Domex 10 mg/20 mg film-coated tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Domex 10 mg/20 mg film-coated tablets

donepezil hydrochloride/memantine hydrochloride

Read the entire leaflet carefully before you start taking 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, ask your doctor or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Leaflet contents

1. What Domex is and what it is used for

2. What you need to know before taking Domex

3. How to take Domex

4. Possible side effects

5. How to store Domex

6. Contents of the pack and other information

1. What Domex is and what it is used for

What Domex is used for

Domex is indicated as a replacement therapy 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 a cholinesterase inhibitor (donepezil) and an NMDA receptor antagonist (memantine). Cholinesterase inhibitors, such as donepezil, increase levels in the brain of a substance involved in memory (acetylcholine) by reducing the rate at which this substance is broken down. Memantine hydrochloride, by inhibiting the activity of NMDA receptors, improves nerve signal transmission and memory.

There is no evidence that Domex prevents or slows 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 ingredients of this medicine (listed in section 6).
• if you are pregnant or think you might be pregnant.

Warnings and precautions

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

• a history of stomach or duodenal ulcer
• a history of epileptic seizures
• a recent myocardial infarction (heart attack), or if you have congestive heart disease or uncontrolled high blood pressure (hypertension)
• seizures
• asthma or chronic lung disease
• difficulty urinating or kidney problems
• liver problems, as Domex is not recommended in patients with severe hepatic impairment
• a heart condition known as "QT interval prolongation" or a history of certain abnormal heart rhythms called torsade de pointes, or if someone in your family has "QT interval prolongation"
• low levels of magnesium or potassium in the blood.

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

If you have renal impairment (kidney problems), your doctor should closely monitor kidney function and, if necessary, adjust the memantine dosage.

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

Inform your doctor if you have any liver disease. Domex may be used in patients with mild to moderate hepatic impairment. Patients with severe hepatic impairment must not take Domex.

You should avoid taking Domex together with other acetylcholinesterase inhibitors and other cholinergic system agonists or antagonists, and with medicines such as amantadine (used to treat Parkinson's disease), ketamine (a medicine generally used to induce anesthesia), dextromethorphan (a medicine used to treat 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 medicines and Domex

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

Inform your doctor or pharmacist if you are using, have recently used, or might need to use any other medicines. It is especially important that you tell your doctor if you are taking any of the following types of medicines:

• Other medicines for Alzheimer's disease, for example galantamine.
• Painkillers or treatments for arthritis such as aspirin, non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or sodium diclofenac.
• Ketoconazole and itraconazole (used to treat fungal infections).
• Quinidine and beta-blockers used to treat irregular heartbeats such as propranolol and atenolol.
• Antibiotics used to treat bacterial infections such as erythromycin, rifampicin.
• Antidepressants such as fluoxetine.
• Phenytoin and carbamazepine (used to treat epilepsy).
• Cholinergic agonists and medicines with anticholinergic activity (acting on the central nervous system) such as tolterodine.
• Amantadina, ketamine, dextromethorphan.
• Dantrolene, baclofen.
• Cimetidine, ranitidine, procainamide, quinidine, quinine, nicotine.
• Hydrochlorothiazide (or any combination containing hydrochlorothiazide).
• Anticonvulsants (substances used to prevent and stop 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
• 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
• painkillers or arthritis treatments, for example, aspirin, non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or sodium diclofenac
• anticholinergic medicines, e.g., tolterodine
• anticonvulsants, e.g., phenytoin, carbamazepine
• medicines 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.

If you are undergoing surgery with general anesthesia, you must inform your doctor that you are taking Domex, as this may affect the amount of anesthetic required.

If you are admitted to hospital, 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 substantially change your diet (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 become pregnant, consult your doctor or pharmacist before using this medicine.

Pregnancy

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

Breastfeeding

Women taking Domex must not breastfeed.

Driving and using machines

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

Furthermore, Domex may affect your reaction ability, so driving or operating machinery may not be appropriate.

3. How to take Domex

Follow exactly the instructions for using this medicine as given by your doctor. If in doubt, consult your doctor or pharmacist again.

Dosage

The recommended dose in adult and elderly patients is 1 tablet taken once daily.

Dosage for patients with renal impairment

If you have kidney problems, your doctor will decide 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 mild or moderate hepatic impairment (liver disease), you may take this medicine. Patients with severe hepatic impairment (liver disease) must not take this medicine.

Use in children and adolescents

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

Method of administration and route of administration

Administered orally, with a small amount of water, at night immediately before going to bed. Tablets may be taken with or without food.

If you experience 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 for as long as it is beneficial to 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, contact your doctor or pharmacist immediately or call the Toxicology Information Service at telephone number: 91 562 04 20, indicating the medicine and the amount ingested.

Symptoms of overdose may include nausea, vomiting, salivation, sweating, decreased heart rate, low blood pressure (dizziness or lightheadedness upon standing), breathing difficulties, 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 missed a dose, wait and take the next dose at the usual time.

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

If you stop taking Domex

Do not stop treatment with this medicine unless your doctor advises you to do so. 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 adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

The following serious adverse effects have been reported with donepezil used as a single ingredient. You must inform your doctor immediately if you notice any of these serious adverse effects, as you may require urgent medical treatment:

• Liver damage, for example, hepatitis. Symptoms of hepatitis include nausea or vomiting, loss of appetite, general malaise, fever, itching, yellowing of the skin and eyes (jaundice), and dark-coloured urine (rare: may affect up to 1 in 1,000 people).
• Ulcers in the stomach or duodenum. Symptoms of ulcers include 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 may cause black, tarry stools or visible rectal bleeding (uncommon: may affect up to 1 in 100 people).
• Seizures or convulsions (uncommon: may affect up to 1 in 100 people).
• Fever with muscle rigidity, sweating, and decreased level of consciousness (these may be symptoms of a condition called "Neuroleptic Malignant Syndrome") (very rare: may affect up to 1 in 10,000 people).
• Weakness, tenderness, or muscle pain, especially if you also feel unwell, have fever, or dark-coloured urine. This may be due to abnormal muscle breakdown, which can be life-threatening and lead to kidney problems (a condition called rhabdomyolysis) (very rare: may affect up to 1 in 10,000 people).

The adverse effects described below reflect the frequencies previously reported for the individual components, donepezil (5–10 mg) or memantine (10–20 mg):

Donepezil

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

• Diarrhoea
• Nausea
• Headache

Common (may affect up to 1 in 10 people)

• Cold
• Loss of appetite
• Hallucinations
• Agitation
• Aggressive behaviour
• Abnormal dreams and nightmares
• Fainting
• Dizziness
• Difficulty sleeping
• Vomiting
• Abdominal discomfort
• Urinary incontinence (difficulty holding 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)

• Slowing of the heart rate (bradycardia)
• Increase in a type of enzyme (muscle creatine kinase) in the blood

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

• Extrapyramidal symptoms (such as tremor or stiffness in the hands or legs)
• Cardiac conduction disturbances

Frequency not known (frequency cannot be estimated from available data):

• Changes in heart activity that may be seen on an electrocardiogram (ECG), known as "QT interval prolongation"
• Fast and irregular heartbeat, fainting which may be symptoms of a potentially life-threatening condition known as torsade de pointes
• Increased libido, hypersexuality
• Pisa syndrome (a condition involving involuntary muscle contraction with abnormal sideways flexion of the body and head)

Memantine

In general, adverse effects are mild to moderate.

Common (may affect up to 1 in 10 people)

• Headache
• Drowsiness
• Constipation
• Elevated liver function tests
• Dizziness
• Balance disorder
• Shortness of breath (difficulty breathing)
• High blood pressure
• Hypersensitivity to the medicine

Uncommon (may affect up to 1 in 100 people)

• Fatigue
• Fungal infections
• Confusion
• Hallucinations
• Vomiting
• Gait disturbance
• Heart failure
• 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)

• Inflammation of the pancreas
• Inflammation of the liver (hepatitis)
• 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 adverse effects

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system: Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Domex

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiry date 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 must not be disposed of via wastewater or household waste. Dispose of empty containers and unused medicines at the SIGRE collection point at your pharmacy. If you are in doubt, ask your pharmacist how to dispose of containers and medicines you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Domex

• The active substances 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).
• The other components are: microcrystalline cellulose, povidone K25, sodium croscarmellose, magnesium stearate, hypromellose, titanium dioxide (E171), and triacetin.

Appearance of the medicine and contents of the pack

Domex 10 mg/20 mg is presented as film-coated tablets, oval, biconvex, white in colour, without a breakline.

The tablets are available in PVC/PCTFE/PVC-aluminium blister packs containing 28 tablets.

Marketing Authorisation 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 most recent revision of this leaflet: October 2022

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