Cervedalo

PACKAGE LEAFLET

Package leaflet: Information for the user

Cevedalo 10 mg/10 mg film-coated tablets, 10 mg/20 mg film-coated tablets

donepezil hydrochloride and memantine hydrochloride
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. 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. Do not give it to other people, even if they have the same symptoms as you, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What Cevedalo is and what it is used for
2. What you need to know before taking Cevedalo
3. How to take Cevedalo
4. Possible side effects
5. How to store Cevedalo
6. Contents of the pack and other information

1. What Cevedalo is and what it is used for

Cevedalo contains the active substances donepezil hydrochloride and memantine hydrochloride. Both belong to a group of medicines known as anti-dementia drugs. Donepezil hydrochloride, as an acetylcholinesterase inhibitor, increases in the brain the levels of a substance (acetylcholine) involved in memory function by slowing down the breakdown of acetylcholine. Memantine hydrochloride is an NMDA receptor antagonist. Memory loss in Alzheimer's disease arises from impaired signal transmission in the brain. The brain contains so-called N-methyl-D-aspartate (NMDA) receptors, which are involved in the transmission of nerve signals important for learning and memory. Memantine hydrochloride acts on these NMDA receptors, improving nerve signal transmission and memory.
Cevedalo should only be used in patients who are already taking donepezil and memantine simultaneously at the same doses as those contained in Cevedalo.
Cevedalo is used to treat the symptoms of dementia in people diagnosed with moderate to severe Alzheimer's disease. Symptoms include memory loss, confusion, and behavioural changes. As a result, people with Alzheimer's disease find it increasingly difficult to carry out their usual daily activities.
Cevedalo is indicated only in adult patients.

2. What you need to know before taking Cevedalo

Do not take Cevedalo

• if you are allergic (hypersensitive) to donepezil or piperidine derivatives, memantine, or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor before taking Cevedalo if you have or have had:

• a history of epileptic seizures or other convulsive episodes (attacks) or seizures. Cevedalo may cause a new seizure. Your doctor will monitor your symptoms.
• recent myocardial infarction (heart attack), a heart condition (particularly sick sinus syndrome or a similar condition – donepezil may slow heart rate), or if you have congestive heart failure or uncontrolled hypertension (high blood pressure).
• a heart condition called "prolonged QT interval" or a history of certain abnormal heart rhythms known as torsades de pointes, or if someone in your family has a prolonged QT interval.
• low levels of magnesium or potassium in the blood.
• stomach or duodenal ulcers, or if you are taking a certain type of painkiller (non-steroidal anti-inflammatory drugs – NSAIDs). Your doctor will monitor your symptoms.
• difficulty urinating. Your doctor will monitor your symptoms.
• asthma or other chronic lung diseases. Symptoms may worsen.

Also inform your doctor if you are pregnant or suspect you may be pregnant.
In these situations, treatment must be carefully supervised and the clinical benefit of Cevedalo must be regularly reassessed by your doctor.
Inform your doctor first if you have kidney or liver disease. Cevedalo can be used in patients with mild to moderate kidney or liver disease. Patients with severe liver disease must not take Cevedalo.
If you have renal impairment (kidney problems), your doctor must carefully monitor kidney function and, if necessary, adjust the doses of donepezil and memantine accordingly.
If you have renal tubular acidosis (RTA, an excess of acid-forming substances in the blood due to kidney dysfunction (poor kidney function)) or severe urinary tract infections (structures that carry urine), your doctor may need to adjust the dose of the medicine.
Concomitant use of medicines called amantadine (used to treat Parkinson's disease), ketamine (generally used as an anaesthetic), dextromethorphan (commonly used to treat cough), and other NMDA antagonists should be avoided.
If you develop signs and symptoms suggestive of neuroleptic malignant syndrome (NMS, a potentially life-threatening disorder characterized by a group of symptoms including fever with muscle rigidity, sweating, and altered level of consciousness) reported in patients taking donepezil (a component of Cevedalo), particularly when taken concomitantly with antipsychotics, or if you experience unexplained high fever without further clinical manifestations of NMS, treatment must be discontinued.
Children and adolescents
Do not give Cevedalo to children or adolescents under 18 years of age.
Other medicines and Cevedalo
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. This includes medicines not prescribed by your doctor but which you have purchased on your own at a pharmacy. It also applies to medicines you might take in the future while continuing to take Cevedalo. This is because such medicines may weaken or strengthen the effects of Cevedalo.
In particular, inform your doctor if you are taking any of the following types of medicines:

• other medicines for Alzheimer's disease, e.g., galantamine
• painkillers or treatment for arthritis, e.g., aspirin, non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or sodium diclofenac
• anticholinergic medicines (generally used to treat movement disorders or intestinal cramps), e.g., tolterodine
• medicines for bacterial infections, e.g., clarithromycin, erythromycin, levofloxacin, moxifloxacin, rifampicin
• antifungal medicines, e.g., ketoconazole and itraconazole
• antiprotozoal agents (used to treat infections caused by protozoa), e.g., quinine
• antidepressants, e.g., fluoxetine, citalopram, escitalopram, amitriptyline
• medicines for psychosis, e.g., pimozide, sertindole, ziprasidone
• anticonvulsants (used to prevent and relieve seizures), e.g., phenytoin, carbamazepine
• antidyskinetics (used to treat Parkinson's disease), e.g., amantadine
• diuretics (used to reduce the amount of water in the body), e.g., hydrochlorothiazide or any combination containing hydrochlorothiazide
• dopaminergic agonists (substances such as L-dopa, bromocriptine)
• medicines for heart conditions or rhythm problems, e.g., quinidine, beta-blockers (propranolol, sotalol, and atenolol), procainamide, amiodarone
• medicines for treating ulcers, e.g., cimetidine, ranitidine
• muscle relaxants, e.g., diazepam, succinylcholine, dantrolene, baclofen
• general anaesthetic, e.g., ketamine
• antitussives (cough suppressants), e.g., dextromethorphan
• neuroleptics (used in the treatment of mental disorders), e.g., clozapine, risperidone
• oral anticoagulants (blood thinners), e.g., clopidogrel, warfarin
• barbiturates (generally used to induce sleep)
• nicotine for nicotine replacement therapy
• over-the-counter medicines (e.g., herbal remedies)

If you are about to undergo surgery requiring general anaesthesia, tell your doctor and anaesthetist that you are taking Cevedalo. This is because the medicine may affect the amount of anaesthetic required.
Inform your doctor or pharmacist of the name of the person assisting you. That person will help you take the medicine as prescribed.
If you go to hospital, make sure the doctors know you are taking Cevedalo.
Cevedalo with food, drinks and alcohol
You should inform your doctor if you have recently changed or plan to substantially change your diet (e.g., switching from a normal diet to a strict vegetarian diet), as your doctor may need to adjust the dose of the medicine.
Cevedalo must not be taken with alcohol because alcohol may alter its effects.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy:
The use of Cevedalo in pregnant women is not recommended.
Breastfeeding:
Women taking Cevedalo must not breastfeed.
Driving and using machines
Alzheimer's disease may impair your ability to drive or operate machinery, and you should not perform these activities unless your doctor tells you it is safe to do so.
Cevedalo may cause fatigue, dizziness, and muscle cramps. If any of these effects occur, you must not drive or operate machinery.
Cevedalo contains sodium
Cevedalo contains less than 1 mmol of sodium (23 mg) per tablet, i.e., essentially "sodium-free".

3. How to take Cevedalo

Take this medicine exactly as directed by your doctor or pharmacist. If
you have any doubts, consult your doctor or pharmacist.
Inform your doctor or pharmacist of the name of the person assisting you.
This person will help you take the medicine as prescribed.
Dosage
The recommended dose of Cevedalo for adults and elderly patients is one 10 mg/20 mg tablet once
daily.
Patients with impaired renal function:
If you have impaired renal function, your doctor will decide on a dose appropriate for your condition. In
this case, monitoring of renal function must be performed by your doctor at regular
intervals.
Administration
Cevedalo should be administered orally once daily. To benefit from the medicine, take it regularly
every evening before going to sleep.
If you experience unusual dreams, nightmares or difficulty sleeping (see section 4), your doctor may
advise you to take Cevedalo in the morning.
Cevedalo should be swallowed with some water. The tablets may be taken with or without
food.
If you take more Cevedalo than you should
If you take more medicine than you should, contact your doctor or the nearest hospital emergency
department immediately. Take this leaflet and any remaining tablets with you.
Symptoms of overdose may include nausea and vomiting, salivation, sweating, slow heart rate, low
blood pressure (dizziness or lightheadedness when standing), breathing problems, loss of
consciousness and seizures (fits) or epileptic seizures.
If you forget to take Cevedalo
If you forget to take Cevedalo, take one tablet the following day at your usual time. Do
not take a double dose to make up for the missed tablet.
If you forget to take the medicine for more than one week, call your doctor before taking the medicine
again.
If you stop taking Cevedalo
Do not stop taking the tablets unless your doctor tells you to. If you stop taking Cevedalo, the benefits
of treatment will gradually disappear.
How long should you take Cevedalo?
Your doctor will advise you on how long you should continue taking the medicine. You should consult
your doctor periodically to have your treatment reviewed and your symptoms assessed.
If you have any questions about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Tell your doctor if you experience any of these side effects while taking Cevedalo.
Serious side effects:
Tell your doctor immediately if you notice any of these serious side effects
during treatment with Cevedalo. Urgent medical treatment may be required.

• Liver problems, for example hepatitis. Symptoms of hepatitis include nausea or vomiting, loss of appetite, general feeling of being unwell, fever, itching, yellowing of the skin and eyes, and dark-coloured urine (may affect up to 1 in 1,000 people)
• Gastric or duodenal ulcers. Symptoms of ulcers include stomach pain and discomfort (indigestion) felt between the navel and the breastbone (may affect up to 1 in 100 people).
• Bleeding in the stomach or intestines. This may cause passage of black, tar-like stools or visible blood from the rectum (may affect up to 1 in 100 people).
• Heart failure (may affect up to 1 in 100 people).
• Venous blood clotting (thrombosis/thromboembolism) (may affect up to 1 in 100 people).
• Convulsive fits (seizures) or convulsions (may affect up to 1 in 100 people).
• Fever with muscle rigidity, sweating, or decreased level of consciousness (a disorder called "neuroleptic malignant syndrome") (may affect up to 1 in 10,000 people).
• Muscle weakness, tenderness, or pain, particularly if you also feel unwell or have a high temperature: this may be caused by abnormal breakdown of skeletal muscle cells (rhabdomyolysis). This breakdown does not always resolve even after stopping Cevedalo, and may be potentially fatal and lead to kidney problems (may affect up to 1 in 10,000 people).
• Inflammation of the pancreas (frequency cannot be determined from available data)
• Changes in heart activity detectable on electrocardiogram (ECG), known as "prolonged QT interval" (frequency cannot be determined from available data)
• Fast or irregular heartbeat, fainting which could be symptoms of a potentially life-threatening condition known as torsades de pointes (frequency cannot be determined from available data)

Other side effects:
Very common (may affect more than 1 in 10 people)

• Diarrhoea
• Nausea or vomiting
• Headache

Common (may affect up to 1 in 10 people)

• Muscle cramps
• Tiredness
• Drowsiness
• Difficulty sleeping (insomnia)
• Cold
• Loss of appetite
• Hallucinations (seeing or hearing things that are not really there)
• Unusual dreams, including nightmares
• Restlessness
• Aggressive behaviour
• Fainting
• Dizziness
• Feeling of stomach discomfort
• Rash
• Itching
• Urinary incontinence
• Pain
• Accidents (patients may be more prone to falls and accidental injuries)
• Constipation
• Vomiting
• Elevated liver function tests
• Balance disorders
• Difficulty breathing
• High blood pressure
• Drug hypersensitivity

Uncommon (may affect up to 1 in 100 people)

• Slow heart rate
• Fungal infections
• Confusion
• Abnormal gait
• Excessive salivation
• Slight increase in serum concentration of muscle creatine kinase

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

• Stiffness, tremor, or uncontrollable movements, especially of the face and tongue, but also of the limbs
• Heart rhythm disorder

Not known (frequency cannot be determined from available data)

• Psychotic reactions
• Increased libido, hypersexuality
• Pisa syndrome (a condition involving involuntary muscle contractions, with abnormal lateral bending of the body and head)

Alzheimer's disease has been associated with depression, suicidal ideation, and suicide. These events have been reported in patients treated with memantine hydrochloride, which is part of Cevedalo.
If any of the side effects worsen, or if you notice any side effect not listed in this leaflet, tell your doctor or pharmacist immediately.
Reporting of side effects
If you get any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Cevedalo

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister after
EXP. The expiry date refers to the last day of that month.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.
This medicine requires no special storage conditions.

6. Package contents and other information

What Cevedalo contains

• The active substances are donepezil hydrochloride and memantine hydrochloride.

Cevedalo 10 mg/10 mg film-coated tablets
Each tablet contains 10 mg of donepezil hydrochloride (equivalent to 10.43 mg of donepezil monohydrate hydrochloride and 9.12 mg of donepezil) and 10 mg of memantine hydrochloride (equivalent to 8.31 mg of memantine).

Cevedalo 10 mg/20 mg film-coated tablets
Each tablet contains 10 mg of donepezil hydrochloride (equivalent to 10.43 mg of donepezil monohydrate hydrochloride and 9.12 mg of donepezil) and 20 mg of memantine hydrochloride (equivalent to 16.62 mg of memantine).

• The excipients are:

Cevedalo 10 mg/10 mg film-coated tablets
Mannitol, microcrystalline cellulose (101), maize starch, hydroxypropylcellulose (≈95,000 Da), sodium croscarmellose, magnesium stearate, coating (Opadry® II 85F20694 blue: partially hydrolysed polyvinyl alcohol, titanium dioxide (E171), macrogol (4000), talc, indigo carmine (E132)).

Cevedalo 10 mg/20 mg film-coated tablets
Mannitol, microcrystalline cellulose (101), maize starch, hydroxypropylcellulose (≈95,000 Da), sodium croscarmellose, magnesium stearate, coating (Opadry® II 85F18422 white: partially hydrolysed polyvinyl alcohol, titanium dioxide (E171), macrogol (4000), talc).

Description of the appearance of Cevedalo and contents of the pack
Cevedalo film-coated tablets 10 mg/10 mg, 10 mg/20 mg are available in packs of 28 film-coated tablets in PVC/PE EVOH OE/PCTFE/aluminium blisters, packed in a cardboard carton.
Donepezil hydrochloride + Memantine hydrochloride 10 mg + 10 mg film-coated tablets are blue, round, convex film-coated tablets with a diameter of 9.0 mm ± 0.2 mm.
Donepezil hydrochloride + Memantine hydrochloride 10 mg + 20 mg film-coated tablets are white to off-white, round, convex film-coated tablets with a diameter of 9.0 mm ± 0.2 mm.

Marketing Authorisation Holder
Istituto Luso Farmaco d’Italia S.p.A. – Milanofiori – Strada 6 – Edificio L – Rozzano, Milan, Italy

Manufacturer
Atlantic Pharma – Produções Farmacêuticas, S.A. - Rua da Tapada Grande, nº2, Abrunheira 2710-089 Sintra, Portugal