Dezipar 10 mg/10 mg film-coated tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Dezipar 10 mg/10 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 others, even if they have the same symptoms as you, because it could harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if such adverse effects are not listed in this leaflet. See section 4.

Leaflet contents

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 adverse effects
5. How to store Dezipar

Pack contents and other information

1. What Dezipar is and what it is used for

What Dezipar is used for

Dezipar is indicated as replacement therapy in adult patients with moderate to severe Alzheimer's disease who are adequately controlled on a stable daily dose of 10 mg donepezil and 10 mg memantine, taken as 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 brain levels of a substance involved in memory (acetylcholine) by reducing the rate of breakdown of this substance. Memantine hydrochloride, by inhibiting the activity of NMDA receptors, improves nerve signal transmission 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 ingredients of this medicine (listed in section 6).
• if you are pregnant or think you might be pregnant.

Warnings and precautions

Consult your doctor before starting 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 myocardial infarction (heart attack), or if you have congestive heart disease or uncontrolled hypertension (high blood pressure).
• a heart condition (such as irregular or very slow heartbeats, heart failure, myocardial infarction)
• a heart condition called "QT interval prolongation" or a history of certain abnormal heart rhythms known as torsade de pointes, or if anyone in your family has "QT interval prolongation"
• low levels of magnesium or potassium in the blood
• seizures
• asthma or chronic lung disease
• difficulty urinating or kidney problems
• liver problems, as the use of Dezipar is not recommended in patients with severe hepatic impairment.

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

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. Dezipar may be used in patients with mild to moderate hepatic impairment. Patients with severe hepatic impairment must not take Dezipar.

You should avoid taking Dezipar 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

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

Other medicines and Dezipar

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

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

• Medicines for heart rhythm problems, for example amiodarone or sotalol

• 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

• Antifungal medicines, such as ketoconazole or itraconazole

• Medication for heart disease, for example quinidine, beta-blockers (propranolol and atenolol)

• Medicines to treat bacterial infections (such as clarithromycin, erythromycin, levofloxacin, moxifloxacin, rifampicin)

• .

• Medicines to treat depression (e.g., citalopram, escitalopram, amitriptyline, fluoxetine)

• Phenytoin and carbamazepine (for treating epilepsy)

• Cholinergic agonists and medicines with anticholinergic activity (acting on the central nervous system) such as tolterodine

• Muscle relaxants, e.g., diazepam, succinylcholine

• General anesthesia

• Over-the-counter medicines, for example, herbal remedies

• 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), 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

• Medicines to treat psychosis (e.g., pimozide, sertindole, ziprasidone)

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

If you are admitted to hospital, 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 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 Dezipar if you are pregnant or think you might be pregnant.

Breastfeeding

Women taking Dezipar must not breastfeed.

Driving and using machines

Your doctor will advise you whether your condition allows you to drive and operate machinery safely.

Furthermore, Dezipar may affect your reaction ability, so driving or operating machinery may be inappropriate.

3. How to take Dezipar

Follow exactly the instructions for use of 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 renal 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 little water, at night immediately before going to bed. If you experience abnormal dreams, nightmares, or difficulty sleeping (see section 4), your doctor may recommend that you take Dezipar in the morning. Tablets may be taken with or without food.

The tablet's 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 Dezipar 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 also experience an increase in the symptoms described in section 4 "Possible adverse effects".

If you forget to take Dezipar

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 Dezipar

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 will experience them.

The following serious adverse effects have been reported only with the use of donepezil as an individual component. You must inform your doctor immediately if you notice any of the following 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, especially if accompanied by feeling unwell, fever, or dark 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)

• Diarrhea
• Nausea
• Headache

Common (may affect up to 1 in 10 people)

• Cold symptoms
• 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 disturbances

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

• Changes in heart activity visible on an electrocardiogram (ECG), known as "QT interval prolongation"
• Fast or 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 contractions with abnormal lateral 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 clot formation 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 effects, consult your doctor or pharmacist, even if they are possible adverse effects not listed in this leaflet. You may 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 Dezipar

Keep this medicine out of the 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 a SIGRE Point at your 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 Dezipar

• The active substances are donepezil hydrochloride and memantine hydrochloride. Each tablet contains 10 mg of donepezil hydrochloride (equivalent to 9.12 mg of donepezil base) and 10 mg of memantine hydrochloride (equivalent to 8.31 mg of memantine).
• The other components (excipients) are: Core: mannitol (E421), microcrystalline cellulose, maize starch, hydroxypropylcellulose, sodium croscarmellose, and magnesium stearate. Coating: partially hydrolysed polyvinyl alcohol, titanium dioxide (E171), macrogol 4000, talc, and indigo carmine (E132).

Appearance of the product and contents of the pack

Dezipar 10 mg/10 mg film-coated tablets are presented as blue, circular (approximately 9 mm in diameter), convex film-coated tablets.

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

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation 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 most recent revision of this leaflet: March 2023

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