roflumilast: package leaflet

Daxas contains the active substance roflumilast, which is an anti-inflammatory medicine called phosphodiesterase-4 inhibitor. Roflumilast reduces the activity of phosphodiesterase-4, a protein occurring naturally in body cells. When the activity of this protein is reduced, there is less inflammation in the lungs. This helps to stop narrowing of airways occurring in chronic obstructive pulmonary disease (COPD). Thus Daxas eases breathing problems.

Daxas is used for maintenance treatment of severe COPD in adults who in the past had frequent worsening of their COPD symptoms (so-called exacerbations) and who have chronic bronchitis.
COPD is a chronic disease of the lungs that results in tightening of the airways (obstruction) and swelling and irritation of the walls of the small air passages (inflammation). This leads to symptoms such as coughing, wheezing, chest tightness or difficulty in breathing. Daxas is to be used in addition to bronchodilators.

Do not take Daxas
- if you are allergic to roflumilast or any of the other ingredients of this medicine (listed in section 6)
- if you have moderate or severe liver problems.

Warnings and precautions
Talk to your doctor or pharmacist before taking Daxas.

Sudden attack of breathlessness
Daxas is not intended for the treatment of a sudden attack of breathlessness (acute bronchospasms). In order to relieve a sudden attack of breathlessness it is very important that your doctor provides you with another medicine to be available to you at all times that can cope with such an attack. Daxas will not help you in this situation.

Body weight
You should check your body weight on a regular basis. Talk to your doctor if, while taking this medicine, you observe an unintentional loss of body weight (not related to a diet or exercise programme).

Other diseases
Daxas is not recommended if you have one or more of the following diseases:
- severe immunological diseases such as HIV infection, multiple sclerosis (MS), lupus erythematosus (LE) or progressive multifocal leukoencephalopathy (PML)
- severe acute infectious diseases such as acute hepatitis
- cancer (except basal-cell carcinoma, a slow-growing type of skin cancer)
- or severe impairment of the heart function
There is a lack of relevant experience with Daxas under these conditions. You should talk to your doctor, if you are diagnosed with any of these diseases.

Experience is also limited in patients with a previous diagnosis of tuberculosis, viral hepatitis, herpes viral infection or herpes zoster. Please talk to your doctor if you have one of these diseases.

Symptoms you should be aware of
You may experience diarrhoea, nausea, abdominal pain or headache during the first weeks of treatment with Daxas. Talk to your doctor if these side effects do not resolve within the first weeks of treatment.

Daxas is not recommended in patients with a history of depression associated with suicidal thinking or behaviour. You may also experience sleeplessness, anxiety, nervousness, or depressive mood. Before starting treatment with Daxas, inform your doctor if you are suffering from any symptoms of this kind and of any additional medicines you may take since some of those could increase the probability of these side effects. You or your caregiver should also immediately inform your doctor of any changes in behaviour or mood and of any suicidal thoughts you may have.

Children and adolescents
Do not give this medicine to children and adolescents under 18 years of age.

Other medicines and Daxas
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, especially the following:
- a medicine containing theophylline (a medicine to treat respiratory diseases), or
- a medicine used for treatment of immunological diseases, such as methotrexate, azathioprine, infliximab, etanercept, or oral corticosteroids to be taken long-term.
- a medicine containing fluvoxamine (a medicine to treat anxiety disorders and depression), enoxacin (a medicine to treat bacterial infections) or cimetidine (a medicine to treat stomach ulcers or heartburn).

The effect of Daxas may be reduced if taken together with rifampicin (an antibiotic medicine) or with phenobarbital, carbamazepine or phenytoin (medicines usually prescribed for the treatment of epilepsy). Ask your doctor for advice.

Daxas may be taken with other medicines used in the treatment of COPD such as inhaled or oral corticosteroids or bronchodilators. Do not stop taking these medicines or reduce their dose unless advised by your doctor.

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.
You should not become pregnant during treatment with this medicine and should use an effective method of contraception during therapy, because Daxas may be harmful for the unborn baby.

Driving and using machines
Daxas has no influence on the ability to drive and use machines.

Daxas contains lactose
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

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

• For the first 28 days - the recommended starting dose is one 250 micrograms tablet once daily.
• The starting dose is a low dose used to help your body get used to the medicine before you start taking the full dose. At this low dose you will not get the full effect from the medicine – therefore it is important that you move on to the full dose (called a ‘maintenance dose’) after 28 days.
• After 28 days - the recommended maintenance dose is one 500 micrograms tablet once daily.

Swallow the tablet with some water. You may take this medicine with or without food. Take the tablet at the same time every day.

You may need to take Daxas for several weeks to achieve its beneficial effect.

If you take more Daxas than you should
If you have taken more tablets than you should, you may experience the following symptoms:
headache, nausea, diarrhoea, dizziness, throbbing of your heart, light-headedness, clamminess and low blood pressure. Tell your doctor or pharmacist straight away. If possible take your medicine and this leaflet with you.

If you forget to take Daxas
If you forget to take a tablet at the usual time, take the tablet as soon as you remember on the same day. If on one day you have forgotten to take a tablet of Daxas, just carry on the next day with the next tablet as usual. Continue taking your medicine at the usual times. Do not take a double dose to make up for a forgotten dose.

If you stop taking Daxas
It is important to continue taking Daxas for as long as prescribed by your doctor, even when you have no symptoms, in order to maintain control of your lung function.

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.

You may experience diarrhoea, nausea, stomach ache or headache during the first weeks of treatment with Daxas. Talk to your doctor if these side effects do not resolve within the first weeks of treatment.

Some side effects could be serious. In clinical studies and post-marketing experience, rare instances of suicidal thinking and behaviour (including suicide) were reported. Please notify your doctor immediately of any suicidal thoughts you may have. You may also experience sleeplessness (common), anxiety (uncommon), nervousness (rare), panic attack (rare) or depressive mood (rare).

In uncommon cases allergic reactions may occur. Allergic reactions may affect the skin and in rare cases cause swelling of the eyelids, face, lips and tongue, possibly leading to difficulties in breathing and/or a drop in blood pressure and accelerated heartbeat. In case of an allergic reaction, stop taking Daxas and contact your doctor immediately, or go immediately to the emergency department in the nearest hospital. Take all your medicines and this leaflet with you and provide full information of your current medications.

Other side effects include the following:

Common side effects (may affect up to 1 in 10 people)
- diarrhoea, nausea, stomach ache
- weight decrease, decreased appetite
- headache

Uncommon side effects (may affect up to 1 in 100 people)
- trembling, sensation of spinning head (vertigo), dizziness
- sensation of rapid or irregular heartbeat (palpitations)
- gastritis, vomiting
- reflux of stomach acid to the gullet (acid regurgitations), indigestion
- rash
- muscle pain, muscle weakness or cramps
- back pain
- feeling of weakness or tiredness, feeling unwell.

Rare side effects (may affect up to 1 in 1,000 people)
- male breast enlargement
- decreased sense of taste
- respiratory tract infections (excluding pneumonia)
- bloody stools, constipation
- elevation of liver or muscle enzymes (seen in blood tests)
- wheals (urticaria).

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 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 blister after EXP. The expiry date refers to the last day of that month.

This medicine 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 Daxas contains
The active substance is roflumilast.

Each Daxas 250 micrograms tablet contains 250 micrograms roflumilast. The other ingredients are lactose monohydrate (see section 2 under “Daxas contains lactose”), maize starch, povidone, magnesium stearate.

What Daxas looks like and contents of the pack
Daxas 250 micrograms tablets are white to off-white, embossed with ‘D’ on one side and ‘250’ on the other side.
Each pack contains 28 tablets.

Marketing Authorisation Holder
AstraZeneca AB
SE-151 85 Södertälje
Sweden

Manufacturer
Corden Pharma GmbH
Otto-Hahn-Strasse 1
68723 Plankstadt
Germany

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

België/Belgique/Belgien
AstraZeneca S.A./N.V.
Tel: +32 2 370 48 11

Lietuva
UAB AstraZeneca Lietuva
Tel: +370 5 2660550

България
АстраЗенека България ЕООД
Тел.: +359 24455000

Luxembourg/Luxemburg
AstraZeneca S.A./N.V.
Tél/Tel: +32 2 370 48 11

Česká republika
AstraZeneca Czech Republic s.r.o.
Tel: +420 222 807 111

Magyarország
AstraZeneca Kft.
Tel.: +36 1 883 6500

Danmark
AstraZeneca A/S
Tlf: +45 43 66 64 62

Malta
Associated Drug Co. Ltd
Tel: +356 2277 8000

Deutschland
AstraZeneca GmbH
Tel: +49 40 809034100

Nederland
AstraZeneca BV
Tel: +31 85 808 9900

Eesti
AstraZeneca
Tel: +372 6549 600

Norge
AstraZeneca AS
Tlf: +47 21 00 64 00

Ελλάδα
AstraZeneca A.E.
Τηλ: +30 210 6871500

Österreich
AstraZeneca Österreich GmbH
Tel: +43 1 711 31 0

España
AstraZeneca Farmacéutica Spain, S.A.
Tel: +34 91 301 91 00

Polska
AstraZeneca Pharma Poland Sp. z o.o.
Tel.: +48 22 245 73 00

France
Portugal

AstraZeneca
Tél: +33 1 41 29 40 00

AstraZeneca Produtos Farmacêuticos, Lda.
Tel: +351 21 434 61 00

Hrvatska
AstraZeneca d.o.o.
Tel: +385 1 4628 000

România
AstraZeneca Pharma SRL
Tel: +40 21 317 60 41

Ireland
AstraZeneca Pharmaceuticals (Ireland) DAC
Tel: +353 1609 7100

Slovenija
AstraZeneca UK Limited
Tel: +386 1 51 35 600

Ísland
Vistor
Sími: +354 535 7000

Slovenská republika
AstraZeneca AB, o.z.
Tel: +421 2 5737 7777

Italia
Simesa S.p.A.
Tel: +39 02 00704500

Suomi/Finland
AstraZeneca Oy
Puh/Tel: +358 10 23 010

Κύπρος
Αλέκτωρ Φαρµακευτική Λτδ
Τηλ: +357 22490305

Sverige
AstraZeneca AB
Tel: +46 8 553 26 000

Latvija
SIA AstraZeneca Latvija
Tel: +371 67377100

This leaflet was last approved in

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

Daxas contains the active substance roflumilast, which is an anti-inflammatory medicine called phosphodiesterase-4 inhibitor. Roflumilast reduces the activity of phosphodiesterase-4, a protein occurring naturally in body cells. When the activity of this protein is reduced, there is less inflammation in the lungs. This helps to stop narrowing of airways occurring in chronic obstructive pulmonary disease (COPD). Thus Daxas eases breathing problems.

Daxas is used for maintenance treatment of severe COPD in adults who in the past had frequent worsening of their COPD symptoms (so-called exacerbations) and who have chronic bronchitis.
COPD is a chronic disease of the lungs that results in tightening of the airways (obstruction) and swelling and irritation of the walls of the small air passages (inflammation). This leads to symptoms such as coughing, wheezing, chest tightness or difficulty in breathing. Daxas is to be used in addition to bronchodilators.

Do not take Daxas
- if you are allergic to roflumilast or any of the other ingredients of this medicine (listed in section 6)
- if you have moderate or severe liver problems.

Warnings and precautions
Talk to your doctor or pharmacist before taking Daxas.

Sudden attack of breathlessness
Daxas is not intended for the treatment of a sudden attack of breathlessness (acute bronchospasms). In order to relieve a sudden attack of breathlessness it is very important that your doctor provides you with another medicine to be available to you at all times that can cope with such an attack. Daxas will not help you in this situation.

Body weight
You should check your body weight on a regular basis. Talk to your doctor if, while taking this medicine, you observe an unintentional loss of body weight (not related to a diet or exercise programme).

Other diseases
Daxas is not recommended if you have one or more of the following diseases:
- severe immunological diseases such as HIV infection, multiple sclerosis (MS), lupus erythematosus (LE) or progressive multifocal leukoencephalopathy (PML)
- severe acute infectious diseases such as acute hepatitis
- cancer (except basal-cell carcinoma, a slow-growing type of skin cancer)
- or severe impairment of the heart function
There is a lack of relevant experience with Daxas under these conditions. You should talk to your doctor, if you are diagnosed with any of these diseases.

Experience is also limited in patients with a previous diagnosis of tuberculosis, viral hepatitis, herpes viral infection or herpes zoster. Please talk to your doctor if you have one of these diseases.

Symptoms you should be aware of
You may experience diarrhoea, nausea, abdominal pain or headache during the first weeks of treatment with Daxas. Talk to your doctor if these side effects do not resolve within the first weeks of treatment.

Daxas is not recommended in patients with a history of depression associated with suicidal thinking or behaviour. You may also experience sleeplessness, anxiety, nervousness, or depressive mood. Before starting treatment with Daxas, inform your doctor if you are suffering from any symptoms of this kind and of any additional medicines you may take since some of those could increase the probability of these side effects. You or your caregiver should also immediately inform your doctor of any changes in behaviour or mood and of any suicidal thoughts you may have.

Children and adolescents
Do not give this medicine to children and adolescents under 18 years of age.

Other medicines and Daxas
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, especially the following:
- a medicine containing theophylline (a medicine to treat respiratory diseases), or
- a medicine used for treatment of immunological diseases, such as methotrexate, azathioprine, infliximab, etanercept, or oral corticosteroids to be taken long-term.
- a medicine containing fluvoxamine (a medicine to treat anxiety disorders and depression), enoxacin (a medicine to treat bacterial infections) or cimetidine (a medicine to treat stomach ulcers or heartburn).

The effect of Daxas may be reduced if taken together with rifampicin (an antibiotic medicine) or with phenobarbital, carbamazepine or phenytoin (medicines usually prescribed for the treatment of epilepsy). Ask your doctor for advice.

Daxas may be taken with other medicines used in the treatment of COPD such as inhaled or oral corticosteroids or bronchodilators. Do not stop taking these medicines or reduce their dose unless advised by your doctor.

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.
You should not become pregnant during treatment with this medicine and should use an effective method of contraception during therapy, because Daxas may be harmful for the unborn baby.

Driving and using machines
Daxas has no influence on the ability to drive and use machines.

Daxas contains lactose
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

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

• For the first 28 days - the recommended starting dose is one 250 micrograms tablet once daily.
• The starting dose is a low dose used to help your body get used to the medicine before you start taking the full dose. At this low dose you will not get the full effect from the medicine – therefore it is important that you move on to the full dose (called a ‘maintenance dose’) after 28 days.
• After 28 days - the recommended maintenance dose is one 500 micrograms tablet once daily.

Swallow the tablet with some water. You may take this medicine with or without food. Take the tablet at the same time every day.

You may need to take Daxas for several weeks to achieve its beneficial effect.

If you take more Daxas than you should
If you have taken more tablets than you should, you may experience the following symptoms:
headache, nausea, diarrhoea, dizziness, throbbing of your heart, light-headedness, clamminess and low blood pressure. Tell your doctor or pharmacist straight away. If possible take your medicine and this leaflet with you.

If you forget to take Daxas
If you forget to take a tablet at the usual time, take the tablet as soon as you remember on the same day. If on one day you have forgotten to take a tablet of Daxas, just carry on the next day with the next tablet as usual. Continue taking your medicine at the usual times. Do not take a double dose to make up for a forgotten dose.

If you stop taking Daxas
It is important to continue taking Daxas for as long as prescribed by your doctor, even when you have no symptoms, in order to maintain control of your lung function.

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.

You may experience diarrhoea, nausea, stomach ache or headache during the first weeks of treatment with Daxas. Talk to your doctor if these side effects do not resolve within the first weeks of treatment.

Some side effects could be serious. In clinical studies and post-marketing experience, rare instances of suicidal thinking and behaviour (including suicide) were reported. Please notify your doctor immediately of any suicidal thoughts you may have. You may also experience sleeplessness (common), anxiety (uncommon), nervousness (rare), panic attack (rare) or depressive mood (rare).

In uncommon cases allergic reactions may occur. Allergic reactions may affect the skin and in rare cases cause swelling of the eyelids, face, lips and tongue, possibly leading to difficulties in breathing and/or a drop in blood pressure and accelerated heartbeat. In case of an allergic reaction, stop taking Daxas and contact your doctor immediately, or go immediately to the emergency department in the nearest hospital. Take all your medicines and this leaflet with you and provide full information of your current medications.

Other side effects include the following:

Common side effects (may affect up to 1 in 10 people)
- diarrhoea, nausea, stomach ache
- weight decrease, decreased appetite
- headache

Uncommon side effects (may affect up to 1 in 100 people)
- trembling, sensation of spinning head (vertigo), dizziness
- sensation of rapid or irregular heartbeat (palpitations)
- gastritis, vomiting
- reflux of stomach acid to the gullet (acid regurgitations), indigestion
- rash
- muscle pain, muscle weakness or cramps
- back pain
- feeling of weakness or tiredness, feeling unwell.

Rare side effects (may affect up to 1 in 1,000 people)
- male breast enlargement
- decreased sense of taste
- respiratory tract infections (excluding pneumonia)
- bloody stools, constipation
- elevation of liver or muscle enzymes (seen in blood tests)
- wheals (urticaria).

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 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 blister after EXP. The expiry date refers to the last day of that month.

This medicine 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 Daxas contains
The active substance is roflumilast.

Each film-coated tablet (tablet) contains 500 micrograms roflumilast.
- The other ingredients are:
- Core: lactose monohydrate (see section 2 under “Daxas contains lactose”), maize starch, povidone, magnesium stearate,
- Coating: hypromellose, macrogol (4000), titanium dioxide (E171), and iron oxide yellow (E172).

What Daxas looks like and contents of the pack
Daxas 500 micrograms film-coated tablets are yellow, D-shaped film-coated tablets, embossed with 'D' on one side.
Each pack contains 10, 14, 28, 30, 84 , 90 or 98 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
AstraZeneca AB
SE-151 85 Södertälje
Sweden

Manufacturer
Corden Pharma GmbH
Otto-Hahn-Strasse 1
68723 Plankstadt
Germany

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

België/Belgique/Belgien
AstraZeneca S.A./N.V.
Tel: +32 2 370 48 11

Lietuva
UAB AstraZeneca Lietuva
Tel: +370 5 2660550

България
АстраЗенека България ЕООД
Тел.: +359 24455000

Luxembourg/Luxemburg
AstraZeneca S.A./N.V.
Tél/Tel: +32 2 370 48 11

Česká republika
AstraZeneca Czech Republic s.r.o.
Tel: +420 222 807 111

Magyarország
AstraZeneca Kft.
Tel.: +36 1 883 6500

Danmark
AstraZeneca A/S
Tlf: +45 43 66 64 62

Malta
Associated Drug Co. Ltd
Tel: +356 2277 8000

Deutschland
AstraZeneca GmbH
Tel: +49 40 809034100

Nederland
AstraZeneca BV
Tel: +31 85 808 9900

Eesti
AstraZeneca
Tel: +372 6549 600

Norge
AstraZeneca AS
Tlf: +47 21 00 64 00

Ελλάδα
AstraZeneca A.E.
Τηλ: +30 210 6871500

Österreich
AstraZeneca Österreich GmbH
Tel: +43 1 711 31 0

España
Polska

AstraZeneca Farmacéutica Spain, S.A.
Tel: +34 91 301 91 00

AstraZeneca Pharma Poland Sp. z o.o.
Tel.: +48 22 245 73 00

France
AstraZeneca
Tél: +33 1 41 29 40 00

Portugal
AstraZeneca Produtos Farmacêuticos, Lda.
Tel: +351 21 434 61 00

Hrvatska
AstraZeneca d.o.o.
Tel: +385 1 4628 000

România
AstraZeneca Pharma SRL
Tel: +40 21 317 60 41

Ireland
AstraZeneca Pharmaceuticals (Ireland) DAC
Tel: +353 1609 7100

Slovenija
AstraZeneca UK Limited
Tel: +386 1 51 35 600

Ísland
Vistor
Sími: +354 535 7000

Slovenská republika
AstraZeneca AB, o.z.
Tel: +421 2 5737 7777

Italia
Simesa S.p.A.
Tel: +39 02 00704500

Suomi/Finland
AstraZeneca Oy
Puh/Tel: +358 10 23 010

Κύπρος
Αλέκτωρ Φαρµακευτική Λτδ
Τηλ: +357 22490305

Sverige
AstraZeneca AB
Tel: +46 8 553 26 000

Latvija
SIA AstraZeneca Latvija
Tel: +371 67377100

This leaflet was last approved in

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