Imbruvica

Package leaflet: Information for the patient

IMBRUVICA 140 mg hard capsules

ibrutinib
Please read 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, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

1. What IMBRUVICA is and what it is used for

What IMBRUVICA is
IMBRUVICA is an anticancer medicine that contains the active substance ibrutinib. It belongs to a
class of medicines called protein kinase inhibitors.
What IMBRUVICA is used for
IMBRUVICA is used in adult patients for the treatment of the following blood cancers:

• Mantle cell lymphoma (MCL), a type of cancer affecting the lymph nodes. IMBRUVICA is used in patients who have not been previously treated for MCL and for whom haematopoietic stem cell transplantation would be suitable, or when the disease has relapsed or has not responded to treatment.
• Chronic lymphocytic leukaemia (CLL), a type of cancer affecting white blood cells called lymphocytes and also involving the lymph nodes. IMBRUVICA is used in patients who have not been previously treated for CLL or when the disease has relapsed or has not responded to treatment.
• Waldenström’s macroglobulinaemia (WM), a type of cancer affecting white blood cells called lymphocytes. It is used in patients who have not been previously treated for WM or when the disease has relapsed, has not responded to treatment, or in patients for whom chemotherapy combined with an antibody is not appropriate.

How IMBRUVICA works
In MCL, CLL and WM, IMBRUVICA works by blocking "Bruton's tyrosine kinase", a protein in the body that helps these cancer cells grow and survive. By blocking this protein, IMBRUVICA helps kill and reduce the number of cancer cells. IMBRUVICA also slows down the progression of cancer.

2. What you need to know before taking IMBRUVICA

Do not take IMBRUVICA

• if you are allergic to ibrutinib or to any of the other ingredients of this medicine (listed in section 6).
• if you are taking a herbal medicine called St. John’s wort, used for depression. If in doubt, consult your doctor, pharmacist, or nurse before taking this medicine.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking IMBRUVICA:

• if you have ever had unusual bruising or bleeding, or if you are taking a medicine or supplement that increases the risk of bleeding (see Other medicines and IMBRUVICA)
• if you have an irregular heartbeat or have previously had an irregular heartbeat or severe heart failure, or if you experience any of the following: shortness of breath, weakness, dizziness, lightheadedness, fainting or near-fainting, chest pain, or swelling in the legs
• if you have liver problems, including if you have ever had or currently have hepatitis B infection (a liver infection)
• if you have high blood pressure
• if you have recently undergone surgery, especially if it may affect how you absorb food or medicines from the stomach or intestines
• if you are scheduled for a surgical procedure: your doctor may ask you to temporarily stop taking IMBRUVICA (3 to 7 days before and after your surgery)
• if you have kidney problems.

If any of the above apply to you (or if you have any doubts), consult your doctor, pharmacist, or nurse before taking or while taking this medicine (see section “Possible side effects”).
While being treated with IMBRUVICA, inform your doctor immediately if you, or someone else, notice: memory loss, difficulty thinking, difficulty walking, or loss of vision—these symptoms may be caused by a rare but serious brain infection that can be fatal (progressive multifocal leukoencephalopathy or PML).
Inform your doctor immediately if you or someone else notices in you: sudden numbness or weakness in the limbs (especially on one side of the body), sudden confusion, difficulty speaking or understanding speech, loss of vision, difficulty walking, loss of balance or coordination, or sudden severe headache without known cause. These may be signs and symptoms of stroke.
Inform your doctor immediately if you experience pain in the upper left part of the abdomen, pain under the left side of the ribcage, or in the upper left shoulder (these may be symptoms of spleen rupture) after stopping IMBRUVICA.

Effects on the heart
Treatment with IMBRUVICA may affect the heart, especially if you already have heart conditions such as rhythm problems, heart failure, high blood pressure, diabetes, or if you are elderly. These effects can be serious and potentially fatal, sometimes causing sudden death. Your heart function will be monitored before and during treatment with IMBRUVICA. Inform your doctor immediately if you experience breathlessness, difficulty breathing when lying down, swelling of the feet, ankles, or legs, or weakness/tiredness during treatment with IMBRUVICA, as these may be signs of heart failure.

Infections
During treatment with IMBRUVICA, you may develop viral, bacterial, or fungal infections. Contact your doctor if you have fever, chills, weakness, mental confusion, body aches, cold or flu-like symptoms, feeling tired or short of breath, or yellowing of the skin or eyes (jaundice). These could be signs of an infection.

Hemophagocytic lymphohistiocytosis
Cases of excessive white blood cell activation associated with inflammation (hemophagocytic lymphohistiocytosis) have been reported, which can be fatal if not diagnosed and treated promptly. If you develop multiple symptoms such as fever, swollen glands, bruising, or skin rashes, contact your doctor immediately.

Tests and monitoring before and during treatment
Tumor lysis syndrome (TLS): Unusual levels of chemical substances in the blood due to rapid destruction of tumor cells have been observed during cancer treatment, and sometimes even without treatment. This may lead to changes in kidney function, abnormal heart rhythm, or seizures. Your doctor or another healthcare provider may perform blood tests to monitor for TLS.

Lymphocytosis: Laboratory tests may show an increase in white blood cells (called "lymphocytes") in the blood during the first weeks of treatment. This is an expected effect and may last for several months. This does not necessarily mean that the hematological cancer is worsening. Your doctor will check your blood cell counts before or during treatment, and in rare cases may need to prescribe another medicine. Ask your doctor to explain the meaning of your test results.

Liver-related events: Your doctor will perform blood tests to check whether your liver is functioning properly, to rule out a liver infection known as viral hepatitis, or to monitor for reactivation of hepatitis B, as this could be fatal.

Children and adolescents
IMBRUVICA must not be used in children and adolescents.

Other medicines and IMBRUVICA
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. This includes medicines that do not require a prescription, herbal medicines, and supplements. This is because IMBRUVICA may affect how other medicines work. In addition, some medicines may affect how IMBRUVICA works.

IMBRUVICA may increase the risk of bleeding. This means you must inform your doctor if you are taking other medicines that increase the risk of bleeding. These include:

• acetylsalicylic acid and non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or naproxen
• blood thinners such as warfarin, heparin, or other anticoagulant medicines
• dietary supplements that may increase the risk of bleeding, such as fish oil, vitamin E, or flaxseed.

If any of the above apply to you (or if you have any doubts), consult your doctor, pharmacist, or nurse before taking IMBRUVICA.

Also inform your doctor if you are taking any of the following medicines – The effects of IMBRUVICA or other medicines may be affected if you take IMBRUVICA together with any of the following:

• medicines called antibiotics, used to treat bacterial infections: clarithromycin, telithromycin, ciprofloxacin, erythromycin, or rifampicin
• medicines for fungal infections: posaconazole, ketoconazole, itraconazole, fluconazole, or voriconazole
• medicines for HIV infection: ritonavir, cobicistat, indinavir, nelfinavir, saquinavir, amprenavir, atazanavir, or fosamprenavir
• medicines to prevent nausea and vomiting associated with chemotherapy: aprepitant
• medicines for depression: nefazodone
• medicines called kinase inhibitors for the treatment of other cancers: crizotinib or imatinib
• medicines called calcium channel blockers for hypertension or angina: diltiazem or verapamil
• medicines called statins for high cholesterol: rosuvastatin
• medicines for arrhythmias: amiodarone or dronedarone
• medicines to prevent or treat epileptic seizures or to treat a painful facial condition called trigeminal neuralgia: carbamazepine or phenytoin.

If any of the above apply to you (or if you have any doubts), consult your doctor, pharmacist, or nurse before taking IMBRUVICA.

If you are taking digoxin, a medicine used for heart problems, or methotrexate, a medicine used to treat other cancers and to reduce immune system activity (e.g., for rheumatoid arthritis or psoriasis), these should be taken at least 6 hours before or after IMBRUVICA.

IMBRUVICA with food
Do not take IMBRUVICA with grapefruit or Seville oranges (bitter oranges), meaning do not eat them, drink their juice, or take supplements that may contain them. This is because they can increase the amount of IMBRUVICA in your blood.

Pregnancy and breastfeeding
Avoid becoming pregnant during treatment with this medicine.
IMBRUVICA must not be used during pregnancy.
There is no information on the safety of IMBRUVICA in pregnant women.
Women of childbearing potential must use a highly effective method of contraception during treatment and for three months after stopping IMBRUVICA to avoid becoming pregnant while on treatment.

• Inform your doctor immediately if you become pregnant.
• Do not breastfeed while being treated with this medicine.

Driving and using machines
After taking IMBRUVICA, you may feel tired or dizzy, which could affect your ability to drive or operate tools or machinery.

IMBRUVICA contains sodium
IMBRUVICA contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially ‘sodium-free’.

3. How to take IMBRUVICA

Take this medicine exactly as directed by your doctor, pharmacist, or nurse. If you have any doubts, consult your doctor, pharmacist, or nurse.

Dosage

Mantle cell lymphoma (MCL)
The recommended dose of IMBRUVICA is four capsules (560 mg) once daily.

Chronic lymphocytic leukemia (CLL)/Waldenström’s macroglobulinemia (WM)
The recommended dose of IMBRUVICA is three capsules (420 mg) once daily.

Your doctor may adjust the dose.

How to take this medicine

• Take the capsules by mouth with a glass of water.
• Take the capsules at approximately the same time each day.
• Swallow the capsules whole; do not open, break, or chew the capsules.

If you take more IMBRUVICA than you should
If you take more IMBRUVICA than prescribed, contact your doctor or go to hospital immediately. Bring the capsules and this leaflet with you.

If you forget to take IMBRUVICA

• If you miss a dose, it can be taken as soon as possible on the same day, returning to your regular schedule the following day.
• Do not take a double dose to make up for the missed dose.
• If you are unsure about when to take your next dose, consult your doctor, pharmacist, or nurse.

If you stop taking IMBRUVICA
Do not stop taking this medicine unless your doctor tells you to.
If you have any questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
The following side effects may occur with this medicine:
If you notice any of the side effects listed in this leaflet, stop taking IMBRUVICA and contact your doctor immediately:
irregular, itchy rash; difficulty breathing; swelling of the face, lips, tongue or throat.
These may be signs of an allergic reaction to the medicine.
Contact your doctor immediately if you notice any of the following side effects:

Patients treated with IMBRUVICA for B-cell tumours:

Very common (affects more than 1 in 10 people)

• fever, chills, muscle aches, feeling of fatigue, cold or flu-like symptoms, shortness of breath – these may be signs of an infection (viral, bacterial or fungal). These may include infections of the nose, sinuses or throat (upper respiratory tract infection), or of the lung or skin
• blood in the stomach, intestines, faeces or urine, heavier menstrual periods or uncontrollable bleeding from a wound
• bruising or increased tendency to bruise
• mouth ulcers
• dizziness
• headache
• constipation
• nausea or vomiting
• indigestion
• diarrhoea: your doctor may give you fluids and salts or another medicine
• rash
• pain in arms or legs
• back or joint pain
• muscle cramps, pain or spasms
• fever
• blood tests showing low number of cells that help blood to clot (platelets), very low white blood cell count
• blood tests showing increased number or percentage of white blood cells
• swollen hands, ankles or feet
• high blood pressure
• increased level of “creatinine” in the blood.

Common (affects up to 1 in 10 people)

• severe infections throughout the body (sepsis)
• urinary tract infections
• nosebleeds, small red or purple spots caused by bleeding under the skin
• heart failure
• irregular heartbeat, weak or irregular pulse, mental confusion, shortness of breath, chest discomfort (symptoms of heart rhythm problems)
• low white blood cell count with fever (febrile neutropenia)
• non-melanoma skin cancer, most frequently squamous cell carcinoma and basal cell carcinoma
• blurred vision
• red skin
• lung inflammation that may lead to permanent damage
• high level of “uric acid” in the blood (shown by blood tests), which may cause gout
• nail breakage
• hives (urticaria)
• sudden kidney injury
• weakness, numbness, tingling or pain in the hands or feet or other parts of the body (peripheral neuropathy).

Uncommon (affects up to 1 in 100 people)

• liver failure, including fatal events
• severe fungal infections
• “reactivation” of hepatitis B (if you previously had hepatitis B, it may reappear)
• bleeding on the surface of the brain
• confusion, headache with language disturbance or feeling faint: these may be signs of serious internal bleeding in the brain
• unusual levels of chemicals in the blood caused by rapid destruction of tumour cells during cancer treatment, and sometimes even without treatment (tumour lysis syndrome)
• allergic reaction, sometimes severe, which may include swelling of the face, lips, mouth, tongue or throat, difficulty swallowing or breathing, itchy rash (urticaria)
• inflammation of subcutaneous fatty tissue
• temporary episode of reduced brain or nerve function due to reduced blood flow, stroke
• bleeding in the eye (in some cases associated with loss of vision)
• cardiac arrest (heart stops beating)
• abnormally rapid heartbeat
• painful skin ulcers (pyoderma gangrenosum) or red, raised and painful skin lesions, fever and increased white blood cell count (may be signs of acute febrile neutrophilic dermatosis or Sweet’s syndrome)
• small red bump on the skin that may bleed easily (pyogenic granuloma)
• inflamed blood vessels in the skin that may lead to a rash (cutaneous vasculitis).

Rare (affects up to 1 in 1,000 people)

• severe increase in white blood cell count in the blood, which may cause cells to clump together
• severe rash with blisters and peeling of the skin, especially around the mouth, nose, eyes and genitals (Stevens-Johnson syndrome).

Patients treated with IMBRUVICA for previously untreated MCL

Very common (affects more than 1 in 10 people)

• blood tests showing low number of cells that help blood to clot (platelets), very low white blood cell count
• low white blood cell count with fever (febrile neutropenia)
• nausea or vomiting
• diarrhoea: your doctor may give you fluids and salts or another medicine
• mouth ulcers
• constipation
• fever
• fever, chills, muscle aches, feeling of fatigue, cold or flu-like symptoms, shortness of breath – these may be signs of an infection (viral, bacterial or fungal). These may include infections of the lungs or skin
• increased level of “creatinine” in the blood
• pain in arms or legs
• weakness, numbness, tingling or pain in the hands or feet or other parts of the body (peripheral neuropathy)
• headache
• sudden kidney injury
• rash
• blood in the stomach, intestines, faeces or urine, heavier menstrual periods or uncontrollable bleeding from a wound
• high blood pressure.

Common (affects up to 1 in 10 people)

• increased white blood cell count
• infections of the nose, sinuses or throat (upper respiratory tract infections)
• irregular heartbeat, weak or irregular pulse, mental confusion, shortness of breath, chest discomfort (symptoms of heart rhythm problems)
• heart failure
• indigestion
• swollen hands, ankles or feet
• lung inflammation that may lead to permanent damage
• severe infections throughout the body (sepsis)
• urinary tract infections
• high level of “uric acid” in the blood (shown by blood tests), which may cause gout
• unusual levels of chemicals in the blood caused by rapid destruction of tumour cells during cancer treatment and sometimes even without treatment (tumour lysis syndrome)
• muscle cramps, pain or spasms
• back or joint pain
• non-melanoma skin cancer, including basal cell carcinoma
• dizziness
• red skin
• nail breakage
• hives (urticaria)
• bruising or increased tendency to bruise
• nosebleeds, small red or purple spots caused by bleeding under the skin.

Uncommon (affects up to 1 in 100 people)

• blurred vision
• severe fungal infections
• bleeding in the eye
• temporary episode of reduced brain or nerve function due to reduced blood flow, stroke
• allergic reaction, sometimes severe, which may include swelling of the face, lips, mouth, tongue or throat, difficulty swallowing or breathing, itchy rash (urticaria)
• inflamed blood vessels in the skin that may lead to a rash (cutaneous vasculitis)
• inflammation of subcutaneous fatty tissue.

Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor, pharmacist or nurse.
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 IMBRUVICA

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 label of the bottle after the word EXP. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
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 IMBRUVICA contains

• The active substance is ibrutinib. Each hard capsule contains 140 mg of ibrutinib.
• The other components are:
  • capsule contents: croscarmellose sodium, magnesium stearate, microcrystalline cellulose, and sodium lauryl sulfate (E487)
  • capsule shell: gelatin and titanium dioxide (E171)
  • printing ink: shellac, iron oxide black (E172), and propylene glycol (E1520).

Description of the appearance of IMBRUVICA and package contents
IMBRUVICA consists of white, opaque hard capsules marked with “ibr 140 mg” in black ink on one side.
The capsules are contained in a plastic bottle with a child-resistant polypropylene closure. Each bottle contains 90 or 120 capsules. Each cardboard box contains one bottle.

Marketing Authorization Holder
Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

Manufacturer
Janssen Pharmaceutica NV
Turnhoutseweg 30
2340 Beerse
Belgium
Janssen-Cilag SpA
Via C. Janssen
Loc. Borgo S. Michele
04100 Latina
Italy

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

België/Belgique/Belgien Lietuva
Janssen-Cilag NV UAB "JOHNSON & JOHNSON"
Tel/Tél: +32 14 64 94 11 Tel: +370 5 278 68 88
[email protected] [email protected]

България Luxembourg/Luxemburg
„Джонсън & Джонсън България” ЕООД Janssen-Cilag NV
Тел.: +359 2 489 94 00 Tél/Tel: +32 14 64 94 11
[email protected] [email protected]

Česká republika Magyarország
Janssen-Cilag s.r.o. Janssen-Cilag Kft.
Tel: +420 227 012 227 Tel.: +36 1 884 2858
[email protected]

Danmark Malta
Janssen-Cilag A/S AM MANGION LTD
Tlf.: +45 45 94 82 82 Tel: +356 2397 6000
[email protected]

Deutschland Nederland
Janssen-Cilag GmbH Janssen-Cilag B.V.
Tel: 0800 086 9247 / +49 2137 955 6955 Tel: +31 76 711 1111
[email protected] [email protected]

Eesti Norge
UAB "JOHNSON & JOHNSON" Eesti filiaal Janssen-Cilag AS
Tel: +372 617 7410 Tlf: +47 24 12 65 00
[email protected] [email protected]

Ελλάδα Österreich
Janssen-Cilag Φαρμακευτική Μονοπρόσωπη Janssen-Cilag Pharma GmbH
Α.Ε.Β.Ε. Tel: +43 1 610 300
Tηλ: +30 210 80 90 000

España Polska
Janssen-Cilag, S.A. Janssen-Cilag Polska Sp. z o.o.
Tel: +34 91 722 81 00 Tel.: +48 22 237 60 00
[email protected]

France Portugal
Janssen-Cilag Janssen-Cilag Farmacêutica, Lda.
Tél: 0 800 25 50 75 / +33 1 55 00 40 03 Tel: +351 214 368 600
[email protected]

Hrvatska România
Johnson & Johnson S.E. d.o.o. Johnson & Johnson România SRL
Tel: +385 1 6610 700 Tel: +40 21 207 1800
[email protected]

Ireland Slovenija
Janssen Sciences Ireland UC Johnson & Johnson d.o.o.
Tel: 1 800 709 122 Tel: +386 1 401 18 00
[email protected] [email protected]

Ísland Slovenská republika
Janssen-Cilag AB Johnson & Johnson, s.r.o.
c/o Vistor ehf. Tel: +421 232 408 400
Sími: +354 535 7000

Italia Suomi/Finland
Janssen-Cilag SpA Janssen-Cilag Oy
Tel: 800 688 777 / +39 02 2510 1 Puh/Tel: +358 207 531 300
[email protected] [email protected]

Κύπρος Sverige
Βαρνάβας Χατζηπαναγής Λτδ Janssen-Cilag AB
Τηλ: +357 22 207 700 Tfn: +46 8 626 50 00
[email protected]

Latvija
UAB "JOHNSON & JOHNSON" filiāle Latvijā
Tel: +371 678 93561
[email protected]

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

Patient Information Leaflet

IMBRUVICA 140 mg film-coated tablets, 280 mg film-coated tablets, 420 mg film-coated tablets, 560 mg film-coated tablets

ibrutinib
Please read 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, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

1. What IMBRUVICA is and what it is used for

What IMBRUVICA is
IMBRUVICA is an anticancer medicine that contains the active substance ibrutinib. It belongs to a
class of medicines called protein kinase inhibitors.
What IMBRUVICA is used for
IMBRUVICA is used in adult patients for the treatment of the following blood cancers:

• Mantle cell lymphoma (MCL), a type of cancer affecting the lymph nodes. IMBRUVICA is used in patients who have not been previously treated for MCL and for whom haematopoietic stem cell transplantation would be suitable, or when the disease has relapsed or has not responded to treatment.
• Chronic lymphocytic leukaemia (CLL), a type of cancer affecting white blood cells called lymphocytes, which also involves the lymph nodes. IMBRUVICA is used in patients who have not been previously treated for CLL or when the disease has relapsed or has not responded to treatment.
• Waldenström's macroglobulinaemia (WM), a type of cancer affecting white blood cells called lymphocytes. It is used in patients who have not been previously treated for WM or when the disease has relapsed, has not responded to treatment, or in patients for whom chemotherapy combined with an antibody is not appropriate.

How IMBRUVICA works
In MCL, CLL and WM, IMBRUVICA works by blocking "Bruton's tyrosine kinase", a protein in the body that helps these cancer cells grow and survive. By blocking this protein, IMBRUVICA helps kill and reduce the number of cancer cells. IMBRUVICA also slows down the progression of cancer.

2. What you should know before taking IMBRUVICA

Do not take IMBRUVICA

• if you are allergic to ibrutinib or any of the other ingredients of this medicine (listed in section 6).
• if you are taking a herbal medicine called St. John’s wort, used for depression. If in doubt, consult your doctor, pharmacist, or nurse before taking this medicine.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking IMBRUVICA:

• if you have ever had unusual bruising or bleeding, or if you are taking a medicine or supplement that increases the risk of bleeding (see Other medicines and IMBRUVICA)
• if you have had an irregular heartbeat or have previously had an irregular heartbeat or severe heart failure, or if you experience any of the following: shortness of breath, weakness, dizziness, lightheadedness, fainting or near-fainting, chest pain, or swelling in the legs
• if you have liver problems, including if you have ever had or currently have hepatitis B infection (a liver infection)
• if you have high blood pressure
• if you have recently undergone surgery, especially if this may affect how you absorb food or medicines from the stomach or intestine
• if you are scheduled for surgery: your doctor may ask you to stop taking IMBRUVICA for a short time (3 to 7 days before and after your surgery)
• if you have kidney problems.

If any of the points listed above apply to you (or if you have any doubts), talk to your doctor, pharmacist, or nurse before taking or while taking this medicine (see section “Possible side effects”).
While taking IMBRUVICA, inform your doctor immediately if you, or someone else, notice: memory loss, difficulty thinking, difficulty walking, or loss of vision – these symptoms may be caused by a rare but serious brain infection that can be fatal (progressive multifocal leukoencephalopathy or PML).
Inform your doctor immediately if you or someone else notices: sudden numbness or weakness in the limbs (especially on one side of the body), sudden confusion, difficulty speaking or understanding speech, loss of vision, difficulty walking, loss of balance or coordination, or sudden severe headache without a known cause. These may be signs and symptoms of stroke.
Inform your doctor immediately if you experience pain in the upper left part of the abdomen, pain under the left side of the rib cage, or in the upper part of the left shoulder (these may be symptoms of spleen rupture) after stopping IMBRUVICA.

Effects on the heart
Treatment with IMBRUVICA may affect the heart, especially if you already have heart conditions such as rhythm problems, heart failure, high blood pressure, diabetes, or if you are elderly. These effects can be serious and potentially fatal, sometimes causing sudden death. Your heart function will be monitored before and during treatment with IMBRUVICA. Inform your doctor immediately if you experience shortness of breath, difficulty breathing when lying down, swelling of the feet, ankles, or legs, or weakness/fatigue during treatment with IMBRUVICA, as these may be signs of heart failure.

Infections
During treatment with IMBRUVICA, you may develop viral, bacterial, or fungal infections. Contact your doctor if you have fever, chills, weakness, mental confusion, body aches, cold or flu-like symptoms, feeling tired, shortness of breath, or yellowing of the skin or eyes (jaundice). These could be signs of an infection.

Hemophagocytic lymphohistiocytosis
Cases of excessive white blood cell activation associated with inflammation (hemophagocytic lymphohistiocytosis) have been reported, which can be fatal if not diagnosed and treated promptly. If you develop multiple symptoms such as fever, swollen glands, bruising, or skin rashes, contact your doctor immediately.

Tests and monitoring before and during treatment
Tumor lysis syndrome (TLS): Unusual levels of chemicals in the blood caused by the rapid breakdown of tumor cells have been observed during cancer treatment, and sometimes even without treatment. This may lead to changes in kidney function, abnormal heartbeat, or seizures. Your doctor or another healthcare provider may perform blood tests to monitor for TLS.

Lymphocytosis: Laboratory tests may show an increase in white blood cells (called "lymphocytes") in the blood during the first few weeks of treatment. This is an expected effect and may last for several months. This does not necessarily mean that your blood cancer is worsening. Your doctor will check your blood cell counts before or during treatment, and in rare cases, you may need another medicine. Ask your doctor to explain what your test results mean.

Liver-related events: Your doctor will perform blood tests to check whether your liver is functioning properly, to rule out a liver infection known as viral hepatitis, or to monitor for reactivation of hepatitis B, which could be fatal.

Children and adolescents
IMBRUVICA must not be used in children and adolescents.

Other medicines and IMBRUVICA
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. This includes medicines not requiring a prescription, herbal medicines, and supplements. This is because IMBRUVICA can affect how other medicines work. In addition, some medicines can affect how IMBRUVICA works.

IMBRUVICA may increase the risk of bleeding. This means you must inform your doctor if you are taking other medicines that increase the risk of bleeding. These include:

• acetylsalicylic acid and non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or naproxen
• blood thinners such as warfarin, heparin, or other anticoagulant medicines
• dietary supplements that may increase the risk of bleeding, such as fish oil, vitamin E, or flaxseed.

If any of the points listed above apply to you (or if you have any doubts), talk to your doctor, pharmacist, or nurse before taking IMBRUVICA.

Also, inform your doctor if you are taking any of the following medicines – The effects of IMBRUVICA or other medicines may be affected if you take IMBRUVICA together with any of the following:

• medicines called antibiotics, used to treat bacterial infections: clarithromycin, telithromycin, ciprofloxacin, erythromycin, or rifampicin
• medicines for fungal infections: posaconazole, ketoconazole, itraconazole, fluconazole, or voriconazole
• medicines for HIV infection: ritonavir, cobicistat, indinavir, nelfinavir, saquinavir, amprenavir, atazanavir, or fosamprenavir
• medicines to prevent nausea and vomiting associated with chemotherapy: aprepitant
• medicines for depression: nefazodone
• medicines called kinase inhibitors for the treatment of other cancers: crizotinib or imatinib
• medicines called calcium channel blockers for hypertension or angina: diltiazem or verapamil
• medicines called statins for high cholesterol: rosuvastatin
• medicines for arrhythmias: amiodarone or dronedarone
• medicines to prevent or treat epileptic seizures or to treat a painful facial condition called trigeminal neuralgia: carbamazepine or phenytoin.

If any of the points listed above apply to you (or if you have any doubts), talk to your doctor, pharmacist, or nurse before taking IMBRUVICA.
If you are taking digoxin, a medicine used for heart problems, or methotrexate, a medicine used to treat other cancers and to reduce immune system activity (e.g. for rheumatoid arthritis or psoriasis), these should be taken at least 6 hours before or after IMBRUVICA.

IMBRUVICA with food
Do not take IMBRUVICA with grapefruit or Seville (bitter) oranges, meaning do not eat them, drink their juice, or take supplements containing them. This is because they can increase the amount of IMBRUVICA in your blood.

Pregnancy and breastfeeding
Avoid becoming pregnant during treatment with this medicine. IMBRUVICA must not be used during pregnancy.
There is no information on the safety of IMBRUVICA in pregnant women.
Women of childbearing potential must use a highly effective method of contraception during and for at least three months after treatment with IMBRUVICA to avoid becoming pregnant while on treatment with IMBRUVICA.

• Inform your doctor immediately if you become pregnant.
• Do not breastfeed while taking this medicine.

Driving and using machines
After taking IMBRUVICA, you may feel tired or dizzy, which may affect your ability to drive or operate tools or machinery.

IMBRUVICA contains lactose
IMBRUVICA contains lactose (a type of sugar). If your doctor has diagnosed you with an intolerance to certain sugars, contact him or her before taking this medicine.

IMBRUVICA contains sodium
IMBRUVICA contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially 'sodium-free'.

3. How to take IMBRUVICA

Take this medicine exactly as your doctor, pharmacist, or nurse has told you. If you are unsure, consult your doctor, pharmacist, or nurse.

Dosage
Mantle cell lymphoma (MCL)
The recommended dose of IMBRUVICA is 560 mg once daily.

Chronic lymphocytic leukemia (CLL)/Waldenström’s macroglobulinemia (WM)
The recommended dose of IMBRUVICA is 420 mg once daily.
Your doctor may adjust the dose.

How to take this medicine

• Take the tablets orally with a glass of water.
• Take the tablets at approximately the same time each day.
• Swallow the tablets whole; do not break or chew the tablets.

If you take more IMBRUVICA than you should
If you take more IMBRUVICA than you should, contact your doctor or go to hospital immediately. Bring the tablets and this leaflet with you.

If you forget to take IMBRUVICA

• If you miss a dose, it can be taken as soon as possible on the same day, returning to your regular schedule the next day.
• Do not take a double dose to make up for a missed dose.
• If you have any doubts about when to take the next dose, consult your doctor, pharmacist, or nurse.

If you stop taking IMBRUVICA
Do not stop taking this medicine unless your doctor tells you to.
If you have any questions about using this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
The following side effects may occur with this medicine:
If you notice any of the side effects listed in this leaflet, stop taking IMBRUVICA and contact your doctor immediately:
irregular, itchy rash, difficulty breathing, swelling of the face, lips, tongue or throat.
These may be signs of an allergic reaction to the medicine.
Contact your doctor immediately if you notice any of the following side effects:

Patients treated with IMBRUVICA for B-cell cancers:

Very common (affects more than 1 in 10 patients)

• fever, chills, muscle pain, feeling tired, cold or flu-like symptoms, shortness of breath – these may be signs of an infection (viral, bacterial or fungal). These may include infections of the nose, sinuses or throat (upper respiratory tract infection), or of the lung or skin
• blood in the stomach, intestines, faeces or urine, heavier menstrual periods or uncontrolled bleeding from a wound
• bruising or increased tendency to bruise
• mouth ulcers
• dizziness
• headache
• constipation
• nausea or vomiting
• indigestion
• diarrhoea: your doctor may give you fluids and salts or another medicine
• rash
• pain in arms or legs
• back or joint pain
• muscle cramps, pain or spasms
• fever
• blood tests showing low number of cells that help blood to clot (platelets), very low white blood cell count
• blood tests showing increased number or percentage of white blood cells
• swollen hands, ankles or feet
• high blood pressure
• increased level of “creatinine” in the blood.

Common (may affect up to 1 in 10 patients)

• serious infections throughout the body (sepsis)
• urinary tract infections
• nosebleeds, small red or purple spots caused by bleeding under the skin
• heart failure
• irregular heartbeats, weak or irregular pulse, mental confusion, shortness of breath, chest discomfort (symptoms of heart rhythm problems)
• low white blood cell count with fever (febrile neutropenia)
• non-melanoma skin cancer, most frequently squamous cell carcinoma and basal cell carcinoma
• blurred vision
• red skin
• hives (urticaria)
• lung inflammation that may lead to permanent damage
• high level of “uric acid” in the blood (shown by blood tests), which may cause gout
• nail breakage
• sudden kidney damage
• weakness, numbness, tingling or pain in hands or feet or other parts of the body (peripheral neuropathy).

Uncommon (may affect up to 1 in 100 patients)

• liver failure, including fatal events
• serious fungal infections
• “reactivation” of hepatitis B (if you previously had hepatitis B, it may reappear)
• bleeding on the surface of the brain
• confusion, headache with speech disturbance or feeling faint: may be signs of serious internal bleeding in the brain
• abnormal levels of chemicals in the blood caused by rapid destruction of tumour cells during cancer treatment, and sometimes even without treatment (tumour lysis syndrome)
• allergic reaction, sometimes severe, which may include swelling of the face, lips, mouth, tongue or throat, difficulty swallowing or breathing, itchy rash (urticaria)
• inflammation of subcutaneous fatty tissue
• temporary episode of reduced brain or nerve function due to reduced blood flow, stroke
• bleeding in the eye (in some cases associated with loss of vision)
• cardiac arrest (the heart stops beating)
• abnormally rapid heartbeat
• painful skin ulcers (pyoderma gangrenosum) or red, raised and painful skin lesions, fever and increased white blood cell count (may be signs of acute febrile neutrophilic dermatosis or Sweet’s syndrome)
• small red bump on the skin that may bleed easily (pyogenic granuloma)
• inflamed blood vessels in the skin that may cause a rash (cutaneous vasculitis).

Rare (may affect up to 1 in 1,000 patients)

• severe increase in white blood cell count in the blood, which may cause cells to clump together
• severe skin rash with blisters and peeling of the skin, especially around the mouth, nose, eyes and genitals (Stevens-Johnson syndrome).

Patients treated with IMBRUVICA for previously untreated MCL

Very common (affects more than 1 in 10 patients)

• blood tests showing low number of cells that help blood to clot (platelets), very low white blood cell count
• low white blood cell count with fever (febrile neutropenia)
• nausea or vomiting
• diarrhoea: your doctor may give you fluids and salts or another medicine
• mouth ulcers
• constipation
• fever
• fever, chills, muscle pain, feeling tired, cold or flu-like symptoms, shortness of breath – these may be signs of an infection (viral, bacterial or fungal). These may include infections of the lungs or skin
• increased level of “creatinine” in the blood
• pain in arms or legs
• weakness, numbness, tingling or pain in hands or feet or other parts of the body (peripheral neuropathy)
• headache
• sudden kidney damage
• rash
• blood in the stomach, intestines, faeces or urine, heavier menstrual periods or uncontrolled bleeding from a wound
• high blood pressure.

Common (may affect up to 1 in 10 patients)

• increased white blood cell count
• infections of the nose, sinuses or throat (upper respiratory tract infections)
• irregular heartbeats, weak or irregular pulse, mental confusion, shortness of breath, chest discomfort (symptoms of heart rhythm problems)
• heart failure
• indigestion
• swollen hands, ankles or feet
• lung inflammation, which may lead to permanent damage
• serious infections throughout the body (sepsis)
• urinary tract infections
• high level of “uric acid” in the blood (shown by blood tests), which may cause gout
• abnormal levels of chemicals in the blood caused by rapid destruction of tumour cells during cancer treatment and sometimes even without treatment (tumour lysis syndrome)
• muscle cramps, pain or spasms
• back or joint pain
• non-melanoma skin cancer, including basal cell carcinoma
• dizziness
• red skin
• nail breakage
• hives (urticaria)
• bruising or increased tendency to bruise
• nosebleeds, small red or purple spots caused by bleeding under the skin.

Uncommon (may affect up to 1 in 100 patients)

• blurred vision
• serious fungal infections
• bleeding in the eye
• temporary episode of reduced brain or nerve function due to reduced blood flow, stroke
• allergic reaction, sometimes severe, which may include swelling of the face, lips, mouth, tongue or throat, difficulty swallowing or breathing, itchy rash (urticaria)
• inflamed blood vessels in the skin that may cause a rash (cutaneous vasculitis)
• inflammation of subcutaneous fatty tissue.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse.
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 IMBRUVICA

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after "EXP". The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
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 IMBRUVICA contains

• The active substance is ibrutinib.
• IMBRUVICA 140 mg film-coated tablets: each tablet contains 140 mg of ibrutinib.
• IMBRUVICA 280 mg film-coated tablets: each tablet contains 280 mg of ibrutinib.
• IMBRUVICA 420 mg film-coated tablets: each tablet contains 420 mg of ibrutinib.
• IMBRUVICA 560 mg film-coated tablets: each tablet contains 560 mg of ibrutinib.
• The other components are:
• Tablet core: anhydrous colloidal silica, sodium croscarmellose, monohydrate lactose (see section 2 “IMBRUVICA contains lactose”), magnesium stearate, microcrystalline cellulose, povidone, sodium lauryl sulfate (E487).
• Film coating: polyvinyl alcohol, macrogol, talc, titanium dioxide (E171); IMBRUVICA 140 mg and IMBRUVICA 420 mg film-coated tablets also contain black iron oxide (E172) and yellow iron oxide (E172); IMBRUVICA 280 mg film-coated tablets also contain black iron oxide (E172) and red iron oxide (E172); IMBRUVICA 560 mg film-coated tablets also contain red iron oxide (E172) and yellow iron oxide (E172).

Description of the appearance of IMBRUVICA and package contents
IMBRUVICA 140 mg film-coated tablets
Yellow-green to green, round tablets (9 mm), marked "ibr" on one side and "140" on the other.
Each 28-day pack contains 28 film-coated tablets in 2 blisters of 14 film-coated tablets each. Each 30-day pack contains 30 film-coated tablets in 3 blisters of 10 film-coated tablets each.
IMBRUVICA 280 mg film-coated tablets
Purple, oblong tablets (15 mm in length and 7 mm in width), marked "ibr" on one side and "280" on the other.
Each 28-day pack contains 28 film-coated tablets in 2 blisters of 14 film-coated tablets each. Each 30-day pack contains 30 film-coated tablets in 3 blisters of 10 film-coated tablets each.
IMBRUVICA 420 mg film-coated tablets
Yellow-green to green, oblong tablets (17.5 mm in length and 7.4 mm in width), marked "ibr" on one side and "420" on the other.
Each 28-day pack contains 28 film-coated tablets in 2 blisters of 14 film-coated tablets each. Each 30-day pack contains 30 film-coated tablets in 3 blisters of 10 film-coated tablets each.
IMBRUVICA 560 mg film-coated tablets
Yellow to orange, oblong tablets (19 mm in length and 8.1 mm in width), marked "ibr" on one side and "560" on the other.
Each 28-day pack contains 28 film-coated tablets in 2 blisters of 14 film-coated tablets each. Each 30-day pack contains 30 film-coated tablets in 3 blisters of 10 film-coated tablets each.

Marketing Authorization Holder
Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

Manufacturer
Janssen-Cilag SpA
Via C. Janssen
Loc. Borgo S. Michele
04100 Latina
Italy

For further information on this medicinal product, please contact the local representative of the Marketing Authorization Holder:

België/Belgique/Belgien Lietuva
Janssen-Cilag NV UAB "JOHNSON & JOHNSON"
Tel/Tél: +32 14 64 94 11 Tel: +370 5 278 68 88
[email protected] [email protected]

България Luxembourg/Luxemburg
„Джонсън & Джонсън България” ЕООД Janssen-Cilag NV
Тел.: +359 2 489 94 00 Tél/Tel: +32 14 64 94 11
[email protected] [email protected]

Česká republika Magyarország
Janssen-Cilag s.r.o. Janssen-Cilag Kft.
Tel: +420 227 012 227 Tel.: +36 1 884 2858
[email protected]

Danmark Malta
Janssen-Cilag A/S AM MANGION LTD
Tlf.: +45 45 94 82 82 Tel: +356 2397 6000
[email protected]

Deutschland Nederland
Janssen-Cilag GmbH Janssen-Cilag B.V.
Tel: 0800 086 9247 / +49 2137 955 6955 Tel: +31 76 711 1111
[email protected] [email protected]

Eesti Norge
UAB "JOHNSON & JOHNSON" Eesti filiaal Janssen-Cilag AS
Tel: +372 617 7410 Tlf: +47 24 12 65 00
[email protected] [email protected]

Ελλάδα Österreich
Janssen-Cilag Φαρμακευτική Μονοπρόσωπη Janssen-Cilag Pharma GmbH
Α.Ε.Β.Ε. Tel: +43 1 610 300
Tηλ: +30 210 80 90 000

España Polska
Janssen-Cilag, S.A. Janssen-Cilag Polska Sp. z o.o.
Tel: +34 91 722 81 00 Tel.: +48 22 237 60 00
[email protected]

France Portugal
Janssen-Cilag Janssen-Cilag Farmacêutica, Lda.
Tél: 0 800 25 50 75 / +33 1 55 00 40 03 Tel: +351 214 368 600
[email protected]

Hrvatska România
Johnson & Johnson S.E. d.o.o. Johnson & Johnson România SRL
Tel: +385 1 6610 700 Tel: +40 21 207 1800
[email protected]

Ireland Slovenija
Janssen Sciences Ireland UC Johnson & Johnson d.o.o.
Tel: 1 800 709 122 Tel: +386 1 401 18 00
[email protected] [email protected]

Ísland Slovenská republika
Janssen-Cilag AB Johnson & Johnson, s.r.o.
c/o Vistor ehf. Tel: +421 232 408 400
Sími: +354 535 7000
[email protected]

Italia Suomi/Finland
Janssen-Cilag SpA Janssen-Cilag Oy
Tel: 800 688 777 / +39 02 2510 1 Puh/Tel: +358 207 531 300
[email protected] [email protected]

Κύπρος Sverige
Βαρνάβας Χατζηπαναγής Λτδ Janssen-Cilag AB
Τηλ: +357 22 207 700 Tfn: +46 8 626 50 00
[email protected]

Latvija
UAB "JOHNSON & JOHNSON" filiāle Latvijā
Tel: +371 678 93561
[email protected]

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