Nintedanib Zentiva

Package Leaflet: Information for the Patient

Nintedanib Zentiva, 100 mg, Soft Capsules

Nintedanib

Read the package leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this package leaflet, you may need to read it again.
• In case of any doubts, consult a doctor or pharmacist.
• This medicine has been prescribed specifically for you, do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If the patient experiences any side effects, including those not listed in this leaflet, they should inform their doctor or pharmacist. See section 4.

Table of Contents of the Package Leaflet

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

Nintedanib Zentiva contains the active substance nintedanib, a medicine belonging to a group of medicines called tyrosine kinase inhibitors, and is used to treat idiopathic pulmonary fibrosis (IPF), other chronic and progressive fibrosing interstitial lung diseases (ILD) with a progressive phenotype, and systemic sclerosis-associated interstitial lung disease (SSc-ILD) in adults.
Idiopathic pulmonary fibrosis (IPF)
IPF is a disease in which the lung tissue gradually becomes thicker, stiffer, and scarred. This scarring reduces the ability to transport oxygen from the lungs to the blood. Deep breathing is difficult. This medicine reduces further scarring and stiffness of the lungs.
Other chronic and progressive fibrosing interstitial lung diseases (ILD) with a progressive phenotype
Besides IPF, there are other diseases in which the lung tissue becomes thicker, stiffer, and scarred over time (lung fibrosis) and worsens continuously (progressive phenotype). Examples of these diseases include allergic alveolitis, autoimmune ILD (e.g., ILD associated with rheumatoid arthritis), idiopathic nonspecific interstitial pneumonia, unclassified idiopathic interstitial pneumonia, and other ILD. This medicine helps reduce further scarring and stiffness of the lungs.
Systemic sclerosis-associated interstitial lung disease (SSc-ILD)
Systemic sclerosis (SSc), also known as scleroderma, is a rare autoimmune disease that affects the connective tissue in many parts of the body. Systemic sclerosis (SSc) causes scarring (fibrosis and stiffness) 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 is referred to as SSc-ILD. Lung fibrosis reduces the ability to supply oxygen to the bloodstream, making breathing difficult. This medicine helps reduce further scarring and stiffness of the lungs.

2. Important information before taking Nintedanib Zentiva

When not to take Nintedanib Zentiva

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

Warnings and precautions

Before starting to take Nintedanib Zentiva, the patient should discuss with their doctor or pharmacist if they:

• have or have had liver problems,
• have or have had kidney problems or have been found to have an increased level of protein in their urine,
• have or have had bleeding problems,
• are taking medicines to prevent blood clotting (such as warfarin, phenprocoumon, heparin),
• are taking pirfenidone, as this may increase the risk of diarrhea, nausea, vomiting, and liver problems,
• have or have had heart problems (e.g., heart attack),
• have recently undergone surgery. Nintedanib may affect wound healing. Therefore, treatment with this medicine is usually interrupted for a while if the patient is to undergo surgery. The doctor will decide when to restart treatment with this medicine.
• have high blood pressure,
• have high blood pressure in the blood vessels of the lungs (pulmonary hypertension),
• have or have had an aneurysm (enlargement and weakening of the wall of a blood vessel) or a rupture of the wall of a blood vessel.

Given 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.
If the patient experiences any of the following while taking this medicine, they should immediately inform their doctor:

• diarrhea. It is essential to treat diarrhea early (see section 4);
• vomiting or nausea;
• unexplained symptoms, such as yellowing of the skin or whites of the eyes (jaundice), dark or brown (tea-colored) urine, pain in the upper right abdomen, more frequent than usual bleeding or bruising, or feeling tired. These may be signs of severe liver problems;
• severe stomach pain, fever, chills, nausea, vomiting, or a hard, swollen stomach or bloating, as these may be signs of a hole in the wall of the intestine (gastrointestinal perforation). The patient should also inform their doctor if they have had stomach ulcers or diverticulitis in the past or are taking non-steroidal anti-inflammatory drugs (NSAIDs) (used to treat pain and swelling) or steroids (used to treat inflammation and allergies), as these factors increase the risk;
• severe abdominal pain or cramps, red blood in the stool, or diarrhea, as these may be signs of inflammation of the intestine due to insufficient blood supply;
• pain, swelling, redness, and increased temperature of a limb, as these may be signs of a blood clot in a vein (a type of blood vessel);
• chest pressure 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 signs of a heart attack;
• severe bleeding;
• bruising, bleeding, fever, fatigue, and confusion. This may be a sign of a condition called thrombotic microangiopathy (TMA).

Children and adolescents

Children and adolescents under 18 years of age should not take Nintedanib Zentiva.

Nintedanib Zentiva and other medicines

The patient should tell their doctor or pharmacist about all medicines they are taking, have recently taken, or might take, including herbal products and medicines obtained without a prescription.
Nintedanib Zentiva may interact with certain other medicines. The following medicines may increase the level of nintedanib in the blood and thus increase 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 affects the immune system (cyclosporine).

The following medicines are examples of medicines that may decrease the level of nintedanib in the blood and thus decrease the effectiveness of Nintedanib Zentiva:

• 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 the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a baby, they should consult their 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 this medicine, a pregnancy test should be performed to ensure the patient is not pregnant. The patient should discuss this with their doctor.
Contraceptives

• Women who may become pregnant must use highly effective contraception to prevent pregnancy while taking Nintedanib Zentiva and for at least 3 months after stopping treatment.
• The patient should discuss the best contraceptive methods with their doctor.
• Vomiting and/or diarrhea or other stomach and intestinal disorders may affect the absorption of oral hormonal contraceptives, such as birth control pills, and may reduce their effectiveness. In such cases, the patient should discuss alternative, more suitable contraceptive methods with their doctor.
• If the patient becomes pregnant or thinks they may be pregnant while taking this medicine, they should immediately inform their doctor or pharmacist.

Breastfeeding
Do not breastfeed while taking this medicine, as there may be a risk of harm to 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 feels nauseous, they should not drive or operate machinery.

3. How to take Nintedanib Zentiva

Take this medicine exactly as the doctor or pharmacist has told the patient. If the patient is unsure, they should ask their doctor or pharmacist.
Take one capsule twice a day, approximately 12 hours apart, at the same time every day, for example, one capsule in the morning and one capsule in the evening. This will help keep a steady level of nintedanib in the patient's blood. Swallow the capsules whole with water; do not suck, chew, or open the capsules. It is recommended to take the capsules with food, i.e., during or immediately before or after a meal. Do not open or crush the capsules (see section 5).

Adults

The recommended dose is one 100 mg capsule twice a day (a total of 200 mg per day).
Do not take more than the recommended dose of two Nintedanib Zentiva 100 mg soft capsules per day.
If the patient cannot tolerate the recommended dose of two Nintedanib Zentiva 100 mg capsules per day (see possible side effects in section 4), the doctor may advise them to stop taking this medicine. Do not reduce the dose or stop treatment without consulting the doctor first.

Taking more than the recommended dose of Nintedanib Zentiva

Contact a doctor or pharmacist immediately.

Missing a dose of Nintedanib Zentiva

Do not take two capsules at the same time if a dose is missed. Take the next dose of Nintedanib Zentiva at the usual time, as prescribed by the doctor or pharmacist.

Stopping treatment with Nintedanib Zentiva

Do not stop taking Nintedanib Zentiva without consulting the doctor first.
It is essential to take this medicine regularly, every day, for as long as the doctor prescribes.
If the patient has any further questions about the use of this medicine, they should ask their doctor or pharmacist.

4. Possible side effects

Like all medicines, Nintedanib Zentiva can cause side effects, although not everybody gets them.
The patient should be aware of the following side effects when taking Nintedanib Zentiva.
Very common(may affect more than 1 in 10 people)
Diarrhea may lead to dehydration: loss of water and essential substances (electrolytes, such as sodium or potassium) from the body. If the patient experiences the first symptoms of diarrhea, they should drink plenty of fluids and contact their doctor immediately. They should start appropriate anti-diarrheal treatment as soon as possible, for example, with loperamide.

Other side effects that have been reported with this medicine.

If the patient experiences any side effects, they should inform their doctor.
Idiopathic pulmonary fibrosis (IPF)
Very common side effects(may affect more than 1 in 10 people)

• nausea,
• abdominal pain,
• abnormal liver function tests.

Common side effects(may affect up to 1 in 10 people)

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

Uncommon side effects(may affect up to 1 in 100 people)

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

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

• kidney failure,
• enlargement and weakening of the wall of a blood vessel or rupture of the wall of a blood vessel (aneurysm and arterial dissection).

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

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

Common side effects(may affect up to 1 in 10 people)

• weight loss,
• high blood pressure (hypertension),
• bleeding,
• severe liver problems,
• rash,
• headache.

Uncommon side effects(may affect up to 1 in 100 people)

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

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

• kidney failure,
• enlargement and weakening of the wall of a blood vessel or rupture of the wall of a blood vessel (aneurysm and arterial dissection).

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

• nausea,
• vomiting,
• abdominal pain,
• abnormal liver function tests.

Common side effects(may affect up to 1 in 10 people)

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

Uncommon side effects(may affect up to 1 in 100 people)

• colitis,
• severe liver problems,
• kidney failure,
• low platelet count (thrombocytopenia),
• rash,
• itching.

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

• heart attack,
• pancreatitis,
• jaundice (yellowing of the skin and whites of the eyes due to high bilirubin levels),
• enlargement and weakening of the wall of a blood vessel or rupture of the wall of a blood vessel (aneurysm and arterial dissection),
• excessive hair loss (alopecia),
• increased protein in the urine (proteinuria).

Reporting side effects

If the patient experiences any side effects, including those not listed in this leaflet, they should inform their doctor or pharmacist, or nurse. Side effects can be reported directly to the Department of Drug Safety, 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
Side effects can also be reported to the marketing authorization holder or its representative.
Reporting side effects will help to gather more information on the safety of this medicine.

5. How to store Nintedanib Zentiva

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. The expiry date refers to the last day of the month.
This medicine does not require any special storage conditions.
Do not use this medicine if the patient notices that the blister containing the capsules is open or that a capsule is damaged.
If the patient comes into contact with the contents of a capsule, they should wash their hands immediately with plenty of water (see section 3).
Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines they no longer use. This 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 100 mg of nintedanib (as nintedanib esylate).
• The other ingredients are: Capsule contents: triglycerides of medium-chain fatty acids, hard fat, polyglycerol 3-diolein Capsule shell: gelatin, glycerol, titanium dioxide (E 171), iron oxide red (E 172), iron oxide yellow (E 172), purified water Ink: shellac, carmine (E 120), propylene glycol (E 1520), simethicone

What Nintedanib Zentiva looks like and contents of the pack

Nintedanib Zentiva 100 mg are non-transparent, elongated soft capsules of peach color, containing a yellow viscous suspension, with a red imprint "NT 100" and a length of 16 mm.
Nintedanib Zentiva 100 mg soft capsules are available in single-dose blisters made of OPA/Aluminum/PVC/Aluminum foil in a cardboard box.
Package sizes:
30 x 1 soft capsules
60 x 1 soft capsules
Not all package sizes may be marketed.

Marketing authorization 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 has been authorized in the Member States of the European Economic Area under the following names:

Germany: Nintedanib Zentiva 100 mg Weichkapseln
Spain: NINTEDANIB ZENTIVA 100 MG CAPSULAS BLANDAS EFG
France: NINTEDANIB ZENTIVA 100 mg, capsule molle
Lithuania: Nintedanib Zentiva 100 mg minkštosios Kapsulės
Latvia: Nintedanib Zentiva 100 mg mīkstās kapsulas
Denmark, Estonia, Finland, Iceland, Poland, Norway, Portugal, Sweden: Nintedanib Zentiva

For further information about this medicine, the patient should contact the representative of the marketing authorization holder in Poland:

Zentiva Polska Sp. z o.o.
ul. Bonifraterska 17
00-203 Warsaw
tel.: +48 22 375 92 00

Date of last revision of the package leaflet: