Tranxilium 50 mg film-coated tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Tranxilium 50 mg film-coated tablets

Clorazepate dipotassium

Package leaflet:

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

1. What Tranxilium is and what it is used for

Tranxilium is a medicine that belongs to the group of tranquilizers, anxiolytics, and benzodiazepine derivatives.

It is indicated in conditions where anxiety or distress reaches a psychiatric level of intensity, with or without psychomotor agitation (disturbance in motor control):

• Anxiety neurosis (a psychiatric disorder characterized by anxiety).
• Phobic and obsessive neuroses (psychiatric disorders characterized by anxiety).
• Anxious-depressive states.
• Anxiety in psychosis (severe mental disorder).
• Chronic alcoholism.
• Alcohol or other drug detoxification and rehabilitation treatments.
• Severe neurovegetative dystonias (disturbances of autonomic nervous centers).

2. What you need to know before taking Tranxilium

Before taking this medicine, you must ensure that you will be able to sleep uninterrupted for 7–8 hours.

If you get up during the night after taking a hypnotic (a medicine that induces sleep), you may experience a slow response to stimuli, increasing the risk of falls and dizziness.

Do not take Tranxilium

• if you are allergic to the active substance (clorazepate dipotassium) or to any of the other components of this medicine (listed in section 6),
• if you are allergic to a group of medicines called benzodiazepines,
• if you have myasthenia gravis (a muscle disorder characterized by abnormal weakness of voluntary muscles),
• if you have severe hepatic insufficiency (serious liver impairment),
• if you have severe respiratory insufficiency (difficulty breathing),
• if you have decompensated respiratory insufficiency (worsening of your usual breathing difficulty),
• if you have sleep apnea syndrome (a disorder characterized by episodes of breathing cessation during sleep),
• administration to children: Tranxilium tablets must not be administered to children.

Warnings and precautions

Talk to your doctor or pharmacist before taking Tranxilium.

The use of this type of medicine may lead to physical and psychological dependence. The risk of dependence increases with higher doses, longer treatment duration, concomitant use of alcohol or certain medicines (anxiolytics, hypnotics, psychotropics), or if you have a history of substance dependence (to medicines or other substances).

If physical dependence develops, abruptly stopping treatment may cause a withdrawal syndrome characterized by headache or muscle pain, marked anxiety, muscle tension, restlessness, agitation, confusion, insomnia, and irritability. In severe cases, the following symptoms have been reported: depersonalization, hyperacusis, tingling and cramps in the limbs, intolerance to light, sound, or physical contact, tremor, hallucinations, or seizures.

Consult your doctor or pharmacist if you experience any of these symptoms. Your doctor will advise you on the duration of treatment (which should not exceed 4 to 12 weeks) and the precise way in which the dose should be gradually reduced before stopping treatment.

Tolerance may develop after prolonged use of this medicine.

This medicine may cause anterograde amnesia, especially if taken at bedtime and when sleep duration is short. To reduce this risk, ensure you can sleep uninterrupted for 7–8 hours.

After stopping treatment, the symptoms that led to treatment may reappear (rebound insomnia and anxiety). This is a temporary phenomenon that may be accompanied by mood changes, anxiety, restlessness, or sleep disturbances. This is more likely to occur if treatment is stopped abruptly; therefore, treatment should be gradually tapered.

Elderly patients are more susceptible to adverse reactions such as drowsiness, dizziness, and muscle weakness, which may lead to falls and potentially serious injuries (see section “4. Possible side effects”). In such cases, dose reduction is recommended.

Psychiatric and paradoxical reactions may occur, such as restlessness, agitation, irritability, aggressiveness, delusions, rage attacks, nightmares, hallucinations, psychosis, inappropriate behavior, and other behavioral adverse effects. If this occurs, consult your doctor about discontinuing treatment. These reactions are more frequent in children and elderly patients.

You must avoid using this medicine together with sodium oxybate due to the risk of respiratory problems (respiratory depression).

Do not take Tranxilium together with opioids (medicines used to relieve severe pain, such as morphine or codeine) unless prescribed by your doctor, due to the possible risk of sedation, respiratory depression, coma, or even death (see “Use of Tranxilium with other medicines”).

If you have suicidal tendencies or depression, use this medicine with extreme caution. Consult your doctor before using this medicine, as it may unmask pre-existing depression. Some studies have shown an increased risk of suicidal thoughts, suicide attempts, and suicide in patients taking certain sedatives and hypnotics, including this medicine. However, it has not been established whether this is caused by the medicine or if other factors may be involved. If you have suicidal thoughts, contact your doctor as soon as possible for further medical advice.

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

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

Use of Tranxilium with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

Exercise special caution with medicines that act on the central nervous system, as they may increase central depression, which could affect your ability to drive or operate machinery.

Exercise particular caution if you are taking any of the following medicines:

• alcohol: avoid medicines containing alcohol, as the sedative effect may be enhanced, affecting your ability to drive or operate machinery,
• hypnotics: medicines to induce sleep,
• anxiolytics/sedatives: medicines to treat anxiety,
• non-benzodiazepine tranquilizers,
• antidepressants: medicines to treat depression,
• antipsychotics: medicines to treat psychosis,
• narcotic analgesics: medicines to treat pain,
• antiepileptics: medicines to treat epilepsy,
• anesthetics,
• sedating H1 antihistamines: medicines to treat allergies,
• morphine derivatives: used to treat pain and cough,
• barbiturates: medicines that cause central nervous system sedation,
• clonidine: a medicine that lowers blood pressure, and related substances,
• cisapride: a medicine to treat gastroesophageal reflux,
• clozapine: a medicine to treat psychosis,
• medicines that inhibit certain liver enzymes (cytochrome P450),
• opioid medicines: using Tranxilium together with opioids (medicines used to relieve severe pain, such as morphine or codeine) may increase the risk of sedation, respiratory depression, coma, and even death. Your doctor will decide whether they can be used together (see section “Warnings and precautions”),
• neuromuscular blockers such as muscle relaxants, curare-like agents.

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

Use of Tranxilium with food, drinks, and alcohol

Alcohol intake should be avoided while taking this medicine. See section “Use of Tranxilium with other medicines: alcohol”.

Pregnancy, breastfeeding, and fertility

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

Pregnancy

There is limited data on the use of Tranxilium 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 plan to have a baby, consult your doctor immediately to reassess the need for treatment.

If you take Tranxilium during the last three months of pregnancy or during labor at high doses, the newborn may experience drowsiness (sedation), breathing problems (respiratory depression), muscle weakness (hypotonia), decreased body temperature (hypothermia), and feeding difficulties (lactation problems leading to poor weight gain).

If taken regularly towards the end of pregnancy, your baby may experience withdrawal symptoms.

In such cases, the newborn should be closely monitored during the postnatal period.

Breastfeeding

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

Driving and using machines

Clorazepate dipotassium may impair your ability to drive or operate machinery, as it may cause drowsiness, reduced attention, or decreased reaction capacity. These effects are more likely at the beginning of treatment or when the dose is increased. Do not drive or operate machinery if you experience any of these effects.

Exercise particular caution when driving or using machines due to the risk of drowsiness, amnesia, impaired concentration, and impaired muscle function associated with the use of this medicine. The combination with other medicines may enhance its sedative effect.

In addition, insufficient sleep periods may further impair alertness (see section “Use of Tranxilium with other medicines”).

Tranxilium 50 mg tablets contain potassium

Patients with renal insufficiency or those on potassium-restricted diets should be aware that this medicine contains 20.83 mg (0.53 mmol) of potassium per tablet.

3. How to take Tranxilium

Follow exactly the instructions for use of this medicine given by your doctor. If in doubt, please consult your doctor or pharmacist again.

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

The route of administration of Tranxilium is oral.

• Adults:

• In outpatients: Half to 2 tablets (25 to 100 mg of clorazepate dipotassium) per day.

• In hospitalized patients, this dose may be considerably increased and may even be doubled.

• In extreme situations (over-acute cases) and under supervision, doses up to 400–500 mg of clorazepate dipotassium per day may be reached, i.e., a maximum daily dose of 10 tablets of Tranxilium 50 mg tablets. It is advisable to initiate treatment with gradually increasing doses.

• In elderly patients and in patients with liver problems (hepatic insufficiency) and/or kidney problems (renal insufficiency), dosage reduction is recommended: for example, half the average dose may be sufficient.

If you take more Tranxilium than you should

Overdose is usually manifested by varying degrees of central nervous system depression, ranging from drowsiness (sleepy feeling) to coma.

Deep sleep is the main sign of an overdose, which may even progress to coma, depending on the dose ingested.

In moderate cases, symptoms include drowsiness, confusion, and lethargy; in more severe cases, ataxia (loss of coordination of movements), hypotonia, hypotension (decrease in blood pressure), respiratory depression, and rarely coma, and very rarely death, may occur.

The prognosis is favorable; overdose does not represent a life-threatening condition, at least in the absence of combination with other central depressants (psychotropic agents, alcohol), provided the patient receives appropriate treatment.

In case of overdose, the patient should be transferred to a specialized center and standard precautionary measures taken: induction of vomiting, gastric lavage, and monitoring of respiratory and cardiovascular parameters. If no improvement occurs after gastric emptying, activated charcoal should be administered to reduce absorption.

Flumazenil may be used for diagnosis and/or treatment of overdose as an antidote.

If you have taken more Tranxilium than you should, contact your doctor, pharmacist, or call the Toxicology Information Service immediately at telephone: 91 562 04 20, indicating the medicine and the amount taken.

If you forget to take Tranxilium

Do not take a double dose to make up for forgotten doses.

If you stop taking Tranxilium

Abrupt discontinuation of treatment may cause withdrawal syndrome, manifested by headache or muscle pain, anxiety, muscle tension, restlessness, confusion, insomnia, and irritability (see section “Warnings and precautions”).

If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

Adverse effects are grouped according to organ systems and their frequency:

Very common: may affect more than 1 in 10 people
Common: may affect up to 1 in 10 people
Uncommon: may affect up to 1 in 100 people
Rare: may affect up to 1 in 1,000 people
Very rare: may affect up to 1 in 10,000 people
Frequency not known: cannot be estimated from the available data.

Adverse effects are related to dose and individual patient sensitivity.

Immune system disorders:

• Uncommon: hypersensitivity reactions.

Psychiatric disorders:

• Frequency not known: slowed thinking, reduced mental reflexes (bradypsychia).
• Paradoxical reactions may occur in some patients (particularly children and elderly patients) (see also section “Warnings and precautions”):

Uncommon: irritability, agitation, confusion.
Frequency not known: aggression, hallucination.

• Frequency not known: rebound syndrome may occur, with worsening of the anxiety that prompted this treatment.
• Frequency not known: prolonged use (especially at high doses) may lead to physical dependence, and discontinuation of treatment may result in withdrawal syndrome (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 (muscular hypotonia).

• Frequency not known: cognitive disturbances such as memory impairment (anterograde amnesia). Anterograde amnesia may develop when using therapeutic doses, with increased risk at higher doses. Amnesic effects may be associated with inappropriate behaviors (see section “Warnings and precautions”), attention disturbances, and speech disorders.

Eye disorders:

• Frequency not known: double vision (diplopia).

Skin and subcutaneous tissue disorders:

• Uncommon: itchy skin rash with spots and papules (pruritic maculopapular rash).

General disorders and administration site conditions:

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

Additionally, the following adverse effects have been reported with benzodiazepines: emotional blunting, reduced alertness, headache, loss of coordination of movements (ataxia), gastrointestinal disturbances, changes in sexual appetite (changes in libido), and amnesic effects which may be associated with inappropriate behaviors.

Psychiatric or paradoxical reactions such as restlessness, delirium, rage attacks, nightmares, psychosis, inappropriate behaviors, and other adverse behavioral 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; discontinuation of treatment may lead to withdrawal or rebound phenomena (see section “Warnings and precautions”).

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

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if they are possible adverse effects not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Tranxilium

Keep out of sight and reach of children.

Store below 30°C. Keep in the original packaging to protect from light and moisture.

Do not use Tranxilium after the expiry date stated on the container after EXP. The expiry date refers to the last day of the month indicated.

Medicines should not be disposed of via wastewater drains or household waste. Dispose of unused medicines and their containers at the SIGRE collection point at your pharmacy. If in doubt, ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Tranxilium 50 mg film-coated tablets

• The active substance 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 medicinal product and contents of the pack

Film-coated pink 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 injectable solution, pack with 1 vial and 1 ampoule.

Marketing Authorization Holder and Manufacturer

Holder:

Neuraxpharm Spain, S.L.U.

Avda. Barcelona, 69,

08970 Sant Joan Despí (Barcelona)

Spain

Manufacturer:

sanofi-aventis, S.A.

Ctra. C35 La Batlloria to Hostalric, km. 63.09

Riells i Viabrea (Girona)

Spain

Date of the most recent review of this leaflet: September 2020

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es/