Vatrana 100 mg Capsules

• VATRANA contains the active substance nintedanib and it is used for the treatment of Idiopathic Pulmonary Fibrosis (IPF), other chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype and systemic sclerosis associated interstitial lung disease (SSc-ILD) in adults.

• Idiopathic pulmonary fibrosis (IPF): 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. VATRANA helps to reduce further scarring and stiffening of the lungs.

• Other chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype 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. VATRANA helps to reduce further scarring and stiffening of the lungs.

• Systemic sclerosis associated interstitial lung disease (SSc-ILD) Systemic sclerosis (SSc), also known as scleroderma, 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. VATRANA helps to reduce further scarring and stiffening of the lungs.

• Do not take VATRANA - if you are hypersensitive (allergic) to nintedanib, peanut or soya, or any of the other ingredients of VATRANA (listed in section 6). - if you are pregnant.

Warnings and precautions

• Take special care and talk to your doctor or pharmacist before taking VATRANA: - if you have or ever had liver problems, - if you have or ever had problems with your kidney, or if an increased amount of protein has been detected in your urine, - if you have or ever had bleeding problems, - if you take medicines (such as warfarin, phenprocoumon or heparin) to prevent blood clotting, - if you take pirfenidone as this may increase the risk of having diarrhoea, nausea, vomiting and liver problems, - if you have or ever had problems with your heart (for example a heart attack) as your doctor will do tests to monitor your heart function, - if you have recently had surgery. VATRANA may affect the way your wounds heal. Therefore, your treatment with VATRANA will usually be stopped for a while if you are having a surgery. Your doctor will decide when to resume your treatment with VATRANA, - 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. Based on this information your doctor may do some blood tests, for example to check your liver function. Your doctor will discuss the results of these tests with you and decide whether you may receive VATRANA.

• Inform your doctor immediately while taking VATRANA: - 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. These 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 being concomitantly treated with anti-inflammatory drugs (NSAIDs) (used for pain relief and swelling) or steroids (used for inflammation and allergies), as this may increase the risk of gastrointestinal perforation; - if you have a combination of severe pain or cramping in your stomach, red blood in your stool or diarrhoea as these could be symptoms of a bowel inflammation from inadequate blood supply; - if you have pain, swelling, reddening, warmth of a limb as these 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 these 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).

Children and adolescents

VATRANA should not be taken by children and adolescents under 18 years of age.

Other medicines and VATRANA

Always tell your healthcare provider if you are taking any other medicine. (This includes complementary or traditional medicines.) VATRANA can interact with certain other medicines. The following medicines are examples that may increase the levels of VATRANA 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 (ciclosporin). The following medicines are examples that may lower the levels of VATRANA in your blood and thus may reduce the effectiveness of VATRANA: - an antibiotic used to treat tuberculosis (rifampicin) - medicines to treat seizures (carbamazepine, phenytoin) - a herbal medicine to treat depression (St. John’s wort).

Do not share medicines prescribed for you with any other person. Always take VATRANA exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are unsure. The usual dose is one capsule of 150 mg 12 hourly (a total of 300 mg per day). Take the capsules 12 hours apart at 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 as in VATRANA 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).

Do not take more than the usual dose of one VATRANA 150 mg capsule 12 hourly. If you do not tolerate the recommended dose of one VATRANA 150 mg capsule 12 hourly (see possible side effects in section 4) your doctor may reduce the daily dose of VATRANA. Do not reduce the dose or stop the treatment by yourself without consulting your doctor first. Your doctor may reduce your usual dose to 100 mg 12 hourly (a total of 200 mg per day). In this case your doctor will prescribe VATRANA 100 mg capsules for your treatment. Do not take more than the usual dose of one VATRANA 100 mg capsule 12 hourly if your daily dose was reduced to 200 mg per day. If you do not tolerate the recommended dose of one VATRANA 100 mg capsule 12 hourly (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. Your doctor will tell you how long your treatment with VATRANA will last. Do not stop treatment early because it will affect the management of your condition. If you have the impression that the effect of VATRANA is too strong or too weak, tell your doctor or pharmacist.

If you take more VATRANA than you should In the event of overdosage, consult your doctor or pharmacist. If neither is available, contact the nearest hospital or poison control centre. If you forget to take VATRANA Do not take two capsules together if you have forgotten to take your earlier dose. You should take your next 100 mg or 150 mg dose of VATRANA as planned at the next scheduled time recommended by your doctor or pharmacist. If you stop taking VATRANA Do not stop taking VATRANA without consulting your doctor first. It is important to take VATRANA every day, as long as your doctor prescribes it for you. If you have any further questions on the use of VATRANA, ask your doctor or pharmacist.

VATRANA can have side effects. Not all side effects reported for VATRANA are included in this leaflet. Should your general health worsen or if you experience any untoward effects while taking VATRANA, please consult your healthcare professional for advice. Diarrhoea is frequently experienced. Diarrhoea may lead to dehydration: a loss of fluid and important salts (electrolytes, such as sodium or potassium) from your body. At the first signs of diarrhoea drink plenty of fluids and contact your doctor immediately. Start appropriate anti-diarrhoeal treatment, e.g., with loperamide, as soon as possible.

The following other side effects were observed during treatment with VATRANA: Idiopathic pulmonary fibrosis (IPF) Frequent - Feeling sick (nausea) - Pain in the lower body (abdomen) - Abnormal liver test results - Vomiting - Loss of appetite - Weight loss - Bleeding - Rash - Headache Less frequent - Pancreatitis - Inflammation of the large bowel - Serious liver problems - Low platelet count (thrombocytopenia) - High blood pressure (hypertension) - Jaundice, that is a yellow colour to the skin and whites of the eyes due to high levels of bilirubin - Itching - Heart attack - Hair loss (alopecia) - Increased amount of protein in your urine (proteinuria) Not known (cannot be estimated from the available data) - Renal failure - An enlargement and weakening of a blood vessel wall or a tear in a blood vessel wall (aneurysms and artery dissections)

Other chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype Frequent - Feeling sick (nausea) - Vomiting - Loss of appetite - Pain in the lower body (abdomen) - Abnormal liver test results - Weight loss - High blood pressure (hypertension) - Bleeding - Serious liver problems - Rash - Headache Less frequent - Pancreatitis - Inflammation of the large bowel - Low platelet count (thrombocytopenia) - Jaundice, that is a yellow colour to the skin and whites of the eyes due to high levels of bilirubin - Itching - Heart attack - Hair loss (alopecia) - Increased amount of protein in your urine (proteinuria) Not known (cannot be estimated from the available data) - Renal failure - An enlargement and weakening of a blood vessel wall or a tear in a blood vessel wall (aneurysms and artery dissections)

Systemic sclerosis associated interstitial lung disease (SSc-ILD) Frequent - Feeling sick (nausea) - Vomiting - Pain in the lower body (abdomen) - Abnormal liver test results - Bleeding - High blood pressure (hypertension) - Loss of appetite - Weight loss - Headache Less frequent - Inflammation of the large bowel - Serious liver problems - Renal failure - Low platelet count (thrombocytopenia) - Rash - Itching Not known (cannot be estimated from the available data) - Heart attack - Pancreatitis - Jaundice, that is a yellow colour to the skin and whites of the eyes due to high levels of bilirubin - An enlargement and weakening of a blood vessel wall or a tear in a blood vessel wall (aneurysms and artery dissections) - Hair loss (alopecia) - Increased amount of protein in your urine (proteinuria)

If you notice any side effects not mentioned in this leaflet, please inform your doctor or pharmacist.

Reporting of side effects If you get 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 to SAHPRA via the “6.04 Adverse Drug Reaction Reporting Form”, found online under SAHPRA’s publications: https://www.sahpra.org.za/Publications/Index/8 . or by e-mail to: [email protected] or telephone: 080 222 6662 (toll free). By reporting side effects, you can help provide more information on the safety of VATRANA.

• Store at or below 25 °C. • Store in the original package in order to protect from exposure to high humidity and avoid excessive heat. • In order to protect from moisture, do not store in the bathroom. • Store all medicines out of reach of children.

• If you are in contact with the content of the capsule, wash off your hands immediately with plenty of water. • Do not use after the expiry date stated on the HDPE container. • Return all unused medicine to your pharmacist. • Do not dispose of unused medicine in drains or sewerage systems (e.g., toilets).