Nipfilan

Package leaflet: Information for the patient

Nipfilan 100 mg soft capsules

Nintedanib
Generic medicine
Please read all of this leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Nipfilan is and what it is used for

Nipfilan contains the active substance nintedanib, a medicine belonging to the class of so-called
tyrosine kinase inhibitors, and is used for the treatment of the following diseases:

Idiopathic pulmonary fibrosis (IPF) in adults
IPF is a condition in which, over time, lung tissue becomes thick, stiff, and scarred. As a result, scarring reduces the ability to transfer oxygen from the lungs into the bloodstream, making deep breathing difficult. This medicine helps reduce the progression of further scarring and lung stiffening.

Other chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype in adults
In addition to IPF, there are other conditions in which, over time, lung tissue becomes thick, stiff, and scarred (pulmonary fibrosis) and continues to worsen (progressive phenotype). Examples of these conditions include hypersensitivity pneumonitis, autoimmune ILDs (e.g., ILD associated with rheumatoid arthritis), idiopathic nonspecific interstitial pneumonia, unclassifiable idiopathic interstitial pneumonia, and other ILDs. This medicine helps reduce the progression of further scarring and lung stiffening.

Clinically significant progressive fibrosing interstitial lung diseases (ILDs) in children and adolescents aged 6 to 17 years
In patients with pediatric interstitial lung disease (chILD), pulmonary fibrosis may occur. When this happens, over time, the lung tissue in children and adolescents becomes thick, stiff, and scarred. This medicine helps reduce the progression of further scarring and lung stiffening.

Interstitial lung disease associated with systemic sclerosis (SSc-ILD) in adults, adolescents, and children aged 6 years and older
Systemic sclerosis (SSc), or scleroderma (and juvenile systemic sclerosis in children and adolescents), is a rare chronic autoimmune disease affecting connective tissue in various 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 referred to as interstitial lung disease (ILD), and the condition is therefore known as SSc-ILD. Pulmonary fibrosis reduces the lungs' ability to transfer oxygen into the blood and impairs respiratory function. This medicine helps reduce the progression of further scarring and lung stiffening.

2. What you should know before taking Nipfilan

Do not take Nipfilan

• if you are allergic to nintedanib or to any of the other ingredients of this medicine (listed in section 6);
• if you are pregnant.

Warnings and precautions
Talk to your doctor or pharmacist before taking Nipfilan:

• 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 blood-thinning medicines (for example, warfarin, phenprocoumon, or heparin) to prevent blood clots;
• if you are taking pirfenidone, which may increase the risk of developing diarrhoea, nausea, vomiting, and liver problems;
• if you have or have had heart problems (for example, a heart attack);
• if you have recently undergone surgery. Nintedanib may impair wound healing. Therefore, treatment with this medicine will usually be stopped for a certain period around the time of surgery. Your doctor will decide when you can restart treatment with this medicine;
• if you have high blood pressure;
• if you have or have had high blood pressure in the blood vessels of the lungs (pulmonary hypertension);
• if you have or have had an aneurysm (a weakened and bulging blood vessel wall) or a tear in the wall of a blood vessel.

Based on this information, your doctor may perform blood tests, for example, to check liver function. Your doctor will discuss the test results with you and decide whether you can receive Nipfilan.
Immediately inform your doctor while taking this medicine:

• if you develop diarrhoea. It is essential to treat diarrhoea early (see section 4);
• if you experience vomiting or feel sick (nausea);
• if you have unexplained symptoms such as yellowing of the skin or the whites of the eyes (jaundice), dark or brown-coloured urine (like tea), pain in the upper right part of the stomach area (abdomen), bleeding or bruising more easily than usual, or feel unusually tired. These may be symptoms of serious liver problems;
• if you have severe stomach pain, fever, chills, feel unwell, vomiting, or abdominal stiffness or swelling, as these may be symptoms of a hole in the intestinal wall (“gastrointestinal perforation”). Inform your doctor also if you have previously had peptic ulcers or diverticular disease, or if you are taking concomitant anti-inflammatory medicines (NSAIDs) (used to relieve pain and treat swelling) or steroids (used for inflammation and allergies), as this may increase this risk;
• if you experience a combination of severe stomach pain or cramps, red blood in the stools, or diarrhoea, as these may be symptoms of intestinal inflammation due to inadequate blood supply;
• if you have pain, swelling, redness, or warmth in a limb, as these may be symptoms of a blood clot in a vein (a type of blood vessel);
• if you feel pressure or pain in your chest, particularly on the left side of your body, pain in your neck, jaw, shoulder, or arm, rapid heartbeat, shortness of breath, nausea, or vomiting, as these may be symptoms of a heart attack;
• if you have significant bleeding;
• if you develop bruises, bleeding, fever, fatigue, or confusion. These may be signs of damage to blood vessels known as thrombotic microangiopathy (TMA);
• if you experience symptoms such as headache, changes in vision, confusion, seizures, or other neurological disturbances such as weakness in one arm or leg, with or without high blood pressure. These may be symptoms of a brain condition called reversible posterior encephalopathy syndrome (PRES).

Children and adolescents
Nipfilan must not be taken by children under 6 years of age.
Your doctor may schedule regular dental check-ups at least once every 6 months until your teeth are fully developed, and monitor your growth annually (bone imaging tests) while you are taking this medicine.

Other medicines and Nipfilan
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including herbal medicines and over-the-counter medicines.
Nipfilan may interact with certain medicines. The following are examples of medicines that may increase nintedanib levels in the blood, potentially increasing the risk of side effects (see section 4):

• a medicine used to treat fungal infections (ketoconazole);
• a medicine used to treat bacterial infections (erythromycin);
• a medicine that modifies the immune system (cyclosporine).

The following are examples of medicines that may decrease nintedanib levels in the blood, potentially reducing the effectiveness of Nipfilan:

• 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, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy
Do not take this medicine during pregnancy, as it may harm the unborn child and cause birth defects.
Before starting treatment with this medicine, you must have a pregnancy test to confirm that you are not pregnant. Speak to your doctor.

Contraception

• Women of childbearing potential must use a highly effective method of contraception to prevent pregnancy when starting Nipfilan, during treatment with Nipfilan, and for at least 3 months after stopping treatment.
• Discuss with your doctor the most appropriate contraceptive methods for your situation.
• Vomiting and/or diarrhoea or other gastrointestinal disorders may affect the absorption of oral hormonal contraceptives, such as the pill, and may reduce their effectiveness. Therefore, if you experience these symptoms, consult your doctor to consider a more appropriate alternative contraceptive method.
• Immediately inform your doctor or pharmacist if you become pregnant or suspect you are pregnant during treatment with this medicine.

Breastfeeding
Do not breastfeed during treatment with this medicine, as there may be a risk of harm to breastfed infants.

Driving and using machines
This medicine may have a slight influence on the ability to drive and use machines. If you do not feel well, you should not drive or operate machinery.

3. How to take Nipfilan

Take this medicine exactly as instructed by your doctor or pharmacist. If
you have any doubts, consult your doctor or pharmacist.
Take the capsules twice daily, approximately 12 hours apart and at similar times each day, for
example one capsule in the morning and one capsule in the evening. This ensures that a constant
level of nintedanib is maintained in the bloodstream. Swallow the capsules whole with water and do
not chew them. It is recommended to take the capsules with food, for example during a meal or
immediately before or after. Do not open or crush the capsule (see section 5).
To make swallowing easier, you may take the capsules with a small amount (one teaspoon) of soft
food, such as apple puree or chocolate pudding, cold or at room temperature. Swallow the capsules
immediately and do not chew them, to ensure they remain intact.
Adults
The recommended dose is one 100 mg capsule twice daily (for a total of 200 mg daily).
Do not take a higher dose than the recommended dose of two Nipfilan 100 mg capsules per
day.
If you do not tolerate the recommended dose of two Nipfilan 100 mg capsules per day (see possible
side effects in section 4), your doctor may advise you to discontinue treatment with this
medicine. Do not reduce the dose or stop treatment without first consulting your doctor.
Use in children and adolescents
The recommended dose depends on the patient's body weight.
Inform your doctor if the patient's weight drops below 13.5 kg at any time during treatment.
Inform your doctor if you have liver problems.
Your doctor will determine the correct dose. Your doctor may adjust the dose as treatment
continues.
If you do not tolerate the recommended daily dose of Nipfilan capsules (for possible side effects, see
section 4), your doctor may reduce the daily dose of Nipfilan.
Do not reduce the dose or stop treatment without first consulting your doctor.
Dosage of Nipfilan capsules according to weight in children and adolescents:

*Nipfilan is available only as 100 mg and 150 mg soft capsules. Therefore, it is not possible to administer
Nipfilan to pediatric patients requiring a dose lower than 100 mg. If an alternative dose is required, other
nintedanib-containing products offering such an option must be used.
If you take more Nipfilan than you should
Contact your doctor or pharmacist immediately.
If you forget to take Nipfilan
Do not take two capsules at the same time if you have missed the previous dose.
Take the next scheduled 100 mg dose of Nipfilan at the next planned and recommended time, as directed by your doctor or pharmacist.
If you stop taking Nipfilan
Do not stop treatment with Nipfilan without first consulting your doctor. It is important to take this medicine every day for the entire duration indicated by your doctor.
If you have any questions about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
You should pay particular attention if you experience the following side effects during treatment with
Nipfilan:
Diarrhoea (very common, may affect more than 1 in 10 people):
Diarrhoea may lead to dehydration: loss of fluids and important salts (electrolytes such as sodium or
potassium) from the body. At the first signs of diarrhoea, drink plenty of fluids and contact your doctor
immediately. Start appropriate treatment for diarrhoea as soon as possible, for example with loperamide.
During treatment with nintedanib (the active substance in this medicine), the following side effects have also been observed.
Contact your doctor if you experience any side effect.

Idiopathic Pulmonary Fibrosis (IPF)
Very common side effects (may affect more than 1 in 10 people)

• Feeling unwell (nausea)
• Pain in the lower part of the body (abdomen)
• Abnormal liver function test results

Common side effects (may affect less than 1 in 10 people)

• Vomiting
• Loss of appetite
• Weight loss
• Bleeding
• Skin rash
• Headache

Uncommon side effects (may affect less than 1 in 100 people)

• Pancreatitis
• Inflammation of the large intestine
• Serious liver problems
• Low platelet count (thrombocytopenia)
• High blood pressure (hypertension)
• Jaundice, i.e. yellowing of the skin and whites of the eyes due to high levels of bilirubin
• Itching (pruritus)
• Heart attack
• Hair loss (alopecia)
• Increased amount of protein in the urine (proteinuria)

Not known (frequency cannot be estimated from the available data)

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

Other chronic fibrosing interstitial lung diseases (ILD) with progressive phenotype
Very common side effects (may affect more than 1 in 10 people)

• Feeling unwell (nausea)
• Vomiting
• Loss of appetite
• Pain in the lower part of the body (abdomen)
• Abnormal liver function test results

Common side effects (may affect less than 1 in 10 people)

• Weight loss
• High blood pressure (hypertension)
• Bleeding
• Serious liver problems
• Skin rash
• Headache

Uncommon side effects (may affect less than 1 in 100 people)

• Pancreatitis
• Inflammation of the large intestine
• Low platelet count (thrombocytopenia)
• Jaundice, i.e. yellowing of the skin and whites of the eyes due to high levels of bilirubin
• Itching (pruritus)
• Heart attack
• Hair loss (alopecia)
• Increased amount of protein in the urine (proteinuria)

Not known (frequency cannot be estimated from the available data)

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

Interstitial lung disease associated with systemic sclerosis (SSc-ILD)
Very common side effects (may affect more than 1 in 10 people)

• Feeling unwell (nausea)
• Vomiting
• Pain in the lower part of the body (abdomen)
• Abnormal liver function test results

Common side effects (may affect less than 1 in 10 people)

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

Uncommon side effects (may affect less than 1 in 100 people)

• Inflammation of the large intestine
• Serious liver problems
• Kidney failure
• Low platelet count (thrombocytopenia)
• Skin rash
• Itching (pruritus)

Not known (frequency cannot be estimated from the available data)

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

Fibrosing interstitial lung diseases (ILD) in children and adolescents
Side effects in children and adolescents are similar to those in adult patients. Contact your doctor if any
side effect occurs.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
Reporting side effects helps provide more information on the safety of this medicine.

5. How to store Nipfilan

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister after
Exp. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not use this medicine if you notice that the blister containing the capsules is open or if a capsule is broken.
If you come into contact with the capsule contents, wash your hands immediately with plenty of water (see section 3).
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Nipfilan contains

• The active substance is nintedanib. Each capsule contains 100 mg of nintedanib (as esilate).
• The other components are:
  • Capsule contents: medium-chain triglycerides, solid semisynthetic glycerides, and polyglycerol-3 dioleate
  • Capsule shell: gelatin, glycerol, titanium dioxide (E171), red iron oxide (E172), yellow iron oxide (E172), purified water.
  • Printing ink: shellac, carmine (E120), propylene glycol (E1520), and simethicone.

Description of the appearance of Nipfilan and package contents
Nipfilan 100 mg capsules are soft gelatin capsules, peach-colored, opaque, oblong, containing a yellow viscous suspension, printed with “NT 100” in red ink, approximately 16 mm in length.
Nipfilan 100 mg soft capsules are available in perforated blisters made of OPA/Al/PVC-Aluminum, divided into unit doses.
Pack sizes:
30 x 1 soft capsule
60 x 1 soft capsule
Multiple packs of 120 (2 packs containing 60 x 1) soft capsules
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
G.L. Pharma GmbH
Schlossplatz 1
8502 Lannach
Austria

Manufacturers
Pharmadox Healthcare Limited
KW20A Kordin Industrial Park
Paola PLA 3000
Malta
Adalvo Limited
Malta Life Sciences Park Building 1 Level 4
Sir Temi Zammit Buildings
San Gwann Industrial Estate, SGN 3000
Malta
QUALIMETRIX S.A.
579 MESOGEION AVENUE AGIA
PARASKEVI, Athens, 15343,
Greece

Distribution License Holder:
G.L. Pharma Italy S.r.l., [email protected]

This medicinal product is authorized in the European Economic Area countries under the following names:
Iceland Nipfilan 100 mg mjúk hylki
Austria Nipfilan 100 mg Weichkapseln
Germany Nipfilan 100 mg Weichkapseln
Italy Nipfilan

Patient information leaflet

Nipfilan 150 mg soft capsules

Nintedanib
Generic medicine
Please read this leaflet carefully before taking this medicine, as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Nipfilan is and what it is used for

Nipfilan contains the active substance nintedanib, a medicine belonging to the class of so-called
tyrosine kinase inhibitors, and is used for the treatment of the following conditions:

Idiopathic pulmonary fibrosis (IPF) in adults
IPF is a condition in which, over time, lung tissue becomes thick, stiff, and scarred. As a result, scarring reduces the ability to transfer oxygen from the lungs into the bloodstream, making deep breathing difficult. This medicine helps reduce the development of further scarring and lung stiffening.

Other chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype in adults
In addition to IPF, there are other conditions in which, over time, lung tissue becomes thick, stiff, and scarred (pulmonary fibrosis) and continues to worsen (progressive phenotype). Examples of these conditions include hypersensitivity pneumonitis, autoimmune ILDs (e.g., ILD associated with rheumatoid arthritis), idiopathic nonspecific interstitial pneumonia, unclassifiable idiopathic interstitial pneumonia, and other ILDs. This medicine helps reduce the development of further scarring and lung stiffening.

Clinically significant progressive fibrosing interstitial lung diseases (ILDs) in children and adolescents aged 6 to 17 years
In patients with pediatric interstitial lung disease (chILD), pulmonary fibrosis may occur. When this happens, the lung tissue of children and adolescents becomes thick, stiff, and scarred over time. This medicine helps reduce further scarring and lung stiffening.

Interstitial lung disease associated with systemic sclerosis (SSc-ILD) in adults, adolescents, and children aged 6 years and older
Systemic sclerosis (SSc), or scleroderma (and juvenile systemic sclerosis in children and adolescents), is a rare chronic autoimmune disease affecting connective tissue in various 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 referred to as interstitial lung disease (ILD), and the condition is therefore called SSc-ILD. Lung fibrosis reduces the lungs' ability to transfer oxygen into the blood and impairs breathing capacity. This medicine helps reduce the development of further scarring and lung stiffening.

2. What you should know before taking Nipfilan

Do not take Nipfilan

• if you are allergic to nintedanib or to any of the other ingredients of this medicine (listed in section 6);
• if you are pregnant.

Warnings and precautions
Talk to your doctor or pharmacist before taking Nipfilan:

• 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 that thin the blood (for example, warfarin, phenprocoumon, or heparin) to prevent blood clots;
• if you are taking pirfenidone, which may increase the risk of developing diarrhoea, nausea, vomiting, and liver problems;
• if you have or have had heart problems (for example, a heart attack);
• if you have recently undergone surgery. Nintedanib may impair wound healing. Therefore, treatment with this medicine will usually be stopped for a certain period around the time of surgery. Your doctor will decide when you can restart treatment with this medicine;
• if you have high blood pressure;
• if you have abnormally high pressure in the blood vessels of your lungs (pulmonary hypertension);
• if you have or have had an aneurysm (a bulge 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 carry out blood tests, for example, to check how well your liver is working. Your doctor will discuss the test results with you and decide whether you can take Nipfilan.
Inform your doctor immediately while taking this medicine:

• if you develop diarrhoea. It is essential to treat diarrhoea early (see section 4);
• if you experience vomiting or feeling unwell (nausea);
• if you have unexplained symptoms such as yellowing of the skin or the whites of the eyes (jaundice), dark or brown-coloured urine (like tea), pain in the upper right part of the stomach area (abdomen), bleeding or bruising more easily than usual, or feeling tired. These may be symptoms of serious liver problems;
• if you have severe stomach pain, fever, chills, feeling unwell, vomiting, or abdominal stiffness or swelling, as these may be symptoms of a hole in the wall of the intestine (“gastrointestinal perforation”). Also inform your doctor if you have previously had peptic ulcers or diverticular disease, or if you are taking concomitant anti-inflammatory medicines (NSAIDs) (used to relieve pain and treat swelling) or steroids (used for inflammation and allergies), as this may increase this risk;
• if you have a combination of severe stomach pain or cramps, red blood in the stools, or diarrhoea, as these may be symptoms of intestinal inflammation due to inadequate blood supply;
• if you have pain, swelling, redness, or warmth in a limb, as these may be symptoms of a blood clot in a vein (a type of blood vessel);
• if you feel pressure or pain in your chest, especially on the left side of your body, pain in your neck, jaw, shoulder, or arm, rapid heartbeat, shortness of breath, nausea, or vomiting, as these may be symptoms of a heart attack;
• if you have significant bleeding;
• if bruising, bleeding, fever, tiredness, and confusion occur. These may be signs of damage to blood vessels known as thrombotic microangiopathy (TMA);
• if you experience symptoms such as headache, changes in vision, confusion, seizures, or other neurological disturbances such as weakness in an arm or leg, with or without high blood pressure. These may be symptoms of a brain condition called reversible posterior encephalopathy syndrome (PRES).

Children and adolescents
Nipfilan must not be taken by children under 6 years of age.
Your doctor may schedule regular dental check-ups at least once every 6 months until your teeth have fully developed and may monitor your growth annually (bone imaging tests) while you are taking this medicine.

Other medicines and Nipfilan
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including herbal medicines and over-the-counter medicines.
Nipfilan may interact with certain medicines. The following are examples of medicines that may increase nintedanib levels in the blood, potentially increasing the risk of side effects (see section 4):

• a medicine used to treat fungal infections (ketoconazole);
• a medicine used to treat bacterial infections (erythromycin);
• a medicine that modifies the immune system (cyclosporine).

The following are examples of medicines that may decrease nintedanib levels in the blood, potentially reducing the effectiveness of Nipfilan:

• 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, think you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy
Do not take this medicine during pregnancy, as it may harm the unborn child and cause birth defects.
Before starting treatment with this medicine, you must have a pregnancy test to confirm that you are not pregnant. Speak to your doctor.

Contraception

• Women of childbearing potential must use a highly effective method of contraception to avoid pregnancy when starting Nipfilan, during treatment with Nipfilan, and for at least 3 months after stopping treatment.
• Discuss with your doctor the most suitable contraceptive methods for your situation.
• Vomiting and/or diarrhoea or other gastrointestinal disorders may affect the absorption of oral hormonal contraceptives, such as the pill, and may reduce their effectiveness. Therefore, if you experience these symptoms, consult your doctor to consider a more appropriate alternative contraceptive method.
• Inform your doctor or pharmacist immediately if you become pregnant or suspect you are pregnant during treatment with this medicine.

Breastfeeding
Do not breastfeed during treatment with this medicine, as there may be a risk of harm to breastfed infants.

Driving and using machines
This medicine may have a slight influence on the ability to drive and use machines. If you do not feel well, you should not drive or operate machinery.

3. How to take Nipfilan

Take this medicine exactly as directed by your doctor or pharmacist. If
you have any doubts, consult your doctor or pharmacist.
Take the capsules twice daily, approximately 12 hours apart and at approximately the same times each day,
for example one capsule in the morning and one capsule in the evening. This ensures that a constant level
of nintedanib is maintained in the bloodstream. Swallow the capsules whole with water and do not chew them.
It is recommended to take the capsules with food, for example during a meal or immediately
before or after. Do not open or crush the capsule (see section 5).
To make swallowing easier, you may take the capsules with a small amount (one teaspoon) of soft food,
such as apple puree or chocolate pudding, cold or at room temperature. Swallow the
capsules immediately and do not chew them, to ensure they remain intact.
Adults
The recommended dose is one 150 mg capsule twice daily (for a total of 300 mg daily).
Do not take a higher dose than the recommended dose of two Nipfilan 150 mg capsules per
day.
If you do not tolerate the recommended dose of two Nipfilan 150 mg capsules per day (see possible
side effects in section 4), your doctor may advise you to reduce the daily dose of Nipfilan.
Do not reduce the dose or stop treatment without first consulting your doctor.
Your doctor may reduce the recommended dose to 100 mg twice daily (for a total of 200 mg
daily). In this case, your doctor will prescribe Nipfilan 100 mg capsules for your
treatment. Do not take more than the recommended dose of two 100 mg Nipfilan capsules per day
if your daily dose has been reduced to 200 mg daily.
Use in children and adolescents
The recommended dose depends on the patient's body weight.
Inform your doctor if the patient's weight drops below 13.5 kg at any time during treatment.
Inform your doctor if you have liver problems.
Your doctor will determine the correct dose. The dose may be adjusted by your doctor as treatment
continues.
If you do not tolerate the recommended daily dose of Nipfilan capsules (for possible
side effects, see section 4), your doctor may reduce the daily dose of Nipfilan.
Do not reduce the dose or stop treatment without first consulting your doctor.
Dosage of Nipfilan capsules according to weight in children and adolescents:

*Nintedanib is available only in 100 mg and 150 mg soft capsules. Therefore, it is not possible to administer
Nintedanib to pediatric patients requiring a dose lower than 100 mg. If an alternative dosage is required,
other nintedanib-containing products offering such an option must be used.
If you take more Nipfilan than you should
Contact your doctor or pharmacist immediately.
If you forget to take Nipfilan
Do not take two capsules at the same time if you have missed a dose.
Take the next 150 mg dose of Nipfilan at the next scheduled time, as prescribed by your doctor or pharmacist.
If you stop taking Nipfilan
Do not stop treatment with Nipfilan without first consulting your doctor. It is important to take this medicine every day for the entire duration prescribed by your doctor.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
You should be particularly cautious if you experience the following side effects during treatment with
Nipfilan:
Diarrhoea ( very common , may affect more than 1 in 10 people):
Diarrhoea may lead to dehydration: loss of fluids and important salts (electrolytes such as sodium or
potassium) from the body. At the first signs of diarrhoea, drink plenty of fluids and contact your doctor
immediately. Start appropriate treatment for diarrhoea as soon as possible, for example with loperamide.
The following side effects have also been observed during treatment with nintedanib (the active substance in this medicine).
Contact your doctor if you experience any side effect.

Idiopathic pulmonary fibrosis (IPF)
Very common side effects (may affect more than 1 in 10 people)

• Feeling unwell (nausea)
• Pain in the lower part of the body (abdomen)
• Abnormal liver function test results

Common side effects (may affect less than 1 in 10 people)

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

Uncommon side effects (may affect less than 1 in 100 people)

• Pancreatitis
• Inflammation of the large intestine (colitis)
• Serious liver problems
• Low platelet count (thrombocytopenia)
• High blood pressure (hypertension)
• Jaundice, i.e. yellowing of the skin and whites of the eyes due to high bilirubin levels
• Itching (pruritus)
• Heart attack
• Hair loss (alopecia)
• Increased protein in the urine (proteinuria)

Not known (frequency cannot be estimated from the available data)

• Kidney failure
• Weakening and widening of a blood vessel wall or a tear in the blood vessel wall (aneurysms and arterial dissections)
• Brain condition with symptoms such as headache, vision changes, confusion, seizures, or other neurological disturbances such as weakness in one arm or leg, with or without high blood pressure (reversible posterior encephalopathy syndrome)

Other chronic fibrosing interstitial lung diseases (ILD) with progressive phenotype
Very common side effects (may affect more than 1 in 10 people)

• Feeling unwell (nausea)
• Vomiting
• Loss of appetite
• Pain in the lower part of the body (abdomen)
• Abnormal liver function test results

Common side effects (may affect less than 1 in 10 people)

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

Uncommon side effects (may affect less than 1 in 100 people)

• Pancreatitis
• Inflammation of the large intestine (colitis)
• Low platelet count (thrombocytopenia)
• Jaundice, i.e. yellowing of the skin and whites of the eyes due to high bilirubin levels
• Itching (pruritus)
• Heart attack
• Hair loss (alopecia)
• Increased protein in the urine (proteinuria)

Not known (frequency cannot be estimated from the available data)

• Kidney failure
• Weakening and widening of a blood vessel wall or a tear in the blood vessel wall (aneurysms and arterial dissections)
• Brain condition with symptoms such as headache, vision changes, confusion, seizures, or other neurological disturbances such as weakness in one arm or one leg, with or without high blood pressure (reversible posterior encephalopathy syndrome)

Interstitial lung disease associated with systemic sclerosis (SSc-ILD)
Very common side effects (may affect more than 1 in 10 people)

• Feeling unwell (nausea)
• Vomiting
• Pain in the lower part of the body (abdomen)
• Abnormal liver function test results

Common side effects (may affect less than 1 in 10 people)

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

Uncommon side effects (may affect less than 1 in 100 people)

• Inflammation of the large intestine (colitis)
• Serious liver problems
• Kidney failure
• Low platelet count (thrombocytopenia)
• Rash
• Itching (pruritus)

Not known (frequency cannot be estimated from the available data)

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

Fibrosing interstitial lung diseases (ILD) in children and adolescents
Side effects in children and adolescents are similar to those observed in adult patients. Contact your doctor if any side effect occurs.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist.
You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Nipfilan

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister after
Exp. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not use this medicine if you notice that the blister containing the capsules is open or if a capsule is broken.
If you come into contact with the capsule contents, wash your hands immediately with plenty of water (see section 3).
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Nipfilan contains

• The active substance is nintedanib. Each capsule contains 150 mg of nintedanib (as esilate).
• The other components are:
  • Capsule contents: medium-chain triglycerides, solid semisynthetic glycerides, and polyglycerol-3 dioleate
  • Capsule shell: gelatin, glycerol, titanium dioxide (E171), red iron oxide (E172), yellow iron oxide (E172), purified water.
  • Printing ink: shellac, black iron oxide (E172), and propylene glycol (E1520).

Description of the appearance of Nipfilan and package contents
Nipfilan 150 mg capsules are brown, opaque, soft gelatin capsules containing a yellow, viscous suspension, imprinted with "NT 150" in black ink, approximately 17 mm in length.
Nipfilan 150 mg soft capsules are available in perforated blisters made of OPA/Al/PVC-Aluminum, divided into single-dose units.
Pack sizes:
30 x 1 soft capsule
60 x 1 soft capsule
Multiple pack of 120 (2 packs of 60 x1) soft capsules
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
G.L. Pharma GmbH
Schlossplatz 1
8502 Lannach
Austria
Manufacturers
Pharmadox Healthcare Limited
KW20A Kordin Industrial Park
Paola PLA 3000
Malta
Adalvo Limited
Malta Life Sciences Park Building 1 Level 4
Sir Temi Zammit Buildings
San Gwann Industrial Estate, SGN 3000
Malta
QUALIMETRIX S.A.
579 MESOGEION AVENUE AGIA
PARASKEVI, Athens, 15343,
Greece

Marketing Authorization Holder in Italy:
G.L. Pharma Italy S.r.l., [email protected]

This medicinal product is authorized in the European Economic Area member states under the following names:
Iceland Nipfilan 150 mg mjúk hylki
Austria Nipfilan 150 mg Weichkapseln
Germany Nipfilan 150 mg Weichkapseln
Italy Nipfilan