DOMEX 10 mg/20 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the Patient

Domex 10 mg/20 mg Film-Coated Tablets

Donepezil Hydrochloride/Memantine Hydrochloride

Read the entire package leaflet carefully before you start taking this medicine, as it contains important information for you.

• Keep this package leaflet, as you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, as it may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects 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 you take Domex
3. How to take Domex
4. Possible side effects
5. Storage of Domex

1. Contents of the pack and further information

1. What is Domex and what is it used for

What Domex is used for

Domex is indicated as a substitution 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 20 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 reducing 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 you take Domex

Do not take Domex

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

Warnings and precautions

Talk to 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 heart attack (heart attack), or if you have congestive heart failure or uncontrolled high blood pressure.
• 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 heart condition called "prolongation of the QT interval" or a history of certain abnormal heart rhythms called torsades de pointes, or if a family member has "prolongation of the 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 (kidney problems), your doctor should closely monitor your kidney function and, if necessary, adjust the doses 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 (urine conduit), your doctor may need to adjust the dose of the medicine.

Tell 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

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

Other medicines and Domex

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Tell your doctor or pharmacist if you are using, have recently used, or could use any other medicine, and especially if you are taking any of the following types of medicines:

• Other medicines for treating 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 treating fungal infections).
• Quinidine and beta-blockers for treating irregular heartbeats, such as propranolol and atenolol.
• Antibiotics for treating bacterial infections, such as erythromycin and rifampicin.
• Antidepressants, such as fluoxetine.
• Phenytoin and carbamazepine (for treating epilepsy).
• Cholinergic agonists and medicines 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 like L-dopa, bromocriptine).
• Neuroleptics (substances used in the treatment of mental illnesses).
• Oral anticoagulants
• medicines for heart rhythm problems, for example, amiodarone or sotalol
• medicines for depression, for example, citalopram, escitalopram, amitriptyline, fluoxetine
• medicines for psychosis, e.g., pimozide, sertindole, or ziprasidone
• medicines for bacterial infections, for example, clarithromycin, erythromycin, levofloxacin, moxifloxacin, rifampicin
• antifungal medicines, such as ketoconazole
• other medicines for Alzheimer's disease, for example, galantamine
• pain relievers or arthritis treatments, for example, aspirin, non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen or diclofenac sodium
• anticholinergic medicines, e.g., tolterodine
• anticonvulsants, e.g., phenytoin, carbamazepine
• medication for heart disease, for example, quinidine, beta-blockers (propranolol and atenolol)
• muscle relaxants, e.g., diazepam, succinylcholine
• general anesthetics
• over-the-counter medicines, for example, 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 tell 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 medicine should not be taken with alcohol, as alcohol may alter the effect of this medicine.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

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

Breastfeeding

Women who are taking Domex should not breastfeed.

Driving and using machines

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

Also, Domex may affect your ability to react, so driving or operating machinery may be inappropriate.

3. How to take Domex

Follow the instructions for administration of this medicine exactly as indicated by your doctor. If you are unsure, consult your doctor or pharmacist again.

Dosage

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

Dosage for patients with renal insufficiency

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 insufficiency

If you have liver failure (a disease that affects the liver) of mild or moderate severity, you can take this medicine. Patients with severe liver failure should not take this medicine.

Use in children and adolescents

Domex is not recommended for use 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 that you take Domex in the morning.

Duration of treatment

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

If you take more Domex than you should

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone: 91 562 04 20, indicating the medicine 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 stop taking Domex

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

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets 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, for example, 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, which can be life-threatening and cause kidney problems (a disease 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 tremor or rigidity of the hands or feet)
• 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 "prolongation of the 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 that involves 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 (difficult breathing)
• High blood pressure
• Hypersensitivity to the medicine.

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 of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this package leaflet. You can also report side effects directly through the national reporting system: Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Domex

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

Do not use this medicine after the expiry date which is stated on the packaging after EXP. The expiry date is the last day of the month indicated.

This medicine does not require any special storage conditions.

Medicines should not be disposed of via wastewater or household waste. Place the packaging and any unused medicine in the SIGRE collection point at your pharmacy. If you are unsure, ask your pharmacist how to dispose of the packaging and any unused medicine. 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 20 mg of memantine hydrochloride (equivalent to 16.62 mg of memantine base).
• 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/20 mg is presented in the form of film-coated tablets, oval, biconvex, white in color, without scores.

The tablets are available in blister packs of PVC/PCTFE/PVC-Aluminum 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 Leaflet: October 2022

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