Clonazepam Tablets USP 0.5mg Taj Pharma

1.NAME OF THE MEDICINAL PRODUCT
a) Clonazepam Tablets USP 0.5mg Taj Pharma
b) Clonazepam Tablets USP 1mg Taj Pharma
c) Clonazepam Tablets USP 2mg Taj Pharma

2. QUALITATIVE AND QUANTITATIVE COMPOSITION
a) Each tablet contains
Clonazepam USP 0.5mg
Excipients q.s.

b) Each tablet contains
Clonazepam USP 1mg
Excipients q.s.

c) Each tablet contains
Clonazepam USP 2mg
Excipients q.s.

For a full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM
Tablet
Round white tablets with cross-score break line

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
Method of administration: Oral use.

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 crossscored 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.

4.3 Contraindications
Known sensitivity to benzodiazepines, such as clonazepam, or to any of the drug’s excipients.
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 ideation and behaviour have been reported in patients treated with antiepileptic 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.

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 on the respiratory system may be aggravated by 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).

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

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 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, the risk of anterograde amnesia, which may 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 by 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 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. 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
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.

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.

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, betablockers, 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.

4.6 Fertility, Pregnancy and lactation
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.

Lactation
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 and
– 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 longterm 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 longterm 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.

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.
3. Further absorption should be prevented using an appropriate method e.g. treatment within 1-2 hours with activated charcoal. If activated charcoal is used airway protection is imperative for drowsy patients.
4. Gastric lavage is unnecessary if these drugs have been taken alone .In case of mixed ingestion gastric lavage may be considered, however not as a routine measure.
5. Patients who are asymptomatic at 4 hours are unlikely to develop symptoms.
6. 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.
7. Flumazenil (Anexate), a benzodiazepine antagoinist is available but should rarely be required. It has a short half-life (about an hour). If CNS depression is severe consider the use of flumazenil. This should only be administered under closely monitored conditionstherefore patients administered flumazenil will require monitoring after its effects have worn off. Flumazenil is to be used with extreme caution in the presence of drugs that reduce seizure threshold (e.g. tricyclic antidepressants). Refer to the prescribing information for flumazenil, for further information on the correct use of this drug.Flumazenil is NOT TO BE USE 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
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. 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 sideeffects.

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.

Metabolism The biotransformation of clonazepam involves oxidative hydroxylation and reduction of the 7-nitro group by the liver with formation of 7-amino or 7-acetylamino compounds, with trace amounts of 3-hydroxy derivatives of all three compounds, and their glucuronide and sulfate conjugates. The nitro compounds are pharmacologically active, whereas the amino compounds are not.

Within 4 – 10 days 50 – 70% of the total radioactivity of a radiolabelled oral dose of clonazepam is excreted in the urine and 10 – 30% in the faeces, almost exclusively in the form of free or conjugated metabolites. Less than 0.5% appears as unchanged clonazepam in the urine.

Elimination
The elimination half-life is between 20 and 60 hours (mean 30 hours).

Pharmacokinetics in special clinical situations
Based on kinetic criteria no dose adjustment is required in patients with renal failure.

5.3 Preclinical safety data
In preclinical murine studies there was at least a two fold increase in teratogenic birth defects at dose levels of 3, 9 and 18 times the human therapeutic dose compared to the controls.

6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Lactose monohydrate
Magnesium stearate
Cellulose microcrystalline
Sodium starch glycolate

6.2 Incompatibilities
Not applicable.

6.3 Shelf life
3 years.

6.4 Special precautions for storage
Store in the original package in order to protect from moisture

6.5 Nature and contents of container
PVC/PVDC/aluminium blister pack. Pack size: 100 tablets

6.6 Special precautions for disposal and other handling
None.

7. Manufactured In India By:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

Package leaflet: Information for the patient

a) Clonazepam Tablets USP 0.5mg Taj Pharma
b) Clonazepam Tablets USP 1mg Taj Pharma
c) Clonazepam Tablets USP 2mg Taj Pharma

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 any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.

What is in this leaflet
1. What Clonazepam is and what it is used for
2. Before you are given Clonazepam
3. How you will be given Clonazepam
4. Possible side effects
5. How Clonazepam is stored
6. Further Information

1. What Clonazepam is and what it is used for
Clonazepam tablets contains a medicine called clonazepam. This belongs to a group of medicines called ‘benzodiazepines’.

Clonazepam is used to treat epilepsy in infants, children and adults.
– It lowers the number of fits (seizures) that you have.
– Any fits that you do have will be less serious.

2. Before you are given Clonazepam
Do not take Clonazepam if you are allergic (hypersensitive) to:
– Clonazepam or any of the other ingredients of Clonazepam (listed in Section 6: Further information).
– Other ‘benzodiazepine’ medicines.
These include diazepam, flurazepam and temazepam.

Do not take Clonazepam if any of the above apply to you. If you are not sure, talk to your doctor or pharmacist before taking Clonazepam.

Do not take Clonazepam if:
– You have breathing problems or lung disease.
– You have severe liver problems.
– You have a condition called ‘myasthenia gravis’ (where your muscles become weak and get tired easily).
– You have a condition called ‘sleep apnoea syndrome’ (where your breathing stops when you are asleep).
– You have problems with alcohol or drug (prescription or recreational) use.

Do not take Clonazepam if any of the above apply to you. If you are not sure, talk to your doctor or pharmacist before taking Clonazepam.

Take special care with Clonazepam
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, immediately contact your doctor.

Check with your doctor or pharmacist before taking Clonazepam if:
– You have liver, kidney or lung problems.
– You have ever had depression.
– You have ever tried to kill yourself.
– A close friend or relative has recently died.
– You regularly drink alcohol or take recreational drugs or you have had problems with alcohol or drug use in the past.
– You have spinal or cerebellar ataxia (where you may become shaky and unsteady, have slurred speech or rapid eye movements).
– You have a rare, inherited blood problem called ‘porphyria’.
– You are elderly or debilitated (weak): your doctor may adjust your dose.
If any of the above apply to you, or if you are not sure, talk to your doctor or pharmacist before you take Clonazepam.

Taking other medicines
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines. This includes medicines that you buy without a prescription and herbal medicines. This is because Clonazepam can affect the way some other medicines work. Also some other medicines can affect the way Clonazepam works.

In particular, tell your doctor or 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 (used to treat stomach problems and heartburn).
– Rifampicin (an antibiotic used to treat infections).
– Medicines used to make you sleep (hypnotics).
– Medicines that help with anxiety (tranquillisers).
– Pain-killers (analgesics) and medicines to relax your muscles (muscle relaxants).

Operations
If you are going to have an anaesthetic for an operation or for dental treatment, it is important to tell your doctor or dentist that you are taking Clonazepam.

Taking Clonazepam with Alcohol
Do not drink alcohol while you are taking Clonazepam. This is because it may cause side effects or cause your fits to return.

Pregnancy and breast-feeding
You must not take Clonazepam if you are pregnant, might become pregnant or are breast-feeding, unless your doctor tells you to. Clonazepam is known to have harmful effects on the unborn child.

Driving and using machines
Talk to your doctor about driving and using machines or tools, whilst you are taking Clonazepam. This is because it can slow down your reactions, particularly when you start taking it. If you are in any doubt about whether you can do a particular activity, talk to your doctor.

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.

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:
– The medicine has been prescribed to treat a medical or dental problem and
– You have taken it according to the instructions given by the prescriber or in the information provided with the medicine and
– 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.

Important information about some of the ingredients of Clonazepam
This medicine contains lactose, which is a type of sugar. If you have been told by your doctor that you cannot tolerate or digest some sugars (have an intolerance to some sugars), talk to your doctor before taking this medicine.

3. How you will be given Clonazepam
Always take Clonazepam exactly as your doctor has told you. You should check with your doctor if you are not sure.
– Your doctor will start you on a low dose of Clonazepam and gradually increase it over 2 to 4 weeks until the right dose has been found for you.
– Your doctor will usually tell you to split your daily dose into three equal amounts which you will take at evenly spaced times throughout the day.
– If the daily dose cannot be split equally, take the largest dose at bedtime.
– Once your doctor has found the right dose for you, they may tell you to take Clonazepam as a single dose in the evening.

Adults and children over 12 years
– The usual starting dose is 1 mg a day, or less.
– This will be increased gradually (usually to between 4 mg and 8 mg a day). The maximum dose is 20 mg a day.

The elderly
– The usual starting dose is 0.5 mg a day, or less.
– This will be increased gradually (usually to between 4 mg and 8 mg a day). The maximum dose is 20 mg a day.

Infants (aged 0 to 1 year)
– The usual starting dose is 0.25 mg a day, or less.
– This will be increased gradually (usually to between 0.5 mg and 1 mg a day).

Small children (aged 1 to 5 years)
– The usual starting dose is 0.25 mg a day, or less.
– This will be increased gradually (usually to between 1 mg and 3 mg a day).

Older children (aged 5 to 12 years)
– The usual starting dose is 0.5 mg a day, or less.
– This will be increased gradually (usually to between 3 mg and 6 mg a day).

If you take more Clonazepam than you should
– If you take more Clonazepam than you should, talk to a doctor or go to a hospital straight away.
Take the medicine pack with you.
– If you take too many tablets, you may feel drowsy, sleepy, light-headed, have a lack of co-ordination or be less responsive than normal.

If you forget to take Clonazepam
– If you forget to take a dose, skip the missed dose. Then take the next dose when it is due.
– Do not take a double dose (two doses at the same time) to make up for a forgotten dose.

Stopping Clonazepam
If you receive long term treatment with Clonazepam (are given the medicine for a long time) you may become dependent upon this medicine and get withdrawal symptoms (see Section 4).
– Do not stop taking your tablets without talking to your doctor. If you do, your fits may return and you may get withdrawal symptoms (see Section 4: Possible side effects).
– If the dose of Clonazepam you take has to be reduced, or stopped, this must be done gradually. Your doctor will let you know how to do this.

If someone else takes your Clonazepam tablets by mistake, they should talk to a doctor or go to a hospital straight away.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible Side Effects
Like all medicines Clonazepam can cause side effects, although not everybody will get them.

Important side effects to look out for: Allergic reactions
If you get an allergic reaction, see a doctor straight away.
The signs may include:
– Sudden swelling of the throat, face, lips and mouth. This may make it difficult to breathe or swallow.
– Sudden swelling of the hands, feet and ankles.
– Skin rash or itching.

Effects on the heart
If you notice any of the following effects, see a doctor straight away.
The signs may include:
– 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.

Effects on behaviour
If you notice any of the following effects, talk to your doctor as they may want you to stop taking Clonazepam. The signs may include:
– Being aggressive, excited, irritable, nervous, agitated, hostile or anxious.
– Problems sleeping, nightmares and vivid dreams.
– Mental problems such as seeing or hearing things that are not really there (hallucinations), delusions (believing in things that are not real) and problems with your speech.
– Types of fits (seizures) that you have not had before.

Infants and children
– If an infant or small child is taking Clonazepam, watch them carefully. This is because they could develop breathing problems, coughing or choking. This can be caused by too much saliva being made.
– Early puberty in children. This is reversible after stopping treatment with Clonazepam.

Other possible side effects
When you start taking Clonazepam you may notice the following effects:
– Feeling drowsy and tired.
– Feeling dizzy and light-headed.
– Weak or floppy muscles or jerky movements (poor co-ordination).
– Feeling unsteady when walking.
If you notice any of these effects, talk to your doctor. Your doctor may be able to help you by giving you a lower dose of Clonazepam and then increasing it slowly.

The following may occur at any time during your treatment

Mind and nervous system
– Poor concentration, confusion and a feeling of being lost (disorientation).
– Feeling restless.
– Difficulty remembering new things.
– Headache.
– Depression.
– Slowing or slurring of speech.
– Poor co-ordination, including feeling unsteady when walking.
– An increase in how often you have fits.

Liver, kidney and blood
– Changes in how well your liver is working (shown by blood tests).
– Loss of bladder control.
– Blood problems. The signs include feeling tired, bruising easily, being short of breath and nose bleeds. Your doctor may want you to have blood tests from time to time.

Stomach and gut
– Feeling sick (nausea).
– Stomach upset. Eyes
– Double vision.
– Jerky movements of the eyes (nystagmus).

Breathing
– Breathing problems (respiratory depression). Early signs include suddenly noisy, difficult and uneven breathing. Your skin may become blue.

Skin and hair
– Skin rashes, hives (lumpy rash) and itchy skin.
– Changes to the colour of your skin.
– Hair loss (the hair usually grows back).

Sexual
– Loss of sex drive.
– Difficulty getting or keeping an erection (erectile dysfunction).

Withdrawal symptoms
Using benzodiazepines like Clonazepam may make you dependent on the medicine.
This means that if you stop treatment quickly, or reduce the dose too quickly, you may get withdrawal symptoms.
The symptoms can include:
– Problems sleeping.
– Muscle pain, shaking (tremor) and feeling restless.
– Feeling very anxious, tense, confused, irritable or agitated, or changes in your mood.
– Increased sweating.
– Headache.

Less common withdrawal symptoms include:
– Feeling sensitive to light, noise and physical contact.
– Seeing or hearing things that are not really there (hallucinations).
– Tingling and feeling numb in your arms and legs.
– A feeling of losing contact with reality.

Injury
– Patients taking benzodiazepine medicines are at risk of falling and breaking bones. This risk is increased in the elderly and those taking other sedatives (including alcohol).

If any of the side effects become serious or troublesome, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Reporting of side effects
If you get any side effects talk to your doctor, nurse or pharmacist. This includes any side effects not listed in this leaflet. By reporting side effects you can help provide more information on the safety of this medicine.

5. How Clonazepam is stored
– Keep out of the sight and reach of children.
– Do not use Clonazepam after the expiry date printed on the pack.
– Do not throw away any left over tablets. Instead, return them to your pharmacist so that they can be disposed of carefully. Only keep them if your doctor tells you to.
– If your tablets become discoloured or shown any other signs of deterioration, please contact your doctor or pharmacist.

6. Further information

What Clonazepam contains
The active ingredient in the tablet is Clonazepam.
a) Each tablet contains: Clonazepam USP 0.5mg
b) Each tablet contains: Clonazepam USP 1mg
c) Each tablet contains: Clonazepam USP 2mg
The 0.5mg tablets also contain the inactive ingredients lactose monohydrate, maize starch, potato starch pregelatinised, talc, magnesium stearate, yellow iron oxide (E172) and red iron oxide (172).

The 2mg tablets also contain the inactive ingredients lactose anhydrous, maize starch pregelatinised, microcrystalline cellulose, magnesium stearate.

What Clonazepam looks like and contents of the pack
Clonazepam tablets are available as round pinkish-buff tablets.
The tablets are supplied in blister strip packs of 60 and 105 tablets.
Not all packs size are available.