Nintedanib Accord: detailed information

Package leaflet: Information for the patient

Nintedanib Accord 100 mg soft capsules

nintedanib
Please read all of this leaflet carefully before you start 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 they have the same symptoms as yours, because it may be harmful.
If you experience any side effect, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of this leaflet

What Nintedanib Accord is and what it is used for
What you need to know before taking Nintedanib Accord
How to take Nintedanib Accord
Possible side effects
How to store Nintedanib Accord
Contents of the pack and other information

1. What is Nintedanib Accord and what is it used for

Nintedanib Accord contains the active substance nintedanib, a medicine belonging to the class of so-called tyrosine kinase inhibitors, and is used to treat 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 lungs' ability to transfer oxygen into the bloodstream, making deep breathing difficult. Nintedanib Accord helps reduce further scarring and stiffening of the lungs.

Other chronic fibrosing interstitial lung diseases (ILD) 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. Nintedanib Accord helps reduce further development of scarring and lung stiffening.

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

Interstitial lung disease associated with systemic sclerosis (SSc-ILD) in adults, children, and adolescents 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 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 known as SSc-ILD. Lung fibrosis reduces the lungs' ability to transfer oxygen to the blood and impairs breathing capacity. Nintedanib Accord helps further reduce the development of scarring and stiffening of the lungs.

2. What you should know before taking Nintedanib Accord

Do not take Nintedanib Accord

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

Warnings and precautions
Talk to your doctor or pharmacist before taking Nintedanib Accord,

if you have or have had liver problems,
if you have or have had kidney problems or if increased levels of protein in your urine have been detected,
if you have or have had bleeding problems,
if you are taking medicines that thin the blood (e.g. 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 (e.g. a heart attack),
if you have recently undergone surgery. Nintedanib may affect wound healing. Therefore, treatment with Nintedanib Accord will usually be stopped for a period of time 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 bulging 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 blood tests, for example, to monitor liver function. Your doctor will discuss the test results with you and decide whether you can receive Nintedanib Accord.
Inform your doctor immediately while taking this medicine

if you develop diarrhoea. It is essential to treat diarrhoea early (see section 4, “Possible side effects”);
if you experience vomiting or nausea;
if you develop unexplained symptoms such as yellowing of the skin or the whites of the eyes (jaundice), dark or brown (tea-coloured) urine, pain in the upper right part of the abdomen, bleeding or bruising more easily than usual, or a feeling of fatigue. 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”). Inform your doctor also if you have previously suffered from 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 stool, 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 the chest, particularly on the left side of the body, pain in the 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, fatigue, and confusion occur. These could 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 posterior reversible encephalopathy syndrome (PRES).

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

Other medicines and Nintedanib Accord
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.
Nintedanib Accord may interact with certain medicines. The following medicines are examples of those that may increase nintedanib levels in the blood, potentially increasing 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 modifies the immune system (cyclosporine)

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

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

Pregnancy and breastfeeding
If you are pregnant, suspect 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 baby and cause birth defects.
Before starting treatment with Nintedanib Accord, 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 treatment with Nintedanib Accord, during treatment with Nintedanib Accord, 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 problems 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 an alternative, more appropriate contraceptive method.
Inform your doctor or pharmacist immediately if you become pregnant or suspect you are pregnant during treatment with Nintedanib Accord.

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

Driving and using machines
Nintedanib Accord has a minor influence on the ability to drive and use machines. If you do not feel well, you must not drive or operate machinery.

Nintedanib Accord contains lecithin
If you are allergic to soy or peanuts, do not take this medicine (see section 2, under “Do not take Nintedanib Accord”).

3. How to take Nintedanib Accord

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 amount 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, either during a meal or immediately before or after. Do not open or crush the capsule (see section 5, below “How to store Nintedanib Accord”).
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 daily dose of 200 mg).
Do not take more than the recommended dose of two Nintedanib Accord 100 mg capsules per day.
If you do not tolerate the recommended dose of two Nintedanib Accord 100 mg capsules per day (see
possible side effects in section 4), your doctor may advise you to stop taking the medicine.
Do not reduce the dose or stop treatment on your own without first consulting your doctor.
Use in children and adolescents
The recommended dose depends on the patient's body weight.
Inform your doctor if at any time during treatment the patient's weight is below 13.5 kg.
Inform your doctor if you have liver problems.
Your doctor will determine the correct dose. Your doctor may adjust the dose during treatment.
If you do not tolerate the recommended daily dose of Nintedanib capsules (see possible side effects in
section 4), your doctor may reduce the daily dose of Nintedanib.
Do not reduce the dose or stop treatment on your own without first consulting your doctor.
Dosing based on body weight 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 Accord is available only as 100 mg and 150 mg soft capsules. Therefore,
Nintedanib Accord cannot be administered to paediatric patients requiring a dose lower than 100 mg.
If an alternative dose is required, other nintedanib-containing products offering this option should be used.
If you take more Nintedanib Accord than you should
Contact your doctor or pharmacist immediately.
If you forget to take Nintedanib Accord
Do not take two capsules at the same time if you have forgotten to take the previous dose. Take the next
dose of Nintedanib Accord at the next scheduled time as recommended by your doctor or pharmacist.
If you stop taking Nintedanib Accord
Do not stop treatment with Nintedanib Accord 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 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 particular attention if you experience the following side effects during treatment with
Nintedanib Accord:
Diarrhoea (very common, may occur in more than 1 in 10 patients):
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 this medicine.
Contact your doctor if you experience any side effect.
Idiopathic pulmonary fibrosis (IPF)
Very common side effects (may occur in more than 1 in 10 patients)

Nausea
Abdominal pain
Abnormal liver function tests

Common side effects (may occur in less than 1 in 10 patients)

Vomiting
Loss of appetite
Weight loss
Bleeding
Rash
Headache (cephalalgia)

Uncommon side effects (may occur in less than 1 in 100 patients)

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
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
Enlargement 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 occur in more than 1 in 10 patients)

Nausea
Vomiting
Loss of appetite
Abdominal pain
Abnormal liver function tests

Common side effects (may occur in less than 1 in 10 patients)

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

Uncommon side effects (may occur in less than 1 in 100 patients)

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
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
Enlargement 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 occur in more than 1 in 10 patients)

Nausea
Vomiting
Abdominal pain
Abnormal liver function tests

Common side effects (may occur in less than 1 in 10 patients)

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

Uncommon side effects (may occur in less than 1 in 100 patients)

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

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
Enlargement 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)
A 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 you experience any side effect.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store nintedanib Accord

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 after Exp. and on the 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 damaged.
If you come into contact with the capsule contents, wash your hands immediately with plenty of water (see section , “How to take Nintedanib Accord”).
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 Nintedanib Accord contains

The active substance is nintedanib. Each soft capsule contains nintedanib esilate equivalent to 100 mg of nintedanib.
The other components are:
Capsule contents: Medium-chain triglycerides, lauric macrogol glycerides, lecithin (E322) (see section 2, "Do not take Nintedanib Accord").
Capsule shell: Gelatin, glycerol, titanium dioxide (E171), red iron oxide (E172), yellow iron oxide (E172).
Printing ink: Shellac, black iron oxide (E172), ammonium hydroxide, and propylene glycol (E1520).

Description of the appearance of Nintedanib Accord and contents of the pack
Nintedanib Accord 100 mg capsules are soft gelatin capsules approximately 16 mm in size, peach-coloured, opaque, and oval-shaped, imprinted with "JF1" in black ink, containing a suspension ranging in colour from bright yellow-green to pale yellow.
Nintedanib Accord 100 mg capsules are available in packs containing:

Aluminium/aluminium blisters available in packs of 30, 60 and 120 soft capsules (multiple pack containing 2 boxes of 60 soft capsules each).
Aluminium/aluminium blisters available in perforated, divisible unit-dose blisters of 30 x 1, 60 x 1 and 120 x 1 soft capsules (multiple pack containing 2 boxes of 60 soft capsules each).

Not all pack sizes may be marketed.

Marketing Authorisation Holder
Accord Healthcare S.L.U.
World Trade Center, Moll de Barcelona, s/n
Edifici Est, 6th Floor
08039 Barcelona, Spain

Manufacturer
Accord Healthcare Polska Sp. z.o.o.
ul. Lutomierska 50,
95-200 Pabianice, Poland
Accord Healthcare B.V.
Winthontlaan 200,
3526 KV Utrecht, The Netherlands
Pharmadox Healthcare Ltd.
KW20A Kordin Industrial Park,
Paola PLA 3000, Malta

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
AT / BE / BG / CY / CZ / DE / DK / EE / ES / FI / FR / HR / HU / IE / IS / IT / LT / LV / LU / MT / NL / NO / PL / PT / RO / SE / SI / SK
Accord Healthcare S.L.U.
Tel: +34 93 301 00 64
EL
Win Medica Α.Ε.
Tel: +30 210 74 88 821

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

Patient information leaflet

Nintedanib Accord 150 mg soft capsules

nintedanib
Please read this entire 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, consult 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 may be harmful.
If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

What Nintedanib Accord is and what it is used for
What you need to know before taking Nintedanib Accord
How to take Nintedanib Accord
Possible side effects
How to store Nintedanib Accord
Contents of the pack and other information

1. What is Nintedanib Accord and what is it used for

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

Idiopathic pulmonary fibrosis (IPF) in adults
IPF is a condition in which lung tissue over time 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. Nintedanib Accord helps reduce further scarring and lung stiffness.

Other chronic fibrosing interstitial lung diseases (ILD) with progressive phenotype in adults
In addition to IPF, there are other conditions in which lung tissue over time 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. Nintedanib Accord helps reduce further scarring and lung stiffness.

Clinically significant progressive fibrosing interstitial lung diseases (ILD) in children and adolescents aged 6 years and older
In children with pediatric interstitial lung disease (chILD), pulmonary fibrosis may occur. When this happens, the lung tissue in children and adolescents becomes thick, stiff, and scarred over time. Nintedanib Accord helps reduce further scarring and lung stiffness.

Interstitial lung disease associated with systemic sclerosis (SSc-ILD) in adults, children, and adolescents 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 known as SSc-ILD. Fibrosis in the lungs reduces the lungs' ability to transfer oxygen to the blood and impairs breathing capacity. Nintedanib Accord helps reduce the development of scarring and lung stiffness.

2. What you need to know before taking Nintedanib Accord

Do not take Nintedanib Accord

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

Warnings and precautions
Talk to your doctor or pharmacist before taking Nintedanib Accord,

if you have or have had liver problems,
if you have or have had kidney problems, or if an increased level of protein in your urine has been detected,
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 affect wound healing. Therefore, treatment with Nintedanib Accord will usually be stopped for a certain period around the time of surgery. Your doctor will decide when you can resume treatment with this medicine,
if you have high blood pressure,
if you have high blood pressure in the blood vessels of the 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 monitor liver function. Your doctor will discuss the test results with you and decide whether you can receive Nintedanib Accord.
Inform your doctor immediately while taking this medicine

if you develop diarrhoea. It is essential to treat diarrhoea early (see section 4, “Possible side effects”);
if you experience vomiting or 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 abdomen, bleeding or bruising more easily than usual, or feel 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 wall of the intestine (“gastrointestinal perforation”). Inform your doctor also if you have previously suffered from 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 stool, 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 the chest, particularly on the left side of the body, pain in the 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, fatigue, and confusion occur. These could 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
Nintedanib Accord must not be taken by children under 6 years of age.
Your doctor may recommend regular dental check-ups at least once every 6 months until your teeth have fully developed, and monitor your growth annually (bone imaging tests) while you are taking this medicine.
Other medicines and Nintedanib Accord
Inform 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.
Nintedanib Accord may interact with certain medicines. The following medicines are some examples of medicines that may increase the levels of nintedanib in the blood, potentially increasing 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 modifies the immune system (cyclosporine).

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

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

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
Do not take this medicine during pregnancy, as it may harm the unborn baby and cause birth defects.
Before starting treatment with Nintedanib Accord, 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 Nintedanib Accord, during treatment with Nintedanib Accord, and for at least 3 months after stopping treatment.
Discuss with your doctor the most suitable contraceptive methods for your case.
Vomiting and/or diarrhoea or other gastrointestinal problems 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 Nintedanib Accord.

Breastfeeding
Do not breastfeed during treatment with Nintedanib Accord, as there is a risk of harm to breastfed infants.
Driving and using machines
Nintedanib Accord has a minor influence on the ability to drive and use machines. If you do not feel well, you should not drive or operate machinery.
Nintedanib Accord contains lecithin
If you are allergic to soy or peanuts, do not take this medicine (see section 2, under “Do not take Nintedanib Accord”).

3. How to take Nintedanib Accord

Take this medicine exactly as directed by your doctor or pharmacist. If you have any doubts,
please 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 amount 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, either during a meal or immediately before or after. Do not open or
crush the capsule (see section 5, “How to store Nintedanib Accord”).
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 per
day).
Do not take a higher dose than the recommended dose of two Nintedanib Accord 150 mg capsules per
day.
If you do not tolerate the recommended dose of two Nintedanib Accord 150 mg capsules per day (see possible
side effects in section 4), your doctor may reduce the daily dose of Nintedanib Accord. 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 per day).
In this case, your doctor will prescribe treatment with Nintedanib Accord 100 mg capsules. Do not take more
than the recommended dose of two Nintedanib Accord 100 mg capsules per day if your dose has been reduced to
200 mg per day.
Use in children and adolescents
The recommended dose depends on the patient's body weight.
Inform your doctor if at any time during treatment the patient's weight is below 13.5
kg.
Inform 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 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 treatment on your own initiative without first consulting your doctor.
Dosing based on body weight for Nintedanib capsules in children and adolescents:

Weight range in kilograms (kg)	Nintedanib Accord 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 Accord is available only in 100 mg and 150 mg soft capsules. Therefore,
Nintedanib Accord cannot be administered to pediatric patients requiring a dose lower than 100 mg.
If an alternative dose is required, other nintedanib-containing products offering such an option should be used.
If you take more Nintedanib Accord than you should
Contact your doctor or pharmacist immediately.
If you forget to take Nintedanib Accord
Do not take two capsules at the same time if you have missed a dose. Take the next dose of Nintedanib Accord as scheduled, at the next planned and recommended time, according to your doctor or pharmacist.
If you stop taking Nintedanib Accord
Do not stop treatment with Nintedanib Accord 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 careful if you experience the following side effects during treatment with
Nintedanib Accord:
Diarrhoea (very common, may occur in more than 1 in 10 patients):
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 this medicine.
Contact your doctor if you experience any side effect.

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

Nausea
Abdominal pain
Abnormal liver function tests

Common side effects (may occur in less than 1 in 10 patients)

Vomiting
Loss of appetite
Weight loss
Bleeding
Rash
Headache (cephalalgia)

Uncommon side effects (may occur in less than 1 in 100 patients)

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 elevated bilirubin levels
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
Dilation and weakening of the wall of a blood vessel or a tear in the wall of a blood vessel (aneurysms and arterial dissections)
A 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 occur in more than 1 in 10 patients)

Nausea
Vomiting
Loss of appetite
Abdominal pain
Abnormal liver function tests

Common side effects (may occur in less than 1 in 10 patients)

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

Uncommon side effects (may occur in less than 1 in 100 patients)

Pancreatitis
Inflammation of the large intestine
Low platelet count (thrombocytopenia)
Jaundice, i.e. yellowing of the skin and whites of the eyes due to elevated bilirubin levels
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
Dilation and weakening of the wall of a blood vessel or a tear in the wall of a blood vessel (aneurysms and arterial dissections)
A 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 occur in more than 1 in 10 patients)

Nausea
Vomiting
Abdominal pain
Abnormal liver function tests

Common side effects (may occur in less than 1 in 10 patients)

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

Uncommon side effects (may occur in less than 1 in 100 patients)

Inflammation of the large intestine
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 elevated bilirubin levels
Dilation 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)
A 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 observed in adult patients.
Contact your doctor if you experience any side effect.

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 through the national reporting system referred to in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Nintedanib Accord

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 after "Exp" and on the 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 damaged. If you come into contact with the capsule contents, wash your hands immediately with plenty of water (see section "How to take Nintedanib Accord").
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 Nintedanib Accord contains

The active substance is nintedanib. Each soft capsule contains nintedanib esilate equivalent to 150 mg of nintedanib.
The other components are:
Capsule contents: Medium-chain triglycerides, macrogol glycerides lauric, lecithin (E322) (see section 2, “Do not take Nintedanib Accord”)
Capsule shell: Gelatin, glycerol, titanium dioxide (E171), red iron oxide (E172), yellow iron oxide (E172)
Printing ink: Shellac, black iron oxide (E172), ammonium hydroxide, and propylene glycol (E1520)

Description of the appearance of Nintedanib Accord and pack contents
Nintedanib Accord 150 mg capsules are approximately 18 mm long, brown, opaque, elongated soft gelatin capsules, printed with “JF2” in black ink, containing a yellow-green to pale yellow suspension.
Nintedanib Accord 150 mg capsules are available in packs containing:

Aluminium/aluminium blisters available in packs of 30 and 60 soft capsules.
Aluminium/aluminium blisters available in unit-dose divisible blisters of 30 x 1 and 60 x 1 soft capsules.

Not all pack sizes may be marketed.

Marketing Authorisation Holder
Accord Healthcare S.L.U.
World Trade Center, Moll de Barcelona, s/n
Edifici Est, 6th Floor
08039 Barcelona
Spain

Manufacturer
Accord Healthcare Polska Sp. z.o.o.
ul. Lutomierska 50,
95-200, Pabianice, Poland
Accord Healthcare B.V.
Winthontlaan 200,
3526 KV Utrecht, Netherlands
Pharmadox Healthcare Ltd.
KW20A Kordin Industrial Park,
Paola PLA 3000, Malta

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