Clonazepam Neuraxpharm 0.5 mg tablets EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Clonazepam Neuraxpharm 0.5 mg tablets EFG

Clonazepam

Read the entire leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to others, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Clonazepam Neuraxpharm is and what it is used for

Clonazepam Neuraxpharm contains the active substance clonazepam. Clonazepam belongs to the group of benzodiazepines and is used to treat seizure disorders (epilepsy).

Clonazepam Neuraxpharm is indicated as adjunctive therapy or when there is lack of response to other medications for the treatment of most types of epilepsy, especially absence seizures, including atypical absence seizures, myoclonic seizures, and atonic seizures.

In infantile spasms and tonic-clonic seizures, Clonazepam Neuraxpharm is indicated only as adjunctive therapy or when there is no response to other medications.

2. What you need to know before taking Clonazepam Neuraxpharm

Do not take Clonazepam Neuraxpharm

• if you are allergic to clonazepam, to other benzodiazepines, or to any of the other ingredients of this medicine listed in section 6;
• if you have a history of alcohol, drug, or medication dependence;
• in case of coma;
• in case of severe respiratory problems;
• in case of severe liver problems, as benzodiazepines may cause hepatic encephalopathy (a brain disorder originating from liver disease);
• if you are breastfeeding (see Pregnancy and breastfeeding).

Warnings and precautions

Talk to your doctor or pharmacist before taking this medicine.

During treatment with clonazepam, you may experience a certain loss of effectiveness.

Liver problems

• If you suffer from severe liver disease, you must not be treated with clonazepam (see Do not take Clonazepam Neuraxpharm). Benzodiazepines may trigger episodes of hepatic encephalopathy in cases of severe liver impairment. Special precautions must be taken when administering this medicine to patients with mild to moderate liver problems, and the lowest possible dose should be given (see section 3).

CNS, psychosis, and depression

• This medicine should only be used with special caution in patients with disorders affecting coordinated muscle group activity (cerebellar or spinocerebellar ataxia).
• Benzodiazepines are not recommended for the primary treatment of psychotic illness. Patients with a history of depression and/or suicide attempts must be closely monitored.
• In patients with depression or anxiety associated with depression, treatment with benzodiazepines may increase symptoms if the underlying condition is not adequately treated with appropriate medications (antidepressants).
• A small number of people treated with antiepileptic medicines such as clonazepam have had thoughts about self-harm or suicide. If you experience such thoughts at any time, contact your doctor immediately.

Myasthenia gravis

• Special care is required if you have myasthenia gravis (a chronic autoimmune neuromuscular disease causing muscle weakness).

Sleep apnea (a condition in which people experience respiratory failure while sleeping)

• If you suffer from sleep apnea (a sleep disorder in which breathing repeatedly stops and starts), benzodiazepines should not be used due to the potential additive effect on respiratory depression.

Sleep apnea appears to be more common in patients with epilepsy; therefore, the relationship between sleep apnea, the occurrence of epileptic seizures, and post-seizure oxygen deficiency should be considered when benzodiazepines are administered. These medicines also have a sedative effect and weaken respiration. For this reason, this medicine should only be prescribed if your doctor considers that the benefits outweigh the potential risks.

Porphyria

• This medicine should be used with caution in patients with porphyria, a disorder affecting hemoglobin formation.

History of alcohol, drug, or medication dependence

• If you have previously experienced problems with alcoholism, drug addiction, or medication dependence, because there is a risk of misuse of the medicine. Taking this medicine may lead to physical or psychological dependence. The risk of dependence increases with dose and duration of treatment; however, it exists even at the correct dose and with shorter treatment periods. This risk is increased if you have a history of alcohol, drug, or medication abuse. If treatment is stopped abruptly, physical dependence may develop and withdrawal symptoms may occur (see below).

Concomitant use of alcohol or central nervous system depressants

The concomitant use of this medicine with alcohol and/or central nervous system (CNS) depressants should be avoided, as this may enhance the effects of clonazepam and cause excessive sedation or anesthesia, as well as clinically relevant depression of cardiovascular and respiratory function, and may even lead to coma or death.

Psychiatric and "paradoxical" reactions

It is known that the use of benzodiazepines may cause hallucinations and opposite effects (so-called "paradoxical reactions" such as restlessness, agitation, irritability, aggressiveness, anxiety, delusions, rage, nightmares, hallucinations, psychosis, behavioral disturbances, and other behavioral disorders (see section 4). If this occurs, treatment with this medicine should be discontinued as directed by your doctor.

These paradoxical reactions are more common in children and elderly patients.

Memory disorders

This medicine may also cause temporary memory impairment (anterograde amnesia) at the prescribed dose. This means, for example, that activities performed after taking the medicine may not be remembered. These effects may be associated with inappropriate behavior. The risk of anterograde amnesia increases if higher doses are administered (see section 4).

Respiratory disorders

Taking clonazepam may cause flattening and slowing of breathing (respiratory depression) (see section 4). This may be more pronounced in individuals who already have breathing difficulties due to airway obstruction or in patients with brain damage, as well as when other respiratory depressant drugs are administered concomitantly.

Generally, this effect can be avoided by careful individual dose adjustment. If you have sleep apnea, persistent respiratory weakness, or pre-existing respiratory organ diseases (e.g., chronic obstructive pulmonary disease), your doctor should individually adjust the dose. The same applies if you are simultaneously treated with other centrally acting medicines or anticonvulsants (see also below, Other medicines and Clonazepam Neuraxpharm).

Epilepsy

If you have epilepsy, treatment with this medicine must never be stopped abruptly, as this could trigger epileptic status. If your doctor considers it necessary to reduce or discontinue the medicine, this should be done gradually. In such cases, combination with other antiepileptic medicines is indicated.

The dose of clonazepam must be carefully adjusted to the individual needs of patients receiving treatment with centrally acting medicines (acting on the brain) or anticonvulsants (antiepileptics) (see section 3).

Side effects on the nervous system and muscles (dizziness, drowsiness, slowed reaction time, reduced muscle tone, vertigo, impaired coordination of muscle groups, and muscle weakness, as well as fatigue and tiredness, which may occur relatively frequently [see section 4]) are generally temporary and usually disappear spontaneously or after dose reduction during treatment. Therefore, individual dose adjustment is necessary. These effects may be partially avoided if your doctor gradually increases the initial dose at the beginning of treatment.

Impairments in motor function may occur, such as slurred or slow speech, unsteady gait and movements, nystagmus (involuntary eye movement), and double vision (see section 4), especially during long-term treatment and with high doses.

An increase in seizure frequency may occur in certain forms of epilepsy during long-term treatment.

Discontinuation of treatment/withdrawal symptoms:

Withdrawal symptoms may occur, particularly when ending prolonged treatment, especially with high doses. Withdrawal symptoms may manifest as headaches, myalgia, anxiety or extreme tension, agitation, inner restlessness, sweating, tremors, sleep disturbances, confusion, and irritability.

In severe cases, the following symptoms may occur: cognitive disturbances related to oneself or the environment, increased sensitivity to sound (hyperacusis), hypersensitivity to light, noise, and physical contact, numbness, and tingling sensations in arms and legs, hallucinations, or epileptic seizures.

Even if the daily dose is abruptly reduced or short-term treatment with Clonazepam Neuraxpharm is suddenly stopped, temporary withdrawal symptoms such as anxiety, tension, and agitation may occur. Side effects may include mood changes, sleep disturbances, and restlessness. Therefore, it is recommended to discontinue treatment by gradually reducing the daily dose.

The risk of withdrawal symptoms increases when benzodiazepines are used together with sedatives during the day (cross-tolerance).

Elderly patients

Benzodiazepines appear to have a stronger effect in elderly individuals than in younger people, even at comparable blood levels. This may be due to age-related changes in the body and organs. Clonazepam should be used with caution in elderly or debilitated patients.

Children and adolescents

In infants and young children, this medicine may increase saliva production and bronchial secretions, so care must be taken to keep the airways clear.

Other medicines and Clonazepam Neuraxpharm

Inform your doctor or pharmacist if you are using, have recently used, or might need to use any other medicines.

Clonazepam may be taken simultaneously with one or more antiepileptic medicines. The likelihood of interaction with these other medicines is low (see section 2).

However, when another medicine is added to treatment, your response should be carefully monitored, as side effects such as drowsiness and lethargy may occur more frequently. In such cases, your doctor will adjust the dose of each medicine to achieve the maximum desired effect.

The concomitant use of this medicine with the following active substances may have effects:

• Medicines that increase the activity of certain liver enzymes (liver enzyme inducers), such as barbiturates, hydantoins, and antiepileptics like phenytoin, phenobarbital, carbamazepine, lamotrigine, and, to a lesser extent, valproate, may accelerate the breakdown of clonazepam and thus reduce the medicine's effectiveness.
• The concentration of phenytoin may be affected by this medicine (depending on dose and individual patient factors, unchanged, increased, or decreased phenytoin levels have been observed).
• Clonazepam may alter plasma concentrations of primidone (levels usually increase). Your doctor should monitor your blood levels of phenytoin or primidone if you are being treated with these active substances and clonazepam simultaneously.
• The combination of clonazepam with valproic acid may occasionally lead to the development of seizure states (of the petit mal type).

The concomitant use of this medicine with the following drugs may also enhance effects and cause excessive sedation or anesthesia, as well as clinically significant depression of cardiovascular and respiratory function:

• hypnotics, sedatives, analgesics, and anesthetics;
• medicines for the treatment of psychological and emotional disorders (antipsychotics, antidepressants, lithium preparations);
• medicines for the treatment of convulsive disorders (antiepileptics);
• certain allergy medicines (sedating antihistamines);
• anxiolytics.

To achieve the best possible effect, the dose should be individually adjusted if you are taking other medicines that affect the central nervous system.

Taking Clonazepam Neuraxpharm with alcohol

Alcohol must not be consumed if you are being treated for epilepsy with clonazepam, as it alters the medicine's effect, affects the success of your treatment, and/or may cause unpredictable side effects.

Pregnancy and breastfeeding

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

During pregnancy, this medicine should only be taken after a strict benefit-risk assessment by your doctor. If you plan to become pregnant during treatment with this medicine or suspect you are pregnant, inform your doctor as soon as possible so they can decide whether you should continue or discontinue treatment.

If treatment with clonazepam is essential during pregnancy, especially during the first three months, your doctor should prescribe clonazepam at the lowest effective dose to control seizures. If possible, combination treatment with other antiepileptics should be avoided.

It should be noted that pregnancy may worsen your epilepsy. Do not stop treatment with your medicine during pregnancy without consulting your doctor, as abruptly stopping treatment or uncontrolled dose reduction may cause epileptic seizures that could harm you or the fetus.

If you take a higher dose of your medicine before or during childbirth, or take it long-term during pregnancy, clonazepam may affect the condition and behavior of the fetus or newborn (including breathing and feeding difficulties, irregular heartbeat, reduced muscle tone, and decreased body temperature).

Do not take this medicine if you are breastfeeding, as small amounts of clonazepam pass into breast milk. Breastfeeding should be discontinued if clonazepam treatment is necessary.

Withdrawal symptoms in the newborn have occasionally been reported when the mother is treated with benzodiazepines.

Driving and use of machines

This medicine, even when used as directed, may impair reaction times to the extent that your ability to drive or operate machinery may be significantly affected. This effect is increased if combined with alcohol consumption. Therefore, you should completely avoid driving vehicles, operating machinery, or performing other hazardous activities, at least during the first few days of treatment.

Your doctor will make an individual decision, taking into account your individual response and the respective dose.

In general, patients with epilepsy should not drive vehicles. It should be noted that, even if your medicine dose is properly adjusted, any dose increase or change in administration time may affect your response capacity depending on your individual sensitivity.

Clonazepam Neuraxpharm contains lactose

If your doctor has informed you that you have an intolerance to certain sugars, consult them before taking this medicine.

3. How to take Clonazepam Neuraxpharm

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

The dose of Clonazepam Neuraxpharm must be individually adjusted for each patient, depending on age, response to the medication, and tolerability.

To avoid side effects at the beginning of treatment, it is important to start with a low initial dose, for example:

Infants and children (≤ 10 years or ≤ 30 kg body weight): 0.01 mg/kg/day to 0.05 mg/kg/day.

Children (≥ 10 years or > 30 kg body weight): 0.25 mg twice daily.

Adolescents (13 to 18 years) and adults: 0.5 mg twice daily.

The dose should be gradually increased until the required daily maintenance dose is reached.

The daily maintenance doses should be reached within 2 to 4 weeks of treatment.

Depending on age, the following maintenance dose guidelines may apply:

For infants and children up to 10 years or 30 kg body weight, the maintenance dose is 0.1 to 0.2 mg/kg/day.

	dose in mg
Children (10 years and older or > 30 kg body weight)	3 – 6
Adolescents (13 to 18 years) and adults	4 – 8

In the case of infants and children, another pharmaceutical form (oral solution) may be more appropriate.

Daily doses should be divided into 3 or 4 single doses taken throughout the day; if necessary, they may be increased.

The maximum recommended daily dose in adults is 20 mg.

Elderly patients

In elderly patients, the lowest possible dose should be used. Particular caution must be exercised in elderly individuals, especially during the initial dose-titration period.

Renal impairment

Studies on the safety and efficacy of clonazepam in patients with renal impairment have not been conducted; however, according to pharmacokinetic studies, dosage adjustment is not required in these patients.

Hepatic impairment

Patients with severe liver dysfunction should not be treated with this medicinal product (see section 2). Patients with mild to moderate hepatic impairment should be treated with the lowest possible dose.

Method of administration

Clonazepam Neuraxpharm is for oral use.

Take Clonazepam Neuraxpharm with plenty of liquid.

The 0.5 mg Clonazepam Neuraxpharm tablets may be divided into equal halves.

Duration of treatment

Antiepileptic treatment is usually long-term. Your doctor will advise you on the duration of treatment.

If you take more Clonazepam than you should

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service at telephone number 91 562 04 20, indicating the name of the medicine and the amount ingested.

Symptoms of overdose:

Benzodiazepines commonly cause dizziness, unsteadiness while walking, joint disorders, and ocular tremor. Overdoses are rarely fatal, but may cause loss of reflexes, apnea, hypotension, respiratory depression, circulatory failure, and loss of consciousness (coma). If coma occurs, it usually lasts only a few hours; however, it may be prolonged and periodic, especially in elderly patients. Seizures may occur more frequently. The respiratory depressant effect of benzodiazepines, such as that of your medicine, exacerbates pre-existing respiratory disorders and is therefore more serious in patients with respiratory diseases.

Benzodiazepines increase the effect of other centrally acting substances, including alcohol.

If you forget to take Clonazepam Neuraxpharm

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

If you stop taking Clonazepam Neuraxpharm

Abrupt interruption or discontinuation of treatment is not recommended; the dose should be gradually reduced.

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.

Very common (may affect up to 1 in 10 people)

• difficulty concentrating
• dizziness
• drowsiness
• prolonged reaction time
• decreased muscle tension
• disturbance in the coordinated activity of muscle groups
• involuntary eye movements
• muscle weakness (see section 2.)
• tiredness
• fatigue

Rare (may affect up to 1 in 1,000 people)

• reduced number of platelets
• headache
• nausea
• upper abdominal pain
• urinary incontinence
• urticaria
• itching
• rash
• temporary hair loss
• changes in skin pigmentation
• erectile dysfunction
• changes in libido

Very rare (may affect up to 1 in 10,000 people)

• generalized seizures
• severe immediate allergic reactions (anaphylaxis)

Frequency not known (cannot be estimated from available data)

• heart failure, including cardiac arrest
• reversible disorders such as slurred or slow speech, motor and gait instability, and eye tremor
• temporary memory lapses (anterograde amnesia, which may be associated with inappropriate behavior; see section 2 "Memory disorders")
• increased frequency of seizures in certain forms of epilepsy (see section 2)
• reversible visual disturbances (double vision)
• flattening and slowing of respiration (respiratory depression)
• falls and fractures (risk may increase when taking sedative medicines or alcohol concomitantly, or in elderly patients)
• allergic reactions
• emotional disturbances and mood changes, confusion, and disorientation have been observed
• "paradoxical" reactions such as restlessness, agitation, irritability, aggressiveness, nervousness, hostility, anxiety, sleep disturbances, delirium, rage, nightmares, abnormal dreams, hallucinations, psychosis, hyperkinesia (hyperactivity), inappropriate behavior, and other behavioral disorders

Clonazepam has a potential for primary dependence. Even if you have taken it daily for a few weeks, there is a risk of developing dependence (see section 2, "History of dependence on alcohol, drugs, or medicines").

For information on withdrawal effects or withdrawal symptoms, see section 2, "Discontinuation of treatment/withdrawal symptoms".

Other adverse effects in children:

• Respiratory disorders: Clonazepam Neuraxpharm may cause increased salivation or bronchial hypersecretion (increased fluid secretion in the bronchi) in infants and young children; therefore, special attention must be paid to maintaining clear airways (see section 2).
• Hormonal disorders: isolated cases of reversible premature development of sexual maturity in children have been reported.

Reporting of adverse effects

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

5. Storage of Clonazepam Neuraxpharm

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the month indicated.

Keep the blister pack in the outer packaging to protect it from light.

Medicines must not be disposed of via wastewater or household waste. Dispose of empty containers and unused medicines at the SIGRE collection point at your pharmacy. If you are unsure, ask your pharmacist how to properly dispose of containers and unused medicines. This will help protect the environment.

6. Contents of the pack and other information

Composition of Clonazepam Neuraxpharm

The active substance is clonazepam.

Each Clonazepam Neuraxpharm 0.5 mg tablet contains 0.5 mg of clonazepam.

The other components are: lactose, pregelatinized starch (corn), magnesium stearate, microcrystalline cellulose.

Appearance of the product and contents of the pack

Clonazepam Neuraxpharm 0.5 mg: round, flat-faced tablet with bevelled edges, marked with a "T" on one side and a score line on the other. The tablet can be divided into two equal parts.

Clonazepam Neuraxpharm is available in PVC/ALU blisters.

Clonazepam Neuraxpharm is presented in cardboard boxes containing 20, 30, 50, 60 or 100 tablets.

Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

Neuraxpharm Spain, S.L.U.

Avda. Barcelona, 69

Sant Joan Despí 08970 – Barcelona

Spain

Manufacturer:

Neuraxpharm Pharmaceuticals, S.L.

Avda. Barcelona, 69

Sant Joan Despí 08970 – Barcelona

Spain

or

Neuraxpharm Arzneimittel GmbH

Elisabeth-Selbert-Str. 23,

40764 Langenfeld

Germany

This medicinal product is authorized in the EEA Member States under the following names:

Germany Clonazepam neuraxpharm 0.5 mg, 1 mg, 2 mg tablets

Portugal Zepacla

Spain Clonazepam Neuraxpharm 0.5 mg, 1 mg, 2 mg tablets

Date of the most recent review of this leaflet: March 2021

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.es/