Consumer medicine information

Lexotan

Bromazepam

BRAND INFORMATION

Brand name

Lexotan

Active ingredient

Bromazepam

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Lexotan.

SUMMARY CMI

Lexotan®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using Lexotan?

Lexotan contains the active ingredient bromazepam. Lexotan is used for anxiety, tension or agitation.

For more information, see Section 1. Why am I using Lexotan? in the full CMI.

2. What should I know before I use Lexotan?

Do not use if you have ever had an allergic reaction to Lexotan or any of the ingredients listed at the end of the CMI. The use of Lexotan may lead to dependence on the medicine. Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use Lexotan? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Lexotan and affect how it works. A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use Lexotan?

  • Take Lexotan exactly as your doctor has prescribed. Your doctor will tell you how many Lexotan 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.
  • 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.

More instructions can be found in Section 4. How do I use Lexotan? in the full CMI.

5. What should I know while using Lexotan?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using Lexotan.
  • Do not take any other medicines without first telling your doctor.
  • Tell your doctor if you become pregnant while taking Lexotan.
Things you should not do
  • Do not take Lexotan for a longer time than your doctor has prescribed.
  • Do not stop taking Lexotan or lower the dose, without first checking with your doctor, especially if you have epilepsy.
Driving or using machines
  • Do not drive or operate machinery until you know how Lexotan affects you.
Drinking alcohol
  • Alcohol may increase the effects of Lexotan. Your doctor may suggest that you avoid alcohol or reduce the amount of alcohol you drink while you are using Lexotan.
Looking after your medicine
  • Store below 30°C.
  • Store in a cool, dry place away from young children.

For more information, see Section 5. What should I know while using Lexotan? in the full CMI.

6. Are there any side effects?

Call your doctor straight away or go straight to the Emergency Department at your nearest hospital if you notice any of the following serious side effects: sudden anxiety or excitation, restlessness, agitation, irritability, anger, abnormal behaviour, hallucinations, delusions, severe sleep disturbances, or difficulties in breathing or shortness of breath. Speak to your doctor if you have any of the following less side effects and they worry you: drowsiness, tiredness, dizziness, unsteadiness, loss of memory, inattentiveness, confusion, lack of concentration, headache, hangover feeling in the morning, slurred speech, or unpleasant dreams. For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

Lexotan®

Active ingredient(s): bromazepam


Consumer Medicine Information (CMI)

This leaflet provides important information about using Lexotan. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using Lexotan.

Where to find information in this leaflet:

1. Why am I using Lexotan?
2. What should I know before I use Lexotan?
3. What if I am taking other medicines?
4. How do I use Lexotan?
5. What should I know while using Lexotan?
6. Are there any side effects?
7. Product details

1. Why am I using Lexotan?

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 to for anxiety. 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.

2. What should I know before I use Lexotan?

Warnings

Lexotan is not recommended as the first choice of treatment of depression, anxiety and/or mental disorder as it can increase the risk of suicide.

Do not use Lexotan if:

  • you are allergic to bromazepam, or any of the ingredients listed at the end of this leaflet.
    Always check the ingredients to make sure you can use this medicine.
  • you have severe and chronic lung disease
  • you have severe liver disease
  • you have temporary stops in breathing during sleep
  • you suffer from severe muscle weakness
  • the package is torn or shows signs of tampering
  • the expiry date (EXP) printed on the pack has passed

Check with your doctor if you:

  • have any other medical conditions, including:
    - liver, kidney or lung disease
    - high or low blood pressure
    - depression, schizophrenia or other mental illness
    - glaucoma (high pressure in the eye)
    - epilepsy (fits)
    - history of alcohol or drug abuse
  • take any medicines for any other condition
  • drink alcohol. Alcohol may increase the effects of Lexotan.
  • Are allergic to any other medicines, foods, dyes or preservatives.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend 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.

Lexotan crosses the placenta and may cause decreased muscle tone, breathing difficulties and sudden drop in body temperature in the newborn infant. Newborn infants born to mothers that have taken this type of medicine throughout pregnancy may be at risk of developing withdrawal symptoms.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

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.

Use in children

  • Do not give Lexotan to children

Dependence

  • The use of benzodiazepines (such as Lexotan) may lead to dependence on the medicine.

3. What if I am taking other medicines?

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

Some medicines may interfere with Lexotan and affect how it works, and some medicines may be affected by Lexotan. These medicines include:

  • other sleeping tablets, sedatives or tranquilizers
  • medicines for depression
  • medicines to control fits
  • medicines for allergies or colds such as antihistamines
  • pain relivers
  • muscle relaxants
  • cimetidine - a medicine used to treat ulcers
  • dilsulfiram - a medicine used in alcohol abuse

Taking central nervous system depressants/ sedatives

Taking central nervous system depressants, such as sedatives, tranquilizers, and hypnotics, while taking Lexotan, have the potential to significantly increase the effects on Lexotan and may lead to addiction or result in death from overdose.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect Lexotan.

4. How do I use Lexotan?

How much to take

  • Take Lexotan exactly as your doctor has prescribed. Your doctor will tell you how many Lexotan 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.
  • 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.
  • Do not stop taking Lexotan or lower the dose, without first checking with your doctor.

When to take Lexotan

  • Lexotan should be taken as directed by your doctor.

How to Lexotan

  • It should be taken on an empty stomach, 30 to 60 minutes before food.

If you forget to use Lexotan

Lexotan should be used regularly at the same time each day.

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

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

If you use too much Lexotan

If you think that you have used too much Lexotan, you may need urgent medical attention.

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

It is important that you recognize these signs of overdose early and take immediate action below.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using Lexotan?

Things you should 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.

All mentions of suicide or violence must be taken seriously. Tell your doctor or a mental health professional immediately if you experience mood changes, restlessness, aggression, rage, hallucinations or any adverse behavioural or unusual behaviour.

Call your doctor straight away if you:

  • become pregnant while taking Lexotan
  • have not taken your medicine exactly as prescribed
  • 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.

Remind any doctor, dentist or pharmacist you visit that you are using Lexotan.

Things you should not do

  • Do not take Lexotan for a longer time than your doctor has prescribed. Lexotan should be taken for short periods only (for example, 2-4 weeks) unless advised by 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. Stopping this medicine suddenly 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.

Do not drive or use any machines or tools 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 your drive a car or operate machinery or do anything else that could be dangerous if you are drowsy, dizzy or not alert.

Drinking alcohol

Tell your doctor if you drink alcohol.

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

Looking after your medicine

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

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place where the temperature stays below 30°C, away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
  • drowsiness, tiredness
  • dizziness
  • loss of memory, inattentiveness, confusion, lack of concentration
  • slurred speech
  • unpleasant dreams
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
  • blurred vision
  • rash
  • tremor
  • loss of appetite
  • dry mouth
  • slurred speech
  • loss of memory, inattentiveness, confusion, lack of concentration
  • sudden anxiety or excitation
  • seeing, feeling or hearing things that are not there
  • nightmares
  • shortness of breath or difficulty in breathing
  • fast, irregular heartbeat with feelings of dizziness or difficulty breathing
  • cardiac arrest
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

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

What Lexotan contains

Active ingredient
(main ingredient)
Bromazepam
Other ingredients
(inactive ingredients)
lactose monohydrate
microcrystalline cellulose
purified talc
magnesium stearate
iron oxide red (3mg)
indigo carmine aluminium lake (6mg)
iron oxide yellow (6mg)
Potential allergensNone.
Lexotan tablets are gluten-free.

Do not take this medicine if you are allergic to any of these ingredients.

What Lexotan looks like

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

(Aust R 52269).

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

(Aust R 52270).

Who distributes Lexotan

Pharmaco Australia Ltd
Level 13, 465 Victoria Avenue
Chatswood
NSW
2067
Phone: 1800 210 564

Under license of CHEPLAPHARM
Arzneimittel GmbH, Germany

This leaflet was prepared in November 2022.

Published by MIMS February 2023

BRAND INFORMATION

Brand name

Lexotan

Active ingredient

Bromazepam

Schedule

S4

 

1 Name of Medicine

Bromazepam.

2 Qualitative and Quantitative Composition

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

Excipients with known effect.

Contains sugars as lactose.
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 /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 /6 on one side and a simple break mark on the other side.

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.

4.2 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.

4.3 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).

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, hallucinations, 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. Co-administration 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 co-administered 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.

4.7 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.

4.8 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.

4.9 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).

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.

6 Pharmaceutical Particulars

6.1 List of Excipients

Microcrystalline cellulose, lactose monohydrate, magnesium stearate, purified talc, iron oxide red (3 mg tablet), indigo carmine aluminium lake (6 mg tablet), iron oxide yellow (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 PVC/Al or PVC/PE/PVDC/Al blister packs of 30 tablets.
Lexotan 6 mg is available in PVC/Al or PVC/PE/PVDC/Al blister packs 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.

6.7 Physicochemical Properties

Chemical structure.


CAS number.

1812-30-2.
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.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription only medicine.

Summary Table of Changes