Memantine: package leaflet

How does Axura work
Axura contains the active substance memantine hydrochloride.
Axura belongs to a group of medicines known as anti-dementia medicines.
Memory loss in Alzheimer’s disease is due to a disturbance of message signals in the brain. The brain contains so-called N-methyl-D-aspartate (NMDA)-receptors that are involved in transmitting nerve signals important in learning and memory. Axura belongs to a group of medicines called NMDA- receptor antagonists. Axura acts on these NMDA-receptors improving the transmission of nerve signals and the memory.

What is Axura used for
Axura is used for the treatment of patients with moderate to severe Alzheimer’s disease.

Do not take Axura
- if you are allergic (hypersensitive) to memantine hydrochloride or any of the other ingredients of Axura tablets (listed in section 6).

Warning and precautions
Talk to your doctor or pharmacist before taking Axura
- if you have a history of epileptic seizures
- if you have recently experienced a myocardial infarction (heart attack), or if you are suffering from congestive heart failure or from an uncontrolled hypertension (high blood pressure).

In these situations the treatment should be carefully supervised, and the clinical benefit of Axura reassessed by your doctor on a regular basis.

If you suffer from renal impairment (kidney problems), your doctor should closely monitor your kidney function and if necessary adapt the memantine doses accordingly.

The use of medicinal products called amantadine (for the treatment of Parkinson´s disease), ketamine (a substance generally used as an anaesthetic), dextromethorphan (generally used to treat cough) and other NMDA-antagonists at the same time should be avoided.

Children and adolescents
Axura is not recommended for children and adolescents under the age of 18 years.

Other medicines and Axura
Please tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

In particular, Axura may change the effects of the following medicines and their dose may need to be adjusted by your doctor:

• amantadine, ketamine, dextromethorphan
• dantrolene, baclofen
• cimetidine, ranitidine, procainamide, quinidine, quinine, nicotine
• hydrochlorothiazide (or any combination with hydrochlorothiazide)
• anticholinergics (substances generally used to treat movement disorders or intestinal cramps)
• anticonvulsants (substances used to prevent and relieve seizures)
• barbiturates (substances generally used to induce sleep)
• dopaminergic agonists (substances such as L-dopa, bromocriptine)
• neuroleptics (substances used in the treatment of mental disorders)
• oral anticoagulants

If you go into hospital, let your doctor know that you are taking Axura.

Axura with food and drink
You should inform your doctor if you have recently changed or intend to change your diet substantially (e.g. from normal diet to strict vegetarian diet) or if you are suffering from states of renal tubulary acidosis (RTA, an excess of acid-forming substances in the blood due to renal dysfunction (poor kidney function)) or severe infections of the urinary tract (structure that carries urine), as your doctor may need to adjust the dose of your medicine.

Pregnancy and breast-feeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy
The use of memantine in pregnant women is not recommended.

Breast-Feeding
Women taking Axura should not breast-feed.

Driving and using machines
Your doctor will tell you whether your illness allows you to drive and to use machines safely.
Also, Axura may change your reactivity, making driving or operating machinery inappropriate.

Axura contains Sodium
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium- free’.

Always take Axura exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

Dosage
The recommended dose of Axura for adults and older people is 20 mg once a day. In order to reduce the risk of side effects this dose is achieved gradually by the following daily treatment scheme:

week 1

half a 10 mg tablet

week 2

one 10 mg tablet

week 3

one and a half 10 mg tablet

week 4 and beyond two 10 mg tablets once a day

The usual starting dose is half a tablet once a day (1x 5 mg) for the first week. This is increased to one tablet once a day (1x 10 mg) in the second week and to 1 and a half tablet once a day in the third week. From the fourth week on, the usual dose is 2 tablets once a day (1x 20 mg).

Dosage in patients with impaired kidney function
If you have impaired kidney function, your doctor will decide upon a dose that suits your condition. In this case, monitoring of your kidney function should be performed by your doctor at specified intervals.

Administration
Axura should be administered orally once a day. To benefit from your medicine you should take it regularly every day at the same time of the day. The tablets should be swallowed with some water.
The tablets can be taken with or without food.

Duration of treatment
Continue to take Axura as long as it is of benefit to you. Your doctor should assess your treatment on a regular basis.

If you take more Axura than you should
- In general, taking too much Axura should not result in any harm to you. You may experience increased symptoms as described in section 4. „Possible side effects“.
- If you take a large overdose of Axura, contact your doctor or get medical advice, as you may need medical attention.

If you forget to take Axura
- If you find you have forgotten to take your dose of Axura, wait and take your next dose at the usual time.
- Do not take a double dose to make up for a forgotten dose.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everybody gets them.

In general, the observed side effects are mild to moderate.

Common (may affect up to 1 in 10 users):
- Headache, sleepiness, constipation, elevated liver function tests, dizziness, balance disorders, shortness of breath, high blood pressure and drug hypersensitivity

Uncommon (may affect up to 1 in 100 users):
- Tiredness, fungal infections, confusion, hallucinations, vomiting, abnormal gait, heart failure and venous blood clotting (thrombosis/thromboembolism)

Very rare (may affect up to 1 in 10,000 users):
- Seizures

Not known (frequency cannot be estimated from the available data):
- Inflammation of the pancreas, inflammation of the liver (hepatitis) and psychotic reactions

Alzheimer's disease has been associated with depression, suicidal ideation and suicide. These events have been reported in patients treated with Axura.

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

Keep out of the sight and reach of children.

Do not use Axura after the expiry date which is stated on the carton and the blister after EXP. The expiry date refers to the last day of that month.

This medicinal product does not require any special storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

What Axura contains
The active substance is memantine hydrochloride. Each film-coated tablet contains 10 mg of memantine hydrochloride equivalent to 8.31 mg memantine.

The other ingredients are microcrystalline cellulose, croscarmellose sodium, colloidal anhydrous silica, and magnesium stearate, all in the tablet core; and hypromellose, macrogol 400, titanium dioxide (E 171) and iron oxide yellow (E 172) all in the tablet coating.

What Axura looks like and contents of the pack
Axura film-coated tablets are presented as pale yellow to yellow, oval shaped film-coated tablets with imprint “M” on both sides right and left of the breakline and on the other side the imprints “1” and “0” left and right of the breakline. The tablet is approximately 11.0 mm long, and 5.0 mm wide.

Axura film-coated tablets are available in blister packs of 14 tablets, 28 tablets, 30 tablets, 42 tablets, 50 tablets, 56 tablets, 98 tablets, 100 tablets, 112 tablets and multipacks of 840 (20 packs of 42) tablets, 980 (10 packs of 98) tablets or 1000 (20 packs of 50) tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder
Merz Pharmaceuticals GmbH
Eckenheimer Landstr. 100

D-60318 Frankfurt/Main
Germany

Manufacturer
Merz Pharma GmbH & Co. KGaA
Eckenheimer Landstr. 100
D-60318 Frankfurt/Main
Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder.

België/Belgique/Belgien
Merz Pharmaceuticals GmbH
Tél/Tel: +49 (0)69 1503-0

Lietuva
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

България
Merz Pharmaceuticals GmbH
Teл.: +49 (0)69 1503-0

Luxembourg/Luxemburg
HANFF Global Health Solutions s.à r.l.
Tél/Tel: +352 45 07 07-1
Česká republika
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

Magyarország
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

Danmark
Merz Pharmaceuticals GmbH
Tlf: +49 (0)69 1503-0

Malta
Clinipharm Co. Ltd
Tel: +356 21 43 74 15

Deutschland
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0
Nederland
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

Eesti
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

Norge
Merz Pharmaceuticals GmbH
Tlf: +49 (0)69 1503-0

Ελλάδα
Merz Pharmaceuticals GmbH
Τηλ: +49 (0)69 1503-0

Österreich
Merz Pharma Austria GmbH
Tel.: +43 1 865 88 95

España
Merz Therapeutics Iberia, S.L.U.
Tel. +34 91 117 89 17

Polska
Centrala Farmaceutyczna CEFARM SA
Tel: +48 22 634 02 22
France
Merz Pharmaceuticals GmbH
Tél: +49 (0)69 1503-0

Portugal
Merz Therapeutics Iberia, S.L.U.
Tel. +34 91 117 89 17

Hrvatska
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

România
Merz Pharmaceuticals GmbH
Tel.: +49 (0)69 1503-0

Ireland
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

Slovenija
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0
Ísland
Slovenská republika

Merz Pharmaceuticals GmbH
Sími.: +49 (0)69 1503-0

Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

Italia
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0
Suomi/Finland
Merz Pharmaceuticals GmbH
Puh/Tel: +49 (0)69 1503-0

Κύπρος
Merz Pharmaceuticals GmbH
Τηλ: +49 (0)69 1503-0
Sverige
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

Latvija
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

This leaflet was last revised in MM/YYYY.
Detailed information on this medicine is available on the European Medicines Agency (EMA) web side: http://www.ema.europa.eu.

How does Axura work
Axura contains the active substance memantine hydrochloride.
Axura belongs to a group of medicines known as anti-dementia medicines.
Memory loss in Alzheimer’s disease is due to a disturbance of message signals in the brain. The brain contains so-called N-methyl-D-aspartate (NMDA)-receptors that are involved in transmitting nerve signals important in learning and memory. Axura belongs to a group of medicines called NMDA- receptor antagonists. Axura acts on these NMDA-receptors improving the transmission of nerve signals and the memory.

What is Axura used for
Axura is used for the treatment of patients with moderate to severe Alzheimer’s disease.

Do not take Axura
- if you are allergic (hypersensitive) to memantine hydrochloride or any of the other ingredients of Axura oral solution (listed in section 6).

Warning and precautions
Talk to your doctor or pharmacist before taking Axura
- if you have a history of epileptic seizures
- if you have recently experienced a myocardial infarction (heart attack), or if you are suffering from congestive heart failure or from an uncontrolled hypertension (high blood pressure).

In these situations the treatment should be carefully supervised, and the clinical benefit of Axura reassessed by your doctor on a regular basis.

If you suffer from renal impairment (kidney problems), your doctor should closely monitor your kidney function and if necessary adapt the memantine doses accordingly.

The use of medicinal products called amantadine (for the treatment of Parkinson´s disease), ketamine

(a substance generally used as an anaesthetic), dextromethorphan (generally used to treat cough) and other NMDA-antagonists at the same time should be avoided.

Children and adolescents
Axura is not recommended for children and adolescents under the age of 18 years.

Other medicines and Axura
Please tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

In particular, Axura may change the effects of the following medicines and their dose may need to be adjusted by your doctor:

• amantadine, ketamine, dextromethorphan
• dantrolene, baclofen
• cimetidine, ranitidine, procainamide, quinidine, quinine, nicotine
• hydrochlorothiazide (or any combination with hydrochlorothiazide)
• anticholinergics (substances generally used to treat movement disorders or intestinal cramps)
• anticonvulsants (substances used to prevent and relieve seizures)
• barbiturates (substances generally used to induce sleep)
• dopaminergic agonists (substances such as L-dopa, bromocriptine)
• neuroleptics (substances used in the treatment of mental disorders)
• oral anticoagulants

If you go into hospital, let your doctor know that you are taking Axura.

Axura with food and drink
You should inform your doctor if you have recently changed or intend to change your diet substantially (e.g. from normal diet to strict vegetarian diet) or if you are suffering from states of renal tubulary acidosis (RTA, an excess of acid-forming substances in the blood due to renal dysfunction (poor kidney function)) or severe infections of the urinary tract (structure that carries urine), as your doctor may need to adjust the dose of your medicine.

Pregnancy and breast-feeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy
The use of memantine in pregnant women is not recommended.

Breast-Feeding
Women taking Axura should not breast-feed.

Driving and using machines
Your doctor will tell you whether your illness allows you to drive and to use machines safely.
Also, Axura may change your reactivity, making driving or operating machinery inappropriate.

Axura contains sorbitol
This medicine contains 100 mg sorbitol in each gram which is equivalent to 200 mg /4 pump actuation. Sorbitol is a source of fructose. If your doctor told you that you have an intolerance to some sugars, or if you have been diagnosed with hereditary fructose intolerance (HFI), a rare genetic disorder in which a person cannot break down fructose, talk to your doctor before you take or receive this medicine.

Furthermore, this medicine contains potassium, less than 1 mmol (39 mg) per dose, i.e. essentially

potassium-free.

Always take Axura exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

Dosage
One pump actuation contains 5mg memantine hydrochloride.
The recommended dose of Axura for adults and older people is four pump actuations, equivalent to 20 mg once a day.
In order to reduce the risk of side effects this dose is achieved gradually by the following daily treatment scheme:

week 1

one pump actuation week 2

two pump actuations week 3

three pump actuations week 4 and beyond four pump actuations

The usual starting dose is one pump actuation (1 x 5 mg) once daily for the first week. This dose is increased in the second week to two pump actuations once daily (1 x 10 mg), and in the third week to three pump actuations (1 x 15 mg) once daily. From the fourth week the recommended dose is four pump actuations once daily (1 x 20 mg).

Dosage in patients with impaired kidney function
If you have impaired kidney function, your doctor will decide upon a dose that suits your condition. In this case, monitoring of your kidney function should be performed by your doctor at specified intervals.

Administration
Axura should be administered orally once a day. To benefit from your medicine you should take it regularly every day at the same time of the day. The solution should be taken with a little water. The solution can be taken with or without food.
For detailed instructions on the preparation and handling of the product see end of this leaflet.

Duration of treatment
Continue to take Axura as long as it is of benefit to you. Your doctor should assess your treatment on a regular basis.

If you take more Axura than you should
- In general, taking too much Axura should not result in any harm to you. You may experience increased symptoms as described in section 4. „Possible side effects“.
- If you take a large overdose of Axura, contact your doctor or get medical advice, as you may need medical attention.

If you forget to take Axura
- If you find you have forgotten to take your dose of Axura, wait and take your next dose at the usual time.
- Do not take a double dose to make up for a forgotten dose.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everybody gets them.

In general, the observed side effects are mild to moderate.

Common (may affect up to 1 in 10 users):
- Headache, sleepiness, constipation, elevated liver function tests, dizziness, balance disorder, shortness of breath, high blood pressure and drug hypersensitivity

Uncommon (may affect up to 1 in 100 users):
- Tiredness, fungal infections, confusion, hallucinations, vomiting, abnormal gait, heart failure and venous blood clotting (thrombosis/thromboembolism)

Very rare (may affect up to 1 in 10,000 users):
- Seizures

Not known (frequency cannot be estimated from the available data):
- Inflammation of the pancreas, inflammation of the liver (hepatitis) and psychotic reactions

Alzheimer's disease has been associated with depression, suicidal ideation and suicide. These events have been reported in patients treated with Axura.

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

Keep out of the sight and reach of children.

Do not use Axura after the expiry date which is stated on the carton and the bottle label after the EXP.
The expiry date refers to the last day of that month.

Do not store above 30°C.

Once opened, the contents of the bottle should be used within 3 months.

The bottle with the mounted pump must be kept and transported in an upright position only.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to protect the environment.

What Axura contains
The active substance is memantine hydrochloride.

Each pump actuation delivers 0.5 ml solution which contains 5 mg of memantine hydrochloride which is equivalent to 4.16 mg memantine.

The other ingredients are: potassium sorbate, sorbitol (E 420) and purified water.

What Axura looks like and contents of the pack
Axura oral solution is presented as a clear, colourless to light yellowish solution.

Axura oral solution is available in bottles of 50 ml, 100 ml or a multipack of 500 ml (10 x 50 ml).

Not all pack sizes may be marketed.

Marketing Authorisation Holder
Merz Pharmaceuticals GmbH
Eckenheimer Landstr. 100
D-60318 Frankfurt/Main
Germany

Manufacturer
Merz Pharma GmbH & Co. KGaA
Eckenheimer Landstr. 100
D-60318 Frankfurt/Main
Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder.

België/Belgique/Belgien
Merz Pharmaceuticals GmbH
Tél/Tel: +49 (0)69 1503-0

Lietuva
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

България
Merz Pharmaceuticals GmbH
Teл.: +49 (0)69 1503-0

Luxembourg/Luxemburg
HANFF Global Health Solutions s.à r.l.
Tél/Tel: +352 45 07 07-1
Česká republika
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

Magyarország
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

Danmark
Merz Pharmaceuticals GmbH
Tlf: +49 (0)69 1503-0

Malta
Clinipharm Co. Ltd
Tel: +356 21 43 74 15

Deutschland
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0
Nederland
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

Eesti
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

Norge
Merz Pharmaceuticals GmbH
Tlf: +49 (0)69 1503-0

Ελλάδα
Merz Pharmaceuticals GmbH
Τηλ: +49 (0)69 1503-0

Österreich
Merz Pharma Austria GmbH
Tel.: +43 1 865 88 95

España
Merz Therapeutics Iberia, S.L.U.
Tel. +34 91 117 89 17

Polska
Centrala Farmaceutyczna CEFARM SA
Tel: +48 22 634 02 22
France
Merz Pharmaceuticals GmbH
Portugal
Merz Therapeutics Iberia, S.L.U.

Tél: +49 (0)69 1503-0

Tel. +34 91 117 89 17

Hrvatska
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

România
Merz Pharmaceuticals GmbH
Tel.: +49 (0)69 1503-0

Ireland
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

Slovenija
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0
Ísland
Merz Pharmaceuticals GmbH
Sími.: +49 (0)69 1503-0

Slovenská republika
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

Italia
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0
Suomi/Finland
Merz Pharmaceuticals GmbH
Puh/Tel: +49 (0)69 1503-0

Κύπρος
Merz Pharmaceuticals GmbH
Τηλ: +49 (0)69 1503-0
Sverige
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

Latvija
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

This leaflet was last revised in MM/YYYY.
Detailed information on this medicine is available on the European Medicines Agency (EMA) web side: http://www.ema.europa.eu.

Instruction for proper use of the pump

The solution must not be poured or pumped directly into the mouth from the bottle or pump. Measure the dose onto a spoon or into a glass of water, using the pump.

Take the screw cap off the bottle:

The cap must be turned anticlockwise, unscrewed completely and removed (fig. 1).

Mounting the dosing pump on the bottle:

Take the dosing pump out of the plastic bag (fig. 2) and place it on top of the bottle. Slide the plastic dip tube carefully into the bottle. Hold the dosing pump onto the neck of the bottle and screw it clockwise until it fits firmly (fig. 3). The dosing pump is only screwed on once when starting the use, and should never be unscrewed.

How the dosing pump works:

The dosing pump head has two positions and is easy to turn:
- anticlockwise to unlock and
- clockwise to lock.

The dosing pump head should not be pushed down while in the locked position. The solution may only be dispensed in the unlocked position. To unlock, turn the pump head in the direction of the arrow until it cannot be turned any further (about one eighth of a turn, fig. 4). The dosing pump is then ready for use.

Preparing the dosing pump:

When used for the first time, the dosing pump does not dispense the correct amount of oral solution.
Therefore, the pump must be prepared (primed) by pushing the dosing pump head down completely five times in succession (fig. 5).

The solution thus dispensed is discarded. The next time the dosing pump head is pushed downwards completely (equivalent to one pump actuation), it dispenses the correct dose (fig. 6).

Correct use of the dosing pump:

Place the bottle on a flat, horizontal surface, for example a table top, and only use it in a upright position. Hold a glass with a little water or a spoon below the nozzle. Push down the dosing pump head in a firm but calm and steady manner - not too slowly (fig. 7, fig. 8).

The dosing pump head can then be released and is ready for the next pump actuation.

The dosing pump must only be used with the Axura solution in the bottle provided, not for other substances or containers. If the pump does not function properly, consult your doctor or a pharmacist.Lock the dosing pump after using Axura.

How does Axura work
Axura contains the active substance memantine hydrochloride.
Axura belongs to a group of medicines known as anti-dementia medicines.
Memory loss in Alzheimer’s disease is due to a disturbance of message signals in the brain. The brain contains so-called N-methyl-D-aspartate (NMDA)-receptors that are involved in transmitting nerve signals important in learning and memory. Axura belongs to a group of medicines called NMDA- receptor antagonists. Axura acts on these NMDA-receptors improving the transmission of nerve signals and the memory.

What is Axura used for
Axura is used for the treatment of patients with moderate to severe Alzheimer’s disease.

Do not take Axura
- if you are allergic (hypersensitive) to memantine hydrochloride or any of the other ingredients of Axura tablets (listed in section 6).

Warning and precautions
Talk to your doctor or pharmacist before taking Axura
- if you have a history of epileptic seizures
- if you have recently experienced a myocardial infarction (heart attack), or if you are suffering from congestive heart failure or from an uncontrolled hypertension (high blood pressure).

In these situations the treatment should be carefully supervised, and the clinical benefit of Axura reassessed by your doctor on a regular basis.

If you suffer from renal impairment (kidney problems), your doctor should closely monitor your kidney function and if necessary adapt the memantine doses accordingly.

The use of medicinal products called amantadine (for the treatment of Parkinson´s disease), ketamine (a substance generally used as an anaesthetic), dextromethorphan (generally used to treat cough) and other NMDA-antagonists at the same time should be avoided.

Children and adolescents
Axura is not recommended for children and adolescents under the age of 18 years.

Other medicines and Axura
Please tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

In particular, Axura may change the effects of the following medicines and their dose may need to be adjusted by your doctor:

• amantadine, ketamine, dextromethorphan
• dantrolene, baclofen
• cimetidine, ranitidine, procainamide, quinidine, quinine, nicotine
• hydrochlorothiazide (or any combination with hydrochlorothiazide)
• anticholinergics (substances generally used to treat movement disorders or intestinal cramps)
• anticonvulsants (substances used to prevent and relieve seizures)
• barbiturates (substances generally used to induce sleep)
• dopaminergic agonists (substances such as L-dopa, bromocriptine)
• neuroleptics (substances used in the treatment of mental disorders)
• oral anticoagulants

If you go into hospital, let your doctor know that you are taking Axura.

Axura with food and drink
You should inform your doctor if you have recently changed or intend to change your diet substantially (e.g. from normal diet to strict vegetarian diet) or if you are suffering from states of renal tubulary acidosis (RTA, an excess of acid-forming substances in the blood due to renal dysfunction (poor kidney function)) or severe infections of the urinary tract (structure that carries urine) as your doctor may need to adjust the dose of your medicine.

Pregnancy and breast-feeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy
The use of memantine in pregnant women is not recommended.

Breast-Feeding
Women taking Axura should not breast-feed.

Driving and using machines
Your doctor will tell you whether your illness allows you to drive and to use machines safely.
Also, Axura may change your reactivity, making driving or operating machinery inappropriate.

Axura contains Sodium
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium- free’.

The Axura treatment initiation pack is only to be used for the beginning of the treatment with Axura.

Always take Axura exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

Dosage
The recommended treatment dose of 20 mg per day is achieved by a gradual increase of the Axura dose during the first 3 weeks of treatment. The treatment scheme is also indicated on the treatment initiation pack. Take one tablet once a day.

Week 1 (day 1-7):
Take one 5 mg tablet once a day (white to off-white, oval shaped) for 7 days.

Week 2 (day 8-14):
Take one 10 mg tablet once a day (pale yellow to yellow, oval shaped) for 7 days.

Week 3 (day 15-21):
Take one 15 mg tablet once a day (orange, oval shaped) for 7 days.

Week 4 (day 22-28):
Take one 20 mg tablet per day (pink, oval shaped) for 7 days.

week 1

5 mg tablet

week 2

10 mg tablet

week 3

15 mg tablet

week 4 and beyond
20 mg tablets once a day

Maintenance dose
The recommended daily dose is 20 mg once a day.
For continuation of the treatment please consult your doctor.

Dosage in patients with impaired kidney function
If you have impaired kidney function, your doctor will decide upon a dose that suits your condition. In this case, monitoring of your kidney function should be performed by your doctor at specified intervals.

Administration
Axura should be administered orally once a day. To benefit from your medicine you should take it regularly every day at the same time of the day. The tablets should be swallowed with some water.
The tablets can be taken with or without food.

Duration of treatment
Continue to take Axura as long as it is of benefit to you. Your doctor should assess your treatment on a regular basis.

If you take more Axura than you should
- In general, taking too much Axura should not result in any harm to you. You may experience increased symptoms as described in section 4. „Possible side effects“.
- If you take a large overdose of Axura, contact your doctor or get medical advice, as you may need medical attention.

If you forget to take Axura

• If you find you have forgotten to take your dose of Axura, wait and take your next dose at the usual time.
• Do not take a double dose to make up for a forgotten dose.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everybody gets them.

In general, the observed side effects are mild to moderate.

Common (may affect up to 1 in 10 users):
- Headache, sleepiness, constipation, elevated liver function tests, dizziness, balance disorders, shortness of breath, high blood pressure and drug hypersensitivity

Uncommon (may affect up to 1 in 100 users):
- Tiredness, fungal infections, confusion, hallucinations, vomiting, abnormal gait, heart failure and venous blood clotting (thrombosis/thromboembolism)

Very rare (may affect up to 1 in 10,000 users):
- Seizures

Not known (frequency cannot be estimated from the available data):
- Inflammation of the pancreas, inflammation of the liver (hepatitis) and psychotic reactions

Alzheimer's disease has been associated with depression, suicidal ideation and suicide. These events have been reported in patients treated with Axura.

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

Keep out of the sight and reach of children.

Do not use Axura after the expiry date which is stated on the carton and the blister after EXP. The expiry date refers to the last day of that month.

This medicinal product does not require any special storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

What Axura contains
The active substance is memantine hydrochloride. Each tablet contains 5/10/15/20 mg of memantine hydrochloride equivalent to 4.15/8.31/12.46/16.62 mg memantine.

The other ingredients for Axura 5/10/15 and 20 mg film-coated tablets are microcrystalline cellulose, croscarmellose sodium, colloidal anhydrous silica, magnesium stearate, all in the tablet core; and hypromellose, macrogol 400, titanium dioxide (E 171) and additional for Axura 10 mg film-coated tablets is iron oxide yellow (E 172) and for Axura 15 mg and Axura 20 mg film-coated tablets are iron oxide yellow and red (E 172), all in the tablet coating.

What Axura looks like and contents of the pack
Axura 5 mg film-coated tablets are presented as white to off-white, oval shaped with engravings ‘5’ on one side and ‘MEM’ on the other side. The tablet is approximately 8.0 mm long, and 4.0 mm wide.
Axura 10 mg film-coated tablets are presented as pale yellow to yellow, oval shaped film-coated tablets with imprint “M” on both sides right and left of the breakline and on the other side the imprints “1” and “0” left and right of the breakline. The tablet is approximately 11.0 mm long, and 5.0 mm wide. The tablet can be divided into equal halves.
Axura 15 mg film-coated tablets are presented as orange coloured, oval shaped with engravings ‘15’ on one side and ‘MEM’ on the other side. The tablet is approximately 12.0 mm long, and 6.3 mm wide.
Axura 20 mg film-coated tablets are presented as pink coloured, oval shaped with engravings ‘20’ on one side and ‘MEM’ on the other side. The tablet is approximately 13.0 mm long, and 7.0 mm wide.

One treatment initiation pack contains 28 tablets in 4 blisters with 7 tablets of Axura 5 mg, 7 tablets of Axura 10 mg, 7 tablets of Axura 15 mg and 7 tablets of Axura 20 mg.

Marketing Authorisation Holder
Merz Pharmaceuticals GmbH
Eckenheimer Landstr. 100
D-60318 Frankfurt/Main
Germany

Manufacturer
Merz Pharma GmbH & Co. KGaA
Eckenheimer Landstr. 100
D-60318 Frankfurt/Main
Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder.

België/Belgique/Belgien
Merz Pharmaceuticals GmbH
Tél/Tel: +49 (0)69 1503-0

Lietuva
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

България
Merz Pharmaceuticals GmbH
Teл.: +49 (0)69 1503-0

Luxembourg/Luxemburg
HANFF Global Health Solutions s.à r.l.
Tél/Tel: +352 45 07 07-1
Česká republika
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

Magyarország
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

Danmark
Merz Pharmaceuticals GmbH
Tlf: +49 (0)69 1503-0

Malta
Clinipharm Co. Ltd
Tel: +356 21 43 74 15

Deutschland
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0
Nederland
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

Eesti
Norge

Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

Merz Pharmaceuticals GmbH
Tlf: +49 (0)69 1503-0

Ελλάδα
Merz Pharmaceuticals GmbH
Τηλ: +49 (0)69 1503-0

Österreich
Merz Pharma Austria GmbH
Tel.: +43 1 865 88 95

España
Merz Therapeutics Iberia, S.L.U.
Tel. +34 91 117 89 17

Polska
Centrala Farmaceutyczna CEFARM SA
Tel: +48 22 634 02 22
France
Merz Pharmaceuticals GmbH
Tél: +49 (0)69 1503-0

Portugal
Merz Therapeutics Iberia, S.L.U.
Tel. +34 91 117 89 17

Hrvatska
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

România
Merz Pharmaceuticals GmbH
Tel.: +49 (0)69 1503-0

Ireland
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

Slovenija
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0
Ísland
Merz Pharmaceuticals GmbH
Sími.: +49 (0)69 1503-0

Slovenská republika
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

Italia
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0
Suomi/Finland
Merz Pharmaceuticals GmbH
Puh/Tel: +49 (0)69 1503-0

Κύπρος
Merz Pharmaceuticals GmbH
Τηλ: +49 (0)69 1503-0
Sverige
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

Latvija
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

This leaflet was last revised in MM/YYYY.
Detailed information on this medicine is available on the European Medicines Agency (EMA) web side: http://www.ema.europa.eu.

How does Axura work
Axura contains the active substance memantine hydrochloride.
Axura belongs to a group of medicines known as anti-dementia medicines.
Memory loss in Alzheimer’s disease is due to a disturbance of message signals in the brain. The brain contains so-called N-methyl-D-aspartate (NMDA)-receptors that are involved in transmitting nerve signals important in learning and memory. Axura belongs to a group of medicines called NMDA- receptor antagonists. Axura acts on these NMDA-receptors improving the transmission of nerve signals and the memory.

What is Axura used for
Axura is used for the treatment of patients with moderate to severe Alzheimer’s disease.

Do not take Axura
- if you are allergic (hypersensitive) to memantine hydrochloride or any of the other ingredients of Axura tablets (listed in section 6).

Warning and precautions
Talk to your doctor or pharmacist before taking Axura
- if you have a history of epileptic seizures
- if you have recently experienced a myocardial infarction (heart attack), or if you are suffering from congestive heart failure or from an uncontrolled hypertension (high blood pressure).

In these situations the treatment should be carefully supervised, and the clinical benefit of Axura reassessed by your doctor on a regular basis.

If you suffer from renal impairment (kidney problems), your doctor should closely monitor your kidney function and if necessary adapt the memantine doses accordingly.

The use of medicinal products called amantadine (for the treatment of Parkinson´s disease), ketamine (a substance generally used as an anaesthetic), dextromethorphan (generally used to treat cough) and other NMDA-antagonists at the same time should be avoided.

Children and adolescents
Axura is not recommended for children and adolescents under the age of 18 years.

Other medicines and Axura
Please tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

In particular, Axura may change the effects of the following medicines and their dose may need to be adjusted by your doctor:

• amantadine, ketamine, dextromethorphan
• dantrolene, baclofen
• cimetidine, ranitidine, procainamide, quinidine, quinine, nicotine
• hydrochlorothiazide (or any combination with hydrochlorothiazide)
• anticholinergics (substances generally used to treat movement disorders or intestinal cramps)
• anticonvulsants (substances used to prevent and relieve seizures)
• barbiturates (substances generally used to induce sleep)
• dopaminergic agonists (substances such as L-dopa, bromocriptine)
• neuroleptics (substances used in the treatment of mental disorders)
• oral anticoagulants

If you go into hospital, let your doctor know that you are taking Axura.

Axura with food and drink
You should inform your doctor if you have recently changed or intend to change your diet substantially (e.g. from normal diet to strict vegetarian diet) or if you are suffering from states of renal tubulary acidosis (RTA, an excess of acid-forming substances in the blood due to renal dysfunction (poor kidney function)) or severe infections of the urinary tract (structure that carries urine),as your doctor may need to adjust the dose of your medicine.

Pregnancy and breast-feeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy
The use of memantine in pregnant women is not recommended.

Breast-Feeding
Women taking Axura should not breast-feed.

Driving and using machines
Your doctor will tell you whether your illness allows you to drive and to use machines safely.
Also, Axura may change your reactivity, making driving or operating machinery inappropriate.

Axura contains Sodium
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium- free’.

Always take Axura exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

Dosage
The recommended dose of Axura for adults and older people is 20 mg once a day.

In order to reduce the risk of side effects this dose is achieved gradually by the following daily treatment scheme. For up-titration other tablet strengths are available.

At the beginning of treatment you will start by using Axura 5 mg film-coated tablets once a day. This dose will be increased weekly by 5 mg until the recommended (maintenance) dose is reached. The recommended maintenance dose is 20 mg once a day, which is reached at the beginning of the 4th week.

Dosage in patients with impaired kidney function
If you have impaired kidney function, your doctor will decide upon a dose that suits your condition. In this case, monitoring of your kidney function should be performed by your doctor at specified intervals.

Administration
Axura should be administered orally once a day. To benefit from your medicine you should take it regularly every day at the same time of the day. The tablets should be swallowed with some water.
The tablets can be taken with or without food.

Duration of treatment
Continue to take Axura as long as it is of benefit to you. Your doctor should assess your treatment on a regular basis.

If you take more Axura than you should
- In general, taking too much Axura should not result in any harm to you. You may experience increased symptoms as described in section 4. „Possible side effects“.
- If you take a large overdose of Axura, contact your doctor or get medical advice, as you may need medical attention.

If you forget to take Axura
- If you find you have forgotten to take your dose of Axura, wait and take your next dose at the usual time.
- Do not take a double dose to make up for a forgotten dose.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everybody gets them.

In general, the observed side effects are mild to moderate.

Common (may affect up to 1 in 10 users):
- Headache, sleepiness, constipation, elevated liver function tests, dizziness, balance disorders, shortness of breath, high blood pressure and drug hypersensitivity

Uncommon (may affect up to 1 in 100 users):
- Tiredness, fungal infections, confusion, hallucinations, vomiting, abnormal gait, heart failure and venous blood clotting (thrombosis/thromboembolism)

Very rare (may affect up to 1 in 10,000 users):
- Seizures

Not known (frequency cannot be estimated from the available data):
- Inflammation of the pancreas, inflammation of the liver (hepatitis) and psychotic reactions

Alzheimer's disease has been associated with depression, suicidal ideation and suicide. These events have been reported in patients treated with Axura.

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

Keep out of the sight and reach of children.

Do not use Axura after the expiry date which is stated on the carton and the blister after EXP. The expiry date refers to the last day of that month.

This medicinal product does not require any special storage conditions.

Do not throw away medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

What Axura contains
The active substance is memantine hydrochloride. Each film-coated tablet contains 20 mg of memantine hydrochloride equivalent to 16.62 mg memantine.

The other ingredients are microcrystalline cellulose, croscarmellose sodium, colloidal anhydrous silica, magnesium stearate, all in the tablet core; and hypromellose, macrogol 400, titanium dioxide (E 171), iron oxide yellow and red (E 172), all in the tablet coating.

What Axura looks like and contents of the pack
Axura film-coated tablets are presented as pink coloured, oval shaped film-coated tablets with engravings ‘20’ on one side and ‘MEM’ on the other side. The tablet is approximately 13.0 mm long, and 7.0 mm wide.

Axura film-coated tablets are available in blister packs of 14 tablets, 28 tablets, 42 tablets, 56 tablets, 98 tablets or in multipacks of 840 (20 x 42) tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder
Merz Pharmaceuticals GmbH
Eckenheimer Landstr. 100
D-60318 Frankfurt/Main
Germany

Manufacturer
Merz Pharma GmbH & Co. KGaA
Eckenheimer Landstr. 100
D-60318 Frankfurt/Main
Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder.

België/Belgique/Belgien
Merz Pharmaceuticals GmbH
Tél/Tel: +49 (0)69 1503-0

Lietuva
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

България
Merz Pharmaceuticals GmbH
Teл.: +49 (0)69 1503-0

Luxembourg/Luxemburg
HANFF Global Health Solutions s.à r.l.
Tél/Tel: +352 45 07 07-1
Česká republika
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

Magyarország
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

Danmark
Merz Pharmaceuticals GmbH
Tlf: +49 (0)69 1503-0

Malta
Clinipharm Co. Ltd
Tel: +356 21 43 74 15

Deutschland
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0
Nederland
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

Eesti
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

Norge
Merz Pharmaceuticals GmbH
Tlf: +49 (0)69 1503-0

Ελλάδα
Merz Pharmaceuticals GmbH
Τηλ: +49 (0)69 1503-0

Österreich
Merz Pharma Austria GmbH
Tel.: +43 1 865 88 95

España
Merz Therapeutics Iberia, S.L.U.
Tel. +34 91 117 89 17

Polska
Centrala Farmaceutyczna CEFARM SA
Tel: +48 22 634 02 22
France
Merz Pharmaceuticals GmbH
Tél: +49 (0)69 1503-0

Portugal
Merz Therapeutics Iberia, S.L.U.
Tel. +34 91 117 89 17

Hrvatska
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

România
Merz Pharmaceuticals GmbH
Tel.: +49 (0)69 1503-0

Ireland
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

Slovenija
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0
Ísland
Merz Pharmaceuticals GmbH
Sími.: +49 (0)69 1503-0

Slovenská republika
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

Italia
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0
Suomi/Finland
Merz Pharmaceuticals GmbH
Puh/Tel: +49 (0)69 1503-0

Κύπρος
Sverige

Merz Pharmaceuticals GmbH
Τηλ: +49 (0)69 1503-0
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

Latvija
Merz Pharmaceuticals GmbH
Tel: +49 (0)69 1503-0

This leaflet was last revised in MM/YYYY.
Detailed information on this medicine is available on the European Medicines Agency (EMA) web side: http://www.ema.europa.eu.

Ebixa contains the active substance memantine hydrochloride. It belongs to a group of medicines known as anti-dementia medicines.
Memory loss in Alzheimer’s disease is due to a disturbance of message signals in the brain. The brain contains so-called N-methyl-D-aspartate (NMDA)-receptors that are involved in transmitting nerve signals important in learning and memory. Ebixa belongs to a group of medicines called NMDA- receptor antagonists. Ebixa acts on these NMDA-receptors improving the transmission of nerve signals and the memory.

Ebixa is used for the treatment of patients with moderate to severe Alzheimer’s disease.

Do not take Ebixa

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

Warning and precautions

Talk to your doctor or pharmacist before taking Ebixa:

• if you have a history of epileptic seizures
• if you have recently experienced a myocardial infarction (heart attack), or if you are suffering from congestive heart failure or from an uncontrolled hypertension (high blood pressure).

In these situations the treatment should be carefully supervised, and the clinical benefit of Ebixa reassessed by your doctor on a regular basis.

If you suffer from renal impairment (kidney problems), your doctor should closely monitor your kidney function and if necessary adapt the memantine doses accordingly.

If you are suffering from states of renal tubulary acidosis (RTA, an excess of acid-forming substances in the blood due to renal dysfunction (poor kidney function)) or severe infections of the urinary tract (structure that carries urine), your doctor may need to adjust the dose of your medicine.

The use of medicinal products called amantadine (for the treatment of Parkinson’s disease), ketamine (a substance generally used as an anaesthetic), dextromethorphan (generally used to treat cough) and other NMDA-antagonists at the same time should be avoided.

Children and adolescents

Ebixa is not recommended for children and adolescents under the age of 18 years.

Other medicines and Ebixa

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

In particular, Ebixa may change the effects of the following medicines and their dose may need to be adjusted by your doctor:

• amantadine, ketamine, dextromethorphan
• dantrolene, baclofen
• cimetidine, ranitidine, procainamide, quinidine, quinine, nicotine
• hydrochlorothiazide (or any combination with hydrochlorothiazide)
• anticholinergics (substances generally used to treat movement disorders or intestinal cramps)
• anticonvulsants (substances used to prevent and relieve seizures)
• barbiturates (substances generally used to induce sleep)
• dopaminergic agonists (substances such as L-dopa, bromocriptine)
• neuroleptics (substances used in the treatment of mental disorders)
• oral anticoagulants

If you go into hospital, let your doctor know that you are taking Ebixa.

Ebixa with food and drink

You should inform your doctor if you have recently changed or intend to change your diet substantially (e.g. from normal diet to strict vegetarian diet), as your doctor may need to adjust the dose of your medicine.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

The use of memantine in pregnant women is not recommended.

Breast-feeding

Women taking Ebixa should not breast-feed.

Driving and using machines

Your doctor will tell you whether your illness allows you to drive and to use machines safely.
Also, Ebixa may change your reactivity, making driving or operating machinery inappropriate.

Ebixa contains Sodium

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium- free’.

Always take Ebixa exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

The recommended dose of Ebixa for adults and older people is 20 mg once a day. In order to reduce the risk of side effects this dose is achieved gradually by the following daily treatment scheme:

week 1

half a 10 mg tablet

week 2

one 10 mg tablet

week 3

one and a half 10 mg tablets

week 4 and beyond two 10 mg tablets once a day

The usual starting dose is half a tablet once a day (1x 5 mg) for the first week. This is increased to one tablet once a day (1x 10 mg) in the second week and to 1 and a half tablets once a day in the third week. From the fourth week on, the usual dose is 2 tablets once a day (1x 20 mg).

Dosage in patients with impaired kidney function

If you have impaired kidney function, your doctor will decide upon a dose that suits your condition. In this case, monitoring of your kidney function should be performed by your doctor at specified intervals.

Administration

Ebixa should be administered orally once a day. To benefit from your medicine you should take it regularly every day at the same time of the day. The tablets should be swallowed with some water.
The tablets can be taken with or without food.

Duration of treatment

Continue to take Ebixa as long as it is of benefit to you. Your doctor should assess your treatment on a regular basis.

If you take more Ebixa than you should

• In general, taking too much Ebixa should not result in any harm to you. You may experience increased symptoms as described in section 4. “Possible side effects”.
• If you take a large overdose of Ebixa, contact your doctor or get medical advice, as you may need medical attention.

If you forget to take Ebixa

• If you find you have forgotten to take your dose of Ebixa, wait and take your next dose at the usual time.
• Do not take a double dose to make up for a forgotten dose.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everybody gets them.

In general, the observed side effects are mild to moderate.

Common (affects 1 to 10 users in 100):
- Headache, sleepiness, constipation, elevated liver function tests, dizziness, balance disorders, shortness of breath, high blood pressure and drug hypersensitivity

Uncommon (affects 1 to 10 users in 1,000):
• Tiredness, fungal infections, confusion, hallucinations, vomiting, abnormal gait, heart failure and venous blood clotting (thrombosis/thromboembolism)

Very Rare (affects less than 1 user in 10,000):
- Seizures

Not known (frequency cannot be estimated from the available data):
- Inflammation of the pancreas, inflammation of the liver (hepatitis) and psychotic reactions

Alzheimer’s disease has been associated with depression, suicidal ideation and suicide. These events have been reported in patients treated with Ebixa.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacis. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

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

Do not use this medicine after the expiry date which is stated on the carton and the blister after EXP.
The expiry date refers to the last day of that month.

This medicinal product does not require any special storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

What Ebixa contains

• The active substance is memantine hydrochloride. Each film-coated tablet contains 10 mg memantine hydrochloride equivalent to 8.31 mg memantine.

• The other ingredients are microcrystalline cellulose, croscarmellose sodium, colloidal anhydrous silica and magnesium stearate, all in the tablet core; and hypromellose, macrogol 400, titanium dioxide (E171) and iron oxide yellow (E172), all in the tablet coating.

What Ebixa looks like and contents of the pack

Ebixa film-coated tablets are presented as pale yellow to yellow, oval shaped film-coated tablet with breaking line and engravings “1 0” on one side and “M M” on the other side. The tablet can be divided into equal doses.

Ebixa film-coated tablets are available in blister packs of 14 tablets, 28 tablets, 30 tablets, 42 tablets, 49 x 1 tablets, 50 tablets, 56 tablets, 56 x 1 tablets, 70 tablets, 84 tablets, 98 tablets, 98 x 1 tablets, 100 tablets, 100 x 1 tablets, 112 tablets, 980 (10 x 98) tablets or 1000 (20 x 50) tablets. The pack sizes 49 x 1, 56 x 1, 98 x 1 and 100 x 1 film-coated tablets are presented in unit dose blister.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

H. Lundbeck A/S
Ottiliavej 9
2500 Valby
Denmark.

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder.

Belgique/België/Belgien
Lundbeck S.A./N.V.
Tél/Tel: +32 2 535 7979

Lietuva
Swixx Biopharma UAB
Tel: +370 5 236 91 40

България
Swixx Biopharma EOOD
Teл.: +359 (0)2 4942 480

Luxembourg/Luxemburg
Lundbeck S.A.
Tél: +32 2 535 7979

Česká republika
Swixx Biopharma s.r.o.
Tel: +420 242 434 222

Magyarország
Swixx Biopharma Kft.
Tel.: +36 1 9206 570

Danmark
Lundbeck Pharma A/S
Tlf: +45 4371 4270
Malta
H. Lundbeck A/S, Denmark
Tel: + 45 36301311

Deutschland
Lundbeck GmbH
Tel: +49 40 23649 0
Nederland
Lundbeck B.V.
Tel: +31 20 697 1901

Eesti
Swixx Biopharma OÜ
Tel: +372 640 1030

Norge
H. Lundbeck AS
Tlf: +47 91 300 800

Ελλάδα
Swixx Biopharma Μ.Α.Ε
Τηλ: +30 214 444 9670

Österreich
Lundbeck Austria GmbH
Tel: +43 1 253 621 6033

España
Lundbeck España S.A.
Tel: +34 93 494 9620

Polska
Swixx Biopharma Sp. z o.o.
Tel.: +48 22 4600 720

France
Lundbeck SAS
Tél: + 33 1 79 41 29 00

Portugal
Produtos Farmacêuticos - Unipessoal Lda.
Tel: +351 21 00 45 900

Hrvatska
Swixx Biopharma d.o.o.
Tel: +385 1 2078 500

România
Swixx Biopharma S.R.L
Tel: +40 37 1530 850

Ireland
Lundbeck (Ireland) Limited
Tel: +353 1 468 9800

Slovenija
Swixx Biopharma d.o.o.
Tel: +386 1 2355 100

Ísland
Vistor hf.
Tel: +354 535 7000

Slovenská republika
Swixx Biopharma s.r.o.
Tel: +421 2 20833 600

Italia
Lundbeck Italia S.p.A.
Tel: +39 02 677 4171

Suomi/Finland
Oy H. Lundbeck Ab
Puh/Tel: +358 2 276 5000

Κύπρος
Swixx Biopharma Μ.Α.Ε
Τηλ: +30 214 444 9670

Sverige
H. Lundbeck AB
Tel: +46 4069 98200

Latvija
Swixx Biopharma SIA
Tel: +371 6 616 47 50

This leaflet was last approved in MM/YYYY

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:
http://www.ema.europa.eu

Ebixa contains the active substance memantine hydrochloride. It belongs to a group of medicines known as anti-dementia medicines.

Memory loss in Alzheimer’s disease is due to a disturbance of message signals in the brain. The brain contains so-called N-methyl-D-aspartate (NMDA)-receptors that are involved in transmitting nerve signals important in learning and memory. Ebixa belongs to a group of medicines called NMDA- receptor antagonists. Ebixa acts on these NMDA-receptors improving the transmission of nerve signals and the memory.

Ebixa is used for the treatment of patients with moderate to severe Alzheimer’s disease.

Do not take Ebixa

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

Warning and precautions

Talk to your doctor or pharmacist before taking Ebixa:

• if you have a history of epileptic seizures
• if you have recently experienced a myocardial infarction (heart attack), or if you are suffering from congestive heart failure or from an uncontrolled hypertension (high blood pressure).

In these situations the treatment should be carefully supervised, and the clinical benefit of Ebixa reassessed by your doctor on a regular basis.

If you suffer from renal impairment (kidney problems), your doctor should closely monitor your kidney function and if necessary adapt the memantine doses accordingly.

If you are suffering from states of renal tubulary acidosis (RTA, an excess of acid-forming substances in the blood due to renal dysfunction (poor kidney function)) or severe infections of the urinary tract (structure that carries urine), your doctor may need to adjust the dose of your medicine.

The use of medicinal products called amantadine (for the treatment of Parkinson’s disease), ketamine (a substance generally used as an anaesthetic), dextromethorphan (generally used to treat cough) and other NMDA-antagonists at the same time should be avoided.

Children and adolescents

Ebixa is not recommended for children and adolescents under the age of 18 years.

Other medicines and Ebixa

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

In particular, Ebixa may change the effects of the following medicines and their dose may need to be adjusted by your doctor:

• amantadine, ketamine, dextromethorphan
• dantrolene, baclofen
• cimetidine, ranitidine, procainamide, quinidine, quinine, nicotine
• hydrochlorothiazide (or any combination with hydrochlorothiazide)
• anticholinergics (substances generally used to treat movement disorders or intestinal cramps)
• anticonvulsants (substances used to prevent and relieve seizures)
• barbiturates (substances generally used to induce sleep)
• dopaminergic agonists (substances such as L-dopa, bromocriptine)
• neuroleptics (substances used in the treatment of mental disorders)
• oral anticoagulants

If you go into hospital, let your doctor know that you are taking Ebixa.

Ebixa with food and drink

You should inform your doctor if you have recently changed or intend to change your diet substantially (e.g. from normal diet to strict vegetarian diet), as your doctor may need to adjust the dose of your medicine.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby,ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

The use of memantine in pregnant women is not recommended.

Breast-feeding

Women taking Ebixa should not breast-feed.

Driving and using machines

Your doctor will tell you whether your illness allows you to drive and to use machines safely.
Also, Ebixa may change your reactivity, making driving or operating machinery inappropriate.

Ebixa contains sorbitol and Potassium

This medicine contains 100 mg sorbitol in each gram which is equivalent to 200 mg /4 pump actuation. Sorbitol is a source of fructose. If your doctor told you that you have an intolerance to some sugars, or if you have been diagnosed with hereditary fructose intolerance (HFI), a rare genetic disorder in which a person cannot break down fructose, talk to your doctor before you take or receive this medicine. Your doctor will advise you.

Furthermore, this medicine contains potassium, less than 1 mmol (39 mg) per dose, i.e. essentially potassium-free.

Always take Ebixa exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

One pump actuation contains 5 mg memantine hydrochloride.
The recommended dose of Ebixa for adults and older people is four pump actuations, equivalent to 20 mg once a day. In order to reduce the risk of side effects this dose is achieved gradually by the following daily treatment scheme:

week 1

one pump actuation

week 2

two pump actuations

week 3

three pump actuations

week 4 and beyond
Four pump actuations

The usual starting dose is one pump actuation once daily (1x 5 mg) for the first week. This dose is increased in the second week to two pump actuations once daily (1 x 10 mg), and in the third week to three pump actuations once daily (1 x 15 mg). From the fourth week the recommended dose is four pump actuations once daily (1x 20 mg).

Dosage in patients with impaired kidney function

If you have impaired kidney function, your doctor will decide upon a dose that suits your condition. In this case, monitoring of your kidney function should be performed by your doctor at specified intervals.

Administration

Ebixa should be administered orally once a day. To benefit from your medicine you should take it regularly every day at the same time of the day. The solution should be taken with a little water. The solution can be taken with or without food.

For detailed instructions on the preparation and handling of the product see end of this leaflet.

Duration of treatment

Continue to take Ebixa as long as it is of benefit to you. Your doctor should assess your treatment on a regular basis.

If you take more Ebixa than you should

• In general, taking too much Ebixa should not result in any harm to you. You may experience increased symptoms as described in section 4. “Possible side effects”.
• If you take a large overdose of Ebixa, contact your doctor or get medical advice, as you may need medical attention.

If you forget to take Ebixa

• If you find you have forgotten to take your dose of Ebixa, wait and take your next dose at the usual time.
• Do not take a double dose to make up for a forgotten dose.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everybody gets them.

In general, the observed side effects are mild to moderate.

Common (affects 1 to 10 users in 100):
- Headache, sleepiness, constipation, elevated liver function tests, dizziness, balance disorders, shortness of breath, high blood pressure and drug hypersensitivity

Uncommon (affects 1 to 10 users in 1,000):
• Tiredness, fungal infections, confusion, hallucinations, vomiting, abnormal gait, heart failure and venous blood clotting (thrombosis/thromboembolism)

Very Rare (affects less than 1 user in 10,000):
- Seizures

Not known (frequency cannot be estimated from the available data):
- Inflammation of the pancreas, inflammation of the liver (hepatitis) and psychotic reactions

Alzheimer’s disease has been associated with depression, suicidal ideation and suicide. These events have been reported in patients treated with Ebixa.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacis. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

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

Do not use this medicine after the expiry date which is stated on the carton and the bottle label after EXP. The expiry date refers to the last day of that month.

Do not store above 30ºC.

Once opened, the contents of the bottle should be used within 3 months.

The bottle with the mounted pump must be kept and transported in an upright position only.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer required. These measures will help protect the environment.

What Ebixa contains

• The active substance is memantine hydrochloride. Each pump actuation delivers 0.5 ml of solution which contains 5 mg of memantine hydrochloride which is equivalent to 4.16 mg memantine.

• The other ingredients are potassium sorbate, sorbitol E420 and purified water.

What Ebixa looks like and contents of the pack

Ebixa oral solution is presented as a clear, colourless to light yellowish solution.

Ebixa oral solution is available in bottles of 50 ml, 100 ml or 10 x 50 ml.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

H. Lundbeck A/S
Ottiliavej 9
2500 Valby
Denmark.

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder.

Belgique/België/Belgien
Lundbeck S.A./N.V.
Tél/Tel: +32 2 535 7979

Lietuva
Swixx Biopharma UAB
Tel: +370 5 236 91 40

България
Swixx Biopharma EOOD
Teл.: +359 (0)2 4942 480

Luxembourg/Luxemburg
Lundbeck S.A.
Tél: +32 2 535 7979

Česká republika
Swixx Biopharma s.r.o.
Tel: +420 242 434 222

Magyarország
Swixx Biopharma Kft.
Tel.: +36 1 9206 570

Danmark
Lundbeck Pharma A/S
Tlf: +45 4371 4270
Malta
H. Lundbeck A/S, Denmark
Tel: + 45 36301311

Deutschland
Lundbeck GmbH
Tel: +49 40 23649 0
Nederland
Lundbeck B.V.
Tel: +31 20 697 1901

Eesti
Swixx Biopharma OÜ
Tel: +372 640 1030

Norge
H. Lundbeck AS
Tlf: +47 91 300 800

Ελλάδα
Swixx Biopharma Μ.Α.Ε
Τηλ: +30 214 444 9670

Österreich
Lundbeck Austria GmbH
Tel: +43 1 253 621 6033

España
Lundbeck España S.A.
Tel: +34 93 494 9620

Polska
Swixx Biopharma Sp. z o.o.
Tel.: +48 22 4600 720

France
Lundbeck SAS
Tél: + 33 1 79 41 29 00

Portugal
Produtos Farmacêuticos - Unipessoal Lda.
Tel: +351 21 00 45 900

Hrvatska
Swixx Biopharma d.o.o.
Tel: +385 1 2078 500

România
Swixx Biopharma S.R.L
Tel: +40 37 1530 850

Ireland
Lundbeck (Ireland) Limited
Tel: +353 1 468 9800

Slovenija
Swixx Biopharma d.o.o.
Tel: +386 1 2355 100

Ísland
Vistor hf.
Tel: +354 535 7000

Slovenská republika
Swixx Biopharma s.r.o.
Tel: +421 2 20833 600

Italia
Lundbeck Italia S.p.A.
Tel: +39 02 677 4171

Suomi/Finland
Oy H. Lundbeck Ab
Puh/Tel: +358 2 276 5000

Κύπρος
Swixx Biopharma Μ.Α.Ε
Τηλ: +30 214 444 9670

Sverige
H. Lundbeck AB
Tel: +46 4069 98200

Latvija
Swixx Biopharma SIA
Tel: +371 6 616 47 50

This leaflet was last approved in MM/YYYY

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:
http://www.ema.europa.eu

Instruction for proper use of the pump

The solution must not be poured or pumped directly into the mouth from the bottle or pump. Measure the dose onto a spoon or into a glass of water, using the pump.

Take the screw cap off the bottle:

The cap must be turned anticlockwise, unscrewed completely and removed (fig. 1).

Mounting the dosing pump on the bottle:

Take the dosing pump out of the plastic bag (fig. 2) and place it on top of the bottle. Slide the plastic dip tube carefully into the bottle. Hold the dosing pump onto the neck of the bottle and screw it clockwise until it fits firmly (fig. 3). The dosing pump is only screwed on once when starting the use, and should never be unscrewed.

How the dosing pump works:

The dosing pump head has two positions and is easy to turn:
- anticlockwise to unlock and
- clockwise to lock.

The dosing pump head should not be pushed down while in the locked position. The solution may only be dispensed in the unlocked position. To unlock, turn the pump head in the direction of the arrow

until it cannot be turned any further (about one eighth of a turn, fig. 4). The dosing pump is then ready for use.

Preparing the dosing pump:

When used for the first time, the dosing pump does not dispense the correct amount of oral solution.
Therefore, the pump must be prepared (primed) by pushing the dosing pump head down completely five times in succession (fig. 5).

The solution thus dispensed is discarded. The next time the dosing pump head is pushed downwards completely (equivalent to one pump actuation), it dispenses the correct dose (fig. 6).

Correct use of the dosing pump:

Place the bottle on a flat, horizontal surface, for example a table top, and only use it in an upright position. Hold a glass with a little water or a spoon below the nozzle. Push down the dosing pump head in a firm but calm and steady manner - not too slowly (fig. 7, fig. 8).

The dosing pump head can then be released and is ready for the next pump actuation.

The dosing pump must only be used with the Ebixa solution in the bottle provided, not for other substances or containers. If the pump does not function properly, consult your doctor or a pharmacist.
Lock the dosing pump after using Ebixa.

Ebixa contains the active substance memantine hydrochloride. It belongs to a group of medicines known as anti-dementia medicines.
Memory loss in Alzheimer’s disease is due to a disturbance of message signals in the brain. The brain contains so-called N-methyl-D-aspartate (NMDA)-receptors that are involved in transmitting nerve signals important in learning and memory. Ebixa belongs to a group of medicines called NMDA- receptor antagonists. Ebixa acts on these NMDA-receptors improving the transmission of nerve signals and the memory.

Ebixa is used for the treatment of patients with moderate to severe Alzheimer’s disease.

Do not take Ebixa

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

Warning and precautions

Talk to your doctor or pharmacist before taking Ebixa:

• if you have a history of epileptic seizures
• if you have recently experienced a myocardial infarction (heart attack), or if you are suffering from congestive heart failure or from an uncontrolled hypertension (high blood pressure).

In these situations the treatment should be carefully supervised, and the clinical benefit of Ebixa reassessed by your doctor on a regular basis.

If you suffer from renal impairment (kidney problems), your doctor should closely monitor your kidney function and if necessary adapt the memantine doses accordingly.

If you are suffering from states of renal tubulary acidosis (RTA, an excess of acid-forming substances in the blood due to renal dysfunction (poor kidney function)) or severe infections of the urinary tract (structure that carries urine), your doctor may need to adjust the dose of your medicine.

The use of medicinal products called amantadine (for the treatment of Parkinson’s disease), ketamine (a substance generally used as an anaesthetic), dextromethorphan (generally used to treat cough) and other NMDA-antagonists at the same time should be avoided.

Children and adolescents

Ebixa is not recommended for children and adolescents under the age of 18 years.

Other medicines and Ebixa

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines,.

In particular, Ebixa may change the effects of the following medicines and their dose may need to be adjusted by your doctor:

• amantadine, ketamine, dextromethorphan
• dantrolene, baclofen
• cimetidine, ranitidine, procainamide, quinidine, quinine, nicotine
• hydrochlorothiazide (or any combination with hydrochlorothiazide)
• anticholinergics (substances generally used to treat movement disorders or intestinal cramps)
• anticonvulsants (substances used to prevent and relieve seizures)
• barbiturates (substances generally used to induce sleep)
• dopaminergic agonists (substances such as L-dopa, bromocriptine)
• neuroleptics (substances used in the treatment of mental disorders)
• oral anticoagulants

If you go into hospital, let your doctor know that you are taking Ebixa.

Ebixa with food and drink

You should inform your doctor if you have recently changed or intend to change your diet substantially (e.g. from normal diet to strict vegetarian diet), as your doctor may need to adjust the dose of your medicine.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding. Think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

The use of memantine in pregnant women is not recommended.

Breast-feeding

Women taking Ebixa should not breast-feed.

Driving and using machines

Your doctor will tell you whether your illness allows you to drive and to use machines safely.
Also, Ebixa may change your reactivity, making driving or operating machinery inappropriate.

Ebixa contains Sodium

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium- free’.

The Ebixa treatment initiation pack is only to be used for the beginning of the treatment with Ebixa.

Always take Ebixa exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

The recommended treatment dose of 20 mg per day is achieved by a gradual increase of the Ebixa dose during the first 3 weeks of treatment. The treatment scheme is also indicated on the treatment initiation pack. Take one tablet once a day.

Week 1 (day 1-7):
Take one 5 mg tablet once a day (white to off-white, oval-oblong) for 7 days.

Week 2 (day 8-14):
Take one 10 mg tablet once a day (pale yellow to yellow, oval shaped) for 7 days.

Week 3 (day 15-21):
Take one 15 mg tablet once a day (grey-orange, oval-oblong) for 7 days.

Week 4 (day 22-28):
Take one 20 mg tablet per day (grey-red, oval-oblong) for 7 days.

week 1

5 mg tablet

week 2

10 mg tablet

week 3

15 mg tablet

week 4 and beyond
20 mg tablets once a day

Maintenance dose

The recommended daily dose is 20 mg once a day.
For continuation of the treatment please consult your doctor.

Dosage in patients with impaired kidney function

If you have impaired kidney function, your doctor will decide upon a dose that suits your condition. In this case, monitoring of your kidney function should be performed by your doctor at specified intervals.

Administration

Ebixa should be administered orally once a day. To benefit from your medicine you should take it regularly every day at the same time of the day. The tablets should be swallowed with some water.
The tablets can be taken with or without food.

Duration of treatment

Continue to take Ebixa as long as it is of benefit to you. Your doctor should assess your treatment on a regular basis.

If you take more Ebixa than you should

• In general, taking too much Ebixa should not result in any harm to you. You may experience increased symptoms as described in section 4. ”Possible side effects”.
• If you take a large overdose of Ebixa, contact your doctor or get medical advice, as you may need medical attention.

If you forget to take Ebixa

• If you find you have forgotten to take your dose of Ebixa, wait and take your next dose at the usual time.
• Do not take a double dose to make up for a forgotten dose.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everybody gets them.

In general, the observed side effects are mild to moderate.

Common (affects 1 to 10 users in 100):
- Headache, sleepiness, constipation, elevated liver function tests, dizziness, balance disorders, shortness of breath, high blood pressure and drug hypersensitivity

Uncommon (affects 1 to 10 users in 1,000):
- Tiredness, fungal infections, confusion, hallucinations, vomiting, abnormal gait, heart failure and venous blood clotting (thrombosis/thromboembolism)

Very Rare (affects less than 1 user in 10,000):
- Seizures

Not known (frequency cannot be estimated from the available data):
- Inflammation of the pancreas, inflammation of the liver (hepatitis) and psychotic reactions

Alzheimer’s disease has been associated with depression, suicidal ideation and suicide. These events have been reported in patients treated with Ebixa.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacis. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

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

Do not use this medicine after the expiry date which is stated on the carton and the blister after EXP.
The expiry date refers to the last day of that month.

This medicinal product does not require any special storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

What Ebixa contains

• The active substance is memantine hydrochloride. Each tablet contains 5/10/15/20 mg ofmemantine hydrochloride equivalent to 4.15/8.31/12.46/16.62 mg memantine.

• The other ingredients for Ebixa 5/10/15 and 20 mg film-coated tablets are microcrystalline cellulose, croscarmellose sodium, colloidal anhydrous silica, magnesium stearate, all in the tablet core; and hypromellose, macrogol 400, titanium dioxide (E 171) and additional for Ebixa 10 mg film-coated tablets is iron oxide yellow (E172) and for Ebixa 15 mg and Ebixa 20 mg film-coated tablets are iron oxide yellow and red (E 172), all in the tablet coating.

What Ebixa looks like and contents of the pack

Ebixa 5 mg film-coated tablets are presented as white to off-white, oval-oblong with imprint ‘5’ on one side and imprint ‘MEM’ on the other side.
Ebixa 10 mg film-coated tablets are presented as pale yellow to yellow, oval shaped film-coated tablet with breaking line and engravings ‘1 0’ on one side and ‘M M’ on the other side. The tablet can be divided into equal doses.
Ebixa 15 mg film-coated tablets are presented as orange to grey-orange, oval-oblong with imprint ‘15’ on one side and imprint ‘MEM’ on the other side.
Ebixa 20 mg film-coated tablets are presented as are pale red to grey-red, oval-oblong with imprint ‘20’ on one side and imprint ‘MEM’ on the other side.
One treatment initiation pack contains 28 tablets in 4 blisters with 7 tablets of Ebixa 5 mg, 7 tablets of Ebixa 10 mg, 7 tablets of Ebixa 15 mg and 7 tablets of Ebixa 20 mg.

Marketing Authorisation Holder and Manufacturer

H. Lundbeck A/S
Ottiliavej 9
2500 Valby
Denmark.

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder.

Belgique/België/Belgien
Lundbeck S.A./N.V.
Tél/Tel: +32 2 535 7979

Lietuva
Swixx Biopharma UAB
Tel: +370 5 236 91 40

България
Swixx Biopharma EOOD
Teл.: +359 (0)2 4942 480

Luxembourg/Luxemburg
Lundbeck S.A.
Tél: +32 2 535 7979

Česká republika
Swixx Biopharma s.r.o.
Tel: +420 242 434 222

Magyarország
Swixx Biopharma Kft.
Tel.: +36 1 9206 570

Danmark
Lundbeck Pharma A/S
Tlf: +45 4371 4270
Malta
H. Lundbeck A/S, Denmark
Tel: + 45 36301311

Deutschland
Lundbeck GmbH
Tel: +49 40 23649 0
Nederland
Lundbeck B.V.
Tel: +31 20 697 1901

Eesti
Swixx Biopharma OÜ
Tel: +372 640 1030

Norge
H. Lundbeck AS
Tlf: +47 91 300 800

Ελλάδα
Swixx Biopharma Μ.Α.Ε
Τηλ: +30 214 444 9670

Österreich
Lundbeck Austria GmbH
Tel: +43 1 253 621 6033

España
Lundbeck España S.A.
Tel: +34 93 494 9620

Polska
Swixx Biopharma Sp. z o.o.
Tel.: +48 22 4600 720

France
Lundbeck SAS
Tél: + 33 1 79 41 29 00

Portugal
Produtos Farmacêuticos - Unipessoal Lda.
Tel: +351 21 00 45 900

Hrvatska
Swixx Biopharma d.o.o.
Tel: +385 1 2078 500

România
Swixx Biopharma S.R.L
Tel: +40 37 1530 850

Ireland
Lundbeck (Ireland) Limited
Tel: +353 1 468 9800

Slovenija
Swixx Biopharma d.o.o.
Tel: +386 1 2355 100

Ísland
Vistor hf.
Tel: +354 535 7000

Slovenská republika
Swixx Biopharma s.r.o.
Tel: +421 2 20833 600

Italia
Lundbeck Italia S.p.A.
Tel: +39 02 677 4171

Suomi/Finland
Oy H. Lundbeck Ab
Puh/Tel: +358 2 276 5000

Κύπρος
Swixx Biopharma Μ.Α.Ε
Τηλ: +30 214 444 9670

Sverige
H. Lundbeck AB
Tel: +46 4069 98200

Latvija
Swixx Biopharma SIA
Tel: +371 6 616 47 50

This leaflet was last approved in MM/YYYY

Other sources of information

Detailed information on this medicine is available on the the European Medicines Agency web site:http://www.ema.europa.eu

Ebixa contains the active substance memantine hydrochloride. It belongs to a group of medicines known as anti-dementia medicines.
Memory loss in Alzheimer’s disease is due to a disturbance of message signals in the brain. The brain contains so-called N-methyl-D-aspartate (NMDA)-receptors that are involved in transmitting nerve signals important in learning and memory. Ebixa belongs to a group of medicines called NMDA- receptor antagonists. Ebixa acts on these NMDA-receptors improving the transmission of nerve signals and the memory.

Ebixa is used for the treatment of patients with moderate to severe Alzheimer’s disease.

Do not take Ebixa

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

Warning and precautions

Talk to your doctor or pharmacist before taking Ebixa:

• if you have a history of epileptic seizures
• if you have recently experienced a myocardial infarction (heart attack), or if you are suffering from congestive heart failure or from an uncontrolled hypertension (high blood pressure).

In these situations the treatment should be carefully supervised, and the clinical benefit of Ebixa reassessed by your doctor on a regular basis.

If you suffer from renal impairment (kidney problems), your doctor should closely monitor your kidney function and if necessary adapt the memantine doses accordingly.

If you are suffering from states of renal tubulary acidosis (RTA, an excess of acid-forming substances in the blood due to renal dysfunction (poor kidney function)) or severe infections of the urinary tract (structure that carries urine), your doctor may need to adjust the dose of your medicine.

The use of medicinal products called amantadine (for the treatment of Parkinson’s disease), ketamine (a substance generally used as an anaesthetic), dextromethorphan (generally used to treat cough) and other NMDA-antagonists at the same time should be avoided.

Children and adolescents
Ebixa is not recommended for children and adolescents under the age of 18 years.

Other medicines and Ebixa

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

In particular, Ebixa may change the effects of the following medicines and their dose may need to be adjusted by your doctor:

• amantadine, ketamine, dextromethorphan
• dantrolene, baclofen
• cimetidine, ranitidine, procainamide, quinidine, quinine, nicotine
• hydrochlorothiazide (or any combination with hydrochlorothiazide)
• anticholinergics (substances generally used to treat movement disorders or intestinal cramps)
• anticonvulsants (substances used to prevent and relieve seizures)
• barbiturates (substances generally used to induce sleep)
• dopaminergic agonists (substances such as L-dopa, bromocriptine)
• neuroleptics (substances used in the treatment of mental disorders)
• oral anticoagulants

If you go into hospital, let your doctor know that you are taking Ebixa.

Ebixa with food and drink

You should inform your doctor if you have recently changed or intend to change your diet substantially (e.g. from normal diet to strict vegetarian diet), as your doctor may need to adjust the dose of your medicine.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby,ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

The use of memantine in pregnant women is not recommended.

Breast-feeding

Women taking Ebixa should not breast-feed.

Driving and using machines

Your doctor will tell you whether your illness allows you to drive and to use machines safely.

Also, Ebixa may change your reactivity, making driving or operating machinery inappropriate.

Ebixa contains Sodium

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium- free’.

Always take Ebixa exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

The recommended dose of Ebixa for adults and older people is 20 mg once a day.

In order to reduce the risk of side effects this dose is achieved gradually by the following daily treatment scheme. For up-titration other tablet strengths are available.

At the beginning of treatment you will start by using Ebixa 5 mg film-coated tablets once a day. This dose will be increased weekly by 5 mg until the recommended (maintenance) dose is reached. The recommended maintenance dose is 20 mg once a day, which is reached at the beginning of the 4th week.

Dosage in patients with impaired kidney function

If you have impaired kidney function, your doctor will decide upon a dose that suits your condition. In this case, monitoring of your kidney function should be performed by your doctor at specified intervals.

Administration

Ebixa should be administered orally once a day. To benefit from your medicine you should take it regularly every day at the same time of the day. The tablets should be swallowed with some water.
The tablets can be taken with or without food.

Duration of treatment

Continue to take Ebixa as long as it is of benefit to you. Your doctor should assess your treatment on a regular basis.

If you take more Ebixa than you should

• In general, taking too much Ebixa should not result in any harm to you. You may experience increased symptoms as described in section 4. “Possible side effects”.
• If you take a large overdose of Ebixa, contact your doctor or get medical advice, as you may need medical attention.

If you forget to take Ebixa

• If you find you have forgotten to take your dose of Ebixa, wait and take your next dose at the usual time.
• Do not take a double dose to make up for a forgotten dose.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everybody gets them.

In general, the observed side effects are mild to moderate.

Common (affects 1 to 10 users in 100):
- Headache, sleepiness, constipation, elevated liver function tests, dizziness, balance disorders, shortness of breath, high blood pressure and drug hypersensitivity

Uncommon (affects 1 to 10 users in 1,000):
- Tiredness, fungal infections, confusion, hallucinations, vomiting, abnormal gait, heart failure and venous blood clotting (thrombosis/thromboembolism)

Very Rare (affects less than 1 user in 10,000):
- Seizures

Not known (frequency cannot be estimated from the available data):
- Inflammation of the pancreas, inflammation of the liver (hepatitis) and psychotic reactions

Alzheimer’s disease has been associated with depression, suicidal ideation and suicide. These events have been reported in patients treated with Ebixa.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacis. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

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

Do not use this medicine after the expiry date which is stated on the carton and the blister after EXP.
The expiry date refers to the last day of that month.

This medicinal product does not require any special storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer required. These measures will help protect the environment.

What Ebixa contains

• The active substance is memantine hydrochloride. Each film-coated tablet contains 20 mg memantine hydrochloride equivalent to 16.62 mg memantine.

• The other ingredients are microcrystalline cellulose, croscarmellose sodium, colloidal anhydrous silica, magnesium stearate, all in the tablet core; and hypromellose, macrogol 400, titanium dioxide (E 171), iron oxide yellow and red (E 172), all in the tablet coating.

What Ebixa looks like and contents of the pack

Ebixa film-coated tablets are presented as pale red to grey-red, oval-oblong film-coated tablets with imprint ‘20’ on one side and imprint ‘MEM’ on the other side.

Ebixa film-coated tablets are available in blister packs of 14 tablets, 28 tablets, 42 tablets, 49 x 1 tablets, 56 tablets, 56 x 1 tablets, 70 tablets, 84 tablets, 98 tablets, 98 x 1 tablets, 100 x 1 tablets, 112 tablets or 840 (20 x 42) tablets. The pack sizes 49 x 1, 56 x 1, 98 x 1 and 100 x 1 film-coated tablets are presented in unit dose blister.

Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer

H. Lundbeck A/S
Ottiliavej 9
2500 Valby
Denmark.

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder.

Belgique/België/Belgien
Lundbeck S.A./N.V.
Tél/Tel: +32 2 535 7979

Lietuva
Swixx Biopharma UAB
Tel: +370 5 236 91 40

България
Swixx Biopharma EOOD
Teл.: +359 (0)2 4942 480

Luxembourg/Luxemburg
Lundbeck S.A.
Tél: +32 2 535 7979

Česká republika
Swixx Biopharma s.r.o.
Tel: +420 242 434 222

Magyarország
Swixx Biopharma Kft.
Tel.: +36 1 9206 570

Danmark
Lundbeck Pharma A/S
Tlf: +45 4371 4270
Malta
H. Lundbeck A/S, Denmark
Tel: + 45 36301311

Deutschland
Lundbeck GmbH
Tel: +49 40 23649 0
Nederland
Lundbeck B.V.
Tel: +31 20 697 1901

Eesti
Swixx Biopharma OÜ
Tel: +372 640 1030

Norge
H. Lundbeck AS
Tlf: +47 91 300 800

Ελλάδα
Swixx Biopharma Μ.Α.Ε
Τηλ: +30 214 444 9670

Österreich
Lundbeck Austria GmbH
Tel: +43 1 253 621 6033

España
Lundbeck España S.A.
Tel: +34 93 494 9620

Polska
Swixx Biopharma Sp. z o.o.
Tel.: +48 22 4600 720

France
Lundbeck SAS
Tél: + 33 1 79 41 29 00

Portugal
Produtos Farmacêuticos - Unipessoal Lda.
Tel: +351 21 00 45 900

Hrvatska
Swixx Biopharma d.o.o.
Tel: +385 1 2078 500

România
Swixx Biopharma S.R.L
Tel: +40 37 1530 850

Ireland
Lundbeck (Ireland) Limited
Tel: +353 1 468 9800

Slovenija
Swixx Biopharma d.o.o.
Tel: +386 1 2355 100

Ísland
Vistor hf.
Tel: +354 535 7000

Slovenská republika
Swixx Biopharma s.r.o.
Tel: +421 2 20833 600

Italia
Lundbeck Italia S.p.A.
Tel: +39 02 677 4171

Suomi/Finland
Oy H. Lundbeck Ab
Puh/Tel: +358 2 276 5000

Κύπρος
Swixx Biopharma Μ.Α.Ε
Τηλ: +30 214 444 9670

Sverige
H. Lundbeck AB
Tel: +46 4069 98200

Latvija
Swixx Biopharma SIA
Tel: +371 6 616 47 50

This leaflet was last approved in MM/YYYY

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:
http://www.ema.europa.eu