Frisium 10

Patient Information Leaflet

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

• Keep this leaflet so that you can read it again if necessary.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not give it to others. This medicine may harm someone else, even if their symptoms are identical.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents:

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 for the treatment of acute and chronic anxiety states, particularly those characterized by: increased anxiety, tension, inner restlessness, agitation, irritability, sleep disturbances of emotional origin, and psychosomatic or psychovegetative 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 condition characterized by rapid fatigue of skeletal muscles), as there is an increased risk of worsening the disease,
• 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 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.

Suicidal behaviour
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 due to taking this medicine or whether there are other causes. If the patient experiences suicidal thoughts, they should contact their doctor as soon as possible for 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 for patients in whom other treatment options are insufficient.
If a decision is made to administer clobazam together with opioids, the 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)
When using benzodiazepines, even at the recommended dose and especially at higher doses, anterograde amnesia may occur (difficulty in learning and remembering new information – new data are not permanently stored).

Tolerance to the medicine
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
The use of benzodiazepines, including Frisium 10, may lead to physical and psychological dependence. The risk is greater with higher doses and longer treatment duration, but it may occur even with 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 dreams, heightened anxiety, tension, restlessness, disorientation and agitation, loss of sense of reality, feelings of loss of identity, hallucinations, symptomatic psychoses (e.g. delirium after withdrawal), numbness and tingling of limbs, muscle pain, tremor, sweating, nausea, vomiting, heightened hearing, hypersensitivity to light, sound 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.

Abrupt discontinuation of benzodiazepines may also lead to a so-called rebound phenomenon, i.e. recurrence of intensified symptoms that Frisium 10 was intended to eliminate (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 and 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 previously 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 minimize the risk of adverse effects.

Severe skin diseases
During treatment with clobazam, severe skin diseases such as Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported in both children and adults. Most of these cases involved 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 a doctor or pharmacist:

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

Frisium 10 and other medicines
Inform your doctor or pharmacist about all medicines currently taken or recently taken, including those available without a prescription.

Exercise caution when using clobazam together with the following medicines:

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

Particular caution should be exercised 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 cause increased concentration of the active drug in the body), e.g. fluconazole, fluvoxamine, ticlopidine, omeprazole,
• medicines metabolized by the CYP2D6 enzyme, e.g. dextromethorphan, pimozide, paroxetine, nebivolol (clobazam may inhibit CYP2D6 enzyme activity).

Frisium 10 with food, drink and alcohol
The 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 effects 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.
The use of Frisium 10 is not recommended during pregnancy or in women of childbearing potential who are not using contraception.
If the patient becomes pregnant or plans to have a child, she should consult her doctor immediately to reassess the need for treatment. Do not stop taking Frisium 10 without consulting your doctor.
A large number of data have not revealed evidence indicating a link between congenital malformations and the use of benzodiazepines. However, some studies have shown an increased risk of cleft lip and cleft palate in newborns compared to the general population.
Cleft lip and cleft palate (sometimes called "hare lip") are congenital defects caused by incomplete fusion of the palate and upper lip during fetal development.
Taking Frisium 10 in the second and/or third trimester of pregnancy may cause reduced fetal movements and changes in fetal heart rate variability.
The use of Frisium 10 towards the end of pregnancy or during delivery may cause 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) in the newborn.
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 in 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, reduced muscle strength) may impair concentration and reaction time and adversely affect the ability to drive vehicles and operate machinery.

Frisium 10 contains monohydrate lactose
Frisium 10 contains monohydrate lactose. If the patient has previously been diagnosed with intolerance to certain sugars, the patient should consult a doctor before taking this medicine.

3. How to use Frisium 10

This medicine should always be used exactly as directed 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 generally 20 mg per day. 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 effects may be 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.

After 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 continuous use of the medicine without breaks should be avoided, as this may lead to dependence.

If clonazepam has been used for a prolonged period, the medicine should not be stopped abruptly. The dose should be reduced gradually 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 per day). If necessary, the dose should 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 per day. 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 effects may occur, requiring the use of low initial doses and gradual dose escalation under strict 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 effects, the doctor will use low initial doses, which will be gradually increased under close supervision.

Method of administration

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

The 10 mg tablets may be divided into equal 5 mg doses.

Clonazepam may be taken independently of meals.

Duration of treatment

The medicine should be taken for as long as directed by your 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 clonazepam, may cause the following symptoms: dizziness, disorientation, and drowsiness, which may worsen to include: impaired body movement coordination, breathing difficulties, decreased blood pressure, 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 taken concurrently.

In the treatment of overdose, the influence of other medicines should be considered.

The doctor may perform gastric lavage, administer intravenous fluids, and provide general supportive treatment, while monitoring 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. Bring 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 the time for the next dose is approaching. 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.

Stopping 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 experiences 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), overstimulation;
• sedation, dizziness, concentration difficulties, slowed or slurred speech / speech disorders (especially when high 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 when high doses are used or after long-term use; transient);
• emotional blunting, memory disturbances (may be associated with unusual behaviour), memory loss (occurring at normally used doses, but especially at higher doses);
• double vision (especially when high doses are used or during long-term treatment; transient);
• rash;
• weight gain (especially when high doses are used or during long-term treatment);
• falls (see “Warnings and precautions”).

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

• dependence (especially with prolonged use), difficulty sleeping, anger outbursts, illusions, 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 when high doses are used or after long-term use), gait disturbances (especially when high doses are used or after long-term use; 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 of 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 sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the stated month.
Do not store above 25°C. Store in the original packaging.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. 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 ingredients are: monohydrate lactose, corn starch, anhydrous colloidal silicon dioxide,
talc, magnesium stearate.

What Frisium 10 looks like and contents of the pack
The pack contains 20 tablets.
For more detailed information, please contact the marketing authorisation holder or the parallel importer.

Marketing authorisation holder in Ireland, country of export:
Atnahs Pharma Netherlands B.V.
Copenhagen Towers
Ørestads Boulevard 108, 5.tv
DK-2300 Copenhagen S
Denmark

Manufacturer:
Opella Healthcare International SAS
56, Route de Choisy
60200 Compiègne
France

Parallel importer:
InPharm Sp. z o.o.
ul. Strumykowa 28/11
03-138 Warsaw
Poland

Repackaged in:
InPharm Sp. z o.o. Services sp. k.
ul. Chełmżyńska 249
04-458 Warsaw
Poland

Marketing authorisation number in Ireland, country of export: PA22657/004/001
Parallel import authorisation number: 308/25