IMBRUVICA 140 mg FILM-COATED TABLETS

2. What you need to know before you take 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 medicine based on a plant called St. John's Wort or hypericum, used for depression. If you are not sure, consult your doctor, pharmacist, or nurse before taking this medicine.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before you start taking IMBRUVICA:

• if you have ever had unusual bleeding or bruising or if you are taking any medicines or supplements that increase your risk of bleeding (see section “Using IMBRUVICA with other medicines”)
• if you have had irregular heartbeats, have a history of irregular heartbeats or severe heart failure, or if you feel any of the following: difficulty breathing, weakness, dizziness, fainting, or feeling like you are going to faint, chest pain, or swollen legs
• if you have liver or kidney problems
• if you have high blood pressure
• if you have recently had surgery, especially if it has affected the absorption of food or medicines in the stomach or intestine
• if you are going to have surgery, your doctor may ask you to stop taking IMBRUVICA for a short period (3 to 7 days) before and after surgery
• if you have had a hepatitis B infection or may have it now. This is because IMBRUVICA may reactivate hepatitis B. Patients will be carefully checked by their doctor for signs of this infection before starting treatment.

If any of the above apply to you (or if you are not sure), talk to your doctor, pharmacist, or nurse before taking this medicine.

When taking IMBRUVICA, tell 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 that can be life-threatening (Progressive Multifocal Leukoencephalopathy or PML).

Tests and checks before and during treatment

Tumour Lysis Syndrome (TLS): There have been cases of abnormal levels of chemicals 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 heartbeats, or seizures. Your doctor or other healthcare professional may do blood tests to check for TLS.

Lymphocytosis: Laboratory tests may show an increase in white blood cells (called “lymphocytes”) in your blood during the first few weeks of treatment. This effect 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 tests before or during treatment and in rare cases may need to give you another medicine. Talk to your doctor about the meaning of the results of these tests.

Children and adolescents

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

Other medicines and IMBRUVICA

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those bought without a prescription, herbal medicines, and supplements. This is because IMBRUVICA may affect the way other medicines work. Also, other medicines may affect the way IMBRUVICA works.

IMBRUVICA may make you bleed more easily.This means you should tell your doctor if you are taking other medicines that increase your risk of bleeding. These include:

• aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or naproxen

• anticoagulants such as warfarin, heparin, or other medicines that prevent blood clots

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

If any of the above apply to you (or if you are not sure), talk to your doctor, pharmacist, or nurse before taking IMBRUVICA.

Tell 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 with any of the following medicines:

• antibiotics 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 high blood pressure or chest pain: diltiazem or verapamil
• medicines called statins to treat high cholesterol: rosuvastatin
• medicines for the heart/antiarrhythmics: amiodarone or dronedarone
• medicines to prevent seizures or to treat epilepsy, or medicines to treat a painful condition of the face called trigeminal neuralgia: carbamazepine or phenytoin.

If any of the above apply to you (or if you are not sure), 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 the activity of the immune system (e.g., for rheumatoid arthritis or psoriasis), you should take it at least 6 hours before or after IMBRUVICA.

Using IMBRUVICA with food

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

Pregnancy and breast-feeding

You should not become pregnant while taking this medicine.

IMBRUVICA should not be used during pregnancy. There is no information on the safety of IMBRUVICA in pregnant women.

Women of childbearing age must use a very effective method of contraception during treatment and for up to 3 months after receiving IMBRUVICA, to prevent pregnancy during treatment with IMBRUVICA. If you use hormonal contraceptives, such as birth control pills or contraceptive devices, you should also use a barrier method of contraception (e.g., condoms).

• Tell your doctor immediately if you become pregnant.
• Do not breast-feed your child while taking this medicine.

Driving and using machines

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

IMBRUVICA contains lactose

IMBRUVICA contains lactose (a type of sugar). If your doctor has told you that you have an intolerance to some sugars, talk to your doctor before taking this medicine.

IMBRUVICA contains sodium

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

3. How to take IMBRUVICA

Always take this medicine exactly as your doctor, pharmacist, or nurse has told you. If you are not sure, talk to your doctor, pharmacist, or nurse.

How much to take

Mantle Cell Lymphoma (MCL)

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

Chronic Lymphocytic Leukaemia (CLL)/Waldenström's Macroglobulinaemia (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 by mouth with a glass of water.
• Take the tablets at about 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, talk to your doctor or go to the hospital immediately.

Take 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 possible on the same day and go back to your normal schedule the next day.
• Do not take a double dose to make up for a forgotten dose.
• If you are not sure, talk to your doctor, pharmacist, or nurse about when to take your next dose.

If you stop taking IMBRUVICA

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

If you have any further questions on the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The following side effects may happen with this medicine:

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

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.

Tell your doctor immediately if you experience any of the following side effects:

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

• fever, chills, body pain, feeling tired, cold or flu symptoms, difficulty breathing: all these can be symptoms of an infection (caused by a virus, bacteria, or fungus). They can include infections of the nose, sinuses, or throat (upper respiratory tract infections), or of the lungs, or of the skin.
• bruising or increased tendency to bruise
• mouth sores
• headache
• constipation
• feeling or being sick (nausea or vomiting)
• diarrhoea, your doctor may need to give you treatment to replace fluids and salts or another medicine
• rash
• pain in arms or legs
• back pain or joint pain
• muscle spasms, muscle pain, or muscle cramps
• low number of platelets, very low number of white blood cells: shown 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 (septicaemia)
• urinary tract infections
• nosebleeds, small red or purple spots caused by bleeding under the skin
• bleeding in the stomach, intestine, stools, or urine, increased bleeding during menstruation, or bleeding from a wound that cannot be stopped
• increased heart rate, missed heartbeats, weak or irregular pulse, dizziness, difficulty breathing, discomfort in the chest (symptoms of heart rhythm disorders)
• increased number or proportion of white blood cells in blood tests
• low white blood cell count with fever (febrile neutropenia)
• abnormal levels of chemicals in the blood, caused by the rapid breakdown of cancer cells during treatment and sometimes even without treatment (tumour lysis syndrome)
• skin cancer other than melanoma, most commonly basal cell carcinoma and squamous cell carcinoma
• feeling dizzy
• blurred vision
• redness of the skin
• high levels of “uric acid” in the blood (shown in blood tests), which can cause gout
• inflammation of the airways (pulmonary) that can lead to permanent damage
• breaking of the 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 problems speaking or feeling like you are going to faint: these can be symptoms of a severe and rare brain haemorrhage

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

• inflammation of the fatty tissue under the skin.

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

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

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

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

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V.

By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of IMBRUVICA

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

Do not use this medicine after the expiry date which is stated on the carton after EXP.

The expiry date is the last day of the month shown.

No special storage conditions are required.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Packaging Contents and Additional Information

Composition of IMBRUVICA

• 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 ingredients are:

• Tablet core: anhydrous colloidal 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 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).

Appearance and Packaging Contents

IMBRUVICA 140 mg film-coated tablets

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

IMBRUVICA 280 mg film-coated tablets

Purple, oblong tablet (15 mm in length and 7 mm in thickness), marked with "ibr" on one side and "280" on the other side. Each 28-day box contains 28 film-coated tablets in 2 cardboard boxes with 14 film-coated tablets each. Each 30-day box contains 30 film-coated tablets in 3 cardboard boxes with 10 film-coated tablets each.

IMBRUVICA 420 mg film-coated tablets

Greenish-yellow to green, oblong tablet (17.5 mm in length and 7.4 mm in thickness), marked with "ibr" on one side and "420" on the other side. Each 28-day box contains 28 film-coated tablets in 2 cardboard boxes with 14 film-coated tablets each. Each 30-day box contains 30 film-coated tablets in 3 cardboard boxes with 10 film-coated tablets each.

IMBRUVICA 560 mg film-coated tablets

Yellow to orange, oblong tablet (19 mm in length and 8.1 mm in thickness), marked with "ibr" on one side and "560" on the other side. Each 28-day box contains 28 film-coated tablets in 2 cardboard boxes with 14 film-coated tablets each. Each 30-day box contains 30 film-coated tablets in 3 cardboard boxes with 10 film-coated tablets each.

Marketing Authorisation 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, please contact the local representative of the Marketing Authorisation Holder:

Date of Last Revision of this Leaflet:

Other Sources of Information

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