OFEV 25 mg SOFT CAPSULES

Introduction

Package Leaflet: Information for the Patient

Ofev 25mg 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 experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Ofev and what is it used for

Ofev contains the active substance nintedanib, a medicine that belongs to the class of drugs known as tyrosine kinase inhibitors, and is used to treat the following diseases:

Idiopathic pulmonary fibrosis (IPF) in adults

IPF is a disease that causes thickening, hardening, and scarring of the tissue in your lungs over time. As a result, the scarring reduces the ability to transfer oxygen from the lungs to the bloodstream, making it difficult to breathe deeply. Ofev helps to reduce the occurrence of further scarring and hardening of the lungs.

Other chronic fibrosing interstitial lung diseases (ILD) with a progressive phenotype in adults

In addition to IPF, there are other diseases in which the tissue in your lungs becomes thickened, hardened, and scarred over time (pulmonary fibrosis) and continues to worsen (progressive phenotype). Some examples of these diseases are hypersensitivity pneumonitis, autoimmune ILD (such as ILD associated with rheumatoid arthritis), idiopathic nonspecific interstitial pneumonia, idiopathic unclassifiable interstitial pneumonia, and other ILD. Ofev helps to reduce the occurrence of further scarring and hardening of the lungs.

Fibrosing interstitial lung diseases (ILD) in children and adolescents from 6 to 17 years of age

Pulmonary fibrosis can occur in patients with childhood interstitial lung disease. In this case, the tissue in the lungs of children and adolescents becomes thickened, hardened, and scarred over time. Ofev helps to reduce the occurrence of further scarring and hardening of the lungs.

Interstitial lung disease associated with systemic sclerosis (SSc-ILD) in adults, adolescents, and children from 6 years of age and older

Systemic sclerosis (SSc), also known as scleroderma (and juvenile systemic sclerosis in children and adolescents), is a rare chronic autoimmune disease that affects the connective tissue in many parts of the body. SSc causes fibrosis (scarring and hardening) 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 the disease is called SSc-ILD. The fibrosis in the lungs reduces the ability to transfer oxygen to the bloodstream and reduces the ability to breathe. Ofev helps to reduce the occurrence of further scarring and hardening 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, peanuts, soy, or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor or pharmacist before you start taking Ofev

• if you have or have had liver problems,
• if you have or have had kidney problems, or if you have been found to have an increased amount of protein in your urine,
• if you have or have had bleeding problems,
• if you are taking medicines to thin your blood (such as warfarin, phenprocoumon, or heparin) to prevent blood clots,
• if you are taking pirfenidone, as this may increase the risk of diarrhea, nausea, vomiting, and liver problems,
• if you have or have had heart problems (such as a heart attack),
• if you have recently undergone surgery. Nintedanib may affect the way wounds heal. Therefore, treatment with Ofev will usually be interrupted for a period of time if you undergo surgery. Your doctor will decide when to restart 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 the wall of a blood vessel) or a tear in the wall of a blood vessel.

Based on this information, your doctor may perform some blood tests, for example, to check your liver function. Your doctor will discuss the results of these tests with you to decide if you can take Ofev.

Tell your doctor immediately while you are taking this medicine

• if you have diarrhea. It is important to treat diarrhea early (see section 4, "Possible side effects");
• if you have vomiting or feel like vomiting (nausea);
• if you have symptoms without an apparent cause such as yellowing of the skin or the whites of the eyes (jaundice), dark or brown urine (the color of tea), pain in the upper right side of the stomach area (abdomen), bleeding, or bruising more easily than normal, or feeling tired. These could be symptoms of serious liver problems;
• if you have severe stomach pain, fever, chills, dizziness, vomiting, or stiffness or swelling of the abdomen, as these could be symptoms of having a hole in the wall of the intestines ("gastrointestinal perforation"). Also, tell your doctor if you have had stomach ulcers or diverticular disease in the past or if you are being treated with anti-inflammatory medicines (NSAIDs) (used to relieve pain and swelling) or steroids (used against inflammation and allergies), as these may increase this risk;
• if you have a combination of severe or colicky stomach pain, blood in your stools, or diarrhea, as these could be symptoms of intestinal inflammation due to insufficient blood supply;
• if you have pain, swelling, redness, or warmth in a limb, as these could be symptoms of having a blood clot in one of your veins (a type of blood vessel);
• if you have pressure or pain in your chest, usually on the left side of your body, pain in your neck, jaw, shoulder, or arm, rapid heartbeat, difficulty breathing, nausea, or vomiting, as these could be symptoms of a heart attack;
• if you have a significant bleeding;
• if you experience bruising, bleeding, fever, fatigue, and confusion, as these may be a sign of a blood vessel injury known as thrombotic microangiopathy (TMA);
• if you experience symptoms such as headache, changes in vision, confusion, seizures, or other neurological disorders such as weakness in an arm or leg, with or without high blood pressure, which could be symptoms of a brain disorder called posterior reversible encephalopathy syndrome (PRES).

Children and adolescents

Children under 6 years of age must not take Ofev.

Your doctor may perform regular dental checks at least every 6 months until the completion of tooth development and monitor your growth once a year (bone imaging study) 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 obtained without a prescription.

Ofev may interact with other medicines. The following medicines may increase the levels of nintedanib in your blood and, therefore, increase 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 your immune system (ciclosporin)

The following medicines are examples that may decrease the levels of nintedanib in your blood and, therefore, reduce the effectiveness of Ofev:

• an antibiotic used to treat tuberculosis (rifampicin)
• medicines used to treat seizures (carbamazepine, phenytoin)
• a herbal medicine used to treat depression (St. John's Wort)

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, 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 may harm the fetus and cause birth defects.

A pregnancy test must be performed to ensure you are not pregnant before starting treatment with Ofev. Talk to your doctor.

Contraception

• Women who may become pregnant must use a highly effective contraceptive method to prevent pregnancy when starting to take Ofev, while taking Ofev, and for at least 3 months after stopping treatment.
• Talk to your doctor about the most suitable contraceptive methods for you.
• Vomiting and/or diarrhea or other gastrointestinal disorders may affect the absorption of hormonal oral contraceptives, such as birth control pills, and may reduce their effectiveness. Therefore, if you experience any of these situations, talk to your doctor to assess an alternative contraceptive method that is more suitable for you.
• Tell your doctor or pharmacist immediately if you become pregnant or think you may be pregnant during treatment with Ofev.

Breastfeeding

Do not breastfeed your baby while taking Ofev, as it may harm the baby.

Driving and using machines

Ofev has a minor influence on the ability to drive and use machines. Do not drive or use machines if you feel dizzy.

Ofev contains soy lecithin

If you are allergic to soy or peanuts, do not take this medicine (see section 2, "Do not take Ofev").

3. How to take Ofev

Always take this medicine exactly as your doctor or pharmacist has told you. If you are not sure, check with your doctor or pharmacist.

Take the capsules twice a day, with approximately 12 hours in between, and at about the same time each day; for example, one capsule in the morning and one capsule in the evening. This will ensure that you maintain a constant level of nintedanib in your blood. Swallow the capsules whole with water, without chewing them. It is recommended to take the capsules with food, i.e., during meals or immediately before or after meals. Do not open or break the capsule (see section 5, "Storage of Ofev").

To make it easier to swallow the capsules, you can take them with a small amount (one teaspoon) of a soft cold or room-temperature food, such as apple sauce or chocolate pudding. Swallow the capsules immediately and do not chew them to ensure they remain intact.

Adults

The recommended dose is one 150 mg capsule twice a day (a total of 300 mg per day).

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 your daily dose of Ofev. Do not reduce the dose or stop treatment yourself without consulting your doctor first.

Your doctor may reduce the recommended dose to 100 mg twice a 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 has been reduced to 200 mg per day.

Use in children and adolescents

The recommended dose depends on the patient's weight.

Tell your doctor if the patient's weight is below 13.5 kg at any time during treatment.

Tell your doctor if you have liver problems.

Your doctor will determine the correct dose. Your doctor may adjust the dose during the course of treatment.

If you do not tolerate the recommended daily dose of Ofev capsules (see possible side effects in section 4), your doctor may reduce the daily dose of Ofev.

Do not reduce the dose or stop treatment yourself without consulting your doctor first.

Dosing based on weight for Ofev capsules in children and adolescents:

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 missed your previous dose. You should take your next dose of Ofev at the next scheduled time and as recommended by your doctor or pharmacist.

If you stop taking Ofev

Do not stop taking Ofev without talking to your doctor first. It is important to take this medicine every day while your doctor prescribes it.

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

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

You should pay special attention if you experience the following adverse effects during treatment with Ofev:

Diarrhea(very frequent, may affect more than 1 in 10 people):

Diarrhea can cause dehydration: a loss of important fluids and salts from the body (electrolytes, such as sodium or potassium). If you experience the first symptoms of diarrhea, drink plenty of fluids and consult your doctor immediately. Start appropriate anti-diarrheal treatment as soon as possible, for example, by taking loperamide.

The following adverse effects have also been observed during treatment with this medicine.

Consult your doctor if you experience any type of adverse effect.

Idiopathic Pulmonary Fibrosis (IPF)

Very frequent adverse effects (may affect more than 1 in 10 people)

• Nausea
• Abdominal pain (lower half of the body)
• Abnormal liver test results

Frequent adverse effects (may affect up to 1 in 10 people)

• Vomiting
• Loss of appetite
• Weight loss
• Bleeding
• Rash
• Headache

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

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

Frequency not known (cannot be estimated from available data)

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

Other Chronic Fibrosing Interstitial Lung Diseases (ILDs)

Very frequent adverse effects (may affect more than 1 in 10 people)

• Nausea
• Vomiting
• Abdominal pain (lower half of the body)
• Abnormal liver test results

Frequent adverse effects (may affect up to 1 in 10 people)

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

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

• Pancreatitis
• Colitis
• Low platelet count (thrombocytopenia)
• Jaundice, i.e., yellow color of the skin and whites of the eyes due to high bilirubin levels
• Itching
• Heart attack
• Hair loss (alopecia)
• Increased protein in the urine (proteinuria)

Frequency not known (cannot be estimated from available data)

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

Very frequent adverse effects (may affect more than 1 in 10 people)

• Nausea
• Vomiting
• Abdominal pain (lower half of the body)
• Abnormal liver test results

Frequent adverse effects (may affect up to 1 in 10 people)

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

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

• Colitis
• Severe liver problems
• Kidney failure
• Low platelet count (thrombocytopenia)
• Rash
• Itching

Frequency not known (cannot be estimated from available data)

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

Chronic Fibrosing Interstitial Lung Diseases (ILDs) in Children and Adolescents

Adverse effects in children and adolescents were similar to those in adult patients.

Report to your doctor if you experience any type of adverse effect.

Reporting of Adverse Effects

If you experience any adverse effects, consult your doctor or pharmacist, even if they are possible adverse effects not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Ofev

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiration date stated on the carton, blister, or bottle. The expiration date is the last day of the month indicated.

Do not store above 25°C.

Blister: Store in the original packaging to protect from moisture.

Bottle: Keep the bottle tightly closed to protect from moisture.

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

If you come into contact with the contents of the capsule, wash your hands immediately with plenty of water (see section 3, "How to take Ofev").

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Package Contents and Additional Information

Ofev Composition

• The active ingredient is nintedanib. Each capsule contains 25 mg of nintedanib (as esilate).
• The other ingredients are:

Product Appearance and Package Contents

Ofev 25 mg capsules are soft gelatin capsules, oval, opaque, and orange in color (approximately 8 × 5 mm), with black printing on one side with the number "25".

There are four package sizes for Ofev 25 mg capsules:

• 60 × 1 soft capsules in precut unit-dose aluminum/aluminum blisters
• 60 soft capsules in a plastic bottle with a screw cap
• 120 soft capsules in a plastic bottle with a screw cap
• 180 soft capsules in a plastic bottle with a screw cap

Not all package sizes may be marketed.

Marketing Authorization 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

You can obtain more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet:

Detailed information on this medicine is available on the European Medicines Agency website: https://www.ema.europa.eu.