140 mg, 280 mg, 420 mg, 560 mg film-coated tablets
ibrutinib
1. What IMBRUVICA is and what it is used for
What IMBRUVICA is
IMBRUVICA is a cancer medicine that contains the active substance ibrutinib. It belongs to a class of drugs called protein kinase inhibitors.
What IMBRUVICA is used for
It is used to treat the following types of blood cancer in adults:
- Mantle cell lymphoma (MCL), a type of cancer that affects the lymph nodes, when the disease has returned or has not responded to treatment.
- Chronic lymphocytic leukemia ( CLL ), a type of cancer that affects the white blood cells called lymphocytes and also involves the lymph nodes. IMBRUVICA is used for patients who have not previously been treated for CLL or when the disease has returned or has not responded to treatment.
- Waldenström’s macroglobulinemia (WM), a type of cancer that affects the white blood cells called lymphocytes . It is used in patients who have not been previously treated for WM or when the disease has returned or has not responded to treatment, or in patients where chemotherapy given with an antibody is not an appropriate treatment
How IMBRUVICA works
In MCL, KLL and WM, IMBRUVICA works by blocking “Bruton’s tyrosine kinase”, a protein in the body that helps these cancer cells to grow and survive. By blocking this protein , IMBRUVICA can help kill and reduce the number of cancer cells. It also slows down the worsening of the cancer.
What you need to 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 an herbal medicine called St. John’s wort , which is used for mild depression and mild anxiety. If you are not sure, talk to your doctor, pharmacist or nurse before taking this medicine.
Warnings and cautions
Talk to your doctor, pharmacist or nurse before taking IMBRUVICA:
- if you have ever had abnormal bruising or bleeding or are being treated with any other medicines or supplements that increase the risk of bleeding (see section Other medicines and IMBRUVICA )
- if you have an irregular heartbeat or have had an irregular heartbeat or severe heart failure , or if you experience any of the following: shortness of breath, weakness, dizziness, fainting, fainting or near fainting, chest pain or swollen legs
- if you have liver problems, including if you have ever had or now have a hepatitis B infection (a liver infection)
- if you have high blood pressure
- if you have recently had any surgery, especially if this may affect the absorption of food or medicine from the stomach or intestines
- if you are planning to have an operation – your doctor may ask you to stop taking IMBRUVICA for a short time (3 to 7 days) before and after the operation
- if you have kidney problems.
If any of the above apply to you (or you are not sure), talk to your doctor or pharmacist before taking this medicine.
When you take IMBRUVICA, tell your doctor immediately if you or anyone else notices the following: memory loss, difficulty thinking, difficulty walking or loss of vision – this may be due to a very rare but serious brain infection that can be fatal ( progressive multifocal leukoencephalopathy or PML).
Tell your doctor immediately if you or anyone else notices the following: sudden numbness or weakness in the arms and legs (especially on one side of the body), sudden confusion, difficulty speaking or understanding speech, loss of vision, difficulty walking, loss of balance or lack of coordination , sudden severe headache without known cause. These may be signs and symptoms of stroke (severe internal bleeding in the brain).
Tell your doctor immediately if you experience pain in the left upper abdomen (abdomen), pain under the chest on the left side or on the top of your left shoulder (this may be a symptom of rupture of the spleen) after stopping IMBRUVICA.
Tell your doctor immediately if you notice shortness of breath, difficulty breathing when lying down, swelling of the feet, ankles or legs and weakness / fatigue (this may be a sign of heart failure ) during treatment with IMBRUVICA.
During treatment with IMBRUVICA you may get viral , bacterial or fungal infections. Contact your doctor if you have a fever, chills, feel weak, confused, have body aches, cold or flu symptoms, feel tired or short of breath, or if your skin or whites of your eyes turn yellow (jaundice). This may be a sign of an infection .
Haemophagocytic lymphohistiocytosis
There have been isolated reports of overactivation of white blood cells associated with inflammation (haemophagocytic lymphohistiocytosis ), which can be fatal if not diagnosed and treated early. If you get more symptoms such as fever, swollen glands , bruising or rash, contact your doctor immediately.
Samples and controls before and during treatment
Tumor light syndrome (TLS): Unusual amounts of chemical substances in the blood caused by rapid breakdown of cancer cells have occurred during cancer treatment and sometimes even without treatment. This can lead to changes in kidney function, abnormal heartbeat or seizures. Your doctor or other healthcare professional may take blood samples to check if you have 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 expected and may persist for a few months. This does not have to mean that your blood cancer has worsened. Your doctor will check your blood levels before or during treatment and in rare cases you may need to be given another medicine. Talk to your doctor about what your test results mean.
Hepatic events: Your doctor will take some blood samples to make sure your liver is working properly and that you do not have a liver infection called viral hepatitis , or that hepatitis B has been reactivated, which can be fatal.
Children and young people
IMBRUVICA should not be used in children and adolescents. This is because 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. This also applies to over-the-counter medicines, herbal medicines and dietary supplements. This is because IMBRUVICA may affect the way other medicines work. Some other medicines may also affect the way IMBRUVICA works.
IMBRUVICA can make you bleed easier. This means that you should tell 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 anticoagulants
- dietary supplements that can increase the risk of bleeding such as fish oil, vitamin E or flaxseed.
If any of the above apply to you (or you are not sure), talk to your doctor, pharmacist or nurse before taking IMBRUVICA.
Also 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:
- drugs called antibiotics and used to treat bacterial infections – clarithromycin, telithromycin, ciprofloxacin , erythromycin or rifampicin
- antifungal drugs – posaconazole, ketoconazole , itraconazole, fluconazole or voriconazole
- HIV medicines – infection – ritonavir, cobicistat, indinavir, nelfinavir, saquvinavir, amprenavir, atazanavir or fosamprenavir
- drugs that counteract nausea and vomiting associated with chemotherapy – aprepitant
- antidepressant – nefazodone
- drugs called kinase inhibitors and used to treat other cancers – krizotinib or imatinib
- drugs called calcium channel blockers and used for high blood pressure or chest pain – diltiazem or verapamil
- drugs called statins for the treatment of high cholesterol – rosuvastatin
- cardiac drugs / antiarrhythmics – amiodarone or dronedarone
- drugs that prevent seizures or for the treatment of epilepsy or drugs for the treatment of a painful condition in the face called trigeminal neuralgia – carbamazepine or phenytoin .
If any of the above apply to you (or you are not sure), talk to your doctor, pharmacist or nurse before taking IMBRUVICA.
If you are taking digoxin , a medicine for heart problems, or methotrexate, a medicine for other cancers and to reduce the activity of the immune system (eg for rheumatoid arthritis or psoriasis ), you should take it at least 6 hours before or after IMBRUVICA.
IMBRUVICA with food
Do not take IMBRUVICA with grapefruit or oranges – this includes eating the fruit, drinking the juice or taking supplements that may contain the fruit. This is because it may increase the amount of IMBRUVICA in the blood.
Pregnancy and breastfeeding
Avoid getting 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 potential must use a very effective method of contraception during and up to three months after receiving IMBRUVICA to avoid becoming pregnant while being treated with IMBRUVICA.
- Tell your doctor immediately if you become pregnant.
- Do not breast-feed 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 tools or machines.
IMBRUVICA contains lactose
IMBRUVICA contains lactose (a sugar). If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
IMBRUVICA contains sodium
This medicine contains less than 1 mmol (23 mg) sodium per dose , ie essentially ‘sodium-free’.
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 daily.
Chronic lymphocytic leukemia ( CLL ) / Waldenström’s macroglobulinemia (WM)
The recommended dose of IMBRUVICA is 420 mg once daily.
Your doctor can adjust your dose .
How to take this medicine
- Take the tablets orally (by mouth) with a glass of water.
- Take the tablets at about the same time each day.
- Swallow the tablets whole. They should not be crushed or chewed.
If you take more IMBRUVICA than you should
If you take more IMBRUVICA than you should, talk to a doctor or go to a hospital immediately. Bring the tablets and this leaflet.
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 the normal schedule the following 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 the 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 product, 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 occur with this medicine:
Stop taking IMBRUVICA and tell your doctor immediately if you notice any of the following side effects:
itchy raised rash, difficulty breathing, swelling of the face, lips, tongue or throat – you may have had an allergic reaction to the medicine.
Tell your doctor immediately if you notice any of the following side effects:
Very common (may affect more than 1 in 10 people)
- fever, chills, body aches, fatigue, cold or flu symptoms, shortness of breath – these can be signs of an infection ( virus , bacteria or fungus). These can include infection of your nose, sinuses or throat (upper respiratory tract infection), or your lungs, or your skin.
- bruising or increased tendency to get bruises
- cold sores
- dizziness
- headache
- constipation
- nausea or vomiting
- diarrhea, your doctor may need to give you fluid and salt replacement or some other medicine
- rash
- pain in arms or legs
- back or joint pain
- muscle cramps, muscle pain or spasm s
- low number of blood cells that help the blood to coagulate ( platelets ), very low number of white blood cells – seen in blood samples
- an increase in the number or proportion of white blood cells , which is seen in blood sampleshigh level of “uric acid” in the blood (shown by blood tests), which can cause gout
- swollen hands, ankles or feet
- high blood pressure
- elevated levels of “creatinine” in the blood.
Common (may affect up to 1 in 10 people)
- severe infection throughout the body ( sepsis )
- infection you in the urinary tract
- nosebleeds, small red or purple spots caused by bleeding under the skin
- blood in the stomach, intestines, feces or urine, heavy menstruation or bleeding that you can not stop from an injury
- heart failure
- fast heart rate, skipped heartbeat, weak or uneven heart rate , fainting, shortness of breath, chest discomfort (symptoms of heart rhythm problems)
- low white blood cell count and fever (febrile neutropenia )
- non- melanoma skin cancer, usually squamous cell carcinoma or basal cell carcinoma
- dimsyn
- reddening of the skin
- inflammation of the lungs that can lead to permanent damage
- nails broken
- weakness, numbness, stinging sensation or pain in your hands or feet or other parts of the body (perfier neuropathy ).
Less common side effects are (may affect up to 1 in 100)
- liver failure, including fatal events
- serious fungal infections
- confusion, headache with slurred speech or fainting – these may be signs of severe internal bleeding in the brain
- Abnormal levels of chemical substances in the blood caused by rapid breakdown of cancer cells have occurred during cancer treatment and sometimes even without treatment (tumor lysis syndrome)
- allergic reaction , sometimes severe, which may include swelling of the face, lips, mouth, tongue or throat, difficulty swallowing or breathing, itchy rash ( hives )
- inflammation of the adipose tissue under the skin
- temporary impaired brain or nerve function caused by lost blood flow, stroke
- bleeding in the eye (in some cases associated with loss of vision)
- painful skin ulcers (pyoderma gangrenosum) or red, raised painful spots on the skin, fever and an increase in white blood cells (this may be a sign of acute febrile neutrophil dermatosis or Sweets syndrome).
Rare side effects are (may affect up to 1 in 1000 users)
- sharp increase in the number of white blood cells that can lead to the blood cells clumping together.
No known frequency (can not be calculated from the available data)
- severe rash with blisters and flaky skin, especially around the mouth, nose, eyes and genitals ( Stevens-Johnson syndrome ).
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist, or nurse. This also applies to any side effects not mentioned in this information. You can also report side effects directly to the Medical Products Agency. By reporting side effects, you can help increase drug safety information.
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 which is stated on the carton after EXP. The expiration date is the last day of the specified month.
No special storage instructions.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.
6. Contents of the packaging and other information
Content declaration
- 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.
- Other ingredients are:
- Tablet core: colloidal anhydrous silica, croscarmellose sodium, lactose monohydrate (see section 2 “IMBRUVICA contains lactose” ), magnesium stearate, microcrystalline cellulose, povidone, sodium lauryl sulphate (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).
What the medicine looks like and contents of the pack
IMBRUVICA 140 mg film-coated tablets
Yellow-green to green round tablets (9 mm) debossed with “ibr” on one side and “140” on the other side. Each 28-day carton contains 28 film-coated tablets in 2 fold packs of 14 film-coated tablets each. Each 30-day carton contains 30 film-coated tablets in 3 fold packs of 10 film-coated tablets in each.
IMBRUVICA 280 mg film-coated tablets
Purple elongated tablets (15 mm long and 7 mm wide) embossed with “ibr” on one side and “280” on the other side. Each 28-day carton contains 28 film-coated tablets in 2 fold packs of 14 film-coated tablets each. Each 30-day carton contains 30 film-coated tablets in 3 fold packs of 10 film-coated tablets in each.
IMBRUVICA 420 mg film-coated tablets
Yellow-green to green oblong tablets (17.5 mm long and 7.4 mm wide) embossed with “ibr” on one side and “420” on the other side. Each 28-day carton contains 28 film-coated tablets in 2 fold packs of 14 film-coated tablets each. Each 30-day carton contains 30 film-coated tablets in 3 fold packs of 10 film-coated tablets in each.
IMBRUVICA 560 mg film-coated tablets
Yellow to orange oblong tablets (19 mm long and 8.1 mm wide) embossed with “ibr” on one side and “560” on the other side. Each 28-day carton contains 28 film-coated tablets in 2 fold packs of 14 film-coated tablets each. Each 30-day carton contains 30 film-coated tablets in 3 fold packs of 10 film-coated tablets in 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