Product Information for the Patient

IMBRUVICA 140 mg Film-Coated Tablets

IMBRUVICA 280 mg Film-Coated Tablets

IMBRUVICA 420 mg Film-Coated Tablets

IMBRUVICA 560 mg Film-Coated Tablets

Ibrutinib

Read this entire product information carefully before starting to take this medicine, as it contains important information for you.

• Keep this product information, as you may need to read it again.
• If you have any doubts, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed only for you, and you must not give it to others, even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this product information. See section 4.

What is IMBRUVICA

IMBRUVICA is a cancer medication that contains the active ingredient ibrutinib, which belongs to a class of medications called protein kinase inhibitors.

What is IMBRUVICA used for

It is used in adults for the treatment of the following blood cancers:

• Mantle Cell Lymphoma (MCL), a type of cancer that affects the lymph nodes, when the disease has relapsed or not responded to treatment.
• Chronic Lymphocytic Leukemia (CLL), a type of cancer that affects the white blood cells in the blood called lymphocytes, which also affects the lymph nodes. IMBRUVICA is used in patients with CLL who have not been previously treated or when the disease has relapsed and not responded to treatment.
• Waldenström Macroglobulinemia (WM), a type of cancer that affects the white blood cells in the blood called lymphocytes. It is used when the disease has relapsed or not responded to treatment or in patients for whom chemotherapy administered with an antibody is not an appropriate treatment.

How IMBRUVICA works

In MCL, CLL, and WM, IMBRUVICA works by blocking Bruton's tyrosine kinase, a protein in the body that helps cancer cells to grow and survive. By blocking this protein, IMBRUVICA helps to destroy and reduce the number of cancer cells. It may also slow down the worsening of the cancer.

Do not take IMBRUVICA

• If you are allergic to ibrutinib or any of the other components of this medication (listed in section 6)
• If you are taking a medication made from a plant called St. John's Wort or hypericum, used for depression. If you are unsure, consult your doctor, pharmacist, or nurse before taking this medication.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to take IMBRUVICA:

• If you have ever had unusual bleeding or bruising, or if you are taking any medication or supplements that increase your risk of bleeding (see section “Use of IMBRUVICA with other medications”)
• If you have had irregular heartbeats, have a history of irregular heartbeats, or severe heart failure, or if you experience any of the following: difficulty breathing, weakness, dizziness, fainting, or near-fainting, chest pain, or swollen legs
• If you have liver or kidney problems
• If you have high blood pressure
• If you have recently undergone surgery, especially if it has affected the absorption of food or medication in the stomach or intestines
• If you are about to undergo surgery, your doctor may ask you to stop taking IMBRUVICA for a short period of time (3 to 7 days) before and after the surgery
• If you have had a Hepatitis B infection or could have it now. This is because IMBRUVICA can reactivate Hepatitis B. Patients will be carefully examined by their doctor to detect signs of this infection before starting treatment.

If any of the above situations apply to you (or if you are unsure), consult your doctor, pharmacist, or nurse before taking this medication.

While taking IMBRUVICA, inform your doctor immediately if you notice or someone notices in you: memory loss, confusion, difficulty walking, or loss of vision – these may be due to a rare but serious brain infection called Leucoencephalopathy Multifocal Progressive (LMP).

Tests and controls before and during treatment

Thrombotic Thrombocytopenic Purpura (TTP): There have been cases of atypical levels of chemical substances in the blood caused by the rapid breakdown of cancer cells during treatment and sometimes even without treatment. This can lead to changes in kidney function, abnormal heart rhythm, or seizures. Your doctor or other healthcare personnel may perform blood tests to check for TTP.

Lymphocytosis: Laboratory tests may show an increase in white blood cells (called “lymphocytes”) in your blood during the first weeks of treatment. This is expected and may last for several months. This does not necessarily mean that your blood cancer is getting worse.

Your doctor will check your blood test before or during treatment and in rare cases may need to administer another medication. Discuss the meaning of the results of these tests with your doctor.

Children and adolescents

IMBRUVICA should not be used in children or adolescents, as it has not been studied in these age groups.

Other medications and IMBRUVICA

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication, including over-the-counter medications, herbal medications, and supplements. This is because IMBRUVICA may affect how other medications work. Additionally, other medications may affect how IMBRUVICA works.

IMBRUVICA may increase your risk of bleeding.That means you should inform your doctor if you are taking other medications that increase your risk of bleeding. This includes:

• Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or naproxen

• Anticoagulants such as warfarin, heparin, or other medications that prevent blood clotting

• Supplements that may increase your risk of bleeding, such as fish oil, vitamin E, or flaxseed.

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

Also inform your doctor if you are taking any of the following medications:The effects of IMBRUVICA or other medications may be influenced if you take IMBRUVICA with any of the following medications:

• Antibiotics to treat bacterial infections: clarithromycin, telithromycin, ciprofloxacin, erythromycin, or rifampicin
• Medications for fungal infections: posaconazole, ketoconazole, itraconazole, fluconazole, or voriconazole
• Medications for HIV infection: ritonavir, cobicistat, indinavir, nelfinavir, saquinavir, atazanavir, or fosamprenavir
• Medications to prevent nausea and vomiting associated with chemotherapy: aprepitant
• Medications for depression: nefazodone
• Medications called kinase inhibitors for the treatment of other cancers: crizotinib or imatinib
• Medications called calcium channel blockers for high blood pressure or chest pain: diltiazem or verapamil
• Medications called statins to treat high cholesterol: rosuvastatin
• Medications for the heart/antiarrhythmics: amiodarone or dronedarone
• Medications to prevent seizures or to treat epilepsy, or medications to treat a painful facial disorder called trigeminal neuralgia: carbamazepine or phenytoin.

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

If you are taking digoxin, a medication used for heart problems, or methotrexate, a medication used to treat other cancers and to reduce the activity of the immune system (e.g., for rheumatoid arthritis or psoriasis), take it at least 6 hours before or after IMBRUVICA.

Use of IMBRUVICA with food

Do not take IMBRUVICA with grapefruit or bitter oranges: This means you cannot eat them, drink their juice, or take a supplement that may contain them. This is because they may increase the amount of IMBRUVICA in your blood.

Pregnancy and breastfeeding

Do not become pregnant during treatment with this medication.

Do not use IMBRUVICA during pregnancy. There is no information available on the safety of IMBRUVICA in pregnant women.

Women of childbearing age should use a very effective contraceptive method during treatment and for three months after receiving IMBRUVICA, to avoid becoming pregnant during treatment with IMBRUVICA. If you use hormonal contraceptives, such as pills or devices, you should also use a barrier method (e.g., condoms).

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

Driving and using machines

You may feel tired or dizzy after taking IMBRUVICA, which may affect your ability to drive or use any tool or machine.

IMBRUVICA contains lactose

IMBRUVICA contains lactose (a type of sugar). If your doctor has told you that you have an intolerance to certain sugars, consult with them before taking this medication.

IMBRUVICA contains sodium

IMBRUVICA contains less than 1 mmol of sodium (23 mg) per dose; this is, essentially “sodium-free”.

Follow exactly the administration instructions for this medication as indicated by your doctor, pharmacist, or nurse. If in doubt, consult your doctor, pharmacist, or nurse again.

How much to take

Mantle Cell Lymphoma (MCL)

The recommended dose of IMBRUVICA is 560 mg once a day.

Chronic Lymphocytic Leukemia (CLL)/Waldenström Macroglobulinemia (WM)

The recommended dose of IMBRUVICA is 420 mg once a day.

Your doctor may need to adjust your dose.

How to take IMBRUVICA

• Take the tablets orally (by mouth) with a glass of water.
• Take the tablets approximately at the same time every 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, consult your doctor or go to the hospital immediately.

Bring the tablets and this leaflet with you.

If you forget to take IMBRUVICA

• If you forget a dose, you can take it as soon as you remember that day and go back to your regular schedule the next day.
• Do not take a double dose to make up for the missed dose.
• If you are unsure, talk to your doctor, pharmacist, or nurse about when to take your next dose.

If you interrupt treatment with IMBRUVICA

Do not stop taking this medication unless your doctor tells you to.

If you have any other questions about the use of this medication, ask your doctor, pharmacist, or nurse.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

The following side effects may occur with this medicine:

Stop taking IMBRUVICA and immediately inform your doctor if you experience any of the following side effects:

skin rash with blisters and itching, difficulty breathing, swelling of the face, lips, tongue, or throat: you may be having an allergic reaction to the medicine.

Immediately inform your doctor if you experience any of the following side effects:

Very common(may affect more than 1 in 10 people)

• fever, chills, body aches, feeling tired, symptoms of a cold or flu, difficulty breathing: all of these can be symptoms of an infection (viral, bacterial, or fungal). They may include upper respiratory tract infections, or infections of the lungs, or skin.
• bruising or a tendency to bruise more easily
• mouth sores
• headache
• constipation
• feeling or being dizzy (nausea or vomiting)
• diarrhea, your doctor may need to administer a fluid and electrolyte replacement treatment or another medicine
• skin rash
• arm or leg pain
• back or joint pain
• muscle cramps, muscle pain, or muscle spasms
• low platelet count, very low white blood cell count: reflected in blood tests
• swollen hands, ankles, or feet
• high blood pressure.

Common(may affect up to 1 in 10 people)

• severe infections that spread throughout the body (septicemia)
• urinary tract infections
• nosebleeds, small red or purple spots caused by bleeding under the skin
• bleeding in the stomach, intestines, stool, or urine, heavier menstrual bleeding or bleeding from a wound that won't stop
• increased heart rate, absent heartbeats, weak or irregular pulse, dizziness, difficulty breathing, chest discomfort (symptoms of heart rhythm disorders)
• increased white blood cell count in blood tests
• febrile neutropenia (low white blood cell count with fever)
• unusual levels of chemicals in the blood, produced by rapid destruction of cancer cells during treatment and in some cases even without treatment (tumor lysis syndrome)
• skin cancer other than melanoma, more frequently basal cell carcinoma and squamous cell carcinoma
• dizziness
• blurred vision
• skin redness
• high levels of "uric acid" in the blood (reflected in blood tests), which can cause gout
• inflammation of the airways (pulmonary) that can lead to permanent damage
• broken nails
• weakness, numbness, tingling, or pain in the hands or feet or other parts of the body (peripheral neuropathy).

Uncommon(may affect up to 1 in 100 people)

• confusion, headache with difficulty speaking or feeling of fainting: these may be symptoms of a severe internal bleeding in the brain

• allergic reaction, sometimes severe, which may include swelling of the face, lip, mouth, tongue, or throat, difficulty swallowing or breathing, skin rash with itching (urticaria)

• inflammation of the subcutaneous tissue.

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

• intense increase in white blood cell count that can cause cells to clump together.

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

• liver insufficiency
• severe skin rash with blisters and skin peeling, particularly around the mouth, nose, eyes, and genitals (Stevens-Johnson syndrome).

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the national notification system included in theAppendix V.

By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the box after CAD.

The expiration date is the last day of the month indicated.

No special storage conditions are required.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications you no longer need. By doing so, you will help protect the environment.

IMBRUVICA Composition

• The active ingredient 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: colloidal anhydrous silica, sodium croscarmellose, lactose monohydrate (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 280 mg film-coated tablets also contain iron oxide black (E172) and iron oxide red (E172);

IMBRUVICA 560 mg film-coated tablets also contain iron oxide red (E172) and iron oxide yellow (E172).

Appearance of the product and contents of the pack

IMBRUVICA 140 mg film-coated tablets

Greenish-yellow to green, round tablet (9 mm), marked with “ibr” on one face and “140” on the other face. Each 28-day pack contains 28 film-coated tablets in 2 cardboard cartons with 14 film-coated tablets in each. Each 30-day pack contains 30 film-coated tablets in 3 cardboard cartons with 10 film-coated tablets in each.

IMBRUVICA 280 mg film-coated tablets

Purple, oblong tablet (15 mm long and 7 mm thick), marked with “ibr” on one face and “280” on the other face. Each 28-day pack contains 28 film-coated tablets in 2 cardboard cartons with 14 film-coated tablets in each. Each 30-day pack contains 30 film-coated tablets in 3 cardboard cartons with 10 film-coated tablets in each.

IMBRUVICA 420 mg film-coated tablets

Greenish-yellow to green, oblong tablet (17.5 mm long and 7.4 mm thick), marked with “ibr” on one face and “420” on the other face. Each 28-day pack contains 28 film-coated tablets in 2 cardboard cartons with 14 film-coated tablets in each. Each 30-day pack contains 30 film-coated tablets in 3 cardboard cartons with 10 film-coated tablets in each.

IMBRUVICA 560 mg film-coated tablets

Yellow to orange, oblong tablet (19 mm long and 8.1 mm thick), marked with “ibr” on one face and “560” on the other face. Each 28-day pack contains 28 film-coated tablets in 2 cardboard cartons with 14 film-coated tablets in each. Each 30-day pack contains 30 film-coated tablets in 3 cardboard cartons with 10 film-coated tablets in each.

Marketing Authorization Holder

Janssen-Cilag International NV

Turnhoutseweg 30

B-2340 Beerse

Belgium

Responsible for manufacturing

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:

Last update of the summary of product characteristics:

Other sources of information

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