TRANXILIUM 15 mg HARD CAPSULES

2. What you need to know before you take Tranxilium

Before taking this medicine, you must be sure that you will be able to sleep uninterrupted for 7-8 hours.

In case you get up at night, after taking a hypnotic (a medicine that induces sleep), a slow response to stimuli may appear with the consequent risk of falls and dizziness.

Do not take Tranxilium

• if you are allergic to the active substance (potassium clorazepate) or to any of the other components of this medicine (listed in section 6),
• if you are allergic to a group of medicines called benzodiazepines,
• if you have myasthenia gravis (a muscular problem characterized by abnormal weakness of the voluntary muscles),
• if you have severe liver failure (severe liver alteration),
• if you have severe respiratory failure (difficulty breathing),
• if you have decompensated respiratory failure (an increase in your usual difficulty breathing),
• if you have sleep apnea syndrome (a disorder characterized by episodes of suspension of breathing during sleep),
• administration to children: the 15 mg capsules should not be administered to children.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Tranxilium.

The use of this type of medicine can lead to the development of physical and psychological dependence. The risk of dependence increases with the dose, the duration of treatment, the combination with alcohol or with certain medicines (anxiolytics, hypnotics, psychotropics), or if you have a history of dependencies (to medicines or other products).

In case of developing physical dependence, sudden interruption of treatment can produce a withdrawal syndrome that manifests with headache or muscle pain, anxiety, muscle tension, restlessness, agitation, confusion, insomnia, and irritability. In severe cases, the following symptoms have been described: depersonalization, hyperacusis, tingling and cramps in the limbs, intolerance to light, sounds, and physical contact, tremors, hallucinations, or convulsions.

Consult your doctor or pharmacist if such symptoms appear. Your doctor will indicate the duration of your treatment (which should not exceed 4 to 12 weeks) and the precise way in which you should gradually reduce the dose until you stop treatment.

A certain tolerance can develop after prolonged use of this medicine.

This medicine can induce anterograde amnesia, especially if used at bedtime and when sleep duration is short. To reduce this risk, you must ensure that you will be able to sleep uninterrupted for 7-8 hours.

When treatment is stopped, the symptoms that made it necessary may reappear (rebound insomnia and anxiety). This is a transient phenomenon that can be accompanied by mood changes, anxiety, restlessness, or sleep disorders. It is more likely to appear if treatment is interrupted abruptly, so it should be gradually reduced.

The elderly are more susceptible to adverse reactions such as drowsiness, dizziness, muscle weakness, which can cause falls and therefore serious injuries (see section "4. Possible side effects"). In these cases, dose reduction is recommended.

Psychiatric and paradoxical reactions such as restlessness, agitation, irritability, aggressiveness, delirium, fits of rage, nightmares, hallucinations, psychosis, inappropriate behavior, and other adverse effects on behavior may appear. In this case, you should consult your doctor about stopping treatment. These reactions are more frequent in children and the elderly.

You should avoid using this medicine in combination with sodium oxybate, due to the risk of respiratory problems (respiratory depression).

Do not take Tranxilium at the same time as opioids (medicines used to relieve intense pain, such as morphine or codeine) unless your doctor prescribes it, due to the possible risk of suffering sedation, respiratory depression, coma, or even death (see "Using Tranxilium with other medicines").

If you have suicidal tendencies and depression, you should use it with extreme caution. Consult your doctor before using this medicine, as it may unmask existing depression. Some studies have shown an increased risk of suicidal ideation, suicide attempt, and suicide in patients taking certain 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 additional medical advice.

Also, consult your doctor if you suffer from any of the following situations:

• depression or anxiety associated with depression (it could precipitate suicide in these patients),
• psychotic disorders,
• respiratory problems,
• liver diseases, the use of benzodiazepines can cause encephalopathy,
• history of alcohol or drug abuse, as it is not recommended to consume alcoholic beverages during treatment,
• kidney problems, dose reduction may be necessary,
• muscle weakness.

Using Tranxilium with other medicines

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

You should be especially careful with those medicines that act on the central nervous system, as these medicines can increase central depression and this could have consequences on your ability to drive or use machines.

You should be especially careful if you are being treated with the following medicines:

• alcohol: you should avoid medicines that contain alcohol, as the sedative effect can be enhanced, which can affect your ability to drive or use machines,
• hypnotics: medicines to induce sleep,
• anxiolytics/sedatives: medicines to treat anxiety,
• non-benzodiazepine tranquilizers,
• antidepressants: medicines to treat depression,
• antipsychotics: medicines for the treatment of psychoses,
• narcotic analgesics: medicines for the treatment of pain,
• antiepileptics: medicines to treat epilepsy,
• anesthetics,
• sedating antihistamines H1: medicines to treat allergies,
• morphine derivatives: used to treat pain and cough,
• barbiturates: medicines that produce sedation of the central nervous system,
• clonidine: a medicine that lowers blood pressure, and related substances,
• cisapride: a medicine to treat gastroesophageal reflux,
• clozapine: a medicine to treat psychoses,
• medicines that inhibit certain liver enzymes (cytochrome P450),
• opioid medicines: the use of Tranxilium at the same time as opioids (medicines used to relieve intense pain, such as morphine or codeine) can increase the risk of suffering sedation, respiratory depression, coma, and even death. Your doctor will decide if you can use them at the same time (see section "Warnings and precautions"),
• neuromuscular depressants such as muscle relaxants, curariform agents.

The risk of developing a withdrawal syndrome increases when Tranxilium is associated with benzodiazepines that have been prescribed as anxiolytics or hypnotics.

Using Tranxilium with food, drinks, and alcohol

You should avoid drinking alcohol while taking this medicine. See section "Using Tranxilium with other medicines: alcohol".

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

There is limited data on the use of Tranxilium in pregnant women. Therefore, it is not recommended to use this medicine during pregnancy and in women of childbearing age who do not use contraceptives.

If you discover that you are pregnant or are planning to have a baby, consult your doctor immediately to reassess the need for treatment.

If you take Tranxilium during the last three months of pregnancy or during childbirth at high doses, the newborn may experience drowsiness (sedation), respiratory problems (respiratory depression), muscle weakness (hypotonia), decreased body temperature (hypothermia), and difficulty feeding (problems with breastfeeding, resulting in low weight gain).

If you take it regularly at the end of pregnancy, your baby may experience withdrawal symptoms.

In this case, the newborn should be closely monitored during the postnatal period.

Breastfeeding

You should not take this medicine during breastfeeding, as it passes into breast milk.

Driving and using machines

Potassium clorazepate can alter your ability to drive or operate machinery, as it can cause drowsiness, reduce your attention, or reduce your reaction capacity. The appearance of these effects is more likely at the start of treatment or when the dose is increased. Do not drive or use machines if you experience any of these effects.

You should pay special attention to driving and using machines due to the risk of drowsiness, amnesia, altered concentration, and muscle function, associated with the use of this medicine. The combination with other medicines can enhance its sedative effect.

Additionally, insufficient sleep periods can increase the deterioration of the state of alertness (see section "Using Tranxilium with other medicines").

3. How to take Tranxilium

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

The duration of this treatment is limited. Your doctor will indicate the duration of your treatment with Tranxilium. Do not stop treatment before, nor interrupt it abruptly, in order to avoid the possibility of appearance of a withdrawal syndrome or rebound insomnia (see section "Warnings and precautions").

The route of administration of Tranxilium is oral.

• Adults: the usual dose ranges from 5 to 30 mg of potassium clorazepate per day, which means a maximum daily dose of 2 capsules (30 mg of potassium clorazepate).

It can be administered in divided doses or in a single dose, preferably before bedtime.

The presentation that best suits the prescribed dose can be used (Tranxilium 5 mg hard capsules, Tranxilium 10 mg hard capsules, Tranxilium 15 mg hard capsules).

• In elderly patients and in patients with liver problems (liver failure) and/or kidney problems (renal failure), it is recommended to reduce the dose: for example, half of the average dose may be sufficient.

If you take more Tranxilium than you should

Overdose is usually manifested by different degrees of central nervous system depression, ranging from drowsiness (feeling of sleep) to coma.

Deep sleep is the main sign of an overdose that can even become a coma, depending on the dose ingested.

In moderate cases, symptoms include drowsiness, confusion, and lethargy; in more severe cases, ataxia (loss of coordination of movements), hypotonia, hypotension (decrease in blood pressure), respiratory depression, rarely coma, and very rarely death.

The prognosis is positive, overdose does not represent a vital threat, at least in the absence of combination with other central depressants (psychotropic agents, alcohol) and as long as the subject is treated.

In case of overdose, the patient should be taken to a specialized center and the usual precautions should be taken: induction of vomiting, gastric lavage, and monitoring of respiratory and cardiovascular parameters. If there is no improvement with stomach emptying, activated charcoal will be administered to reduce absorption.

Flumazenil can be used for the diagnosis and/or treatment of overdose as an antidote.

If you have taken more Tranxilium than you should, consult your doctor, pharmacist, or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medicine and the amount taken.

If you forget to take Tranxilium

Do not take a double dose to make up for forgotten doses.

If you stop taking Tranxilium

Abrupt interruption of treatment can produce a withdrawal syndrome that manifests with headache or muscle pain, anxiety, muscle tension, restlessness, confusion, insomnia, and irritability (see section "Warnings and precautions").

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

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Adverse effects are presented grouped by organ and system classification and by frequency:

Very common: may affect more than 1 in 10 patients

Common: may affect up to 1 in 10 patients

Uncommon: may affect up to 1 in 100 patients

Rare: may affect up to 1 in 1,000 patients

Very rare: may affect up to 1 in 10,000 patients

Frequency not known: cannot be estimated from the available data.

Adverse effects are related to the dose and the individual patient's sensitivity.

Immune System Disorders:

• Uncommon: hypersensitivity reactions.

Psychiatric Disorders:

• Frequency not known: slow thinking, reduction of mental reflexes (bradypsychia).
• In some patients (particularly children and elderly patients), paradoxical reactions may be observed (see also the section "Warnings and Precautions"):

Uncommon: irritability, agitation, confusion.

Frequency not known: aggression, hallucination.

• Frequency not known: rebound syndrome with worsening of the anxiety that motivated this treatment may appear.
• Frequency not known: prolonged use (especially at high doses) may lead to the development of physical dependence, and withdrawal of treatment leads to withdrawal syndrome (see section "Warnings and Precautions"). This occurs more rapidly with short-half-life benzodiazepines than with long-half-life benzodiazepines (several days).

Nervous System Disorders:

• Very common: somnolence (particularly in elderly patients and especially during the day if used as a hypnotic).
• Common: dizziness.
• Uncommon: decreased muscle tone (muscular hypotonia).
• Frequency not known: cognitive disorders such as memory impairment (anterograde amnesia). Anterograde amnesia may develop when using therapeutic doses, with a higher risk when increasing the dose. Amnestic effects may be associated with inappropriate behavior (see section "Warnings and Precautions"), attention disturbance, and speech disorders.

Ocular Disorders:

• Frequency not known: double vision (diplopia).

Skin and Subcutaneous Tissue Disorders:

• Uncommon: pruritic and maculopapular rash.

General Disorders and Administration Site Conditions:

• Common: asthenia.
• Frequency not known: falls (see section "Warnings and Precautions").

Additionally, the following adverse effects have been reported with benzodiazepines: emotional bluntness, reduced alertness, headache, loss of movement coordination (ataxia), gastrointestinal disorders, changes in sexual appetite (changes in libido), and amnestic effects that may be associated with inappropriate behavior.

Psychiatric or paradoxical reactions with restlessness, delirium, rage, nightmares, psychosis, and inappropriate behavior and other adverse effects on behavior.

Depression: the use of benzodiazepines may unmask a pre-existing depression.

Dependence: administration of the product (even at therapeutic doses) may lead to the development of physical dependence: withdrawal of treatment may lead to the development of withdrawal or rebound phenomena (see section "Warnings and Precautions").

Psychological dependence may occur. Cases of benzodiazepine abuse have been reported.

Reporting of Adverse Effects

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

5. Storage of Tranxilium

Keep out of sight and reach of children.

Store below 30°C. Store in the original packaging to protect it from light and moisture.

Do not use Tranxilium after the expiration date stated on the packaging after CAD. The expiration date is the last day of the month indicated.

Medicines should not be disposed of via wastewater or household waste. Deposit the packaging and medicines you no longer need at the SIGRE Point in the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This way, you will help protect the environment.

6. Package Contents and Additional Information

Composition of Tranxilium 5 mg Hard Capsules

• The active ingredient is potassium clorazepate. Each capsule contains 5 mg of potassium clorazepate.
• The other ingredients are:

• potassium carbonate, talc
• capsule: erythrosine (E-127), titanium dioxide (E-171), gelatin.

Appearance of the Product and Package Contents

Pink and white capsules.

Each package contains 30 hard capsules.

Other Presentations:

• Tranxilium 10 mg hard capsules, package with 30 capsules.
• Tranxilium 15 mg hard capsules, package with 20 capsules.
• Tranxilium 50 mg film-coated tablets, package with 20 film-coated tablets.
• Tranxilium 20 mg powder and solvent for solution for injection, package with 1 vial and 1 ampoule.

Marketing Authorization Holder and Manufacturer

Holder:

Neuraxpharm Spain, S.L.U.

Avda. Barcelona, 69,

08970 Sant Joan Despí (Barcelona)

Spain

Manufacturer:

sanofi-aventis, S.A.

Crta. C35 La Batlloria a Hostalric, km. 63,09

Riells i Viabrea (Gerona)

Spain

Famar Italia S.p.A.

Via Zambeletti 25, Baranzate

20021, Italy

Date of the Last Revision of this Prospectus:

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/