"The U.S. Food and Drug Administration today approved Iclusig (ponatinib) to treat adults with chronic myeloid leukemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL), two rare blood and bone marrow diseases."...
Bosulif Side Effects Center
Medical Editor: John P. Cunha, DO, FACOEP
Bosulif (bosutinib) is a kinase inhibitor used to treat adult patients with chronic, accelerated, or blast phase Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) with resistance or intolerance to prior therapy. Common side effects include diarrhea, nausea, low blood platelet count (thrombocytopenia), vomiting, abdominal pain, rash, anemia, fever, and fatigue.
The recommended dose and schedule of Bosulif is 500 mg orally once daily with food. Bosulif may interact with ketoconazole, rifampin, proton pump inhibitors, St. John's wort, and digoxin. Tell your doctor all medications and supplements you use. Bosulif is not recommended for use during pregnancy. It may harm a fetus. Women should use contraception to prevent pregnancy during and for at least 30 days after completing treatment with Bosulif. Because of potential risk to a nursing infant, breastfeeding is not recommended; consult your doctor.
Our Bosulif (bosutinib) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
What is Patient Information in Detail?
Easy-to-read and understand detailed drug information and pill images for the patient or caregiver from Cerner Multum.
Bosulif in Detail - Patient Information: Side Effects
Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.
Stop using bosutinib and call your doctor at once if you have:
- severe or ongoing nausea, vomiting, stomach pain, or diarrhea;
- black, bloody, or tarry stools, coughing up blood or vomit that looks like coffee grounds;
- fever, chills, body aches, flu symptoms, sores in your mouth and throat;
- pale skin, easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin;
- upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);
- swelling in your hands or feet, rapid weight gain;
- pain in your chest, on your left side, or behind your breastbone;
- pain when you breathe, fast or uneven heart rate, feeling short of breath (especially when lying down);
- anxiety, sweating, wheezing, gasping for breath, cough with foamy mucus; or
- feeling weak, tired, dizzy, or light-headed.
Common side effects may include:
- headache, dizziness, tired feeling;
- mild stomach discomfort;
- joint pain, back pain;
- mild itching or rash; or
- cold symptoms such as stuffy nose, sneezing, sore throat.
Read the entire detailed patient monograph for Bosulif (Bosutinib Tablets) »
What is Prescribing information?
The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.
Bosulif FDA Prescribing Information: Side Effects
The following adverse reactions are discussed in greater detail in other sections of the labeling:
- Gastrointestinal toxicity [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS].
- Myelosuppression [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS].
- Hepatic toxicity [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS].
- Fluid retention [see WARNINGS AND PRECAUTIONS].
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Serious adverse reactions reported include anaphylactic shock [see CONTRAINDICATIONS], myelosuppression, gastrointestinal toxicity (diarrhea), fluid retention, hepatotoxicity and rash.
Adverse reactions of any toxicity grade reported for greater than 20% of patients in the Phase ½ safety population (n=546) were diarrhea (82%), nausea (46%), thrombocytopenia (41%), vomiting (39%), abdominal pain (37%), rash (35%), anemia (27%), pyrexia (26%), and fatigue (24%).
Imatinib-Resistant or -Intolerant Ph+ Chronic Phase (CP), Accelerated Phase (AP), and Blast Phase (BP) CML
The single-arm Phase ½ clinical trial enrolled patients with Ph+ chronic, accelerated, or blast phase chronic myelogenous leukemia (CML) and Ph+ acute lymphoblastic leukemia (ALL) with resistance or intolerance to prior therapy. The safety population (received at least 1 dose of BOSULIF) included 546 CML patients. Within the safety population there were 287 patients with CP CML previously treated with imatinib only who had a median duration of BOSULIF treatment of 24 months, and a median dose intensity of 484 mg/day. There were 119 patients with CP CML previously treated with both imatinib and at least 1 additional TKI who had a median duration of BOSULIF treatment of 9 months and a median dose intensity of 475 mg/day. There were 76 patients with AP CML, and 64 patients with BP CML. In the patients with AP CML and BP CML, the median duration of BOSULIF treatment was 10 months and 3 months, respectively. The median dose intensity was 483 mg/day, and 500 mg/day, in the AP CML and BP CML cohorts, respectively.
Table 2 identifies adverse reactions greater than or equal to 10% for all grades and grades 3 or 4 for the Phase ½ CML safety population.
Table 2: Adverse Reactions (10% or greater) in
patients with CML
|System Organ Class Preferred Term||CP CML
|All CP and AdvP CML
|All Grades||Grade 3/4||All Grades||Grade 3/4||All Grades||Grade 3/4|
|Diarrhea||342 (84)||38 (9)||107 (76)||7 (5)||449 (82)||45 (8)|
|Nausea||186 (46)||5 (1)||66 (47)||3 (2)||252 (46)||8 (1)|
|Abdominal Paina||162 (40)||6 (1)||41 (29)||7 (5)||203 (37)||13 (2)|
|Vomiting||152 (37)||12 (3)||59 (42)||5 (4)||211 (39)||17 (3)|
|Blood and Lymphatic System Disorders|
|Thrombocytopenia||163 (40)||105 (26)||59 (42)||52 (37)||222 (41)||157 (29)|
|Anemia||94 (23)||35 (9)||52 (37)||37 (26)||146 (27)||72 (13)|
|Neutropenia||65 (16)||43 (11)||26 (19)||25 (18)||91 (17)||68 (12)|
|General Disorders and Administrative Site Conditions|
|Fatigueb||104 (26)||6 (1)||28 (20)||6 (4)||132 (24)||12 (2)|
|Pyrexia||90 (22)||2 ( < 1)||51 (36)||4 (3)||141 (26)||6 (1)|
|Edemac||56 (14)||1 ( < 1)||19 (14)||1 (1)||75 (14)||2 ( < 1)|
|Asthenia||45 (11)||5 (1)||14 (10)||1 (1)||59 (11)||6 (1)|
|Infections and Infestations|
|Respiratory tract infectiond||49 (12)||2 ( < 1)||14 (10)||0||63 (12)||2 ( < 1)|
|Nasopharyngitis||47 (12)||0||7 (5)||0||54 (10)||0|
|Alanine aminotransferase increased||81 (20)||30 (7)||14(10)||7(5)||95(17)||37(7)|
|Aspartate aminotransferase increased||64 (16)||15 (4)||15(11)||4 (3)||79(14)||19(3)|
|Metabolism and nutrition disorder|
|Decreased appetite||53 (13)||3 (1)||19 (14)||0||72 (13)||3 (1)|
|Musculoskeletal and Connective Tissue Disorder|
|Arthralgia||58 (14)||2 ( < 1)||18 (13)||0||76 (14)||2 ( < 1)|
|Back pain||49 (12)||3 (1)||10 (7)||2 (1)||59 (11)||5 (1)|
|Nervous System Disorders|
|Headache||82 (20)||3 (1)||25 (18)||6 (4)||107 (20)||9 (2)|
|Dizziness||39 (10)||0||18 (13)||1 (1)||57 (10)||1 ( < 1)|
|Respiratory, Thoracic and Mediastinal Disorders|
|Dyspnea||41 (10)||4 (1)||26 (19)||8 (6)||67 (12)||12 (2)|
|Skin and Subcutaneous Disorders|
|Rashe||140 (34)||32 (8)||49 (35)||6 (4)||189 (35)||38 (7)|
|Pruritus||43 (11)||3 (1)||11 (8)||0||54 (10)||3 (1)|
|CP CML = Chronic Phase CML;
AdvP CML = Advanced Phase CML (includes patients with Accelerated Phase and
Blast Phase CML)
aAbdominal pain includes the following preferred terms: Abdominal pain, Abdominal pain upper, Abdominal pain lower, Abdominal tenderness, Gastrointestinal pain, Abdominal discomfort
bFatigue includes the following preferred terms: Fatigue, Malaise
cEdema includes the following preferred terms: Edema, Edema peripheral, Localized edema, Face edema
dRespiratory tract infection includes the following preferred terms: Respiratory tract infection, Upper respiratory tract infection, Lower respiratory tract infection, Viral upper respiratory tract infection, Respiratory tract infection viral
eRash includes the following preferred terms: Rash, Rash macular, Rash pruritic, Rash generalized, Rash papular, Rash maculo-papular
In the single-arm Phase ½ clinical trial, one patient (0.2%) experienced QTcF interval of greater than 500 ms. Patients with uncontrolled or significant cardiovascular disease including QT interval prolongation were excluded by protocol. Table 3 identifies the clinically relevant or severe Grade 3/4 laboratory test abnormalities for the Phase ½ CML safety population.
Table 3: Number (%) of
Patients with Clinically Relevant or Severe Grade 3/4 Laboratory Test
Abnormalities In the Phase ½ Clinical Study, Safety Population
|All CP and AdvP CML
|Platelet Count (Low) less than 50×109/L||102 (25)||80 (57)||182 (33)|
|Absolute Neutrophil Count less than 1×109/L||74 (18)||52 (37)||126 (23)|
|Hemoglobin (Low) less than 80 g/L||53 (13)||49 (35)||102 (19)|
|SGPT/ALT greater than 5.0×ULN||39 (10)||8 (6)||47 (9)|
|SGOT/AST greater than 5.0×ULN||17 (4)||4 (3)||21 (4)|
|Lipase greater than 2×ULN||33 (8)||4 (3)||37 (7)|
|Phosphorus (Low) less than 0.6 mmol/L||30 (7)||10 (7)||40 (7)|
|Total Bilirubin greater than 3.0×ULN||3 (1)||2 (1)||5 (1)|
Additional Data from Multiple Clinical Trials
The following adverse reactions were reported in patients in clinical trials with BOSULIF (less than 10% of BOSULIF-treated patients). They represent an evaluation of the adverse reaction data from 870 patients with Ph+ leukemia who received at least 1 dose of single-agent BOSULIF. These adverse reactions are presented by system organ class and are ranked by frequency. These adverse reactions are included based on clinical relevance and ranked in order of decreasing seriousness within each category.
Ear and Labyrinth Disorders: 1% and less than 10% -tinnitus
General Disorders and Administrative Site Conditions: 1% and less than 10% -chest painb, pain
Hepatobiliary Disorders: 1% and less than 10% -hepatotoxicityc, abnormal hepatic functiond; 0.1% and less than 1% -liver injury
Immune System Disorders: 1% and less than 10% -drug hypersensitivity; 0.1% and less than 1% -anaphylactic shock
Investigations: 1% and less than 10% -electrocardiogram QT prolonged, increased blood creatine phosphokinase, increased blood creatinine
Metabolism and Nutrition Disorder: 1% and less than 10% -hyperkalemia, dehydration
Musculoskeletal and Connective Tissue Disorder: 1% and less than 10% -myalgia
Nervous System Disorders: 1% and less than 10% -dysgeusia
Renal and Urinary Disorders: 1% and less than 10% -acute renal failure, renal failure
aGastrointestinal hemorrhage includes the
following preferred terms: gastrointestinal hemorrhage, gastric hemorrhage,
upper gastrointestinal hemorrhage
bChest pain includes the following preferred terms: chest pain, chest discomfort
cHepatotoxicity includes the following preferred terms: hepatotoxicity, toxic hepatitis, cytolytic hepatitis
dAbnormal hepatic function includes the following preferred terms: abnormal hepatic function, liver disorder
ePneumonia includes the following preferred terms: pneumonia, bronchopneumonia, lobar pneumonia, primary atypical pneumonia
Read the entire FDA prescribing information for Bosulif (Bosutinib Tablets) »
Additional Bosulif Information
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