RIVOTRIL 2.5 mg/ml ORAL SOLUTION DROPS

2. What you need to know before you take Rivotril

Do not take Rivotril

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

If you are not sure about these aspects, 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 any liver or kidney disease,
• if you are elderly, suffer from muscle weakness, sleep apnea, or have respiratory difficulties (feeling of suffocation),
• 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 hereditary galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption,
• if you have other diseases,
• if you are taking other medicines, especially epilepsy medicines, sleep aids (hypnotics), pain relievers (analgesics), mental illness medicines (neuroleptics), depression medicines (antidepressants), or lithium,
• if you have drug or alcohol dependence problems,
• if you have had depression and/or have attempted suicide,
• if you have ataxia (lack of coordination of voluntary movements).

A small number of people who have been treated with antiepileptics such as 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 medicines

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

For example, tranquilizers, sleep-inducing medicines, and other medicines that affect the central nervous system can increase the effect of Rivotril.

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

Your doctor may prescribe Rivotril along with other epilepsy medicines, in which 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 can modify its effects, reducing the effectiveness of the treatment or producing unforeseen side effects.

Risk of dependence

The use of benzodiazepines can cause dependence, mainly when the medicine is taken continuously for a long time. To minimize this risk, the following precautions should be taken into account:

• 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 he can decide if the treatment should be continued.

Pregnancy and breastfeeding

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

Driving and using machines

Rivotril can cause symptoms such as drowsiness, dizziness, or changes in vision, and reduce your reaction ability. These effects, as well as the disease itself, can make it difficult for you to drive vehicles or operate machines. Therefore, do not drive, operate machines, or engage in other activities that require special attention until your doctor assesses your response to this medicine.

Rivotril contains propylene glycol

Warnings about excipients:

This medicine contains 10.2 g of propylene glycol in each 2.5 mg/ml vial. It can cause symptoms similar to those of alcohol, which can reduce the ability to drive or operate machinery.

3. How to take Rivotril

Precaution:Do not administer the drops directly from the vial. Use a spoon.

After each opening of the vial, make sure the dropper is firmly attached to the neck of the vial before administering the drops.

Follow the administration instructions of this medicine exactly as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

Depending on your response to the medicine, the nature of your disease, and your weight, your doctor will indicate the correct dose for you, starting with a low initial dose and gradually increasing the dose 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 can be increased by 0.5 mg (0.2 ml or 5 drops) every 3 days until the seizures are well controlled or side effects prevent further dose increases. The maintenance dose should be adjusted for each patient. It is usually sufficient with a maintenance dose of 3-6 mg daily (which is equivalent to 1.2-2.4 ml or 30-60 drops).

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

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

Use in hepatic impairment and advanced age

Use the minimum necessary dose in advanced age and mild or moderate hepatic impairment. Do not administer in severe hepatic impairment.

Use in children and adolescents

• Infants and children under 10 years (or up to 30 kg body weight): 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 can be increased by 0.25-0.50 mg (0.1-0.2 ml or 2.5-5 drops) every 3 days, until the seizures are well controlled or side effects prevent further dose increases.

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

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

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

If the baby is less than 4 weeks old, consult your doctor or pharmacist, especially if the baby has been given other medicines containing propylene glycol or alcohol (see section 2 "warnings about excipients").

• Children and adolescents from 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 can 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, which is equivalent to 1.2-1.4 ml or 30-60 drops/day).

As with all epilepsy medicines, treatment with Rivotril should not be stopped abruptly, but rather gradually reduced.

Guidelines for correct administration

To use the dropper vial, it must be kept in a vertical position, with the mouth facing down. If the solution does not come out immediately, gently shake the vial, tap it lightly with your finger, or turn it over several times in a row.

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

Never administer the drops directly from the container to the mouth.

DO NOT change the dose indicated 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 indicate when you should finish treatment with Rivotril.

This treatment can last a lifetime, so if you want to stop taking Rivotril, you should always consult your doctor, as stopping treatment abruptly can cause withdrawal symptoms, such as tremors.

If you take more Rivotril than you should

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

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

Warning:

The medicine flumazenil (benzodiazepine antagonist) is not indicated in epileptic patients treated with benzodiazepines. In these patients, flumazenil can cause convulsions.

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If you take more Rivotril than you should

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, Telephone 91 562.04.20. It is recommended to take the package leaflet and the medicine package to the healthcare professional.

If you forget to take Rivotril

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

If you stop taking Rivotril

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

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

4. Possible side effects

Like all medicines, Rivotril can cause side effects, although not everybody gets them.

The following side effects have been described:

• Involuntary and uncontrolled eye movement (nystagmus).
• Somnolence (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 the number of platelets).
• 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 ability to concentrate, 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 by the action of the medicine): 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 medicines that depress the respiratory center are administered at the same time. In general, this effect can be avoided by careful individual dose adjustment.
• 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.

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 diplopia (double vision) 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 of side effects

If you experience any side effects, consult your doctor or pharmacist, even if it is a side effect not listed in this leaflet. You can also report them directly through the Spanish Medicines Surveillance System for Human Use: www.notificaRAM.es/. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Rivotril

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

Store in the original package.

Do not store above 30°C.

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

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

Once the vial is opened, the contents must be used within 120 days.

Medicines should not be disposed of via wastewater or household waste. Deposit the packages and medicines you no longer need in the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of packages and medicines you no longer need. This will help protect the environment.

6. Contents of the pack and further information

Composition of Rivotril

• The active ingredient is clonazepam (DCI). It is presented in a solution with 2.5 mg of active substance per ml (1 ml = 25 drops).
• The other ingredients 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 pack

Rivotril is presented in a package containing a 10 ml amber glass vial (solution containing 2.5 mg per ml (1 drop = 0.1 mg 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 last revision of this leaflet: November 2020

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