RIVOTRIL 1 mg/ml CONCENTRATE AND SOLVENT FOR INJECTABLE SOLUTION

Introduction

Leaflet:informationfor the user

Rivotril 1 mg/ml concentrate and solvent for injectable solution

clonazepam

Read the entire leaflet carefully before starting to use this medication, as it contains important information for you.

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

Contents of the leaflet:

1. What is Rivotril and what is it used for
2. What you need to know before starting to use Rivotril
3. How to use Rivotril
4. Possible side effects

5 Storage of Rivotril

1. Package contents and additional information

1. What is Rivotril and what is it used for

Rivotril contains clonazepam as an active ingredient, which belongs to a group of medications known as benzodiazepines. Clonazepam has anticonvulsant properties, i.e., it prevents tremors (seizures).

It is used in most forms of infant and child epilepsy, especially petit mal and tonic-clonic seizures.

It is also indicated in adult epilepsy, in focal seizures, and in status epilepticus.

2. What you need to know before starting to use Rivotril

Do not use Rivotril

• if you are allergic (hypersensitive) to the active substance or to any of the other components of this medication (listed in section 6)
• if you are allergic (hypersensitive) to other medications in the benzodiazepine group
• if you have severe and persistent respiratory difficulties (shortness of breath), severe liver failure (the liver cannot perform its functions), or if you have drug or alcohol dependence problems, unless it has been strictly indicated by your doctor

If you are unsure about these aspects, consult your doctor.

Children

Rivotril should not be used in neonates, especially in premature babies.

Warnings and precautions

Consult your doctor or pharmacist before starting to use Rivotril.

A loss of effect may occur during treatment with Rivotril.

Rivotril should be used with special caution in the following situations:

• if you have liver or kidney disease,
• if you are elderly, suffer from muscle weakness, sleep apnea, or have respiratory difficulties (shortness of breath),
• if you have allergies,
• if you have porphyria (a disease that can affect the nervous system and make the skin very sensitive to the sun),
• if you have other diseases,
• if you are taking other medications, especially medications for epilepsy, sleep aids (hypnotics), pain medications (analgesics), medications for mental illnesses (neuroleptics), medications for depression (antidepressants), or lithium,
• if you have drug or alcohol dependence problems,
• if you have had depression and/or attempted suicide,
• if you have ataxia (lack of coordination of voluntary movements).

A small number of people who were being treated with antiepileptics like Rivotril have had thoughts of self-harm or suicide. If you have these thoughts at any time, contact your doctor immediately.

Before starting treatment with Rivotril, your doctor will decide if you can take a lower dose or not take it at all.

Taking Rivotril with other medications

Tell your doctor or pharmacist that you are using, have recently used, or may need to use any other medication. This is very important, as the use of several medications at the same time can increase or decrease their effect.

For example, tranquilizers, sleep aids, and other medications that affect the central nervous system can increase the effect of Rivotril.

Therefore, you should not take Rivotril with other medications without consulting your doctor. When your doctor authorizes it, you can start taking it.

Your doctor may prescribe Rivotril along with other medications for epilepsy, in which case your doctor will adjust the dose of each medication to achieve the desired effect.

Taking Rivotril with alcohol

You should avoid drinking alcohol during treatment with Rivotril, as it can modify its effects, reducing the effectiveness of the treatment or producing unforeseen side effects.

Risk of dependence

The use of benzodiazepines can lead to dependence, mainly when the medication is taken continuously for a long time. To minimize this risk, the following precautions should be taken:

• The use of benzodiazepines will only be done under medical prescription (never because they have worked for other patients) and never advise them to other people.
• Do not increase the prescribed doses in any way, nor prolong the treatment for longer than recommended.
• Consult your doctor regularly so that they can decide if treatment should be continued.

Pregnancy and breastfeeding

Consult your doctor or pharmacist if you are pregnant or breastfeeding. This is because large amounts of benzyl alcohol can accumulate in your body and cause side effects (metabolic acidosis). (See information included in the warning about excipients)

Driving and using machines

Rivotril acts on the central nervous system and can produce: drowsiness, dizziness, visual disturbances, and decreased reaction capacity. These effects, as well as the disease itself, make it advisable to be cautious when driving vehicles or operating hazardous machinery, especially while the patient's particular sensitivity to the medication has not been established.

Rivotril contains ethanol, benzyl alcohol, and propylene glycol

Ask your doctor or pharmacist for advice if your child is under 5 years old, if you have liver or kidney disease, or if you are pregnant or breastfeeding. This is because the excipients can cause side effects. Your doctor may need to adjust the dose if you or your child are using other medications that contain benzyl alcohol, propylene glycol, or alcohol.

Warnings about excipients:

Rivotril contains 15.9% ethanol (alcohol), which corresponds to an amount of 159 mg per 1 ml, equivalent to 4.0 ml of beer or 1.7 ml of wine. This medication is harmful to people with alcoholism. The alcohol content should be taken into account in the case of pregnant or breastfeeding women, children, and high-risk groups, such as patients with liver disease or epilepsy.

Rivotril contains 30 mg of benzyl alcohol in each 1 mg/ml ampoule.

Benzyl alcohol can cause allergic reactions.

Consult your doctor or pharmacist if you have liver or kidney disease. This is because large amounts of benzyl alcohol can accumulate in the body and cause side effects (metabolic acidosis).

Benzyl alcohol has been linked to the risk of serious side effects, including respiratory problems ("gasping syndrome") in children.

Do not administer this medication to your newborn (up to 4 weeks old) unless your doctor has recommended it.

This medication should not be used for more than one week in children under 3 years old unless indicated by your doctor or pharmacist.

Rivotril contains 16 mg of propylene glycol in each 1 mg/ml ampoule.

It can produce symptoms similar to those of alcohol, which can decrease the ability to drive or operate machinery.

3. How to use Rivotril

Follow your doctor's instructions for administering this medication exactly. In case of doubt, consult your doctor or pharmacist again.

Depending on your response to the medication, the nature of your disease, and your weight, your doctor will indicate the correct dose for you. Rivotril will be administered intravenously or, less frequently, intramuscularly.

The injectable form is used in the treatment of status epilepticus, with the following recommended doses:

• Infants and children: slow intravenous injection of half an ampoule (0.5 mg).
• Adults: slow intravenous injection of one ampoule (1 mg).

These doses can be repeated if necessary, even by intramuscular injection or slow intravenous infusion. The patient will always follow the instructions of their doctor, as they are the only ones who can decide the most convenient dose in each case.

Your child should not receive more than two repeated doses in one day if they are under 5 years old.

As with all medications for treating epilepsy, you should not stop treatment with Rivotril abruptly, but rather reduce it gradually.

Guidelines for correct administration

Rivotril can be administered intramuscularly or by slow intravenous injection. Before use, the two ampoules contained in the package (the medication and the water for injection) should be mixed, and once the injectable solution is prepared, it should be administered immediately.

Intravenous infusion:

Rivotril (only the ampoule with the active substance) can be diluted in a proportion of 1 ampoule (1 mg) in at least 85 ml (e.g., dilute the contents of 3 ampoules in 250 ml). Rivotril can be diluted for infusion in the following solutions to avoid precipitation of the active substance: 0.9% NaCl or 0.45% NaCl + 2.5% glucose solution or 5% or 10% glucose solutions.

The use of infusion bags or equipment containing PVC/PUR/silicone may cause a decrease in clonazepam concentrations.

For intravenous administration, it is necessary to choose a vein of sufficient thickness and perform the injection very slowly, maintaining continuous monitoring of respiration and blood pressure.

In adults, the injection rate should not exceed 0.25-0.5 mg/min (0.5-1.0 ml/min of the prepared solution). The administered dose should not exceed 10 mg.

If the injection is too rapid or the vein thickness is insufficient, there is a risk of thrombophlebitis, which can be complicated by thrombosis.

Use in children

Rivotril should not be used in children under 27 days old (see also section 2).

Duration of treatment

Your doctor will indicate when you should finish treatment with Rivotril. The duration of therapy with Rivotril varies depending on the nature of your disease and your individual response to treatment. In many cases, treatment will continue with Rivotril tablets.

If you want to stop taking Rivotril, you should always consult your doctor, as suddenly stopping treatment can cause withdrawal symptoms, such as tremors.

If you use more Rivotril than you should

The symptoms of overdose or intoxication vary significantly from person to person, depending on age, weight, and individual response to the medication. Symptoms can range from fatigue and dizziness to ataxia (lack of coordination of voluntary movements), drowsiness (sleep), lack of breathing, absence of reflexes, hypotension (low blood pressure), and stupor (low response to stimuli), and finally, coma with respiratory depression and circulatory failure. Seizures can occur, especially in patients with medication concentrations in the blood above the recommended levels.

Treatment for intoxication will consist of monitoring (close surveillance) of respiration, heart rate, and blood pressure; intravenous hydration, general support measures, and emergency measures in case of airway obstruction. In case of hypotension (low blood pressure), sympathomimetic medications can be administered.

Warning:

The medication flumazenil (benzodiazepine antagonist) is not indicated in patients with epilepsy treated with benzodiazepines. In these patients, flumazenil can cause seizures.

In case of overdose or accidental ingestion, consult the Toxicology Information Service, Telephone 91 562.04.20.

If you interrupt treatment with Rivotril

When administration is stopped, restlessness, anxiety, insomnia, lack of concentration, headache, and sweating may appear. It is not recommended to interrupt medication abruptly, but rather to gradually reduce the dose, always following the doctor's instructions.

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

4. Possible side effects

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

The following side effects have been reported:

• Involuntary and uncontrolled eye movement (nystagmus).
• Drowsiness (sleep), slowness of reflexes, hypotonia, muscle weakness, dizziness, fatigue, ataxia (lack of coordination of voluntary movements). These side effects are usually transient and generally disappear without the need to interrupt treatment.
• Anterograde amnesia.
• Thrombocytopenia (decrease in platelet count).
• Urticaria (allergy), itching, skin rash (redness of the skin), temporary hair loss, changes in skin pigmentation (color).
• Headache.
• Nausea and epigastric discomfort (in the upper part of the abdomen).
• Urinary incontinence (loss of bladder control).
• Impotence, decreased libido (decreased sexual desire).
• Allergic reactions and anaphylactic shock (severe allergic reaction).

• Generalized epileptic seizures.

• Decreased concentration capacity, restlessness, confusion, disorientation.
• Emotional and mood changes.
• Depression, which may be due to an underlying disease.
• Paradoxical reactions (appearance of reactions contrary to those expected from the action of the medication): restlessness, irritability, aggressive behavior, agitation, nervousness, hostility, anxiety, sleep disorders, delirium, anger, nightmares, intense dreams, hallucinations, psychosis, hyperactivity, behavioral changes.
• Respiratory depression (slow and shallow breathing), especially if clonazepam is administered intravenously. The risk of respiratory depression is higher in patients with airway obstruction or previous brain damage. Respiratory depression can also occur when other medications that depress the respiratory center are administered at the same time. This effect can usually be avoided by careful individual adjustment of the dose.

• Increased risk of falls and fractures in elderly patients and patients taking other sedatives (including alcoholic beverages) at the same time.

• Heart failure (the heart does not pump blood well) and heart attack.
• Dependence and withdrawal syndrome.
• Risk of thrombophlebitis, or even thrombosis, if the injection rate is excessive or the vein thickness is not adequate.

When treatment is prolonged or high doses are used, reversible disorders such as dysarthria (difficulty articulating words), ataxia (lack of coordination of voluntary movements), and double vision (diplopia) may appear.

In some forms of epilepsy, an increase in the frequency of seizures (convulsions) may occur during long-term treatment.

It is known that the use of benzodiazepines can cause anterograde amnesia (difficulty remembering recent events), and the risk of this side effect increases with the dose.

Other side effects in children:

• Increased salivation and bronchial secretions in infants and young children, so it is necessary to pay special attention to keeping the airways clear.
• Precocious puberty (rapid body development) in children of both sexes.

Reporting side effects

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

5. Storage of Rivotril

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date shown on the label.

The expiration date is the last day of the month indicated.

Do not store above 30°C. Keep the ampoules in their original packaging to protect them from light.

Mixtures for infusion, once prepared, are stable for 24 hours at 30°C.

Medications should not be thrown down the drain or into the trash. Deposit the packaging and medications you no longer need in the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. This way, you will help protect the environment.

6. Packaging Content and Additional Information

Composition ofRivotril

• The active ingredient is clonazepam.
• Ampoules with 1 mg of active ingredient.

The other components are 159 mg of ethanol, 30 mg of benzyl alcohol, glacial acetic acid, and propylene glycol.

• Ampoule of solvent containing water for injectable preparations.

Appearance of the Product and Packaging Content

Rivotril is presented in packages of 1, 5, or 50 ampoules of concentrate, which include 1, 5, or 50 ampoules of solvent, respectively.

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

Cheplapharm Arzneimittel GmbH

Ziegelhof 24

17489 Greifswald

Germany

Manufacturer:

Cenexi

52 rue Marcel et Jacques Gaucher

94120 Fontenay-sous-Bois,

France

Local Representative:

Laboratorios Rubió, S.A.

C/ Industria, 29 - Pol. Ind. Comte de Sert

08755 Castellbisbal, Barcelona

Spain

Date of the Last Revision of this Leaflet:February 2025

Other Sources of Information:

Detailed 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/