Bosutinib

Bosutinib is an FDA-registered drug product whose active ingredient is BOSUTINIB. It is labelled by Dr. Reddy's Laboratories Inc. taken by oral and marketed as a human prescription drug product. Identifiers on file: NDC 75907-405, application ANDA209624, label effective 20260525. It is one of 4 FDA drug label records sharing the active ingredient BOSUTINIB. This page reproduces the FDA-approved label text so you can check what a product is, who makes it and how it is supplied before discussing it with a pharmacist or prescriber.

Across FDA labelling, products containing BOSUTINIB are most often described in connection with: adult patients, prior therapy, bosutinib tablets, chronic phase, myelogenous leukemia, cml newly-diagnosed, resistant intolerant, see clinical. Wording differs between labels, and the full indications section on this page takes precedence when it is present.

1 INDICATIONS AND USAGE Bosutinib tablets are indicated for the treatment of: Adult patients with chronic phase (CP) Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML), newly-diagnosed or resistant or intolerant to prior therapy [see Clinical Studies ( 14.1 , 14.2 )] . Adult patients with accelerated phase (AP), or blast phase (BP) Ph+ CML with resistance or intolerance to prior therapy [see Clinical Studies (14.2 )]. Pediatric use information is approved for PF PRISM CV’s BOSULIF ® (bosutinib) tablets. However, due to PF PRISM CV’s marketing exclusivity rights, this drug product is not labeled with that information. Bosutinib tablets are a kinase inhibitor indicated for the treatment of adult patients with chronic phase Ph+ chronic myelogenous leukemia (CML), newly-diagnosed or resistant or intolerant to prior therapy. ( 1 ) adult patients with accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy. ( 1 )

2 DOSAGE AND ADMINISTRATION Adult patients with newly-diagnosed chronic phase Ph+ CML: 400 mg orally once daily with food. ( 2.1 ) Adult patients with chronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy: 500 mg orally once daily with food. ( 2.1 ) Consider dose escalation by increments of 100 mg once daily to a maximum of 600 mg daily in adult patients who do not reach complete hematologic, cytogenetic, or molecular response and do not have Grade 3 or greater adverse reactions. ( 2.2 ) Adjust dosage for toxicity and organ impairment ( 2 ) 2.1 Recommended Dosage The recommended dosage is taken orally once daily with food. Swallow tablets whole. Do not cut, crush, break or chew tablets. Continue treatment with bosutinib tablets until disease progression or intolerance to therapy. If a dose is missed beyond 12 hours, the patient should skip the dose and take the usual prescribed dose on the following day. Dosage in Adult Patients with Newly-Diagnosed CP Ph+ CML The recommended dosage of bosutinib tablet is 400 mg orally once daily with food. Dosage in Adult Patients with CP, AP, or BP Ph+ CML with Resistance or Intolerance to Prior Therapy The recommended dosage of bosutinib tablet is 500 mg orally once daily with food. Pediatric use information is approved for PF PRISM CV’s BOSULIF ® (bosutinib) tablets. However, due to PF PRISM CV’s marketing exclusivity rights, this drug product is not labeled with that information . 2.2 Dose Escalation In clinical studies of adult patients with Ph+ CML, dose escalation by increments of 100 mg once daily to a maximum of 600 mg once daily was allowed in patients who did not achieve or maintain a hematologic, cytogenetic, or molecular response and who did not have Grade 3 or higher adverse reactions at the recommended starting dosage. The maximum dose in adult patients is 600 mg once daily. Pediatric use information is approved for PF PRISM CV’s BOSULIF ® (bosutinib) tablets. However, due to PF PRISM CV’s marketing exclusivity rights, this drug product is not labeled with that information. 2.3 Dosage Adjustments for Non-Hematologic Adverse Reactions Elevated liver transaminases: If elevations in liver transaminases greater than 5×institutional upper limit of normal (ULN) occur, withhold bosutinib tablets until recovery to less than or equal to 2.5×ULN and resume at 400 mg once daily thereafter. If recovery takes longer than 4 weeks, discontinue bosutinib tablets. If transaminase elevations greater than or equal to 3×ULN occur concurrently with bilirubin elevations greater than 2×ULN and alkaline phosphatase less than 2×ULN (Hy’s law case definition), discontinue bosutinib tablets [see Warnings and Precautions (5.3 )]. Diarrhea: For National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade 3 to 4 diarrhea (increase of greater than or equal to 7 stools/day over baseline/pretreatment), withhold bosutinib tablets until recovery to Grade less than or equal to 1. Bosutinib tablets may be resumed at 400 mg once daily [see Warnings and Precautions (5.1 )] . For other clinically significant, moderate or severe non-hematological toxicity, withhold bosutinib tablets until the toxicity has resolved, then consider resuming bosutinib tablets at a dose reduced by 100 mg taken once daily. If clinically appropriate, consider re-escalating the dose of bosutinib tablets to the starting dose taken once daily. Pediatric use information is approved for PF PRISM CV’s BOSULIF ® (bosutinib) tablets. However, due to PF PRISM CV’s marketing exclusivity rights, this drug product is not labeled with that information. 2.4 Dosage Adjustments for Myelosuppression Dose reductions for severe or persistent neutropenia and thrombocytopenia are described below (Table 3). Table 3: Dose Adjustments for Neutropenia and Thrombocytopenia in Adult Patients ANC a less than 1,000×10 6 /L or Platelets less than 50,000×10 6 /L Withhold bosutinib tablets until ANC greater than or equal to 1,000×10 6 /L and platelets greater than or equal to 50,000×10 6 /L. Resume treatment with bosutinib tablets at the same dose if recovery occurs within 2 weeks. If blood counts remain low for greater than 2 weeks, upon recovery, reduce dose by 100 mg and resume treatment. If cytopenia recurs, reduce dose by an additional 100 mg upon recovery and resume treatment. a Absolute Neutrophil Count Pediatric use information is approved for PF PRISM CV’s BOSULIF ® (bosutinib) tablets. However, due to PF PRISM CV’s marketing exclusivity rights, this drug product is not labeled with that information. 2.5 Dosage Adjustments for Renal Impairment or Hepatic Impairment The recommended starting doses for patients with renal and hepatic impairment are described in Table 4 below. Table 4: Dose Adjustments for Renal and Hepatic Impairment in Adult Patients R ecommended Starting Dosage N ewly-diagnosed chronic phase Ph+ CML C hronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy Normal renal and hepatic function 400 mg daily 500 mg daily Renal impairment Creatinine clearance 30 to 50 mL/min 300 mg daily 400 mg daily Creatinine clearance less than 30 mL/min 200 mg daily 300 mg daily Hepatic impairment Mild (Child-Pugh A), Moderate (Child-Pugh B) or Severe (Child-Pugh C) 200 mg daily 200 mg daily [see Use in Specific Populations (8.6 , 8.7 ) and Clinical Pharmacology (12.3 )] . Pediatric use information is approved for PF PRISM CV’s BOSULIF ® (bosutinib) tablets. However, due to PF PRISM CV’s marketing exclusivity rights, this drug product is not labeled with that information.

4 CONTRAINDICATIONS Bosutinib tablets are contraindicated in patients with a history of hypersensitivity to bosutinib. Reactions have included anaphylaxis [see Adverse Reactions (6.1 )]. Hypersensitivity to bosutinib. ( 4 )

6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: • Gastrointestinal toxicity [see Warnings and Precautions (5.1) ]. • Myelosuppression [see Warnings and Precautions (5.2) ]. • Hepatic toxicity [see Warnings and Precautions (5.3 )]. • Cardiovascular toxicity [see Warnings and Precautions (5.4) ]. • Fluid retention [see Warnings and Precautions (5.5) ]. • Renal toxicity [see Warnings and Precautions (5.6) ]. Most common adverse reactions (≥20%), in adult patients with CML are diarrhea, abdominal pain, vomiting, nausea, rash, fatigue, hepatic dysfunction, headache, pyrexia, respiratory tract infection. The most common laboratory abnormalities (≥20%) in adult patients are creatinine increased, hemoglobin decreased, lymphocyte count decreased, platelets decreased, ALT increased, calcium decreased, white blood cell count decreased, AST increased, absolute neutrophil count decreased, glucose increased, phosphorus decreased, urate increased, alkaline phosphatase increased, lipase increased, creatine kinase increased, and amylase increased. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Dr. Reddy's Laboratories Inc., at 1-888-375-3784 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience 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. The most common adverse reactions, in ≥20% of adults with newly diagnosed CP Ph+ CML or CP, AP, or BP Ph+ CML with resistance or intolerance to prior therapy (N=814) were diarrhea (80%), rash (44%), nausea (44%), abdominal pain (43%), vomiting (33%), fatigue (33%), hepatic dysfunction (33%), respiratory tract infection (25%), pyrexia (24%), and headache (21%). The most common laboratory abnormalities that worsened from baseline in ≥20% of adults were creatinine increased (93%), hemoglobin decreased (90%), lymphocyte count decreased (72%), platelets decreased (69%), ALT increased (58%), calcium decreased (53%), white blood cell count decreased (52%), absolute neutrophils count decreased (50%), AST increased (50%), glucose increased (46%), phosphorus decreased (44%), urate increased (41%), alkaline phosphatase increased (40%), lipase increased (36%), creatine kinase increased (29%), and amylase increased (24%). Adverse Reactions in Adult Patients With Newly-Diagnosed CP CML The clinical trial randomized and treated 533 patients with newly-diagnosed CP CML to receive bosutinib 400 mg daily or imatinib 400 mg daily as single agents (Newly-Diagnosed CP CML Study) [see Clinical Studies (14.1) ] . The safety population (received at least 1 dose of bosutinib) included: two hundred sixty-eight (268) patients with newly-diagnosed CP CML had a median duration of bosutinib treatment of 55 months (range: 0.3 to 60 months) and a median dose intensity of 394 mg/day. Serious adverse reactions occurred in 22% of patients with newly-diagnosed CP CML who received bosutinib. Serious adverse reactions reported in >2% of patients included hepatic dysfunction (4.1%), pneumonia (3.4%), coronary artery disease (3.4%), and gastroenteritis (2.2%). Fatal adverse reactions occurred in 3 patients (1.1%) due to coronary artery disease (0.4%), cardiac failure acute (0.4%), and renal failure (0.4%). Permanent discontinuation of bosutinib due to an adverse reaction occurred in 20% of patients with newly-diagnosed CP CML who received bosutinib. Adverse reactions which resulted in permanent discontinuation in > 2% of patients included hepatic dysfunction (9%). Dose modifications (dose interruption or reductions) of bosutinib due to an adverse reaction occurred in 68% of patients with newly-diagnosed CP CML. Adverse reactions which required dose interruptions or reductions in >5% of patients included hepatic dysfunction (27%), thrombocytopenia (16%), diarrhea (16%), lipase increased (10%), neutropenia (7%), abdominal pain (6%), rash (5%). The most common adverse reactions, in >20% of bosutinib-treated patients with newly-diagnosed CML (N=268) were diarrhea (75%), hepatic dysfunction (45%), rash (40%), abdominal pain (39%), nausea (37%), fatigue (33%), respiratory tract infection (27%), headache (22%), and vomiting (21%). The most common laboratory abnormalities that worsened from baseline in ≥20% of patients were creatinine increased (94%), hemoglobin decreased (89%), lymphocyte count decreased (84%), ALT increased (68%), platelet count decreased (68%), glucose increased (57%), AST increased (56%), calcium decreased (55%), phosphorus decreased (54%), lipase increased (53%), white blood cell count decreased (50%), absolute neutrophil count decreased (42%), alkaline phosphatase increased (41%), creatine kinase increased (36%), and amylase increased (32%). Table 7 identifies adverse reactions greater than or equal to 10% for All Grades and Grades 3 or 4 (3/4) for the Phase 3 CP CML safety population. Table 7: Adverse Reactions (10% or Greater) in Patients With Newly-Diagnosed CML in Bosutinib 400 mg Study* System Organ Class Preferred Term B osutinib 400 mg C hronic Phase CML (N= 268) Imatinib 400 mg C hronic Phase CML (N= 265) A l l Grades % G rade 3/4 % A l l Grades % G rade 3/4 % Gastrointestinal disorders Diarrhea 75 9 40 1 Abdominal pain a 39 2 27 1 Nausea 37 0 42 0 Vomiting 21 1 20 0 Hepatobiliary disorders Constipation 13 0 6 0 Skin and subcutaneous tissue disorders Hepatic dysfunction f 45 27 15 4 Rash d 40 2 30 2 Pruritus 11 <1 4 0 General disorders and administration-site conditions Fatigue b 33 1 30 <1 Pyrexia 17 1 11 0 Edema g 15 0 46 2 Infections and infestations Respiratory tract infection e 27 1 25 <1 Nervous system disorders Headache 22 1 15 1 Musculoskeletal and connective tissue disorders Arthralgia 18 1 18 <1 Back pain 12 <1 9 <1 Respiratory, thoracic, and mediastinal disorders Cough 11 0 10 0 Dyspnea 11 1 6 1 Metabolism and nutrition disorders Decreased appetite 11 <1 6 0 Vascular disorders Hypertension c 10 5 11 5 *Based on a Minimum of 57 Months of Follow-up. Adverse drug reactions are based on all-causality treatment-emergent adverse events. The commonality stratification is based on 'All Grades' under Total column. 'Grade 3', 'Grade 4' columns indicate maximum toxicity. a Abdominal pain includes the following preferred terms: Abdominal discomfort, Abdominal pain, Abdominal pain lower, Abdominal pain upper, Abdominal tenderness, Dyspepsia, Epigastric discomfort, Gastrointestinal pain. b Fatigue includes the following preferred terms: Asthenia, Fatigue, Malaise. c Hypertension* includes the preferred terms: Blood pressure systolic increased, Hypertension, Hypertensive crisis, Hypertensive heart disease, Retinopathy hypertensive. f Hepatic dysfunction includes the preferred terms: Alanine aminotransferase increased, Aspartate aminotransferase, Aspartate aminotransferase increased, Bilirubin conjugated increased, Blood alkaline phosphatase increased, Blood bilirubin increased, Drug-induced liver injury, Gamma-glutamyltransferase increased, Hepatic enzyme increased, Hepatic steatosis, Hepatitis, Hepatitis toxic, Hepatocellular injury, Hepatotoxicity, Hyperbilirubinemia, Jaundice, Liver disorder, Liver function test increased, Ocular icterus, Transaminases increased. g Edema includes the following preferred terms: Eye edema, Eyelid edema, Face edema, Edema, Edema peripheral, Orbital edema, Periorbital edema, Periorbital swelling, Peripheral swelling, Swelling, Swelling face, Swelling of eyelid, Swollen tongue. d Rash includes the following preferred terms: Acne, Blister, Dermatitis, Dermatitis acneiform, Dermatitis bullous, Dermatitis exfoliative generalized, Drug reaction with eosinophilia and systemic symptoms, Dyshidrotic eczema, Eczema, Eczema asteatotic, Erythema, Erythema nodosum, Genital rash, Lichen planus, Perivascular dermatitis, Photosensitivity reaction, Psoriasis, Rash, Rash erythematous, Rash macular, Rash maculo-papular, Rash papular, Rash pruritic, Rash pustular, Rash vesicular, Seborrhoeic keratosis, Skin discoloration, Skin exfoliation, Skin hypopigmentation, Skin irritation, Skin lesion, Stasis dermatitis. e Respiratory tract infection includes the following preferred terms: Nasopharyngitis, Respiratory tract congestion, Respiratory tract infection, Respiratory tract infection viral, Upper respiratory tract infection. In the randomized study in patients with newly-diagnosed CP CML, one patient in the group treated with bosutinib experienced a Grade 3 QTcF prolongation (>500 msec). Patients with uncontrolled or significant cardiovascular disease including QT interval prolongation were excluded by protocol. Table 8 identifies the clinically relevant or severe Grade 3/4 laboratory test abnormalities for the Phase 3 newly-diagnosed CML safety population. Table 8: Select Laboratory Abnormalities (>20%) That Worsened From Baseline in Patients with Newly-Diagnosed CML in Bosutinib 400 mg Study* B osutinib N= 268 % Imatinib N= 265 % All Grade Grade 3 to 4 All Grade Grade 3 to 4 Hematology Parameters Platelet Count decreased 68 14 60 6 Absolute Neutrophil Count decreased 42 9 65 20 Hemoglobin decreased 89 9 90 7 White Blood Cell Count decreased 50 6 70 8 Lymphocyte Count decreased 84 12 82 14 B i ochemistry Parameters SGPT/ALT increased 68 26 28 3 SGOT/AST increased 56 13 29 3.4 Lipase increased 53 19 35 8 Phosphorus decreased 54 9 69 21 Amylase increased 32 3.4 18 2.3 Alkaline Phosphatase increased 41 0 43 0.4 Calcium decreased 55 1.5 57 1.1 Glucose increased 57 3 65 3.4 Creatine Kinase increased 36 3 65 5 Creatinine increased 94 1.1 98 0.8 *Based on a Minimum of 57 Months of Follow-up. Abbreviations: ALT=alanine aminotransferase; AST=aspartate aminotransferase; CML=chronic myelogenous leukemia; SGPT=serum glutamic-pyruvic transaminase; SGOT=serum glutamic-oxaloacetic transaminase; N/n=number of patients; ULN=upper limit of normal. Graded using CTCAE v 4.03 Adverse Reactions in Adult Patients With Imatinib-Resistant or -Intolerant Ph+ CP, AP, and BP CML The single-arm clinical trial enrolled patients with Ph+ CP, AP, or BP CML and with resistance or intolerance to prior therapy [see Clinical Studies (14.2 )]. The safety population (received at least 1 dose of bosutinib) included 546 CML patients: two hundred eighty-four (284) patients with CP CML previously treated with imatinib only who had a median duration of bosutinib treatment of 26 months (range: 0.2 to 155 months), and a median dose intensity of 437 mg/day. one hundred nineteen (119) patients with CP CML previously treated with both imatinib and at least 1 additional tyrosine kinase inhibitor (TKI) who had a median duration of bosutinib treatment of 9 months (range: 0.2 to 148 months) and a median dose intensity of 427 mg/day. one hundred forty-three (143) patients with advanced phase (AdvP) CML including 79 patients with AP CML and 64 patients with BP CML. In the patients with AP CML and BP CML, the median duration of bosutinib treatment was 10 months (range: 0.1 to 140 months) and 3 months (range: 0.03 to 71 months), respectively. The median dose intensity was 406 mg/day, and 456 mg/day, in the AP CML and BP CML cohorts, respectively. Serious adverse reactions occurred in 30% of patients in the safety population of the single-arm trial in patients with CML (N=546) who were resistant or intolerant to prior therapy. Serious adverse reactions reported in >2% of patients included pneumonia (7%), pleural effusion (6%), pyrexia (3.7%), coronary artery disease (3.5%), dyspnea (2.6%), rash (2.2%), thrombocytopenia (2%), abdominal pain (2%), and diarrhea (2%). Fatal adverse reactions occurred in 12 patients (2.2%) due to coronary artery disease (0.9%), pneumonia (0.4%), respiratory failure (0.4%), gastrointestinal hemorrhage (0.2%), acute kidney injury (0.2%), and acute pulmonary edema (0.2%). Permanent discontinuation of bosutinib due to an adverse reaction occurred in 22% of patients with CML who were resistant or intolerant to prior therapy. Adverse reactions which resulted in permanent discontinuation in >2% of patients included thrombocytopenia (6%), hepatic dysfunction (3.3%), and neutropenia (2%). Dose modifications (dose interruption or reductions) of bosutinib due to an adverse reaction occurred in 66% of patients with CML who were resistant or intolerant to prior therapy. Adverse reactions which required dose interruptions or reductions in >5% of patients included thrombocytopenia (24%), diarrhea (14%), rash (13%), hepatic dysfunction (10%), neutropenia (9%), pleural effusion (8%), vomiting (7%), anemia (6%), and abdominal pain (6%). The most common adverse reactions, in ≥20% of patients in the safety population of the single-arm trial in patients with CML (N=546) who were resistant or intolerant to prior therapy were diarrhea (83%), nausea (47%), rash (46%), abdominal pain (45%), vomiting (39%), fatigue (33%), pyrexia (28%), hepatic dysfunction (27%), respiratory tract infection (24%), cough (23%), and headache (21%). The most common laboratory abnormalities that worsened from baseline in ≥20% were creatinine increased (93%), hemoglobin decreased (91%), lymphocyte decreased (80%), platelets decreased (69%), absolute neutrophil count (54%), ALT increased (53%), calcium decreased (53%), white blood cell count decreased (52%), urate increased (48%), AST increased (47%), phosphorus decreased (39%), alkaline phosphatase increased (39%), lipase increased (28%), magnesium increased (25%), potassium decreased (24%), potassium increased (23%). See Table 10 for Grade 3/4 laboratory abnormalities. Table 9 identifies adverse reactions greater than or equal to 10% for All Grades and Grades 3 or 4 for the Phase 1/2 CML safety population based on long-term follow-up. Table 9: Adverse Reactions (10% or Greater) in Patients With CML Who Were Resistant or Intolerant to Prior Therapy in Single-Arm Trial* System Organ Class Preferred Term C P CML (N= 403) A dvP CML (N= 143) A l l Grades % G rade 3/4 % A l l Grades % G rade 3/4 % Gastrointestinal disorders Diarrhea 85 10 76 4 Abdominal pain a 49 2 36 7 Nausea 47 1 48 2 Vomiting 38 3 43 3 Constipation 15 <1 17 1 Skin and subcutaneous tissue disorders Rash e 48 9 42 5 Pruritus 12 1 7 0 General disorders and administration- site conditions Fatigue 35 3 27 6 Pyrexia 25 1 37 3 Edema c 19 <1 17 1 Chest pain g 8 1 12 1 Hepatobiliary disorders Hepatic dysfunction h 29 11 21 10 Infections and infestations Respiratory tract infection f 27 <1 17 0 Influenza i 11 1 3 0 Pneumonia d 10 4 18 12 Respiratory, thoracic, and mediastinal disorders Cough 24 0 22 0 Pleural effusion 14 4 9 4 Dyspnea 12 2 20 6 Nervous system disorders Headache 21 1 18 4 Dizziness 11 0 14 1 Musculoskeletal and connective tissue disorders Arthralgia 19 1 15 0 Back pain 14 1 8 1 Metabolism and nutrition disorders Decreased appetite 14 1 14 0 Vascular disorders Hypertension b 11 3 8 3 ADR Definition * Based on a Minimum of 105 Months of Follow-up. Adverse drug reactions are based on all-causality treatment-emergent adverse events. The commonality stratification is based on 'All Grades' under Total column. 'Grade 3', 'Grade 4' columns indicate maximum toxicity a Abdominal pain includes the following preferred terms: Abdominal discomfort, Abdominal pain, Abdominal pain lower, Abdominal pain upper, Abdominal tenderness, Dyspepsia, Epigastric discomfort, Gastrointestinal pain, Hepatic pain. g Chest pain includes the following preferred terms: Chest discomfort, Chest pain. h Hepatic dysfunction includes the following preferred terms: Alanine aminotransferase increased, Aspartate aminotransferase increased, Bilirubin conjugated increased, Blood alkaline phosphatase increased, Blood bilirubin increased, Blood bilirubin unconjugated increased, Gamma-glutamyltransferase increased, Hepatic enzyme increased, Hepatic function abnormal, Hepatic steatosis, Hepatitis toxic, Hepatomegaly, Hepatotoxicity, Hyperbilirubinemia, Liver disorder, Liver function test abnormal, Liver function test increased, Transaminases increased. b Hypertension* includes the following preferred terms: Blood pressure increased, Blood pressure systolic increased, Essential hypertension, Hypertension, Hypertensive crisis, Retinopathy hypertensive. iInfluenza includes the following preferred terms: H1N1 influenza, Influenza. c Edema includes the following preferred terms: Eye edema, Eyelid edema, Face edema, Generalized edema, Localized edema, Edema, Edema peripheral, Penile edema, Periorbital edema, Periorbital swelling, Peripheral swelling, Scrotal edema, Scrotal swelling, Swelling, Swelling face, Swelling of eyelid, Testicular edema, Tongue edema. d Pneumonia includes the following preferred terms: Atypical pneumonia, Lower respiratory tract congestion, Lower respiratory tract infection, Pneumonia, Pneumonia aspiration, Pneumonia bacterial, Pneumonia fungal, Pneumonia necrotising, Pneumonia streptococcal. e Rash includes the following preferred terms: Acarodermatitis, Acne, Angular cheilitis, Blister, Dermatitis, Dermatitis acneiform, Dermatitis psoriasiform, Drug eruption, Eczema, Eczema asteatotic, Erythema, Erythema annulare, Exfoliative rash, Lichenoid keratosis, Palmar erythema, Photosensitivity reaction, Pigmentation disorder, Psoriasis, Pyoderma gangrenosum, Pyogenic granuloma, Rash, Rash erythematous, Rash generalised, Rash macular, Rash maculo-papular, Rash pruritic, Rash pustular, Seborrhoeic dermatitis, Seborrhoeic keratosis, Skin depigmentation, Skin discoloration, Skin disorder, Skin exfoliation, Skin hyperpigmentation, Skin hypopigmentation, Skin irritation, Skin lesion, Skin plaque, Skin toxicity, Stasis dermatitis. f Respiratory tract infection includes the following preferred terms: Nasopharyngitis, Respiratory tract congestion, Respiratory tract infection, Respiratory tract infection viral, Upper respiratory tract infection, Viral upper respiratory tract infection. *ADR identified post-marketing In the single-arm study in patients with CML who were resistant or intolerant to prior therapy, 2 patients (0.4%) experienced QTcF interval of greater than 500 milliseconds. Patients with uncontrolled or significant cardiovascular disease including QT interval prolongation were excluded by protocol. Table 10 identifies the clinically relevant or severe Grade 3/4 laboratory test abnormalities for the safety population of the study in patients with CML who were resistant or intolerant to prior therapy based on long-term follow-up. Table 10: Number (%) of Patients With Clinically Relevant All Grade or Grade 3/4 Laboratory Test Abnormalities in the Safety Population of the Study of Patients With CML Who Were Resistant or Intolerant to Prior Therapy* C P CML N= 403% A dvP CML N= 143 % All grade Grade 3/4 All grade Grade 3/4 H e m atology Parameters Platelet Count decreased 66 26 80 57 Absolute Neutrophil Count decreased 50 16 66 39 Hemoglobin decreased 89 13 97 38 Lymphocyte decreased 79 14 82 21 White Blood Cell Count decreased 51 7 57 27 Biochemistry Parameters SGPT/ALT increased 58 11 39 6 SGOT/AST increased 50 5 37 3.5 Lipase increased 32 12 19 6 Phosphorus decreased 41 8 33 7 Total Bilirubin increased 16 0.7 22 2.8 Creatinine increased 95 3 87 1.4 Alkaline Phosphatase increased 39 0 39 1.4 Glucose increased 42 2.7 39 6 Sodium increased 23 0.5 11 0 Sodium decreased 18 2.2 27 6 Calcium decreased 55 4.7 45 3.5 Urate increased 49 6 43 6 Magnesium increased 27 7 18 4.9 Potassium decreased 22 1.7 29 4.9 Potassium increased 25 2.7 19 2.1 *Based on a Minimum of 105 Months of Follow-up. Abbreviations: AdvP=advanced phase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; CML=chronic myelogenous leukemia; CP=chronic phase; N/n=number of patients; SGPT=serum glutamate-pyruvate transaminase; SGOT=serum glutamate-oxaloacetate aminotransferase; ULN=upper limit of normal. Additional Adverse Reactions From Multiple Clinical Trials The following adverse reactions were reported in patients in clinical trials with bosutinib (less than 10% of bosutinib-treated patients). They represent an evaluation of the adverse reaction data from all 1,372 patients with leukemia who received at least 1 dose of single-agent bosutinib. 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. Blood and Lymphatic System Disorders: 0.1% and less than 1% - Febrile neutropenia Cardiac Disorders: 1% and less than 10% -Cardiac ischemia (includes Acute coronary syndrome, Acute myocardial infarction, Angina pectoris, Angina unstable, Arteriosclerosis coronary artery, Coronary artery disease, Coronary artery occlusion, Coronary artery stenosis, Myocardial infarction, Myocardial ischemia, Troponin increased), Pericardial effusion, Cardiac failure (includes Cardiac failure, Cardiac failure acute, Cardiac failure chronic, Cardiac failure congestive, Cardiogenic shock, Cardiorenal syndrome, Ejection fraction decreased, Left ventricular failure); 0.1% and less than 1% - Pericarditis Ear and Labyrinth Disorders: 1% and less than 10% - Tinnitus Endocrine Disorders: 1% and less than 10% - Hypothyroidism; 0.1% and less than 1% - Hyperthyroidism Gastrointestinal Disorders: 1% and less than 10% - Gastritis, Pancreatitis (includes Edematous pancreatitis, Pancreatic enzymes increased, Pancreatitis, Pancreatitis acute, Pancreatitis chronic), Gastrointestinal hemorrhage (includes Anal hemorrhage, Gastric hemorrhage, Gastrointestinal hemorrhage, Intestinal hemorrhage, Lower gastrointestinal hemorrhage, Rectal hemorrhage, Upper gastrointestinal hemorrhage) General Disorders and Administrative Site Conditions: 1% and less than 10% - Pain Immune System Disorders: 1% and less than 10% - Drug hypersensitivity; 0.1% and less than 1% - Anaphylactic shock Infections and Infestations: 1% and less than 10% - Bronchitis Investigations: 1% and less than 10% - Electrocardiogram QT prolonged (includes Electrocardiogram QT prolonged, Long QT syndrome) Metabolism and Nutrition Disorders: 1% and less than 10% - Dehydration Musculoskeletal and Connective Tissue Disorders: 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 kidney injury, Renal impairment, Renal failure Respiratory, Thoracic and Mediastinal Disorders: 1% and less than 10% - Pulmonary hypertension (includes Pulmonary hypertension, Pulmonary arterial hypertension, Pulmonary arterial pressure increased); 0.1% and less than 1% - Acute pulmonary edema (includes Acute pulmonary edema, Pulmonary edema), Interstitial lung disease, Respiratory failure Skin and Subcutaneous Disorders: 0.1% and less than 1% - Erythema multiforme, Cutaneous vasculitis Pediatric use information is approved for PF PRISM CV’s BOSULIF ® (bosutinib) tablets. However, due to PF PRISM CV’s marketing exclusivity rights, this drug product is not labeled with that information. 6.2 Postmarketing Experience The following additional adverse reactions have been identified during post-approval use of bosutinib. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and Lymphatic System Disorders: Thrombotic microangiopathy Skin and Subcutaneous Tissue Disorders : Stevens-Johnson syndrome

FDA lists 4 drug label records with BOSUTINIB as the active ingredient. The most common dosage forms and the manufacturers with the most records are summarised below; strengths, pack sizes and inactive ingredients can still differ between apparently similar products.

What is Bosutinib used for?
1 INDICATIONS AND USAGE Bosutinib tablets are indicated for the treatment of: Adult patients with chronic phase (CP) Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML), newly-diagnosed or resistant or intolerant to prior therapy [see Clinical Studies ( 14.1 , 14.2 )] . Adult patients with accelerated phase (AP), or blast phase (BP) Ph+ CML with resistance or intolerance to …

Who makes Bosutinib?
Dr. Reddy's Laboratories Inc. is the labeler of record for Bosutinib. 4 FDA label records share the active ingredient BOSUTINIB, so generic and branded versions may come from different companies; the manufacturer named on your pack is the one that matters for any enquiry.

What form does Bosutinib come in?
administered by oral. Strengths and pack sizes vary by label, so compare the NDC on your pack with the identifier listed on this page.

Is Bosutinib prescription or over-the-counter?
The FDA label for this product is recorded as human prescription drug. Marketing status can differ between strengths and countries, so check the dispensing rules where you live.

Are there other products containing BOSUTINIB?
Yes. 4 FDA drug label records list BOSUTINIB as the active ingredient. Products with the same active ingredient can usually be substituted only when a prescriber or pharmacist confirms it is appropriate.

Has Bosutinib been recalled?
No FDA recall record in our database matches this product name or manufacturer. Recall data is updated periodically, so a very recent notice may not appear here yet.

Where does this information come from?
All content is reproduced from FDA Structured Product Labelling data via openFDA. It is provided for identification and reference only and is not medical advice.