Nintedanib zentiva

Package leaflet: Information for the patient

Nintedanib Zentiva, 150 mg,
soft capsules
Nintedanibum
Please read this leaflet carefully before taking this medicine, as it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm other people, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Leaflet contents

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

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

Nintedanib Zentiva contains the active substance nintedanib, a medicine belonging to a group of drugs known as tyrosine kinase inhibitors, and is used to treat the following conditions:

Idiopathic pulmonary fibrosis (IPF) in adults
IPF is a disease in which lung tissue gradually becomes thicker, stiffer, and scarred. This scarring reduces the ability of the lungs to transfer oxygen into the bloodstream. Deep breathing becomes difficult. This medicine helps slow further scarring and stiffening of the lungs.

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

Clinically significant, progressive fibrosing interstitial lung diseases (ILD) in children and adolescents aged 6 to 17 years
In patients with childhood interstitial lung disease (chILD), lung fibrosis may occur. In such cases, the lung tissue in children and adolescents gradually becomes thickened, stiff, and scarred over time. Nintedanib Zentiva helps reduce further scarring and stiffening of the lungs.

Interstitial lung disease associated with systemic sclerosis (SSc-ILD) in adults, adolescents, and children aged 6 years and older
Systemic sclerosis (SSc), also known as scleroderma (and juvenile systemic sclerosis in children and adolescents), is a rare autoimmune disease affecting 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. The presence of fibrosis in the lungs is called interstitial lung disease (ILD), and thus the condition is referred to as SSc-ILD. Lung fibrosis reduces the ability to deliver oxygen into the bloodstream, making breathing difficult. This medicine helps reduce further scarring and stiffening of the lungs.

2. Important information before taking Nintedanib Zentiva

When not to take Nintedanib Zentiva

• if the patient is allergic to nintedanib or to any of the other ingredients of this medicine (listed in section 6),
• if the patient is pregnant.

Warnings and precautions
Before starting treatment with Nintedanib Zentiva, discuss with your doctor or pharmacist if:

• the patient has or has had liver problems,
• the patient has or has had kidney problems or if protein in the urine has been detected,
• the patient has or has had bleeding problems,
• the patient is taking medicines that reduce blood clotting (such as warfarin, phenprocoumon, heparin) to prevent blood clots,
• the patient is taking pirfenidone, as this may increase the risk of diarrhoea, nausea, vomiting and liver problems,
• the patient has or has had heart problems (e.g. heart attack),
• the patient has recently undergone surgery. Nintedanib may affect wound healing. Therefore, treatment with nintedanib is usually temporarily discontinued if the patient undergoes surgery. Your doctor will decide when to resume treatment with this medicine.
• if the patient has hypertension,
• if the patient has pulmonary hypertension (high blood pressure in the blood vessels of the lungs),
• if the patient has or has had an aneurysm (a weakened and bulging blood vessel wall) or a tear in the blood vessel wall.

Based on this information, the doctor may perform blood tests, for example, to check liver function. The doctor will discuss the results of these tests with the patient and decide whether the patient can take Nintedanib Zentiva.

The patient should inform the doctor immediately if, while taking this medicine:

• diarrhoea occurs. Early treatment of diarrhoea is important (see section 4);
• the patient experiences vomiting or nausea;
• unexplained symptoms occur, such as yellowing of the skin or whites of the eyes (jaundice), dark or brown (tea-coloured) urine, pain in the upper right part of the abdomen, more frequent bleeding or bruising than usual, or feeling tired. These may be symptoms of serious liver problems;
• severe stomach pain, fever, chills, nausea, vomiting, or a hard abdomen or bloating occur, as these may be symptoms of a perforation in the intestinal wall (gastrointestinal perforation). The doctor should also be informed if the patient has previously had:
  • peptic ulcers or diverticular disease of the intestine, or if the patient is taking
  • anti-inflammatory medicines (non-steroidal anti-inflammatory drugs, NSAIDs) (used to treat pain and swelling) or steroids (used to treat inflammatory and allergic conditions) at the same time, as these factors increase this risk;
• severe abdominal pain or cramps, red blood in the stool, or diarrhoea occur, as these may be symptoms of intestinal inflammation due to inadequate blood supply to the intestine;
• pain, swelling, redness and increased temperature in a limb occur, as these may be symptoms of a blood clot forming in a vein (a type of blood vessel);
• the patient experiences chest tightness or pain, typically on the left side of the body, pain in the neck, jaw, arm or hand, rapid heartbeat, shortness of breath, nausea, vomiting, as these may be symptoms of a heart attack;
• the patient experiences serious bleeding;
• the patient develops bruising, bleeding, fever, fatigue and confusion. This may be a sign of damage to blood vessels called thrombotic microangiopathy (TMA);
• symptoms such as headache, changes in vision, disorientation, seizures or other neurological disturbances, such as weakness in arms or legs, occur, with or without high blood pressure. These may be symptoms of a brain disorder called posterior reversible encephalopathy syndrome (PRES).

Children and adolescents
Nintedanib Zentiva must not be used in children under 6 years of age.
The doctor may perform regular dental examinations at least every 6 months until tooth development is complete and monitor the patient's growth once a year (bone imaging) during treatment with this medicine.

Nintedanib Zentiva and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take, including herbal products and over-the-counter medicines.
Nintedanib Zentiva may interact with certain other medicines. The following medicines may increase the blood levels of nintedanib and thereby increase the risk of adverse effects (see section 4):

• a medicine used to treat fungal infections (ketoconazole),
• a medicine used to treat bacterial infections (erythromycin),
• a medicine affecting the immune system (cyclosporine).

The following medicines are examples of those that may reduce the blood levels of nintedanib and thereby reduce the effectiveness of Nintedanib Zentiva:

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

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using this medicine.

Pregnancy
Do not take this medicine during pregnancy, as it may harm the unborn child and cause congenital malformations.
Before starting treatment with this medicine, a pregnancy test must be performed to confirm that the patient is not pregnant. The patient should discuss this with her doctor.

Contraceptive methods

• Women of childbearing potential must use a highly effective method of contraception to prevent pregnancy, both when starting treatment with Nintedanib Zentiva, throughout the entire treatment period, and for at least 3 months after stopping treatment.
• The best contraceptive methods should be discussed with the treating doctor.
• Vomiting and/or diarrhoea or other gastrointestinal disorders may affect the absorption of oral hormonal contraceptives, such as contraceptive pills, and may reduce their effectiveness. Therefore, if such disorders occur, the use of an alternative, more appropriate contraceptive method should be discussed with the doctor.
• If the patient becomes pregnant or suspects she may be pregnant during treatment with this medicine, she should immediately inform her doctor or pharmacist.

Breastfeeding
Breastfeeding must not be used during treatment with this medicine, as there is a risk of adverse effects in the breastfed child.

Driving and using machines
This medicine may have a minor influence on the ability to drive and use machines.
If the patient experiences nausea, he or she should not drive or operate machinery.

3. How to take Nintedanib Zentiva

This medicine should always be taken as directed by the physician or pharmacist.
If in doubt, consult the physician or pharmacist.
Take the capsules twice daily, approximately 12 hours apart, at the same time each day, for example one capsule in the morning and one in the evening. This will ensure a constant level of nintedanib in the patient's bloodstream. The capsules must be swallowed whole with water; do not suck or chew the capsules. It is recommended to take the capsules with food, i.e. during, immediately before, or immediately after a meal. The capsules must not be opened or crushed (see section 5).
To facilitate swallowing, the capsules may be taken with a small amount (one teaspoon) of cold or soft food at room temperature, such as apple sauce or chocolate pudding. The mixture must be swallowed immediately and must not be chewed, so that the capsule remains intact.

Adults
The recommended dose is one capsule containing 150 mg taken twice daily (total 300 mg daily).
The dose should not exceed the recommended two soft capsules of Nintedanib Zentiva 150 mg per day.
If the patient does not tolerate the recommended dose of two capsules of Nintedanib Zentiva 150 mg per day (see possible adverse reactions in section 4), the physician may reduce the daily dose of Nintedanib Zentiva. Do not reduce the dose or discontinue treatment on your own without first consulting your physician!
The physician may reduce the recommended dose to 100 mg twice daily (total 200 mg daily). In such a case, the physician will prescribe Nintedanib Zentiva 100 mg soft capsules for continued treatment. Do not exceed the recommended dose of two soft capsules of Nintedanib Zentiva 100 mg per day if the patient's 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 the physician if at any time during treatment the patient's body weight drops below 13.5 kg. Inform the physician if the patient has liver problems.
The physician will determine the correct dose. The physician may adjust the dose as treatment progresses.
If the patient does not tolerate the recommended dose of Nintedanib Zentiva capsules per day (see possible adverse reactions in section 4), the physician may reduce the daily dose of Nintedanib Zentiva. Do not reduce the dose or discontinue treatment on your own without first consulting your physician.
Dosing of Nintedanib Zentiva capsules in children and adolescents according to body weight:

Nintedanib Zentiva is available only in the form of soft capsules with a dose of 100 mg and 150 mg.
Therefore, it is not possible to administer the medicinal product Nintedanib Zentiva to paediatric
patients who require a dose lower than the full 100 mg dose. If an alternative dose is required, other
products containing nintedanib which offer this possibility should be used.
Taking more Nintedanib Zentiva than recommended
Contact your doctor or pharmacist immediately.
If you miss a dose of Nintedanib Zentiva
Do not take two capsules together if you have missed a previous dose. Take the next dose of
Nintedanib Zentiva according to your usual schedule and at the dose recommended by your doctor
or pharmacist.
Stopping Nintedanib Zentiva
Do not stop taking Nintedanib Zentiva without first consulting your doctor. It is important to take the
medicine regularly every day for as long as your doctor has instructed.
If you have any further questions regarding the use of this medicine, consult your doctor or
pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Special attention should be paid to the occurrence of the following adverse reactions during
treatment with Nintedanib Zentiva.
Diarrhoea (Very common, may occur in more than 1 in 10 patients)
Diarrhoea may lead to dehydration: loss of water and important substances (electrolytes, such as
sodium or potassium) from the body. If the first symptoms of diarrhoea occur, drink plenty of fluids
and contact your doctor immediately. Anti-diarrhoeal treatment, for example with loperamide,
should be started as soon as possible.
The following other adverse reactions have been observed during treatment with this medicine.
If any adverse reactions occur, inform your doctor.
Idiopathic pulmonary fibrosis (IPF)
Very common adverse reactions (may occur in more than 1 in 10 patients)

• nausea,
• abdominal pain,
• abnormal liver function test results.

Common adverse reactions (may occur in less than 1 in 10 patients)

• vomiting,
• loss of appetite,
• weight decrease,
• bleeding,
• rash,
• headache.

Uncommon adverse reactions (may occur in less than 1 in 100 patients)

• pancreatitis,
• 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,
• heart attack,
• excessive hair loss (alopecia),
• increased protein concentration in urine (proteinuria).

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

• renal failure,
• enlargement and weakening of a blood vessel wall or rupture of a blood vessel wall (aneurysm and arterial dissection).
• brain disorder with symptoms such as headache, visual disturbances, confusion, seizures, or other neurological disturbances such as weakness in arms or legs, with or without high blood pressure (posterior reversible encephalopathy syndrome).

Other chronic fibrosing interstitial lung diseases (ILD) with progressive phenotype
Very common adverse reactions (may occur in more than 1 in 10 patients)

• nausea,
• vomiting,
• loss of appetite,
• abdominal pain,
• abnormal liver function test results.

Common adverse reactions (may occur in less than 1 in 10 patients)

• weight decrease,
• high blood pressure (hypertension),
• bleeding,
• serious liver problems,
• rash,
• headache.

Uncommon adverse reactions (may occur in less than 1 in 100 patients)

• pancreatitis,
• colitis,
• low platelet count (thrombocytopenia),
• jaundice, i.e. yellowing of the skin and whites of the eyes due to high bilirubin levels,
• itching,
• heart attack,
• excessive hair loss (alopecia),
• increased protein concentration in urine (proteinuria).

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

• renal failure,
• enlargement and weakening of a blood vessel wall or rupture of a blood vessel wall (aneurysm and arterial dissection).
• brain disorder with symptoms such as headache, visual disturbances, confusion, seizures, or other neurological disturbances such as weakness in arms or legs, with or without high blood pressure (posterior reversible encephalopathy syndrome).

Systemic sclerosis-associated interstitial lung disease (SSc-ILD)
Very common adverse reactions (may occur in more than 1 in 10 patients)

• nausea,
• vomiting,
• abdominal pain,
• abnormal liver function test results.

Common adverse reactions (may occur in less than 1 in 10 patients)

• bleeding,
• high blood pressure (hypertension),
• loss of appetite,
• weight decrease,
• headache.

Uncommon adverse reactions (may occur in less than 1 in 100 patients)

• colitis,
• serious liver problems,
• renal failure,
• low platelet count (thrombocytopenia),
• rash,
• itching.

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

• heart attack,
• pancreatitis,
• jaundice, i.e. yellowing of the skin and whites of the eyes due to high bilirubin levels,
• enlargement and weakening of a blood vessel wall or rupture of a blood vessel wall (aneurysm and arterial dissection),
• excessive hair loss (alopecia),
• increased protein concentration in urine (proteinuria).
• brain disorder with symptoms such as headache, visual disturbances, confusion, seizures, or other neurological disturbances such as weakness in arms or legs, with or without high blood pressure (posterior reversible encephalopathy syndrome).

Fibrosing interstitial lung diseases (ILD) in children and adolescents
Adverse reactions in children and adolescents were similar to those observed in adult patients.
Consult your doctor if any adverse reactions occur in the patient.
Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: 22 49-21-301, fax: 22 49-21-309,
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder or its representative.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Nintedanib Zentiva

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister. The expiry date refers to the last day of the stated month.
This medicine does not require any special storage conditions.
Do not use this medicine if the blister pack containing the capsules is open or if a capsule appears damaged or broken.
In case of contact with the capsule contents, wash hands immediately with plenty of water (see section 3).
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Nintedanib Zentiva contains

• The active substance is nintedanib. Each capsule contains 150 mg of nintedanib (as nintedanib esilate).
• The other ingredients are:
  Capsule contents: medium-chain triglycerides, solid fat, polyglycerol 3-dioleate
  Capsule shell: gelatin, glycerol, titanium dioxide (E 171), iron oxide red (E 172), iron oxide yellow (E 172), purified water
  Printing ink: shellac, iron oxide black (E 172) and propylene glycol (E 1520)

What Nintedanib Zentiva looks like and contents of the pack
Nintedanib Zentiva 150 mg is an opaque, brown, elongated soft capsule containing a yellow, viscous suspension, printed in black with "NT 150", 17 mm in length.
Nintedanib Zentiva 150 mg soft capsules are available in perforated unit dose blisters made of OPA/Aluminium/PVC/Aluminium, packed in a cardboard box.
Pack sizes:
30 x 1 soft capsule
60 x 1 soft capsule
120 x 1 soft capsule
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Zentiva, k.s.
U kabelovny 130
Dolní Měcholupy
102 37 Prague 10
Czech Republic

Manufacturer/Importer
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 San Gwann
Malta
QUALIMETRIX S.A.
579 MESOGEION AVENUE AGIA PARASKEVI,
15343 Athens
Greece

This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Germany: Nintedanib Zentiva 150 mg Weichkapseln
Spain: NINTEDANIB ZENTIVA 150 MG CAPSULAS BLANDAS EFG
France: NINTEDANIB ZENTIVA 150 mg, capsule molle
Lithuania: Nintedanib Zentiva 150 mg minkštosios Kapsulės
Latvia: Nintedanib Zentiva 150 mg mīkstās kapsulas
Denmark, Estonia, Finland, Iceland, Poland, Norway, Portugal, Sweden: Nintedanib Zentiva

For more detailed information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
Zentiva Polska Sp. z o.o.
ul. Bonifraterska 17
00-203 Warsaw
tel.: +48 22 375 92 00