Package Insert: Information for the User

Tranxilium15 mg Hard Capsules

Potassium Chlorazepate

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

It is indicated in all manifestations of anxiety that may appear in everyday psychological disorders and whose intensity does not reach a psychiatric dimension:

• Anxiety states, isolated or associated with a disease (organic condition), with or without insomnia.
• Depressive states with an anxiety component, from restlessness to anguish.
• Behavior disorders due to anxiety: irritability and character disorders, hyperemotivity (reacting strongly to emotions) and affective conflicts.
• Sleep disorders: insomnia, nocturnal anxiety, awakening anxiety.
• Neurovegetative dystonias (alteration of various nervous centers) of diverse location and moderate intensity.
• Anxiety in older people (senile) and in seriously ill patients.
• Menopausal anxiety in women.
• Anxiety linked to the prescription of a surgical intervention.
• Post-traumatic syndrome (anxiety problems due to a past trauma).

General anxiety or anguish, isolated or associated with depressive states.

Before taking this medication, 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 (sleep-inducing medication), you may experience a slow response to stimuli, which can lead to 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 (increased difficulty breathing),
• if you have sleep apnea syndrome (a disorder characterized by episodes of suspended breathing during sleep),
• if you are a child: 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 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 dependence (on medications or other substances).

In case of physical dependence, abrupt discontinuation of treatment may cause 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, hyperacusis, paresthesia, intolerance to light, sound, 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 manner in which you should gradually reduce the dose until you stop treatment.

You may develop some tolerance 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 reduce this risk, ensure that you will be able to sleep uninterrupted for 7-8 hours.

After discontinuing treatment, rebound insomnia and anxiety may reappear. 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 gradually reduced.

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

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

You should avoid using this medication and oxibutate sodium together, as this may increase the risk of respiratory problems (respiratory depression).

Do not take Tranxilium at the same time as opioids (medications used to relieve intense pain, such as morphine or codeine) unless your doctor prescribes it, as this 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 are other reasons. If you have suicidal thoughts, contact your doctor as soon as possible for additional medical advice.

Also consult your doctor if you have any of the following situations:

• depression or anxiety associated with depression (suicide risk may be precipitated in these patients),
• psychotic disorders,
• respiratory problems,
• liver diseases, the use of benzodiazepines may cause encephalopathy,
• history of substance abuse, as it is not recommended to consume alcoholic beverages during treatment,
• kidney problems, a dose reduction may be necessary,
• 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 should be particularly careful with medications that act on the central nervous system, as these medications may increase central depression and this may have consequences for your ability to drive or use machines.

You should be particularly careful if you are being treated with the following medications:

• alcohol: avoid medications containing alcohol, as this may potentiate the sedative effect, which may affect your ability to drive or use machines,
• hypnotics: sleep-inducing medications,
• anxiolytics/sedatives: medications for anxiety,
• non-benzodiazepine tranquilizers,
• antidepressants: medications for depression,
• antipsychotics: medications for psychosis,
• narcotic analgesics: medications for pain relief,
• antiepileptic medications: medications for epilepsy,
• anesthetics,
• sedating H1 antihistamines: medications for allergies,
• morphine derivatives: used for pain relief and cough,
• barbiturates: medications that induce sedation of the central nervous system,
• clonidine: a medication that lowers blood pressure, and related substances,
• cisapride: a medication for gastroesophageal reflux,
• clozapine: a medication for psychosis,
• enzymes that inhibit certain liver 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, drinks, and alcohol

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

Pregnancy, breastfeeding, and fertility

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

Pregnancy

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

If you discover that 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 drowsiness (sedation), respiratory problems (respiratory depression), muscle weakness (hypotonia), decreased body temperature (hypothermia), and difficulty feeding (breastfeeding problems leading to poor 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.

Breastfeeding

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

Driving and using machines

Clorazepate dipotassium may affect 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 particularly 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. The combination with other medications may potentiate its sedative effect.

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

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 the treatment before, nor interrupt it abruptly, in order to avoid the possibility of the appearance of a withdrawal syndrome or rebound insomnia (see section “Warnings and precautions”).

The administration route of Tranxilium is oral.

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

It can be administered in fractional doses or in a single dose, preferably before going to bed.

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 (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 typically manifests itself by different degrees of depression of the central nervous system, ranging from somnolence (feeling 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 somnolence, 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 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 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 itself by 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

Frequency not known: cannot be estimated from available data.

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

Immune system disorders:

• Uncommon: hypersensitivity reactions.

Mental and behavioral 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 physical dependence, and withdrawal symptoms may occur upon discontinuation of treatment (see section “Warnings and precautions”). 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: decreased muscle tone (hypotonia).
• Frequency not known: 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 section “Warnings and precautions”), altered attention, and speech disorders.

Eye disorders:

• Frequency not known: double vision (diplopia).

Skin and subcutaneous tissue disorders:

• Uncommon: pruritic skin rash, maculopapular rash.

General disorders and administration site conditions:

• Common: asthenia.
• Frequency not known: falls (see section“Warnings and precautions”).

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 pre-existing depression.

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

Psychoactive 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 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. Deposit the containers and medicines you no longer need at the SIGRE collection point of the pharmacy. If in doubt, ask your pharmacist how to dispose of the containers and medicines you no longer need. In this way, you will help protect the environment.

Composition of Tranxilium 15 mg hard capsules

• The active ingredient is clorazepate dipotassium. Each capsule contains 15 mg of clorazepate dipotassium.
• The other components are:

- potassium carbonate, talc

- capsule: erythrosine (E-127), indigotin (E-132), iron oxide black (E-172), titanium dioxide (E-171), gelatin.

Appearance of the product and contents of the packaging

Blue and pink capsules.

Each package contains 20 hard capsules.

Other presentations:

• Tranxilium 5 mg hard capsules, package with 30 capsules.
• Tranxilium 10 mg hard capsules, package with 30 capsules.
• Tranxilium 50 mg film-coated tablets, package with 20 film-coated tablets.
• Tranxilium 20 mg powder and solvent for injection solution, package 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/