Clonazepam 2mg tablets

United Kingdom - English - eMC (Electronic Medicines Compendium)

Buy It Now

Active ingredient:
Clonazepam
Available from:
Star Pharmaceuticals Ltd
ATC code:
N03AE01
INN (International Name):
Clonazepam
Dosage:
2mg
Pharmaceutical form:
Tablet
Administration route:
Oral
Class:
Schedule 4 (CD Benz)
Prescription type:
Valid as a prescribable product
Product summary:
BNF: 04080100; GTIN: 5050114176714
Authorization number:
; PL 20636/1767

Clonazepam Auden 500 microgram and 2 mg Tablets

EAS3565a

EAS3565a

Package leaflet: Information for the user

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.

If you have any further questions, ask your doctor or pharmacist.

This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness

are the same as yours.

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

See section 4.

What is in this leaflet

1. What Clonazepam is and what it is used for

2. What you need to know before you take Clonazepam

3. How to take Clonazepam

4. Possible side effects

5. How to store Clonazepam

6. Contents of the pack and other information

1.

What Clonazepam is and what it is used for

The name of your medicine is Clonazepam Auden 500 microgram and 2 mg Tablets (called Clonazepam in this leaflet).

Clonazepam belongs to a group of medicines called ‘benzodiazepines’. It is used to treat epilepsy. Clonazepam works by

preventing seizures or fits.

2.

What you need to know before you take Clonazepam

Do not take Clonazepam:

if you are allergic to clonazepam or any of the other ingredients of this medicine (listed in section 6).

if you are allergic to other benzodiazepine medicines. These include diazepam, chlordiazepoxide, bromazepam and

flurazepam.

if you have lung disease.

if you have myasthenia gravis (severe muscle weakness)

if you suffer from sleeping disorders, such as difficulty breathing while asleep (sleep apnoea)

if you have a severe liver condition

if you have problems with alcohol or drug (prescription or recreational) use

Warnings and precautions

Talk to your doctor or pharmacist before taking Clonazepam if:

you have a lung, liver or kidney condition

you have a history of depression or have attempted suicide

you have recently suffered a death of a close friend or relative

you regularly drink alcohol or use recreational drugs

you have porphyria (a disease that affects the skin and/or nervous system)

you suffer from cerebellar ataxia (you have a problem co-ordinating movement)

A small number of people being treated with anti-epileptics such as Clonazepam have had thoughts of harming or killing

themselves. If at any time you have these thoughts, contact your doctor immediately.

Other medicines and Clonazepam

Tell your doctor of pharmacist if you are taking, have recently taken or might take any other medicines.

In particular tell your doctor of pharmacist if you are taking any of the following medicines:

other medicines to treat epilepsy, such as carbamazepine, hydantoins, phenobarbital, phenytoin, primidone or sodium

valproate

cimetidine (medicine used to treat stomach problems)

rifampicin (an antibiotic)

anaesthetics

medicines to make you sleep (hypnotics)

medicines that help with anxiety (tranquillisers)

pain killers (analgesics) or medicines to relax your muscles (muscle relaxants)

If you any of the above applies to you (or you are not sure), talk to your doctor or pharmacist before taking Clonazepam.

Concomitant use of Clonazepam and sedative medicines such as benzodiazepines or related drugs increases the risk of

drowsiness, difficulties in breathing (respiratory depression), coma and may be life-threatening. Because of this, concomitant

use should only be considered when other treatment options are not possible.

However if your doctor does prescribe Clonazepam together with sedative medicines the dose and duration of concomitant

treatment should be limited by your doctor.

Please tell your doctor about all sedative medicines you are taking, and follow your doctor’s dose recommendation closely. It

could be helpful to inform friends or relatives to be aware of the signs and symptoms stated above. Contact your doctor when

experiencing such symptoms.

Clonazepam with alcohol

Do not drink alcohol whilst taking Clonazepam as it may cause fits (epileptic seizures) and increase the risk of having side

effects.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or

pharmacist for advice before taking this medicine.

Driving and using machines

Clonazepam may affect your ability to drive, operate machinery and other hazardous activities, particularly in the first few

days of treatment. This may be made worse if you drink alcohol. Increasing the dose of clonazepam or changing the time

that you take it may also slow your reactions. You should not drive unless your doctor says you can.

The medicine can affect your ability to drive as it may make you sleepy or dizzy.

Do not drive while taking this medicine until you know how it affects you.

It is an offence to drive if this medicine affects your ability to drive.

However, you would not be committing an offence if:

o The medicine has been prescribed to treat a medical or dental problem and

o You have taken it according to the instructions given by the prescriber or in the information provided with the

medicine and

o It was not affecting your ability to drive safely.

Talk to your doctor or pharmacist if you are not sure whether it is safe for you to drive while taking this medicine.”

Dependence

When taking this medicine there is a risk of dependence which increases with the dose and duration of treatment and also in

patients with a history of alcohol and/or drug abuse.

Clonazepam contains lactose

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this

medicinal product

.

3.

How to take Clonazepam

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you

are not sure.

The recommended dose is:

Clonazepam is taken 3-4 times a day. It is started at a low dose and increased over 2-4 weeks until the right dose for you is

reached (the maintenance dose). The maximum dose is 20 mg in a 24 hour period. Swallow the tablets with water. The

tablets can be broken in half to give a smaller dose.

Adults

The starting dose should be no more than 1.0 mg in a 24 hour period. The maintenance dose is usually a total of 4 to 8 mg in

a 24 hour period, but your doctor may tell you to take more.

Elderly

The starting dose should be no more than 0.5 mg in a 24 hour period, as elderly people are sensitive to the effects of

clonazepam and may become confused to begin with. The maintenance dose is usually a total of 4 to 8 mg in a 24 hour

period, but your doctor may tell you to take more.

Use in children and adolescents

Infants: The starting dose should be no more than 0.25 mg in a 24 hour period (half a 0.5 mg tablet) and the maintenance

dose is usually a total of 0.5 - 1 mg in a 24 hour period.

Children 1-5 years: The starting dose should be no more than 0.25 mg in a 24 hour period (half a 0.5 mg tablet) and the

maintenance dose is usually a total of 1 – 3 mg in a 24 hour period.

Children 5-12 years: The starting dose should be no more than 0.5 mg in a 24 hour period (one tablet) and the maintenance

dose is usually a total of 3 – 6 mg in a 24 hour period.

If you take more Clonazepam than you should

If you take too many tablets or someone else accidentally takes your medicine, contact you doctor, pharmacist or nearest

hospital immediately.

If you forget to take Clonazepam

If you forget to take a dose, simply take the next dose when it is due. Do not take a double dose to make up for a forgotten

dose.

If you stop taking Clonazepam

Do not suddenly stop taking Clonazepam

. If you need to stop taking Clonazepam, your doctor will tell you how to stop

slowly to reduce any side effects as you can get withdrawal symptoms if you stop suddenly. These symptoms may include

problems with sleeping, muscle pain, anxiety (sometimes severe), tension, restlessness, confusion, severe mood changes,

irritability, sweating, shakes (tremor), headaches and agitation. In serious cases, withdrawal effects can also include being

oversensitive to light, noise and touch, hallucinations, tingling, numbness and a feeling of being unreal.

If you think the effect of Clonazepam is too strong or too weak, talk to your doctor. Do NOT change the dose yourself.

4.

Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Tell your doctor immediately if you experience any of the following serious side effects – you may need urgent medical

treatment:

Changes in behaviour: aggressiveness, excitability, nervousness, hostility, anxiety, problems sleeping, nightmares, vivid

dreams, irritability, agitation, extreme mood changes and new types of seizures may occur.

Allergic reactions can occur (such as itching, swelling of the tongue, eyes, lips and hands).

The following side effects have been reported:

Memory loss (amnesia) after a traumatic event which may be linked with some strange behaviour (more likely with higher

doses).

Depression.

Loss of sex drive, impotence.

Dependence on clonazepam – this is more of a risk when the dose is high or the treatment is for a long time, and is

especially likely to occur in patients with a history of alcoholism or drug abuse.

Dizziness, light-headedness, sleepiness, tiredness, lack of co-ordination, poor concentration, restlessness, confusion,

disorientation, floppiness and weakness of the muscles, headache. Particularly at the start of treatment. The side effects

are usually short-lived and may disappear by adjusting the dose.

Breathlessness, swelling of the ankles, cough, tiredness and a racing heart.

Chest pain which may spread to your neck and shoulders and down your left arm.

Feeling unsteady when walking.

Platelet count bruising easily, being short of breath and nose bleeds.

Slurring of speech, lack of co-ordination of movement, double vision, rapid eye movements are all reversible effects that

may occur particularly if on long-term or high-dose treatment.

Increase in number of fits (epileptic seizures) may occur during long-term treatment or in patients with a rare condition

called porphyria.

Infants and small children may start to dribble or drool because of increased production of saliva and secretions from the

airways. Children should therefore be watched carefully as this might cause problems in breathing and/or severe choking

and coughing.

Rarely, nausea and stomach problems can occur.

Rarely there may be hives, rashes, short-term hair loss or change in skin colouring.

Rarely, urinary incontinence (not being able to control when to pass water) may occur.

There have been some isolated reports of:

changes to your blood or liver function (seen in test results).

early development of puberty in children. This effect is reversible.

Withdrawal symptoms

Stopping Clonazepam suddenly may cause withdrawal symptoms. These include, shakes (tremors), sweating, agitation,

problems sleeping, anxiety (sometimes severe), headaches, muscle pain, tension, restlessness, confusion, irritabilityand fits

(epileptic seizures). In severe cases the following effects may happen: a feeling of being unreal, oversensitivity to noise,

light and touch, numbness and tingling of the hands and feet or hallucinations.

Gradual withdrawal of Clonazepam will help to reduce these effects.

Injury

Patients taking benzodiazepine medicines are at risk of falling and breaking bones. The risk is increased in the elderly and

those taking other sedatives (including alcohol).

Reporting of side effects:

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

You can also report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA

Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the

safety of this medicine.

5.

How to store Clonazepam

Keep this medicine out of the sight and reach of children,

Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of

that month.

Keep the blister in the outer carton in order to protect from light. Do not throw away any medicines via wastewater or

household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the

environment.

6.

Contents of the pack and other information

What Clonazepam contains

The active substance is clonazepam.

The other ingredients are lactose monohydrate, magnesium stearate, microcrystalline cellulose and sodium starch

glycolate.

What Clonazepam looks like and contents of the pack

Clonazepam Auden 500 micrograms Tablets are white round tablets cross-scored and marked ‘CLN 0.5’.

Clonazepam Auden 2 mg Tablets are white round tablets cross-scored and marked ‘CLN 2’.

Clonazepam Tables are available in pack sizes of 100.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation holder

TEVA UK Limited,

Eastbourne,

BN22 9AG,

Manufacturer

Actavis Group PTC ehf

Reykjavikurvegur 76-78,

Hafnarfjorour, IS-220,

Iceland

This leaflet was last revised in October 2018.

PL 00289/2247

PL 00289/2248

150 mm

210 mm

35 mm

300 mm

PHARMACODE

SAMPLE

± 0.5

± 0.5

± 0.5

Unprinted area

EAS3565a

EAS3565a

What is in this leaflet

1. What Clonazepam is and what it is used for

2. What you need to know before you take Clonazepam

3. How to take Clonazepam

4. Possible side effects

5. How to store Clonazepam

6. Contents of the pack and other information

1.

What Clonazepam is and what it is used for

The name of your medicine is Clonazepam Auden 500 microgram and 2 mg Tablets (called Clonazepam in this leaflet).

Clonazepam belongs to a group of medicines called ‘benzodiazepines’. It is used to treat epilepsy. Clonazepam works by

preventing seizures or fits.

2.

What you need to know before you take Clonazepam

Do not take Clonazepam:

if you are allergic to clonazepam or any of the other ingredients of this medicine (listed in section 6).

if you are allergic to other benzodiazepine medicines. These include diazepam, chlordiazepoxide, bromazepam and

flurazepam.

if you have lung disease.

if you have myasthenia gravis (severe muscle weakness)

if you suffer from sleeping disorders, such as difficulty breathing while asleep (sleep apnoea)

if you have a severe liver condition

if you have problems with alcohol or drug (prescription or recreational) use

Warnings and precautions

Talk to your doctor or pharmacist before taking Clonazepam if:

you have a lung, liver or kidney condition

you have a history of depression or have attempted suicide

you have recently suffered a death of a close friend or relative

you regularly drink alcohol or use recreational drugs

you have porphyria (a disease that affects the skin and/or nervous system)

you suffer from cerebellar ataxia (you have a problem co-ordinating movement)

A small number of people being treated with anti-epileptics such as Clonazepam have had thoughts of harming or killing

themselves. If at any time you have these thoughts, contact your doctor immediately.

Other medicines and Clonazepam

Tell your doctor of pharmacist if you are taking, have recently taken or might take any other medicines.

In particular tell your doctor of pharmacist if you are taking any of the following medicines:

other medicines to treat epilepsy, such as carbamazepine, hydantoins, phenobarbital, phenytoin, primidone or sodium

valproate

cimetidine (medicine used to treat stomach problems)

rifampicin (an antibiotic)

anaesthetics

medicines to make you sleep (hypnotics)

medicines that help with anxiety (tranquillisers)

pain killers (analgesics) or medicines to relax your muscles (muscle relaxants)

If you any of the above applies to you (or you are not sure), talk to your doctor or pharmacist before taking Clonazepam.

Concomitant use of Clonazepam and sedative medicines such as benzodiazepines or related drugs increases the risk of

drowsiness, difficulties in breathing (respiratory depression), coma and may be life-threatening. Because of this, concomitant

use should only be considered when other treatment options are not possible.

However if your doctor does prescribe Clonazepam together with sedative medicines the dose and duration of concomitant

treatment should be limited by your doctor.

Please tell your doctor about all sedative medicines you are taking, and follow your doctor’s dose recommendation closely. It

could be helpful to inform friends or relatives to be aware of the signs and symptoms stated above. Contact your doctor when

experiencing such symptoms.

Clonazepam with alcohol

Do not drink alcohol whilst taking Clonazepam as it may cause fits (epileptic seizures) and increase the risk of having side

effects.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or

pharmacist for advice before taking this medicine.

Driving and using machines

Clonazepam may affect your ability to drive, operate machinery and other hazardous activities, particularly in the first few

days of treatment. This may be made worse if you drink alcohol. Increasing the dose of clonazepam or changing the time

that you take it may also slow your reactions. You should not drive unless your doctor says you can.

The medicine can affect your ability to drive as it may make you sleepy or dizzy.

Do not drive while taking this medicine until you know how it affects you.

It is an offence to drive if this medicine affects your ability to drive.

However, you would not be committing an offence if:

o The medicine has been prescribed to treat a medical or dental problem and

o You have taken it according to the instructions given by the prescriber or in the information provided with the

medicine and

o It was not affecting your ability to drive safely.

Talk to your doctor or pharmacist if you are not sure whether it is safe for you to drive while taking this medicine.”

Dependence

When taking this medicine there is a risk of dependence which increases with the dose and duration of treatment and also in

patients with a history of alcohol and/or drug abuse.

Clonazepam contains lactose

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this

medicinal product

.

3.

How to take Clonazepam

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you

are not sure.

The recommended dose is:

Clonazepam is taken 3-4 times a day. It is started at a low dose and increased over 2-4 weeks until the right dose for you is

reached (the maintenance dose). The maximum dose is 20 mg in a 24 hour period. Swallow the tablets with water. The

tablets can be broken in half to give a smaller dose.

Adults

The starting dose should be no more than 1.0 mg in a 24 hour period. The maintenance dose is usually a total of 4 to 8 mg in

a 24 hour period, but your doctor may tell you to take more.

Elderly

The starting dose should be no more than 0.5 mg in a 24 hour period, as elderly people are sensitive to the effects of

clonazepam and may become confused to begin with. The maintenance dose is usually a total of 4 to 8 mg in a 24 hour

period, but your doctor may tell you to take more.

Use in children and adolescents

Infants: The starting dose should be no more than 0.25 mg in a 24 hour period (half a 0.5 mg tablet) and the maintenance

dose is usually a total of 0.5 - 1 mg in a 24 hour period.

Children 1-5 years: The starting dose should be no more than 0.25 mg in a 24 hour period (half a 0.5 mg tablet) and the

maintenance dose is usually a total of 1 – 3 mg in a 24 hour period.

Children 5-12 years: The starting dose should be no more than 0.5 mg in a 24 hour period (one tablet) and the maintenance

dose is usually a total of 3 – 6 mg in a 24 hour period.

If you take more Clonazepam than you should

If you take too many tablets or someone else accidentally takes your medicine, contact you doctor, pharmacist or nearest

hospital immediately.

If you forget to take Clonazepam

If you forget to take a dose, simply take the next dose when it is due. Do not take a double dose to make up for a forgotten

dose.

If you stop taking Clonazepam

Do not suddenly stop taking Clonazepam

. If you need to stop taking Clonazepam, your doctor will tell you how to stop

slowly to reduce any side effects as you can get withdrawal symptoms if you stop suddenly. These symptoms may include

problems with sleeping, muscle pain, anxiety (sometimes severe), tension, restlessness, confusion, severe mood changes,

irritability, sweating, shakes (tremor), headaches and agitation. In serious cases, withdrawal effects can also include being

oversensitive to light, noise and touch, hallucinations, tingling, numbness and a feeling of being unreal.

If you think the effect of Clonazepam is too strong or too weak, talk to your doctor. Do NOT change the dose yourself.

4.

Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Tell your doctor immediately if you experience any of the following serious side effects – you may need urgent medical

treatment:

Changes in behaviour: aggressiveness, excitability, nervousness, hostility, anxiety, problems sleeping, nightmares, vivid

dreams, irritability, agitation, extreme mood changes and new types of seizures may occur.

Allergic reactions can occur (such as itching, swelling of the tongue, eyes, lips and hands).

The following side effects have been reported:

Memory loss (amnesia) after a traumatic event which may be linked with some strange behaviour (more likely with higher

doses).

Depression.

Loss of sex drive, impotence.

Dependence on clonazepam – this is more of a risk when the dose is high or the treatment is for a long time, and is

especially likely to occur in patients with a history of alcoholism or drug abuse.

Dizziness, light-headedness, sleepiness, tiredness, lack of co-ordination, poor concentration, restlessness, confusion,

disorientation, floppiness and weakness of the muscles, headache. Particularly at the start of treatment. The side effects

are usually short-lived and may disappear by adjusting the dose.

Breathlessness, swelling of the ankles, cough, tiredness and a racing heart.

Chest pain which may spread to your neck and shoulders and down your left arm.

Feeling unsteady when walking.

Platelet count bruising easily, being short of breath and nose bleeds.

Slurring of speech, lack of co-ordination of movement, double vision, rapid eye movements are all reversible effects that

may occur particularly if on long-term or high-dose treatment.

Increase in number of fits (epileptic seizures) may occur during long-term treatment or in patients with a rare condition

called porphyria.

Infants and small children may start to dribble or drool because of increased production of saliva and secretions from the

airways. Children should therefore be watched carefully as this might cause problems in breathing and/or severe choking

and coughing.

Rarely, nausea and stomach problems can occur.

Rarely there may be hives, rashes, short-term hair loss or change in skin colouring.

Rarely, urinary incontinence (not being able to control when to pass water) may occur.

There have been some isolated reports of:

changes to your blood or liver function (seen in test results).

early development of puberty in children. This effect is reversible.

Withdrawal symptoms

Stopping Clonazepam suddenly may cause withdrawal symptoms. These include, shakes (tremors), sweating, agitation,

problems sleeping, anxiety (sometimes severe), headaches, muscle pain, tension, restlessness, confusion, irritabilityand fits

(epileptic seizures). In severe cases the following effects may happen: a feeling of being unreal, oversensitivity to noise,

light and touch, numbness and tingling of the hands and feet or hallucinations.

Gradual withdrawal of Clonazepam will help to reduce these effects.

Injury

Patients taking benzodiazepine medicines are at risk of falling and breaking bones. The risk is increased in the elderly and

those taking other sedatives (including alcohol).

Reporting of side effects:

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

You can also report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA

Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the

safety of this medicine.

5.

How to store Clonazepam

Keep this medicine out of the sight and reach of children,

Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of

that month.

Keep the blister in the outer carton in order to protect from light. Do not throw away any medicines via wastewater or

household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the

environment.

6.

Contents of the pack and other information

What Clonazepam contains

The active substance is clonazepam.

The other ingredients are lactose monohydrate, magnesium stearate, microcrystalline cellulose and sodium starch

glycolate.

What Clonazepam looks like and contents of the pack

Clonazepam Auden 500 micrograms Tablets are white round tablets cross-scored and marked ‘CLN 0.5’.

Clonazepam Auden 2 mg Tablets are white round tablets cross-scored and marked ‘CLN 2’.

Clonazepam Tables are available in pack sizes of 100.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation holder

TEVA UK Limited,

Eastbourne,

BN22 9AG,

Manufacturer

Actavis Group PTC ehf

Reykjavikurvegur 76-78,

Hafnarfjorour, IS-220,

Iceland

This leaflet was last revised in October 2018.

PL 00289/2247

PL 00289/2248

SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT

Clonazepam Auden 2mg Tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 2 mg clonazepam.

Excipients with known effect:

Each tablet contains 142mg lactose monohydrate

For the full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM

Tablet

Round white tablets with cross-score break line, marked ‘CLN 2’.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications

All clinical forms of epileptic disease and seizures in infants, children and adults,

especially absence seizures (petit mal), including atypical absence; primary or

secondarily generalised tonic-clonic seizures (grand mal); partial (focal) seizures with

elementary or complex symptomatology; various forms of myoclonic seizures,

myoclonus and associated abnormal movements.

4.2

Posology and method of administration

Posology

Mode of administration:

Treatment should be started with low doses. The dose may be increased progressively

until the maintenance dose suited to the individual patient has been found. The cross-

scored tablets facilitate the administration of lower daily doses in the initial stages of

treatment.

The dosage of clonazepam must be adjusted to the needs of each individual and

depends on the individual response to therapy. The maintenance dosage must be

determined according to clinical response and tolerance.

The daily dose should be divided into 3 or 4 doses throughout the day. If doses are

not equally divided, the largest dose should be given before retiring. Once the

maintenance dose level has been reached, the daily amount may be given in a single

dose in the evening.

Simultaneous administration of more than one antiepileptic drug is a common

practice in the treatment of epilepsy and may be undertaken with clonazepam. The

dosage of each drug may be required to be adjusted to obtain the optimum effect. If

status epilepticus occurs in a patient receiving oral clonazepam, intravenous

clonazepam may still control the status. Before adding clonazepam to an existing

anticonvulsant regimen, it should be considered that the use of multiple

anticonvulsants may result in an increase of undesired effects. If necessary, larger

doses may be given at the discretion of the physician, up to a maximum of 20 mg

daily. The maintenance dose should be attained after 2-4 weeks of treatment.

Adults

Initial dose not to exceed 1 mg/day.

The maintenance dosage for adults normally falls with the range 4 – 8 mg.

Elderly

Initial dose should not exceed 0.5 mg/day. The elderly are particularly sensitive to

the effects of centrally depressant drugs and may experience confusion.

Children and Infants

Children should receive the 0.5 mg tablets to ensure optimum dosage adjustment.

Initial dose should not exceed 0.25 mg/day for infants and small children (1-5 yrs).

Initial dose should not exceed 0.5 mg/day for older children.

The maintenance dosage normally falls within the ranges:

Infants (0 - 1 year)

0.5 – 1 mg/day

Small children (1 – 5 years)

1 – 3 mg/day

School children (5-12 years)

3 – 6 mg/day

In some forms of childhood epilepsy, certain patients may cease to be adequately

controlled by clonazepam. Control may be re-established by increasing the dose or

interrupting treatment with clonazepam for 2 or 3 weeks. During the interruption in

therapy, careful observation and other drugs may be needed.

Hepatic Impairment

In patients with mild to moderate hepatic impairment the dose should be adjusted to

individual requirements and will probably be lower.

Method of administration

For oral administration.

4.3

Contraindications

Hypersensitivity to the active substance or any of the excipients listed in section

6.1.Acute pulmonary insufficiency; severe respiratory insufficiency, sleep apnoea

syndrome, myasthenia gravis, severe hepatic insufficiency.

Clonazepam must not be used in patients in a coma, or in patients known to be

abusing pharmaceuticals, drugs or alcohol.

4.4

Special warnings and precautions for use

Suicidal behaviour:

Suicidal ideation and behaviour have been reported in patients treated with anti-

epileptic agents in several indications. A meta-analysis of randomised placebo

controlled trials of anti-epileptic drugs has also shown a small increased risk of

suicidal ideation and behaviour. The mechanism of this risk is not known and the

available data do not exclude the possibility of an increased risk for clonazepam.

Therefore patients should be monitored for signs of suicidal ideation and behaviours

and appropriate treatment should be considered. Patients (and caregivers of patients)

should be advised to seek medical advice should signs of suicidal ideation or

behaviour emerge.

Patients with a history of depression and/or suicide attempts should be kept under

close supervision.

Use with caution in patients with chronic pulmonary insufficiency, or with renal or

hepatic function impairment, and in the elderly or debilitated. In these cases dosage

should generally be reduced.

Carefully adjust dosage to individual requirements in patients with pre-existing

disease of the liver or the respiratory system (e.g. chronic obstructive pulmonary

disease) and in patients undergoing treatment with other centrally acting medications

or anticonvulsant (antiepileptic) agents (see Section 4.5. Interaction with other

medicinal products and other forms of interaction).

Do not interrupt treatment abruptly. As with all other antiepileptic drugs, treatment

must be withdrawn gradually, by reducing the dose due to the risk of precipitating

status epilepticus. This precaution must also be taken when withdrawing another drug

while the patient is still receiving clonazepam therapy.

Prolonged use of benzodiazepines may result in dependence with withdrawal

symptoms on cessation of use.

Use with particular caution in patients with spinal or cerebellar ataxia, in the event of

acute intoxication with alcohol or drugs and in patients with severe liver damage (e.g.

cirrhosis of the liver).

The concomitant use of Clonazepam with alcohol or/and CNS depressants should be

avoided. Such concomitant use has the potential to increase the clinical effects of

Clonazepam possibly including severe sedation, clinically relevant respiratory and/or

cardio-vascular depression (see 4.5).

Use with extreme caution in patients with a history of alcohol or drug abuse.

Risk from concomitant use of opioids:

Concomitant use of Clonazepam and opioids may result in sedation, respiratory

depression, coma and death. Because of these risks, concomitant prescribing of

sedative medicines such as benzodiazepines or related drugs with opioids should be

reserved for patients for whom alternative treatment options are not possible. If a

decision is made to prescribe Clonazepam concomitantly with opioids, the lowest

effective dose should be used, and the duration of treatment should be as short as

possible.

The patients should be followed closely for signs and symptoms of respiratory

depression and sedation. In this respect, it is strongly recommended to inform patients

and their caregivers (where applicable) to be aware of these symptoms (see section

“Interaction with other medicinal products and other forms of interaction“).

Clonazepam may cause increased production of saliva and bronchial secretion in

infants and small children. Therefore special attention must be paid to maintaining

patency of the airways.

Effects

respiratory

system

aggravated

pre-existing

airways

obstruction or brain damage or if other medications which depress respiration have

been given. As a rule, this effect can be avoided by careful adjustment of the dose to

individual requirements.

Clonazepam is considered to be probably non porphyrinogenic, although there is

some conflicting evidence. In rare cases, clonazepam has induced convulsions in

patients with porphyria.

Like all drugs of this type, clonazepam may, depending on dosage, administration and

individual susceptibility, modify the patient’s reactions (e.g. driving ability,

behaviour in traffic) (See section 4.7).

Use in epileptic patients

As a general rule, epileptic patients are not allowed to drive. Even when adequately

controlled on Clonazepam, it should be remembered that any increase in dosage or

alteration

timings

dosage

modify

patients'

reactions,

depending

individual susceptibility.

In cases of loss or bereavement, psychological adjustment may be inhibited by

benzodiazepines.

Galactose intolerance

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase

deficiency of glucose-galactose malabsorption should not take this medicine.

Dependence

Use of benzodiazepines may lead to the development of physical and psychological

dependence upon these products (see 4.8). In particular long-term or high-dose

treatment, may lead to reversible disorders such as dysarthria, reduced coordination

of movements and gait disorder (ataxia), nystagmus and double vision (diplopia).

Furthermore,

risk

anterograde

amnesia,

which

occur

using

benzodiazepines at therapeutic dosages, increases at higher dosages. Amnestic effects

may be associated with inappropriate behaviour. With certain forms of epilepsy, an

increase in the frequency of seizures (see 4.8) during long-term treatment is possible.

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

withdrawal

symptoms.

During

long-term

treatment,

withdrawal

symptoms may develop after a lengthy period of use, especially with high doses or if

the daily dose is reduced rapidly or abruptly discontinued. The symptoms include

tremor, sweating, agitation, sleep disturbances and anxiety, headaches, muscle pain,

extreme anxiety, tension, restlessness, confusion, irritability and epileptic seizures

which may be associated with the underlying disease. In severe cases the following

symptoms may occur: derealisation, depersonalisation, hyperacusis, numbness and

tingling of the extremities, hypersensitivity to light, noise and physical contact or

hallucinations.

Since

risk

withdrawal

symptoms

greater

after

abrupt

discontinuation of treatment, abrupt withdrawal of the drug should therefore be

avoided and treatment - even if only of short duration - should be terminated by

gradually reducing the daily dose. The risk of withdrawal symptoms is increased

when benzodiazepines are used together with day-time sedatives (crossed tolerance).

4.5

Interaction with other medicinal products and other forms of interaction

Coadministration with alcohol

Alcohol in combination with clonazepam may modify the effects of the drug,

compromise the success of therapy or give rise to unpredictable side-effects. Under

no circumstances should alcohol be consumed while under treatment with

clonazepam.

Antiepileptic drugs

When used in conjunction with other antiepileptic drugs, side-effects such as sedation

and apathy, and toxicity may be more evident, particularly with hydantoins or

phenobarbital and combinations including them. This requires extra care in adjusting

dosage in the initial stages of treatment. The combination of clonazepam and sodium

valproate has, rarely, been associated with the development of absence status

epilepticus. Although some patients tolerate and benefit from this combination of

drugs, this potential hazard should be borne in mind when its use is considered.

The antiepileptic drugs phenytoin, phenobarbital, carbamazepine and valproate may

increase the clearance of clonazepam thereby decreasing the plasma concentrations of

the latter during combined treatment.

Pharmacokinetic interactions: Clonazepam itself does not induce the enzymes

responsible for its own metabolism.

The SSRI (selective serotonin reuptake inhibitors) sertraline and fluoxetine do not

affect the pharmacokinetics of clonazepam when administered concomitantly.

Special Precautions

The plasma concentration of clonazepam is often reduced by carbamazepine,

phenobarbital, phenytoin or primidone, and possibly by theophylline.

Concurrent treatment with phenytoin or primidone can change the plasma

concentration of phenytoin or primidone (usually increases).

There is an increased risk of prolonged sedation and respiratory depression when

clonazepam is given with amprenavir.

Metabolism of clonazepam is inhibited (i.e. increased plasma concentration) by

cimetidine, disulfiram, fluvoxamine and ritonavir.

Metabolism of clonazepam may possibly be accelerated by rifampicin.

Clonazepam may possibly antagonise effects of levodopa.

There are enhanced hypotensive and sedative effects when clonazepam is given with

alpha-blockers or with moxonidine.

There is an enhanced hypotensive effect when clonazepam is given with ACE

inhibitors, adrenergic neurone blockers, angiotensin-II receptor antagonists, beta-

blockers, calcium channel blockers, clonidine, diazoxide, diuretics, hydralazine,

methyldopa, minoxidil, nitrates or nitroprusside.

There is an increased sedative effect when clonazepam is given with alcohol, general

anaesthetics, tricyclic and tricyclic-related antidepressants, antihistamine (less so for

non-sedating antihistamines and not usually for topically applied antihistamines),

antipsychotics, baclofen, lofexidine, mirtazapine, nabilone, opioid analgesics,

tizanidine.

Opioids:

The concomitant use of sedative medicines such as benzodiazepines or related drugs

such as Clonazepam with opioids increases the risk of sedation, respiratory

depression, coma and death because of additive CNS depressant effect. The dosage

and duration of concomitant use should be limited (see section “ Special warnings

and precautions for use ”).

4.6

Fertility, pregnancy and lactation

Fertility

Preclinical studies in animals have shown reproductive toxicity and from preclinical

studies it cannot be excluded that clonazepam possesses the possibility of producing

congenital malformations (see section 5.3 Preclinical safety data).

From epidemiological evaluations there is evidence that anticonvulsant drugs act as

teratogens. However, it is difficult to determine from published epidemiological

reports which drug or combination of drugs is responsible for defects in the newborn.

The possibility also exists that other factors e.g. genetic factors or the epileptic

condition itself may be more important than drug therapy in leading to birth defects.

Clonazepam should only be administered to pregnant women if the potential benefits

outweigh the risk to the foetus.

Pregnancy

Clonazepam has harmful pharmacological effects on pregnancy and the

foetus/newborn child.

Clonazepam should not be used during pregnancy unless clearly necessary.

Administration of high doses in the last trimester of pregnancy or during labour can

cause irregularities in the heart beat of the unborn child and hypothermia, hypotonia,

mild respiratory depression and poor sucking in the neonate. Infants born to mothers

who took benzodiazepines chronically during the later stages of pregnancy may have

developed physical dependence and may be at some risk for developing withdrawal

symptoms in the post-natal period.

It should be borne in mind that both pregnancy itself and abrupt discontinuation of the

medication can cause exacerbation of epilepsy.

Breastfeeding

Clonazepam passes into the maternal milk in small amounts. Therefore, clonazepam

should not be used in mothers who breastfeed unless clearly necessary.

4.7

Effects on ability to drive and use machines

Driving, operating machinery and other hazardous activities should be avoided when

using clonazepam especially during the first few days of treatment. Even when

adequately controlled on clonazepam, increases in dosage or alteration in timings of

dosage may modify patients’ reactions, depending on individual susceptibility.

Clonazepam can slow reaction to such an extent that the ability to drive a vehicle or

operate machinery is impaired. This effect is aggravated by consumption of alcohol.

Driving, operating machinery and other hazardous activities should therefore be

avoided altogether or at least during the first few days of treatment.

The decision for allowing the patient to drive rests with their doctor and should be

based on the patient’s response to treatment and the dosage involved.

This medicine can impair cognitive function and can affect a patient’s ability

to drive safely. This class of medicine is in the list of drugs included in

regulations under 5a of the Road Traffic Act 1988. When prescribing this

medicine, patients should be told:

The medicine is likely to affect your ability to drive

Do not drive until you know how the medicine affects you

It is an offence to drive while under the influence of this medicine

However, you would not be committing an offence (called ‘statutory

defence’) if:

-

The medicine has been prescribed to treat a medical or dental problem

-

You have taken it according to the instructions given by the prescriber

and in the information provided with the medicine and

-

It was not affecting your ability to drive safely”

4.8

Undesirable effects

The side effects marked with an asterisk (*) are usually transitory and disappear

spontaneously as treatment continues or with dose reduction. They tend to occur early

in treatment and can be greatly reduced, if not avoided, by commencing with low

dosages followed by progressive increases.

Blood and the lymphatic system disorders

Isolated cases of blood dyscrasias.

Immune system disorders

Allergic reaction and a very few cases of anaphylaxis and angioedema.

Endocrine disorders

Isolated cases of reversible development of premature secondary sex characteristics in

children (incomplete precocious puberty) have been reported.

Psychiatric disorders and Paradoxical Reactions

Anterograde amnesia (risk increases at higher dosages). Amnestic effects may be

associated with inappropriate behaviour. Depression, loss of libido, impotence.

Use of benzodiazepines may lead to the development of physical and psychological

dependence upon these products. The risk of dependence increases with dose and

duration of treatment and is particularly pronounced in predisposed patients with a

history of alcoholism or drug abuse (see section 4.4) .

Paradoxical effects such as aggressiveness, excitability, nervousness, hostility,

anxiety, sleep disturbances, nightmares, vivid dreams, irritability, agitation, psychotic

disorders and activation of new types of seizures may occur. If these occur, the

benefit of continuing the drug should be weighed against the adverse effect. It may

be necessary to add another suitable drug to the regimen or to discontinue

clonazepam therapy.

Nervous system disorders

Dizziness*, light-headedness*, somnolence*, fatigue*, co-ordination disturbances*,

poor concentration, restlessness, confusion and disorientation, headache.

Dysarthria and ataxia* are reversible disorders and occur particularly in long-term or

high-dose treatment.

These undesirable effects occur relatively frequently and may disappear gradually in

the course of the treatment or on reduction of the dosage. They can be partially

prevented by increasing the dose slowly at the start of treatment.

Headache was observed in rare cases. Causing of generalised fits was observed very

rarely.

Particularly in long-term or high-dose treatment, reversible disorders such as

dysarthria, reduced coordination of movements and gait disorder (ataxia) and

nystagmus may occur. Anterograde amnesia may occur using benzodiazepines at

therapeutic dosages, the risk increasing at higher dosages. Amnestic effects may be

associated with inappropriate behaviour. Although Clonazepam has been given

uneventfully to patients with porphyria, rarely it may induce convulsions in these

patients

With certain forms of epilepsy, an increase in the frequency of seizures during long-

term treatment is possible.

Rarely, convulsions may be induced in patients with porphyria.

Eye disorders

Double vision and nystagmus are reversible disorders and occur particularly in long-

term or high-dose treatment.

Common: nystagmus

Cardiac Disorders

Cardiac failure including cardiac arrest has been reported.

Respiratory, thoracic and mediastinal disorders

Rarely respiratory depression may occur with intravenous clonazepam, particularly if

other depressant drugs have been administered. This effect may be aggravated by

pre-existing airways obstruction or brain damage or if other medications which

depress respiration have been given .This effect can usually be avoided by careful

adjustment of the dose to individual requirements.

In infants and small children, and particularly those with a degree of mental

impairment, salivary or bronchial hypersecretion with drooling may occur.

Supervision of the airway may be required.

Gastrointestinal disorders

Rarely: nausea, gastrointestinal symptoms.

Hepato-biliary disorders

Isolated cases of abnormal liver function tests have been reported.

Skin and subcutaneous tissue disorders

Rarely: urticaria, pruritus, transient hair loss, pigmentation changes.

Musculoskeletal, connective tissue and bone disorders

Muscle weakness*, occasional muscular hypotonia*

Renal and urinary disorders

Rarely: urinary incontinence.

Reproductive System and Breast Disorders

In rare cases erectile dysfunction or loss of libido may occur.

General disorders and administration site conditions

Withdrawal: Once physical dependence has developed, abrupt termination of

treatment will be accompanied by withdrawal symptoms. During long-term

treatment, withdrawal symptoms may develop, especially withdrawing from high

doses or if the daily dose is reduced rapidly or abruptly discontinued. The symptoms

include: tremor, sweating, agitation, sleep disturbances and anxiety, headaches,

muscle pain, extreme anxiety, tension, restlessness, confusion, irritability and

epileptic seizures which may be associated with the underlying disease. In severe

cases the following symptoms may occur: derealisation, depersonalisation,

hyperacusis, numbness and tingling of the extremities, hypersensitivity to light, noise

and physical contact or hallucinations. Since the risk of withdrawal symptoms is

greater after abrupt discontinuation of treatment, discontinuation should be carried

out by gradually reducing the daily dose.

Injury, Poisoning and Procedural Complications

An increased risk for falls and fractures has been reported in elderly benzodiazepine

users.

Investigations

In rare cases decreased platelet count may occur. As with other benzodiazepines,

isolated cases of blood dyscrasias. Dependence and withdrawal, (see 4.4).

Paediatric population

For paediatric specific events please refer to the information listed under headings:

Endocrine Disorders and

Respiratory, Thoracic and Mediastinal System Disorders in section 4.8.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal

product is important. It allows continued monitoring of the benefit/risk balance

of the medicinal product. Healthcare professionals are asked to report any

suspected adverse reactions via Yellow Card Scheme at:

www.mhra.gov.uk/yellowcard

or search for MHRA Yellow Card in the

Google Play or Apple App Store.

4.9

Overdose

As with other benzodiazepine drugs, overdosage should not present undue problems

of management or threat to life. Patients have recovered from overdoses in excess of

60mg without special treatment. Severe somnolence with muscle hypotonia will be

present.

Symptoms:

The symptoms of overdosage or intoxication vary greatly from person to person

depending on age, bodyweight and individual response. 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 usually lasts only a few hours but in elderly people it may be more

protracted and cyclical. Benzodiazepine respiratory depressant effects are more

serious in patients with severe chronic obstructive airways disease.

Benzodiazepines potentiate the effects of other central nervous system depressants,

including alcohol.

Management:

1. Maintain a clear airway and adequate ventilation if indicated.

2. The benefit of gastric decontamination is uncertain. Consider activated charcoal

(50g for an adult, 10-15g for a child) in adults or children who have taken more than

0.4mg/kg within 1 hour, provided they are not too drowsy.

PAR Clonazepam 0.5mg and 2mg tablets

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1

Public Assessment Report

Decentralised Procedure

Clonazepam 0.5mg and 2mg Tablets

(clonazepam)

UK/H/1890/01-02/DC

UK licence number: PL 20620/0045-6

NRIM Limited

PAR Clonazepam 0.5mg and 2mg tablets

PL 20620/0045-6; UK/H/1890/01-02/DC

2

LAY SUMMARY

On 29

June 2010, the MHRA granted NRIM Limited Marketing Authorisations (licences)

for the medicinal products Clonazepam 0.5mg and 2mg Tablets (PL 20620/0045-6,

UK/H/1890/01-02/DC). These are prescription-only medicines (POM).

Clonazepam tablets contain the active ingredient, clonazepam, which belongs to a group of

medicines called ‘benzodiazepines’. Clonazepam tablets are used to treat an illness called

epilepsy and work by preventing seizures or fits.

No new or unexpected safety concerns arose from these applications and it was, therefore,

judged that the benefits of Clonazepam 0.5mg and 2mg Tablets outweigh the risks; hence

Marketing Authorisations have been granted.

PAR Clonazepam 0.5mg and 2mg tablets

PL 20620/0045-6; UK/H/1890/01-02/DC

3

TABLE OF CONTENTS

Module 1: Information about initial procedure

Page 4

Module 2: Summary of Product Characteristics

Page 5

Module 3: Product Information Leaflet

Page 13

Module 4: Labelling

Page 15

Module 5: Scientific discussion during initial procedure

Page 19

I Introduction

Page 19

II About the product

Page 21

III Scientific Overview and discussion

Page 22

III.1 Quality aspects

Page 22

III.2 Non-clinical aspects

Page 25

III.3 Clinical aspects

Page 25

IV Overall conclusions and benefit-risk assessment

Page 28

Module 6: Steps taken after initial procedure

Page 29

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Module 1

Information about Initial Procedure

Product Name

Clonazepam 0.5mg and 2mg Tablets

Type of Application

Generic, Article 10.1

Active Substance

Clonazepam

Form

Tablets

Strength

0.5mg and 2mg

MA Holder

NRIM Limited

Marlborough House

298, Regents Park Road

Finchley N3 2UA

London, United Kingdom

Reference Member State

(RMS)

Concerned Member

State (CMS)

Hungary

Procedure Number

UK/H/1890/01-02/DC

Timetable

End of Procedure: Day 210 – 10

June 2010

PAR Clonazepam 0.5mg and 2mg tablets

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5

Module 2

Summary of Product Characteristics

The UK Summary of Product Characteristics (SmPC) for Clonazepam 0.5mg and 2mg Tablets

(PL 20620/0045-6) is as follows. Differences between the individual SmPCs are highlighted:

1

NAME OF THE MEDICINAL PRODUCT

Clonazepam 0.5mg Tablets

Clonazepam 2mg Tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each Tablet contains 0.5mg / 2mg of clonazepam.

Also contains 73.0mg of Lactose per tablet.

For a full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM

Tablets.

For Clonazepam 0.5mg Tablets (PL 20620/0045) - Peach coloured flat circular bevelled tablets, cross-

scored on one side and plain on the other side.

For Clonazepam 2mg Tablets (PL 20620/0046) – White to off white flat circular bevelled tablets,

cross-scored on one side and plain on the other side.

The tablets can be divided in to equal quarters.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications

All clinical forms of epileptic disease and seizures in infants, children and adults, especially absence

seizures (petit mal) including atypical absence; primary or secondarily generalised tonic-clonic (grand

mal), tonic or clonic seizures; partial (focal) seizures with elementary or complex symptomatology;

various forms of myoclonic seizures, myoclonus and associated abnormal movements.

4.2

Posology and method of administration

Route of administration

Oral

Recommended dosage

The scored 0.5mg tablets facilitate the administration of lower daily doses in the initial stages of

treatment.

Adults

Initial dosage should not exceed 1mg/day. The maintenance dosage for adults normally falls within the

range 4 to 8mg.

Elderly

The elderly are particularly sensitive to the effects of centrally depressant drugs and may experience

confusion. It is recommended that the initial dosage of clonazepam should not exceed 0.5mg/day.

These are total daily dosages which should be divided into 3 or 4 doses taken at intervals throughout

the day. If necessary, larger doses may be given at the discretion of the physician, up to a maximum of

20mg daily. The maintenance dose should be attained after 2 to 4 weeks of treatment.

Infants and children

To ensure optimum dosage adjustment, children should be given the 0.5mg tablets.

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Initial dosage should not exceed 0.25mg/day for infants and small children (1 to 5 years) and

0.5mg/day for older children. The maintenance dosage normally falls within the ranges:

School children (5 to 12 years) 3 to 6mg

Small children (1 to 5 years) 1 to 3mg

Infants (0 to 1 year) 0.5 to 1mg

In some forms of childhood epilepsy, certain patients may cease to be adequately controlled by

clonazepam. Control may be re-established by increasing the dose, or interrupting treatment with

clonazepam for 2 or 3 weeks. During the interruption in therapy, careful observation and other drugs

may be needed.

Mode of administration

Treatment should be started with low doses. The dose may be increased progressively until the

maintenance dose suited to the individual patient has been found.

The dosage of clonazepam must be adjusted to the needs of each individual and depends on the

individual response to therapy. The maintenance dosage must be determined according to clinical

response and tolerance.

The daily dose should be divided into 3 equal doses. If doses are not equally divided, the largest dose

should be given before retiring. Once the maintenance dose level has been reached, the daily amount

may be given in a single dose in the evening.

Simultaneous administration of more than one antiepileptic drug is a common practice in the treatment

of epilepsy and may be undertaken with clonazepam. The dosage of each drug may be required to be

adjusted to obtain the optimum effect. If status epilepticus occurs in a patient receiving oral

clonazepam, intravenous clonazepam may still control the status. Before adding clonazepam to an

existing anticonvulsant regimen, it should be considered that the use of multiple anticonvulsants may

result in an increase of undesired effects

4.3

Contraindications

Patients with known sensitivity to benzodiazepines; or any of the drugs excipients; acute pulmonary

insufficiency; severe respiratory insufficiency, sleep apnoea syndrome, myasthenia gravis, severe

hepatic insufficiency.

4.4

Special warnings and precautions for use

Suicidal ideation and behaviour have been reported in patients treated with anti-epileptic agents in

several indications. A meta-analysis of randomised placebo controlled trials of anti-epileptic drugs has

also shown a small increased risk of suicidal ideation and behaviour. The mechanism of this risk is not

known and the available data do not exclude the possibility of an increased risk for clonazepam.

Therefore patients should be monitored for signs of suicidal ideation and behaviours and appropriate

treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical

advice should signs of suicidal ideation or behaviour emerge.

Patients with a history of depression and/or suicide attempts should be kept under close supervision.

Clonazepam should be used with caution in patients with chronic pulmonary insufficiency, or with

impairment of renal or hepatic function, and in the elderly or the debilitated. In these cases dosage

should generally be reduced.

As with all other antiepileptic drugs, treatment with clonazepam even if of short duration, must not be

abruptly interrupted, but must be withdrawn by gradually reducing the dose in view of the risk of

precipitating status epilepticus. This precaution must also be taken when withdrawing another drug

while the patient is still receiving clonazepam therapy.

Prolonged use of benzodiazepines may result in dependence development with withdrawal symptoms

on cessation of use.

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Clonazepam may be used only with particular caution in patients with spinal or cerebellar ataxia, in the

event of acute intoxication with alcohol or drugs and in patients with severe liver damage (e.g.

cirrhosis of the liver).

Benzodiazepines should be used with extreme caution in patients with a history of alcohol or drug

abuse.

In infants and small children clonazepam may cause increased production of saliva and bronchial

secretion. Therefore special attention must be paid to maintaining patency of the airways.

The dosage of clonazepam must be carefully adjusted to individual requirements in patients with pre-

existing disease of the respiratory system (e.g. chronic obstructive pulmonary disease) or liver and in

patients undergoing treatment with other centrally acting medications or anticonvulsant (antiepileptic)

agents (see section 4.5).

Like all drugs of this type, clonazepam may, depending on dosage, administration and individual

susceptibility, modify the patient's reactions (e.g. driving ability, behaviour in traffic).

In cases of loss or bereavement, psychological adjustment may be inhibited by benzodiazepines.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-

galactose malabsorption, should not take this medicine.

4.5

Interaction with other medicinal products and other forms of interaction

Since alcohol can provoke epileptic seizures, irrespective of therapy, patients must under no

circumstances drink alcohol while under treatment. In combination with clonazepam, alcohol may

modify the effects of the drug, compromise the success of therapy or give rise to unpredictable side-

effects.

When clonazepam is used in conjunction with other antiepileptic drugs, side-effects such as sedation

and apathy, and toxicity may be more evident, particularly with hydantoins or phenobarbital and

combinations including them. This requires extra care in adjusting dosage in the initial stages of

treatment. The combination of clonazepam and sodium valproate has, rarely, been associated with the

development of absence status epilepticus. Although some patients tolerate and benefit from this

combination of drugs, this potential hazard should be borne in mind when its use is considered.

The antiepileptic drugs phenytoin, phenobarbital, carbamazepine and valproate may induce the

metabolism of clonazepam causing higher clearance and lower plasma concentrations of the latter

during combined treatment.

The selective serotonine reuptake inhibitors sertraline and fluoxetine do not affect the

pharmacokinetics of clonazepam when administered concomitantly.

Known inhibitors of hepatic enzymes, e.g. cimetidine, have been shown to reduce the clearance of

benzodiazepines and may potentiate their action and known inducers of hepatic enzymes, e.g.

rifampicin, may increase the clearance of benzodiazepines.

In concurrent treatment with phenytoin or primidone, a change, usually a rise in the serum

concentration of these two substances has occasionally been observed.

Concurrent use of clonazepam and other centrally acting medications, e.g. other anticonvulsant

(antiepileptic) agents, anaesthetics, hypnotics, psychoactive drugs and some analgesics as well as

muscle-relaxants may result in mutual potentiation of drug effects. This is especially true in the

presence of alcohol. In combination therapy with centrally-acting medications, the dosage of each drug

must be adjusted to achieve the optimum effect.

4.6

Pregnancy and lactation

Preclinical studies in animals have shown reproductive toxicity (see section 5.3 Preclinical safety data).

From epidemiological evaluations there is evidence that anticonvulsant drugs act as teratogens.

Clonazepam has harmful pharmacological effects on pregnancy and the foetus/newborn child.

Administration of high doses in the last trimester of pregnancy or during labour can cause irregularities

in the heart beat of the unborn child and hypothermia, hypotonia, mild respiratory depression and poor

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sucking in the neonate. Infants born to mothers who took benzodiazepines chronically during the later

stages of pregnancy may have developed physical dependence and may be at some risk for developing

withdrawal symptoms in the post-natal period. Therefore clonazepam should not be used in pregnancy

unless clearly necessary.

Clonazepam has been found to pass into the maternal milk in small amounts. Therefore clonazepam

should not be used in mothers who breastfeed unless clearly necessary.

4.7

Effects on ability to drive and use machines

Epileptic patients are not allowed to drive, even when adequately controlled on clonazepam, it should

be remembered that any increase in dosage or alteration in timings of dosage may modify patients’

reactions, depending on individual susceptibility. Even if taken as directed, clonazepam can slow

reactions to such an extent that the ability to drive a vehicle or operate machinery is impaired. This

effect is aggravated by consumption of alcohol. Driving, operating machinery and other hazardous

activities should therefore be avoided altogether or at least during the first few days of treatment. The

decision on this question rests with the patient's physician and should be based on the patient's response

to treatment and the dosage involved.

4.8

Undesirable effects

Clonazepam is well tolerated and adverse reactions have generally been mild and reversible. The

following have been reported as adverse events in clinical trials or reported from routine use, but in

many cases a relationship to treatment with clonazepam has not been established.

The following definitions of frequencies are used:

Common

> 1/100

Uncommon

> 1/1000 and < 1/100

Rare

< 1/1000

Common:

Psychiatric: poor concentration, restlessness, confusion and disorientation have been observed.

Anterograde amnesia may occur using benzodiazepines at therapeutic dosage, the risk increasing at

higher dosages. Amnesic effects may be associated with inappropriate behaviour.

Neurological: dizziness, ataxia, somnolence, and co-ordination disturbances; such effects are usually

transient and disappear spontaneously as treatment continues or with dosage reduction. They tend to

occur early in treatment and can be greatly reduced, if not avoided, by commencing with low dosages

followed by progressive increases.

Musculoskeletal: muscle weakness

General: fatigue, light-headedness

Uncommon:

Musculoskeletal: occasional muscular hypotonia

Psychiatric: use of benzodiazepines may lead to the development of physical and psychological

dependence upon these products. The risk of dependence increases with dose and duration of treatment

and is particularly pronounced in predisposed patients with a history of alcoholism or drug abuse.

Rare:

Haematological: as with other benzodiazepines, isolated cases of blood dyscrasias have been reported.

Psychiatric: depression may occur in patients treated with clonazepam, but it may be also associated

with the underlying disease

Neurological: particularly in long-term use, or with high-dose treatment, there are reports of reversible

disorders such as a slowing or slurring of speech (dysarthria), reduced co-ordination of movements and

gait (ataxia). Seizures may also occur in pre-disposed patients (see

Special

Warnings and Precautions

for Use

PAR Clonazepam 0.5mg and 2mg tablets

PL 20620/0045-6; UK/H/1890/01-02/DC

9

Eye Disorders: double vision and nystagmus.

Gastrointestinal: gastrointestinal symptoms including nausea.

Respiratory: respiratory depression may occur with intravenous clonazepam, particularly if other

depressant drugs have been administered. As a rule, this effect can be avoided by careful adjustment of

the dose in individual requirements.

Hepatic: abnormal liver function tests have been reported.

Skin: there are a few reports of urticaria, pruritus, transient hair loss and pigmentation changes.

Allergic reactions including a very few cases of anaphylaxis and angioedema have been reported to

occur with benzodiazepines.

Urinary: urinary incontinence.

Reproductive: decrease in sexual drive (loss of libido), and impotence have been reported. Isolated

cases of reversible development of premature secondary sex characteristics in children (incomplete

precocious puberty) have also been reported.

General: headache.

Withdrawal symptoms: once physical dependence has developed, abrupt termination of treatment will

be accompanied by withdrawal symptoms. During long-term treatment, withdrawal symptoms may

develop, especially with high doses or if the daily dose is reduced rapidly or abruptly discontinued. The

symptoms include tremor, sweating, agitation, sleep disturbances and anxiety which may be extreme,

headaches, muscle pain, tension, restlessness, confusion, irritability and epileptic seizures which may

be associated with the underlying disease. In severe cases the following symptoms may occur:

derealisation, depersonalisation, hyperacusis, numbness and tingling of the extremities,

hypersensitivity to light, noise and physical contact or hallucinations. Since the risk of withdrawal

symptoms is greater after abrupt discontinuation of treatment, abrupt withdrawal of the drug should

therefore be avoided and treatment - even if only of short duration - should be terminated by gradually

reducing the daily dose.

Special Warnings and Special Precautions for Use.

In infants and small children, and particularly those with a degree of mental impairment, clonazepam

may give rise to salivary or bronchial hyper secretion with drooling. Supervision of the airway may be

required.

With certain forms of epilepsy, an increase in the frequency of seizures during long-term treatment is

possible. Clonazepam generally has a beneficial effect on behaviour disturbances in epileptic patients.

In certain cases, paradoxical effects such as aggressiveness, excitability, nervousness, hostility, anxiety,

sleep disturbances, nightmares, vivid dreams, irritability, agitation, psychotic disorders and activation

of new types of seizures may be precipitated. If these occur, the benefit of continuing the drug should

be weighed against the adverse effect. The addition to the regimen of another suitable drug may be

necessary or, in some cases, it may be advisable to discontinue clonazepam therapy.

Although clonazepam has been given uneventfully to patients with porphyria, there are rare reports of

induced convulsions in these patients.

An increased risk of falls and fractures has been recorded in elderly benzodiazepine users.

4.9

Overdose

As with other benzodiazepine drugs, overdosage should not present undue problems of management or

threat to life. Patients have recovered from overdoses in excess of 60mg without special treatment.

Severe somnolence with muscle hypotonia will be present.

Symptoms:

The symptoms of overdosage or intoxication vary greatly from person to person depending on age,

bodyweight and individual response. Benzodiazepines commonly cause drowsiness, ataxia, dysarthria

and nystagmus. Overdose of clonazepam is seldom life-threatening if the drug is taken alone, but may

PAR Clonazepam 0.5mg and 2mg tablets

PL 20620/0045-6; UK/H/1890/01-02/DC

10

lead to coma, areflexia, apnoea, hypotension and cardiorespiratory depression. Coma usually lasts only

a few hours but in elderly people it may be more protracted and cyclical. Benzodiazepine respiratory

depressant effects are more serious in patients with severe chronic obstructive airways disease.

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

Management:

Maintain a clear airway and adequate ventilation if indicated.

The benefit of gastric decontamination is uncertain. Consider activated charcoal (50g for an adult,

10-15g for a child) in adults or children, who have taken more than 0.4mg/kg within 1 hour,

provided they are not too drowsy.

Gastric lavage is unnecessary if these drugs have been taken alone.

Patients who are asymptomatic at 4 hours are unlikely to develop symptoms.

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.

Flumazenil (Anexate), a benzodiazepine antagonist is available but should rarely be required. It

has a short half-life (about an hour). Flumazenil is

NOT TO BE USED IN MIXED OVERDOSE

OR AS A “DIAGNOSTIC TEST”

(see separate prescribing information).

Warning

The use of flumazenil is not recommended in epileptic patients who have been receiving

benzodiazepine treatment for a prolonged period. Although flumazenil exerts a slight intrinsic

anticonvulsant effect, its abrupt suppression of the protective effect of a benzodiazepine agonist can

give rise to convulsions in epileptic patients.

If excitation occurs, barbiturates should not be used.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmcotherapeutic group: benzodiazepine derivative

ATC Code: N03AE01

Clonazepam exhibits pharmacological properties which are common to benzodiazepines and include

anticonvulsive, sedative, muscle relaxing and anxiolytic effects. Animal data and

electroencephalographic investigations in man have shown that clonazepam rapidly suppresses many

types of paroxysmal activity including the spike and wave discharge in absence seizures (petit mal),

slow spike wave, generalised spike wave, spikes with temporal or other locations as well as irregular

spikes and waves.

Generalised EEG abnormalities are more readily suppressed by clonazepam than are focal EEG

abnormalities such as focal spikes. Clonazepam has beneficial effects in generalised and focal

epilepsies.

5.2

Pharmacokinetic properties

Absorption

Clonazepam is quickly and completely absorbed after oral administration of clonazepam. Peak plasma

concentrations are reached in most cases within 1 - 4 hours after an oral dose. Bioavailability is 90%

after oral administration.

Routine monitoring of plasma concentrations of clonazepam is of unproven value since this does not

appear to correlate well with either therapeutic response or side-effects.

Distribution

The mean volume of distribution of clonazepam is estimated at about 3 l/kg. Clonazepam must be

assumed to cross the placental barrier and has been detected in maternal milk.

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