Rivotril 1 mg/ml concentrate and solvent for solution for injection

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Rivotril 1 mg/ml concentrate and solvent for injection solution

clonazepam

Read the entire leaflet carefully before you start using 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, ask your doctor or pharmacist.
• This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms as you, because it could 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 Rivotril is and what it is used for
2. What you need to know before using Rivotril
3. How to use Rivotril
4. Possible side effects
5. Storage of Rivotril
6. Contents of the pack and other information

1. What Rivotril is and what it is used for

Rivotril contains clonazepam as the active ingredient, which belongs to a group of medicines known as benzodiazepines. Clonazepam has anticonvulsant properties, meaning it prevents seizures.

It is used in most forms of epilepsy in infants and children, particularly absence seizures (petit mal) and tonic-clonic seizures.

It is also indicated in adult epilepsies, for focal seizures, and in epileptic "status".

2. What you need to know before using Rivotril

Do not use Rivotril

• if you are allergic (hypersensitive) to the active substance or to any of the other components of this medicine (listed in section 6)
• if you are allergic (hypersensitive) to other medicines in the benzodiazepine group
• if you have severe and persistent breathing difficulties (feeling of suffocation), severe liver failure (the liver cannot perform its functions), or if you have drug or alcohol dependence, unless strictly prescribed by your doctor

If you are unsure about any of these points, consult your doctor.

Children

Rivotril must not be used in neonates, especially in premature infants.

Warnings and precautions

Talk to your doctor or pharmacist before starting to use Rivotril.

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 breathing difficulties (feeling of suffocation),
• if you have allergies,
• if you have porphyria (a disease that may affect the nervous system and makes the skin very sensitive to sunlight),
• if you have other illnesses,
• if you are taking other medicines, especially medicines for epilepsy, sleeping aids (hypnotics), painkillers (analgesics), medicines for mental disorders (neuroleptics), antidepressants, or lithium,
• if you have drug or alcohol dependence,
• if you have or have had depression and/or have attempted suicide,
• if you have ataxia (lack of coordination of voluntary movements).

A small number of patients treated with antiepileptic medicines such as Rivotril have experienced thoughts of self-harm or suicide. If you have such thoughts at any time, contact your doctor immediately.

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

Taking Rivotril with other medicines

Inform your doctor or pharmacist if you are currently using, have recently used, or might need to use any other medicines. This is very important because taking several medicines at the same time may increase or decrease their effects.

For example, the effect of Rivotril may be increased by sedatives, sleep-inducing medicines, and other medicines that affect the central nervous system.

Therefore, you must not take Rivotril together with other medicines without consulting your doctor. You may start taking it only when your doctor authorizes you to do so.

Your doctor may prescribe Rivotril together with other antiepileptic medicines; in this case, your doctor will adjust the dose of each medicine to achieve the desired effect.

Taking Rivotril with alcohol

You should avoid drinking alcohol during treatment with Rivotril, as it may alter its effects, reducing treatment efficacy or causing unexpected adverse effects.

Risk of dependence

The use of benzodiazepines may lead to dependence, mainly when the medicine is taken continuously over a long period. To minimize this risk as much as possible, the following precautions should be observed:

• Benzodiazepines should only be taken under medical prescription (never because they worked for other patients), and you should never recommend them to others.
• Do not increase the doses prescribed by your doctor, nor extend the treatment beyond the recommended duration.
• Consult your doctor regularly so they can decide whether treatment should continue.

Pregnancy and breastfeeding

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

Driving and using machines

Rivotril acts on the central nervous system and may cause: drowsiness, dizziness, visual disturbances, and reduced reaction capacity. These effects, as well as the underlying illness itself, mean that caution is advised when driving vehicles or operating dangerous machinery, especially until the individual patient's sensitivity to the medicine has been established.

Rivotril contains ethanol, benzyl alcohol, and propylene glycol

Ask your doctor or pharmacist for advice if your child is under 5 years of age, if you have liver or kidney disease, or if you are pregnant or breastfeeding. This is because the excipients may cause adverse effects. Your doctor may need to adjust the dose if you or your child are taking other medicines containing benzyl alcohol, propylene glycol, or alcohol.

Excipient warning:

Rivotril contains 15.9% ethanol (alcohol), corresponding to 159 mg per 1 ml, equivalent to 4.0 ml of beer or 1.7 ml of wine. This medicine may be harmful for individuals with alcoholism. The alcohol content should be taken into account in 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 may cause allergic reactions.

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

Benzyl alcohol has been associated with the risk of serious adverse effects, including breathing problems ("gasping syndrome") in children.

Do not administer this medicine to your newborn (up to 4 weeks of age) unless specifically recommended by your doctor.

This medicine should not be used for longer than one week in children under 3 years of age unless directed by your doctor or pharmacist.

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

It may produce symptoms similar to those of alcohol, thereby reducing the ability to drive or operate machinery.

3. How to use Rivotril

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

Depending on your response to the medicine, the nature of your illness, and your body weight, your doctor will determine the correct dose for you. Rivotril will be administered intravenously or, more rarely, intramuscularly.

The injectable form is used in the treatment of epileptic "status", 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 may be repeated if necessary, even by intramuscular route or by slow intravenous infusion. The patient must always follow their doctor's instructions, as only the doctor can decide the most appropriate dose in each individual case.

Your child must not receive more than two repeated doses in a single day if under 5 years of age.

As with all antiepileptic medicines, Rivotril treatment must not be stopped abruptly, but should be tapered off gradually.

Instructions for correct administration

Rivotril can be administered intramuscularly or by slow intravenous injection. Before use, the two ampoules contained in the package (the one containing the medicine and the one with sterile water) must be mixed, and once the injectable solution has been prepared, it must be administered immediately.

Intravenous infusion:

Rivotril (only the ampoule containing the active substance) may be diluted at a ratio of 1 ampoule (1 mg) in at least 85 ml (for example, dilute the contents of 3 ampoules in 250 ml). Rivotril may be diluted for infusion in the following solutions to prevent precipitation of the active ingredient: 0.9% NaCl, 0.45% NaCl + 2.5% glucose solution, or 5% or 10% glucose solutions.

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

For intravenous administration, a sufficiently large vein must be selected, and the injection must be performed very slowly, with continuous monitoring of respiration and blood pressure.

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

If the injection is too rapid or the vein is too small, there is a risk of thrombophlebitis, which may lead to thrombosis.

Use in children

Rivotril must not be used in children under 27 days of age (see also section 2).

Duration of treatment

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

If you wish to stop taking Rivotril, you must always consult your doctor, as stopping treatment suddenly may cause withdrawal symptoms such as tremors.

If you use more Rivotril than you should

Symptoms of overdose or intoxication vary significantly from person to person, depending on age, weight, and individual response to the medicine. Symptoms may range from fatigue and dizziness to ataxia (lack of coordination of voluntary movements), somnolence (drowsiness), respiratory depression, absence of reflexes, hypotension (low blood pressure), and stupor (reduced responsiveness to stimuli), and ultimately coma with respiratory depression and circulatory failure. Seizures may occur, especially in patients with blood levels of the drug above the recommended range.

Treatment of intoxication consists of monitoring (close observation) of respiration, heart rate, and blood pressure; intravenous hydration; general supportive measures; and emergency interventions in case of airway obstruction. In cases of hypotension (low blood pressure), sympathomimetic drugs may be administered.

Warning:

The drug flumazenil (benzodiazepine antagonist) is not indicated in epileptic patients treated with benzodiazepines. In these patients, flumazenil may provoke seizures.

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

If you interrupt treatment with Rivotril

Upon discontinuation, symptoms such as restlessness, anxiety, insomnia, difficulty concentrating, headache, and sweating may occur. Abrupt interruption of the medication is generally not recommended; instead, the dose should be gradually reduced, always in accordance with your doctor's instructions.

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

4. Possible adverse effects

Like all medicines, Rivotril may cause adverse effects, although not everyone experiences them.

The following adverse effects have been reported:

• Involuntary and uncontrolled eye movements (nystagmus).

• Somnolence (drowsiness), slowed reflexes, hypotonia, muscle weakness, dizziness, fatigue, ataxia (lack of coordination of voluntary movements). These adverse effects are usually transient and generally disappear without the need to discontinue treatment.

• Anterograde amnesia.

• Thrombocytopenia (decreased platelet count).

• Urticaria (allergy), itching, skin rash (redness of the skin), temporary hair loss, changes in skin pigmentation (skin color).

• Headache.

• Nausea and epigastric discomfort (in the upper abdomen).

• Urinary incontinence (lack of control over urine).

• Impotence, decreased libido (reduced sexual desire).

• Allergic reactions and anaphylactic shock (severe allergic reaction).

• Generalized epileptic seizures.

• Decreased ability to concentrate, restlessness, confusion, disorientation.

• Emotional and mood disturbances.

• Depression, which may be due to an underlying medical condition.

• Paradoxical reactions (appearance of reactions opposite to those expected from the drug's action): restlessness, irritability, aggressive behavior, agitation, nervousness, hostility, anxiety, sleep disturbances, delirium, rage, nightmares, vivid dreams, hallucinations, psychosis, hyperactivity, behavioral disturbances.

• 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 pre-existing brain damage. Respiratory depression may also occur when other drugs that depress the respiratory center are administered concomitantly. In general, this effect can be avoided by careful individual dose adjustment.

• Increased risk of falls and fractures in elderly patients and in patients taking other sedatives simultaneously (including alcoholic beverages).

• Heart failure (the heart does not pump blood effectively) and heart attack.

• Dependence and withdrawal syndrome.

• Risk of thrombophlebitis, or even thrombosis, if the injection rate is too fast or if the vein is not of adequate size.

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

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

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

Other adverse effects in children:

• Hypersalivation (increased saliva production) and increased bronchial secretions in infants and young children, requiring special attention to maintain clear airways.
• Incomplete precocious puberty (rapid body development) in children of both sexes.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is an effect 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 Rivotril

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiry date stated on the label.

The expiry date refers to the last day of the month indicated.

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

Intravenous mixtures, once prepared, are stable for 24 hours at 30°C.

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

6. Contents of the pack and other information

Composition of Rivotril

• The active substance is clonazepam.
• Vials containing 1 mg of active substance.

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

• Solvent vial containing water for injections.

Appearance of the product and contents of the pack

Rivotril is available in packs containing 1, 5 or 50 vials of concentrate, each accompanied by 1, 5 or 50 solvent vials, respectively.

Only certain pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation 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 most recent review 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/