Leaflet:informationfor the user

Rivotril 1 mg/ml concentrate and solvent for injectable solution

Clonazepam

Read this 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, consult your doctor or pharmacist.

-This medicine has been prescribed for you only and should not be given to others, even if they have the same symptoms as you, as it may harm them.

-If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

1.What is Rivotril and what it is used for

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

3.How to use Rivotril

4.Possible side effects

5Storage of Rivotril

6.Contents of the pack and additional information

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

It is used in most forms of infantile and child epilepsy, especially petit mal and tonic-clonic seizures. It is also indicated in adult epilepsy, focal seizures, and status epilepticus.

Do not use Rivotril

• if you are allergic (hypersensitive) to the active ingredient or 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 (sensation of choking), 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 unsure about these aspects, consult your doctor.

Warnings and precautions

Consult your doctor or pharmacist before starting to use Rivotril.

You may experience a loss of effect 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, have muscle weakness, sleep apnea, or respiratory difficulties (sensation of choking),
• if you have allergies,
• if you have porphyria (a disease that can affect the nervous system and makes your skin very sensitive to the sun),
• if you have hereditary intolerance to galactose, lactase deficiency of Lapp, or malabsorption of glucose or galactose,
• if you have other diseases,
• if you are taking other medications, especially medications for epilepsy, sleep aids (hypnotics), pain medications (analgesics), mental health medications (neuroléptics), depression medications (antidepresivos), or lithium,
• if you have drug or alcohol dependence problems,
• if you have depression and/or have attempted suicide,
• if you have ataxia (discoordination of voluntary movements).

A reduced number of people who were treated with antiepileptic medications like Rivotril have had thoughts of self-harm or suicide. If you ever have these thoughts, contact your doctor immediately.

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

Taking Rivotril with other medications

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

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

Therefore, do 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 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 taking alcohol during treatment with Rivotril, as it can modify its effects by reducing the effectiveness of the treatment or producing unforeseen adverse effects.

Risk of dependence

The use of benzodiazepines can cause dependence, mainly when the medication is taken continuously for a long time. To prevent this risk, follow these precautions:

• Take benzodiazepines only under medical prescription (never because they have worked for other patients) and never advise others to take them.
• Do not increase the prescribed doses or prolong the treatment longer than recommended.
• Consult your doctor regularly to decide whether to continue treatment.

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 adverse effects (metabolic acidosis). (see warning about excipients)

Driving and operating machinery

Rivotril acts on the central nervous system and can cause: drowsiness, dizziness, visual disturbances, and decreased reaction capacity. These effects, as well as the underlying disease, make it advisable to exercise caution when driving vehicles or operating hazardous machinery, especially until your individual sensitivity to the medication is established.

Rivotril contains ethanol, benzyl alcohol, and propylene glycol

Warnings about excipients:

This medication contains 15.9% ethanol (alcohol), which corresponds to 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 women, breastfeeding women, children, and high-risk groups, such as patients with liver disease or epilepsy.

This medication 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 your body and cause adverse effects (metabolic acidosis).

Benzyl alcohol has been linked to the risk of severe adverse effects, including respiratory problems ("breathing syndrome") in children.

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

This medication should not be used for more than a week in children under 3 years of age, unless your doctor or pharmacist advises it.

This medication contains 16 g of propylene glycol in each 1 mg/ml ampoule.

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

If the baby is under 4 weeks old, consult your doctor or pharmacist, especially if the baby has been given other medications containing propylene glycol or alcohol.

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

Depending on your response to the medication, the nature of your illness, 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" epilepsy, recommending the following doses:

• Newborns and children: slow intravenous injection of half a vial (0.5 mg).
• Adults: slow intravenous injection of one vial (1 mg).

These doses can be repeated as needed, even intramuscularly or by slow intravenous infusion. The patient will always follow the instructions of their doctor, as only they can decide on the most suitable dose in each case.

As with all medications for treating epilepsy, do not stop treatment with Rivotril abruptly, but rather taper it off gradually.

Guidelines for correct administration

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

Intravenous infusion:

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

The use of bags or infusion 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 breathing and blood pressure.

In adults, the injection speed 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 fast or the vein thickness is insufficient, there is a risk of thrombophlebitis that can complicate with thrombosis.

Treatment duration

Your doctor will indicate when to stop treatment with Rivotril, 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 want to stop taking Rivotril, you must always consult your doctor as stopping treatment abruptly may cause withdrawal symptoms such as tremors.

If you use moreRivotrilthan you should

The symptoms of overdose or intoxication vary greatly from person to person, depending on age, weight, and individual response to the medication. Symptoms can range from fatigue and dizziness to ataxia (discoordination 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 insufficiency. Convulsions may occur, especially in patients with blood concentrations of the medication above the recommended levels.

The treatment of intoxication will consist of close monitoring of breathing, heart rate, and blood pressure; gastric lavage, intravenous hydration, general supportive measures, and emergency measures in case of respiratory tract obstruction. In case of hypotension (low blood pressure), sympathomimetic medications may be administered.

Warning:

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

If you take more Rivotril than you should, contact your doctor immediately or go to the nearest hospital. Bring the medication with you.

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

If you forgot to use Rivotril

Do not take a double dose to compensate for the missed doses.

If you interrupt treatment withRivotril

Stopping administration may cause restlessness, anxiety, insomnia, lack of concentration, headache, and sweating. It is generally not recommended to stop medication abruptly, but rather to taper off the dose gradually, in accordance with the doctor's instructions.

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

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

The following side effects have been described:

• Uncontrollable and involuntary movement of the eyes (nystagmus).
• Drowsiness (sleep), slowness of reflexes, hypotonia, muscle weakness, dizziness, fatigue, ataxia (discoordination of voluntary movements). These side effects are usually temporary 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, alterations in skin pigmentation (color).
• Headache.
• Nausea and epigastric discomfort (in the upper 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 ability, restlessness, confusion, disorientation.
• Emotional and mood alterations.
• Depression, which may be due to an underlying disease.
• Paradoxical reactions (appearance of reactions contrary to those expected by the action of the medication): restlessness, irritability, aggressive behavior, agitation, nervousness, hostility, anxiety, sleep disorders, delirium, anger, nightmares, intense dreams, hallucinations, psychosis, hyperactivity, behavioral alterations.
• Respiratory depression (slow and shallow breathing), especially if clonazepam is administered intravenously. The risk of respiratory depression is higher in patients with respiratory tract obstruction or previous brain damage. Respiratory depression may also occur when other central nervous system depressants are administered simultaneously. This effect can usually be prevented by careful individual dose adjustment.

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

• Heart failure (heart not pumping blood well) and myocardial infarction.
• Dependence and withdrawal syndrome.
• Risk of thrombophlebitis, or even thrombosis, if the injection speed is excessive or the vein diameter is not adequate.

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

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 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 (excessive saliva production) and bronchial secretions in infants and young children, so it is essential to pay special attention to keeping the airways clear.
• Incomplete premature 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 a side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use: www.notificaRAM.es/. By reporting side effects, you can contribute to providing more information on the safety of this medication.

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

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

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

Do not store at a temperature above30°C. Store the ampoules in the original packaging to protect them from light.

Prepared infusion mixtures are stable for 24 hours at 30°C.

Medicines should not be disposed of through drains or in the trash. Dispose of containers and unused medications at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of containers and unused medications. By doing so, you will help protect the environment.

Composition ofRivotril

• The active ingredient is clonazepam (DCI). Ampoules with 1mg of active ingredient.
• Theother components are 159 mg of ethanol, 30 mg of benzyl alcohol, glacial acetic acid and propylene glycol.
• The diluent ampoule contains water for injection preparations.

Appearance of the product and contents of the packaging

Rivotril is marketed in packaging of 1, 5 or 50 ampoules of concentrate, which also include 1, 5 or 50 ampoules of solvent, respectively.

Holder of the marketing authorization and responsible manufacturer

Holder of the marketing authorization:

CHEPLAPHARM Arzneimittel GmbH

Ziegelhof 24

17489 Greifswald

Germany

Manufacturers:

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

Last review date of this leaflet: November 2020

Other sources of information:

The detailed and updated information on this medication is available on thewebsite of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/