RIVASTIGMINE COMBIX 2 mg/ml ORAL SOLUTION

2. What you need to know before taking Rivastigmine Combix

Do not takeRivastigmine Combix

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

If you are in any of these situations, inform your doctor and do not take rivastigmine.

Warnings and Precautions

Consult your doctor before starting to take Rivastigmine:

• if you have or have ever 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 potassium or magnesium levels.
• if you have or have ever had an active stomach ulcer.
• if you have or have ever had difficulty urinating.
• if you have or have ever had seizures.
• if you have or have ever had asthma or severe respiratory disease.
• if you have or have ever had kidney function impairment.
• if you have or have ever had liver function impairment.
• if you suffer from tremors.
• if you have low body weight.
• if you have gastrointestinal reactions such as a feeling of dizziness (nausea), vomiting, and diarrhea. You may become dehydrated (lose a large amount of fluid) if vomiting or diarrhea is prolonged.

If you are in any of these situations, your doctor may consider it necessary to monitor you more closely while you are being treated.

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

Children and Adolescents

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

Other Medications and Rivastigmine Combix

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

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

Rivastigmine 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.

In case you need to undergo surgery while taking rivastigmine, inform your doctor before any anesthetic is administered, as rivastigmine may enhance the effects of some muscle relaxants during anesthesia.

Caution should be exercised when using rivastigmine 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 can lead to fainting or loss of consciousness.

Caution should be exercised when using rivastigmine 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, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medication.

If you are pregnant, it is necessary to evaluate the benefits of using rivastigmine against the potential adverse effects for the fetus. Rivastigmine should not be used during pregnancy unless it is clearly necessary.

You should not breastfeed while being treated with rivastigmine.

Driving and Using Machines

Your doctor will inform you if your condition allows you to drive or use machinery safely. Rivastigmine 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 or use machinery, or perform other tasks that require your attention.

Rivastigmine Combix contains Sodium Benzoate (E211) and Sodium

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

This medication contains less than 1 mmol of sodium (23 mg) per ml; this is, essentially "sodium-free".

3. How to take Rivastigmine Combix

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

How to start treatment

Your doctor will indicate what dose of rivastigmine you should take.

• Normally, treatment starts with a low dose.
• Your doctor will gradually increase the dose depending on how you respond to 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 check your weight while you are taking this medication.

If you have not taken rivastigmine 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 rivastigmine.
• To benefit from your medication, take it every day.
• Take rivastigmine twice a day (in the morning and at night), with meals.

For exact dosing, the packages contain a graduated oral syringe. Using this syringe, extract the prescribed amount of rivastigmine from the bottle.

The syringe is inserted into the pierced cap, the bottle is inverted, the plunger is pulled until the liquid reaches the mark in mg, 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 rivastigmine can be taken directly from the syringe.

If you take more Rivastigmine Combix than you should

If you accidentally take more rivastigmine 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 Toxicology Information Service, phone 91 562 04 20, indicating the medication and the amount taken. Some people who have accidentally taken higher doses have experienced nausea, vomiting, diarrhea, high blood pressure, and hallucinations. There may also be a slowing of the heart rate and fainting.

If you forget to take Rivastigmine Combix

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

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

4. Possible side effects

Like all medications, this medication can cause side effects, although not everyone will experience them.

You may have side effects more frequently when starting your treatment or when your dose is increased. Generally, side effects will slowly disappear as your body gets used to the medication.

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

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

Common(may affect up to 1 in 10 people)

• Anxiety
• Sweating
• Headache
• Heartburn
• Weight loss
• Stomach pain
• Feeling of agitation
• Feeling of fatigue or weakness
• Feeling of general discomfort
• Tremors 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
• Skin 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)
• Heart rhythm problems such as fast or slow heart rate
• Gastrointestinal bleeding - manifested as blood in the stool or when vomiting
• Pancreatitis - signs include severe pain in the upper abdomen, often with nausea or vomiting
• Worsening of Parkinson's disease symptoms or development of similar symptoms - such as muscle stiffness, difficulty moving

Not known(cannot be estimated from available data):

• Severe vomiting that can cause a tear in the digestive tube that connects the mouth to the stomach (esophagus)

• Dehydration (loss of a large amount of fluid)
• Liver disorders (yellowing of the skin, yellowing of the whites of the eyes, abnormal darkening of urine or unexplained nausea, vomiting, fatigue, and loss of appetite)
• Aggression, feeling of restlessness
• Irregular heart rhythm
• Pisa syndrome (a 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)

• Tremors
• Fainting
• Accidental falls

Common(may affect up to 1 in 10 people)

• Anxiety
• Feeling of restlessness
• Fast or slow heart rate
• Difficulty sleeping
• Excessive saliva and dehydration
• Abnormally slow movements or movements that cannot be controlled
• 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 heartbeat and loss of movement control

Not known(cannot be estimated from available data)

• Pisa syndrome (a 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 the oral solution:

Common(may affect up to 1 in 10 people)

• Fever
• Severe confusion
• Urinary incontinence (inability to properly control urine)

Uncommon(may affect up to 1 in 100 people)

• Hyperactivity (high level of activity, restlessness)

Not known(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 you may require medical attention.

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 is not listed in this package leaflet. You can also report them directly through the Spanish Medication Surveillance System for Human Use: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Rivastigmine Combix

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

Do not use Rivastigmine Combix after the expiration date stated on the package after CAD. The expiration date is the last day of the month indicated.

No special storage conditions are required. Use Rivastigmine Combix within one month after opening the bottle.

Medications should not be disposed of through wastewater or household waste. Deposit the packages and medications you no longer need at the SIGRE collection point in your pharmacy. Ask your pharmacist how to dispose of packages and medications you no longer need. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Rivastigmine Combix

• The active ingredient is rivastigmine hydrogen tartrate. Each ml contains rivastigmine hydrogen tartrate equivalent to 2.0 mg of rivastigmine base.
• The other ingredients are sodium benzoate (E211), water-soluble quinoline yellow (E104), and purified water.

Appearance of the Product and Package Contents

Rivastigmine Combix oral solution is presented as a clear, yellow solution (2.0 mg/ml rivastigmine base) in 120 ml amber glass bottles with a child-resistant closure. A dosing oral syringe is included with the oral solution.

Marketing Authorization Holder

Combix Laboratories, S.L.U.

Badajoz Street 2, Building 2

28223 Pozuelo de Alarcón (Madrid)

Spain

Manufacturer

Industria Química y Farmacéutica VIR, S.A.

Laguna Street 66-68-70, Urtinsa II Industrial Park

28923 Alcorcón (Madrid)

Spain

Date of the last revision of this package leaflet: January 2025

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