DOMEX 10 MG/10 MG FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the Patient

Domex 10 mg/10 mg Film-Coated Tablets

Donepezil Hydrochloride/Memantine Hydrochloride

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

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

Contents of the Package Leaflet

1. What is Domex and what is it used for
2. What you need to know before taking Domex
3. How to take Domex
4. Possible side effects
5. Storage of Domex

Package Contents and Additional Information

1. What is Domex and what is it used for

What Domex is used for

Domex is indicated as a replacement treatment in adult patients with moderate to severe Alzheimer's disease who are adequately controlled with a stable daily dose of 10 mg of donepezil and 10 mg of memantine, taken as a free combination.

How Domex works

Domex is a combination of an acetylcholinesterase inhibitor (donepezil) and an NMDA receptor antagonist (memantine). Acetylcholinesterase inhibitors, such as donepezil, increase the levels of a substance related to memory (acetylcholine) in the brain by decreasing the breakdown of this substance. Memantine hydrochloride, by inhibiting the activity of NMDA receptors, improves the transmission of nerve signals and memory.

There is no evidence that Domex prevents or slows down the underlying disease process in patients with Alzheimer's disease.

2. What you need to know before taking Domex

Do not take Domex

• if you are allergic to memantine hydrochloride, donepezil hydrochloride, piperidine derivatives, or any of the other components of this medication (listed in section 6).
• if you are pregnant or think you may be pregnant.

Warnings and Precautions

Consult your doctor before starting to take Domex if you have or have had:

• a history of stomach or duodenal ulcers
• a history of epileptic seizures
• if you have recently had a myocardial infarction (heart attack), or if you suffer from congestive heart failure or uncontrolled hypertension.
• seizures
• asthma or chronic lung disease
• difficulty urinating or kidney problems
• liver problems, as the use of Domex is not recommended in patients with severe liver failure
• a cardiac condition called "prolonged QT interval" or a history of certain abnormal heart rhythms called torsades de pointes, or if a family member has "prolonged QT interval"

low levels of magnesium or potassium in the blood.

In the above situations, treatment should be carefully supervised, and your doctor should regularly reassess the clinical benefit of Domex.

If you have kidney failure, your doctor should closely monitor your kidney function and, if necessary, adjust the dose of memantine.

If you have renal tubular acidosis (RTA, excess of acid-producing substances in the blood due to kidney dysfunction) or severe urinary tract infections, your doctor may need to adjust the dose of the medication.

Inform your doctor if you have any liver disease. Domex can be used in patients with mild to moderate liver failure. Patients with severe liver failure should not take Domex.

You should avoid taking Domex with other acetylcholinesterase inhibitors and other agonists or antagonists of the cholinergic system, with medications such as amantadine (for the treatment of Parkinson's disease), ketamine (a medication generally used to produce anesthesia), dextromethorphan (a medication for the treatment of cough), and other NMDA antagonists.

Children and Adolescents

The use of Domex is not recommended in children and adolescents under 18 years of age.

Other Medications and Domex

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

Inform your doctor or pharmacist if you are using, have recently used, or may need to use any other medication, and especially if you are taking any of the following types of medications:

• Other medications for the treatment of Alzheimer's disease, such as galantamine.
• Pain relievers or treatments for arthritis, such as aspirin, non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen or diclofenac sodium.
• Ketoconazole and itraconazole (for the treatment of fungal infections).
• Quinidine and beta-blockers for the treatment of irregular heartbeats, such as propranolol and atenolol.
• Antibiotics for the treatment of bacterial infections, such as erythromycin and rifampicin.
• Antidepressants, such as fluoxetine.
• Phenytoin and carbamazepine (for the treatment of epilepsy).
• Cholinergic agonists and medications with anticholinergic activity (with action on the central nervous system) such as tolterodine.
• Amantadine, ketamine, dextromethorphan.
• Dantrolene, baclofen.
• Cimetidine, ranitidine, procainamide, quinidine, quinine, nicotine.
• Hydrochlorothiazide (or any combination with hydrochlorothiazide).
• Anticonvulsants (substances used to prevent and eliminate seizures).
• Barbiturates (substances generally used to induce sleep).
• Dopaminergic agonists (substances such as L-dopa, bromocriptine).
• Neuroleptics (substances used in the treatment of mental illnesses).
• Oral anticoagulants
• medications for heart rhythm problems, such as amiodarone or sotalol
• medications for depression, such as citalopram, escitalopram, amitriptyline, fluoxetine
• medications for psychosis, e.g., pimozide, sertindole, or ziprasidone
• medications for bacterial infections, such as clarithromycin, erythromycin, levofloxacin, moxifloxacin, rifampicin
• antifungal medications, such as ketoconazole
• other medications for Alzheimer's disease, such as galantamine
• pain relievers or treatments for arthritis, such as aspirin, non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen or diclofenac sodium
• anticholinergic medications, e.g., tolterodine
• anticonvulsants, e.g., phenytoin, carbamazepine
• medications for heart disease, such as quinidine, beta-blockers (propranolol and atenolol)
• muscle relaxants, e.g., diazepam, succinylcholine
• general anesthetics
• over-the-counter medications, such as herbal remedies.

In the event of surgical intervention with general anesthesia, you should inform your doctor that you are taking Domex, as this may affect the amount of anesthetic needed.

If you are hospitalized, inform your doctor that you are taking Domex.

Taking Domex with Food, Drinks, and Alcohol

You should inform your doctor if you have recently changed or intend to change your diet substantially (e.g., from a normal diet to a strict vegetarian diet).

This medication should not be taken with alcohol, as alcohol may alter the effect of this medication.

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.

Pregnancy

Do not take Domex if you are pregnant or think you may be pregnant.

Breastfeeding

Women taking Domex should not breastfeed.

Driving and Using Machines

Your doctor will inform you whether your condition allows you to drive and use machines safely.

Additionally, Domex may alter your reaction ability, so driving or operating machines may be inappropriate.

3. How to Take Domex

Follow your doctor's instructions for taking this medication exactly. If you are unsure, consult your doctor or pharmacist again.

Dosage

The recommended dose in adult and elderly patients is 1 tablet administered once a day.

Dosage for Patients with Renal Impairment

If you have kidney problems, your doctor will decide on the appropriate dose for your condition. In this case, your doctor should periodically monitor your kidney function.

Dosage for Patients with Hepatic Impairment

If you have liver failure of mild or moderate severity, you can take this medication. Patients with severe liver failure should not take this medication.

Use in Children and Adolescents

The use of this medication is not recommended in children and adolescents under 18 years of age.

Method of Administration and Route of Administration

It is administered orally, with a little water, at night immediately before bedtime. The tablets can be taken with or without food.

If you have abnormal dreams, nightmares, or difficulty sleeping (see section 4), your doctor may recommend taking Domex in the morning.

The score line should not be used to divide the tablet.

Duration of Treatment

Continue taking this medication as long as it is beneficial for you. Your doctor should periodically evaluate the effects of your treatment.

If You Take More Domex Than You Should

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

The symptoms of overdose may include nausea, vomiting, drooling, sweating, decreased heart rate, low blood pressure (dizziness or fainting when standing up), breathing problems, loss of consciousness, and seizures. You may experience an increase in the symptoms described in section 4 "Possible Side Effects".

If You Forget to Take Domex

If you realize you have forgotten to take your dose, wait and take the next dose at the usual time.

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

If You Interrupt Treatment with Domex

Do not interrupt treatment with this medication unless your doctor tells you to. If you stop taking this medication, the benefits of treatment will gradually disappear.

If you have any other questions 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.

The following serious side effectshave been reported only with the use of donepezil as an individual component. You should inform your doctor immediately if you notice any of these serious side effects, as you may need urgent medical treatment:

• Liver damage, such as hepatitis. The symptoms of hepatitis are nausea or vomiting, loss of appetite, general malaise, fever, itching, yellowing of the skin and eyes, and dark-colored urine (rare: may affect up to 1 in 1,000 people).
• Ulcers in the stomach or duodenum. The symptoms of ulcers are stomach pain and discomfort (indigestion) between the navel and the sternum (uncommon: may affect up to 1 in 100 people).
• Bleeding in the stomach or intestine. This can cause you to have black, tarry stools or visible blood from the rectum (uncommon: may affect up to 1 in 100 people).
• Seizures or convulsions (uncommon: may affect up to 1 in 100 people).
• Fever with muscle stiffness, sweating, decreased level of consciousness (may be symptoms of a condition called "Neuroleptic Malignant Syndrome") (very rare: may affect up to 1 in 10,000 people).
• Weakness, sensitivity, or muscle pain, particularly if you also feel unwell, have a fever, or have dark-colored urine. This may be due to abnormal muscle destruction that can be fatal and cause kidney problems (a condition called rhabdomyolysis) (very rare: may affect up to 1 in 10,000 people).

The following side effects are described for the individual components, donepezil (5-10 mg) or memantine (10-20 mg):

Donepezil

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

• Diarrhea
• Nausea
• Headache

Common (may affect up to 1 in 10 people)

• Cold
• Loss of appetite
• Hallucinations
• Agitation
• Aggressive behavior
• Abnormal dreams and nightmares
• Fainting
• Dizziness
• Difficulty sleeping
• Vomiting
• Abdominal discomfort
• Urinary incontinence (difficulty retaining urine)
• Rash
• Itching
• Muscle cramps
• Fatigue
• Pain
• Accidents (patients may be more prone to falls and accidental injuries)

Uncommon (may affect up to 1 in 100 people)

• Decreased heart rate (bradycardia)
• Increased levels of a type of enzyme (creatinine kinase) in the blood

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

• Extrapyramidal symptoms (such as tremors or rigidity of the hands or legs)
• Alterations in cardiac conduction

Frequency Not Known (frequency cannot be estimated from available data):

• Changes in cardiac activity that can be observed in an electrocardiogram (ECG) called "prolonged QT interval"
• Rapid and irregular heartbeat, fainting that can be symptoms of a potentially life-threatening disorder known as torsades de pointes
• Increased libido, hypersexuality
• Pisa syndrome (a condition involving involuntary muscle contraction with abnormal flexion of the body and head to one side)

Memantine

In general, side effects are mild to moderate.

Common (may affect up to 1 in 10 people)

• Headache
• Somnolence
• Constipation
• Elevated liver function tests
• Dizziness
• Balance disorders
• Shortness of breath (difficulty breathing)
• High blood pressure
• Hypersensitivity to the medication.

Uncommon (may affect up to 1 in 100 people)

• Fatigue
• Fungal infections
• Confusion
• Hallucinations
• Vomiting
• Gait disturbances
• Heart failure
• Formation of blood clots in the venous system (thrombosis/thromboembolism).

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

• Seizures

Frequency Not Known (frequency cannot be estimated from available data)

• Pancreatitis
• Hepatitis (inflammation of the liver)
• Psychotic reactions.

Alzheimer's disease has been associated with depression, suicidal ideation, and suicide. These events have been reported in patients treated with memantine.

Reporting Side Effects

If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this package leaflet. You can also report them directly through the national reporting system: Spanish Pharmacovigilance System for Human Use Medications: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Domex

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

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

This medication does not require special storage conditions.

Medications should not be disposed of through wastewater or household waste. Deposit the packaging and any unused medication in the SIGRE collection point at the pharmacy. If you have any questions, ask your pharmacist how to dispose of the packaging and any unused medication. This will help protect the environment.

6. Packaging Content and Additional Information

Composition of Domex

• The active ingredients are donepezil hydrochloride and memantine hydrochloride. Each tablet contains 10 mg of donepezil hydrochloride (equivalent to 9.14 mg of donepezil base) and 10 mg of memantine hydrochloride (equivalent to 8.31 mg of memantine).
• The other components are: microcrystalline cellulose, povidone K25, sodium croscarmellose, magnesium stearate, hypromellose, titanium dioxide (E171), and triacetin.

Appearance of the Product and Packaging Content

Domex 10 mg/10 mg is presented in the form of film-coated tablets, oblong, biconvex, white in color, with a score line on one of the faces. The score line should not be used to divide the tablet.

The tablets are available in packs with PVC/PCTFE/PVC-Aluminum blisters containing 28 tablets.

Marketing Authorization Holder and Manufacturer

Laboratorios Alter, S.A.

C/ Mateo Inurria, 30

28036, Madrid

Spain

or

Laboratorios Alter, S.A.

C/ Zeus, 6

Polígono Industrial R2

28880, Meco (Madrid)

Spain

Date of the Last Revision of this Prospectus: October 2022

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/).