OFEV 100 mg soft capsules

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 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 abdominal stiffness or swelling, as these could be symptoms of 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 at the same time with non-steroidal anti-inflammatory drugs (NSAIDs) (used to relieve pain and swelling) or steroids (used against inflammation and allergies), as this may increase the risk;
• if you have a combination of severe or colicky stomach pain, blood in your stool, 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 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, tiredness, 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 should not take Ofev.

Your doctor may perform regular dental checks 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 (cyclosporine)

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 should 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 avoid 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 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

Take this medicine exactly as your doctor or pharmacist has told you. If you are not sure, ask your doctor or pharmacist.

Take the capsules twice a day, with approximately 12 hours between doses, and at about the same time each day; for example, one capsule in the morning and one capsule in the evening. This will help keep the level of nintedanib in your blood constant. 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 100 mg capsule twice a day (a total of 200 mg per day).

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 recommend that you stop taking this medicine. Do not reduce the dose or stop treatment yourself without talking to your doctor first.

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 talking to 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 product, 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 1in 10people):

Diarrhea can cause dehydration: a loss of fluids and important 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 1in 10people)

• Nausea
• Abdominal pain
• Abnormal liver test results

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

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

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

• Pancreatitis
• Colitis
• Severe liver problems
• Low platelet count (thrombocytopenia)
• High blood pressure (hypertension)
• Jaundice, i.e., yellow color in 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)
• Cerebral 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 1in 10people)

• Nausea
• Vomiting
• Loss of appetite
• Abdominal pain
• Abnormal liver test results

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

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

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

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

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)
• Cerebral 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)

Systemic Sclerosis-Associated Interstitial Lung Disease (SSc-ILD)

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

• Nausea
• Vomiting
• Abdominal pain
• Abnormal liver test results

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

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

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

• 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 in 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)
• Cerebral 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.

Adverse Effect Reporting

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect 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 contribute to providing more information on the safety of this medicine.

5. Storage of Ofev

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

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

Do not store above 25°C.

Store in the original packaging 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 100 mg of nintedanib (as esilate).
• The other ingredients are:

Capsule contents: medium-chain triglycerides, hard fat, soy lecithin (E322) (see section 2, "Do not take Ofev")

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

Product Appearance and Package Contents

Ofev 100 mg capsules are soft gelatin capsules, oblong, opaque, and peach-colored (approximately 16 × 6 mm), marked on one side with the Boehringer Ingelheim company logo and the number "100".

There are two package sizes for Ofev 100 mg capsules:

• 30 × 1 soft capsules in precut unit-dose aluminum/aluminum blisters
• 60 × 1 soft capsules in precut unit-dose aluminum/aluminum blisters

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.