Rivotril 2.5 mg/ml oral solution drops

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Rivotril 2.5 mg/ml oral drops solution

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, 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 reactions, consult your doctor or pharmacist, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet contents:

1. What Rivotril is and what it is used for
2. What you need to know before taking Rivotril
3. How to take Rivotril
4. Possible side effects
5. How to store 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 (convulsions).

It is used in most forms of epilepsy in infants and children, particularly petit mal and tonic-clonic seizures. It is also indicated in adult epilepsies, for focal seizures, and in epileptic "status" epilepticus.

2. What you need to know before taking Rivotril

Do not take Rivotril

• if you are allergic (hypersensitive) to the active substance or to any of the other ingredients 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 (liver unable to 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.

Warnings and precautions

Consult your doctor or pharmacist before starting to take 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 breathing difficulties (feeling of suffocation),
• if you have allergies,
• if you have porphyria (a disease that may affect the nervous system and causes the skin to be very sensitive to sunlight),
• if you have hereditary galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption,
• if you have other diseases,
• if you are taking other medicines, especially antiepileptic drugs, sleeping pills (hypnotics), painkillers (analgesics), medicines for mental illnesses (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 suicidal thoughts or thoughts of self-harm. If you experience 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 should not take it at all.

Taking Rivotril with other medicines

Inform your doctor or pharmacist if you are 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 tranquilizers, sleep-inducing medicines, and other medicines affecting 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 alcohol during treatment with Rivotril, as it may alter its effects, reducing the treatment's 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, the following precautions should be observed:

• Benzodiazepines should only be taken on 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 that they can decide whether treatment should continue.

Pregnancy and breastfeeding

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

Driving and using machines

Rivotril may cause symptoms such as drowsiness, dizziness, or visual disturbances, and may reduce reaction capability. These effects, as well as the underlying illness itself, may impair your ability to drive vehicles or operate machinery. Therefore, do not drive, operate machinery, or perform other activities requiring special attention until your doctor has assessed your response to this medicine.

Rivotril contains propylene glycol

Excipient warnings:

This medicine contains 10.2 g of propylene glycol in each 2.5 mg/ml vial. It may produce symptoms similar to those of alcohol, thereby reducing your ability to drive or operate machinery.

3. How to take Rivotril

Caution: Do not administer the drops directly from the bottle. Use a spoon.

After each opening of the bottle, ensure that the dropper is securely attached to the neck of the bottle before administering the drops.

Always follow your doctor's instructions on how to take this medicine. If in doubt, consult your doctor or pharmacist again.

Depending on your response to the medication, the nature of your condition, and your body weight, your doctor will determine the correct dose for you, starting with a low initial dose and gradually increasing it until the desired effect is achieved.

• Adults: The initial dose should not exceed 1.5 mg/day (equivalent to 0.6 ml/day or 15 drops/day), divided into three doses. This dose may be increased by 0.5 mg (0.2 ml or 5 drops) every 3 days until seizures are well controlled or until adverse effects prevent further dose increases. The maintenance dose should be individually adjusted for each patient. A daily maintenance dose of 3–6 mg (equivalent to 1.2–2.4 ml or 30–60 drops) is usually sufficient.

The maximum daily dose of 20 mg (equivalent to 8 ml or 200 drops) must never be exceeded in adults.

To facilitate dose adjustment, it is recommended to use the 0.5 mg scored tablets in children and adults during the initial phase of treatment.

Use in hepatic impairment and elderly patients

Use the lowest necessary dose in elderly patients and in cases of mild to moderate liver impairment. Do not administer in severe liver disease.

Use in children and adolescents

• Infants and children under 10 years of age (or weighing less than 30 kg): The initial dose is 0.01–0.03 mg/kg/day (0.004–0.012 ml/kg/day), divided into two or three doses. This dose may be increased by 0.25–0.50 mg (0.1–0.2 ml or 2.5–5 drops) every 3 days until seizures are well controlled or until adverse effects prevent further dose increases.

The approximate maintenance dose is 0.1 mg/kg/day (0.04 ml/kg/day).

The maximum daily dose of 0.2 mg/kg/day (0.08 ml/kg/day) must never be exceeded in infants and children under 10 years of age.

To facilitate dose adjustment, the use of drops (1 drop = 0.1 mg of active substance) is recommended for infants.

If the infant is less than 4 weeks old, consult your doctor or pharmacist, especially if the infant has been given other medicines containing propylene glycol or alcohol. (See section 2 “Warnings about excipients”).

• Children and adolescents aged 10–16 years: The initial dose is 1–1.5 mg/day (0.4–0.6 ml/day or 10–15 drops/day), divided into two or three doses. This dose may be increased by 0.25–0.5 mg (0.1–0.2 ml or 2.5–5 drops) every 3 days until the maintenance dose is reached (usually 3–6 mg/day, equivalent to 1.2–1.4 ml or 30–60 drops/day).

As with all antiepileptic medications, treatment with Rivotril must not be stopped abruptly; it should be gradually tapered off.

Instructions for correct administration

To use the dropper bottle, hold it vertically with the mouth facing downward. If the solution does not come out immediately, gently shake the bottle, tap it lightly with your finger, or invert it several times consecutively.

The drops should be administered using a spoon and may be mixed with water, tea, or fruit juice.

The drops must never be administered directly from the container into the mouth.

DO NOT change the dose prescribed by your doctor.

Consult your doctor if you think the effect of this medicine is too strong or too weak.

Duration of treatment

Your doctor will advise you when to stop treatment with Rivotril.

This treatment may last a lifetime. Therefore, if you wish to stop taking Rivotril, you must always consult your doctor first, as stopping treatment suddenly may cause withdrawal symptoms such as tremors.

If you take 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 muscle 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, particularly in patients with blood levels of the drug above the recommended range.

Treatment of intoxication includes monitoring (close observation) of respiration, heart rate, and blood pressure; gastric lavage, 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 (a benzodiazepine antagonist) is not indicated in epileptic patients treated with benzodiazepines. In these patients, flumazenil may provoke seizures.

If you take more Rivotril than you should

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately or call the Toxicology Information Service at telephone number 91 562.04.20. It is recommended to bring the package leaflet and the medicine container to the healthcare professional.

If you forget to take Rivotril

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

If you stop taking Rivotril

Upon discontinuation, symptoms such as restlessness, anxiety, insomnia, difficulty concentrating, headache, and sweating may occur. Abrupt interruption of treatment is generally not recommended; instead, the dose should be gradually reduced according to 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 (reduced 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 condition.

• Paradoxical reactions (occurrence 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 prior brain damage. Respiratory depression may also occur when other respiratory depressant medicines are taken concomitantly. Generally, this effect can be avoided by careful individual dose adjustment.

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

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

• Dependence and withdrawal syndrome.

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 frequency (convulsions) may occur during long-term treatment.

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

Other adverse effects in children:

• Hypersalivation (increased saliva production) and bronchial secretions in infants and young children, thus 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 adverse 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.

Store in the original packaging.

Do not store above 30°C.

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

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

Once the bottle is opened, the contents should be used within 120 days.

Medicines must not be disposed of via wastewater or with household waste. Dispose of unused medicines and their containers at the SIGRE collection point at your pharmacy. If you are unsure, ask your pharmacist how to dispose of medicines and containers you no longer need. This helps protect the environment.

6. Package contents and additional information

Composition of Rivotril

• The active substance is clonazepam (INN). It is presented as a solution containing 2.5 mg of active substance per ml (1 ml = 25 drops).
• The other components of the solution are sodium saccharin, peach flavor, glacial acetic acid, propylene glycol, and brilliant blue FCF (E 133).

Appearance of the product and contents of the package

Rivotril is supplied in a package containing a 10 ml amber glass bottle (solution containing 2.5 mg per ml (1 drop = 0.1 mg of active substance)).

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

CHEPLAPHARM Arzneimittel GmbH

Ziegelhof 24

17489 Greifswald

Germany

Manufacturer:

Delpharm Milano S.r.l.

Via Carnevale, 1

20054, Segrate (MI), Italy

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: November 2020

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