Package leaflet: Information for the patient

Ofev 25 mg soft capsules

nintedanib
Read this leaflet carefully before taking this medicine because it contains
important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet

What Ofev is and what it is used for
What you need to know before taking Ofev
How to take Ofev
Possible side effects
How to store Ofev
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 tyrosine kinase inhibitors, and is used to treat the following conditions:

Idiopathic pulmonary fibrosis (IPF) in adults
IPF is a condition in which lung tissue becomes thick, stiff, and scarred over time. As a result, scarring reduces the ability to transfer oxygen from the lungs into the bloodstream, making deep breathing difficult. Ofev helps reduce the further progression of scarring and lung stiffening.

Other chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype in adults
In addition to IPF, there are other conditions in which lung tissue becomes thick, stiff, and scarred (pulmonary fibrosis) and continues to worsen over time (progressive phenotype). Examples of these conditions include hypersensitivity pneumonitis, autoimmune ILDs (e.g., ILD associated with rheumatoid arthritis), idiopathic nonspecific interstitial pneumonia, unclassifiable idiopathic interstitial pneumonia, and other ILDs. Ofev helps reduce the further progression of scarring and lung stiffening.

Clinically significant progressive fibrosing interstitial lung diseases (ILDs) in children and adolescents aged 6 to 17 years
In children with pediatric interstitial lung disease (chILD), pulmonary fibrosis may develop. When this occurs, the lung tissue in children and adolescents becomes thick, stiff, and scarred over time. Ofev helps reduce the further progression of scarring and lung stiffening.

Interstitial lung disease associated with systemic sclerosis (SSc-ILD) in adults, children, and adolescents aged 6 to 17 years
Systemic sclerosis (SSc), or scleroderma (and juvenile systemic sclerosis in children and adolescents), is a rare chronic autoimmune disease affecting connective tissue in various 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, this is known as interstitial lung disease (ILD), and the condition is referred to as SSc-ILD. Lung fibrosis reduces the lungs' ability to transfer oxygen into the blood and impairs breathing capacity. Ofev helps reduce the further progression of scarring and lung stiffening.

2. What you need to know before taking Ofev

Do not take Ofev

if you are pregnant,
if you are allergic to nintedanib, peanuts, or soy, or to 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 kidney problems or if protein has been detected in your urine,
if you have or have had bleeding problems,
if you are taking blood-thinning medicines (for example warfarin, phenprocoumon, or heparin) to prevent blood clots,
if you are taking pirfenidone, which may increase the risk of developing diarrhoea, nausea, vomiting, and liver problems,
if you have or have had heart problems (for example a heart attack),
if you have recently undergone surgery. Nintedanib may affect wound healing. Therefore, treatment with Ofev is usually interrupted for a certain period around the time of surgery. Your doctor will decide when you can resume treatment with this medicine,
if you have high blood pressure,
if you have high blood pressure in the blood vessels of the lungs (pulmonary hypertension),
if you have or have had an aneurysm (a bulging and weakening of a blood vessel wall) or a tear in the wall of a blood vessel.

Based on this information, your doctor may perform blood tests, for example, to check liver function. Your doctor will discuss the test results with you and decide whether you can take Ofev.
Immediately inform your doctor while taking this medicine

if you have diarrhoea. It is important to treat diarrhoea early (see section 4, “Possible side effects”);
if you vomit or feel unwell (nausea);
if you experience unexplained symptoms such as yellowing of the skin or the whites of the eyes (jaundice), dark or brown-coloured urine (like tea), pain in the upper right part of the stomach area (abdomen), bleeding or bruising more easily than usual, or a feeling of tiredness. These could be symptoms of serious liver problems;
if you have severe stomach pain, fever, chills, feeling unwell, vomiting, or abdominal stiffness or swelling, as these could be symptoms of a hole in the wall of the intestine (“gastrointestinal perforation”). Inform your doctor also if you have previously suffered from peptic ulcers or diverticular disease, or if you are taking concomitant anti-inflammatory medicines (NSAIDs) (used to relieve pain and treat swelling) or steroids (used for inflammation and allergies), as this may increase this risk;
if you experience a combination of severe stomach pain or cramps, red blood in the stools, or diarrhoea, as these could be symptoms of intestinal inflammation due to inadequate blood supply;
if you have pain, swelling, redness, or warmth in a limb, as these could be symptoms of a blood clot in a vein (a type of blood vessel);
if you feel pressure or pain in the chest, particularly on the left side of the body, pain in the neck, jaw, shoulder, or arm, rapid heartbeat, shortness of breath, nausea, vomiting, as these could be symptoms of a heart attack;
if you have significant bleeding;
if bruises, bleeding, fever, fatigue, and confusion occur. These could be signs of damage to blood vessels known as thrombotic microangiopathy (TMA);
if you experience symptoms such as headache, changes in vision, confusion, seizures, or other neurological disturbances such as weakness in an arm or leg, with or without high blood pressure. These may be symptoms of a brain condition called posterior reversible encephalopathy syndrome (PRES).

Children and adolescents
Ofev must not be taken by children under 6 years of age.
Your doctor may schedule regular dental check-ups at least once every 6 months until full dental development is complete, and monitor your growth annually (bone imaging tests) while you are taking this medicine.

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 over-the-counter medicines.
Ofev may interact with certain medicines. The following medicines are examples of medicines that may increase nintedanib levels in the blood, potentially increasing the risk of side effects (see section 4, “Possible side effects”):

a medicine used to treat fungal infections (ketoconazole),
a medicine used to treat bacterial infections (erythromycin),
a medicine that affects the immune system (cyclosporine).

The following medicines are examples of medicines that may decrease nintedanib levels in the blood, potentially reducing the effectiveness of Ofev:

an antibiotic used to treat tuberculosis (rifampicin),
medicines used to treat epilepsy (carbamazepine, phenytoin),
a herbal medicine used to treat depression (St. John’s wort).

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy
Do not take this medicine during pregnancy, as it may harm the unborn baby and cause birth defects.
Before starting treatment with Ofev, you must take a pregnancy test to confirm that you are not pregnant. Speak to your doctor.

Contraception

Women of childbearing potential must use a highly effective method of contraception to prevent pregnancy when starting Ofev, during treatment with Ofev, and for at least 3 months after stopping treatment.
Speak to your doctor to evaluate the most suitable contraceptive methods for you.
Vomiting and/or diarrhoea or other gastrointestinal problems may affect the absorption of oral hormonal contraceptives, such as the pill, and may reduce their effectiveness. Therefore, if you experience these symptoms, speak to your doctor to consider a more appropriate alternative contraceptive method.
Immediately inform your doctor or pharmacist if you become pregnant or suspect pregnancy during treatment with Ofev.

Breastfeeding
Do not breastfeed during treatment with Ofev, as there is a possible risk of harm to breastfed infants.

Driving and using machines
Ofev has a minor influence on the ability to drive and use machines. If you do not feel well, you must not drive or operate machinery.

Ofev contains soy lecithin
If you are allergic to soy or peanuts, do not take this medicine (see section 2, under “Do not take Ofev”).

3. How to take Ofev

Take this medicine exactly as your doctor or pharmacist has told you. If
you have any doubts, consult your doctor or pharmacist.
Take the capsules twice daily, approximately 12 hours apart and at approximately the same time each day,
for example one capsule in the morning and one capsule in the evening. This ensures that a
constant amount of nintedanib is maintained in the bloodstream. Swallow the capsules whole with water and do not
chew them. It is recommended to take the capsules with food, either during a meal or
immediately before or after. Do not open or crush the capsule (see section 5, under “How
to store Ofev”).
To make swallowing easier, you may take the capsules with a small amount (one teaspoon) of soft
food, such as apple puree or chocolate pudding, cold or at room temperature. Swallow the
capsules immediately and do not chew them, to ensure they remain intact.
Adults
The recommended dose is one 150 mg capsule twice daily (for a total of 300 mg daily).
Do not take a higher dose 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 (for possible
side effects, see section 4), your doctor may reduce the daily dose of Ofev. Do not reduce the dose
or stop treatment without first consulting your doctor.
Your doctor may reduce the recommended dose to 100 mg twice daily (for a total of 200 mg daily).
In this case, your doctor will prescribe treatment with Ofev 100 mg capsules. Do not take a higher dose
than the recommended dose of two Ofev 100 mg capsules per day if your dose has been reduced to 200 mg daily.
Use in children and adolescents
The recommended dose depends on the patient's body weight.
Inform your doctor if the patient's weight drops below 13.5 kg at any time during treatment.
Inform your doctor if you have liver problems.
Your doctor will determine the correct dose. The dose may be adjusted as treatment progresses.
If you do not tolerate the recommended daily dose of Ofev capsules (for possible side effects,
see section 4), your doctor may reduce the daily dose of Ofev.
Do not reduce the dose or stop treatment without first consulting your doctor.
Dosing of Ofev capsules according to weight in children and adolescents:

Weight range in kilograms (kg)	Ofev dose in milligrams (mg)
13.5 - 22.9 kg	50 mg (two 25 mg capsules) twice daily
23.0 - 33.4 kg	75 mg (three 25 mg capsules) twice daily
33.5 - 57.4 kg	100 mg (one 100 mg capsule or four 25 mg capsules) twice daily
≥ 57.5 kg	150 mg (one 150 mg capsule or six 25 mg capsules) twice daily

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 at the same time if you have forgotten to take the previous dose.
Take the next dose of Ofev at the next scheduled time, as planned and recommended by your doctor or pharmacist.
If you stop taking Ofev
Do not stop treatment with Ofev without first consulting your doctor. It is important to take this medicine every day for the entire duration indicated by your doctor.
If you have any doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
You should pay particular attention if you experience the following side effects during treatment with
Ofev:
Diarrhoea (very common, may affect more than 1 in 10 people):
Diarrhoea may lead to dehydration: loss of fluids and important salts (electrolytes such as sodium or
potassium) from the body. At the first signs of diarrhoea, drink plenty of fluids and contact your doctor immediately. Start appropriate treatment for diarrhoea as soon as possible, for example with loperamide.
The following side effects have also been observed during treatment with this medicine.
Contact your doctor if you experience any side effect.

Idiopathic pulmonary fibrosis (IPF)
Very common side effects (may affect more than 1 in 10 people)

Feeling unwell (nausea)
Pain in the lower part of the body (abdomen)
Abnormal liver function tests

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

Vomiting
Loss of appetite
Weight loss
Bleeding
Rash
Headache (cephalalgia)

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

Pancreatitis
Inflammation of the large intestine
Severe liver problems
Low platelet count (thrombocytopenia)
High blood pressure (hypertension)
Jaundice, i.e. yellowing of the skin and whites of the eyes due to high levels of bilirubin
Itching (pruritus)
Heart attack
Hair loss (alopecia)
Increased amount of protein in the urine (proteinuria)

Not known (frequency cannot be estimated from the available data)

Kidney failure
Enlargement and weakening of the wall of a blood vessel or a tear in the wall of a blood vessel (aneurysms and arterial dissections)
Brain condition with symptoms such as headache, changes in vision, confusion, seizures, or other neurological disturbances such as weakness in an arm or leg, with or without high blood pressure (reversible posterior encephalopathy syndrome)

Other chronic fibrosing interstitial lung diseases (ILD) with progressive phenotype
Very common side effects (may affect more than 1 in 10 people)

Feeling unwell (nausea)
Vomiting
Loss of appetite
Pain in the lower part of the body (abdomen)
Abnormal liver function tests

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

Weight loss
High blood pressure (hypertension)
Bleeding
Severe liver problems
Rash
Headache (cephalalgia)

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

Pancreatitis
Inflammation of the large intestine
Low platelet count (thrombocytopenia)
Jaundice, i.e. yellowing of the skin and whites of the eyes due to high levels of bilirubin
Itching (pruritus)
Heart attack
Hair loss (alopecia)
Increased amount of protein in the urine (proteinuria)

Not known (frequency cannot be estimated from the available data)

Kidney failure
Enlargement and weakening of the wall of a blood vessel or a tear in the wall of a blood vessel (aneurysms and arterial dissections)
Brain condition with symptoms such as headache, changes in vision, confusion, seizures, or other neurological disturbances such as weakness in an arm or leg, with or without high blood pressure (reversible posterior encephalopathy syndrome)

Interstitial lung disease associated with systemic sclerosis (SSc-ILD)
Very common side effects (may affect more than 1 in 10 people)

Feeling unwell (nausea)
Vomiting
Pain in the lower part of the body (abdomen)
Abnormal liver function tests

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

Bleeding
High blood pressure (hypertension)
Loss of appetite
Weight loss
Headache (cephalalgia)

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

Inflammation of the large intestine
Severe liver problems
Kidney failure
Low platelet count (thrombocytopenia)
Rash
Itching (pruritus)

Not known (frequency cannot be estimated from the available data)

Heart attack
Pancreatitis
Jaundice, i.e. yellowing of the skin and whites of the eyes due to high levels of bilirubin
Enlargement and weakening of the wall of a blood vessel or a tear in the wall of a blood vessel (aneurysms and arterial dissections)
Hair loss (alopecia)
Increased amount of protein in the urine (proteinuria)
Brain condition with symptoms such as headache, changes in vision, confusion, seizures, or other neurological disturbances such as weakness in an arm or leg, with or without high blood pressure (reversible posterior encephalopathy syndrome)

Fibrosing interstitial lung diseases (ILD) in children and adolescents
Side effects in children and adolescents are similar to those in adult patients.
Contact your doctor if you experience any side effect.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. 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 stated on the pack, blister or bottle. The expiry date refers to the last day of that month.
Do not store Ofev above 25 °C.
Blister: Store in the original packaging to protect the medicine from moisture.
Bottle: Keep the bottle tightly closed to protect the medicine from moisture.
Do not use this medicine if you notice that the blister containing the capsules is open or if a capsule is damaged.
If you come into contact with the capsule contents, wash your hands immediately with plenty of water (see section 3, "How to take Ofev").
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Ofev contains

The active substance is nintedanib. Each capsule contains 25 mg of nintedanib (as esilate).
The other components are:
Capsule contents: Medium-chain triglycerides, semi-synthetic solid glycerides, soybean lecithin (E322) (see section 2, under "Do not take Ofev")
Capsule shell: Gelatin, glycerol (85%), titanium dioxide (E171), red iron oxide (E172), yellow iron oxide (E172)
Printing ink: Shellac, black iron oxide (E172), propylene glycol (E1520)

Description of the appearance of Ofev and contents of the pack
Ofev 25 mg soft capsules are orange, opaque, oval soft gelatin capsules (approximately 8 × 5 mm), printed in black with "25" on one side.
Four pack sizes of Ofev 25 mg soft capsules are available:

60 × 1 soft capsules in aluminium/aluminium blister packs, divided into unit doses
60 soft capsules in a plastic bottle with screw cap
120 soft capsules in a plastic bottle with screw cap
180 soft capsules in a plastic bottle with screw cap

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 further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien
Boehringer Ingelheim SComm
Tél/Tel: +32 2 773 33 11

Lietuva
Boehringer Ingelheim RCV GmbH & Co KG
Lietuvos filialas
Tel: +370 5 2595942

България
Бьорингер Ингелхайм РЦВ ГмбХ и Ко. КГ – клон България
Tel: +359 2 958 79 98

Luxembourg/Luxemburg
Boehringer Ingelheim SComm
Tél/Tel: +32 2 773 33 11

Česká republika
Boehringer Ingelheim spol. s r.o.
Tel: +420 234 655 111

Magyarország
Boehringer Ingelheim RCV GmbH & Co KG
Magyarországi Fióktelepe
Tel: +36 1 299 89 00

Danmark
Boehringer Ingelheim Danmark A/S
Tlf: +45 39 15 88 88

Malta
Boehringer Ingelheim Ireland Ltd.
Tel: +353 1 295 9620

Deutschland
Boehringer Ingelheim Pharma GmbH & Co. KG
Tel: +49 (0) 800 77 90 900

Nederland
Boehringer Ingelheim B.V.
Tel: +31 (0) 800 22 55 889

Eesti
Boehringer Ingelheim RCV GmbH & Co KG
Eesti Filiaal
Tel: +372 612 8000

Norge
Boehringer Ingelheim Danmark
Norwegian branch
Tlf: +47 66 76 13 00

Ελλάδα
Boehringer Ingelheim Ελλάς Μονοπρόσωπη A.E.
Tηλ: +30 2 10 89 06 300

Österreich
Boehringer Ingelheim RCV GmbH & Co KG
Tel: +43 1 80 105-7870

España
Boehringer Ingelheim España, S.A.
Tel: +34 93 404 51 00

Polska
Boehringer Ingelheim Sp. z o.o.
Tel: +48 22 699 0 699

France
Boehringer Ingelheim France S.A.S.
Tél: +33 3 26 50 45 33

Portugal
Boehringer Ingelheim Portugal, Lda.
Tel: +351 21 313 53 00

Hrvatska
Boehringer Ingelheim Zagreb d.o.o.
Tel: +385 1 2444 600

România
Boehringer Ingelheim RCV GmbH & Co KG
Viena – Sucursala Bucureşti
Tel: +40 21 302 2800

Ireland
Boehringer Ingelheim Ireland Ltd.
Tel: +353 1 295 9620

Slovenija
Boehringer Ingelheim RCV GmbH & Co KG
Podružnica Ljubljana
Tel: +386 1 586 40 00

Ísland
Vistor ehf.
Sími: +354 535 7000

Slovenská republika
Boehringer Ingelheim RCV GmbH & Co KG
organizačná zložka
Tel: +421 2 5810 1211

Italia
Boehringer Ingelheim Italia S.p.A.
Tel: +39 02 5355 1

Suomi/Finland
Boehringer Ingelheim Finland Ky
Puh/Tel: +358 10 3102 800

Κύπρος
Boehringer Ingelheim Ελλάς Μονοπρόσωπη A.E.
Tηλ: +30 2 10 89 06 300

Sverige
Boehringer Ingelheim AB
Tel: +46 8 721 21 00

Latvija
Boehringer Ingelheim RCV GmbH & Co KG
Latvijas filiāle
Tel: +371 67 240 011

United Kingdom (Northern Ireland)
Boehringer Ingelheim Ireland Ltd.
Tel: +353 1 295 9620

More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu.

Patient information leaflet

Ofev 100 mg soft capsules

nintedanib
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as yours, because it could be harmful.
If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

What Ofev is and what it is used for
What you need to know before taking Ofev
How to take Ofev
Possible side effects
How to store Ofev
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 tyrosine kinase inhibitors, and is used to treat the following conditions:
Idiopathic pulmonary fibrosis (IPF) in adults
IPF is a condition in which, over time, lung tissue becomes thick, stiff, and scarred. As a result, scarring reduces the ability to transfer oxygen from the lungs into the bloodstream, making deep breathing difficult. Ofev helps reduce further development of scarring and lung stiffening.
Other chronic fibrosing interstitial lung diseases (ILD) with a progressive phenotype in adults
In addition to IPF, there are other conditions in which, over time, lung tissue becomes thick, stiff, and scarred (pulmonary fibrosis) and continues to worsen (progressive phenotype). Examples of these conditions include hypersensitivity pneumonitis, autoimmune ILDs (e.g. ILD associated with rheumatoid arthritis), idiopathic nonspecific interstitial pneumonia, unclassifiable idiopathic interstitial pneumonia, and other ILDs. Ofev helps reduce further development of scarring and lung stiffening.
Clinically significant progressive fibrosing interstitial lung diseases (ILD) in children and adolescents aged 6 to 17 years
In children with pediatric interstitial lung disease (chILD), pulmonary fibrosis may occur. When this happens, lung tissue in children and adolescents becomes thick, stiff, and scarred over time. Ofev helps reduce further development of scarring and lung stiffening.
Interstitial lung disease associated with systemic sclerosis (SSc-ILD) in adults, children, and adolescents aged 6 to 17 years
Systemic sclerosis (SSc), or scleroderma (and juvenile systemic sclerosis in children and adolescents), is a rare chronic autoimmune disease affecting connective tissue in various 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 referred to as interstitial lung disease (ILD), and the condition is known as SSc-ILD. Fibrosis in the lungs reduces their ability to transfer oxygen into the blood and impairs breathing capacity. Ofev helps reduce further development of scarring and lung stiffening.

2. What you should know before taking Ofev

Do not take Ofev

if you are pregnant,
if you are allergic to nintedanib, peanuts, or soy, or to 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 kidney problems or if increased levels of protein have been detected in your urine,
if you have or have had bleeding problems,
if you are taking blood-thinning medicines (for example, warfarin, phenprocoumon, or heparin) to prevent blood clots,
if you are taking pirfenidone, which may increase the risk of developing diarrhoea, nausea, vomiting, and liver problems,
if you have or have had heart problems (for example, a heart attack),
if you have recently undergone surgery. Nintedanib may affect wound healing. Therefore, treatment with Ofev is usually stopped for a period of time around the time of surgery. Your doctor will decide when you can restart treatment with this medicine,
if you have high blood pressure,
if you have high blood pressure in the blood vessels of the lungs (pulmonary hypertension),
if you have or have had an aneurysm (a bulge and weakening of a blood vessel wall) or a tear in the wall of a blood vessel.

Based on this information, your doctor may carry out blood tests, for example, to check liver function. Your doctor will discuss the test results with you and decide whether you can take Ofev.
Inform your doctor immediately while taking this medicine

if you have diarrhoea. It is important to treat diarrhoea early (see section 4, “Possible side effects”);
if you vomit or feel unwell (nausea);
if you experience unexplained symptoms such as yellowing of the skin or the whites of the eyes (jaundice), dark or brown-coloured urine (like tea), pain in the upper right part of the stomach area (abdomen), bleeding or bruising more easily than usual, or feeling tired. These could be signs of serious liver problems;
if you have severe stomach pain, fever, chills, feeling unwell, vomiting, or abdominal stiffness or swelling, as these could be symptoms of a hole in the wall of the intestine (“gastrointestinal perforation”). Inform your doctor also if you have previously suffered from peptic ulcers or diverticular disease, or if you are taking concomitant anti-inflammatory medicines (NSAIDs) (used to relieve pain and treat swelling) or steroids (used for inflammation and allergies), as this may increase this risk;
if you experience a combination of severe stomach pain or cramps, red blood in the stools, or diarrhoea, as these could be symptoms of intestinal inflammation due to inadequate blood supply;
if you have pain, swelling, redness, or warmth in a limb, as these could be symptoms of a blood clot in a vein (a type of blood vessel);
if you feel pressure or pain in the chest, particularly on the left side of the body, pain in the neck, jaw, shoulder, or arm, rapid heartbeat, shortness of breath, nausea, vomiting, as these could be symptoms of a heart attack;
if you have significant bleeding;
if bruises, bleeding, fever, fatigue, and confusion occur. These could be signs of damage to blood vessels known as thrombotic microangiopathy (TMA);
if you experience symptoms such as headache, changes in vision, confusion, seizures, or other neurological disturbances such as weakness in an arm or leg, with or without high blood pressure. These may be symptoms of a brain condition called posterior reversible encephalopathy syndrome (PRES).

Children and adolescents
Ofev must not be taken by children under 6 years of age.
Your doctor may recommend regular dental check-ups at least once every 6 months until full dental development is complete, and monitor your growth annually (bone imaging exams) while you are taking this medicine.
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 without a prescription.
Ofev may interact with certain medicines. The following medicines are some examples of medicines that may increase nintedanib levels in the blood, potentially increasing the risk of side effects (see section 4, “Possible side effects”):

a medicine used to treat fungal infections (ketoconazole)
a medicine used to treat bacterial infections (erythromycin)
a medicine that affects the immune system (cyclosporine)

The following medicines are some examples of medicines that may decrease nintedanib levels in the blood, potentially reducing the effectiveness of Ofev:

an antibiotic used to treat tuberculosis (rifampicin)
medicines used to treat epilepsy (carbamazepine, phenytoin)
a herbal medicine used to treat depression (St. John’s wort)

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
Do not take this medicine during pregnancy, as it may harm the unborn baby and cause birth defects.
Before starting treatment with Ofev, you must have a pregnancy test to confirm that you are not pregnant. Talk to your doctor.
Contraception

Women of childbearing potential must use a highly effective method of contraception to avoid pregnancy when starting Ofev, during treatment with Ofev, and for at least 3 months after stopping treatment.
Talk to your doctor to evaluate the most suitable contraceptive methods for you.
Vomiting and/or diarrhoea or other gastrointestinal problems may affect the absorption of oral hormonal contraceptives, such as the pill, and may reduce their effectiveness. Therefore, if you experience these problems, talk to your doctor to consider a more appropriate alternative contraceptive method.
Inform your doctor or pharmacist immediately if you become pregnant or suspect you are pregnant during treatment with Ofev.

Breastfeeding
Do not breastfeed during treatment with Ofev, as there is a risk of harm to breastfed infants.
Driving and using machines
Ofev has a minor influence on the ability to drive and use machines. If you do not feel well, you should not drive or use machines.
Ofev contains soy lecithin
If you are allergic to soy or peanuts, do not take this medicine (see section 2, under “Do not take Ofev”).

3. How to take Ofev

Adults
The recommended dose is one 100 mg capsule twice daily (for a total daily dose of 200 mg).
Do not take a higher dose 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 (for possible side effects, see section 4), your doctor may advise you to discontinue treatment with this medicine. Do not reduce the dose or stop treatment without first consulting your doctor.

Use in children and adolescents
The recommended dose depends on the patient's body weight.
Inform your doctor if the patient's weight drops below 13.5 kg at any time during treatment.
Inform your doctor if you have liver problems.
Your doctor will determine the correct dose. Your doctor may adjust the dose as treatment progresses.
If you do not tolerate the recommended daily dose of Ofev capsules (for possible side effects, see section 4), your doctor may reduce the daily dose of Ofev.
Do not reduce the dose or stop treatment without first consulting your doctor.
Dosing of Ofev capsules according to weight in children and adolescents:

Weight range in kilograms (kg)	Ofev dose in milligrams (mg)
13.5 ‑ 22.9 kg	50 mg (two 25 mg capsules) twice daily
23.0 ‑ 33.4 kg	75 mg (three 25 mg capsules) twice daily
33.5 ‑ 57.4 kg	100 mg (one 100 mg capsule or four 25 mg capsules) twice daily
≥ 57.5 kg	150 mg (one 150 mg capsule or six 25 mg capsules) twice daily

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 at the same time if you have missed a previous dose.
Take the next dose of Ofev at the next scheduled time, as planned and recommended by your doctor or pharmacist.
If you stop taking Ofev
Do not stop treatment with Ofev without first consulting your doctor. It is important to take this medicine every day for the entire duration prescribed by your doctor.
If you have any doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
You should be particularly cautious if you experience the following side effects during treatment with
Ofev:
Diarrhoea (very common, may affect more than 1 in 10 people):
Diarrhoea may lead to dehydration: loss of fluids and important salts (electrolytes such as sodium or
potassium) from the body. At the first signs of diarrhoea, drink plenty of fluids and contact your doctor
immediately. Start appropriate treatment for diarrhoea as soon as possible, for example with loperamide.
The following side effects have also been observed during treatment with this medicine.
Contact your doctor if you experience any side effect.

Idiopathic pulmonary fibrosis (IPF)
Very common side effects (may affect more than 1 in 10 people)

Feeling unwell (nausea)
Pain in the lower part of the body (abdomen)
Abnormal liver function tests

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

Vomiting
Loss of appetite
Weight loss
Bleeding
Rash
Headache (cephalalgia)

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

Pancreatitis
Inflammation of the large intestine
Severe liver problems
Low platelet count (thrombocytopenia)
High blood pressure (hypertension)
Jaundice, i.e. yellowing of the skin and whites of the eyes due to elevated bilirubin levels
Itching (pruritus)
Heart attack
Hair loss (alopecia)
Increased levels of protein in the urine (proteinuria)

Not known (frequency cannot be estimated from the available data)

Kidney failure
Enlargement and weakening of the wall of a blood vessel or a tear in the wall of a blood vessel (aneurysms and arterial dissections)
Brain condition with symptoms such as headache, vision changes, confusion, seizures, or other neurological disturbances such as weakness in an arm or leg, with or without high blood pressure (reversible posterior encephalopathy syndrome)

Other chronic fibrosing interstitial lung diseases (ILD) with progressive phenotype
Very common side effects (may affect more than 1 in 10 people)

Feeling unwell (nausea)
Vomiting
Loss of appetite
Pain in the lower part of the body (abdomen)
Abnormal liver function tests

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

Weight loss
High blood pressure (hypertension)
Bleeding
Severe liver problems
Rash
Headache (cephalalgia)

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

Pancreatitis
Inflammation of the large intestine
Low platelet count (thrombocytopenia)
Jaundice, i.e. yellowing of the skin and whites of the eyes due to elevated bilirubin levels
Itching (pruritus)
Heart attack
Hair loss (alopecia)
Increased levels of protein in the urine (proteinuria)

Not known (frequency cannot be estimated from the available data)

Kidney failure
Enlargement and weakening of the wall of a blood vessel or a tear in the wall of a blood vessel (aneurysms and arterial dissections)
Brain condition with symptoms such as headache, vision changes, confusion, seizures, or other neurological disturbances such as weakness in an arm or leg, with or without high blood pressure (reversible posterior encephalopathy syndrome)

Interstitial lung disease associated with systemic sclerosis (SSc-ILD)
Very common side effects (may affect more than 1 in 10 people)

Feeling unwell (nausea)
Vomiting
Pain in the lower part of the body (abdomen)
Abnormal liver function tests

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

Bleeding
High blood pressure (hypertension)
Loss of appetite
Weight loss
Headache (cephalalgia)

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

Inflammation of the large intestine
Severe liver problems
Kidney failure
Low platelet count (thrombocytopenia)
Rash
Itching (pruritus)

Not known (frequency cannot be estimated from the available data)

Heart attack
Pancreatitis
Jaundice, i.e. yellowing of the skin and whites of the eyes due to elevated bilirubin levels
Enlargement and weakening of the wall of a blood vessel or a tear in the wall of a blood vessel (aneurysms and arterial dissections)
Hair loss (alopecia)
Increased levels of protein in the urine (proteinuria)
Brain condition with symptoms such as headache, vision changes, confusion, seizures, or other neurological disturbances such as weakness in an arm or leg, with or without high blood pressure (reversible posterior encephalopathy syndrome)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. 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 stated on the carton and blister. The expiry date refers to the last day of that month.
Do not store Ofev above 25 °C.
Keep the medicine in the original packaging to protect it from moisture.
Do not use this medicine if you notice that the blister containing the capsules is open or if a capsule is damaged.
If you come into contact with the capsule contents, wash your hands immediately with plenty of water (see section 3, "How to take Ofev").
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Ofev contains

The active substance is nintedanib. Each capsule contains 100 mg of nintedanib (as esilate).
The other components are:
Capsule contents: Medium-chain triglycerides, semi-synthetic solid glycerides, soy lecithin (E322) (see section 2, under "Do not take Ofev")
Capsule shell: Gelatin, glycerol (85%), titanium dioxide (E171), red iron oxide (E172), yellow iron oxide (E172)

Description of the appearance of Ofev and contents of the pack
Ofev 100 mg soft capsules are peach-coloured, opaque, oblong soft gelatin capsules (approximately 16 × 6 mm), with the Boehringer Ingelheim company logo and “100” printed on one side.
Two pack sizes of Ofev 100 mg soft capsules are available:

30 × 1 soft capsule in aluminium/aluminium blisters, divided into unit doses
60 × 1 soft capsule in aluminium/aluminium blisters, divided into unit doses

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 further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien
Boehringer Ingelheim SComm
Tél/Tel: +32 2 773 33 11

България
Бьорингер Ингелхайм РЦВ ГмбХ и Ко. КГ – клон България
Тел: +359 2 958 79 98