Bosulif 100 mg hard capsules

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Bosulif 50mg hard capsules

Bosulif 100mg hard capsules

bosutinib

Read all of this leaflet carefully before you start taking this medicine, because it contains important information for you and your caregiver.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Bosulif is and what it is used for

Bosulif contains the active substance bosutinib. Bosulif is used to treat adult and pediatric patients from 6 years of age who have a type of leukemia called Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in the chronic phase (CP) when newly diagnosed, or for whom previous medicines to treat CML have not been effective or are not suitable. It is also used to treat adult patients with Ph+ CML in the accelerated phase (AP) or blast phase (BP) for whom previous CML treatments have not been effective or are not suitable.

In patients with Ph+ CML, a change in DNA (genetic material) triggers a signal that causes the body to produce an excessive number of a specific type of white blood cells called granulocytes. Bosulif blocks this signal and thereby stops the production of these cells.

If you have any questions about how Bosulif works or why it has been prescribed for you, consult your doctor.

2. What you need to know before taking Bosulif

Do not take Bosulif

• if you are allergic to bosutinib or any of the other ingredients of this medicine (listed in section 6).
• if your doctor has told you that you have impaired liver function.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before taking Bosulif:

• if you have or have previously had liver problems. Inform your doctor if you have a history of liver problems, including any type of hepatitis (liver infection or inflammation), or a history of any signs and symptoms of liver problems (see section 4 “Possible side effects”), as Bosulif may affect liver function. Your doctor should perform blood tests to check your liver function before starting treatment with Bosulif and during the first 3 months of treatment, or as clinically indicated.

• if you have diarrhea and vomiting. Inform your doctor if you experience any signs or symptoms of stomach or intestinal problems (see section 4 “Possible side effects”). Your doctor may provide you with an antidiarrheal or antiemetic and/or fluids to reduce symptoms. Your doctor may also temporarily interrupt, reduce the dose, or permanently discontinue treatment with Bosulif (see section 3 “How to take Bosulif”). Consult your doctor if using anti-nausea or anti-vomiting treatment together with Bosulif may increase the risk of cardiac arrhythmias.

• if you have bleeding problems. Inform your doctor if you experience any signs or symptoms of blood problems (see section 4 “Possible side effects”), as Bosulif reduces the blood’s ability to stop bleeding. During the first month, your doctor should perform complete blood counts weekly, and then monthly. Your doctor may also temporarily interrupt, reduce the dose, or permanently discontinue treatment with Bosulif (see section 3 “How to take Bosulif”).

• 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 when urinating, new cough, or new sore throat, as Bosulif reduces the blood’s ability to fight infections.

• 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). Your doctor will monitor fluid retention and treat your symptoms.

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

• if you have been told you have an abnormal heart rhythm. Inform your doctor if you have arrhythmias or an abnormal electrical signal called "QT interval prolongation." These conditions are always important, but even more so if you have frequent or prolonged diarrhea as mentioned above. If you faint (lose consciousness) or experience irregular heartbeats during treatment with Bosulif, inform your doctor immediately, as these may be signs of a serious heart condition (see section 2 “What you need to know before taking Bosulif”). Your doctor will perform an electrocardiogram (ECG) before starting treatment. Your doctor will also perform a blood test before and during treatment, and if low levels of potassium or magnesium are detected, will provide treatment to correct these low levels.

• if you have been told you have kidney problems. Inform your doctor if you urinate more frequently and produce larger amounts of light-colored urine, or if you urinate less frequently and produce smaller amounts of dark-colored urine. Also inform your doctor if you lose weight or experience swelling of the feet, ankles, legs, hands, or face. Your doctor will check how well your kidneys are functioning before treatment and will closely monitor kidney function during treatment with bosutinib.

• if you have ever had or may currently have a hepatitis B virus infection. This is because Bosulif could cause hepatitis B to become active again, which may be fatal in some cases. Before starting treatment, your doctor will test you for hepatitis B. If you have this infection, your doctor will closely monitor you for signs or symptoms of reactivation throughout treatment and for several months after stopping treatment.

• if you have or have previously had pancreas problems. Inform your doctor if you experience abdominal pain or discomfort. If you have abdominal pain and blood tests show high levels of lipase, an enzyme that helps the body break down fat from food, your doctor may suspend treatment and perform tests to rule out pancreas problems.

• if you experience any of these symptoms: severe skin rashes. Inform your doctor if you develop any of the following signs and symptoms of a painful red or purple rash that spreads and if blisters and/or other lesions begin to appear on mucous membranes (e.g., mouth and lips). If you develop a severe skin reaction during treatment, your doctor will permanently discontinue treatment.

• if you notice any of these symptoms: flank pain, blood in the urine, or decreased urine output. If your condition is severe, your body may not be able to eliminate all waste products from dying cancer cells. This is known as tumor lysis syndrome and may lead to kidney failure and heart problems within 48 hours after the first dose of Bosulif. Your doctor will ensure you are adequately hydrated and give you other medications to help prevent this. Your doctor will perform a blood test to check for high levels of uric acid and provide treatment to correct high levels before starting study treatment.

Sun/UV Protection

During treatment with bosutinib, you may be more sensitive to sunlight or UV rays. It is important to cover exposed skin and use sunscreen with a high sun protection factor (SPF).

Patients of Asian origin

If you are of Asian origin, you may have a higher risk of adverse effects with Bosulif. Your doctor will closely monitor for the possible occurrence of serious adverse effects, especially when the dose is increased.

Children and adolescents

Bosulif is not recommended for children under 6 years of age. This medicine has not been studied in children under 1 year of age.

Other medicines and Bosulif

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines, including over-the-counter medicines, vitamins, and herbal supplements. Some medicines may affect the levels of Bosulif in your body. You should inform your doctor if you are taking medicines containing any of the following active substances:

The following active substances 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 lower blood pressure in people with high blood pressure.
• ritonavir, lopinavir/ritonavir, indinavir, nelfinavir, saquinavir, atazanavir, amprenavir, fosamprenavir, and darunavir, used to treat human immunodeficiency virus (HIV)/AIDS infection.
• 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-small cell lung cancer.

The following active substances 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 (an herbal remedy available without prescription), used to treat depression.
• efavirenz and etravirine, used to treat HIV/AIDS infections.
• modafinil, used to treat certain types of sleep disorders.

You should avoid using these medicines during treatment with Bosulif. If you are taking any of them, inform your doctor. Your doctor may adjust the doses of these medicines, adjust your Bosulif dose, or switch you to a different medicine.

The following active substances may affect heart rate:

• amiodarone, disopyramide, procainamide, quinidine, and sotalol, used to treat heart disorders.
• chloroquine and halofantrine, used to treat malaria.
• clarithromycin and moxifloxacin, 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 breast milk production.
• methadone, used to treat pain.

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

Acid-reducing drugs

Proton pump inhibitors (PPIs) should be used with caution during treatment with Bosulif, as they may reduce the effectiveness of Bosulif. Your doctor may consider using short-acting antacids as an alternative to PPIs and may schedule the administration of Bosulif and antacids at different times (e.g., take Bosulif in the morning and antacids at night), whenever possible.

The medicines listed in this leaflet may not be the only ones that could interact with Bosulif; if you are unsure whether the above applies to you or your child, ask your doctor.

Taking Bosulif with food and drink

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

Pregnancy, breastfeeding, and fertility

Bosulif should not be used during pregnancy unless clearly necessary, as Bosulif could harm the unborn baby. If you are pregnant or think you may be pregnant, consult your doctor before starting Bosulif.

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

Ask about sperm preservation before starting treatment if desired, due to the risk that Bosulif treatment may reduce fertility.

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

Driving and using machines

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

Bosulif contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per 50 mg or 100 mg hard capsule; essentially “sodium-free”.

3. How to take Bosulif

Follow exactly the instructions for using this medicine as provided by your doctor. If you are unsure, consult your doctor or pharmacist again.

Bosulif will only be prescribed by a doctor experienced in the use of medicines for treating leukemia.

Dosage and method of administration

Adults

The recommended dose is 400 mg once daily for patients with newly diagnosed CML. The recommended dose is 500 mg once daily for patients for whom previous medications used to treat CML have not been effective or are not suitable. If you are unable to tolerate the recommended dose or are not responding adequately to treatment with Bosulif, your doctor may further adjust your dose.

Children and adolescents (from 6 years of age)

The recommended dose is 300 mg/m² based on body surface area once daily for pediatric patients with newly diagnosed disease. The recommended dose is 400 mg/m² based on body surface area once daily for pediatric patients who are resistant or intolerant.

The following table provides dosage recommendations. As appropriate, the recommended dose can be achieved by combining different film-coated tablet and/or hard capsule presentations (see the package leaflet for film-coated tablets).

Bosutinib doses for pediatric patients who are newly diagnosed (ND) and for those who are resistant or intolerant (R/I)

• maximum initial dose (corresponding to the maximum initial dose in the indication for adults)

If you are unable to tolerate the recommended dose or are not responding properly to treatment with Bosulif, your doctor may further adjust your dose.

Take the capsule(s) once daily with food. The hard capsule must be swallowed whole.

Dose preparation instructions for patients unable to swallow

For patients who cannot swallow the capsules whole, the capsules may be opened and their contents mixed with apple sauce or yogurt. The mixture of the contents of the hard capsule with apple sauce or yogurt should not be considered a substitute for an appropriate meal; the dose must be taken with food to improve gastrointestinal tolerability.

Remove from the package the number of hard capsules required to prepare the prescribed dose. Place the amount of apple sauce or yogurt indicated in the table below, at room temperature, into a clean container. Carefully open each hard capsule, add the entire contents of the capsule to the apple sauce or yogurt, and then mix thoroughly to ensure complete dispersion of the dose. The entire mixture must be consumed immediately without chewing. Do not store the mixture for later use. If not all of the mixture is ingested, do not take an additional dose; wait until the next day to resume dosing. To facilitate administration, the recommended volume of apple sauce or yogurt is provided in the table below.

Bosulif dosing using hard capsules and volumes of soft food

If you take more Bosulif than you should

If you accidentally take too many Bosulif capsules or a higher dose than required, seek medical advice immediately. If possible, show the doctor the pack or this leaflet. You may require 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 following day.

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

If you stop taking Bosulif

Do not stop taking Bosulif unless your doctor tells you to. If you are unable to take the medicine as directed by your doctor, or if you think you no longer need it, consult your doctor immediately.

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

4. Possible adverse effects

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

Serious adverse effects

You should consult your doctor immediately if you experience any serious adverse effects (see also section 2 “What you need to know before you start taking Bosulif”):

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

• reduction in the number of platelets (thrombocytopenia), red blood cells (anemia), or neutrophils (a type of white blood cells) (neutropenia), which may cause abnormal bleeding, fever, or frequent bruising without injury (you may have a disorder of the blood or lymphatic system) (see section 2 “What you need to know before you start taking Bosulif”).
• fluid around the lungs (pleural effusion).

Common (may affect up to 1 in 10 people):

• decrease in white blood cell count (leukopenia).
• bleeding from the stomach or intestines (gastrointestinal hemorrhage), which may include blood in vomit, stools, or urine, or black, tarry stools (see section 2 “What you need to know before you start taking Bosulif”).
• chest pain.
• toxic liver injury (hepatotoxicity), abnormal liver function, including liver disorder (abnormal liver function), which may be accompanied by itching, yellowing of the eyes and skin, dark urine, pain or discomfort in the upper right part of the stomach, or fever (see section 2 “What you need to know before you start taking Bosulif”).
• heart not pumping blood properly (heart failure).
• reduced blood flow to the heart (cardiac ischemia).
• lung infection (pneumonia).
• change in heart rhythm (prolongation of QT interval on electrocardiogram) that may lead to fainting, dizziness, or palpitations.
• increased blood pressure (hypertension).
• high level of potassium in the blood (hyperkalemia).
• acute kidney injury, kidney failure, kidney impairment.
• fluid around the heart (pericardial effusion).
• allergic reaction (hypersensitivity to the medicine).
• abnormally high blood pressure in the arteries of the lungs (pulmonary hypertension).
• acute inflammation of the pancreas (acute pancreatitis).

Uncommon (may affect up to 1 in 100 people):

• fever associated with low white blood cell count (febrile neutropenia).
• liver damage (hepatic injury).
• life-threatening allergic reaction (anaphylactic shock).
• abnormal accumulation of fluid in the lungs (acute pulmonary edema).
• skin rash (drug eruption).
• skin peeling, scaly rash (exfoliative rash).
• inflammation of the lining of the heart or pericardium (pericarditis).
• marked decrease in the number of granulocytes (a type of white blood cell, granulocytopenia).
• serious skin disorder (erythema multiforme).
• nausea, difficulty breathing, irregular heartbeat, muscle cramps, seizures, cloudy urine, and fatigue related to abnormal laboratory test results (elevated potassium, uric acid, and phosphorus in the blood, and decreased calcium in the blood), which may lead to changes in kidney function and acute kidney failure (tumor lysis syndrome [TLS]).
• respiratory failure.
• inflammation of blood vessels in the skin, which may cause a skin rash or bruising (cutaneous vasculitis).

Frequency not known (cannot be estimated from available data):

• serious skin disorder (Stevens-Johnson syndrome, toxic epidermal necrolysis), which may include painful red or purple rash spreading and forming blisters and/or other lesions starting in mucous membranes (e.g., mouth and lips) due to an allergic reaction.
• interstitial lung disease (disorders causing scarring in the lungs): signs include cough, difficulty breathing, and painful breathing.
  • reactivation (recurrence) of hepatitis B if you have had hepatitis B in the past (a liver infection).

Other adverse effects that may occur with Bosulif are:

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

• diarrhea, vomiting, stomach pain (abdominal pain), nausea.
• fever (pyrexia), swelling of hands, feet, or face (edema), fatigue, weakness.
• respiratory tract infection.
• nasopharyngitis.
• abnormal blood test results indicating possible effects of Bosulif on the liver (elevated alanine aminotransferase [ALT], elevated aspartate aminotransferase [AST]) and/or pancreas (elevated lipase), kidneys (elevated blood creatinine).
• decreased appetite.
• joint pain (arthralgia), back pain.
• headache.
• skin rash, with itching of the skin and/or generalized (rash).
• cough.
• difficulty breathing (dyspnea).
• feeling of unsteadiness (dizziness).

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

• stomach irritation (gastritis).

• pain.

• influenza, bronchitis.

• abnormalities in blood tests indicating possible effects of Bosulif on the heart (elevated blood creatine phosphokinase), liver (elevated blood bilirubin, elevated gamma-glutamyl transferase [GGT]), and/or pancreas (elevated amylase).

• low blood phosphorus (hypophosphatemia), excessive loss of body fluids (dehydration).

• muscle pain (myalgia).

• altered sense of taste (dysgeusia).

• ringing in the ears (tinnitus).

• hives (urticaria), acne.

• sensitivity to UV rays from sunlight and other light sources (photosensitivity reaction).

• itching (pruritus).

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system listed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Bosulif

• 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 bottle and outer packaging after “EXP”. The expiry date refers to the last day of the stated month.
• Do not store above 30 °C. Store in the original packaging to protect from light.
• Do not use this medicine if you notice that the packaging is damaged or shows signs of tampering.
• Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to properly dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Package contents and other information

Composition of Bosulif

Hard capsules:

• The active substance is bosutinib. Bosulif hard capsules are available in various strengths.

Bosulif 50 mg: each hard capsule contains 50 mg of bosutinib (as monohydrate).

Bosulif 100 mg: each hard capsule contains 100 mg of bosutinib (as monohydrate).

• The other components are: mannitol (E421), microcrystalline cellulose (E460), sodium croscarmellose (E468), poloxamer 188, povidone (E1201) and magnesium stearate (E470b). The capsule shell contains gelatin, titanium dioxide (E171), yellow iron oxide (E172) and red iron oxide (E172). The printing ink contains shellac (E904), propylene glycol (E1520), concentrated ammonium solution (E527), black iron oxide (E172), potassium hydroxide (E525) (see section 2 “Bosulif contains sodium”).

Appearance of the product and contents of the pack

Bosulif 50 mg hard capsules have a white body/orange cap with “BOS 50” printed on the body and “Pfizer” printed on the cap in black ink. Bosulif 50 mg hard capsules are supplied in bottles containing 30 hard capsules.

Bosulif 100 mg hard capsules have a white body/brown-red cap with “BOS 100” printed on the body and “Pfizer” printed on the cap in black ink. Bosulif 100 mg hard capsules are supplied in bottles containing 150 hard capsules.

Only certain pack sizes may be marketed.

Marketing Authorisation Holder

Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Brussels
Belgium

Manufacturer

Pfizer Manufacturing Deutschland GmbH
Mooswaldallee 1
79108 Freiburg im Breisgau
Germany

For more information about this medicine, contact the local representative of the Marketing Authorisation Holder:

Date of the most recent review of this summary:

Detailed information on this medicine is available on the website of the European Medicines Agency: https://www.ema.europa.eu.