TRANSENE

Patient Information Leaflet

Transene 5 mg hard capsules, 10 mg hard capsules

Potassium clorazepate
Please read all of this leaflet carefully before you take this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Transene is and what it is used for

Transene contains chlordiazepoxide dipotassium, which belongs to a class of medicines called benzodiazepines, used to reduce and treat certain disorders of the nervous system and mental health, including anxiety and distress states.
Transene is indicated for the treatment of:

• anxiety, a mental state characterized by a feeling of worry and fear, varying in intensity and duration;
• tension, a mental state characterized by intense worry and agitation;
• other physical and mental disorders associated with a psychological condition known as anxiety syndrome, characterized by intense and persistent fear, worry, and anguish, not due to a specific or apparent external cause or stimulus. Transene is indicated only when the disorder is severe, disabling, and causes significant distress.

2. What you need to know before taking Transene

Do not take Transene

• if you are allergic to potassium clorazepate or to any of the other ingredients of this medicine (listed in section 6);
• if you are allergic to other benzodiazepines or benzodiazepine-like substances;
• if you have a disease characterized by severe muscle weakness (myasthenia gravis);
• if you have severe breathing difficulties (severe respiratory insufficiency);
• if you have serious problems with liver function (severe hepatic insufficiency);
• if you suffer from episodes of breathing interruption or slowing during nighttime rest (sleep apnea syndrome);
• if you have increased pressure inside the eye (glaucoma);
• if you suffer from psychological conditions characterized by feelings of inadequacy and guilt, insecurity, discomfort in work, social, family, and interpersonal relationships, anger, and loss of interest (depressive neuroses);
• if you suffer from mental disorders characterized by loss of contact with reality, altered self-reflection and perception of personal experiences, impaired awareness, unrealistic and abstract thoughts, impaired judgment, and bizarre or disorganized behavior (psychotic reactions);
• if you are a child or adolescent under 18 years of age (see "Warnings and precautions").

Warnings and precautions
Talk to your doctor or pharmacist before taking Transene.
Psychiatric and paradoxical reactions
When using benzodiazepines and other benzodiazepine-like substances such as Transene, unusual reactions (paradoxical reactions) may occur, such as: restlessness, agitation, irritability, aggressiveness, delirium, rage attacks (anger), nightmares, seeing or hearing things that do not exist (hallucinations), severe mental disturbances affecting behavioral control and actions (psychosis), behavioral changes. If this happens to you, you must stop using Transene.
These reactions are more common in children and elderly patients.
Patients with kidney problems
If you suffer from kidney problems (renal insufficiency), your doctor will determine the appropriate dose for you.
Elderly or debilitated patients
If you are elderly or debilitated, your doctor will prescribe a lower initial dose and may gradually increase it later (see "How to take Transene"). Elderly patients have a higher risk of experiencing unwanted effects such as drowsiness, reduced alertness (sedation), dizziness, muscle weakness, which may lead to falls and consequently to serious injuries (see "Possible side effects"). If this occurs, a dose reduction is necessary.
Patients with respiratory problems
If you suffer from severe respiratory problems (respiratory insufficiency), you should take a lower dose because respiratory depression may occur, which could itself be the cause of anxiety and might require hospitalization. You must avoid concomitant use of Transene and sodium oxybate due to increased risk of respiratory depression (see "Other medicines and Transene").
Patients with liver problems
If you suffer from severe liver function impairment (severe hepatic insufficiency), you must not use Transene, as it may worsen brain damage (encephalopathy).
Suicidal tendencies and patients with depression or anxiety associated with depression
Some studies have shown an increased risk of suicidal thoughts, suicide attempts, and suicide in patients—whether or not they have depression—who were 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 further advice.
Transene must not be used alone to treat depression or anxiety associated with depression, as there is an increased risk of suicide.
Patients with history of alcohol or drug abuse
Transene must be used with particular caution if you have previously abused drugs or alcohol.
Patients affected by myasthenia
If you suffer from a disease characterized by severe muscle weakness (myasthenia), treatment with benzodiazepines and benzodiazepine-like agents may worsen your symptoms. You should use Transene only exceptionally and under close medical supervision.
Tolerance
After repeated use for several weeks, the effectiveness of Transene may decrease. This phenomenon is known as "tolerance."
Dependence
The use of benzodiazepines and benzodiazepine-like agents may lead to the development of severe physical disturbances when treatment is stopped (physical dependence) and a psychological desire not to discontinue taking the medicine (psychological dependence). The risk of dependence increases with higher doses, longer treatment duration, and concomitant use of other medicines (e.g., psychotropic medicines acting on psychological and mental activity; anxiolytics used to relieve and treat anxiety; hypnotics inducing sleep, including benzodiazepines). The risk is greater if you are or have previously been abusing medicines, drugs, or alcohol.
Once physical dependence has developed, abruptly stopping treatment may lead to withdrawal symptoms such as headache, muscle pain, extreme anxiety, tension, restlessness, confusion, irritability, and, in rare cases, tremors. In severe cases, the following symptoms may occur: perceiving the surrounding reality as vague, distant, and alien (derealization), feeling one's body as foreign and feeling like an external observer of one's own body and thoughts (depersonalization), hearing disorder characterized by discomfort from common sounds (hyperacusis), loss of sensation in part of the body (numbness), tingling and itching sensations in hands and feet (paresthesia), abnormal and exaggerated reaction (hypersensitivity) to light, noise, and physical contact, seeing and hearing things that do not exist (hallucinations), or epileptic seizures (convulsions).
Rebound insomnia and anxiety
When stopping treatment, you may develop a transient syndrome consisting of a return, in a more severe form, of the symptoms that led to treatment with the medicine. This may also be accompanied by other reactions such as mood changes, anxiety, restlessness, or sleep disturbances. This syndrome is more likely to occur if the medicine is stopped abruptly; therefore, treatment with Transene should be discontinued gradually.
Duration of treatment
The duration of treatment should be as short as possible (see "How to take Transene") and should not exceed 8–12 weeks, including the tapering-off phase. The treatment duration must not be prolonged without medical evaluation. However, in case of prolonged treatment, your doctor will periodically monitor your liver, kidney, and blood function (blood counts).
At the beginning of treatment, your doctor will explain that this treatment will be of limited duration and how you should gradually reduce the dose.
It is important that you are aware of the possible occurrence of the previously listed disorders: insomnia, rebound anxiety, and withdrawal. Do not switch this medicine—even to another benzodiazepine—without first consulting your doctor.
Memory disturbances
Benzodiazepines and benzodiazepine-like agents may cause memory disturbances (anterograde amnesia). This effect most often occurs several hours after taking the medicine. To reduce the risk, ensure you can sleep uninterrupted for 7–8 hours. (See "Possible side effects").
Children and adolescents
This medicine must not be used in children and adolescents under 18 years of age.
Other medicines and Transene
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
The effects of Transene may be influenced by or may influence the following medicines:

• medicines with central nervous system depressant effects (morphine derivatives such as buprenorphine [cough suppressants and painkillers], barbiturates, other benzodiazepines, neuroleptic antipsychotics, hypnotics, anxiolytics/sedatives, antidepressants, narcotic analgesics, antiepileptics, anesthetics, sedative antihistamines, clonidine, and similar substances): concomitant use of Transene with these medicines may increase the central nervous system depressant effect, with serious consequences especially for those who drive vehicles or operate machinery;
• highly effective painkillers (narcotic analgesics): increased euphoria may occur, which could lead to increased psychological dependence (desire not to discontinue taking the medicine);
• medicines used to achieve muscle relaxation (neuromuscular blockers, such as curare-like agents and muscle relaxants): may enhance the muscle-relaxing effect;
• other benzodiazepines used as anxiolytics (to reduce anxiety and distress) or hypnotics (to induce sleep): risk of developing withdrawal symptoms when treatment is abruptly stopped;
• medicines that inhibit the activity of specific substances in liver cells (liver enzymes, especially cytochrome P450): concomitant use of these medicines may increase the activity of Transene;
• cisapride (used to treat heartburn): increases the sedative effect of Transene. This may make driving and operating machinery dangerous;
• clozapine (used to treat mental illnesses): combining clozapine and Transene increases the risk of severe and sudden reduction in blood circulation (collapse) with respiratory and/or cardiac arrest;
• sodium oxybate (used to stabilize nighttime sleep and reduce daytime sleep attacks): concomitant use of Transene and sodium oxybate causes breathing problems, even severe ones. You must avoid concomitant use of Transene and sodium oxybate.

Concomitant use of Transene and opioids (strong analgesics, medicines for addiction therapy, and some cough medicines) increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and may be life-threatening. For this reason, concomitant use should be considered only when other treatment options are not feasible.
However, if your doctor prescribes Transene together with opioids, the dose and duration of concomitant treatment must be limited by your doctor.
Inform your doctor about all opioid medicines you are taking and carefully follow the doctor's dosage recommendations. It may be helpful to inform friends or family members to watch for the signs and symptoms listed above.
Contact your doctor if you experience such symptoms.
Transene and alcohol
Do not take Transene with alcohol.
The calming (sedative) effect may be increased if the medicine is taken with alcohol, negatively affecting your ability to drive or operate machinery.
Pregnancy, breastfeeding, and fertility
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
Do not use Transene during the first three months of pregnancy.
There are limited data on the use of Transene in pregnant women. Therefore, the use of this medicine is not recommended during pregnancy or in women of childbearing potential who are not using contraception.
If you discover you are pregnant or are planning to have a baby, consult your doctor immediately to reassess the need for treatment.
If you take Transene at high doses during the last three months of pregnancy or during childbirth, your baby may experience drowsiness (sedation), breathing problems (respiratory depression), muscle weakness (hypotonia), decreased body temperature (hypothermia), and feeding difficulties (breastfeeding problems leading to poor weight gain).
If taken regularly in the late stages of pregnancy, your baby may develop withdrawal symptoms. In such cases, the newborn must be closely monitored during the postnatal period.
Breastfeeding
Since Transene passes into breast milk, you must not take this medicine if you are breastfeeding.
Driving and operating machinery
Transene impairs your ability to drive vehicles and operate machinery because it may make you feel drowsy or confused and cause loss of concentration and muscle function.
Therefore, you must not drive or operate machinery until you know how this medicine affects you. Furthermore, if you have not had sufficient sleep, these effects may be intensified.
Concomitant use of other medicines and alcohol may excessively increase the calming effect (see "Other medicines and Transene").

3. How to take Transene

Take this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
This medicine is intended for use in adults only.
Treatment duration should be as short as possible. Your doctor will monitor you regularly and carefully assess the duration of treatment. Generally, total treatment duration should not exceed 8–12 weeks, including the gradual withdrawal phase.
In certain cases, it may be necessary to extend the maximum treatment period; in such cases, this must only be done after consulting your doctor.
Treatment should be initiated with the lowest recommended dose. Do not exceed the maximum dose.

Use in adults
The recommended dose is 10–30 mg daily, taken orally in 2–3 divided doses.

Use in the elderly
If you are elderly, your doctor will carefully determine the dose, possibly reducing the doses indicated above (see "Warnings and precautions").
Your doctor will monitor you regularly at the beginning of treatment to evaluate whether lower doses should be used, in order to prevent excessive intake (overdose) due to accumulation of the medicine in your body.

If you take more Transene than you should
In case of accidental ingestion/overdose of Transene, contact your doctor immediately or go to the nearest hospital.
Taking an excessive dose of this medicine usually results in central nervous system disturbances: from slowed mental function to loss of consciousness (coma). In mild cases, symptoms include drowsiness (obnubilation), confusion, and sleepiness (lethargy). In more severe cases, symptoms may include loss of coordination (ataxia), muscle weakness (hypotonia), low blood pressure (hypotension), respiratory depression, rarely coma, and very rarely death.

If you forget to take Transene
Do not take a double dose to make up for the missed dose.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Side effects depend on the dose taken and on your individual response to the medicine.

Very common side effects (may affect more than 1 in 10 people)

• drowsiness (particularly in elderly people)*

Common side effects (may affect up to 1 in 10 people)

• weakness/physical fatigue (asthenia)
• dizziness (vertigo)*

Uncommon side effects (may affect up to 1 in 100 people)

• allergic reactions (hypersensitivity)
• irritability
• agitation
• confusion*
• skin irritation with redness and swelling (maculopapular rash) and itching
• reduced muscle tone (muscular hypotonia)

Side effects with unknown frequency (frequency cannot be estimated from the available data)

• reduced emotional responsiveness (emotional blunting)*
• reduced attention*
• fatigue*
• headache*
• muscle weakness*
• loss of coordination of movements (ataxia)*
• double vision*
• stomach and intestinal disorders
• changes in sexual desire
• skin reactions
• dry mouth
• blurred vision
• changes in blood tests specific for monitoring liver and kidney function
• reduced number of red blood cells in the blood (reduced haematocrit)
• recurrence of the same symptoms that led to treatment with the medicine (rebound symptoms), including worsening of the anxiety that required treatment
• memory loss (anterograde amnesia), which may be associated with inappropriate behaviour (see "Warnings and precautions"). The risk increases with higher doses
• depression: a pre-existing, previously unrecognized depressive state may emerge
• unusual mental side effects (paradoxical reactions) such as: restlessness, agitation, irritability, aggression, delirium, rage attacks (anger), nightmares, seeing or hearing things that do not exist (hallucinations), severe mental disturbances affecting control of behaviour and actions (psychosis), changes in behaviour, slowing of mental functions. These side effects can be serious and are more frequent in children and elderly people
• severe physical disturbances when treatment is discontinued (physical dependence)
• physical dependence, withdrawal symptoms following discontinuation of treatment (see "Warnings and precautions")
• desire to continue taking the medicine (psychological dependence)
• excessive use (abuse) of this medicine and other benzodiazepines
• falls (see "Warnings and precautions")
• learning (cognitive) disorders such as: memory loss (anterograde amnesia), attention and language disturbances

*These side effects occur mainly at the beginning of treatment and usually disappear with subsequent doses.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Transene

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after "Exp.". The expiry
date refers to the last day of that month.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Transene 5 mg hard capsules contain

• The active substance is clorazepate dipotassium. Each capsule contains 5 mg of clorazepate dipotassium.
• The other components are potassium carbonate and talc.
• The capsule excipients are: erythrosine, titanium dioxide, gelatin.

What Transene 10 mg hard capsules contain

• The active substance is clorazepate dipotassium. Each capsule contains 10 mg of clorazepate dipotassium.
• The other components are potassium carbonate and talc.
• The capsule excipients are: erythrosine, titanium dioxide, gelatin.

Description of the appearance of Transene and package contents
Transene is available as hard capsules:

• Box containing 30 hard capsules of 5 mg in blister packs
• Box containing 30 hard capsules of 10 mg in blister packs

Marketing Authorization Holder
Neuraxpharm Italy S.p.A.
Via Piceno Aprutina, 47,
63100 - Ascoli Piceno (AP),
Italy
Manufacturer
SANOFI WINTHROP INDUSTRIES - 1, rue de la Vierge - 33440 AMBARES – FRANCE
SANOFI-AVENTIS S.A. – ctra. la Batlloria a Holstalric – 17404 Riells I Viabrea – Girona
SPAIN