Package Insert: Information for the User

Tranxilium 50 mg Film-Coated Tablets

Potassium Chlorazepate

Tranxilium is a medication that belongs to the group of tranquilizers, anxiolytics, derived from benzodiazepines.

It is indicated in situations where anxiety or anguish reaches a psychiatric intensity, accompanied or not by psychomotor agitation (alteration of movement control):

• Anxiety neurosis (psychiatric disease that runs with anxiety).
• Phobic and obsessive neurosis (psychiatric diseases that run with anxiety).
• Anxious-depressive states.
• Anxiety in psychosis (severe mental disorder).
• Chronic alcoholism.
• Detoxification and dehabituation cures for ethanol or other drugs.
• Severe neurovegetative dystonias (alteration of vegetative nervous centers).

Before taking this medication, make sure you will be able to sleep uninterrupted for 7-8 hours.

If you wake up during the night after taking a hypnotic (sleep-inducing medication), you may experience a slow response to stimuli, which can increase the risk of falls and dizziness.

Do not take Tranxilium

• if you are allergic to the active ingredient (clorazepate dipotassium) or any of the other components of this medication (listed in section 6),
• if you are allergic to a group of medications called benzodiazepines,
• if you have myasthenia gravis (a muscle disorder characterized by abnormal muscle weakness),
• if you have severe liver dysfunction (severe liver damage),
• if you have severe respiratory insufficiency (difficulty breathing),
• if you have severe respiratory insufficiency (worsening of your usual difficulty breathing),
• if you have sleep apnea syndrome (a disorder characterized by episodes of suspended breathing during sleep),
• if you are to be administered to children: Tranxilium tablets 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 medication may lead to physical and psychological dependence. The risk of dependence increases with the dose, duration of treatment, combination with alcohol or certain medications (anxiolytics, hypnotics, psychotropics), or if you have a history of dependencies (to medications or other substances).

If physical dependence develops, abrupt discontinuation of treatment may produce a withdrawal syndrome characterized by headache or muscle pain, anxiety, muscle tension, restlessness, agitation, confusion, insomnia, and irritability. In severe cases, the following symptoms have been described: depersonalization, hyperacusia, paresthesia, intolerance to light, sound, and physical contact, tremor, 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 manner in which you should reduce the dose gradually until you stop treatment.

Tolerance may develop after prolonged use of this medication.

This medication may induce anterograde amnesia, especially if used before bedtime and when the duration of sleep is short. To minimize this risk, ensure that you will be able to sleep uninterrupted for 7-8 hours.

After discontinuation of treatment, rebound insomnia and anxiety may recur. This is a transient phenomenon that may be accompanied by mood changes, anxiety, restlessness, or sleep disorders. It is more likely to occur if treatment is discontinued abruptly, so it should be tapered gradually.

Older adults are more susceptible to adverse reactions such as somnolence, dizziness, muscle weakness, which may cause falls and severe injuries (see section “4. Possible adverse reactions”). In these cases, a dose reduction is recommended.

Psychiatric and paradoxical reactions such as restlessness, agitation, irritability, aggression, delirium, anger attacks, nightmares, hallucinations, psychosis, inappropriate behavior, and other adverse effects on behavior may occur. In this case, consult your doctor about discontinuing treatment. These reactions are more frequent in children and older adults.

Avoid using this medication in combination with oxibate sodium, as it may increase the risk of respiratory problems (respiratory depression).

Do not take Tranxilium with opioids (medications used to relieve intense pain, such as morphine or codeine) unless your doctor prescribes it, as it may increase the risk of sedation, respiratory depression, coma, or even death (see “Use of Tranxilium with other medications”).

If you have suicidal tendencies and depression, use with extreme caution. Consult your doctor before using this medication, as it may unmask an existing depression. Some studies have shown an increased risk of suicidal ideation, attempted suicide, and suicide in patients taking certain sedatives and hypnotics, including this medication. However, it has not been established whether this is caused by the medication 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 experience any of the following situations:

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

Use of Tranxilium with other medications

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

You must be especially careful with medications that act on the central nervous system, as they may increase central depression and this could affect your ability to drive or use machines.

You must be especially careful if you are being treated with the following medications:

• alcohol: avoid medications containing alcohol, as it may potentiate the sedative effect, which may affect your ability to drive or use machines,
• hypnotics: medications to induce sleep,
• anxiolytics/sedatives: medications to treat anxiety,
• non-benzodiazepine tranquilizers,
• antidepressants: medications to treat depression,
• antipsychotics: medications for the treatment of psychoses,
• narcotic analgesics: medications for pain relief,
• antiepileptics: medications to treat epilepsy,
• anesthetics,
• H1 antihistamines: medications to treat allergies,
• morphine derivatives: used to treat pain and cough,
• barbiturates: medications that produce sedation of the central nervous system,
• clonidine: medication that lowers blood pressure, and related substances,
• cisapride: medication to treat gastroesophageal reflux,
• clozapine: medication to treat psychoses,
• enzymes that inhibit certain hepatic enzymes (cytochrome P450),
• opioid medications: the use of Tranxilium with 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 together (see “Warnings and precautions”),
• neuromuscular blockers such as muscle relaxants, curarizants.

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

Use of Tranxilium with food, beverages, and alcohol

Avoid consuming alcohol while taking this medication. See section “Use of Tranxilium with other medications: alcohol”.

Pregnancy, lactation, and fertility

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor or pharmacist before using this medication.

Pregnancy

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

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

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

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.

Lactation

This medication should not be taken during lactation, as it passes into breast milk.

Driving and using machines

Clorazepate dipotassium may impair your ability to drive or use machines, 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 use machines if you experience any of these effects.

You should be especially careful when driving and using machines due to the risk of drowsiness, amnesia, alteration of concentration, and muscle function associated with the use of this medication. Combination with other medications may potentiate its sedative effect.

Additionally, periods of insufficient sleep may exacerbate the deterioration of alertness (see section “Use of Tranxilium with other medications”).

Tranxilium 50 mg tablets contain potassium

Patients with renal insufficiency or those on low-potassium diets should note that this medication contains 20.83 mg (0.53 mmol) of potassium per tablet.

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

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

The administration route of Tranxilium is oral.

• Adults:

• Outpatients: Half to 2 tablets (25 to 100 mg of clorazepate dipotassium) per day.
• Patients hospitalized, this dose can be significantly increased and even doubled.
• In extreme situations (overaggressive) and under control, it can reach up to 400 - 500 mg of clorazepate dipotassium per day, that is, a maximum daily dose of 10 Tranxilium 50 mg tablets. It is advisable to establish the treatment gradually increasing.

• Patients of advanced age and patients with liver (hepatic insufficiency) and/or kidney (renal insufficiency) problems, 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 usually manifests itself by different degrees of depression of the central nervous system, ranging from drowsiness (sensation of sleep) to coma.

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

In moderate cases, symptoms include drowsiness, confusion, and lethargy; in more serious 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, the overdose does not represent a vital threat, at least in the absence of combination with other central depressants (psychoactive agents, alcohol) and always provided the subject is treated.

In case of overdose, the patient should be transported to a specialized center and the usual precautions taken: induction of vomiting, gastric lavage, and monitoring of respiratory and cardiovascular parameters. If improvement does not occur with stomach emptying, activated charcoal should be administered to reduce absorption.

Flumazenil may 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 Toxicological Information Service, phone: 91 562 04 20, indicating the medication and the amount taken.

If you forget to take Tranxilium

Do not take a double dose to compensate for the missed doses.

If you interrupt treatment with Tranxilium

Abrupt discontinuation of treatment may produce withdrawal syndrome, which manifests as 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 medication, ask your doctor or pharmacist.

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

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

Very common:may affect more than1 in 10 patients

Common:may affect up to1 in 10 patients

Uncommon:may affect up to1 in 100 patients

Rare:may affect up to1 in 1,000 patients

Very rare:may affect up to1 in 10,000 patients

Unknown frequency: cannot be estimated from available data.

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

Immune system disorders:

• Uncommon: hypersensitivity reactions.

Mental disorders:

• Unknown frequency: slow thinking, reduced mental reflexes (bradypsychia).
• In some patients (particularly children and elderly patients) paradoxical reactions may be observed (see also the "Warnings and precautions" section):

Uncommon: irritability, agitation, confusion.

Unknown frequency: aggression, hallucination.

• Unknown frequency: rebound syndrome with worsening of the anxiety that motivated this treatment may appear.
• Unknown frequency: prolonged use (especially at high doses) may lead to physical dependence, and withdrawal symptoms may occur upon discontinuation of treatment (see the "Warnings and precautions" section). This occurs more rapidly with short-acting benzodiazepines than with long-acting benzodiazepines (several days).

Nervous system disorders:

• Very common: drowsiness (particularly in elderly patients and especially during the day if used as a hypnotic).

• Common: dizziness.
• Uncommon: muscle tone decrease (hypotonia).
• Unknown frequency: cognitive disorders such as memory alteration (anterograde amnesia). Anterograde amnesia may develop at therapeutic doses, with a higher risk at increased doses. Amnestic effects may be associated with inappropriate behavior (see the "Warnings and precautions" section), altered attention, and speech disorders.

Eye disorders:

• Unknown frequency: double vision (diplopia).

Skin and subcutaneous tissue disorders:

• Uncommon: pruritic skin rash, maculopapular rash.

General disorders and administration site conditions:

• Common: asthenia.
• Unknown frequency: falls (see the "Warnings and precautions" section).

In addition, the following side effects have been reported with benzodiazepines: emotional numbing, reduced alertness, headache, loss of coordination of movements (ataxia), gastrointestinal disturbances, changes in sexual appetite (changes in libido), and amnestic effects that may be associated with inappropriate behavior.

Psychiatric or paradoxical reactions with restlessness, delirium, anger attacks, nightmares, psychosis, and inappropriate behavior and other behavioral side effects.

Depression: the use of benzodiazepines may unmask an underlying depression.

Dependence: administration of the product (even at therapeutic doses) may lead to physical dependence: withdrawal symptoms may occur upon discontinuation of treatment (see the "Warnings and precautions" section).

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

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through theSpanish System for the 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.

Keep out of sight and reach of children.

Store below30°C. Store in the original packaging to protect it from light and humidity.

Do not use Tranxilium 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 medicines you no longer need at the SIGRE collection point of the pharmacy. If in doubt, ask your pharmacist how to dispose of packaging and medicines you no longer need. By doing so, you will help protect the environment.

Composition of Tranxilium 50 mg film-coated tablets

• The active ingredient is clorazepate dipotassium. Each tablet contains 50 mg of clorazepate dipotassium.
• The other components are:
• Core: potassium carbonate, mannitol, aluminium erythrosine lake (E127), magnesium stearate, talc.
• Coating: talc, hypromellose, diethyl phthalate, opaspray Pink K-1-1537.

Appearance of the product and content of the packaging

Pink film-coated tablets.

Each pack contains 20 film-coated tablets.

Other presentations:

• Tranxilium 5 mg hard capsules, pack with 30 capsules.
• Tranxilium 10 mg hard capsules, pack with 30 capsules.
• Tranxilium 15 mg hard capsules, pack with 20 capsules.
• Tranxilium 20 mg powder and solvent for injection solution, pack with 1 vial and 1 ampoule.

Holder of the marketing authorization and responsible for manufacturing

Holder:

Neuraxpharm Spain, S.L.U.

Avda. Barcelona, 69,

08970 Sant Joan Despí (Barcelona)

Spain

Responsible for manufacturing:

sanofi-aventis, S.A.

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

Riells i Viabrea (Gerona)

Spain

Last review date of this leaflet: September 2020

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