B. PACKAGE LEAFLET

Package leaflet: Information for the patient

Ofev 100 mg soft capsules nintedanib

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• – Keep this leaflet. You may need to read it again.

• – If you have any further questions, ask your doctor or pharmacist.

• – This medicine has been prescribed for you only. Do not pass it on to others. It may harm them,

even if their signs of illness are the same as yours.

- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

• 1. What Ofev is and what it is used for

• 2. What you need to know before you take Ofev

• 3. How to take Ofev

• 4. Possible side effects

• 5. How to store Ofev

• 6. Contents of the pack and other information

1. What Ofev is and what it is used for

Ofev contains the active substance nintedanib, a medicine belonging to the class of so-called tyrosine kinase inhibitors, and it is used for the treatment of idiopathic pulmonary fibrosis (IPF), other chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype and systemic sclerosis associated interstitial lung disease (SSc-ILD) in adults.

Idiopathic pulmonary fibrosis (IPF)

IPF is a condition in which the tissue in your lungs becomes thickened, stiff and scarred over time. As a result, scarring reduces the ability to transfer oxygen from the lungs into the bloodstream and it becomes difficult to breathe deeply. Ofev helps to reduce further scarring and stiffening of the lungs.

Other chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype

Besides IPF, there are other conditions in which the tissue in your lungs becomes thickened, stiff, and scarred over time (lung fibrosis) and keeps worsening (progressive phenotype). Examples of these conditions are hypersensitivity pneumonitis, autoimmune ILDs (e.g. rheumatoid arthritis associated ILD), idiopathic nonspecific interstitial pneumonia, unclassifiable idiopathic interstitial pneumonia, and other ILDs. Ofev helps to reduce further scarring and stiffening of the lungs.

Systemic sclerosis associated interstitial lung disease (SSc-ILD)

Systemic sclerosis (SSc), also known as scleroderma, is a rare chronic autoimmune disease that affects connective tissue in many parts of the body. SSc causes fibrosis (scarring and stiffening) of the skin and other internal organs such as the lungs. When the lungs are affected by fibrosis, it is called interstitial lung disease (ILD), and so the condition is called SSc-ILD. Fibrosis in the lungs reduces the ability to transfer oxygen into the bloodstream, and breathing capacity is reduced. Ofev helps to reduce further scarring and stiffening of the lungs.

2. What you need to know before you take Ofev

Do not take Ofev

– if you are pregnant,

• – if you are allergic to nintedanib, peanut or soya, or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor or pharmacist before taking Ofev,

• – if you have or have had liver problems,

• – if you have or have had problems with your kidneys, or if an increased amount of protein has been detected in your urine,

• – if you have or have had bleeding problems,

• – if you take blood-thinning medicines (such as warfarin, phenprocoumon or heparin) to prevent blood clotting,

• – if you take pirfenidone as this may increase the risk of having diarrhoea, nausea, vomiting and liver problems,

• – if you have or have had problems with your heart (for example a heart attack),

• – if you have recently had surgery. Nintedanib may affect the way your wounds heal. Therefore, your treatment with Ofev will usually be stopped for a while if you are having a surgery. Your doctor will decide when to resume your treatment with this medicine.

• – if you have high blood pressure,

• – if you have abnormally high blood pressure in the blood vessels of the lungs (pulmonary hypertension),

• – if you have or have had an aneurysm (enlargement and weakening of a blood vessel wall) or a tear in a blood vessel wall.

Based on this information your doctor may do some blood tests, for example to check your liver function. Your doctor will discuss the results of these tests with you and decide whether you may receive Ofev.

Inform your doctor immediately while taking this medicine,

• – if you get diarrhoea. Treating diarrhoea early is important (see section 4);

• – if you vomit or feel sick (nausea);

• – if you have unexplained symptoms such as yellowing of your skin or the white part of your eyes (jaundice), dark or brown (tea coloured) urine, pain on the upper right side of your stomach area (abdomen), bleeding or bruising more easily than normal, or feeling tired. This could be symptoms of serious liver problems;

• – if you have severe pain in your stomach, fever, chills, sickness, vomiting, or abdominal rigidity or bloating, as these could be symptoms of a hole in the wall of your gut (‘gastrointestinal perforation’). Also, tell your doctor if you had peptic ulcers or diverticular disease in the past, or are concomitantly treated with anti-inflammatory drugs (NSAIDs) (used to treat pain relief and swelling) or steroids (used for inflammation and allergies), as this may increase this risk;

• – if you have a combination of severe pain or cramping in your stomach, red blood in your stool or diarrhea as these could be symptoms of a bowel inflammation from inadequate blood supply;

• – if you have pain, swelling, reddening, warmth of a limb as this could be symptoms of a blood clot in one of your veins (a type of blood vessel);

• – if you have chest pressure or pain, typically on the left side of the body, pain in the neck, jaw, shoulder or arm, a fast heartbeat, shortness of breath, nausea, vomiting, as this could be symptoms of a heart attack;

• – if you have any major bleeding.

• – if you experience bruising, bleeding, fever, fatigue and confusion. This may be a sign of damage to blood vessels known as thrombotic microangiopat­hy (TMA).

Children and adolescents

Ofev should not be taken by children and adolescents under 18 years of age.

Other medicines and Ofev

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including herbal medicines and medicines obtained without a prescription.

Ofev can interact with certain other medicines. The following medicines are examples that may increase the levels of nintedanib in your blood, and hence may increase the risk for side effects (see section 4):

• – a medicine used to treat fungal infections (ketoconazole)

• – a medicine used to treat bacterial infections (erythromycin)

• – a medicine that affects your immune system (cyclosporine)

The following medicines are examples that may lower the levels of nintedanib in your blood and thus may reduce the effectiveness of Ofev:

• – an antibiotic used to treat tuberculosis (rifampicin)

• – medicines to treat seizures (carbamazepine, phenytoin)

• – a herbal medicine to treat depression (St. John’s Wort)

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

Do not take this medicine during pregnancy, as it can harm your unborn baby and cause birth defects.

You must have a pregnancy test done to ensure you are not pregnant before starting treatment with Ofev. Please talk to your doctor.

Contraception

• – Women who can become pregnant must use a highly effective method of birth control to prevent pregnancy when they start taking Ofev, while they are taking Ofev and for at least 3 months after stopping treatment.

• – You should discuss the most appropriate methods of contraception for you with your doctor.

• – Vomiting and/or diarrhoea or other gastrointestinal conditions can affect the absorption of oral hormonal contraceptives, such as birth control pills, and may reduce their effectiveness­.Therefore, if experiencing these, talk to your doctor to discuss an alternative more appropriate method of contraception.

• – Tell your doctor or pharmacist immediately if you become pregnant or think you may be pregnant during treatment with Ofev.

Breast-feeding

Do not breast-feed during the treatment with Ofev since there may be a risk of harm to the breast-fed child.

Driving and using machines

Ofev may have minor influence on your ability to drive and use machines. You should not drive or use machines if you feel sick.

Ofev contains soya lecithin

If you are allergic to soya or peanut, do not take this medicine (see section 2).

3. How to take Ofev

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

The recommended dose is one capsule of 100 mg twice daily (a total of 200 mg per day). Take the capsules twice daily approximately 12 hours apart at about the same time every day, for example one capsule in the morning and one capsule in the evening. This ensures that a steady amount of nintedanib is maintained in your blood stream. Swallow the whole capsules with water and do not chew the capsules. It is recommended that you take the capsules with food, i.e. during or immediately before or after a meal. Do not open or crush the capsule (see section 5).

Do not take more than the recommended dose of two Ofev 100 mg capsules per day.

If you do not tolerate the recommended dose of two Ofev 100 mg capsules per day (see possible side effects in section 4) your doctor may advise you to stop taking this medicine. Do not reduce the dose or stop the treatment by yourself without consulting your doctor first.

If you take more Ofev than you should

Contact your doctor or pharmacist immediately.

If you forget to take Ofev

Do not take two capsules together if you have forgotten to take your earlier dose. You should take your next 100 mg dose of Ofev as planned at the next scheduled time recommended by your doctor or pharmacist.

If you stop taking Ofev

Do not stop taking Ofev without consulting your doctor first. It is important to take this medicine every day, as long as your doctor prescribes it for you.

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

4. Possible side effects

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

You need to pay special attention if you get the following side effects during treatment with Ofev:

Diarrhoea (very common, may affect more than 1 in 10 people):

Diarrhoea may lead to dehydration: a loss of fluid and important salts (electrolytes, such as sodium or potassium) from your body. At the first signs of diarrhoea drink plenty of fluids and contact your doctor immediately. Start appropriate anti-diarrhoeal treatment, e.g. with loperamide, as soon as possible.

The following other side effects were observed during treatment with this medicine.

Talk to your doctor if you get any side effects.

Idiopathic pulmonary fibrosis (IPF)

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

• – Feeling sick (nausea)

• – Pain in the lower body (abdomen)

• – Abnormal liver test results

Common side effects (may affect up to 1 in 10 people)

• – Vomiting

• – Loss of appetite

• – Weight loss

• – Bleeding

• – Rash

• – Headache

Uncommon side effects (may affect up to 1 in 100 people)

• – Pancreatitis

• – Inflammation of the large bowel

• – Serious liver problems

• – Low platelet count (thrombocytopenia)

• – High blood pressure (hypertension)

• – Jaundice, that is a yellow colour to the skin and whites of the eyes due to high levels of bilirubin

• – Itching

• – Heart attack

• – Hair loss (alopecia)

• – Increased amount of protein in your urine (proteinuria)

Not known (cannot be estimated from the available data)

• – Renal failure

• – An enlargement and weakening of a blood vessel wall or a tear in a blood vessel wall (aneurysms and artery dissections)

Other chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype

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

• – Feeling sick (nausea)

• – Vomiting

• – Loss of appetite

• – Pain in the lower body (abdomen)

• – Abnormal liver test results

Common side effects (may affect up to 1 in 10 people)

• – Weight loss

• – High blood pressure (hypertension)

• – Bleeding

• – Serious liver problems

• – Rash

• – Headache

Uncommon side effects (may affect up to 1 in 100 people)

• – Pancreatitis

• – Inflammation ofthe large bowel

• – Low platelet count (thrombocytopenia)

• – Jaundice, that is a yellow colour to the skin and whites of the eyes due to high levels of bilirubin

• – Itching

• – Heart attack

• – Hair loss (alopecia)

• – Increased amount of protein in your urine (proteinuria)

Not known (cannot be estimated from the available data)

• – Renal failure

• – An enlargement and weakening of a blood vessel wall or a tear in a blood vessel wall (aneurysms and artery dissections)

Systemic sclerosis associated interstitial lung disease (SSc-ILD)

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

• – Feeling sick (nausea)

• – Vomiting

• – Pain in the lower body (abdomen)

• – Abnormal liver test results

Common side effects (may affect up to 1 in 10 people)

• – Bleeding

• – High blood pressure (hypertension)

• – Loss of appetite

• – Weight loss

• – Headache

Uncommon side effects (may affect up to 1 in 100 people)

• – Inflammation of the large bowel

• – Serious liver problems

• – Renal failure

• – Low platelet count (thrombocytopenia)

• – Rash

• – Itching

Not known (cannot be estimated from the available data)

• – Heart attack

• – Pancreatitis

• – Jaundice, that is a yellow colour to the skin and whites of the eyes due to high levels of bilirubin

• – An enlargement and weakening of a blood vessel wall or a tear in a blood vessel wall (aneurysms and artery dissections)

• – Hair loss (alopecia)

• – Increased amount of protein in your urine (proteinuria)

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. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Ofev

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

Do not store Ofev above 25°C.

Store in the original package in order to protect from moisture.

Do not use this medicine if you notice that the blister containing the capsules is opened or a capsule is broken.

If you are in contact with the content of the capsule, wash off your hands immediately with plenty of water (see section 3).

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.

6. Contents of the pack and other information

What Ofev contains

• – The active substance is nintedanib. Each capsule contains 100 mg nintedanib (as esilate).

• – The other ingredients are:

Capsule fill: Triglycerides, medium-chain, hard fat, soya lecithin (E322) (see section 2)

Capsule shell: Gelatin, glycerol (85%), titanium dioxide (E171), iron oxide red (E172), iron

oxide yellow (E172)

Printing ink: Shellac glaze, iron oxide black (E172), propylene glycol (E1520)

What Ofev looks like and contents of the pack

Ofev 100 mg capsules are peach-coloured, opaque, oblong soft-gelatin capsules imprinted on one side in black with the Boehringer Ingelheim company symbol and the figure “100”.

Two pack-sizes of Ofev 100 mg capsules are available:

• – 30 × 1 soft capsules in aluminium/aluminium perforated unit dose blisters

• – 60 × 1 soft capsules in aluminium/aluminium perforated unit dose blisters

Not all pack-sizes may be marketed.

Marketing Authorisation Holder

Boehringer Ingelheim International GmbH

Binger Strasse 173

55216 Ingelheim am Rhein

Germany

Manufacturer

Boehringer Ingelheim Pharma GmbH & Co. KG

Binger Strasse 173

55216 Ingelheim am Rhein

Germany

Boehringer Ingelheim France

100–104 Avenue de France

75013 Paris

France

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

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site:.

Package leaflet: Information for the patient

Ofev 150 mg soft capsules nintedanib

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• – Keep this leaflet. You may need to read it again.

• – If you have any further questions, ask your doctor or pharmacist.

• – This medicine has been prescribed for you only. Do not pass it on to others. It may harm them,

even if their signs of illness are the same as yours.

- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

• 1. What Ofev is and what it is used for

• 2. What you need to know before you take Ofev

• 3. How to take Ofev

• 4. Possible side effects

• 5. How to store Ofev

• 6. Contents of the pack and other information

1. What Ofev is and what it is used for

Ofev contains the active substance nintedanib, a medicine belonging to the class of so-called tyrosine kinase inhibitors, and it is used for the treatment of idiopathic pulmonary fibrosis (IPF), other chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype and systemic sclerosis associated interstitial lung disease (SSc-ILD) in adults.

Idiopathic pulmonary fibrosis (IPF)

IPF is a condition in which the tissue in your lungs becomes thickened, stiff and scarred over time. As a result, scarring reduces the ability to transfer oxygen from the lungs into the bloodstream and it becomes difficult to breathe deeply. Ofev helps to reduce further scarring and stiffening of the lungs.

Other chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype

Besides IPF, there are other conditions in which the tissue in your lungs becomes thickened, stiff, and scarred over time (lung fibrosis) and keeps worsening (progressive phenotype). Examples of these conditions are hypersensitivity pneumonitis, autoimmune ILDs (e.g. rheumatoid arthritis associated ILD), idiopathic nonspecific interstitial pneumonia, unclassifiable idiopathic interstitial pneumonia, and other ILDs. Ofev helps to reduce further scarring and stiffening of the lungs.

Systemic sclerosis associated interstitial lung disease (SSc-ILD)

Systemic sclerosis (SSc), also known as scleroderma, is a rare chronic autoimmune disease that affects connective tissue in many parts of the body. SSc causes fibrosis (scarring and stiffening) of the skin and other internal organs such as the lungs. When the lungs are affected by fibrosis, it is called interstitial lung disease (ILD), and so the condition is called SSc-ILD. Fibrosis in the lungs reduces the ability to transfer oxygen into the bloodstream, and breathing capacity is reduced. Ofev helps to reduce further scarring and stiffening of the lungs.

2. What you need to know before you take Ofev

Do not take Ofev

• – if you are pregnant,

• – if you are allergic to nintedanib, peanut or soya, or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor or pharmacist before taking Ofev,

• – if you have or have had liver problems,

• – if you have or have had problems with your kidneys, or if an increased amount of protein has been detected in your urine,

• – if you have or have had bleeding problems,

• – if you take blood-thinning medicines (such as warfarin, phenprocoumon or heparin) to prevent blood clotting,

• – if you take pirfenidone as this may increase the risk of having diarrhoea, nausea, vomiting and liver problems,

• – if you have or have had problems with your heart (for example a heart attack),

• – if you have recently had surgery. Nintedanib may affect the way your wounds heal. Therefore, your treatment with Ofev will usually be stopped for a while if you are having a surgery. Your doctor will decide when to resume your treatment with this medicine.

• – if you have high blood pressure,

• – if you have abnormally high blood pressure in the blood vessels of the lungs (pulmonary hypertension),

• – if you have or have had an aneurysm (enlargement and weakening of a blood vessel wall) or a tear in a blood vessel wall.

Based on this information your doctor may do some blood tests, for example to check your liver function. Your doctor will discuss the results of these tests with you and decide whether you may receive Ofev.

Inform your doctor immediately while taking this medicine,

• – if you get diarrhoea. Treating diarrhoea early is important (see section 4);

• – if you vomit or feel sick (nausea);

• – if you have unexplained symptoms such as yellowing of your skin or the white part of your eyes (jaundice), dark or brown (tea coloured) urine, pain on the upper right side of your stomach area (abdomen), bleeding or bruising more easily than normal, or feeling tired. This could be symptoms of serious liver problems;

• – if you have severe pain in your stomach, fever, chills, sickness, vomiting, or abdominal rigidity or bloating, as these could be symptoms of a hole in the wall of your gut (‘gastrointestinal perforation’). Also, tell your doctor if you had peptic ulcers or diverticular disease in the past, or are concomitantly treated with anti-inflammatory drugs (NSAIDs) (used to treat pain relief and swelling) or steroids (used for inflammation and allergies), as this may increase this risk;

• – if you have a combination of severe pain or cramping in your stomach, red blood in your stool or diarrhea as these could be symptoms of a bowel inflammation from inadequate blood supply;

• – if you have pain, swelling, reddening, warmth of a limb as this could be symptoms of a blood clot in one of your veins (a type of blood vessel);

• – if you have chest pressure or pain, typically on the left side of the body, pain in the neck, jaw, shoulder or arm, a fast heartbeat, shortness of breath, nausea, vomiting, as this could be symptoms of a heart attack;

• – if you have any major bleeding.

• – if you experience bruising, bleeding, fever, fatigue and confusion. This may be a sign of damage to blood vessels known as thrombotic microangiopat­hy (TMA).

Children and adolescents

Ofev should not be taken by children and adolescents under 18 years of age.

Other medicines and Ofev

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including herbal medicines and medicines obtained without a prescription.

Ofev can interact with certain other medicines. The following medicines are examples that may increase the levels of nintedanib in your blood, and hence may increase the risk for side effects (see section 4):

• – a medicine used to treat fungal infections (ketoconazole)

• – a medicine used to treat bacterial infections (erythromycin)

• – a medicine that affects your immune system (cyclosporine)

The following medicines are examples that may lower the levels of nintedanib in your blood and thus may reduce the effectiveness of Ofev:

• – an antibiotic used to treat tuberculosis (rifampicin)

• – medicines to treat seizures (carbamazepine, phenytoin)

• – a herbal medicine to treat depression (St. John’s Wort)

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

Do not take this medicine during pregnancy, as it can harm your unborn baby and cause birth defects.

You must have a pregnancy test done to ensure you are not pregnant before starting treatment with Ofev. Please talk to your doctor.

Contraception

• – Women who can become pregnant must use a highly effective method of birth control to prevent pregnancy when they start taking Ofev while they are taking Ofev and for at least 3 months after stopping treatment.

• – You should discuss the most appropriate methods of contraception for you with your doctor.

• – Vomiting and/or diarrhoea or other gastrointestinal conditions can affect the absorption of oral hormonal contraceptives, such as birth control pills, and may reduce their effectiveness. Therefore, if experiencing these, talk to your doctor to discuss an alternative more appropriate method of contraception.

• – Tell your doctor or pharmacist immediately if you become pregnant or think you may be pregnant during treatment with Ofev.

Breast-feeding

Do not breast-feed during the treatment with Ofev since there may be a risk of harm to the breast-fed child.

Driving and using machines

Ofev may have minor influence on your ability to drive and use machines. You should not drive or use machines if you feel sick.

Ofev contains soya lecithin

If you are allergic to soya or peanut, do not take this medicine (see section 2).

3. How to take Ofev

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

The recommended dose is one capsule of 150 mg twice daily (a total of 300 mg per day). Take the capsules twice daily approximately 12 hours apart at about the same time every day, for example one capsule in the morning and one capsule in the evening. This ensures that a steady amount of nintedanib is maintained in your blood stream. Swallow the whole capsules with water and do not chew the capsules. It is recommended that you take the capsules with food, i.e. during or immediately before or after a meal. Do not open or crush the capsule (see section 5).

Do not take more than the recommended dose of two Ofev 150 mg capsules per day.

If you do not tolerate the recommended dose of two Ofev 150 mg capsules per day (see possible side effects in section 4) your doctor may reduce the daily dose of Ofev. Do not reduce the dose or stop the treatment by yourself without consulting your doctor first.

Your doctor may reduce your recommended dose to two times 100 mg per day (a total of 200 mg per day). In this case your doctor will prescribe Ofev 100 mg capsules for your treatment. Do not take more than the recommended dose of two Ofev 100 mg capsules per day if your daily dose was reduced to 200 mg per day.

If you take more Ofev than you should

Contact your doctor or pharmacist immediately.

If you forget to take Ofev

Do not take two capsules together if you have forgotten to take your earlier dose.You should take your next 150 mg dose of Ofev as planned at the next scheduled time recommended by your doctor or pharmacist.

If you stop taking Ofev

Do not stop taking Ofev without consulting your doctor first. It is important to take this medicine every day, as long as your doctor prescribes it for you.

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

4. Possible side effects

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

You need to pay special attention if you get the following side effects during treatment with Ofev:

Diarrhoea (very common, may affect more than 1 in 10 people):

Diarrhoea may lead to dehydration: a loss of fluid and important salts (electrolytes, such as sodium or potassium) from your body. At the first signs of diarrhoea drink plenty of fluids and contact your doctor immediately. Start appropriate anti-diarrhoeal treatment, e.g. with loperamide, as soon as possible.

The following other side effects were observed during treatment with this medicine.

Talk to your doctor if you get any side effects.

Idiopathic pulmonary fibrosis (IPF)

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

• – Feeling sick (nausea)

• – Pain in the lower body (abdomen)

• – Abnormal liver test results.

Common side effects (may affect up to 1 in 10 people)

• – Vomiting

• – Loss of appetite

• – Weight loss

• – Bleeding

• – Rash

• – Headache

Uncommon side effects (may affect up to 1 in 100 people)

• – Pancreatitis

• – Inflammation of the large bowel

• – Serious liver problems

• – Low platelet count (thrombocytopenia)

• – High blood pressure (hypertension)

• – Jaundice, that is a yellow colour to the skin and whites of the eyes due to high levels of bilirubin

• – Itching

• – Heart attack

• – Hair loss (alopecia)

• – Increased amount of protein in your urine (proteinuria)

Not known (cannot be estimated from the available data)

• – Renal failure

• – An enlargement and weakening of a blood vessel wall or a tear in a blood vessel wall (aneurysms and artery dissections)

Other chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype

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

• – Feeling sick (nausea)

• – Vomiting

• – Loss of appetite

• – Pain in the lower body (abdomen)

• – Abnormal liver test results

Common side effects (may affect up to 1 in 10 people)

• – Weight loss

• – High blood pressure (hypertension)

• – Bleeding

• – Serious liver problems

• – Rash

• – Headache

Uncommon side effects (may affect up to 1 in 100 people)

• – Pancreatitis

• – Inflammation ofthe large bowel

• – Low platelet count (thrombocytopenia)

• – Jaundice, that is a yellow colour to the skin and whites ofthe eyes due to high levels of bilirubin

• – Itching

• – Heart attack

• – Hair loss (alopecia)

• – Increased amount of protein in your urine (proteinuria)

Not known (cannot be estimated from the available data)

• – Renal failure

• – An enlargement and weakening of a blood vessel wall or a tear in a blood vessel wall (aneurysms and artery dissections)

Systemic sclerosis associated interstitial lung disease (SSc-ILD)

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

• – Feeling sick (nausea)

• – Vomiting

• – Pain in the lower body (abdomen)

• – Abnormal liver test results

Common side effects (may affect up to 1 in 10 people)

• – Bleeding

• – High blood pressure (hypertension)

• – Loss of appetite

• – Weight loss

• – Headache

Uncommon side effects (may affect up to 1 in 100 people)

• – Inflammation of the large bowel

• – Serious liver problems

• – Renal failure

• – Low platelet count (thrombocytopenia)

• – Rash

• – Itching

Not known (cannot be estimated from the available data)

• – Heart attack

• – Pancreatitis

• – Jaundice, that is a yellow colour to the skin and whites of the eyes due to high levels of bilirubin

• – An enlargement and weakening of a blood vessel wall or a tear in a blood vessel wall (aneurysms and artery dissections)

• – Hair loss (alopecia)

• – Increased amount of protein in your urine (proteinuria)

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. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Ofev

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

Do not store Ofev above 25°C.

Store in the original package in order to protect from moisture.

Do not use this medicine if you notice that the blister containing the capsules is opened or a capsule is broken.

If you are in contact with the content of the capsule, wash off your hands immediately with plenty of water (see section 3).

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.

6. Contents of the pack and other information

What Ofev contains

• – The active substance is nintedanib. Each capsule contains 150 mg nintedanib (as esilate).

• – The other ingredients are:

Capsule fill: Triglycerides, medium-chain, hard fat, soya lecithin (E322) (see section 2)

Capsule shell: Gelatin, glycerol (85%), titanium dioxide (E171), iron oxide red (E172), iron oxide yellow (E172)

Printing ink: Shellac glaze, iron oxide black (E172), propylene glycol (E1520)

What Ofev looks like and contents of the pack

Ofev 100 mg capsules are peach-coloured, opaque, oblong soft-gelatin capsules imprinted on one side in black with the Boehringer Ingelheim company symbol and the figure “100”.

Two pack-sizes of Ofev 100 mg capsules are available:

• – 30 × 1 soft capsules in aluminium/aluminium perforated unit dose blisters

• – 60 × 1 soft capsules in aluminium/aluminium perforated unit dose blisters

Not all pack-sizes may be marketed.

Marketing Authorisation Holder

Boehringer Ingelheim International GmbH

Binger Strasse 173

55216 Ingelheim am Rhein

Germany

Manufacturer

Boehringer Ingelheim Pharma GmbH & Co. KG

Binger Strasse 173

55216 Ingelheim am Rhein

Germany

Boehringer Ingelheim France

100–104 Avenue de France

75013 Paris

France

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

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site:.

Package leaflet: Information for the patient

Ofev 150 mg soft capsules nintedanib

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• – Keep this leaflet. You may need to read it again.

• – If you have any further questions, ask your doctor or pharmacist.

• – This medicine has been prescribed for you only. Do not pass it on to others. It may harm them,

even if their signs of illness are the same as yours.

– If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

• 1. What Ofev is and what it is used for

• 2. What you need to know before you take Ofev

• 3. How to take Ofev

• 4. Possible side effects

• 5. How to store Ofev

• 6. Contents of the pack and other information

1. What Ofev is and what it is used for

Ofev contains the active substance nintedanib, a medicine belonging to the class of so-called tyrosine kinase inhibitors, and it is used for the treatment of idiopathic pulmonary fibrosis (IPF), other chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype and systemic sclerosis associated interstitial lung disease (SSc-ILD) in adults.

Idiopathic pulmonary fibrosis (IPF)

IPF is a condition in which the tissue in your lungs becomes thickened, stiff and scarred over time. As a result, scarring reduces the ability to transfer oxygen from the lungs into the bloodstream and it becomes difficult to breathe deeply. Ofev helps to reduce further scarring and stiffening of the lungs.

Other chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype

Besides IPF, there are other conditions in which the tissue in your lungs becomes thickened, stiff, and scarred over time (lung fibrosis) and keeps worsening (progressive phenotype). Examples of these conditions are hypersensitivity pneumonitis, autoimmune ILDs (e.g. rheumatoid arthritis associated ILD), idiopathic nonspecific interstitial pneumonia, unclassifiable idiopathic interstitial pneumonia, and other ILDs. Ofev helps to reduce further scarring and stiffening of the lungs.

Systemic sclerosis associated interstitial lung disease (SSc-ILD)

Systemic sclerosis (SSc), also known as scleroderma, is a rare chronic autoimmune disease that affects connective tissue in many parts of the body. SSc causes fibrosis (scarring and stiffening) of the skin and other internal organs such as the lungs. When the lungs are affected by fibrosis, it is called interstitial lung disease (ILD), and so the condition is called SSc-ILD. Fibrosis in the lungs reduces the ability to transfer oxygen into the bloodstream, and breathing capacity is reduced. Ofev helps to reduce further scarring and stiffening of the lungs.

2. What you need to know before you take Ofev

Do not take Ofev

• – if you are pregnant,

• – if you are allergic to nintedanib, peanut or soya, or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor or pharmacist before taking Ofev,

• – if you have or have had liver problems,

• – if you have or have had problems with your kidneys, or if an increased amount of protein has been detected in your urine,

• – if you have or have had bleeding problems,

• – if you take blood-thinning medicines (such as warfarin, phenprocoumon or heparin) to prevent blood clotting,

• – if you take pirfenidone as this may increase the risk of having diarrhoea, nausea, vomiting and liver problems,

• – if you have or have had problems with your heart (for example a heart attack),

• – if you have recently had surgery. Nintedanib may affect the way your wounds heal. Therefore, your treatment with Ofev will usually be stopped for a while if you are having a surgery. Your doctor will decide when to resume your treatment with this medicine.

• – if you have high blood pressure,

• – if you have abnormally high blood pressure in the blood vessels of the lungs (pulmonary hypertension),

• – if you have or have had an aneurysm (enlargement and weakening of a blood vessel wall) or a tear in a blood vessel wall.

Based on this information your doctor may do some blood tests, for example to check your liver function. Your doctor will discuss the results of these tests with you and decide whether you may receive Ofev.

Inform your doctor immediately while taking this medicine,

• – if you get diarrhoea. Treating diarrhoea early is important (see section 4);

• – if you vomit or feel sick (nausea);

• – if you have unexplained symptoms such as yellowing of your skin or the white part of your eyes (jaundice), dark or brown (tea coloured) urine, pain on the upper right side of your stomach area (abdomen), bleeding or bruising more easily than normal, or feeling tired. This could be symptoms of serious liver problems;

• – if you have severe pain in your stomach, fever, chills, sickness, vomiting, or abdominal rigidity or bloating, as these could be symptoms of a hole in the wall of your gut (‘gastrointestinal perforation’). Also, tell your doctor if you had peptic ulcers or diverticular disease in the past, or are concomitantly treated with anti-inflammatory drugs (NSAIDs) (used to treat pain relief and swelling) or steroids (used for inflammation and allergies), as this may increase this risk;

• – if you have a combination of severe pain or cramping in your stomach, red blood in your stool or diarrhea as these could be symptoms of a bowel inflammation from inadequate blood supply;

• – if you have pain, swelling, reddening, warmth of a limb as this could be symptoms of a blood clot in one of your veins (a type of blood vessel);

• – if you have chest pressure or pain, typically on the left side of the body, pain in the neck, jaw, shoulder or arm, a fast heartbeat, shortness of breath, nausea, vomiting, as this could be symptoms of a heart attack;

• – if you have any major bleeding.

• – if you experience bruising, bleeding, fever, fatigue and confusion. This may be a sign of damage to blood vessels known as thrombotic microangiopat­hy (TMA).

Children and adolescents

Ofev should not be taken by children and adolescents under 18 years of age.

Other medicines and Ofev

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including herbal medicines and medicines obtained without a prescription.

Ofev can interact with certain other medicines. The following medicines are examples that may increase the levels of nintedanib in your blood, and hence may increase the risk for side effects (see section 4):

• – a medicine used to treat fungal infections (ketoconazole)

• – a medicine used to treat bacterial infections (erythromycin)

• – a medicine that affects your immune system (cyclosporine)

The following medicines are examples that may lower the levels of nintedanib in your blood and thus may reduce the effectiveness of Ofev:

• – an antibiotic used to treat tuberculosis (rifampicin)

• – medicines to treat seizures (carbamazepine, phenytoin)

• – a herbal medicine to treat depression (St. John’s Wort)

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

Do not take this medicine during pregnancy, as it can harm your unborn baby and cause birth defects.

You must have a pregnancy test done to ensure you are not pregnant before starting treatment with Ofev. Please talk to your doctor.

Contraception

• – Women who can become pregnant must use a highly effective method of birth control to prevent pregnancy when they start taking Ofev while they are taking Ofev and for at least 3 months after stopping treatment.

• – You should discuss the most appropriate methods of contraception for you with your doctor.

• – Vomiting and/or diarrhoea or other gastrointestinal conditions can affect the absorption of oral hormonal contraceptives, such as birth control pills, and may reduce their effectiveness. Therefore, if experiencing these, talk to your doctor to discuss an alternative more appropriate method of contraception.

• – Tell your doctor or pharmacist immediately if you become pregnant or think you may be pregnant during treatment with Ofev.

Breast-feeding

Do not breast-feed during the treatment with Ofev since there may be a risk of harm to the breast-fed child.

Driving and using machines

Ofev may have minor influence on your ability to drive and use machines. You should not drive or use machines if you feel sick.

Ofev contains soya lecithin

If you are allergic to soya or peanut, do not take this medicine (see section 2).

3. How to take Ofev

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

The recommended dose is one capsule of 150 mg twice daily (a total of 300 mg per day). Take the capsules twice daily approximately 12 hours apart at about the same time every day, for example one capsule in the morning and one capsule in the evening. This ensures that a steady amount of nintedanib is maintained in your blood stream. Swallow the whole capsules with water and do not chew the capsules. It is recommended that you take the capsules with food, i.e. during or immediately before or after a meal. Do not open or crush the capsule (see section 5).

Do not take more than the recommended dose of two Ofev 150 mg capsules per day.

If you do not tolerate the recommended dose of two Ofev 150 mg capsules per day (see possible side effects in section 4) your doctor may reduce the daily dose of Ofev. Do not reduce the dose or stop the treatment by yourself without consulting your doctor first.

Your doctor may reduce your recommended dose to two times 100 mg per day (a total of 200 mg per day). In this case your doctor will prescribe Ofev 100 mg capsules for your treatment. Do not take more than the recommended dose of two Ofev 100 mg capsules per day if your daily dose was reduced to 200 mg per day.

If you take more Ofev than you should

Contact your doctor or pharmacist immediately.

If you forget to take Ofev

Do not take two capsules together if you have forgotten to take your earlier dose.You should take your next 150 mg dose of Ofev as planned at the next scheduled time recommended by your doctor or pharmacist.

If you stop taking Ofev

Do not stop taking Ofev without consulting your doctor first. It is important to take this medicine every day, as long as your doctor prescribes it for you.

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

4. Possible side effects

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

You need to pay special attention if you get the following side effects during treatment with Ofev:

Diarrhoea (very common, may affect more than 1 in 10 people):

Diarrhoea may lead to dehydration: a loss of fluid and important salts (electrolytes, such as sodium or potassium) from your body. At the first signs of diarrhoea drink plenty of fluids and contact your doctor immediately. Start appropriate anti-diarrhoeal treatment, e.g. with loperamide, as soon as possible.

The following other side effects were observed during treatment with this medicine.

Talk to your doctor if you get any side effects.

Idiopathic pulmonary fibrosis (IPF)

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

• – Feeling sick (nausea)

• – Pain in the lower body (abdomen)

• – Abnormal liver test results.

Common side effects (may affect up to 1 in 10 people)

• – Vomiting

• – Loss of appetite

• – Weight loss

• – Bleeding

• – Rash

• – Headache

Uncommon side effects (may affect up to 1 in 100 people)

• – Pancreatitis

• – Inflammation of the large bowel

• – Serious liver problems

• – Low platelet count (thrombocytopenia)

• – High blood pressure (hypertension)

• – Jaundice, that is a yellow colour to the skin and whites of the eyes due to high levels of bilirubin

• – Itching

• – Heart attack

• – Hair loss (alopecia)

• – Increased amount of protein in your urine (proteinuria)

Not known (cannot be estimated from the available data)

• – Renal failure

• – An enlargement and weakening of a blood vessel wall or a tear in a blood vessel wall (aneurysms and artery dissections)

Other chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype

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

• – Feeling sick (nausea)

• – Vomiting

• – Loss of appetite

• – Pain in the lower body (abdomen)

• – Abnormal liver test results

Common side effects (may affect up to 1 in 10 people)

• – Weight loss

• – High blood pressure (hypertension)

• – Bleeding

• – Serious liver problems

• – Rash

• – Headache

Uncommon side effects (may affect up to 1 in 100 people)

• – Pancreatitis

• – Inflammation ofthe large bowel

• – Low platelet count (thrombocytopenia)

• – Jaundice, that is a yellow colour to the skin and whites ofthe eyes due to high levels of bilirubin

• – Itching

• – Heart attack

• – Hair loss (alopecia)

• – Increased amount of protein in your urine (proteinuria)

Not known (cannot be estimated from the available data)

• – Renal failure

• – An enlargement and weakening of a blood vessel wall or a tear in a blood vessel wall (aneurysms and artery dissections)

Systemic sclerosis associated interstitial lung disease (SSc-ILD)

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

• – Feeling sick (nausea)

• – Vomiting

• – Pain in the lower body (abdomen)

• – Abnormal liver test results

Common side effects (may affect up to 1 in 10 people)

• – Bleeding

• – High blood pressure (hypertension)

• – Loss of appetite

• – Weight loss

• – Headache

Uncommon side effects (may affect up to 1 in 100 people)

• – Inflammation of the large bowel

• – Serious liver problems

• – Renal failure

• – Low platelet count (thrombocytopenia)

• – Rash

• – Itching

Not known (cannot be estimated from the available data)

• – Heart attack

• – Pancreatitis

• – Jaundice, that is a yellow colour to the skin and whites of the eyes due to high levels of bilirubin

• – An enlargement and weakening of a blood vessel wall or a tear in a blood vessel wall (aneurysms and artery dissections)

• – Hair loss (alopecia)

• – Increased amount of protein in your urine (proteinuria)

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. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Ofev

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

Do not store Ofev above 25°C.

Store in the original package in order to protect from moisture.

Do not use this medicine if you notice that the blister containing the capsules is opened or a capsule is broken.

If you are in contact with the content of the capsule, wash off your hands immediately with plenty of water (see section 3).

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.

6. Contents of the pack and other information

What Ofev contains

• – The active substance is nintedanib. Each capsule contains 150 mg nintedanib (as esilate).

• – The other ingredients are:

Capsule fill: Triglycerides, medium-chain, hard fat, soya lecithin (E322) (see section 2)

Capsule shell: Gelatin, glycerol (85%), titanium dioxide (E171), iron oxide red (E172), iron oxide yellow (E172)

Printing ink: Shellac glaze, iron oxide black (E172), propylene glycol (E1520)

What Ofev looks like and contents of the pack

Ofev 150 mg capsules are brown-coloured, opaque, oblong soft-gelatin capsules imprinted on one side in black with the Boehringer Ingelheim company symbol and the figure “150”.

Two pack-sizes of Ofev 150 mg capsules are available:

• – 30 × 1 soft capsules in aluminium/aluminium perforated unit dose blisters

• – 60 × 1 soft capsules in aluminium/aluminium perforated unit dose blisters