Package Insert: Information for the User

Noiafren 10 mg Tablets

Clobazam

Read this entire package insert carefully before starting to take this medication, as it contains important information for you.

• Keep this package insert, as you may need to refer to it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed only for you, and you should not give it to others who may have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

6. Contents of the pack and additional information

The active ingredient of Noiafren, clobazam, belongs to a group of medications called benzodiazepines, used to reduce anxiety and to combat seizures, and for their few sedative and muscle-relaxing effects.

This medication is used for:

Adults:

• acute or chronic anxiety states that may manifest themselves especially in the form of anxiety, tension, internal unrest, excitement, irritability, emotional sleep disturbances, mood alterations, as well as digestive, cardiac, or respiratory problems. In these latter cases, the doctor must rule out the possible existence of an organic cause.

• anxiety during severe neurosis, anxiety accompanying depressive states (in association with an antidepressant treatment), or psychoses (associated with neuroleptics), as well as in alcohol detoxification cures and in predelirium (alcohol withdrawal syndrome).

Adults and children over 6 years old:

• as an adjunctive treatment for epilepsy, especially partial forms (seizures originating in a specific region of the brain), with or without secondary generalization (seizures that occur in both brain hemispheres), that are not completely controlled by conventional treatment.

Do not take Noiafren 10 mg

• if you are allergic (hypersensitive) to clobazam, or to the group of benzodiazepines in general, or to any of the other components of this medication (listed in section 6)
• if you have breathing difficulties
• if you suffer from severe muscle problems (myasthenia gravis)
• if you suffer from increased intraocular pressure (glaucoma)
• if you have severe respiratory insufficiency
• if you have severe liver dysfunction
• if you have sleep apnea
• in women during lactation.

Noiafren should not be administered to children from 6 months to 3 years, except in exceptional cases where antiepileptic treatment is essential.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Noiafren, and also:

• before taking any product that is not a medication and contains cannabidiol, as it may increase the adverse effects of clobazam
• if you are consuming any medication that contains cannabidiol, as it may increase the adverse effects of clobazam.

Before starting treatment, inform your doctor if you have any other diseases or conditions.

Alcohol

It is recommended that patients abstain from drinking alcohol during treatment with clobazam (increased risk of sedation and other adverse effects).

Use with opioids

Do not take Noiafren at the same time as opioids (medications used to relieve intense pain, such as morphine or codeine) unless your doctor prescribes it, due to the possible risk of sedation, respiratory depression, coma, or even death (see “Taking Noiafren 10 mg with other medications”).

Dependence

The use of benzodiazepines can lead to dependence. This occurs mainly after taking the medication continuously for a long time. To minimize the risk of dependence, the following precautions should be taken:

• the use of benzodiazepines should be made only under medical prescription (never because they have worked in other patients) and never recommended to others.
• do not increase the prescribed doses, or prolong the treatment longer than recommended.
• consult your doctor regularly to decide if the treatment should continue.

In patients with a history of drug or alcohol dependence, there may be an increased risk of developing dependence.

When benzodiazepines are withdrawn, especially if it happens suddenly, it may cause a rebound phenomenon or a withdrawal syndrome. This rebound phenomenon is characterized by the sudden appearance of the symptoms that originally led to treatment with clobazam (e.g. anxiety, seizures). This may be accompanied by other reactions, including mood changes, anxiety, or sleep disorders and restlessness.

Once physical dependence has developed, abrupt termination of treatment with clobazam may be accompanied by withdrawal symptoms, or when switching abruptly from a long-acting benzodiazepine (e.g. Noiafren) to a short-acting one.

Memory loss (amnesia)

Noiafren may cause anterograde amnesia, i.e. you may not remember what happened after taking the medication. Therefore, it is recommended that the patient can sleep uninterruptedly for 7-8 hours after taking the medication.

Psychotic and "paradoxical" reactions

It is known that with the use of Noiafren, intranquility, agitation, irritability, aggression, delirium, anger attacks, nightmares, hallucinations, delusional ideas (psychosis), inappropriate behavior, and other adverse effects on behavior may occur.

If this happens, stop taking Noiafren and contact your doctor. These reactions are more frequent in children and in elderly patients.

Tolerance in epilepsy

When using Noiafren to treat epilepsy, inform your doctor if you notice that after continuous use for several weeks, the effectiveness of the treatment decreases.

Severe skin reactions

Severe skin reactions, including Stevens-Johnson syndrome (SSJ) and toxic epidermal necrolysis (TEN), have been reported in both children and adults. Most reported cases involved the simultaneous use of other medications, including antiepileptic medications (for treating epilepsy), associated with severe skin reactions.

These skin reactions may be associated with a fatal outcome. Consult your doctor when any signs of these severe skin reactions appear.

Discontinue treatment if any of these severe skin reactions are suspected, and your doctor should consider an alternative treatment.

Respiratory depression

Noiafren may cause respiratory depression, especially at high doses. Inform your doctor if you have respiratory insufficiency, so that they can monitor you. Your doctor will decide if it is necessary to reduce the dose of Noiafren.

Renal and hepatic insufficiency

Inform your doctor if you have renal or hepatic insufficiency, so that they can monitor you. Your doctor will decide if it is necessary to reduce the dose of Noiafren.

Muscle weakness

Noiafren may cause muscle weakness. Inform your doctor if you have muscle weakness before starting treatment with Noiafren, or if you have spinal or cerebellar ataxia (a type of atrophy of the spinal cord or brain characterized by lack of coordination of movements).

Clobazam is contraindicated in patients with myasthenia gravis.

Some studies have shown an increased risk of suicidal thoughts, attempts, and suicide in patients taking certain sedatives and hypnotics, including this medication. However, a causal relationship has not been established, and there may be other reasons. If you have suicidal thoughts, contact your doctor as soon as possible for further medical advice (see section 4).

Children

Benzodiazepines should not be administered to children without a careful evaluation by a doctor.

Older adults

Older adults should be cautious due to increased sensitivity to adverse reactions such as drowsiness, dizziness, muscle weakness, increased risk of falls that can result in serious injuries. If you are an older adult, your doctor may prescribe a lower dose and monitor your response to treatment. Please follow your doctor's instructions carefully.

Patients metabolizing CYP2C19

In the case of patients who are poor metabolizers of CYP2C19, it may be necessary to adjust the dose.

Taking Noiafren 10 mg with other medications

Inform your doctor or pharmacist that you are using, have used recently, or may need to use any other medication. This is extremely important because the simultaneous use of more than one medication may increase or decrease its effect.

Therefore, do not take other medications at the same time as Noiafren unless your doctor is informed and approves it in advance.

Central nervous system depressants

There may be an increase in the effect of Noiafren on the brain and nerves when Noiafren is taken with antipsychotics (for treating psychosis, a type of mental illness), hypnotics (to facilitate sleep), narcotic analgesics (to treat intense pain), anxiolytics (to treat anxiety), certain antidepressants, anticonvulsants (to treat seizures), anesthetics, sedating antihistamines (which produce sedation), or other sedatives.

Opioid medications

The use of Noiafren at the same time as opioids (medications used to relieve intense pain, such as morphine or codeine) may increase the risk of sedation, respiratory depression, coma, or even death. Your doctor will decide if you can use them or not at the same time (see “Warnings and precautions”).

Anticonvulsant medications

If Noiafren is taken at the same time as anticonvulsants in the treatment of epilepsy (carbamazepine, valproic acid, stiripentol, and phenytoin), your doctor may adjust your dose, based on your response to treatment.

Narcotic analgesics

When Noiafren is taken at the same time as narcotic analgesics (to treat pain), it may increase the possible euphoria, which may lead to increased psychological dependence.

Muscle relaxants

When Noiafren is taken at the same time as muscle relaxants or nitrous oxide, it may increase the relaxing effects.

Adjust the dose when Noiafren is taken with the following medications:

• productsthat contain cannabidiol (medications or non-medication products)
• ticlopidine -antiplatelet medicationto prevent thrombus formation
• fluconazole - to treat fungal infections
• fluvoxamine - to treat depression
• omeprazole - to treat stomach problems
• dextromethorphan - to treat cough
• pimozide - to treat psychosis, anxiety, and schizophrenia
• paroxetine - to treat depression and anxiety
• nevibolol - to treat high blood pressure and arrhythmias -heart rate changes.

Taking Noiafren 10 mg with food, drinks, and alcohol

Avoid drinking alcoholic beverages during treatment. The effect of alcohol may potentiate sedation, and this may affect your ability to drive or operate machinery. If you need more information on this point, consult your doctor.

It is recommended not to drink alcohol during treatment with Noiafren.

Pregnancy, lactation, and fertility

This medication is not recommended for use during pregnancy and in women of childbearing age who are not using contraceptives.

If you discover that you are pregnant or plan to become pregnant, consult your doctor immediately to reevaluate the need for treatment. Do not stop taking Noiafren without consulting your doctor.

A large number of data have not shown evidence of malformations associated with the use of benzodiazepines. However, some studies have shown a potentially 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 malformation that occurs at birth caused by incomplete fusion of the palate and upper lip.

Reduced fetal movement and variability in fetal heart rate may occur after taking clobazam during the second and/or third trimester of pregnancy.

If Noiafren is taken at the end of pregnancy or during delivery, your baby may show sedation (sedation), muscle weakness (hypotonia or neonatal hypotonic syndrome), low body temperature (hypothermia), difficulty feeding (lactation problems that may result in poor weight gain), and respiratory problems (respiratory depression, sometimes severe).

If this medication is taken regularly at the end of pregnancy, your baby may exhibit withdrawal symptoms such as agitation or tremors. In this case, the newborn should be closely monitored in the postnatal period.

Driving and operating machinery

Clobazam may alter your ability to drive or operate machinery, as it may cause drowsiness, decrease your attention, or decrease your reaction time. The appearance of these effects is more likely at the beginning of treatment or when the dose is increased. Do not drive or operate machinery if you experience any of these effects.

Noiafren 10 mg contains lactose

This medication contains lactose. If your doctor has indicated that you have an intolerance to certain sugars, consult with them before taking this medication.

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

Your doctor will prescribe the appropriate dose depending on the nature of your illness, age, and weight.

Your doctor will indicate the duration of your treatment with Noiafren, do not stop it before. In most cases, only a short treatment period is needed. Your doctor will monitor you at least every 4 weeks. Treatment of anxiety generally should not exceed 8 weeks.

Treatment should begin with the lowest dose. Do not exceed the maximum dose.

In elderly patients or those with liver or kidney problems, muscle weakness, or lack of movement coordination, your doctor will prescribe a lower dose.

The tablets can be taken whole or crushed, mixed or not with food, and with a sufficient amount of liquid (approximately a glass). If the dose is to be divided into several daily doses, the largest one should be taken at night.

The tablets can be divided into two equal halves of 5 mg.

To avoid withdrawal symptoms, do not stop taking Noiafren abruptly, especially if you have been taking it for a long time.

Remember to take your medication.

Each individual dose should not exceed the indicated limits, and the total daily dose should not either, unless your doctor prescribes a higher dose.

Dosage in the treatment of anxiety states

• In adults, the initial dose is usually 2 tablets (20 mg of clobazam) per day. If necessary, your doctor may increase the dose to 3 tablets per day.
• In patients with liver or kidney disease, and elderly patients, initial low doses are required, with gradual increases, under the careful observation of your doctor (see "Warnings and precautions").
• In elderly patients, a maintenance dose of 1 tablet (10 mg of clobazam) to 1 and a half tablets (15 mg of clobazam) per day is usually sufficient.

Once symptoms have improved, your doctor may reduce the dose.

Dosage in the treatment of uncontrolled partial epilepsy by conventional treatment

• The initial dose is 5 to 15 mg per day. Your doctor may gradually increase the dosage based on your response to treatment, up to a maximum dose of 80 mg per day. Regarding the duration of treatment, your doctor will evaluate you after a time not exceeding 4 weeks, and from then on frequently, to assess whether you should continue or not with the treatment. When ending treatment, even in cases of insufficient results, the dose should be gradually reduced, as otherwise it may lead to a greater predisposition to a crisis.

• In patients with liver or kidney disease, and elderly patients, initial low doses are required, with gradual increases, under the careful observation of your doctor (see "Warnings and precautions").

• In children over 6 years old: the initial dose should be 5 mg per day. The maintenance dose should be 0.3 to 1.0 mg per kg of body weight per day. It is not recommended to administer to children under 6 years old due to the lack of tablets with the required dose.

Never change the dose that has been prescribed to you. If you think the medication's effect is too strong or too weak, consult your doctor.

If you take more Noiafren 10 mg than you should

Consult your doctor, pharmacist, nearest hospital, or call the Toxicological Information Service, phone 91 562 04 20, indicating the medication and the amount taken. It is recommended to bring the packaging and the medication's leaflet to the healthcare professional.

Overdose may lead to central nervous system depression, associated with drowsiness, confusion, and lethargy, which may progress to lack of movement coordination, respiratory depression, hypotension, and, rarely, coma. The risk of death increases in cases of combined intoxication with other central nervous system depressants, including alcohol.

Like other benzodiazepines, overdose does not represent a vital threat unless its administration is combined with other central depressants (including alcohol).

If you forgot to take Noiafren 10 mg

Do not take a double dose to compensate for the missed doses. You should continue with the normal dose of the next intake.

If you interrupt treatment with Noiafren 10 mg

Upon cessation of administration, restlessness, anxiety, insomnia, lack of concentration, headache, and hot flashes may appear. It is not recommended, in general, to interrupt medication abruptly, but rather to gradually reduce the dose according to the doctor's instructions.

If you have any other doubts about the use of this product, ask your doctor or pharmacist.

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

Side effects are classified according to their frequency of occurrence as:

• Very common: may affect more than 1 in 10 patients
• Common: may affect between 1 and 10 in 100 patients
• Uncommon: may affect between 1 and 10 in 1,000 patients
• Rare: may affect between 1 and 10 in 10,000 patients
• Very rare: may affect less than 1 in 10,000 patients
• Frequency not known (cannot be estimated from available data).

Metabolic and nutritional disorders

Common: decreased appetite.

Psychiatric disorders

Common: irritability, aggression, restlessness, depression (the use of benzodiazepines may unmask an existing depression), tolerance to the medication (especially in long-term treatments), agitation

Uncommon: abnormal behavior, confusion, anxiety, delirium, nightmare,loss of libido (sexual desire) especially when taking high doses or in long-term treatments, which are reversible.

Frequency not known: dependence on the medication (especially in long-term treatments), insomnia (especially at the beginning of treatment), outbursts of anger, hallucination, psychotic disorders (mental disorders), poor sleep, suicidal tendencies.

Nervous system disorders

Very common: drowsiness (sleep) especially at the beginning of treatment and when high doses are used

Common: sedation, dizziness, attention disturbances, speech disorders (slowing or difficulty articulating words) especially when taking high doses or in long-term treatments, which are reversible, headache, tremor, ataxia (lack of coordination of movements)

Uncommon: inability to feel emotions, retrograde amnesia (that is, not remembering what happened, at normal doses but especially at high doses), memory alteration, amnesia

Frequency not known: cognitive disorders (disorders of knowledge), alteration of consciousness (particularly in elderly patients, may be combined with respiratory disorders), nystagmus (muscle spasms in the eyes) particularly with high doses or in long-term treatments, gait instability (especially with high doses or in long-term treatments, which are reversible).

Eye disorders

Uncommon: diplopia (double vision), especially with high doses or in long-term treatments, which are reversible.

Respiratory, thoracic and mediastinal disorders

Frequency not known: respiratory depression, respiratory insufficiency (particularly in patients with respiratory function problems, for example in patients with asthma or brain damage) (see sections “Do not take Noiafren 10 mg” and “Warnings and precautions”).

Gastrointestinal disorders

Common: dry mouth, nausea, constipation.

Skin and subcutaneous tissue disorders

Uncommon: rash.

Frequency not known: urticaria, Stevens-Johnson syndrome (severe vesicular skin and mucous membrane reactions), toxic epidermal necrolysis (severe skin disease characterized by the appearance of rashes, blisters, including some cases with fatal outcome).

Musculoskeletal and connective tissue disorders

Frequency not known: muscle spasms, muscle weakness.

General disorders and administration site conditions

Very common: fatigue, especially at the beginning of treatment and when high doses are used

Frequency not known: slow response to stimuli, hypothermia (low body temperature).

Complementary examinations

Uncommon: weight gain (especially with high doses or in long-term treatments).

Accidents, poisoning and complications of therapeutic procedures

Uncommon: falls.

Reporting of side effects:

If you experience any type of side effect, consult your doctor or pharmacist, even if it ispossible side effects that do not appear in this leaflet. You can also report them directly through the Spanish System of Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

This product does not require special conditions for conservation.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Medicines should not be disposed of through drains or in the trash. Dispose of packaging and medications that you no longer need at the SIGRE collection point of the pharmacy. If in doubt, ask your pharmacist how to dispose of packaging and medications that you no longer need. In this way, you will help protect the environment.

Composition of Noiafren 10 mg

• The active ingredient is clobazam. Each tablet contains 10 mg of clobazam.
• The other components are lactose monohydrate, cornstarch, anhydrous colloidal silica, talc, and magnesium stearate.

Appearance of the product and contents of the packaging

Noiafren is presented in the form ofwhite, round, biconvex, and scored tablets, engraved with the letters B and GL on either side of the score.The score serves to divide the tablets into two equal halves of 5 mg.

Each package contains 20 tablets.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization:

Atnahs Pharma Netherlands B.V.

Copenhagen Towers

Ørestads Boulevard 108, 5.tv

DK-2300 København S

Denmark

Responsible for manufacturing:

Opella Healthcare International SAS

56, Route de Choisy

F-60200 Compiègne

France

O

Famar Health Care Services Madrid, S.A.U.

Avda. de Leganés, 62

28923 Alcorcón (Madrid)

Spain

Local representative:

Pharmanovia A/S

Copenhagen Towers

Ørestads Boulevard 108, 5.tv

DK-2300 København S

Denmark

Last review date of this leaflet: November 2020

The detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/