Nintedanib 100 mg Soft Capsule

• 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.

1. What Nintedanib capsules are and what are they used for
2. What you need to know before you take Nintedanib capsules
3. How to take Nintedanib capsules
4. Possible side effects
5. How to store Nintedanib capsules
6. Contents of the pack and other information

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. Nintedanib helps to reduce further scarring and stiffening of the lungs.

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. Nintedanib helps to reduce further scarring and stiffening of the lungs.

Lung fibrosis may occur in patients with Childhood Interstitial Lung Disease (chILD). When this is the case, the tissue in the lungs of children and adolescents becomes thickened, stiff, and scarred over time. Nintedanib helps to reduce further scarring and stiffening of the lungs.

Systemic sclerosis (SSc), also known as scleroderma (and juvenile systemic sclerosis in children and adolescents), 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. Nintedanib helps to reduce further scarring and stiffening of the lungs.

By blocking the activity of a group of proteins which are involved in the development of new blood vessels that cancer cells need to supply them with nutrition and oxygen, nintedanib can help stop the growth and spread of the cancer.

Nintedanib capsules are used in combination with another cancer medicine (docetaxel) to treat a cancer of the lung called non-small cell lung cancer (NSCLC). It is for adult patients whose NSCLC is of a certain type (“adenocarcinoma”) and who had already received one treatment with another medicine to treat this cancer but whose tumour started to grow again.

• if you are allergic to nintedanib, peanut or soya, or any of the other ingredients of this medicine (listed in section 6).
• for the treatment of IPF, ILD or SSc-ILD if you are pregnant.

Talk to your doctor or pharmacist before taking this medicine:

• 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, particularly recent bleeding in the lung.
• if you take blood-thinning medicines (such as warfarin, phenprocoumon, heparin or acetylsalicylic acid) to prevent blood clotting. Treatment with nintedanib may lead to a higher risk of bleeding.
• 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 or plan to have a surgery. Nintedanib may affect the way your wounds heal. Therefore, your treatment with nintedanib 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.
• if you have cancer that has spread to the brain.

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

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, diarrhoea, constipation, nausea or vomiting as these could be symptoms of a bowel inflammation from reduced blood flow (‘ischaemic colitis’).
• if you have pain, swelling, reddening, warmth of a limb or if you experience chest pain and difficulty to breathe 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).
• if you experience symptoms such as headache, vision changes, confusion, seizure or other neurologic disturbances such as weakness in an arm or a leg, with or without high blood pressure. This could be symptoms of a brain condition called posterior reversible encephalopathy syndrome (PRES).
• if you develop fever, chills, fast breathing or a fast heartbeat. These could be signs of infection or infection of the blood (sepsis) (see section 4).
• if any side effect(s) you may get (see section 4) becomes serious.

Idiopathic pulmonary fibrosis (IPF), other chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype and systemic sclerosis associated interstitial lung disease (SSc-ILD) Nintedanib should not be taken by children under 6 years of age.

Your doctor may perform regular dental examinations at least every 6 months until development of teeth is completed and monitor your growth annually (bone imaging) while you take this medicine.

Non-small cell lung cancer (NSCLC)

This medicine has not been studied in children or adolescents to treat a cancer of the lung (NSCLC) and is therefore not to be taken by children and adolescents below the age of 18 years.

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.

Nintedanib capsules 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 nintedanib:

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

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 nintedanib. 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 nintedanib, while they are taking nintedanib 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 nintedanib.

Breast-feeding

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

Fertility

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

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

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

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). For the ease of swallowing, you can take the capsules with a small amount (one teaspoonful) of cold or room temperature soft food, such as apple sauce or chocolate pudding. Swallow immediately and do not chew the capsule to ensure it stays intact.

Adults:

• For Nintedanib 100 mg capsules:
  The recommended dose is one capsule of 100 mg twice daily (a total of 200 mg per day). Do not take more than the recommended dose of two Nintedanib 100 mg capsules per day.
  If you do not tolerate the recommended dose of two Nintedanib 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.
• For Nintedanib 150 mg capsules
  The recommended dose is one capsule of 150 mg twice daily (a total of 300 mg per day).
  Do not take more than the recommended dose of two Nintedanib 150 mg capsules per day.
  If you do not tolerate the recommended dose of two Nintedanib 150 mg capsules per day (see possible side effects in section 4) your doctor may reduce the daily dose of Nintedanib capsules. 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 Nintedanib 100 mg capsules for your treatment. Do not take more than the recommended dose of two Nintedanib 100 mg capsules per day if your daily dose was reduced to 200 mg per day.

Use in children and adolescents

The recommended dose depends on the weight of the patient.

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

Tell 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 dose of Nintedanib capsules per day (see possible side effects in section 4) your doctor may reduce the daily dose of nintedanib.

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

Weight-based dosing for Nintedanib capsules in children and adolescents:

Weight range in kilograms (kg) Nintedanib 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 and above 150 mg (one 150 mg capsule or six 25 mg capsules*) twice daily

*Nintedanib is only available as 100 mg and 150 mg soft capsules. Thus, it is not possible to administer Nintedanib to paediatric patients that require less than a full 100 mg dose. If an alternative dose is required, other Nintedanib products offering such an option should be used.

Do not take Nintedanib capsules on the same day as your chemotherapy treatment with docetaxel.

Swallow the capsules whole with water and do not chew them. It is recommended to 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).

The recommended dose is:

• Nintedanib 100 mg capsules: four capsules per day (this is a total of 400 mg nintedanib per day). Do not take more than this dose.
  This daily dose should be split into two doses of two capsules about 12 hours apart, for example two capsules in the morning and two capsules in the evening.
• Nintedanib 150 mg capsules: two capsules per day (this is a total of 300 mg nintedanib per day). Do not take more than this dose.
  This daily dose should be split into two doses of one capsule about 12 hours apart, for example one capsule in the morning and one capsule in the evening.

These two doses should be taken at around the same time each day. Taking the medicine this way ensures that a steady amount of nintedanib is maintained in the body.

Dose reduction

• Nintedanib 100 mg capsules: If you cannot tolerate the recommended dose of 400 mg per day because of side effects (see section 4), your doctor may reduce the daily dose of this medicine. Do not reduce the dose or stop the treatment yourself without consulting your doctor first.
  Your doctor may reduce your recommended dose to 300 mg per day (two capsules of 150 mg). In this case your doctor will prescribe Nintedanib 150 mg capsules for your treatment.
  If necessary, your doctor may further reduce your daily dose to 200 mg per day (two capsules of 100 mg). You will be prescribed the appropriate capsule strength by your doctor if this happens.
  In both cases, you should take one capsule of the appropriate strength twice daily approximately
  12 hours apart with food (for example in the morning and in the evening) at about the same time of the day.
• Nintedanib 150 mg capsules: If you cannot tolerate the recommended dose of 300 mg per day because of side effects (see section 4), your doctor may reduce your recommended daily dose of this medicine to 200 mg per day (two capsules of 100 mg). In this case your doctor will prescribe Nintedanib 100 mg capsules for your treatment.
  You should take one capsule of this strength twice daily approximately 12 hours apart with food (for example in the morning and in the evening) at about the same time of the day. Do not reduce the dose or stop the treatment yourself without consulting your doctor first.

In case your doctor has stopped your chemotherapy with docetaxel you should continue to take Nintedanib capsules twice daily.

Contact your doctor or pharmacist immediately.

Do not take a double dose if you have forgotten to take your earlier dose. You should take your next dose of Nintedanib capsules as planned at the next scheduled time recommended by your doctor or pharmacist.

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

Non-small cell lung cancer (NSCLC)

If you do not take this medicine as prescribed by your doctor, this cancer treatment may not work properly.

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard, or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

• The active substance is nintedanib.
  Each 100 mg capsule contains 100 mg nintedanib (as esylate).
  Each 150 mg capsule contains 150 mg nintedanib (as esylate).
• The other ingredients are:
  Capsule fill: Triglycerides, medium chain, hard fat, lauroyl polyoxy-6 glycerides, and soya lecithin (E322) (see section 2).
  Capsule shell: Gelatine, glycerine, titanium dioxide (E171), iron oxide yellow (E172) and iron oxide red (E172).
  Imprinting ink: Iron oxide black (E172), hypromellose (E464), isopropyl alcohol, propylene glycol (E1520) and purified water.

Nintedanib 100 mg capsules are peach-coloured, opaque, oblong soft-gelatine capsules (approximately 16 mm × 6 mm), containing a yellow coloured oily dispersion, imprinted with 'N100' in black ink.

Nintedanib 150 mg capsules are brown-coloured, opaque, oblong soft-gelatine capsules (approximately 18 mm× 7 mm) containing a yellow coloured oily dispersion, imprinted with 'N150' in black ink.

Nintedanib capsules are available as 60 × 1 capsules in aluminium/aluminium perforated unit dose blisters.

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