Package Insert: Information for the User

Rivastigmina Combix 2 mg/ml Oral Solution EFG

Rivastigmina Hydrogen Tartrate

Read this package insert carefully before starting to take this medication, as it contains important information for you.

• Keep this package insert, as you may need to refer to it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed only for you, 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 any adverse effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

The active ingredient of Rivastigmina Combix is rivastigmina.

Rivastigmina belongs to a group of substances called cholinesterase inhibitors. In patients with Alzheimer's disease or Parkinson's disease-related dementia, certain nerve cells die in the brain, causing low levels of acetylcholine neurotransmitters (a substance that allows nerve cells to communicate with each other). Rivastigmina acts by blocking the enzymes that break down acetylcholine: acetylcholinesterase and butyrylcholinesterase. By blocking these enzymes, Rivastigmina Combix allows an increase in acetylcholine in the brain, helping to reduce the symptoms of Alzheimer's disease and dementia associated with Parkinson's disease.

Rivastigmina is used for the treatment of adult patients with mild to moderately severe Alzheimer's disease, a progressive brain disorder that gradually affects memory, intellectual capacity, and behavior. The capsules and oral solution are also used for the treatment of dementia in adult patients with Parkinson's disease.

Do not takeRivastigmina Combix

• if you are allergic to rivastigmina (the active ingredient of Rivastigmina Combix) or to any of the other components of this medication (listed in section 6).
• if you have a skin reaction that extends beyond the size of the patch, if there is a more intense local reaction (such as blisters, increased skin inflammation, swelling) and if there is no improvement within 48 hours after removing the transdermal patch.

If you find yourself in any of these situations, inform your doctor and do not take rivastigmina.

Warnings and precautions

Consult your doctor before starting to take Rivastigmina:

• if you have or have had any heart problems such as irregular or slow heart rhythm, QTc prolongation, family history of QTc prolongation, torsades de pointes, or if you have low blood levels of potassium or magnesium.
• if you have or have had any active stomach ulcers.
• if you have or have had any difficulty urinating.
• if you have or have had any seizures.
• if you have or have had any asthma or severe respiratory disease.
• if you have or have had any kidney function deterioration.
• if you have or have had any liver function deterioration.
• if you suffer from tremors.
• if you have a low body weight.
• if you have gastrointestinal reactions such as dizziness (nausea), vomiting, and diarrhea. You may become dehydrated (loss of a large amount of fluid) if vomiting or diarrhea are prolonged.

If you find yourself in any of these situations, your doctor may consider the need for closer monitoring while you are on treatment.

If you have not taken rivastigmina for more than three days, do not take the next dose until you have consulted your doctor.

Children and adolescents

Rivastigminashould not be used in the pediatric population for the treatment of Alzheimer's disease.

Other medications and Rivastigmina Combix

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication.

Rivastigmina should not be administered at the same time as other medications with similar effects to rivastigmina. Rivastigmina may interfere with anticholinergic medications (used to relieve muscle cramps or spasms, for the treatment of Parkinson's disease, or to prevent travel sickness).

Rivastigmina should not be administered at the same time as metoclopramide (a medication used to relieve or prevent nausea and vomiting). Taking the two medications together may cause problems such as stiffness in the limbs and hand tremors.

If you need to undergo surgery while taking rivastigmina, inform your doctor before any anesthetic is administered, as rivastigmina may exacerbate the effects of some muscle relaxants during anesthesia.

Care should be taken when rivastigmina is used with beta blockers (medications such as atenolol used to treat hypertension, angina, and other heart conditions). Taking the two medications together may cause complications such as a decrease in heart rate (bradycardia) that may lead to fainting or loss of consciousness.

Care should be taken when rivastigmina is used with other medications that may affect heart rhythm or the heart's electrical system (QT prolongation).

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor or pharmacist before using this medication.

If you are pregnant, the benefits of usingrivastigminamust be weighed against the possible adverse effects on the fetus. Rivastigmina should not be used during pregnancy unless it is clearly necessary.

You should not breastfeed during treatment with rivastigmina.

Driving and operating machinery

Your doctor will inform you if your condition allows you to drive or use machinery safely. Rivastigmina may cause dizziness and drowsiness, mainly at the start of treatment or when increasing the dose. If you feel dizzy or drowsy, do not drive, use machinery, or perform other tasks that require your attention.

Rivastigmina Combix contains benzoate sodium (E211) and sodium

One of the inactive ingredients of Rivastigmina Combix oral solution is benzoate sodium (E211). Benzoic acid is slightly irritating to skin, eyes, and mucous membranes. This medication contains 3 mg of benzoate sodium (E211) in each 3 ml of oral solution.

This medication contains less than 1 mmol of sodium (23 mg) per ml; it is essentially “sodium-free”.

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

Starting Treatment

Your doctor will tell you what dose of rivastigmina you should take.

• Normally, treatment starts with a low dose.
• Your doctor will gradually increase the dose depending on how you respond to the treatment.
• The highest dose you should take is 6.0 mg twice a day.

Your doctor will regularly check if the medication is working for you. Your doctor will also monitor your weight while you are taking this medication.

If you have not taken rivastigmina for more than three days, do not take the next dose until you have consulted your doctor.

Taking this Medication

• Inform your caregiver that you are taking rivastigmina.
• To benefit from your medication, take it every day.
• Take rivastigmina twice a day (in the morning and at night), with meals.

For an exact dosage, the containers have an oral syringe graduated.Using this syringe, extract the prescribed amount of rivastigmina from the bottle.

The syringe is inserted into the perforated stopper, the bottle is turned upside down, the plunger is pulled until the liquid reaches the mg mark, the bottle is returned to its initial position, and the syringe is removed.

The syringe should be cleaned and dried after each use.

Each dose of rivastigmina can be taken directly from the syringe.

If you take more Rivastigmina Combix than you should

If you accidentally take more rivastigmina than you should, inform your doctor. You may require medical attention.

In case of overdose or accidental ingestion, consult your doctor, pharmacist, or call the Toxicological Information Service, phone 91 562 04 20, indicating

the medication and the amount taken. Some people who have accidentally taken higher doses have experienced dizziness (nausea), vomiting, diarrhea, high blood pressure, and hallucinations. It may also cause a slowing of heart rate and fainting.

If you forget to take Rivastigmina Combix

If you forget your rivastigmina dose, wait and take the next dose at the usual time. Do not take a double dose to make up for the missed doses.

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

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

You may experience side effects more frequently when you start treatment or when your dose is increased. Side effects usually disappear gradually as your body gets used to the medicine.

Very common(may affect more than 1 in 10 people)

• Dizziness
• Loss of appetite
• Stomach problems such as dizziness (nausea), vomiting, diarrhea

Common(may affect up to 1 in 10 people)

• Anxiety
• Sweating
• Headache
• Heartburn
• Weight loss
• Abdominal pain
• Restlessness
• Feeling tired or weak
• General feeling of discomfort
• Shakiness or feeling of confusion
• Decreased appetite
• Nightmares

Uncommon(may affect up to 1 in 100 people)

• Depression
• Difficulty sleeping
• Fainting or accidental falls
• Changes in liver function

Rare(may affect up to 1 in 1,000 people)

• Chest pain
• Cutaneous rash, itching
• Seizures (convulsions)
• Ulcers in the stomach or intestine

Very rare(may affect up to 1 in 10,000 people)

• High blood pressure
• Urinary tract infection
• Seeing things that do not exist (hallucinations)
• Problems with heart rhythm such as rapid or slow heart rate
• Gastrointestinal bleeding – presents as blood in the stool or vomiting blood
• Pancreatitis – symptoms include severe pain in the upper abdomen, often with dizziness (nausea) or vomiting
• Worsening of Parkinson's disease symptoms or development of similar symptoms - such as muscle stiffness, difficulty moving, and muscle weakness

Unknown(cannot be estimated from available data):

• Intense vomiting that may cause tearing of part of the digestive tube that connects your mouth to your stomach (esophagus)

• Dehydration (loss of a large amount of fluid)
• Hepatic disorders (yellowing of the skin, yellowing of the white of the eyes, abnormal darkening of the urine or unexplained nausea, vomiting, fatigue, and loss of appetite)
• Aggression, feeling of restlessness
• Irregular heart rhythm
• Torticollis (condition that involves involuntary muscle contraction and abnormal tilting of the body and head to one side)

Patients with dementia or Parkinson's disease

These patients experience some side effects more frequently and also have some additional side effects:

Very common(may affect more than 1 in 10 people)

• Tremor
• Fainting
• Accidental falls

Common(may affect up to 1 in 10 people)

• Anxiety
• Feeling of unease
• Irregular heart rhythm
• Difficulty sleeping
• Excessive saliva and dehydration
• Abnormally slow or uncontrolled movements
• Worsening of Parkinson's disease symptoms or development of similar symptoms - such as muscle stiffness, difficulty moving, and muscle weakness

Uncommon(may affect up to 1 in 100 people)

• Irregular heart rhythm and loss of motor control

Unknown(cannot be estimated from available data)

• Torticollis (condition that involves involuntary muscle contraction and abnormal tilting of the body and head to one side)

Other side effects observed in rivastigmine transdermal patches and that may appear with oral solution:

Common(may affect up to 1 in 10 people)

• Fever
• Severe confusion
• Urinary incontinence (inability to stop urinating properly)

Uncommon(may affect up to 1 in 100 people)

Unknown(cannot be estimated from available data)

• Allergic reaction where the patch was applied, such as blisters or skin inflammation

If you experience any of these side effects, contact your doctor as they may require medical assistance.

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible 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:https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use Rivastigmina Combix this medication after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

No special storage conditions are required. Use Rivastigmina Combix in the month following the first opening of the bottle.

Medicines should not be thrown down the drains or in the trash. Dispose of the packaging and medicines that you no longer need at the SIGRE point of the pharmacy.Ask your pharmacist how to dispose of the packaging and medicines that you no longer need. In this way, you will help protect the environment.

Composition of Rivastigmina Combix

• The active ingredient is rivastigmina hydrogentartrate. Each ml contains rivastigmina hydrogentartrate equivalent to 2.0 mg of rivastigmina base.
• The other components are sodium benzoate (E211), water-soluble quinoline yellow dye (E104) and purified water.

Appearance of the product and contents of the packaging

Rivastigmina Combix oral solution is presented in the form of a transparent, yellow (2.0 mg/ml rivastigmina base) 120 ml solution in amber glass bottles with a child-resistant closure. Along with the oral solution, a syringe for oral dosing is included.

Holder of the Marketing Authorization

Combix, S.L.U.

C/ Badajoz 2, Edificio 2

28223 Pozuelo de Alarcón (Madrid)

Spain

Responsible for manufacturing

Industria Química y Farmacéutica VIR, S.A.

C/ Laguna 66-68-70, Pol. Industrial Urtinsa II

28923 Alcorcón (Madrid)

Spain

Last review date of this leaflet: January 2025

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