DEZIPAR 10 MG/20 MG FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the Patient

Dezipar 10 mg/20 mg Film-Coated Tablets

Donepezil Hydrochloride/Memantine Hydrochloride

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

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

Contents of the Package Leaflet

1. What Dezipar is and what it is used for
2. What you need to know before taking Dezipar
3. How to take Dezipar
4. Possible side effects
5. Storage of Dezipar

Contents of the pack and further information

1. What Dezipar is and what it is used for

What Dezipar is used for

Dezipar is indicated as a replacement 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 Dezipar works

Dezipar 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 decreasing the breakdown of this substance. Memantine hydrochloride, by inhibiting the activity of NMDA receptors, improves the transmission of nerve signals and memory.

2. What you need to know before taking Dezipar

Do not take Dezipar

• 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 Dezipar 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.
• a heart condition (such as irregular or very slow heartbeats, heart failure, heart attack)
• 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
• seizures
• asthma or chronic lung disease
• difficulty urinating or kidney problems
• liver problems, as Dezipar is not recommended for patients with severe liver failure.

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

If you have kidney failure (kidney problems), your doctor should closely monitor your kidney function and, if necessary, adjust the dose 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 (urinary tract), your doctor may need to adjust the dose of the medication.

Tell your doctor if you have any liver disease. Dezipar can be used in patients with mild to moderate liver failure. Patients with severe liver failure should not take Dezipar.

You should avoid taking Dezipar 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

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

Other medications and Dezipar

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

Tell your doctor or pharmacist if you are using, have recently used, or may need to use any other medication, especially if you are taking any of the following medications:

• Medications for heart rhythm problems, such as amiodarone or sotalol.
• Other medications 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.
• Antifungal medications, such as ketoconazole or itraconazole.
• Medications for heart disease, such as quinidine, beta-blockers (propranolol and atenolol).
• Medications for treating bacterial infections (such as clarithromycin, erythromycin, levofloxacin, moxifloxacin, rifampicin).
• Medications for treating depression (e.g., citalopram, escitalopram, amitriptyline, fluoxetine).
• Phenytoin and carbamazepine (for treating epilepsy).
• Cholinergic agonists and medications with anticholinergic activity (with action on the central nervous system) such as tolterodine.
• Muscle relaxants, e.g., diazepam, succinylcholine.
• General anesthesia.
• Over-the-counter medications, such as herbal remedies.
• 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) e.g., phenytoin, 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.
• Medications for treating psychoses (e.g., pimozide, sertindol, ziprasidone).

In the event of surgical intervention with general anesthesia, you should inform your doctor that you are taking Dezipar, as this may affect the amount of anesthetic needed.

If you are hospitalized, inform your doctor that you are taking Dezipar.

Taking Dezipar with food, drinks, and alcohol

You should inform 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 medication should not be taken with alcohol, as alcohol may alter the effect of this medication.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medication.

Pregnancy

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

Breastfeeding

Women taking Dezipar should not breastfeed.

Driving and using machines

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

Also, Dezipar may alter your reaction ability, so driving or operating machines may be inappropriate.

3. How to take Dezipar

Follow the administration instructions of this medication exactly 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 impairment

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 impairment

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

Use in children and adolescents

Dezipar 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. If you have abnormal dreams, nightmares, or difficulty sleeping (see section 4), your doctor may recommend that you take Dezipar in the morning. The tablets can be taken with or without food.

Duration of treatment

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

If you take more Dezipar than you should

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology 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 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 Dezipar

If you realize that 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 treatment with Dezipar

Do not stop treatment with 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.

4. Possible side effects

Like all medications, this medication can cause side effects, although not everyone 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 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 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 that 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 (creatine kinase) in the blood

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

• Extrapyramidal symptoms (such as tremors or rigidity of the hands or legs)
• Alterations in cardiac conduction

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

• Changes in cardiac activity that can be seen on 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 (difficulty breathing)
• High blood pressure
• Hypersensitivity to the medication.

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, consult your doctor or pharmacist, even if they are side effects not listed in this package leaflet. You can also report them directly through the national reporting system: Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Dezipar

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date stated 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 wastewater or household waste. Deposit the packaging and medications you no longer need at the SIGRE collection point in the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. This will help protect the environment.

6. Contents of the pack and further information

Composition of Dezipar

• The active ingredients are donepezil hydrochloride and memantine hydrochloride. Each tablet contains 10 mg of donepezil hydrochloride (equivalent to 9.12 mg of donepezil base) and 20 mg of memantine hydrochloride (equivalent to 16.62 mg of memantine base).
• The other components (excipients) are: Core: mannitol (E421), microcrystalline cellulose, cornstarch, hydroxypropylcellulose, sodium croscarmellose, and magnesium stearate. Coating: partially hydrolyzed polyvinyl alcohol, titanium dioxide (E171), macrogol 4000, and talc.

Appearance of the product and contents of the pack

Dezipar 10 mg/20 mg film-coated tablets are presented in the form of white or off-white, circular (approximately 9 mm in diameter), and convex film-coated tablets.

The tablets are available in PVC/PE.EVOH.PE/PCTFE-Aluminum blister packs containing 28 tablets.

Marketing authorization holder and manufacturer

Marketing authorization holder

Zambon S.A.U.

C/Maresme, 5. Polígono Can Bernades-Subirà

08130 Sta. Perpètua de la Mogoda – Barcelona

Spain

Manufacturer

Atlantic Pharma – Produções Farmacêuticas, S.A.

Rua da Tapada Grande, nº2, Abrunheira

2710-228 Sintra

Portugal

Date of the last revision of this package leaflet: March 2023

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