Tranxilium 5 mg hard capsules

Patient Information Leaflet

Introduction

Patient Information Leaflet

Tranxilium 5 mg hard capsules

Potassium clorazepate

Contents of the 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. Storage of 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 for all manifestations of anxiety that may occur in everyday psychological disorders, provided their intensity does not reach a psychiatric level:

• States of anxiety, isolated or associated with an illness (organic condition), with or without insomnia.
• Depressive states accompanied by anxiety, ranging from restlessness to anguish.
• Behavioral disorders due to anxiety: irritability and personality disturbances, hyperemotionality (exaggerated emotional response), and affective conflicts.
• Sleep disorders: insomnia, nocturnal anxiety, and anxiety upon waking.
• Neurovegetative dystonias (dysfunction of autonomic nervous centers) of varying location and moderate intensity.
• Anxiety in elderly (senile) individuals and in severely ill patients.
• Anxiety in menopausal women.
• Anxiety related to the prescription of a surgical procedure.
• Post-traumatic stress syndrome (anxiety problems due to a past trauma).

In general, isolated anxiety or anguish, or associated with depressive states.

2. What you need to know before starting 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 delayed response to stimuli, increasing the risk of falls and dizziness.

Do not take Tranxilium

• if you are allergic to the active substance (dipotassium clorazepate) or to any of the other ingredients 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: the 5 mg capsules must not be administered to children under 30 months of age.

Warnings and precautions

Talk to your doctor or pharmacist before starting Tranxilium.

Using 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, psychotropic drugs), or if you have a history of dependency (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 such symptoms occur. Your doctor will advise you on the duration of your treatment (which should not exceed 4 to 12 weeks) and on how to gradually reduce the dose before stopping treatment.

Tolerance may develop with 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 that you can sleep uninterrupted for 7–8 hours.

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

Elderly individuals are more susceptible to adverse reactions such as drowsiness, dizziness, and muscle weakness, which may lead to falls and 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 adverse behavioral effects. In such cases, consult your doctor about discontinuing treatment. These reactions are more common in children and elderly patients.

Treatment duration in children should be as short as possible.

Avoid concomitant use of this medicine 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 it, 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 is not established whether this is caused by the medicine or if other factors may be involved. If you experience suicidal thoughts, contact your doctor immediately 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 alcohol consumption is not recommended during treatment,
• kidney problems, which may require dose reduction,
• 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 medicine.

Exercise particular caution with medicines that act on the central nervous system, as they may enhance central depression, potentially affecting your ability to drive or operate machinery.

Be especially careful 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 used to induce sleep,
• anxiolytics/sedatives: medicines used to treat anxiety,
• non-benzodiazepine tranquilizers,
• antidepressants: medicines used to treat depression,
• antipsychotics: medicines used to treat psychosis,
• narcotic analgesics: medicines used to treat pain,
• antiepileptics: medicines used to treat epilepsy,
• anesthetics,
• sedating H1 antihistamines: medicines used 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 used to treat gastroesophageal reflux,
• clozapine: a medicine used 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 you can use them 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 consumption 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 are planning 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 during pregnancy and in women of childbearing age who are not using contraception is not recommended.

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 Tranxilium during the last three months of pregnancy or during childbirth 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

Do not take this medicine while breastfeeding, as it passes into breast milk.

Driving and use of machines

Dipotassium clorazepate may impair your ability to drive or operate machinery, as it may cause drowsiness, reduced attention, or decreased reaction time. 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 operating machinery due to the risk of drowsiness, amnesia, impaired concentration, and impaired muscle function associated with this medicine. The combination with other medicines may enhance its sedative effect.

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

Tranxilium 5 mg capsules contain potassium

Patients with renal insufficiency or those on low-potassium diets should be aware that this medicine contains 6.6 mg (0.17 mmol) of potassium per capsule.

3. How to take Tranxilium

Follow exactly the instructions given by your doctor for taking this medicine. If in doubt, 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 or interrupt it abruptly, in order to avoid the possible occurrence of withdrawal syndrome or rebound insomnia (see section “Warnings and precautions”).

The route of administration of Tranxilium is oral.

• Adults: the usual dose ranges from 1 to 6 capsules (5 to 30 mg of clorazepate dipotassium) of Tranxilium 5 mg capsules per day, meaning a maximum daily dose of 6 capsules (30 mg of clorazepate dipotassium).

It may be administered in divided doses or as a single dose, preferably before going to bed.

The formulation best suited to the prescribed dose may 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, a reduced dose is recommended: for example, half the average dose may be sufficient.

• Paediatric population: use should only be recommended in exceptional cases. The duration of treatment should be as short as possible.

The 5 mg capsules must not be administered to children under 30 months of age.

If you take more Tranxilium than you should

Overdose is usually manifested by varying degrees of central nervous system depression, ranging from drowsiness (feeling sleepy) 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 (decreased blood pressure), respiratory depression, rarely coma, and very rarely death may occur.

The prognosis is favourable; 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 taken to a specialized centre 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 number: 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

Abruptly stopping 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 may cause adverse effects, although not everyone experiences them.

Adverse effects are grouped according to organ system classification and 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 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-medium half-life benzodiazepines than with long half-life 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 (muscle hypotonia).
• Frequency not known: cognitive disorders such as memory impairment (anterograde amnesia). Anterograde amnesia may occur with 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 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 motor coordination (ataxia), gastrointestinal disturbances, changes in sexual appetite (changes in libido), and amnesic effects that may be associated with inappropriate behaviors.

Paradoxical or psychiatric reactions including 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 it is a possible adverse effect 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 the 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 packaging after EXP. The expiry date is the last day of the month indicated.

Medicines should not be disposed of via wastewater or household waste. Dispose of unused medicines and their packaging at the SIGRE Point at your pharmacy. If in doubt, ask your pharmacist how to dispose of unused medicines and packaging. This will help protect the environment.

6. Contents of the pack and other information

Composition of Tranxilium 5 mg hard capsules

• The active substance is dipotassium clorazepate. Each capsule contains 5 mg of dipotassium clorazepate.

• The other components are:

• potassium carbonate, talc

• capsule: erythrosine (E-127), titanium dioxide (E-171), gelatin.

Appearance of the product and contents of the pack

Pink and white capsules.

Each pack contains 30 hard capsules.

Other presentations:

• Tranxilium 10 mg hard capsules, pack containing 30 hard capsules.
• Tranxilium 15 mg hard capsules, pack containing 20 hard capsules.
• Tranxilium 50 mg film-coated tablets, pack containing 20 film-coated tablets.
• Tranxilium 20 mg powder and solvent for solution for injection, pack containing 1 vial and 1 ampoule.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

Neuraxpharm Spain, S.L.U.

Avda. Barcelona, 69,

08970 Sant Joan Despí (Barcelona)

Spain

Manufacturer:

sanofi-aventis, S.A.

Crta. C35 La Batlloria to Hostalric, km. 63.09

Riells i Viabrea (Girona)

Spain

Famar Italia S.p.A.

Via Zambeletti 25, Baranzate

20021, Italy

Date of the most recent revision of this leaflet:

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