CLONAZEPAM NEURAXPHARM 2 mg TABLETS

Introduction

Package Leaflet: Information for the User

Clonazepam Neuraxpharm 2 mg Tablets EFG

Clonazepam

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

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

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

Clonazepam Neuraxpharm is indicated as adjunctive therapy or when other medications have failed to treat most types of epilepsy, especially absence seizures, including atypical absence seizures, myoclonic and astatic seizures.

In infantile spasms and tonic-clonic seizures, Clonazepam Neuraxpharm is indicated only as adjunctive therapy or when other medications have failed.

2. What you need to know before you take Clonazepam Neuraxpharm

Do not take Clonazepam Neuraxpharm

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

Warnings and precautions

Consult your doctor or pharmacist before starting to take this medicine.

During treatment with clonazepam, you may experience some loss of efficacy.

Liver problems

• If you have severe liver problems, you should not be treated with clonazepam (see Do not take Clonazepam Neuraxpharm). Benzodiazepines may be a causative factor for episodes of hepatic encephalopathy in the case of severe liver impairment. Special precautions should be taken when administering this medicine to patients with mild to moderate liver problems, so 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 of the interaction between muscle groups (cerebellar or spinocerebellar ataxia).
• Benzodiazepines are not recommended for the primary treatment of psychotic illness. Patients with a history of depression and/or suicidal attempts should be kept under close supervision.
• In patients with depression or anxiety associated with depression, treatment with benzodiazepines may increase symptoms if there is no adequate treatment of the underlying disease with appropriate medications (antidepressants).
• A small number of people who have been treated with antiepileptics such as clonazepam have had thoughts of self-harm or suicide. If you have these thoughts at any time, contact your doctor immediately.

Myasthenia gravis

• Special care should be taken if you have myasthenia gravis (a chronic autoimmune neuromuscular disease that causes muscle weakness).

Sleep apnea (a disease in which people suffer from respiratory failure while sleeping)

• If you have sleep apnea (a sleep disorder in which breathing stops and starts repeatedly), you should not use benzodiazepines due to the possible additional effect on respiratory depression.

Sleep apnea seems to be more frequent in patients with epilepsy; therefore, the relationship between sleep apnea, the occurrence of epileptic seizures, and lack of oxygen after a seizure when benzodiazepines are administered should be taken into account. They also have a sedative effect and weaken breathing. For this reason, this medicine should only be prescribed if your doctor expects the benefits to outweigh the possible risks.

Porphyria

• This medicine should be used with caution in patients with porphyria, a disease in which hemoglobin formation is altered.

History of dependence on alcohol, drugs, or medications

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

Concomitant use of alcohol or CNS depressant medications

The concomitant use of this medicine with alcohol and/or CNS depressants should be avoided, as it may increase the effects of clonazepam and cause excessive sedation or anesthesia, as well as a clinically significant depression of cardiovascular and respiratory function, and even lead to coma or death.

Psychiatric and "paradoxical" reactions

It is known that the use of benzodiazepines can cause hallucinations, as well as opposite effects (so-called "paradoxical reactions", such as restlessness, agitation, irritability, aggression, anxiety, delirium, anger, nightmares, hallucinations, psychosis, behavioral changes, and other disorders of conduct (see section 4)). If this occurs, treatment with this medicine should be discontinued according to the doctor's instructions.

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

Memory disorders

This medicine can also cause temporary memory failures (anterograde amnesia) at the prescribed dose. This means, for example, that activities performed after taking the medicine will 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

When taking clonazepam, a flattening and slowing of breathing (respiratory depression) may occur (see section 4). This may be more pronounced in people who already have difficulty breathing due to obstruction of the airways or in patients with brain damage, as well as when other respiratory depressant medications are administered concomitantly.

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

Epilepsy

If you have epilepsy, you should never stop treatment with this medicine abruptly, as this may cause the onset of an "epileptic status". If your doctor considers it necessary to reduce the dose or discontinue the medicine, it should be done gradually. In these cases, combination with other antiepileptics is indicated.

The dose of clonazepam should be carefully adjusted to the individual needs of patients receiving treatment with central-acting or anticonvulsant medications (see section 3).

The side effects on the nervous system and muscles (dizziness, drowsiness, slowing of reaction time, decrease in muscle tone, vertigo, disorders of the interaction between 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 reducing the dose during treatment. Therefore, it is necessary to adjust the doses individually. These effects can be partially avoided if the doctor gradually increases the initial dose at the start of treatment.

Disorders of regression capacity, such as slow or slurred speech, unstable movements and gait, ocular tremor, and double vision (see section 4), may occur, especially during long-term treatment and with high doses.

An increase in the frequency of seizures may occur in certain forms of epilepsy in the context of long-term treatment.

Discontinuation of treatment/withdrawal symptoms:

Withdrawal symptoms may appear, particularly when a prolonged treatment is terminated, especially with high doses. Withdrawal symptoms may manifest as headaches, myalgias, anxiety or extreme tension, excitement, inner restlessness, sweating, tremors, sleep disorders, confusion, and irritability.

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

Both when the daily dose is suddenly reduced or when treatment with Clonazepam Neuraxpharm is suddenly stopped, even after short-term treatment, temporary withdrawal symptoms such as anxiety and states of tension and agitation may appear. Side effects may include mood changes, sleep disorders, and restlessness. Therefore, it is recommended to end treatment with a gradual reduction of the daily dose.

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

Elderly patients

Benzodiazepines seem to have a more intense effect in elderly patients than in young patients, even with 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 cause an increase in saliva production and bronchial secretion, so care should be taken to keep the airways clear.

Other medications and Clonazepam Neuraxpharm

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

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

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

The concomitant use of the 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 efficacy of the medicine.
• The concentration of phenytoin may be affected by the medicine (depending on the dose and individual patient factors, unchanged, increased, or decreased phenytoin levels were detected).
• clonazepam may alter the plasma concentrations of primidone (usually increased). Your doctor should check your phenytoin or primidone blood levels if you are being treated with these active substances and clonazepam simultaneously.
• The combination of clonazepam with valproic acid may occasionally cause the development of convulsive states (of the petit mal type).

The concomitant use of the medicine with the following medications may also increase the effects and cause excessive sedation or anesthesia, as well as a 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 medicines for allergies (sedating antihistamines);
• anxiolytics.

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

Taking Clonazepam Neuraxpharm with alcohol

You should not consume alcohol if you are being treated for epilepsy with clonazepam, as it alters the effect of the medicine, 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 are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

During pregnancy, this medicine should only be taken after a rigorous benefit/risk assessment by your doctor. If you wish to become pregnant during treatment with this medicine or suspect that you are pregnant, inform your doctor as soon as possible, so that he/she can decide whether to continue or discontinue treatment.

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

It should be taken into account that pregnancy may worsen your epilepsy. Do not stop treatment with your medicine during pregnancy without consulting your doctor, as sudden discontinuation of treatment or uncontrolled reduction of the dose may cause epileptic seizures that can harm you or the fetus.

If you take a higher dose of your medicine before or during childbirth, as well as long-term intake during pregnancy, clonazepam may affect the state and behavior of the fetus or newborn (including breathing and feeding problems, irregular heartbeats, 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 it is necessary to take clonazepam.

Occasionally, symptoms of withdrawal have been reported in the newborn when the mother is treated with benzodiazepines.

Driving and using machines

This medicine, even when used as intended, may alter reaction times to the point where the ability to drive or use machinery is significantly impaired. This is increased if combined with alcohol consumption. Therefore, driving vehicles, operating machinery, or performing other hazardous activities should be completely avoided, at least during the first days of treatment.

Your doctor will decide individually, taking into account your individual reaction and the respective dose.

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

Clonazepam Neuraxpharm contains lactose

If your doctor has told you that you have an intolerance to some sugars, contact them before taking this medicine.

3. How to take Clonazepam Neuraxpharm

Follow the administration instructions for this medication exactly as indicated by your doctor. If in doubt, consult your doctor or pharmacist again.

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

To avoid side effects at the beginning of treatment, it is essential 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 a day

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

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

The daily maintenance doses should be achieved over 2 to 4 weeks of treatment.

Depending on age, the following guidelines can be applied for maintenance doses:

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.

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

The daily doses should be distributed in 3 or 4 single doses throughout the day;if necessary, they can be increased.

The maximum recommended dose in adults is 20 mg per day.

Elderly patients

In elderly patients, the lowest possible dose should be used. Special care should be taken if it is an elderly person, especially during the period of gradual dose increase.

Renal impairment

No studies have been conducted on the safety and efficacy of clonazepam in patients with renal impairment; however, according to pharmacokinetic studies, no dose adjustment is required in these patients.

Hepatic impairment

Patients with severe hepatic disorders should not be treated with this medication (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 2 mg tablets of Clonazepam Neuraxpharm can be divided into equal halves or quarters.

Duration of treatment

Epilepsy 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, Phone 91 562 04 20, indicating the medication and the amount ingested.

Overdose symptoms:

Benzodiazepines usually cause dizziness, instability when walking, joint disorders, and eye tremors. Overdoses are only fatal in very rare cases but can cause loss of reflexes, apnea, hypotension, respiratory depression, and circulatory failure, as well as loss of consciousness (coma). If coma occurs, it will only last a few hours; however, it can also be more prolonged and periodic, especially in elderly patients. Seizures can occur more frequently. The respiratory depressant effect of benzodiazepines, like your medication, exacerbates existing respiratory disorders and is therefore more severe in patients with respiratory diseases.

Benzodiazepines increase the effect of other central-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 treatment with Clonazepam Neuraxpharm

It is not recommended to interrupt or abruptly stop the medication; instead, the dose should be gradually reduced.

If you have any other doubts about the use of this medication, ask your doctor or pharmacist.

4. Possible side effects

Like all medications, this medication can cause side effects, although not everyone will experience them.

Very common (may affect 1 in 10 people)

• difficulty concentrating
• dizziness
• drowsiness
• prolonged reaction time
• decreased muscle tension
• alteration of the coordinated interaction of muscle groups
• involuntary eye movements
• muscle weakness (see section 2)
• fatigue
• weakness

Rare (may affect 1 in 1,000 people)

• reduction in platelet count
• headache
• nausea
• pain in the upper abdomen
• urinary incontinence
• hives
• itching
• rash
• temporary hair loss
• changes in skin color
• erectile dysfunction
• changes in libido

Very rare (may affect 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 slow or slurred speech, instability of movements and gait, eye tremors
• 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 breathing (respiratory depression)

• falls and fractures (the risk may increase when taking sedative medications or alcohol at the same time or if you are elderly)
• allergic reactions
• emotional and mood disorders, confusion, and disorientation have been observed
• "paradoxical" reactions such as restlessness, agitation, irritability, aggression, nervousness, hostility, anxiety, sleep disorders, delirium, anger, nightmares, abnormal dreams, hallucinations, psychosis, hyperkinesia (hyperactivity), inappropriate behavior, and other behavioral disorders

Clonazepam has a primary dependence potential. Although you may have taken it daily for several weeks, there is a risk of developing dependence (see section 2, "History of dependence on alcohol, drugs, or medications").

Regarding withdrawal effects or withdrawal symptoms, see section 2, "Discontinuation of treatment/withdrawal symptoms".

Other side effects in children:

• Respiratory disorders:Clonazepam Neuraxpharm may cause increased saliva production or hypersecretion of the bronchi in infants and young children, so it is essential to pay special attention to keeping the airways clear (see section 2).
• Hormonal disorders:individual cases of reversible premature development of sexual maturity in children have been reported.

Reporting side effects

If you experience side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Clonazepam Neuraxpharm

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date shown on the packaging. The expiration date is the last day of the month indicated.

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

Medications should not be disposed of through wastewater or household waste. Deposit the packaging and any unused medications at the SIGRE collection point in your pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and any unused medications. This will help protect the environment.

6. Package contents and additional information

Composition of Clonazepam Neuraxpharm

The active ingredient is clonazepam.

Each 2 mg tablet of Clonazepam Neuraxpharm contains 2 mg of clonazepam.

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

Appearance of the product and package contents

Clonazepam Neuraxpharm 2 mg: round, flat-faced tablet with a beveled edge, marked with "T2" on one side and a double score (in the form of a cross) on the other. The tablet can be divided into equal halves or quarters.

Clonazepam Neuraxpharm is available in PVC/ALU blisters.

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

Only some 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 medication is authorized in EEA member states with 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 last revision of this leaflet:March 2021

Detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.es/