Frisium 10

Package leaflet: Information for the patient

Warning! Keep the leaflet! Information on the immediate packaging in a foreign language.
Frisium 10 (Frisium 10 mg)
10 mg, tablets
Clobazam
Frisium 10 and Frisium 10 mg are different trade names for the same medicine.
Please read the leaflet carefully before using the medicine, as it contains
important information for the patient.

• Keep this leaflet for future reference.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If you experience any adverse reactions, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents of the leaflet:

1. What Frisium 10 is and what it is used for
2. Important information before taking Frisium 10
3. How to take Frisium 10
4. Possible side effects
5. How to store Frisium 10
6. Contents of the pack and other information

1. What Frisium 10 is and what it is used for

Frisium 10 is an anxiolytic and anticonvulsant medicine belonging to a group of medicines called benzodiazepines.
Frisium 10 is indicated in the treatment of acute and chronic anxiety states, particularly characterized by: increased anxiety, tension, inner restlessness, agitation, irritability, emotionally-induced sleep disturbances, psychovegetative and psychosomatic disorders (e.g. affecting the cardiovascular or gastrointestinal system).
Before initiating treatment for anxiety states associated with mood disorders, the doctor will determine whether the patient suffers from depressive disorders requiring additional or different treatment.
The medicine may also be used as an adjunctive treatment in epilepsy when previous anticonvulsant therapy has not provided satisfactory results.

2. Important information before using Frisium 10

When not to use Frisium 10:

• if the patient is allergic to clobazam or any of the other ingredients of this medicine (listed in section 6),
• if the patient suffers from myasthenia gravis (a disease characterised by rapid fatigue of skeletal muscles), as there is an increased risk of worsening the condition,
• if the patient has acute respiratory disorders (risk of worsening),
• if the patient has sleep apnoea syndrome (risk of worsening),
• if the patient has severe liver function disorders (risk of inducing hepatic coma – encephalopathy),
• during breastfeeding.

Benzodiazepines must not be administered to children without careful assessment of the necessity of using these medicines.
Frisium 10 must not be used in children aged from 6 months to 6 years, except in
special cases for the treatment of seizures with absolute indications.
Warnings and precautions
Before starting treatment with Frisium 10, consult a doctor or pharmacist.
Suicide
Some studies have shown an increased risk of suicidal thoughts, suicide attempts and
suicide in patients taking certain sedative and hypnotic medicines, including this one. However,
it has not been established whether this is caused by taking this medicine or whether other causes exist. If
the patient has suicidal thoughts, they should contact their doctor as soon as possible to obtain
further medical advice (see section 4).
Risk associated with concomitant use of opioids and benzodiazepines
Concomitant use of benzodiazepines, including clobazam, and opioids may cause sedation,
respiratory depression, coma and death. Due to these risks, the doctor will prescribe opioids and benzodiazepines together only in patients for whom other treatment methods are insufficient.
If a decision is made to administer clobazam together with opioids, both medicines will be prescribed
at the lowest effective dose and for the shortest possible duration of concomitant use.
Anterograde amnesia (inability to remember events after taking the medicine)
During treatment with benzodiazepines, even at the recommended dose, and particularly at higher doses,
anterograde amnesia (difficulty in learning and remembering new information – new
data are not permanently stored) may occur.
Tolerance
When treating epilepsy with benzodiazepines, including clobazam, particular caution should be exercised due to the possibility of reduced anticonvulsant effect (development of tolerance) during treatment.
Physical and psychological dependence
Use of benzodiazepines, including Frisium 10, may lead to physical and
psychological dependence. The risk is greater when higher doses are used and treatment duration is longer, but it may occur even after daily use of therapeutic doses for several weeks.
This risk is increased in patients with a history of alcohol or drug dependence.
Withdrawal symptoms
If physical dependence develops, abrupt discontinuation of clobazam treatment may lead to
withdrawal symptoms. These include headache, sleep disturbances, increased frequency of vivid dreams, heightened anxiety, tension, restlessness, disorientation and agitation, loss of reality perception, feelings of depersonalisation, hallucinations, reactive psychoses (e.g. delirium after discontinuation), numbness and tingling of limbs, muscle pain, tremor, sweating, nausea,
vomiting, hypersensitivity to sound, light and physical contact, and seizures.
Withdrawal symptoms may also occur after abrupt switching from a long-acting benzodiazepine (e.g. Frisium 10) to a short-acting benzodiazepine.
If benzodiazepine administration is suddenly discontinued, a so-called rebound phenomenon may also occur,
i.e. recurrence of intensified symptoms that Frisium 10 was intended to suppress (e.g. anxiety states, seizures). This may be accompanied by sudden mood changes, anxiety, sleep disturbances and restlessness.
Elderly patients
In elderly patients, due to increased susceptibility to adverse effects such as:
drowsiness, dizziness, muscle weakness, there is an increased risk of falls, which may result in
serious injury. Dose reduction is recommended (see sections 3 and 4).
If the patient has experienced any of the symptoms listed below, inform the doctor before taking the medicine:

• chronic or acute respiratory insufficiency (clobazam may cause respiratory disturbances),
• muscle weakness or ataxia (unsteadiness, impaired coordination of body movements) in the past (clobazam may cause muscle weakness),
• kidney or liver function disorders (may result in increased susceptibility to adverse effects),
• personality disorders (risk of suicidal behaviour). Patients should use Frisium 10 only under strict medical supervision. The treating doctor may decide to reduce the dose in such cases to minimise the risk of adverse effects.

Severe skin diseases
During treatment with clobazam, both in children and adults, severe
skin diseases such as Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported.
Most of these cases occurred during concomitant use of other medicines, e.g. antiepileptic drugs.
These conditions may even lead to patient death. The doctor will monitor the patient for signs of severe skin diseases, especially during the first 8 weeks of treatment. If symptoms suggestive of Stevens-Johnson syndrome or
toxic epidermal necrolysis occur, the doctor will advise immediate discontinuation of
clobazam. Treatment with this medicine will not be continued, and the doctor will consider alternative treatment options.
Cannabidiol
Consult your doctor or pharmacist:

• before taking any non-medicinal products containing cannabidiol, as they may exacerbate adverse effects caused by clobazam,
• if the patient is taking any medicinal products containing cannabidiol, as they may exacerbate adverse effects caused by clobazam.

Frisium 10 and other medicines
Inform your doctor or pharmacist about all medicines currently taken or recently
used, including those available without a prescription.
Exercise caution when using clobazam concomitantly with the following medicines:

• antiepileptic drugs used in epilepsy treatment, such as: valproic acid, phenytoin, carbamazepine, stiripentol. When these medicines are used concomitantly with clobazam, the doctor will adjust the dose of Frisium 10 (interactions with the patient's basic antiepileptic drugs may occur),
• antipsychotic medicines,
• anxiolytic medicines,
• antidepressants,
• sedative antihistamines (medicines used for allergies),
• anaesthetics and muscle relaxants (risk of enhanced effect),
• hypnotic medicines,
• opioid analgesics (risk of enhanced euphoria, which may increase psychological dependence),
• other medicines with sedative effects, especially when clobazam is administered at higher doses (may lead to enhanced central nervous system depression),
• opioids, as concomitant use of clobazam and opioids increases the risk of sedation, respiratory depression, coma and death due to enhanced central nervous system depression,
• products (medicinal or non-medicinal) containing cannabidiol,
• ticlopidine – an antiplatelet drug used to prevent blood clots,
• fluconazole – used in the treatment of fungal diseases,
• fluvoxamine – used in the treatment of depression,
• omeprazole – used in the treatment of stomach diseases.

Exercise particular caution when using clobazam in patients who have experienced
poisoning with the above-mentioned medicines or with lithium.
The doctor may change (adjust) the dosage of clobazam when the following medicines are used:

• medicines that inhibit clobazam metabolism (may increase active drug concentration in the body), e.g. fluconazole, fluvoxamine, ticlopidine, omeprazole,
• medicines metabolised by the CYP2D6 enzyme, e.g. dextromethorphan, pimozide, paroxetine, nebivolol (clobazam may inhibit CYP2D6 enzyme activity).

Frisium 10 with food, drink and alcohol
This medicine can be taken before a meal or independently of meals.
During treatment with clobazam, alcohol consumption should be avoided (increased risk of excessive
sedation and other adverse effects).
Pregnancy, breastfeeding and effect on fertility
Pregnancy
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a
child, she should consult her doctor before using this medicine.
Use of Frisium 10 is not recommended during pregnancy or in women of childbearing age who are not using contraception.
If the patient discovers she is pregnant or plans to have a child, she should immediately consult her doctor to reassess the need for treatment. Do not discontinue Frisium 10 without consulting your doctor.
A large amount of data has not revealed evidence linking congenital malformations to the use of benzodiazepines. However, some studies have shown an increased risk of cleft lip and palate in newborns compared to the general population.
Cleft lip and palate (sometimes called "hare lip") is a congenital defect
caused by incomplete fusion of the palate and upper lip during fetal development.
Taking Frisium 10 during the second and/or third trimester of pregnancy may lead to
reduced fetal movements and fetal heart rate variability.
Use of Frisium 10 towards the end of pregnancy or during delivery may cause the newborn to experience
drowsiness (sedation), muscle weakness (hypotonia or "floppy infant syndrome"), low
body temperature (hypothermia), feeding difficulties (sucking problems leading to poor
weight gain) and breathing problems (respiratory depression, sometimes severe).
If Frisium 10 is taken regularly in late pregnancy, withdrawal symptoms such as agitation or tremor may occur in the newborn. In such cases, the newborn should be closely monitored during the postnatal period.
Clobazam crosses the placenta.
Breastfeeding
Frisium 10 must not be used during breastfeeding, as the active substance
(clobazam) passes into breast milk.

Driving and operating machinery
Some adverse effects (e.g. sedation, amnesia, muscle weakness) may
impair concentration ability and reaction time and may adversely affect the ability to drive
vehicles and operate machinery.
Frisium 10 contains lactose
Frisium 10 contains lactose. If the patient has previously been diagnosed with intolerance to certain
sugars, the patient should contact the doctor before taking this medicine.

3. How to use Frisium 10

This medicine should always be used exactly as prescribed by your doctor. If in doubt, consult your doctor or pharmacist.

Dosage in the treatment of anxiety disorders

Adults: The usual recommended starting dose is 20 mg daily. If necessary, the daily dose may be increased to 30 mg. It is not recommended to exceed a total daily dose of 30 mg.

Elderly patients: In elderly patients, the effect of the medicine may be enhanced and susceptibility to adverse reactions increased, requiring the use of low initial doses and gradual dose escalation under close supervision (see "Warnings and precautions"). A daily maintenance dose of 10 to 15 mg is usually sufficient.

Once improvement has been achieved, the dose may be reduced.

If the daily dose is divided, the larger part should be taken in the evening.

The duration of treatment should be as short as possible and should not exceed 8–12 weeks (including the period of gradual dose reduction). The patient should be re-evaluated after no more than 4 weeks and then at regular intervals to determine the need for continued treatment.

In exceptional cases, longer use than the maximum recommended period may be necessary. Treatment must not be prolonged without re-evaluation of the patient's clinical condition by a specialist. Prolonged uninterrupted use should be avoided, as this may lead to dependence.

If clobazam has been used for a prolonged period, the medicine should not be stopped abruptly. The dose should be gradually reduced under medical supervision to avoid withdrawal symptoms (see "Warnings and precautions").

Dosage in the treatment of epilepsy, in combination with one or more anticonvulsant medicines

Adults: Treatment should be initiated with a low starting dose (5 to 15 mg daily). If necessary, the dose may be gradually increased up to a maximum daily dose of approximately 80 mg.

Children aged 6 years and older: Treatment should be initiated with a starting dose of 5 mg daily. A maintenance dose of 0.3 to 1 mg/kg body weight is usually sufficient.

There are no dosage recommendations for children under 6 years of age due to the lack of an appropriate formulation ensuring safe use and accurate dosing.

Elderly patients: In elderly patients, increased susceptibility to adverse reactions may occur, requiring the use of low initial doses and gradual dose escalation under close supervision (see "Warnings and precautions").

If the daily dose is divided, the larger part should be taken in the evening.

Doses up to 30 mg may also be taken as a single dose in the evening.

Duration of treatment: The patient should be re-evaluated after no more than 4 weeks and then at regular intervals to determine the need for continued treatment.

Before completely discontinuing the medicine, even in the absence of therapeutic effect, the dose should be gradually reduced, as seizures and other withdrawal symptoms may occur during too rapid dose reduction.

Special patient groups

Patients with renal or hepatic impairment

Due to the possible enhanced effect of the medicine and increased frequency of adverse reactions, the doctor will use low initial doses, gradually increasing them under close supervision.

Method of administration

The tablets may be taken whole or crushed and mixed with apple puree.

The tablets may be divided into equal 5 mg doses.

Clobazam may be administered independently of meals.

Duration of treatment

The medicine should be taken for as long as prescribed by the doctor.

If you feel that the effect of Frisium 10 is too strong or too weak, consult your doctor.

Use of a higher than recommended dose of Frisium 10

Overdose and poisoning with benzodiazepines, including clobazam, may cause the following symptoms: dizziness, disorientation, and drowsiness, which may worsen to include impaired body movement coordination, respiratory depression, hypotension, and in rare cases, coma. Overdose symptoms are more pronounced and, under certain circumstances, may be life-threatening when other central nervous system depressants, including alcohol, have been co-administered.

In treating overdose, the effects of other medicines should be taken into account.

The doctor may perform gastric lavage, administer intravenous fluids, and provide general supportive treatment, including monitoring of consciousness, respiratory function, pulse, and blood pressure.

In case of ingestion of a higher than recommended dose of the medicine, contact your doctor immediately or go to the nearest hospital emergency department. Take the medicine in its original packaging so that the medical staff can clearly identify which medicine was taken.

Missed dose of Frisium 10

If a dose is missed, take it as soon as possible, unless it is almost time for the next dose. Do not take two doses at the same time or within a short interval. If in doubt, consult your doctor.

Stopping Frisium 10

Do not stop treatment with Frisium 10 or change the dose without consulting your doctor.

Discontinuing treatment without medical advice may worsen the patient's condition.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
The adverse effects are listed below according to their frequency of occurrence:

Very common (occurring in more than 1 in 10 people):

• drowsiness, especially at the beginning of treatment and when higher doses are used;
• fatigue, especially at the beginning of treatment and when higher doses are used;

Common (occurring in less than 1 in 10 people):

• decreased appetite;
• irritability, aggression, restlessness, depression (existing depression may be unmasked), drug tolerance (especially with prolonged use), excitement;
• sedation, dizziness, concentration disturbances, slowed or slurred speech / speech disorders (especially when higher doses are used or during long-term treatment; transient), headache, tremor, impaired body movement coordination;
• dry mouth, constipation, nausea;

Uncommon (occurring in less than 1 in 100 people):

• unusual behaviour, confusion, anxiety, hallucinations, nightmares, decreased libido (especially with high doses or prolonged use; transient);
• emotional blunting, memory disturbances (may be associated with unusual behaviour), memory impairment (occurring with usually prescribed doses, but especially with higher doses);
• double vision (especially with high doses or prolonged treatment; transient);
• rash;
• weight gain (especially with high doses or prolonged treatment);
• falls (see “Warnings and precautions”);

Frequency not known (cannot be estimated from available data):

• dependence (especially with prolonged use), difficulty sleeping, anger outbursts, hallucinations, psychotic reactions, poor quality of sleep, suicidal tendencies;
• cognitive disturbances, altered state of consciousness (especially in elderly patients, sometimes accompanied by breathing disturbances), nystagmus (especially with high doses or prolonged use), gait disturbances (especially with high doses or prolonged treatment; transient);
• respiratory centre depression, respiratory failure (especially in patients with pre-existing respiratory disorders (e.g. bronchial asthma) or in patients with brain damage) (see “When not to take Frisium 10” and “Warnings and precautions”);
• urticaria; Stevens-Johnson syndrome, toxic epidermal necrolysis (in some cases potentially fatal);
• muscle spasms, muscle weakness;
• slowed response to stimuli, excessive lowering of body temperature.

Other adverse effects may occur in some individuals during treatment with Frisium 10.
Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: + 48 22 49 21 301, fax: + 48 22 49 21 309, website: https://smz.ezdrowie.gov.pl.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Frisium 10

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the container. The expiry date refers to the last day of the specified month.
No special storage instructions apply.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Frisium 10 contains
The active substance is clobazam. Each tablet contains 10 mg of clobazam.
The other components are: lactose, corn starch, colloidal anhydrous silica, talc,
magnesium stearate.
What Frisium 10 looks like and contents of the pack
The pack contains 20 round, white tablets.
For further information, please contact the marketing authorisation holder or the parallel importer.
Marketing authorisation holder in Greece, the country of export:
Sanofi-Aventis Monoprosopi AEBE, Sygrou Avenue 348, Building A, 176 74 Kallithea, Greece
Manufacturer:
Opella Healthcare International SAS, 56, Route de Choisy, 60200 Compiegne, France
Parallel importer:
InPharm Sp. z o.o., Strumykowa 28/11, 03-138 Warsaw, Poland
Repackaged in:
InPharm Sp. z o.o. Services sp. k., Chełmżyńska 249, 04-458 Warsaw, Poland
Marketing authorisation number in Greece, the country of export: 45231/16.09.2009
Parallel import authorisation number: 331/20