Tranxene

Package Leaflet: Information for the Patient

Warning! The leaflet should be kept. Information on the immediate packaging in a foreign language.

TRANXENE, 5 mg, hard capsules

Dipotassium clorazepate

The patient should carefully read the contents of the leaflet before using the medicinal product, as it contains important information for the patient.

• The leaflet should be kept so that it can be re-read if necessary.
• In case of any doubts, the patient should consult a doctor or pharmacist.
• This medicinal product has been prescribed specifically for the patient. It should not be given to others. The medicinal product may harm another person, even if the symptoms of their illness are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should inform their doctor or pharmacist. See section 4.

Table of Contents of the Leaflet

• 1. What is Tranxene and what is it used for
• 2. Important information before using Tranxene
• 3. How to use Tranxene
• 4. Possible side effects
• 5. How to store Tranxene
• 6. Contents of the pack and other information

1. What is Tranxene and what is it used for

Tranxene is available in the form of hard capsules and contains the active substance clorazepate. Clorazepate belongs to a group of medicinal products called benzodiazepines. It has anxiolytic, muscle relaxant, sedative, hypnotic, and anticonvulsant effects. Tranxene is used:

• for short-term anxiety and anxiety disorders, especially as an adjunct in the treatment of neurosis,
• for alcohol withdrawal syndrome (alcoholic hallucinations, states preceding delirium tremens). Pharmacological treatment is indicated only in situations where symptoms are severe, disrupt normal functioning, or are bothersome to the patient.

2. Important information before using Tranxene

When not to use Tranxene:

• if the patient is hypersensitive to the active substance or any of the other ingredients of the medicinal product (listed in section 6),
• if the patient has severe respiratory failure,
• if the patient has sleep apnea syndrome,
• if the patient has myasthenia gravis (a disease characterized by rapid fatigue and muscle weakness),
• if the patient has severe liver failure,
• in children:
• 5 mg capsules should not be used in children under 9 years of age.

Warnings and precautions

Any treatment with benzodiazepines may lead to the development of psychological and physical dependence. Factors predisposing to the development of dependence include: duration of treatment, dose of the medicinal product, concomitant use of other psychoactive medicinal products, concomitant use of alcohol, dependence on other medicinal products or substances in the history. In case of dependence, withdrawal symptoms may occur after the end of treatment: insomnia, headaches, increased anxiety, muscle pain, increased muscle tension, and very rarely irritability, agitation, and even confusion. In exceptional cases, tremors, hallucinations, and seizures may occur. The duration of treatment should be as short as possible and should not exceed 4 to 12 weeks. The doctor will inform the patient how to end the therapy (gradual reduction of the dose of the medicinal product - over several days to several weeks). Ending treatment: sudden ending of clorazepate treatment may lead to the occurrence of withdrawal symptoms, especially in the case of long-term treatment, as well as suspected dependence on the medicinal product. During long-term use, tolerance to the medicinal product may occur. During treatment with the medicinal product, anterograde amnesia may occur, especially when benzodiazepines are used directly before going to sleep, and the duration of sleep is short (early awakenings caused by external factors). To minimize the risk of anterograde amnesia, it is recommended to ensure conditions for continuous, uninterrupted 7-8 hours of sleep. During the use of benzodiazepines, the following may occur: anxiety, agitation, irritability, aggression, delusions, anger, nightmares, hallucinations, psychoses, atypical behavior, and other behavioral disorders. These symptoms occur more frequently in children and elderly patients. If the above symptoms occur, the use of the medicinal product should be discontinued. Concomitant use of benzodiazepines and opioids may cause sedation, respiratory depression, coma, and death. Due to these risks, the doctor will prescribe opioids and benzodiazepines concomitantly only to patients for whom other treatment options are insufficient. If the decision is made to use clorazepate concomitantly with opioids, the medicinal products will be prescribed in the smallest effective dose and for the shortest possible duration of concomitant use. Some studies have shown an increased risk of suicidal thoughts, suicide attempts, and suicides in patients taking certain sedative and hypnotic medicinal products, including this medicinal product. However, it has not been established whether this is caused by the use of this medicinal product or if there are other causes. If the patient has suicidal thoughts, they should contact their doctor as soon as possible to receive further medical advice. Anxiolytic benzodiazepines should not be used to treat depression and mental disorders. Benzodiazepines may mask the symptoms of depression and should not be used as the only treatment for depression (antidepressants should be used). Treatment with benzodiazepines alone may increase suicidal tendencies. Benzodiazepines should be used with great caution in patients with a history of alcohol and other medicinal product dependence (including narcotics), as they are at risk of developing physical and psychological dependence. In elderly patients and patients with renal impairment, it may be necessary to adjust the dose of the medicinal product (see section 3. How to use Tranxene). In patients with liver function disorders, great caution should be exercised; in patients with liver failure, encephalopathy may occur. In patients with respiratory failure, the use of benzodiazepines may cause breathing problems (worsening of hypoxia may be the cause of anxiety and may require hospitalization in the intensive care unit). Concomitant use of several benzodiazepines is not beneficial and may increase the risk of dependence. Benzodiazepines are not recommended for use in patients with psychoses. Elderly patients are more sensitive to the occurrence of side effects, such as drowsiness, dizziness, muscle weakness, which may lead to falls and, consequently, to serious injuries. It is recommended to reduce the dose of the medicinal product.

Tranxene with food, drinks, and alcohol

Food does not affect the absorption of the medicinal product from the gastrointestinal tract. Tranxene can be taken during meals or on an empty stomach. During treatment with clorazepate, it is not recommended to consume alcoholic beverages.

Pregnancy, breastfeeding, and fertility

Data on the use of clorazepate in pregnant women are limited. Therefore, it is not recommended to use this medicinal product during pregnancy or in women of childbearing age who do not use contraception. If the patient is pregnant, suspects that she may be pregnant, or plans to have a child, she should consult her doctor to reassess the need for treatment. If the patient takes clorazepate in high doses during the last three months of pregnancy or during childbirth, the child may experience drowsiness (sedation), breathing problems (respiratory depression), muscle weakness (hypotonia), decreased body temperature (hypothermia), and feeding difficulties (problems with sucking, resulting in poor weight gain). If the patient regularly takes clorazepate at the end of pregnancy, the child may experience withdrawal syndrome. In such a case, the newborn should be closely monitored during the postpartum period. Tranxene should not be used during breastfeeding.

Driving and using machines

During treatment with the medicinal product, the patient should not drive vehicles or operate machines. The ability to drive vehicles and operate machines may be impaired during treatment with clorazepate due to the occurrence of concentration disorders, drowsiness, and anterograde amnesia. Concomitant use of other medicinal products may enhance the sedative effect of clorazepate (see section Tranxene and other medicinal products).

Tranxene and other medicinal products

The patient should inform their doctor about all medicinal products they are currently taking or have recently taken, as well as any medicinal products they plan to take, even those that are available without a prescription. The risk of withdrawal symptoms increases during concomitant use of other anxiolytic and hypnotic benzodiazepines. During treatment, the patient should avoid consuming alcohol and taking medicinal products containing alcohol. Alcohol enhances the sedative effect of benzodiazepines. The patient should exercise caution when using Tranxene concomitantly with:

• medicinal products with a depressant effect on the central nervous system, such as opioids, morphine derivatives, including buprenorphine (analgesics, antitussives, and medicinal products used in other therapies), neuroleptics, barbiturates, some antidepressants, antihistamines with a sedative effect, sedatives other than benzodiazepines, clonidine, and medicinal products with a similar effect;
• cisapride (a medicinal product that stimulates gastrointestinal motility) due to the possibility of increased sedative effect of benzodiazepines;
• clozapine (a neuroleptic medicinal product) due to the increased risk of respiratory and cardiac arrest;
• curare and its derivatives (medicinal products that reduce skeletal muscle tension) due to the additive effect.

Concomitant use of benzodiazepines and opioids increases the risk of sedation, respiratory depression, coma, and death due to the enhanced depressant effect on the central nervous system. The patient should avoid concomitant use of benzodiazepines and sodium oxybate due to the increased risk of respiratory depression. The patient should not use benzodiazepines and benzodiazepine-like medicinal products concomitantly.

3. How to use Tranxene

This medicinal product should always be used in accordance with the doctor's recommendations. In case of doubts, the patient should consult their doctor. Treatment should be started with an initial dose, gradually increasing the dose to avoid the occurrence of side effects. The maximum dose of 30 mg per day should not be exceeded. The duration of treatment should be as short as possible and should not exceed 8 to 12 weeks, including the period of dose reduction. During treatment, the patient should be regularly monitored to adjust the dose or frequency of administration of the medicinal product if necessary. Due to the possibility of withdrawal symptoms, the medicinal product should be discontinued cautiously, gradually reducing the daily dose. Adults: The therapeutic dose is 5 to 30 mg per day. Treatment is recommended to be started with a dose of 5 mg per day. The daily dose can be taken once a day, in the evening. Use in children and adolescents: Tranxene is not recommended for use in this age group due to limited data on its use in the treatment of anxiety. Only in exceptional cases, a specialist doctor may use this medicinal product in children over 9 years of age: at a dose of 0.5 mg/kg body weight per day in divided doses. For elderly patients: the dose should be reduced by 50%; treatment should be as short as possible. For patients with renal impairment: the dose of the medicinal product should be reduced by 50%. Patients with liver function disorders should exercise caution when using the medicinal product; in patients with liver failure, encephalopathy may occur. If the patient feels that the effect of Tranxene is too strong or too weak, they should consult their doctor.

Using a higher than recommended dose of Tranxene

The main symptom of severe overdose is deep sleep, which, depending on the dose of the medicinal product taken, may progress to coma. The prognosis is favorable if the patient has not taken other psychoactive medicinal products and receives appropriate treatment. The patient should be hospitalized in the intensive care unit, where their respiratory and cardiovascular systems will be monitored. If it has not been more than an hour since the medicinal product was taken and the patient is conscious, vomiting should be induced, and if the patient is unconscious, the doctor will perform gastric lavage, ensuring the protection of the upper airways. If more than an hour has passed since the overdose, activated charcoal can be administered to reduce the absorption of the medicinal product from the gastrointestinal tract. After a minor overdose, the following may occur: drowsiness, disorientation, lethargy; after a severe overdose: coordination disorders, decreased muscle tone, hypotension, breathing disorders, rarely coma, and very rarely death. The doctor may use flumazenil to diagnose and/or treat benzodiazepine overdose. In case of overdose, the patient should immediately consult their doctor.

Missing a dose of Tranxene

If the patient misses a dose, they should take it as soon as possible, unless it is almost time for the next dose. The patient should not take a double dose to make up for the missed dose. In case of doubts, the patient should consult their doctor.

4. Possible side effects

Like all medicinal products, Tranxene can cause side effects, although not everybody gets them. The frequency and severity of side effects depend on the individual sensitivity of the patient and the dose of the medicinal product used. The following side effects may occur:

Very common(may occur in more than 1 in 10 patients):

• drowsiness (especially in elderly patients)

Common(may occur in up to 1 in 10 patients):

• dizziness
• weakness

Uncommon(may occur in up to 1 in 100 patients):

• hypersensitivity reactions
• irritability, agitation, confusion
• decreased muscle tone
• maculopapular and pruritic skin rashes

Frequency not known(frequency cannot be estimated from the available data):

• slowing of mental processes
• paradoxical reactions (especially in children and elderly patients)
• aggression, hallucinations
• so-called rebound syndrome with more severe anxiety than that for which treatment was indicated
• physical dependence in case of long-term treatment (especially with high doses) and, after discontinuation of the medicinal product, withdrawal symptoms
• cognitive function disorders, such as memory impairment (anterograde amnesia), attention disorders, and speech disorders
• falls

Additionally, the following side effects have been reported during the use of benzodiazepines:

• emotional numbing, decreased alertness, headache,
• coordination disorders,
• double vision,
• gastrointestinal disorders,
• libido disorders,
• memory impairment (amnesia), which may be associated with atypical behavior.
• psychotic and paradoxical reactions with anxiety, delusions, anger, nightmares, hallucinations, psychoses, atypical behavior, and other behavioral disorders.

During the use of benzodiazepines, previously undiagnosed depression may become apparent. Psychic dependence may occur. Cases of benzodiazepine abuse have been reported.

Reporting side effects

If the patient experiences any side effects, including any side effects not listed in this leaflet, they should inform their doctor or pharmacist. Side effects can be reported directly to the Department of Pharmacovigilance of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, Tel: +48 22 49 21 301, Fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl. By reporting side effects, it is possible to gather more information on the safety of the medicinal product.

5. How to store Tranxene

The medicinal product should be stored out of sight and reach of children. There are no special recommendations for storage. The medicinal product should not be used after the expiration date stated on the packaging. The expiration date refers to the last day of the specified month. Medicinal products should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicinal products that are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

What Tranxene contains

Each hard capsule contains the active substance dipotassium clorazepate 5 mg and the excipients potassium carbonate, talc. The capsule shell contains gelatin, titanium dioxide, erythrosine.

What Tranxene looks like and contents of the pack

The pack contains 30 hard capsules. For more detailed information, the patient should contact the marketing authorization holder or the parallel importer.

Marketing authorization holder in Portugal, the country of export:

Sanofi – Produtos Farmacêuticos, Lda., Empreendimento Lagoas Park - Edifício 7, 3º piso, 2740-244 Porto Salvo, Portugal

Manufacturer:

Sanofi Aventis, S.A. (Riells), Carretera de la Batlloria a Hostalric, km. 63, 09, 17404 Riells i Viabrea, Girona, Spain

Parallel importer:

Delfarma Sp. z o.o., ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź

Repackaged by:

Polfarmex S.A., ul. Józefów 9, 99-300 Kutno, Delfarma Sp. z o.o., ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź

Marketing authorization number in Portugal, the country of export:

5842398, 8341867, 4507786

Parallel import authorization number: 30/15

Date of leaflet approval: 14.01.2025

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