FRISIUM 10 mg Soft Capsule

Зміст інструкції

1. FRISIUM 10 mg hard capsules
   1. What is Frisium and what is it used for
   2. What you need to know before taking Frisium
   3. How to take Frisium
   4. Possible side effects
   5. How to store Frisium
   6. Contents of the pack and other information

FRISIUM 10 mg hard capsules

clobazam
Read this leaflet carefully before taking this medicine as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What is Frisium and what is it used for

Frisium contains clobazam which belongs to a class of medicines called “anxiolytics;
benzodiazepines”.
Frisium is indicated for the treatment of anxiety, tension and other disorders associated with anxiety
(somatic or psychiatric manifestations), difficulty sleeping or falling asleep (insomnia).
Medicines of the same class as Frisium (benzodiazepines) are indicated only when the disorder is
severe, disabling and subjects the individual to severe distress.

2. What you need to know before taking Frisium

Do not take Frisium

• if you are allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6).
• if you suffer from a disease characterized by severe muscle weakness (myasthenia gravis).
• if you suffer from severe breathing problems (severe respiratory failure, for example severe chronic obstructive pulmonary disease).
• if you suffer from severe liver problems (severe hepatic insufficiency).
• if you suffer from breathlessness during the night (sleep apnea syndrome).
• if you suffer from lack of coordination of body movements (spinal and cerebellar ataxia).
• if you are breastfeeding (see “Pregnancy and breastfeeding”).
• if you are a child under 3 years of age.

Warnings and precautions
Talk to your doctor or pharmacist before taking Frisium and in particular:

• before taking any non-medicinal product containing cannabidiol, as it may increase the undesirable effects of clobazam
• if you are taking any medicinal product containing cannabidiol, as it may increase the undesirable effects of clobazam. Patients with altered metabolism (poor CYP2C19 metabolism) If you suffer from an altered metabolism called “poor CYP2C19 metabolism” your doctor will appropriately adjust the dose of Frisium (for example a low initial dose).

Alcohol
Do not drink alcohol during therapy with Frisium, due to the increased risk of excessive (sedation) and other undesirable effects.
Tolerance
After repeated use for several weeks, a certain reduction in the effect of this medicine may occur.
Dependence
The use of medicines of the same class as Frisium (benzodiazepines) can lead to the development of dependence (the need to continue taking the medicine). The risk of dependence increases with the dose and duration of treatment; it is greater in patients with a history of drug or alcohol abuse. If you have previously been addicted to drugs or alcohol, with the use of Frisium, as with all other drugs belonging to the benzodiazepine class, the risk of developing dependence may be greater.
The risk of dependence is present even if you take clobazam every day for only a few weeks and is possible not only with the administration of particularly high doses, but also for the recommended therapeutic dosage.
Avoid using Frisium for prolonged periods without interruption, as dependence may develop. If you have developed physical dependence, abrupt discontinuation of treatment will be accompanied by the following withdrawal symptoms:

• headache,
• muscle pain,
• extreme anxiety,
• tension,
• restlessness,
• confusion,
• irritability.

In severe cases, the following symptoms may also occur:

• feeling detached from reality (derealization),
• feeling estranged from one's own body (depersonalization),
• hearing disorders, with intolerance to noises (hyperacusis),
• numbness,
• tingling of the extremities,
• hypersensitivity to light,
• hypersensitivity to noise and physical contact,
• hallucinations,
• mental disorders (symptomatic psychoses) or seizures.

Other disorders may be:

• depression,
• insomnia,
• increased dreams,
• sweating,
• persistent ringing in the ears (tinnitus),
• involuntary movements,
• nausea,
• vomiting,
• altered sensitivity (paresthesia),
• perceptual changes,
• abdominal and muscle cramps,
• tremor,
• muscle pain (myalgia),
• agitation,
• palpitations,
• increased heart rate (tachycardia),
• panic attacks,
• dizziness,
• increased reflexes (hyperreflexia),
• loss of short-term memory,
• increased body temperature (hyperthermia).

Rebound insomnia and anxiety
When stopping the medicine, a transient situation may occur consisting of the reappearance, in an accentuated form, of the disorders that had led to treatment with the medicine. This situation may be accompanied by other reactions, including mood changes, anxiety, restlessness or sleep disturbances. This situation is more likely to occur if the medicine is stopped abruptly, so discontinue treatment with Frisium gradually. It is important that you are aware of the possibility of these disorders if you stop treatment with Frisium.
Duration of treatment
The duration of treatment should be as short as possible (see “How to take Frisium”), according to your doctor's instructions, but should not exceed four weeks for insomnia and eight to twelve weeks in the case of anxiety, including the period of gradual discontinuation. The duration of treatment should not be prolonged beyond this period without your doctor re-evaluating the situation. At the beginning of therapy, your doctor will explain that this treatment will be of limited duration and how you should gradually reduce the dose. In addition, your doctor will warn you that changing suddenly to medicines similar to Frisium, called “short-acting benzodiazepines”, is not advisable, as this change can cause withdrawal symptoms. As with other benzodiazepines, in the case of prolonged treatment, it is appropriate to assess the therapeutic benefit, due to the possible onset of habituation and dependence.

• Memory disorders (amnesia) Frisium can cause memory disorders (anterograde amnesia) both when used at normal doses, but especially at high doses. This happens more often several hours after taking the medicine: to reduce the risk, make sure you can sleep uninterruptedly for 7-8 hours (see “Possible side effects”).

Psychiatric and “paradoxical” reactions
When using medicines similar to Frisium (benzodiazepines), reactions such as:

• restlessness,
• agitation,
• irritability,
• aggression,
• delusion,
• anger,
• nightmares,
• hallucinations,
• mental disorders (psychosis),
• changes in behavior.

If these disorders occur, contact your doctor and stop using Frisium. These reactions are more likely to occur in children and the elderly as well as in patients with a disease called “organic brain syndrome” (a reduction in mental functioning).
Severe skin reactions
Severe skin diseases (cutaneous) potentially fatal (Stevens-Johnson syndrome and toxic epidermal necrolysis), have been reported with the use of Frisium, in both children and adults. These diseases initially appear with red spots or circular patches that are often accompanied by blisters and blisters, peeling of the skin, especially on the central part of the body, ulcers in the mouth, throat, nose and genitals, red and swollen eyes (conjunctivitis). Often there are flu-like symptoms. In most cases, these effects occur with the concomitant use of Frisium with drugs, including those used to treat epilepsy (antiepileptics). The highest risk of developing severe skin reactions occurs in the first 8 weeks of treatment. If these disorders occur, discontinue treatment with Frisium and contact your doctor immediately. If you have developed these disorders with the use of Frisium, you should no longer use the medicine (see “Possible side effects”).
Elderly patients
If you are an elderly patient, the use of medicines such as Frisium may lead to an increased risk of falls due to undesirable effects such as lack of muscle coordination (ataxia), muscle weakness, dizziness, drowsiness, fatigue and exhaustion. Falls can lead to serious injuries. If you are an elderly patient, you will receive a lower dose of medicine (see “How to take Frisium”).
Patients with severe respiratory alterations (chronic respiratory failure)
If you suffer from severe respiratory alterations (chronic respiratory failure), your doctor will prescribe you a lower dose due to the risk of worsening breathing (respiratory depression; see also “Do not take Frisium”). If you suffer from a respiratory condition called “acute respiratory failure”, your doctor will periodically check your respiratory function.
Clobazam is contraindicated in patients with severe respiratory failure (see “Do not take Frisium”).
Muscle weakness
Frisium can cause muscle weakness. Therefore, if you already suffer from muscle weakness, your doctor will monitor you and may reduce the dose of clobazam you are taking. Do not take Frisium if you suffer from a disease characterized by severe muscle weakness called “myasthenia gravis” (see “Do not take Frisium”).
Patients with severe liver impairment (hepatic insufficiency)
If you suffer from severe liver impairment (severe hepatic insufficiency) and/or a brain disease called “encephalopathy”, you should take this medicine with caution, as Frisium, like all medicines of the same class (benzodiazepines), can trigger a condition called “hepatic encephalopathy” (brain disorders caused by a severe malfunction of the liver). If your liver and kidney function is impaired, your doctor will reduce your dose because you may have an increased reactivity to clobazam and a greater possibility of experiencing side effects. In case of prolonged treatment, your doctor will subject you to frequent checks of liver and kidney function.
Frisium and medicines of the same class (benzodiazepines) are not recommended for the primary treatment of mental illness (psychotic). Benzodiazepines should not be used alone to treat depression or anxiety associated with depression (because there is a risk of suicide). Some studies have shown an increased risk of suicidal thoughts, suicide attempts and suicide in patients taking some sedatives and hypnotics, including this medicine. However, it has not been established whether this is caused by the medicine or if there may be other reasons. If you have suicidal thoughts, contact your doctor as soon as possible for further advice (see section 4). Use Frisium and medicines of the same class (benzodiazepines) with extreme caution if you have previously abused drugs or alcohol.

Children and adolescents
Frisium should not be given to children under 3 years of age. In older children, Frisium should not be given without the doctor having carefully assessed the actual need for treatment and the duration of treatment should be as short as possible.

Other medicines and Frisium
Inform your doctor or pharmacist if you are taking, have recently taken or might take
any other medicine.
The concomitant use of Frisium and opioids (strong painkillers, medicines for addiction therapy and
some medicines for cough) increases the risk of drowsiness, difficulty in breathing
(respiratory depression), coma and can be life-threatening. For this reason, concomitant use
should only be considered when other treatment options are not possible.
However, if your doctor prescribes Frisium together with opioids, the dose and duration of treatment
concomitantly must be limited by the doctor.
Inform your doctor about all opioid medicines you are taking and carefully follow your
doctor's dosage recommendations. It may be helpful to inform friends or relatives to pay
attention to the signs and symptoms listed above.
Contact your doctor if you experience these symptoms.
Be careful if you take Frisium with:

• medicines for mental illnesses (antipsychotics),
• hypnotics,
• anxiolytics/sedatives,
• antidepressants,
• medicines for pain called “narcotic analgesics”,
• antiepileptics,
• anaesthetics,
• medicines for allergies that cause drowsiness (sedative antihistamines).

The association of Frisium with these medicines may cause an increase in the depressive effect on the
Central Nervous System.
Particular caution is necessary when using Frisium in case of undesirable effects caused by these
medicines or by lithium.
The effects of Frisium may be influenced by or influence the following medicines:

• Medicines for convulsions (anticonvulsants) If Frisium is used simultaneously with anticonvulsants in epilepsy therapy, your doctor will carefully monitor you with an electroencephalogram (EEG monitoring) and adjust the dosage as there may be interactions with anticonvulsant therapy. If you are taking Frisium with a medicine called “valproic acid”, or a medicine called “phenytoin”, there may be an increase in the blood levels of these drugs, so your doctor will subject you to appropriate checks.

If you are using Frisium together with a medicine called “Stiripentol” there may be an increase in
the blood levels of Frisium with a risk of overdose. The doctor will carefully monitor the dose of Frisium and
if necessary adjust the dose.

• Medicines for moderate to severe pain (narcotic analgesics) If you are using Frisium in conjunction with narcotic analgesics, you may experience an increase in euphoria leading to an increase in dependence.
• Medicines for relaxing muscles (muscle relaxants) The use of Frisium together with these medicines, including nitrous oxide, may increase the effect of these drugs.
• Inhibitors of a protein called “CYP2C19” Medicines that limit the activity of a protein called “CYP2C19” may affect the effect of Frisium. A dose adjustment of Frisium may be necessary. Inform your doctor if you are taking one of the following medicines:
• products containing cannabidiol (medicinal or non-medicinal products),
• ticlopidine, a medicine to prevent blood clots
• fluconazole, used in the treatment of fungal infections
• fluvoxamine, used in the treatment of depression
• omeprazole, used to treat stomach problems.
• medicines that are metabolized by a protein called “CYP2D6” (CYP2D6 substrates), for example dextromethorphan, pimozide, paroxetine, nebivolol. A dose adjustment of these drugs may be necessary.

The following associations should be considered carefully:

• buprenorphine (used for pain): increased risk of respiratory depression, which can lead to death. The doctor will carefully assess the need for this association and inform you of the need to comply with the prescribed doses;
• clozapine (used for mental illnesses): increased risk of collapse with respiratory and/or cardiac arrest.

The administration of theophylline or aminophylline (used for asthma) may reduce the effects of
medicines belonging to the same class as Frisium (benzodiazepines).

Frisium with alcohol
Do not take Frisium with alcohol. The simultaneous consumption of alcohol may increase the effects of
it: this negatively affects the ability to drive or operate machinery.

Pregnancy and breastfeeding
If you are pregnant, suspect you are pregnant or are planning a pregnancy, or if you are breastfeeding with breast
milk, ask your doctor or pharmacist for advice before taking this medicine.
Frisium, like all benzodiazepines, should not be administered during labour and
breastfeeding.
The use of this medicine during pregnancy is not recommended and if you are a woman
of childbearing potential who is not using contraception.
If you discover you are pregnant or are planning to have a baby, consult your
doctor immediately to reassess the need for treatment. Do not stop taking Frisium without
talking to your doctor.

Pregnancy
A large amount of data has not shown malformations associated with the use of benzodiazepines.
However, some studies have shown a potential increase in the risk of cleft lip and palate in
newborns, compared to that in the general population.
Cleft lip and palate is a birth defect caused by incomplete fusion of the palate and upper lip.
A reduction in fetal movement and variability in fetal heart rate may occur after
taking clobazam during the second and/or third trimester of pregnancy.
If Frisium is taken late in pregnancy or during labour, the baby may show
drowsiness (sedation), muscle weakness (hypotonia or “floppy infant” syndrome), a drop
in body temperature (hypothermia), difficulty feeding (feeding problems causing poor weight gain) and breathing problems (respiratory depression, sometimes severe).
If taken regularly late in pregnancy, the baby may experience withdrawal symptoms
such as agitation or tremor. In this case, the newborn must be carefully monitored during the
postnatal period.

Breastfeeding
Do not take Frisium during breastfeeding because, like all medicines belonging to the
same class (benzodiazepines), it is excreted in breast milk.

Driving and using machines
At higher doses and in case of particular individual sensitivity, Frisium may affect the
ability to react; this should be particularly taken into account when taking alcohol
at the same time.
Sedation, memory loss (amnesia), altered concentration and muscle function may negatively affect the ability to drive and operate machinery. If the
duration of sleep has been insufficient, the probability that vigilance is altered may be increased.

Frisium contains lactose
If your doctor has diagnosed you with intolerance to certain sugars, contact him before taking
this medicine.

3. How to take Frisium

Take this medicine following exactly the instructions of your doctor or pharmacist. If you
have any doubts, consult your doctor or pharmacist.
The dosage and duration of treatment should be adapted case by case at the doctor's discretion, based on
the indications, the severity of the clinical picture and the variability of the individual response.
Treatment should be started with the lowest dose.
The maximum dose should not be exceeded.
You will be monitored regularly at the beginning of treatment to reduce, if necessary, the dose or the
frequency of intake, to prevent overdose due to accumulation.
The recommended dose is

• Adults Generally 2 capsules per day, increasing if necessary to 3 capsules per day. In particularly severe forms, the daily dosage may be increased at the doctor's discretion. Once improvement of the clinical picture is obtained, the dosage may be reduced. Elderly or debilitated patients often only 1 capsule per day is sufficient. If the daily dose is divided throughout the day, it is advisable to administer the single highest dose in the evening before going to bed. Daily doses up to 30 mg can also be administered in a single dose in the evening.
• Patients with altered liver and/or kidney function In these patients, accentuated reactivity and greater sensitivity to undesirable effects may occur. Consequently, therapy should be started with reduced doses, which may be gradually increased while continuing treatment, which should always be carried out under close medical supervision.

Predisposed subjects, if treated with high doses and for prolonged periods, may develop dependence,
as happens with other medicines with hypnotic, sedative and tranquilizing activity.

• Elderly patients In these patients, increased reactivity and greater sensitivity to undesirable effects may occur. Consequently, therapy should be started with reduced doses, which may be gradually increased under close medical supervision.
• Anxiety The treatment should be as short as possible. The doctor will monitor you regularly and carefully assess the need for continued treatment, especially if you do not have evident disorders. The overall duration of treatment, generally, should not exceed 8-12 weeks, including a period of gradual discontinuation. In certain cases, an extension beyond the maximum treatment period may be necessary; in such cases, the doctor will re-evaluate your condition.
• Insomnia The treatment should be as short as possible. The duration of treatment, generally, varies from a few days to two weeks, up to a maximum of four weeks, including a period of gradual discontinuation. In certain cases, an extension beyond the maximum treatment period may be necessary; in such a case, it should not occur without re-evaluation of the patient's condition. Take the medicine at bedtime. Do not use Frisium for the treatment of insomnia if you are under 18 years of age without a careful assessment of your actual need by the doctor. The single dose for patients under 18 years of age depends on their age, weight and general condition.

If you take more Frisium than you should
Do not take a double dose to make up for a missed dose.
In case of accidental ingestion/intake of an excessive dose of Frisium, immediately inform
your doctor or go to the nearest hospital.
As with other benzodiazepines, an overdose should not pose a risk to life, unless there is concomitant intake of other medicines that depress the Central Nervous System (including alcohol).
Benzodiazepine overdose usually manifests with varying degrees of depression of the central nervous system ranging from loss of sensory and mental abilities (obnubilation), to
mental confusion and continuous sleep (lethargy).
In more severe cases, the disorders may include loss of muscle coordination (ataxia),
decreased muscle strength (hypotonia), decreased blood pressure (hypotension),
respiratory depression, rarely coma and very rarely death.
If you have any doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

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

• drowsiness
• fatigue (asthenia)

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

• swelling of the face, hands and feet, lips, tongue or throat (angioedema)
• irritability*
• aggressiveness*
• states of acute agitation*
• depression (a pre-existing depressive state may be unmasked)
• drug tolerance (especially during prolonged use - see “Warnings and precautions”)
• agitation*
• dizziness
• sedation
• attention disorders
• slowed speech/speech disorders
• distortion of taste (dysgeusia)
• slowing of physical and mental activities (psychomotor)
• headache (cephalalgia)
• fine tremor of the fingers
• loss of muscle coordination (ataxia)
• increased heart rate (tachycardia)
• vomiting
• nausea
• pain in the upper abdomen
• constipation (stipsi) and dry mouth
• decreased appetite
• itching
• urination disorders
• sweating

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

• memory loss (amnesia) and/or inappropriate behaviour
• confusion
• anxiety*
• delirium*
• nightmares*
• decreased sexual desire
• blunting of emotions
• weakening of memory
• decreased ability to memorize new information (anterograde amnesia)
• double vision (diplopia). This disorder occurs particularly at high doses or in long-term treatments and is reversible.
• skin reactions such as redness (rash)
• weight gain. This reaction occurs particularly at high doses or in long-term treatments and is reversible.
• falls

Rare side effects (may affect up to 1 in 1000)

• allergic reactions (anaphylactic/anaphylactoid reactions)

Side effects with unknown frequency(frequency cannot be estimated on the basis of available data):

• dependence (especially during prolonged use - see “Warnings and precautions”)
• difficulty falling asleep or staying asleep*
• outbursts of anger*
• hallucinations*
• psychotic reactions*
• poor sleep quality
• suicidal tendencies*
• muscle spasms*
• learning (cognitive) disorders
• loss of consciousness, after prolonged use of Frisium or medicines of the same class (benzodiazepines) and particularly in the elderly, sometimes in association with respiratory disorders; these effects sometimes persist for a considerable period of time. Oscillatory, rhythmic and involuntary eye movements (nystagmus), this reaction occurs particularly at high doses or in long-term treatments
• instability in gait and other motor functions. These reactions occur particularly at high doses or in long-term treatments and are reversible
• decreased alertness
• asthenia
• vertigo
• respiratory depression, especially at high doses. If you have pre-existing impaired respiratory function (e.g. if you suffer from bronchial asthma) or if you suffer from brain damage, respiratory failure may occur or worsen
• urticaria
• severe skin diseases: “Stevens-Johnson Syndrome”, “Toxic Epidermal Necrolysis” which manifest with severe alterations of skin and mucous membranes, with the appearance of blisters and also general disorders such as fever, vomiting, diarrhoea. These disorders can be fatal
• muscle weakness
• slowed reaction times
• decreased body temperature (hypothermia)

* These psychiatric disorders (paradoxical reactions) may occur especially in the elderly and
children. If these reactions occur, discontinue treatment with Frisium.
.

• Adverse reactions of the benzodiazepine class

Dependence
The use of benzodiazepines (even at therapeutic doses) can lead to the development of physical
dependence: discontinuation of therapy can cause rebound or withdrawal phenomena (see
“Warnings and precautions”). Psychological dependence can occur. Abuse of benzodiazepines has been
reported. Once physical dependence has developed, abrupt discontinuation of treatment may be
accompanied by withdrawal symptoms. These may consist of extreme anxiety, tension, restlessness,
confusion, irritability, headache and muscle pain. In severe cases, the following symptoms may appear:
feeling out of reality (derealization), feeling estranged from one's own body (depersonalization),
hallucinations, altered sensitivity (paresthesia) of the limbs, hypersensitivity to light, noise and
physical contact, hearing disorders, with intolerance to noises (hyperacusis) and seizures. In the case of
use of benzodiazepines with short duration of action, withdrawal symptoms may become manifest
between one dose and the next, especially at high doses. This is unlikely to occur with Frisium,
because it is not a benzodiazepine with a short duration of action.
Rebound insomnia
Upon discontinuation of treatment, a transient disorder such as insomnia may occur, which recurs in
aggravated form following treatment with benzodiazepines. Because, after sudden discontinuation of
treatment, the risk of rebound/withdrawal phenomena is higher, gradually decrease the dose.
Depression
During the use of benzodiazepines, a pre-existing depressive state may be unmasked. Benzodiazepines
and similar compounds can cause reactions such as: restlessness, irritability, aggressiveness, delirium,
anger, nightmares, hallucinations, psychosis, altered behaviour. Such reactions can be quite serious.
They are more likely to occur in children and the elderly.

• In addition, other rare adverse effects have been reported, including: yellowing of the skin and eyes (jaundice), increased values of some blood tests (bilirubin, liver transaminases, increased alkaline phosphatase), even severe decreases in blood cells (thrombocytopenia, agranulocytosis, pancytopenia), a condition called “SIAD” (syndrome of inappropriate secretion of the antidiuretic hormone), with fluid retention in the body.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, please tell your
doctor or pharmacist. You can also report side effects directly through the national reporting system at
www.aifa.gov.it/content/segnalazioni-reazioni-avverse .
By reporting side effects you can help provide more information on the safety of
this medicine.

5. How to store Frisium

Do not store at a temperature above 25°C.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the pack after “Exp”. The expiry
date refers to the last day of that month.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Frisium contains

• The active ingredient is clobazam. 1 hard capsule contains 10 mg of clobazam.
• The other ingredients are: lactose, corn starch, talc, magnesium stearate. Capsule components: gelatin, titanium dioxide (E 171).

Description of the appearance of Frisium and contents of the pack
Frisium is presented in the form ofHard capsules.
Pack of 30 capsules.

Marketing Authorisation Holder
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)
Sanofi S.r.l.
strada statale 17, km 22
67019 Scoppito (AQ)