Product Information for the User

Bosulif 100Film-Coated Tablets

Bosulif 400Film-Coated Tablets

Bosulif 500Film-Coated Tablets

bosutinib

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 questions, consult your doctor or pharmacist.
• This medicine has been prescribed to you alone, 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 adverse effects, consult your doctor, even if they are not listed in this product information. See section 4.

Bosulif contains the active ingredient bosutinib. It is used to treat adult patients who have a type of leukemia called chronic myeloid leukemia (CML) with a positive Philadelphia chromosome (Ph-positive) who have recently been diagnosed or for whom previous medications to treat CML have not been effective or are not suitable. Ph-positive CML is a blood cancer that causes the body to produce an excessive amount of a specific type of white blood cells called granulocytes.

If you have any doubts about how Bosulif works or why you have been prescribed this medication, consult your doctor.

Do not take Bosulif

• if you are allergic to bosutinib or any of the other ingredients in this medication (listed in section6).
• if your doctor has told you that you have a damaged liver and it does not function normally.

Warnings and precautions

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

• if you have, or have had in the past, liver problems.Inform your doctor if you have a history of liver problems, including any type of hepatitis (infection or inflammation of the liver), or a history of any of the following signs and symptoms of liver problems: itching, yellow eyes or skin, dark urine, and pain or discomfort in the upper right side of the stomach. Your doctor should perform blood tests to check your liver function before starting treatment with Bosulif and during the first 3months of treatment with Bosulif, or as clinically indicated.

• if you have diarrheaand vomiting.Inform your doctor if you experience any of the following signs andsymptoms: increased frequency of bowel movements, increased frequency of vomiting episodes, blood in the vomit, in the stool, or in the urine, or the appearance of black stools (“tarry stools”). Consult your doctor if the treatment for vomiting may increase the risk of cardiac arrhythmias.Especially,consult your doctor if you want to use anymedication that contains domperidone for the treatment of nausea and/or vomiting. The treatment of nausea or vomiting with medications of this type, if used together with Bosulif, may increase the risk of life-threatening cardiac arrhythmias.

• if you have bleeding problems.Inform your doctor if you experience any of the following signs and symptoms, such as abnormal bleeding or petechiae without any injury.

• if you have an infection.Inform your doctor if you experience any of the following signs and symptoms, such as fever, urinary problems such as burning sensation while urinating, new-onset cough, or new-onset sore throat.

• if you have fluid retention.Inform your doctor if you experience any of the following signs and symptoms of fluid retention during treatment with Bosulif, such as swelling of the ankles, feet, or legs; difficulty breathing, chest pain, or cough (all of which may be signs of fluid retention in the lungs or chest).

• if you have heart problems.Inform your doctor if you have any cardiac alteration, such as heart failure and a decrease in blood flow to the heart that may cause a heart attack.Seek immediate medical help if you experience difficulty breathing, weight gain, chest pain, or swelling of the hands, feet, or ankles.

• if you have been told that you have an abnormal heart rhythm. Inform your doctor if you have arrhythmias or an abnormal electrical signal called “prolongation of the QT interval.”These problems are always important, but even more so if you have frequent or prolonged diarrhea as mentioned earlier.If you faint (lose consciousness) or experience irregular heartbeats during treatment with Bosulif, inform your doctor immediately, as they may be signs of a serious heart disease.

• if you have been told that you have kidney problems.Inform your doctor if you urinate more frequently and produce larger amounts of urine with a clear color, or if you urinate less frequently and produce smaller amounts of urine with a dark color.Inform your doctor also if you lose weight or experience swelling of the feet, ankles, legs, hands, or face.

-if you have ever had or may have a hepatitis B virus infection.This is because Bosulif may reactivate hepatitis B, which can be fatal in some cases. The doctor should carefully check for signs of this infection before starting treatment.

• if you have or have had pancreas problems.Inform your doctor if you experience abdominal pain or discomfort.

• if you have any of these symptoms: severe skin eruptions.Inform your doctor if you experience any of the following signs and symptoms of painful red or purple rash that spreads and if blisters and/or other lesions appear on the mucous membrane (e.g., the mouth and lips).

• if you experience any of these symptoms: pain in the side, blood in the urine, or decreased urine output.If your disease is very severe, your body may not be able to eliminate all the waste products of dying cancer cells. This is called tumor lysis syndrome and can cause kidney failure and heart problems within 48hours after the first dose of Bosulif. Your doctor will ensure that you are adequately hydrated and will give you other medications to help prevent it.

Sol/UV protection

During treatment with bosutinib, you may be more sensitive to the sun or UV rays. It is essential to cover exposed areas of the body and use high-factor sunscreen (SPF).

Children and adolescents

Bosulif is not recommended for individuals under 18years of age.This medication has not beenstudied in children or adolescents.

Other medications and Bosulif

Inform your doctor or pharmacist if you are taking, have taken recently, or may take any other medication, including over-the-counter medications, vitamins, and herbal supplements. Some medications may affect the concentrations of Bosulif in your body. You should inform your doctor if you are using medications that contain active ingredients such as the following:

These active ingredients may increase the risk of adverse effects with Bosulif:

• ketoconazole, itraconazole, voriconazole, posaconazole, and fluconazole, used to treat fungal infections.
• clarithromycin, telithromycin, erythromycin, and ciprofloxacin, used to treat bacterial infections.
• nefazodone, used to treat depression.
• mibefradil, diltiazem, and verapamil, used to reduce blood pressure in people with high blood pressure.
• ritonavir, lopinavir/ritonavir, indinavir, nelfinavir, saquinavir, atazanavir, amprenavir, fosamprenavir, and darunavir, used to treat HIV/AIDS.
• boceprevir and telaprevir, used to treat hepatitis C.
• aprepitant, used to prevent and control nausea and vomiting.
• imatinib, used to treat a type of leukemia.
• crizotinib, used to treat a type of lung cancer called non-microcytic lung cancer.

These active ingredients may reduce the effectiveness of Bosulif:

• rifampicin, used to treat tuberculosis.
• phenytoin and carbamazepine, used to treat epilepsy.
• bosentan, used to reduce high blood pressure in the lungs (pulmonary hypertension).
• nafcillin, an antibiotic used to treat bacterial infections.
• St. John's Wort (a medicinal herb obtained without a prescription), used to treat depression.
• efavirenz and etravirine, used to treat HIV/AIDS.
• modafinil, used to treat certain types of sleep disorders.

You should avoid using these medications during treatment with Bosulif. If you are using any of them, inform your doctor. Your doctor may change the doses of these medications, change the dose of Bosulif, or have you use a different medication.

These active ingredients may affect heart rate:

• amiodarone, disopyramide, procainamide, quinidine, and sotalol, used to treat cardiac disorders.
• chloroquine and halofantrine, used to treat malaria.
• clarithromycin and moxifloxacin, which are antibiotics used to treat bacterial infections.
• haloperidol, used to treat psychotic disorders such as schizophrenia.
• domperidone, used to treat nausea and vomiting, or to stimulate milk production.
• methadone, used to treat pain.

These medications should be taken with caution during treatment with Bosulif. If you are taking any of them, inform your doctor.

It is possible that the medications listed in this prospectus may not be the only ones that could interact with Bosulif.

Taking Bosulif with food and drinks

Do not take Bosulif with grapefruit or grapefruit juice, as it may increase the risk of adverse effects.

Pregnancy, breastfeeding, and fertility

Bosulif should not be used during pregnancy unless it is clearly necessary, as Bosulif may harm the fetus. If you are pregnant or think you may be pregnant, consult your doctor before starting treatment with Bosulif.

Women taking Bosulif should be advised to use effective contraceptive methods during treatment and for at least 1month after the last dose. Vomiting and diarrhea may reduce the effectiveness of oral contraceptives.

Request information on sperm preservation before starting treatment, if desired, given the risk of reduced fertility during treatment with Bosulif.

If you are breastfeeding, inform your doctor. Do not breastfeed during treatment with Bosulif, as it may harm the baby.

Driving and operating machinery

If you experience dizziness, blurred vision, or unusual fatigue, do not drive or operate machinery until these adverse effects have disappeared.

Bosulif containssodium

This medication contains less than 1mmol of sodium (23mg) per 100mg, 400mg, or 500mg tablet; it is essentially“sodium-free.”

Follow exactly the administration instructions for this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

Bosulif will only be prescribed by a doctor who has experience with medications used to treat leukemia.

Dose and Administration Form

The recommended dose is 400 mg once a day for patients with newly diagnosed LMC. The recommended dose is 500 mg once a day for patients whose previous medications for treating LMC have not been effective or are not suitable. In case of moderate or severe kidney problems, your doctor will reduce the dose by 100 mg once a day for moderate kidney problems and an additional 100 mg once a day for severe kidney problems. Your doctor may adjust the dose using 100 mg tablets, based on your health status, in response to treatment, and/or adverse effects you may experience. Take the tablet(s) once a day, with food. Swallow the tablet(s) whole with a little water.

If you take more Bosulif than you should

If you accidentally take too many Bosulif tablets or a higher dose than you need, go to a doctor immediately. If possible, show the doctor the packaging or this leaflet. You may need medical attention.

If you forget to take Bosulif

If less than 12 hours have passed, take the recommended dose. If more than 12 hours have passed, take your next dose at the usual time the next day.

Do not take a double dose to make up for missed doses.

If you interrupt treatment with Bosulif

Do not stop taking Bosulif unless your doctor tells you to. If you cannot take the medication as indicated by your doctor or think you no longer need it, consult your doctor immediately.

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

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

You should consult your doctor immediately if you experience any severe side effects (see also section 2 “What you need to know before starting to take Bosulif”):

Blood disorders.Inform your doctor immediately if you experience any of the following symptoms: bleeding, fever, or frequent rashes (you may have a blood or lymphatic system disorder).

Liver disorders.Inform your doctor immediately if you experience any of the following symptoms: itching, yellow eyes or skin, dark urine, and pain or discomfort in the upper right side of the stomach or fever.

Stomach/intestinal disorders.Inform your doctor if you experience any of the following: stomach pain, heartburn, diarrhea, constipation, nausea, or vomiting.

Cardiac problems.Inform your doctor if you experience any of the following: cardiac alteration, such as heart failure, decreased blood flow to the heart, an abnormal electrical signal called “prolongation of the QT interval,” or if you faint (lose consciousness) or experience an irregular heart rate during Bosulif treatment.

Reactivation of hepatitis B virus.Recurrence (reactivation) of hepatitis B infection if you have had hepatitis B in the past (a liver infection).

Severe skin reactions.Inform your doctor immediately if you experience any of the following symptoms: painful red or purple rash that spreads and if blisters and/or other lesions appear on the mucous membrane (e.g., the mouth and lips).

The side effects that may appear with Bosulif are:

Very common side effects (may affect more than 1 in 10 patients):

• Decreased platelet, red blood cell, and/or neutrophil count (a type of white blood cell).
• D diarrhea, vomiting, stomach pain, nausea.
• Fever, swelling of the hands, feet, or face, fatigue, weakness.
• Respiratory tract infection.
• Pharyngitis.
• Alteration of blood tests indicating that Bosulif is affecting the liver and/or pancreas, kidneys.
• Decreased appetite.
• Muscle pain.
• Headache.
• Skin rash, with itching on the skin and/or generalized.
• Cough.
• Dyspnea.
• Sensation of instability (dizziness).
• Liquid in the lungs (pleural effusion).
• Itching.

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

• Decreased white blood cell count (leucopenia).
• Stomach irritation (gastritis), bleeding in the stomach or intestine.
• Chest pain, pain.
• Liver damage, abnormal liver function, including liver disorder.
• Pulmonary infection (pneumonia), flu, bronchitis.
• Heart not pumping blood as it should (heart failure).
• Decreased heart rate that predisposes to fainting, dizziness, and palpitations.
• Increased blood pressure.
• Elevated potassium in the blood, decreased phosphorus in the blood, excessive loss of body fluids (dehydration).
• Muscle pain.
• Alteration of taste (dysgeusia).
• Acute renal failure, renal failure, renal deterioration.
• Liquid around the heart (pericardial effusion).
• Tinnitus (ringing in the ears).
• Urticaria (hives), acne.
• Phototoxicity (sensitivity to UV rays from the sun and other light sources).
• Allergic reaction.
• Abnormally high blood pressure in the pulmonary arteries (pulmonary hypertension).
• Acute pancreatitis (inflammation of the pancreas).
• Respiratory insufficiency.

Rare side effects (may affect up to 1 in 100 patients):

• Fever associated with low white blood cell count (neutropenic fever).
• Liver damage.
• Life-threatening allergic reaction (anaphylactic shock).
• Abnormal accumulation of fluid in the lungs (acute pulmonary edema).
• Skin rash.
• Pericarditis (inflammation of the heart or pericardium).
• Significant decrease in granulocyte count (a type of white blood cell).
• Severe skin disorder (erythema multiforme).
• Nausea, difficulty breathing, irregular heartbeats, muscle cramps, seizures, urine turbidity, and fatigue related to abnormal laboratory test results (elevated potassium, uric acid, and phosphorus in the blood, and decreased calcium in the blood) that may cause renal dysfunction and acute renal failure (tumor lysis syndrome [TLS]).

Unknown frequency (cannot be estimated from available data):

• Severe skin disorder (Stevens-Johnson syndrome, toxic epidermal necrolysis) caused by an allergic reaction, exfoliative dermatitis (peeling)
• Pulmonary interstitial disease (diseases that cause scarring in the lungs): symptoms are cough, difficulty breathing, and painful breathing).

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 theSpanish System for Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es.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 aluminum foil of the blister pack and on the packaging after “EXP”. The expiration date is the last day of the month indicated.
• This medication does not require special storage conditions.
• Do not use this medication if you observe that the packaging is damaged or shows signs of having been altered.
• Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. This will help protect the environment.

Composition of Bosulif

• The active ingredient is bosutinib. Bosulif film-coated tablets are available in various doses.

Bosulif 100mg: each film-coated tablet contains 100mg of bosutinib (as monohydrate).

Bosulif 400mg: each film-coated tablet contains 400mg of bosutinib (as monohydrate).

Bosulif 500mg: each film-coated tablet contains 500mg of bosutinib (as monohydrate).

• The other components are: microcrystalline cellulose (E460), sodium croscarmellose (E468), poloxamer 188, povidone (E1201), and magnesium stearate (E470b). The film coating contains polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc (E553b), and yellow iron oxide (E172, in Bosulif 100mg and 400mg) or red iron oxide (E172, in Bosulif 400mg and 500mg).

Appearance of the product and contents of the pack

Bosulif 100mg film-coated tablets are yellow, oval-shaped, biconvex, marked with the legend “Pfizer” on one face and with “100” on the other.

Bosulif100mg is available in blisters containing 14 or 15 tablets in packs of 28 or 30 tablets or 112 tablets.

Bosulif 400mg film-coated tablets are orange, oval-shaped, biconvex, marked with the legend “Pfizer” on one face and with “400” on the other.

Bosulif400mg is available in blisters containing 14 or 15 tablets in packs of 28 or 30 tablets.

Bosulif 500mg film-coated tablets are red, oval-shaped, biconvex, marked with the legend “Pfizer” on one face and with “500” on the other.

Bosulif 500mg is available in blisters containing 14 or 15tablets in packs of 28 or 30tablets.

Only some pack sizes may be marketed.

Marketing authorisation holder

Pfizer Europe MA EEIG

Boulevard de la Plaine 17

1050 Bruxelles

Bélgica

Responsible for manufacturing

PfizerManufacturing Deutschland GmbH

Betriebsst?tte Freiburg

Mooswaldallee 1

79090 Freiburg

Alemania

For further information about this medicinal product, please contact the local representative of the marketing authorisation holder:

Date of the last revision of this leaflet:11/2024.

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