Domex 10 mg/10 mg film-coated tablets

Patient Information Leaflet

Introduction

Patient Information Leaflet

Domex 10 mg/10 mg film-coated tablets

donepezil hydrochloride/memantine hydrochloride

Read the entire leaflet carefully before you start taking this medicine, as 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 others, 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

Pack contents 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 10 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 brain levels of a substance involved in memory (acetylcholine) by reducing its breakdown rate. Memantine hydrochloride, by inhibiting NMDA receptor activity, 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 components 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
• recent myocardial infarction (heart attack), or if you have congestive heart disease or uncontrolled hypertension (high blood pressure)
• 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 must 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 with other acetylcholinesterase inhibitors and other cholinergic agonists or antagonists, and with medicines such as amantadine (for the treatment of Parkinson's disease), ketamine (a medicine generally used to induce anesthesia), dextromethorphan (a medicine 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 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 to inform 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 (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, rifampicin.
• Antidepressants such as fluoxetine.
• Phenytoin and carbamazepine (for treating epilepsy).
• Cholinergic agonists and medicines with anticholinergic activity (acting on the central nervous system) such as tolterodine.
• Amantadine, 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 treatment for arthritis, 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
• medicines obtained without a prescription, 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 might be pregnant, or plan 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 condition allows you to drive or operate machinery safely.

In addition, Domex may affect your reaction capabilities, so driving or operating machinery may be inappropriate.

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

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

Method of administration and route

Administered orally, with a little water, at night immediately before going to bed. The 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.

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

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: 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 adverse 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 treatment with this medicine unless instructed by your doctor. 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 experiences them.

The following serious adverse effects have been reported with donepezil used alone. 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-colored 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).
• Muscle weakness, tenderness, or pain, particularly if you also feel unwell, have fever, or have dark-colored urine. This may be due to abnormal muscle breakdown, which can be fatal 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)

• 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 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 disorders

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

• Changes in heart activity seen on an electrocardiogram (ECG), known as "QT interval prolongation"
• Fast and irregular heartbeat, fainting, which may be symptoms of a potentially life-threatening disorder known as torsade de pointes
• Increased libido, hypersexuality
• Pisa syndrome (a condition involving involuntary muscle contractions causing 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
• Somnolence (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 which is stated on the packaging after EXP. The expiry date corresponds to 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 containers and unused medicines at the SIGRE collection point at the pharmacy. If you have any doubts, ask your pharmacist how to dispose of containers and unused medicines. 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 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 medicine and contents of the pack

Domex 10 mg/10 mg is presented as film-coated, oblong, biconvex, white tablets with a score line on one side. The score line is not intended for dividing the tablet.

The tablets are available in PVC/PCTFE/PVC-Aluminum blister packs 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 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/).