Tranxene

Package leaflet: Information for the patient

Caution! Keep the leaflet. Information on the immediate packaging in a foreign language.
TRANXENE
10 mg, hard capsules
Chlorazepate dipotassium
Please read carefully all the information in this leaflet before taking the medicine, as it contains
important information for the patient.

• Keep this leaflet so that you can read it again if necessary.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any adverse reactions, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents of the leaflet

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

1. What Tranxene is and what it is used for

Tranxene is available in the form of capsules and contains the active substance chlordiazepoxide. Chlordiazepoxide
belongs to a group of medicines called benzodiazepines. It has anxiolytic, muscle relaxant, sedative, hypnotic, and anticonvulsant effects.
Tranxene is used:

• in short-term anxiety and nervousness, particularly as temporary supportive treatment in neurosis,
• in alcohol withdrawal syndrome (alcohol hallucinosis, states preceding delirium tremens). Pharmacological treatment is indicated only when symptoms are severe, interfere with normal functioning, or are distressing to the patient.

2. Important information before using Tranxene

When not to use Tranxene:

• if the patient is allergic to the active substance or to any of the other ingredients of the medicine (listed in section 6),
• if the patient has severe respiratory insufficiency,
• if the patient has sleep apnoea syndrome,
• if the patient suffers from myasthenia gravis (a disease characterised by rapid fatigue and muscle weakness),
• if the patient has severe hepatic insufficiency,
• in children: Tranxene 10 mg hard capsules must not be used in children.

Warnings and precautions
Any treatment with benzodiazepines may lead to the development of psychological and physical dependence. Factors predisposing to dependence include: duration of treatment, dose of the medicine, concomitant use of other medicines such as psychotropic agents, anxiolytics or hypnotics, concurrent alcohol consumption, and history of drug or substance abuse.
In case of dependence, withdrawal symptoms may occur after discontinuation of treatment: insomnia, headache, increased anxiety, muscle pain, increased muscle tension, 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 physician will inform the patient how to discontinue therapy (gradual dose reduction over several days to several weeks).
Discontinuation of treatment: abrupt discontinuation of treatment with clorazepate may lead to withdrawal symptoms, especially after prolonged treatment or when drug dependence is suspected.
With long-term use, tolerance to the drug may develop (reduced effectiveness of the drug).
Amnesia may occur during treatment, particularly when benzodiazepines are taken immediately before going to bed and sleep duration is short (early awakenings caused by external factors). To minimise the risk of amnesia, it is recommended to ensure conditions for continuous, uninterrupted sleep of 7–8 hours.
During treatment with benzodiazepines, the following may occur: anxiety, agitation, irritability, aggression, delusions, anger, nightmares, hallucinations, psychoses, unusual behaviour and other behavioural disturbances. These symptoms occur more frequently in children and elderly patients. If any of the above symptoms occur, the use of the medicine should be discontinued.
Concomitant use of benzodiazepines, including clorazepate, and opioids may result in sedation, respiratory depression, coma and death. Due to these risks, the physician will prescribe opioids and benzodiazepines together only to patients for whom other treatment options are insufficient.
If a decision is made to use clorazepate together with opioids, both medicines will be prescribed at the lowest effective dose and for the shortest possible duration of concomitant use.
Some studies have shown an increased risk of suicidal thoughts, suicide attempts and suicide in patients taking certain sedative and hypnotic medicines, including this medicine. However, it has not been established whether this is caused by taking this medicine or whether there are other causes. If the patient experiences suicidal thoughts, they should contact their doctor as soon as possible to obtain further medical advice.
Anxiolytic benzodiazepines should not be used to treat depression and psychiatric disorders.
Benzodiazepines may mask symptoms of depression and should not be used as the sole 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 or drug (including narcotics) dependence, as they are at increased risk of developing physical and psychological dependence.
In elderly patients and patients with renal insufficiency, dose adjustment of the medicine may be necessary (see section 3. How to use Tranxene).
In patients with hepatic dysfunction, benzodiazepines should be used with extreme caution; hepatic encephalopathy may occur in patients with liver insufficiency.
In patients with respiratory insufficiency, the use of benzodiazepines may cause breathing problems (worsening of hypoxia may lead to anxiety and may require admission to an intensive care unit).
Concomitant use of multiple benzodiazepines is not beneficial and may increase the risk of dependence.
Benzodiazepines are not recommended for use in patients with psychosis.
Elderly patients are more susceptible to adverse effects such as drowsiness, dizziness and muscle weakness, which may lead to falls and consequently to serious injuries. Dose reduction is recommended.

Tranxene with food, drink and alcohol
Food does not affect the absorption of the medicine from the gastrointestinal tract.
Tranxene may be taken during meals or on an empty stomach.
Alcoholic beverages should not be consumed during treatment with clorazepate.

Pregnancy, breastfeeding and fertility
Data on the use of clorazepate in pregnant women are limited. Therefore, the use of this medicine during pregnancy and in women of childbearing potential who are not using contraception is not recommended.
If the patient is pregnant, suspects she may be pregnant, or is planning to become pregnant, she should consult her doctor to reassess the need for treatment.
If the patient takes high doses of clorazepate during the last three months of pregnancy or during delivery, the newborn may experience drowsiness (sedation), breathing problems (respiratory depression), muscle weakness (hypotonia), low body temperature (hypothermia) and feeding difficulties (sucking problems leading to poor weight gain).
If the patient regularly takes clorazepate towards the end of pregnancy, the newborn may develop withdrawal syndrome. In such cases, the newborn should be closely monitored during the postnatal period.
Tranxene should not be used during breastfeeding.

Driving and operating machinery
Patients should not drive or operate machinery while taking this medicine. The ability to drive and operate machinery may be impaired during treatment with clorazepate due to disturbances in concentration, drowsiness and anterograde amnesia. Concomitant use of other medicines may intensify the sedative effect of clorazepate (see section Tranxene with other medicines).

Tranxene with other medicines
Inform your doctor about all medicines currently or recently taken, including those available without a prescription, as well as any medicines the patient plans to take.
The risk of withdrawal symptoms increases with concomitant use of other anxiolytic and hypnotic benzodiazepines.
Alcohol consumption and use of medicines containing alcohol should be avoided during treatment. Alcohol enhances the sedative effect of benzodiazepines.
Caution is advised when using Tranxene concomitantly with:

• medicines with central nervous system depressant effects, such as: opioids, morphine derivatives including buprenorphine (analgesics, antitussives and those used in other therapies), neuroleptics, barbiturates, certain antidepressants, sedating antihistamines (antiallergic medicines), non-benzodiazepine sedatives, clonidine and medicines with similar effects;

• cisapride (a medicine stimulating gastrointestinal motility) due to the possibility of enhanced sedative effects of benzodiazepines;

• clozapine (a neuroleptic medicine) due to increased risk of collapse with respiratory and/or cardiac arrest;

• curare and its derivatives (medicines reducing skeletal muscle tension) due to additive effects.

Concomitant use of benzodiazepines and opioids increases the risk of sedation, respiratory depression, coma and death due to enhanced central nervous system depression.
Concomitant use of benzodiazepines and sodium oxybate should be avoided due to increased risk of respiratory depression.

3. How to use Tranxene

This medicine should always be taken as prescribed by the doctor. In case of doubt, consult the doctor.
Tranxene is available in 5 mg and 10 mg doses.
Treatment should begin with an initial dose, gradually increasing the dose to avoid unwanted 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 tapering-off period. During treatment, the patient should be monitored regularly so that the dose or frequency of administration may be reduced if necessary. Due to the risk of withdrawal symptoms, the medicine should be discontinued cautiously, gradually reducing the daily dose.

Adults:
The therapeutic dose ranges from 5 to 30 mg per day.
Treatment should be initiated at a dose of 5 mg per day.
The daily dose may be taken once daily, in the evening.

Use in children and adolescents:
Tranxene 10 mg is intended for use in adults only.
Elderly patients should receive a 50% lower dose; treatment should be as short as possible.
Patients with impaired kidney function should receive a 50% lower dose.
Patients with impaired liver function must exercise caution when using this medicine; hepatic encephalopathy (neurological dysfunction due to toxins accumulating in the body as a result of liver damage) may occur in patients with liver insufficiency.
If the effect of Tranxene seems too strong or too weak, consult the doctor.

Taking more Tranxene than prescribed
The main symptom of severe overdose is deep sleep, which may progress to coma depending on the amount ingested.
The prognosis is favorable if the patient has not taken other psychotropic drugs simultaneously and receives appropriate treatment.
The patient should be admitted to a hospital intensive care unit where respiratory and cardiovascular functions will be monitored.
If less than one hour has passed since ingestion and the patient is conscious, vomiting should be induced. If the patient is unconscious, the doctor should perform gastric lavage, remembering to secure the upper airways. If more than one hour has passed since overdose, activated charcoal may be administered to reduce drug absorption from the gastrointestinal tract.
After a mild overdose, symptoms include drowsiness, disorientation, and lethargy; after a more severe overdose: impaired body coordination, reduced muscle tone, hypotension, respiratory disturbances, rarely coma, and very rarely death.
The doctor may administer flumazenil to diagnose and/or treat benzodiazepine overdose.
In case of overdose, seek immediate medical help.

Missed dose of Tranxene
If a dose is missed, take it as soon as possible unless the next dose is due soon. Do not take a double dose to make up for a missed dose. In case of doubt, consult the doctor.

4. Possible adverse reactions

Like any medicine, Tranxene may cause adverse reactions, although not everyone experiences them.
The frequency and severity of adverse reactions depend on the individual patient's sensitivity and the dose administered.

The following adverse reactions 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, restlessness, confusion
• decreased muscle tone
• maculopapular and itchy skin rashes

Frequency unknown (cannot be estimated from available data):

• slowing of mental processes
• paradoxical reactions (especially in children and elderly patients)
• aggression, hallucinations
• so-called rebound syndrome with increased anxiety compared to the condition that led to treatment
• physical dependence with long-term treatment (especially at high doses), and withdrawal symptoms after discontinuation of the medicine*
• cognitive disturbances such as memory impairment (anterograde amnesia*), attention disorders, and speech disturbances
• falls*
  * see section: "Warnings and precautions"

Additionally, the following adverse reactions have been reported during benzodiazepine use:

• emotional blunting, reduced alertness, headache,
• impaired coordination of body movements,
• double vision,
• gastrointestinal disturbances,
• decreased libido,
• occurrence of memory loss (amnesia), which may be associated with abnormal behaviour,
• psychiatric and paradoxical reactions with anxiety, delusions, rage attacks, nightmares, psychoses, unusual behaviour, and other behavioural disturbances.

Benzodiazepine use may unmask previously existing, undiagnosed depression.
Psychological dependence may occur. Cases of benzodiazepine abuse have been reported.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C, 02-222 Warsaw, Phone: +48 22 49 21 301, Fax: +48 22 49 21 309,
website: https://smz.ezdrowie.gov.pl
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store the medicine Tranxene

Keep this medicine out of sight and reach of children.
No special storage instructions apply.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the packaging and other information

What Tranxene contains
Each hard capsule contains the active substance dipotassium clorazepate (10 mg) and the following excipients: potassium carbonate, talc.
Capsule shell:
Body: gelatin, titanium dioxide (E 171), erythrosine (E 127).
Cap: gelatin, titanium dioxide (E 171), erythrosine (E 127).
What Tranxene looks like and contents of the pack
The pack contains 30 hard capsules.
The capsule is opaque, with a light pink cap and body, having a smooth, glossy surface, containing a homogeneous powder which is white or yellowish in colour.
For further information, please contact the marketing authorisation holder or the parallel importer.
Marketing Authorisation Holder in Portugal, country of export:
Neuraxpharm Portugal, Unipessoal Lda.
Avenida Dom João II, nº 35
Edifício Infante, 6º I
1990-083 Lisbon
Portugal
Manufacturer:
Sanofi Aventis, S.A.
Carretera de la Batlloria a Hostalric km. 63, 09
17404 Riells i Viabrea Gerona
Spain
Parallel Importer:
Delfarma Sp. z o.o., ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź
Relabelled and/or repackaged in:
Delfarma Sp. z o.o., ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź
Portugal, country of export, MA number: 5842497
Parallel Import Licence Number: 252/18