Package Insert: Information for the Patient

Domex 10 mg/10 mg Film-Coated Tablets

Donepezil Hydrochloride/Memantine Hydrochloride

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

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

Contents of the package and additional information

How Domex is used

Domex is indicated as a substitute treatment in adult patients with moderate to severe Alzheimer's disease adequately controlled with a 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 brain levels of a substance related to memory (acetylcholine) by reducing the rate of decomposition of this substance. 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.

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:

• stomach or duodenal ulcers
• seizure disorders
• recent myocardial infarction (heart attack), or if you have congestive heart failure or uncontrolled high blood pressure.
• convulsions
• asthma or chronic lung disease
• difficulty urinating or kidney problems
• liver problems, as Domex is not recommended for patients with severe liver insufficiency
• a heart condition called "prolongation of the QT interval" or a history of certain abnormal heart rhythms called torsade de pointes, or if someone in your family has "prolongation of the QT interval"

low levels of magnesium or potassium in the blood.

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

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

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

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

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

Children and adolescents

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

Other medications and Domex

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

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication, especially, it is essential to inform your doctorif you are taking any of the following types ofmedications:

• other medications for Alzheimer's disease, for example, galantamine.
• Analgesics or treatments for arthritis such as aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or diclofenac sodium.
• Ketoconazole and itraconazole (to treat 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.
• Phenobarbital and carbamazepine (to treat epilepsy).
• Cholinergic agonists and medications with anticholinergic activity (acting at 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).
• Dopamine agonists (substances such as L-dopa, bromocriptine).
• Neuroleptics (substances used in the treatment of mental illnesses).
• Oral anticoagulants
• medications for heart rhythm problems, for example amiodarone or sotalol
• medications for depression, for example citalopram, escitalopram, amitriptyline, fluoxetine
• medications for psychosis, p. e.g. pimozide, sertindole or ziprasidone
• medications for bacterial infections, for example, clarithromycin, erythromycin, levofloxacin, moxifloxacin, rifampicin
• antifungal medications, such as ketoconazole
• other medications for Alzheimer's disease, for example, galantamine
• analgesics or treatments for arthritis, for example, aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or diclofenac sodium
• anticholinergic medications, p. e.g. tolterodine
• anticonvulsants, p. e.g., phenytoin, carbamazepine
• heart medications, for example quinidine, beta-blockers (propranolol and atenolol)
• muscle relaxants, p. e.g., diazepam, succinylcholine
• general anesthetics
• over-the-counter medications, 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 admitted to a hospital, inform your doctor that you are taking Domex.

Domex with food, drinks, and alcohol

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

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

Pregnancy,breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or intend 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 operating machinery

Your doctor will inform you if your condition allows you to drive and use machinery safely.

Domex may also alter your reaction time, making driving or operating machinery inappropriate.

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, 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 insufficiency

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

Dosage for patients with hepatic insufficiency

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

Use in children and adolescents

This medication is not recommended for use in children and adolescents under 18 years old.

Form of use and route of administration

It is administered orally, with a little water, at night immediately before going to bed. 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 groove should not be used to split the tablet.

Treatment duration

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

If you take moreDomexthan 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 medication and the amount ingested.

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

If you forgot 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 compensate for the missed doses.

If you interrupt treatment withDomex

Do not stop taking 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.

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

The followingserious side effectshave been reported only with the use of donepezil as a single component. Inform your doctor immediately if you notice any of the following 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 discomfort, 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 breastbone (infrequent: may affect up to 1 in 100 people).
• Bleeding in the stomach or intestine. This may cause you to have black, tar-like stools or visible blood from the rectum (infrequent: may affect up to 1 in 100 people).
• Seizures (infrequent: 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 are also feeling unwell, have a fever, or your urine is dark. 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 side effects listed 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)

• Common 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)

Infrequent (may affect up to 1 in 100 people)

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

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

• Extrapyramidal symptoms (such as tremor or stiffness of the hands or legs)
• Conduction disorders of the heart

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

• Changes in heart activity that can be seen on an electrocardiogram (ECG) called "prolongation of the QT interval"
• Fast and irregular heartbeat, fainting that may be symptoms of a potentially fatal condition called torsade de pointes
• Increased libido, hypersexuality
• Pisa syndrome (a condition that involves involuntary muscle contractions with abnormal flexion of the body and head to one side)

Memantine

Generally, the side effects are mild to moderate.

Common (may affect up to 1 in 10 people)

• Headache
• Drowsiness
• Constipation
• Increased liver function tests
• Dizziness
• Balance disorder
• Shortness of breath (difficult breathing)
• High blood pressure
• Medication hypersensitivity.

Infrequent (may affect up to 1 in 100 people)

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

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

• Seizures

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

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

Alzheimer's disease has been associated with depression, suicidal ideation, and suicide. There have been reports of these events in patients treated with memantine.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the national notification system: Spanish System of Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

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

This medication does not require special conservation conditions.

Medications should not be disposed of through drains or trash. Dispose of packaging and medications you no longer need at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of packaging and medications you no longer need. By doing so, you will help protect the environment.

Composition of Domex

Appearance of the product and contents of the packaging

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

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

Holder of the marketing authorization and responsible for manufacturing

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

Last review date of this leaflet: October 2022

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