Package Insert: Information for the Patient

Donepezilo/memantina TecniGen 10 mg/20 mg Film-Coated Tablets

Donepezil hydrochloride/memantine hydrochloride

Read this 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.

What it is used forDonepezilo/memantina

Donepezilo/memantina is indicated as a replacement treatment in adult patients with moderate to severe Alzheimer's disease adequately controlled with a daily dose of 10 mg of donepezilo and 20 mg of memantina, taken as a free combination.

How it worksDonepezilo/memantina

Donepezilo/memantina is a combination of an acetylcholinesterase inhibitor (donepezilo) and an NMDA receptor antagonist (memantina). Acetylcholinesterase inhibitors, such as donepezilo, increase the levels in the brain of a substance related to memory (acetylcholine) by reducing the rate of decomposition of this substance. Memantine hydrochloride, by inhibiting the activity of NMDA receptors, improves the transmission of nerve signals and memory.

Do not take Donepezilo/memantina

• if you are allergic to memantine hydrochloride, donepezil hydrochloride, piperidine derivatives, or any of the other ingredients 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 Donepezilo/memantina if you have or have had:

• stomach or duodenal ulcers
• seizure disorders
• heart disease (such as irregular or slow heartbeats, heart failure, heart attack) or uncontrolled high blood pressure
• 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
• seizures
• asthma or chronic lung disease
• difficulty urinating or kidney problems
• liver problems, as Donepezilo/memantina is not recommended for patients with severe liver insufficiency.

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

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 (RTA, 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. Donepezilo/memantina can be used in patients with mild to moderate liver insufficiency. Patients with severe liver insufficiency should not take Donepezilo/memantina.

You should avoid taking Donepezilo/memantina 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

Donepezilo/memantina is not recommended for use in children and adolescents under 18 years old.

Other medications and Donepezilo/memantina

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 if you are taking any of the following medications:

• Other medications for Alzheimer's disease, such as galantamine.
• Pain relievers or arthritis treatment, such as aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen or diclofenac sodium.
• Antifungal medications, such as ketoconazole and itraconazole (for fungal infections).
• Medications for heart disease, such as quinidine, beta-blockers (propranolol and atenolol).
• Medications for abnormal heart rhythms, such as amiodarone or sotalol.
• Medications for depression, such as citalopram, escitalopram, amitriptyline, fluoxetine.
• Medications for psychosis, p.ej., pimozide, sertindole, ziprasidone.
• Medications for bacterial infections, such as clarithromycin, erythromycin, levofloxacin, moxifloxacin, rifampicin.
• Phenitoin and carbamazepine (for epilepsy treatment).
• Cholinergic agonists and anticholinergic medications (acting on the central nervous system) such as tolterodine.
• Muscle relaxants (for muscle relaxation), p. ej., diazepam, succinylcholine.
• General anesthetics.
• Amantadine, ketamine, dextromethorphan.
• Dantrolene, baclofen.
• Cimetidine, ranitidine, procainamide, quinidine, quinine, nicotine.
• Hidrochlorothiazide (or any combination with hidrochlorothiazide).
• Anticonvulsants (substances used to prevent and eliminate seizures), p. ej., phenitoin, carbamazepine.
• 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.
• Over-the-counter medications, such as herbal remedies.

In case of surgical intervention with general anesthesia, inform your doctor that you are taking Donepezilo/memantina, as this may affect the amount of anesthetic needed.

If you are admitted to a hospital, inform your doctor that you are taking Donepezilo/memantina.

Donepezilo/memantina with food, drinks, and alcohol

Inform your doctor if you have recently changed or plan 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, or think you may be pregnant, consult your doctor or pharmacist before using this medication.

Pregnancy

Do not take Donepezilo/memantina if you are pregnant or think you may be pregnant.

Breastfeeding

Women taking Donepezilo/memantina should not breastfeed.

Driving and operating machinery

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

Donepezilo/memantina 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. If you have abnormal dreams, nightmares, or difficulty sleeping (see section 4), your doctor may recommend taking donepezil/memantine in the morning. The tablets can be taken with or without food.

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 more Donepezil/memantine 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 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 Donepezil/memantine

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 with Donepezil/memantine

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 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 tremors or stiffness of the hands or legs)
• Alterations in heart conduction

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, 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
• Heatitis (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 storage 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 Donepezilo/memantina

Appearance of the product and content of the packaging

Donepezilo/memantina TecniGen 10 mg/20 mg film-coated tabletsare presented in the form of film-coated tablets of white or off-white color, circular in shape (approximately 9 mm in diameter) and convex.

The tablets are available in packaging with PVC/PE.EVOH.PE/PCTFE-Aluminum blisters that contain 28 tablets.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Tecnimede España Industria Farmacéutica, S.A.

Avda. de Bruselas, 13, 3rd floor.

28108 Alcobendas (Madrid) Spain

Responsible for manufacturing

Atlantic Pharma – Produções Farmacêuticas, S.A.

Rua da Tapada Grande, nº2, Abrunheira

2710-089 Sintra

Portugal

Last review date of this leaflet: September 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/).