Clobazam Tablets USP 20mg Taj Pharma

1.Name of the medicinal product
a) Clobazam Tablets USP 10mg Taj Pharma
b) Clobazam Tablets USP 20mg Taj Pharma

2. Qualitative and quantitative composition
a) Each tablet contains:
Clobazam USP 10mg,
Excipients q.s.

b) Each tablet contains:
Clobazam USP 20mg,
Excipients q.s.

3. Pharmaceutical form
Tablet
White to off-white, circular tablet, one-side scored

4. Clinical particulars

4.1 Therapeutic indications
Clobazam is a 1,5-benzodiazepine indicated for the short-term relief (2-4 weeks) only of anxiety that is severe, disabling or subjecting the individual to unacceptable distress, occurring alone or in association with insomnia or short term psychosomatic, organic or psychotic illness. The use of clobazam to treat short-term “mild” anxiety is inappropriate and unsuitable.

Before treatment of anxiety states associated with emotional instability, it must first be determined whether the patient suffers from a depressive disorder requiring adjunctive or different treatment. Indeed, in patients with anxiety associated with depression, clobazam must be used only in conjunction with adequate concomitant treatment. Use of benzodiazepine (such as clobazam) alone, can precipitate suicide in such patients.

In patients with schizophrenic or other psychotic illnesses, use of benzodiazepines is recommended only for adjunctive, i.e. not for primary treatment.

Clobazam may be used as adjunctive therapy in epilepsy.

4.2 Posology and method of administration
Treatment of anxiety
The usual anxiolytic dose for adults is 20-30mg daily in divided doses or as a single dose given at night. Doses up to 60mg daily have been used in the treatment of adult in-patients with severe anxiety.

The lowest dose that can control symptoms should be used. After improvement of the symptoms, the dose may be reduced.

It should not be used for longer than 4 weeks. Long term chronic use as an anxiolytic is not recommended. In certain cases, extension beyond the maximum treatment period may be necessary; treatment must not be extended without re-evaluation of the patient’s status using special expertise. It is strongly recommended that prolonged periods of uninterrupted treatment be avoided, since they may lead to dependence. Treatment should always be withdrawn gradually. Patients who have taken Clobazam for a long time may require a longer period during which doses are reduced.

Anxiolytic treatment should be limited to the lowest possible dose for the shortest possible time (see CSM advice). Dependence is particularly likely in patients with a history of alcohol or drug abuse and in patients with marked personality disorders.

CSM advice:

Benzodiazepines are indicated for the short-term relief (two to four weeks only) of anxiety that is severe, disabling or subjecting the individual to unacceptable distress, occurring alone or in association with insomnia or short-term psychosomatic, organic or psychotic illness.
Benzodiazepines should be used to treat insomnia only when it is severe, disabling, or subjecting the individual to extreme distress.

Withdrawal of a benzodiazepine should be gradual because abrupt withdrawal may produce confusion, toxic psychosis, convulsions, or a condition resembling delirium tremens. The benzodiazepine withdrawal syndrome may develop at any time up to 3 weeks after stopping a long-acting benzodiazepine, but may occur within a few hours in the case of a short-acting one. It is characterised by insomnia, anxiety, loss of appetite and of body-weight, tremor, perspiration, tinnitus, and perceptual disturbances. These symptoms may be similar to the original complaint and encourage further prescribing; some symptoms may continue for weeks or months after stopping benzodiazepines.

A benzodiazepine can be withdrawn in steps of about one-eighth (range one-tenth to one-quarter) of the daily dose every fortnight. A suggested withdrawal protocol for patients who have difficulty is as follows:

Transfer patient to equivalent daily dose of diazepam preferably taken at night
Reduce diazepam dose in fortnightly steps of 2 or 2.5mg; if withdrawal symptoms occur, maintain this dose until symptoms improve
Reduce dose further, if necessary in smaller fortnightly steps; it is better to reduce too slowly rather than too quickly
Stop completely; time needed for withdrawal can vary from about 4 weeks to a year or more

Counselling may help; beta-blockers should only be tried if other measures fail; antidepressants should be used only for clinical depression or for panic disorder; avoid antipsychotics (which may aggravate withdrawal symptoms).

Elderly: Doses of 10-20mg daily in anxiety may be used in the elderly, who are more sensitive to the effects of psychoactive agents. Treatment requires low initial doses and gradual dose increments under careful observation.

Treatment of epilepsy in association with one or more other anticonvulsants

By mouth

Adults: In epilepsy a starting dose of 20-30mg daily is recommended, increasing as necessary up to a maximum of 60mg daily.

Adjunctive therapy for epilepsy

Monotherapy under specialist supervision for catamenial (menstruation) seizures (usually for 7–10 days just before and during menstruation)

Cluster seizures

Paediatric patients aged 6 years and above:

When prescribed for children treatment requires low initial doses and gradual dose increments under careful observation. It is recommended that normally treatment should be started at 5mg daily. A maintenance dose of 0.3 to 1mg/kg body weight daily is usually sufficient.

As there is no age appropriate formulation to enable safe and accurate dosing, no dosage recommendations can be made in children under 6 years of age.

Tablets should be swallowed without chewing with sufficient amount of liquid (1/2 glass)

The patient must be re-assessed after a period not exceeding 4 weeks and regularly thereafter in order to evaluate the need for continued treatment. A break in therapy may be beneficial if drug exhaustion develops, recommencing therapy at a low dose. At the end of treatment (including in poor-responding patients), since the risk of withdrawal phenomena/rebound phenomena is greater after abrupt discontinuation of treatment, it is recommended to gradually decrease the dosage.

4.3 Contraindications
Clobazam 10mg Tablets must not be used:

– in patients with hypersensitivity to benzodiazepines or any of the excipients of Clobazam 10 mg Tablets – see section 6.1

– In patients with any history of drug or alcohol dependence (increased risk of development of dependence).

– In patients with myasthenia gravis (risk of aggravation of muscle weakness).

– In patients with severe respiratory insufficiency (risk of deterioration).

– In patients with sleep apnoea syndrome (risk of deterioration).

– In patients with severe hepatic insufficiencies (risk of precipitating encephalopathy).

– During the first trimester of pregnancy (for use during second and third trimester, see section 4.6 Pregnancy and Lactation).

– In breast-feeding women.

Benzodiazepines must not be given to children without careful assessment of the need for their use. Clobazam must not be used in children between the ages of 6 months and 3 years, other than in exceptional cases for anticonvulsant treatment where there is a compelling indication. As there is no age appropriate formulation to enable safe and accurate dosing, no dosage recommendations can be made in children under 6 years of age (see section 4.2).

4.4 Special warnings and precautions for use

Amnesia
Amnesia may occur with benzodiazepines. In case of loss or bereavement psychological adjustment may be inhibited by benzodiazepines.

Special caution is necessary if clobazam is used in patients with myasthenia gravis, spinal or cerebellar ataxia or sleep apnoea. A dose reduction may be necessary.

Muscle weakness
Clobazam can cause muscle weakness. Therefore, in patients with pre-existing muscle weakness or spinal or cerebellar ataxia or sleep apnoea, special observation is required and a dose reduction may be necessary. Clobazam is contraindicated in patients with myasthenia gravis.
Depression and personality disorders
Disinhibiting effects may be manifested in various ways. Suicide may be precipitated in patients who are depressed and aggressive behaviour towards self and others may be precipitated. Extreme caution should therefore be used in prescribing benzodiazepines in patients with personality disorders.
Dependence
Use of benzodiazepines – including clobazam – may lead to the development of physical and psychic dependence upon these products. The risk of dependence increases with dose and duration of treatment; it is also greater in patients with a history of alcohol or drug abuse. Therefore the duration of treatment should be as short as possible (see Posology).

Once physical dependence has developed, abrupt termination of treatment will be accompanied by withdrawal symptoms (or rebound phenomena). Rebound phenomena are characterised by a recurrence in enhanced form of the symptoms which originally led to clobazam treatment. This may be accompanied by other reactions including mood changes, anxiety or sleep disturbances and restlessness.

A withdrawal syndrome may also occur when abruptly changing over from a benzodiazepine with a long duration of action (for example, Clobazam) to one with a short duration of action.

Serious Skin Reaction
Serious skin reactions, including Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported with clobazam in both children and adults during the postmarketing experience. A majority of the reported cases involved the concomitant use of other drugs, including antiepileptic drugs that are associated with serious skin reactions. SJS/TEN could be associated with a fatal outcome. Patients should be closely monitored for signs or symptoms of SJS/TEN, especially during the first 8 weeks of treatment. Clobazam should be immediately discontinued when SJS/TEN is suspected. If signs or symptoms suggest SJS/TEN, use of this drug should not be resumed and alternative therapy should be considered (see section 4.8).
Respiratory Depression
Respiratory function should be monitored in patients with chronic or acute severe respiratory insufficiency and a dose reduction of clobazam may be necessary. Clobazam is contraindicated in patients with severe respiratory insufficiency (please refer to section 4.3 Contraindications).
Renal and hepatic impairment
In patients with impairment of renal or hepatic function, responsiveness to clobazam and susceptibility to adverse effects are increased, and a dose reduction may be necessary. In long-term treatment renal and hepatic function must be checked regularly.
Elderly patients
In the elderly, due to the increased sensitivity to adverse reactions such as drowsiness, dizziness, muscle weakness, there is an increased risk of fall that may result in serious injury. A dose reduction is recommended.
Tolerance in epilepsy
In the treatment of epilepsy with benzodiazepines – including clobazam – consideration must be given to the possibility of a decrease in anticonvulsant efficacy (development of tolerance) in the course of treatment.
CYP2C19 poor metabolisers
In patients who are CYP2C19 poor metabolisers, levels of the active metabolite N-desmethylclobazam are expected to be increased as compared to extensive metabolisers. As this may lead to increased side effects, dosage adjustment of clobazam may be necessary (e.g. low starting dose with careful dose titration (please refer to section 5.2)).
Alcohol
It is recommended that patients abstain from drinking alcohol during treatment with clobazam (increased risk of sedation and other adverse effects) (please refer to section 4.5).
Risk from concomitant use of opioids:
Concomitant use of Clobazam 10mg Tablets 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 such as Clobazam 10mg Tablets with opioids should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe Clobazam 10mg Tablets concomitantly with opioids, the lowest effective dose should be used, and the duration of treatment should be as short as possible (see also general dose recommendation in section 4.2).

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 4.5).

Clobazam 10mg Tablets contain lactose; 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
• Central nervous system depressant drugs
Especially when clobazam is administered at higher doses, an enhancement of the central depressive effect may occur in cases of concomitant use with antipsychotics (neuroleptics), hypnotics, anxiolytics/sedatives, antidepressant agents, narcotic analgesics, anticonvulsant drugs, anaesthetics and sedative antihistamines. Special caution is also necessary when clobazam is administered in cases of intoxication with such substances or with lithium.

Alcohol
Concomitant consumption of alcohol can increase the bioavailability of clobazam by 50% and therefore increase the effects of clobazam (e.g.; sedation). This affects the ability to drive or use machines.
Anticonvulsants
Addition of clobazam to established anticonvulsant medication (e.g., phenytoin, valproic acid) may cause a change in plasma levels of these drugs. If used as an adjuvant in epilepsy the dosage of Clobazam should be determined by monitoring the EEG and the plasma levels of the other drugs checked.

Phenytoin and carbamazepine may cause an increase in the metabolic conversion of clobazam to the active metabolite N-desmethyl clobazam. Stiripentol increases plasma levels of clobazam and its active metabolite N-desmethylclobazam, through inhibition of CYP3A and CYP2C19. Monitoring of blood levels is recommended, prior to initiation of stiripentol, and then once new steady-state concentration has been reached, i.e. after 2 weeks approximately.

Narcotic analgesics
If clobazam is used concomitantly with narcotic analgesics, possible euphoria may be enhanced; this may lead to increased psychological dependence.
Muscle relaxants
The effects of muscle relaxants, analgesics and nitrous oxide may be enhanced.
CYP 2C19 inhibitors
Strong and moderate inhibitors of CYP2C19 may result in increased exposure to N-desmethylclobazam (N-CLB), the active metabolite of clobazam. Dosage adjustment of clobazam may be necessary when co-administered with strong (e.g. fluconazole, fluvoxamine, ticlopidine) or moderate (e.g. omeprazole) CYP2C19 inhibitors (please refer to Section 5.2).
CYP 2D6 substrates
Clobazam is a weak CYP2D6 inhibitor. Dose adjustment of drugs metabolized by CYP2D6 (e.g. dextromethorphan, pimozide, paroxetine, nebivolol may be necessary.

Concurrent treatment with drugs that inhibit the cytochrome P-450 enzyme (mono-oxygenase) system (e.g. cimetidine) may enhance and prolong the effect of clobazam.

Opioids
The concomitant use of sedative medicines such as benzodiazepines or related drugs such as Clobazam 10mg Tablets 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 4.4).

4.6 Fertility, pregnancy and lactation
There are limited amount of data from the use of Clobazam in pregnant women.

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. In animal studies, no congenital malformations have been found in mice, rats and rabbits.

In the postmarketing safety database, limited data on exposed pregnancies are available with clobazam. Some of those cases reported fetal or neonatal disorders.

If the product is prescribed to a woman of childbearing potential, she should be warned to contact her physician regarding discontinuation of the product if she intends to become pregnant or suspects that she is pregnant.

If, for compelling medical reasons, the product is administered during the late phase of pregnancy, or during labour at high doses, effects on the neonate such as hypothermia, hypotonia, moderate respiratory depression and difficulties in drinking (signs and symptoms of so-called “floppy infant syndrome”), can be expected due to the pharmacological action of the compound.

Moreover, infants born to mothers who took benzodiazepines during the latter stage of pregnancy may have developed physical dependence and may be at some risk for developing withdrawal symptoms in the postnatal period. Appropriate monitoring of the newborn in the postnatal period is recommended.

As a precautionary measure it is preferable to avoid the use of clobazam during pregnancy. Clobazam should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Since benzodiazepines are found in the breast milk, benzodiazepines should not be given to breast feeding mothers.

4.7 Effects on ability to drive and use machines
Sedation, amnesia, impaired concentration and impaired muscular function may adversely affect the ability to drive or to use machines. If insufficient sleep duration occurs, the likelihood of impaired alertness may be increased (see also Interactions).

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:

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 and in the information provided with the medicine and

o It was not affecting your ability to drive safely

4.8 Undesirable effects
Nervous system disorders

Clobazam may cause sedation, leading to fatigue and sleepiness, especially at the beginning of treatment and when higher doses are used. Side-effects such as slowing of reaction time, muscle weakness, ataxia, confusion, drowsiness, dizziness, numbed emotions and headaches, or a fine tremor of the fingers have been reported. These are more likely to occur at the beginning of treatment and often disappear with continued treatment or a reduction in dose.

Disorders of articulation, unsteadiness of gait and other motor functions, or loss of libido may occur, particularly with high doses or in long-term treatment. These reactions are reversible.

After prolonged use of benzodiazepines, impairment of consciousness, sometimes combined with respiratory disorders, has been reported in very rare cases, particularly in elderly patients: it sometimes persists for some length of time. These disorders have not been seen so far under clobazam treatment.

Anterograde amnesia may occur, especially at higher dose levels. Amnesia effects may be associated with inappropriate behaviour.

Psychiatric disorders

Paradoxical reactions, such as restlessness, irritability, difficulty in falling asleep or sleeping through, acute agitational states, , anxiety, aggressiveness , delusion, fits of rage, nightmare, hallucinations, psychotic reactions suicidal tendencies or frequent muscle spasms may occur, especially in elderly and in children. In the event of such reactions, treatment with clobazam must be discontinued.

Pre-existing depression may be unmasked during benzodiazepine use.

Tolerance and physical and/or psychic dependence may develop, especially during prolonged use. Discontinuation of the therapy may result in withdrawal or rebound phenomena (see Warnings and Precautions). Abuse of benzodiazepines has been reported.

When used as an adjuvant in the treatment of epilepsy, this preparation may in rare cases cause restlessness and muscle weakness.

As with other benzodiazepines, the therapeutic benefit must be balanced against the risk of habituation and dependence during prolonged use.

Eye disorders

Visual disorders (e.g., double vision, nystagmus). Such reactions occur particularly with high doses or in long-term treatment, and are reversible.

Respiratory, thoracic and mediastinal disorders

Clobazam may cause respiratory depression, especially if administered in high doses. Therefore, particularly in patients with pre-existing compromised respiratory function (i.e., in patients with bronchial asthma) or brain damage, respiratory insufficiency may occur or deteriorate.

Gastrointestinal disorders

Dryness of the mouth, constipation, loss of appetite, nausea

Skin and subcutaneous tissue disorders

Cutaneous reactions, such as rash or urticaria may develop in very rare cases. Stevens-Johnson syndrome, Toxic Epidermal Necrolysis

Metabolism and nutrition disorders

Weight gain, may occur particularly with high doses or in long-term treatment. This reaction is reversible.

General disorders

Fall

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
Overdose of benzodiazepines is usually manifested by degrees of central nervous system depression ranging from drowsiness to coma. In mild cases, symptoms include drowsiness, mental confusion and lethargy, in more serious cases, symptoms may include ataxia, hypotonia, hypotension, respiratory depression, rarely coma and very rarely death. As with other benzodiazepines, overdose should not present a threat to life unless combined with other CNS depressants (including alcohol).

In the management of overdose, it is recommended that the possible involvement of multiple agents be taken into consideration.

Following overdose with oral benzodiazepines, vomiting should be induced (within one hour) if the patient is conscious, or gastric lavage undertaken with the airway protected if the patient is unconscious. If there is no advantage in emptying the stomach, activated charcoal should be given to reduce absorption. Special attention should be paid to respiratory and cardiovascular functions in intensive care.

Secondary elimination of clobazam (by forced diuresis or haemodialysis) is ineffective.

Consideration should be given to the use of flumazenil as a benzodiazepine antagonist.

5. Pharmacological properties

5.1 Pharmacodynamic properties
(Nervous System, Psycholeptics, Anxiolytics, Benzodiazepine derivatives, Clobazam)

Clobazam is a 1,5-benzodiazepine. In single doses up to 20mg or in divided doses up to 30mg, clobazam does not affect psychomotor function, skilled performance, memory or higher mental functions.

5.2 Pharmacokinetic properties

Absorption
After oral administration, clobazam is rapidly and extensively absorbed.

Time to peak plasma concentrations (Tmax) is achieved from 0.5 – 4.0 hrs.

The administration of clobazam tablets with food or crushed in applesauce slows the rate of absorption by approximately 1 hour, but it does not affect the overall extent of absorption. Clobazam can be given without regard to meals.

Concomitant intake of alcohol can increase the bioavailability of clobazam by 50%.

Distribution
After a single dose of 20 mg clobazam, marked interindividual variability in maximum plasma concentrations (222 to 709 ng/ml) was observed after 0.25 to 4 hours. Clobazam is lipophilic and distributes rapidly throughout the body. Based on a population pharmacokinetic analysis, the apparent volume of distribution at steady state was approximately 102 L, and is concentration independent over the therapeutic range. Approximately 80 – 90% of clobazam is bound to plasma protein.

Clobazam accumulates approximately 23 fold to steady state while the active metabolite Ndesmethylclobazam (NCLB) accumulates approximately 20 fold following clobazam twice daily administration. Steady state concentrations are reached within approximately 2 weeks.

Metabolism
Clobazam is rapidly and extensively metabolized in the liver. Clobazam metabolism occurs primarily by hepatic demethylation to Ndesmethylclobazam (NCLB), mediated by CYP3A4 and to a lesser extent by CYP2C19. NCLB is an active metabolite and the main circulating metabolite found in human plasma.

NCLB undergoes further biotransformation in the liver to form 4hydroxyNdesmethylclobazam, primarily mediated by CYP2C19.

CYP2C19 poor metabolizers exhibit a 5fold higher plasma concentration of NCLB compared to extensive metabolizers.

Clobazam is a weak CYP2D6 inhibitor. Coadministration with dextromethorphan led to increases of 90% in AUC and 59% in Cmax values for dextromethorphan.

Concomitant administration of 400 mg ketoconazole (CYP3A4 inhibitor) increased Clobazam AUC by 54% with no effect on Cmax. These changes are not considered clinically relevant.

Elimination
Based on a population pharmacokinetic analysis, plasma elimination half lives of clobazam and NCLB were estimated to be 36 hours and 79 hours respectively.

Clobazam is cleared mainly by hepatic metabolism with subsequent renal elimination. In a mass balance study, approximately 80% of the administered dose was recovered in urine and about 11% in the faeces. Less than 1 % of unchanged clobazam and less than 10% of unchanged N-CLB are excreted through the kidneys.

5.3 Preclinical safety data
None applicable

6. Pharmaceutical particulars

6.1 List of excipients
Lactose monohydrate
Cellulose microcrystalline
Sodium starch glycolate
Talc
Magnesium stearate.

6.2 Incompatibilities
None known

6.3 Shelf life
3 years

6.4 Special precautions for storage
The medicinal product does not require any special storage instructions.

6.5 Nature and contents of container
Carton containing 30 tablets in 3 x PVC/aluminium blister strips each of 10 tablets.

6.6 Special precautions for disposal and other handling
No special requirements.

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

Clobazam Tablets USP 20mg TajPharma

Package leaflet: Information for the patient

a) Clobazam Tablets USP 10mg Taj Pharma
b) Clobazam Tablets USP 20mg 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 Clobazam is and what it is used for
2. Before you are given Clobazam
3. How you will be given Clobazam
4. Possible side effects
5. How Clobazam is stored
6. Further Information

1. What Clobazam is and what it is used for
Clobazam contains a medicine called clobazam. This belongs to a group of medicines called benzodiazepines. It works by having a calming effect on the brain.

Clobazam can be used for:

Severe anxiety over a short time
Epilepsy (fits) over a longer time
Mental illness such as schizophrenia (in combination with other treatments)

2. Before you are given Clobazam
Do not take Clobazam if:

You are allergic (hypersensitive) to clobazam, other benzodiazepine medicines or any of the other ingredients of Clobazam (see section 6). Signs of an allergic reaction include: a rash, swallowing or breathing problems, swelling of your lips, face, throat or tongue.
You are in the first three months of pregnancy or think you might be pregnant (see below under ‘Pregnancy, breast-feeding and fertility’ for more information).
You are breast-feeding.
You have ever had problems with drugs or alcohol dependence in the past.
You suffer from an illness that causes muscle weakness (called ‘myasthenia gravis’).
You have liver problems.
You have breathing problems.
You stop breathing for short periods during sleep (called ‘sleep apnoea syndrome’).
The patient is under 6 years old.

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

Warnings and precautions
Talk to your doctor or pharmacist before taking Clobazam if:

You have problems with controlling your movements (called ‘spinal or cerebellar ataxia’).
You have depression, irrational fears and obsessions.
You have delusions (believing things which are not true) or hallucinations (sensing things which are not there).
You have kidney problems.
You have ever become dependent upon another drug or alcohol. Alcohol should not be taken during treatment with Clobazam as there is an increased risk of experiencing side effects.
You are over 65. This is due to the increased sensitivity to adverse reactions in the elderly such as drowsiness, dizziness and muscle weakness. There is also an increased risk of fall that may result in serious injury.
You have difficulty digesting medicines. Some patients liver may not metabolise (break down) medicines adequately. In these patients the medicine may remain in the body for a longer period of time. This may result in side effects.If you are known to poorly metabolise certain medicines please speak to your doctor.

Drowsiness, difficulties breathing, coma and death may occur if Clobazam is taken together with opioids. Clobazam and opioids should only be used concomitantly, when other treatment options are inadequate. Please tell your doctor about all opioid medicines you are taking and follow your doctor’s dosage recommendations closely.

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

Other medicines and Clobazam
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This includes medicines you buy without a prescription, including herbal medicines. This is because Clobazam can affect the way some other medicines work. Also some medicines can affect the way Clobazam works.

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

Medicines for epilepsy (such as phenytoin, carbamazepine, stiripentol or valproic acid).
Medicines for depression (such as Monoamine Oxidase Inhibitors (MAOIs) or tricyclic anti-depressants such as trazodone, or Selective Serotonin Re-uptake Inhibitors (SSRIs) such as fluvoxamine or paroxetine).
Medicines for severe mental illness called ‘antipsychotics’ (such as chlorpromazine, haloperidol, clozapine and pimozide).
Painkillers (such as medicines containing codeine, dihydrocodeine or morphine).
Sleeping tablets (such as zolpidem).
Tranquilisers (such as diazepam, temazepam or lorazepam).
Muscle relaxants (such as baclofen).
Antihistamines that make you sleepy (such as chlorphenamine, promethazine or diphenenhydramine).
Lithium – used for a mental illness called ‘manic-depressive illness’ (mood changes between a state of high excitability or exaggerated emotions and depression).
Cimetidine – used to treat ulcers and heartburn.
Omeprazole – used to treat the symptoms of acid reflux such as heartburn or acid regurgitation.
Ticlopidine – an antiplatelet medication used in patients with an increased risk of stroke.
Fluconazole – used in the treatment of fungal conditions.
Dextromethorphan – used to relieve dry, irritating coughs.
Nebivolol – used to treat high blood pressure.

Concomitant use of Clobazam and opioids increases the risk of drowsiness, difficulties breathing, coma and death. Follow your doctor’s dosage recommendations closely.

If you are not sure if any of the above apply to you talk to your doctor or pharmacist

Anaesthetics
If you are going to have an anaesthetic, tell your doctor or anaesthetist you are taking Clobazam. This is because your doctor may need to change the amount of anaesthetic or muscle relaxants to give you.

Clobazam with alcohol
Do not drink alcohol while taking Clobazam. This is because there is increased risk of sleepiness and other side effects.

Pregnancy, breast-feeding and fertility
Do not take Clobazam if you are:

A woman of childbearing potential and are not using contraception.
In the first three months of pregnancy.
Breast-feeding or planning to breast-feed. This is because it may pass into the mother’s milk.

Talk to your doctor before taking this medicine if you are pregnant, plan to get pregnant, or think you may be pregnant. This is because Clobazam is not recommended for use in pregnant women.

However, your doctor may give you this medicine during late pregnancy or during labour

If this happens, there is a risk of having a baby with a low body temperature, floppiness, breathing or feeding problems.
If this medicine is taken regularly in late pregnancy, your baby may get withdrawal symptoms. In this case the newborn should be closely monitored during the postnatal period.

Driving and using machines
You may feel sleepy or have concentration or memory problems after taking this medicine. You may also experience double vision or you may react more slowly to things. If this happens, do not drive or use any tools or machines.

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.

Clobazam contains lactose
If you have been told by your doctor that you cannot tolerate some sugars, talk to your doctor before taking this medicine.

3. How you will be given Clobazam
Always take Clobazam exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

Taking this medicine
Swallow the tablets whole, or crushed and mixed with apple sauce. The tablets can be divided into equal halves of 5 mg. Clobazam can be taken with or without food.

If you feel the effect of your medicine is too weak or too strong, do not change the dose yourself, but ask your doctor.
Keep taking Clobazam until your doctor tells you to stop.
Clobazam is usually given for 2-4 weeks. After that, your doctor will decide whether you should keep taking this medicine

Adults

The usual dose is 20 mg to 30 mg each day. This can be taken as two separate doses or as a single dose at night.
Your doctor may increase your dose to up to 60 mg each day.
Your doctor may lower the dose to suit you.

Children (6 years and above)

The usual dose is 5 mg each day

Elderly

The usual dose for anxiety is 10 mg to 20 mg each day.

If you take more Clobazam than you should
If you take more Clobazam than you should, tell your doctor or go to your nearest hospital casualty department straight away. Do not drive yourself, because you may start to feel sleepy. Remember to take with you any tablets that are left and the pack. This is so the doctor knows what you have taken.

If you forget to take Clobazam

If you forget a dose, take it as soon as you remember it.
However, if it is nearly time for the next dose, skip the missed dose.
Do nottake a double dose to make up for a forgotten tablet.

If you stop taking Clobazam
Keep taking this medicine until your doctor tells you to stop. Do not stop taking Clobazam just because you feel better

When your doctor says that you can stop taking Clobazam, you need to do this gradually. Your doctor will help you to do this.
Stopping the tablets can make you feel stressed (anxiety), confused or depressed. You may also lose your appetite and have difficulty sleeping. Tell your doctor if this happens.

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

4. Possible Side Effects
Like all medicines, Clobazam can cause side effects, although not everybody gets them.

You may feel ill after taking the tablets, or notice unusual or unexpected symptoms. If this happens, tell your doctor.

Tell your doctor straight away if you have any of the following side effects:

Common side effects (may affect up to 1 in 10 people:

Feeling irritable or restless.

Uncommon side effects (may affect up to 1 in 100 people):

Poor memory while taking Clobazam (amnesia) or showing unusual behaviour.
Feeling anxious.
Believing things which are not true (delusions).
Increased possibility of tripping or falling, especially in elderly patients .

Not known (frequency cannot be estimated from available data):

Sleeping problems that get worse after taking this medicine.
Sensing things which are not there (hallucinations).
Being less aware of your environment, especially in the elderly.
Feeling suicidal.
Blistering or bleeding of the skin around the lips, eyes, mouth, nose and genitals. Also flu-like symptoms and fever. Thismay be something called ‘Stevens-Johnson Syndrome’.
A severe blistering rash where layers of the skin may peel off to leave large areas of raw exposed skin over the body. Also a feeling of being generally unwell, fever, chills and aching muscles. This is something called ‘Toxic Epidermal Necrolysis’.

If you get any of the above side effects, your doctor may decide that your treatment needs to be stopped. These side-effects are more likely to happen in elderly people and children.

Tell your doctor or pharmacist if any of the following side effects get serious or lasts longer than a few days, or if you notice any side effects not listed in this leaflet.

Very common side effects (may affect more than 1 in 10 people):

Difficulty in staying awake or alert

Common side effects (may affect up to 1 in 10 people):

Feeling sleepy or dizzy.
Feeling agitated or being aggressive.
Short attention span.
Difficulty in speaking.
Shaking fingers (tremor).
Problems with walking or other movement problems.
Clobazam having less effect than normal (especially in long term use).
Dry mouth, constipation.
Loss of appetite, feeling sick (nausea).

Uncommon side effects (may affect up to 1 in 100 people):

Loss of sexual drive.
Memory difficulties, confusion.
Double vision.
Skin rash.
Weight gain.

Not known (frequency cannot be estimated from available data):

Becoming dependent on Clobazam (‘physical or mental dependence’) (especially in long term use).
A feeling of being out of touch with reality and being unable to think or judge clearly (psychosis).
Feeling angry.
Changes in the way you walk.
Breathing problems.
Sensitivity to sunlight.
Itchy, lumpy rash (urticaria).
Muscle spasms or muscle weakness.
Reacting to things more slowly than usual.
Rapid uncontrollable movement of the eyes.
Learning problems.
Abnormally low body temperature.

If you take this medicine for a long time, you are more likely to get the following side effects: anxiety, confusion, depression, loss of appetite and difficulty sleeping.

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 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 Clobazam is stored
Keep out of the sight and reach of children.
Do not use Clobazam after the expiry date which is stated on the label after EXP. The expiry date refers to the last day of that month.
If your tablets go out of date take them to your pharmacist for safe disposal.
Store below 25°C.
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. Further information

What Clobazam contains
Each tablet contains clobazam as active ingredient.
a) Each tablet contains:Clobazam USP 10mg.
b) Each tablet contains: Clobazam USP 20mg.
They also contain the following inactive ingredients: lactose, maize starch, talc, colloidal silicon dioxide and magnesium stearate.

What Clobazam looks like and contents of the pack
The tablets are white and round. Clobazam is presented in a blister pack of 30 tablets.