special dosage instructions.

Paediatric use.

Bromazepam is not recommended in children as there is insufficient evidence of safety and efficacy in this group.

Use in elderly.

Elderly patients require lower doses (see Section 4.4 Special Warnings and Precautions for Use).

Use in hepatic impairment.

Patients with severe hepatic impairment should not be treated with Lexotan tablets (see Section 4.3 Contraindications). In patients with mild or moderate hepatic impairment, the lowest dose possible should be given.

4.7 Effects on Ability to Drive and Use Machines

As with all patients taking CNS depressant medications, patients receiving Lexotan should be warned not to operate dangerous machinery or motor vehicles until it is known that they do not become drowsy or dizzy from Lexotan therapy. Sedation, amnesia and impaired muscular function may adversely affect the ability to drive or operate machinery. This is increased if the patient has taken alcohol concomitantly with Lexotan (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions). Abilities may be impaired on the day following use.

4.9 Overdose

Symptoms.

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. Overdose of Lexotan is seldom life threatening if the drug is taken alone, but may lead to areflexia, apnoea, ataxia, hypotonia, hypotension, cardiorespiratory depression and coma. Coma 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. When combined with other CNS depressants, the effects of overdosage are likely to be severe and may prove fatal.

Treatment.

Treatment of overdose is symptomatic; institute supportive measures as indicated by the patient's clinical state. If the overdosage is known to be small, observation of the patient and monitoring of their vital signs only may be appropriate. In adults or children who have taken an overdose of benzodiazepines within 1-2 hours, consider activated charcoal with airway protection if indicated.
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 to be used with extreme caution in the presence of medicines 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 medicine.
Haemoperfusion and haemodialysis are not useful in benzodiazepine intoxication.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Microcrystalline cellulose, lactose monohydrate, magnesium stearate, talc, iron oxide red CI 77491 (172(ii)) (3 mg tablet), indigotine CI 73015 (132) (6 mg tablet), iron oxide yellow CI 77492 (172(iii)) (6 mg tablet).

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 30 °C.

6.5 Nature and Contents of Container

Lexotan 3 mg is available in a blister pack of 30 tablets.
Lexotan 6 mg is available in a blister pack of 30 tablets.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

Summary Table of Changes