VARGATEF 150 mg SOFT GEL CAPSULES

2. What you need to know before you take Vargatef

Do not take Vargatef

• 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 starting treatment with this medicine

• if you have or have had liver problems or if you have or have had bleeding problems, in particular recent bleeding in the lung
• 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 are taking medicines to thin your blood (such as warfarin, phenprocoumon, heparin, or acetylsalicylic acid) to prevent blood clots. Treatment with Vargatef may increase the risk of bleeding
• if you have recently undergone surgery or have planned surgery. Nintedanib may affect the way wounds heal. Therefore, treatment with Vargatef will usually be interrupted if you undergo surgery. Your doctor will decide when to resume treatment with this medicine
• if you have cancer that has spread to the brain
• if you have high blood pressure
• 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 and to determine how quickly your blood can clot. Your doctor will discuss the results of these tests with you to decide if you can receive Vargatef.

Tell your doctor immediately while taking this medicine

• if you have diarrhea. It is important to treat diarrhea as soon as the first symptoms appear (see section 4)
• 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 fever, chills, rapid breathing, or a rapid heart rate, which could be signs of infection or blood infection (sepsis) (see section 4)
• if you experience severe abdominal pain, fever, chills, dizziness, vomiting, or abdominal stiffness or swelling, as these could be symptoms of having a hole in the wall of the intestines (“gastrointestinal perforation”)
• if you experience a combination of some or all of the following symptoms: severe and sudden abdominal pain, blood in the stool, diarrhea or constipation, nausea, and vomiting, as these could be symptoms of intestinal inflammation due to reduced blood flow (“ischemic colitis”)
• if you experience pain, swelling, redness, or warmth in a limb or if you experience chest pain and difficulty breathing, as these could be symptoms of having a blood clot in one of your veins
• if you have a significant bleeding
• if you experience pressure or pain in the chest, usually on the left side of the body, pain in the neck, jaw, shoulder, or arm, a rapid heart rate, difficulty breathing, nausea, or vomiting, as these could be symptoms of a heart attack
• 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)
• if any of the side effects you may have (see section 4) worsen

Children and adolescents

This medicine has not been studied in children or adolescents to treat lung cancer (NSCLC) and, therefore, children and adolescents under 18 years of age should not take it.

Other medicines and Vargatef

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.

This medicine may interact with other medicines. The following medicines may increase the levels of nintedanib in the blood, the active substance of Vargatef, and therefore increase the risk of side effects (see section 4):

• Ketoconazole (used to treat fungal infections)
• Erythromycin (used to treat bacterial infections)

The following medicines may decrease the levels of nintedanib in the blood and thus reduce the effectiveness of Vargatef:

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

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.

Contraception

• Women who can become pregnant must use a highly effective method of contraception to avoid becoming pregnant when starting to take Vargatef, while taking Vargatef, and for at least three months after finishing treatment.
• Consult your doctor to determine which contraceptive methods are most suitable.
• 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, consult your doctor to assess an alternative contraceptive method that is more suitable.
• Tell your doctor or pharmacist immediately if you become pregnant or think you may be pregnant during treatment with Vargatef.

Breastfeeding

It is not known whether the medicine passes into breast milk and may harm the breastfed baby. Therefore, women should not breastfeed their baby during treatment with Vargatef.

Fertility

The effect of this medicine on human fertility has not been studied.

Driving and using machines

Vargatef has little influence on the ability to drive and use machines. Do not drive or use machines if you feel dizzy.

Vargatef contains soy

The capsules contain soy lecithin. If you are allergic to peanuts or soy, do not take this medicine.

3. How to take Vargatef

Follow exactly the instructions for administration of this medicine given by your doctor or pharmacist. If you are in doubt, consult your doctor or pharmacist again.

Do not take Vargatef on the same day that you receive chemotherapy treatment with docetaxel.

Swallow the capsules whole with water, without chewing them. It is recommended to take the capsule with food, i.e., during meals or immediately before or after meals.

Do not open or break the capsule (see section 5).

The recommended dose is two capsules per day (for a total of 300 mg of nintedanib per day). Do not take a higher dose than this.

This daily dose should be divided into two doses of one capsule with approximately 12 hours in between, for example, one capsule in the morning and one capsule in the evening. The two doses should be taken at approximately the same time every day. If you take the medicine in this way, you will ensure that a constant level of nintedanib is maintained in the body.

Dose reduction

If you cannot tolerate the recommended dose of 300 mg per day due to the occurrence of side effects (see section 4), your doctor may reduce the recommended daily dose of Vargatef to 200 mg per day (two 100 mg capsules). In this case, your doctor will prescribe Vargatef 100 mg soft capsules for your treatment.

You should take one capsule of this concentration twice a day with food, with approximately 12 hours in between (e.g., in the morning and in the evening) and at approximately the same time of day.

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

If your doctor has interrupted chemotherapy with docetaxel, you should continue taking Vargatef twice a day.

If you take more Vargatef than you should

Contact your doctor or pharmacist immediately.

If you forget to take Vargatef

Do not take a double dose to make up for forgotten doses. Take your next dose of Vargatef according to the established schedule and at the recommended dose prescribed by your doctor or pharmacist.

If you stop taking Vargatef

Do not stop taking Vargatef without consulting your doctor first. It is important to take this medicine every day while your doctor prescribes it. If you do not take this medicine as prescribed by your doctor, this cancer treatment may not work properly.

If you have any other questions about 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 should pay special attention if you experience the following side effects during treatment with Vargatef:

• Diarrhea(very common, may affect more than 1 in 10 people)

Diarrhea can cause a loss of important fluids and salts (electrolytes, such as sodium or potassium) from the body. At the first symptoms of diarrhea, drink plenty of fluids and consult your doctor immediately. Start appropriate antidiarrheal treatment as soon as possible, for example, by taking loperamide, after consulting your doctor.

• Febrile neutropeniaandsepsis(common, may affect up to 1 in 10 people)

Treatment with Vargatef may cause a reduction in the number of a type of white blood cell (neutropenia), which are important for the body to react adequately to bacterial or fungal infections. As a consequence of neutropenia, fever (febrile neutropenia) and blood infection (sepsis) may occur. Tell your doctor immediately if you have fever, chills, rapid breathing, or a rapid heart rate.

During treatment with Vargatef, your doctor will perform periodic blood tests to check your blood cells and see if there are signs of infection, such as inflammation, fever, or fatigue.

The following side effects have been observed during treatment with this medicine:

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

• Diarrhea; see above
• Pain, numbness, and/or tingling in the fingers of the hands or feet (peripheral neuropathy)
• Feeling like vomiting (nausea)
• Vomiting

• Abdominal pain

• Bleeding

• Decrease in the number of white blood cells (neutropenia)
• Inflammation of the mucous membranes lining the digestive tract, including ulcers and sores in the mouth (mucositis, including stomatitis)
• Rash
• Decreased appetite

• Electrolyte imbalance

• Increased values of liver enzymes (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase in blood), which are detected in blood tests
• Hair loss (alopecia)

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

• Blood infection (sepsis); see above
• Decrease in the number of white blood cells accompanied by fever (febrile neutropenia)
• Blood clots in the veins (venous thromboembolism), especially in the legs (symptoms include pain, redness, swelling, and warmth in a limb), which can move through the blood vessels to the lungs and cause chest pain and difficulty breathing (if you notice any of these symptoms, seek medical attention immediately)
• High blood pressure (hypertension)
• Loss of fluids (dehydration)

• Abscesses
• Low platelet count (thrombocytopenia)
• Jaundice (hyperbilirubinemia)
• Increased values of liver enzymes (gamma-glutamyltransferase) in the blood, which are detected in blood tests
• Weight loss
• Itching
• Headache
• Increased amount of protein in the urine (proteinuria)

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

• Appearance of holes in the wall of the intestines (gastrointestinal perforation)
• Serious liver problems
• Pancreatitis (inflammation of the pancreas)
• Heart attack
• Kidney failure

Frequency not known (cannot be estimated from the available data)

• Inflammation of the large intestine
• Enlargement and weakening of the wall of a blood vessel or tear in the wall of a blood vessel (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)

Reporting of side effects

If you experience 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 through the national reporting system included in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Vargatef

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

Do not use this medicine after the expiry date which is stated on the carton and blister packs. The expiry date is the last day of the month shown.

Do not store above 25°C.

Store in the original package 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).

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Package Contents and Additional Information

Compositionof Vargatef

The active ingredient is nintedanib. Each soft capsule contains 150 mg of nintedanib (as esilate).

The excipients are:

Capsulecontent:Medium-chain triglycerides, hard fat, soy lecithin (E322)

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

Appearanceof the Productand Package Contents

Vargatef 150 mg soft capsules (capsules) are oblong, opaque, and brown in color (approximately 18 x 7 mm), marked on one side with the Boehringer Ingelheim company logo and "150".

A carton contains 60 capsules (6 aluminum blisters with 10 capsules each).

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 request more information about this medicinal product by contacting the local representative of the marketing authorization holder:

Date of the Last Revision of this Leaflet:

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu.