ASH Clinical News ACN_4.5_FULL_ISSUE_DIGITAL - Page 25

a
Thrombocytopenia includes the following preferred terms : Platelet count decreased , Thrombocytopenia . b
Rash includes the following preferred terms : Acne , Dermatitis , Dermatitis acneiform , Dermatitis allergic , Dermatitis exfoliative , Drug eruption , Drug reaction with eosinophilia and systemic symptoms , Exfoliative rash , Photosensitivity reaction , Rash , Rash erythematous , Rash generalized , Rash macular , Rash maculo-papular , Rash papular , Rash pruritic , Urticaria . c
Abdominal pain includes the following preferred terms : Abdominal discomfort , Abdominal pain , Abdominal pain lower , Abdominal pain upper , Abdominal tenderness , Gastrointestinal pain .
d
Anemia includes the following preferred terms : Anemia , Hemoglobin decreased . e
Fatigue includes the following preferred terms : Fatigue , Malaise . f
Lipase increased includes the following preferred terms : Hyperlipasemia , Lipase increased . g
Respiratory tract infection includes the following preferred terms : Lower respiratory tract infection , Respiratory tract infection , Respiratory tract infection viral , Upper respiratory tract infection , Viral upper respiratory tract infection .
h
Neutropenia includes the following preferred terms : Neutropenia , Neutrophil count decreased . i
Edema includes the following preferred terms : Edema , Edema peripheral , Face edema , Localized edema . j
Leukopenia includes the following preferred terms : Leukopenia , White blood cell count decreased . k
Chest pain included the following preferred terms : Chest discomfort , Chest pain .
In the single-arm study in patients with CML who were resistant or intolerant to prior therapy , 1 patient ( 0.2 %) experienced QTcF interval of greater than 500 msec . Patients with uncontrolled or significant cardiovascular disease , including QT interval prolongation , were excluded by protocol .
Clinically Relevant or Grade 3 / 4 Laboratory Test Abnormalities ( CP [ n /%]; AdvP [ n /%]; all CP and AdvP [ n /%]) in Patients with CML Who Were Resistant or Intolerant to Prior Therapy , Safety Population ( CP n = 403 ; AdvP n = 143 ; All CP and AdvP n = 546 ), Based on a Minimum of 48 Months of Follow-up : Hematology parameters were platelet count ( low ) less than 50 x 10 9 / L ( 105 / 26 ; 82 / 57 ; 187 / 34 ), absolute neutrophil count less than 1 x 10 9 / L ( 65 / 16 ; 55 / 39 ; 120 / 22 ), hemoglobin ( low ) less than 80 g / L ( 51 / 13 ; 54 / 38 ; 105 / 19 ). Biochemistry parameters were SGPT / ALT greater than 5.0 x ULN ( 43 / 11 ; 8 / 6 ; 51 / 9 ), SGOT / AST greater than 5.0 x ULN ( 19 / 5 ; 5 / 4 ; 24 / 4 ), lipase greater than 2 x ULN ( 42 / 10 ; 9 / 6 ; 51 / 9 ), phosphorus ( low ) less than 0.6 mmol / L ( 30 / 7 ; 10 / 7 ; 40 / 7 ), total bilirubin greater than 3.0 x ULN ( 3 / 1 ; 4 / 3 ; 7 / 1 ) .
Additional Adverse Reactions 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 1272 patients with 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 .
Blood and Lymphatic System Disorders : less than 0.01 % - Febrile neutropenia , Granulocytopenia Cardiac Disorders : 1 % and less than 10 % - Pericardial effusion ; 0.1 % and less than 1 % - Pericarditis Ear and Labyrinth Disorders : 1 % and less than 10 % - Tinnitus Vascular Disorders : 1 % and less than 10 % - Hypertension Gastrointestinal Disorders : 1 % and less than 10 % - Gastritis ; 0.1 % and less than 1 % - Pancreatitis ( includes Pancreatitis , Pancreatitis acute ), Gastrointestinal hemorrhage ( includes Anal hemorrhage , Gastric hemorrhage , Gastrointestinal hemorrhage , Intestinal hemorrhage , Lower gastrointestinal hemorrhage , Rectal hemorrhage )
General Disorders and Administrative Site Conditions : 1 % and less than 10 % - Pain Hepatobiliary Disorders : 1 % and less than 10 % - Hepatotoxicity ( includes Hepatotoxicity , Hepatitis , Hepatitis toxic , Liver disorder ), Hepatic function abnormal ( includes Hepatic function abnormal , Liver function test abnormal , Transaminases increased ); 0.1 % and less than 1 % - Liver injury ( includes Liver injury , Drug-induced liver injury )
Immune System Disorders : 0.1 % and less than 1 % - Anaphylactic shock , Drug hypersensitivity Infections and Infestations : 1 % and less than 10 % - Pneumonia ( includes pneumonia , atypical pneumonia ), influenza , bronchitis
Investigations : 1 % and less than 10 % - Electrocardiogram QT prolonged ( includes Electrocardiogram QT prolonged , Long QT syndrome ), Blood bilirubin increased ( includes Blood bilirubin increased , Hyperbilirubinaemia ), Blood creatine phosphokinase increased , Amylase increased , GGT increased
Metabolism and Nutrition Disorders : 1 % and less than 10 % - Hypophosphatemia ( includes Hypophosphatemia , Blood phosphorus decreased ), Hyperkalemia ( includes Hyperkalemia , Blood potassium increased ), 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 , Acute renal failure , Renal failure
Respiratory , Thoracic , and Mediastinal Disorders : 0.1 % and less than 1 % - Acute pulmonary edema , Respiratory failure , Pulmonary hypertension
Skin and Subcutaneous Disorders : 0.1 % and less than 1 % - Erythema multiforme Post-Marketing Experience The following additional adverse reactions have been identified during post-approval use of BOSULIF . 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 .
Skin and Subcutaneous Tissue Disorders : Stevens-Johnson syndrome
DRUG INTERACTIONS Effect of Other Drugs on BOSULIF Strong or Moderate CYP3A Inhibitors : Concomitant use with a strong or moderate CYP3A inhibitor increased bosutinib C max and AUC compared to BOSULIF alone , which may increase the risk of toxicities . Avoid the concomitant use of strong or moderate CYP3A inhibitors with BOSULIF .
Strong CYP3A Inducers : Concomitant use with a strong CYP3A inducer decreased bosutinib C max and AUC compared to BOSULIF alone , which may reduce BOSULIF efficacy . Avoid the concomitant use of strong CYP3A inducers with BOSULIF .
Proton Pump Inhibitors ( PPI ): Concomitant use with a PPI decreased bosutinib C max and AUC compared to BOSULIF alone , which may reduce BOSULIF efficacy . As an alternative to PPIs , use short-acting antacids or H2 blockers and separate dosing by more than 2 hours from BOSULIF dosing .
USE IN SPECIFIC POPULATIONS Pregnancy : Based on findings from animal studies and its mechanism of action , BOSULIF can cause fetal harm when administered to a pregnant woman . There are no available data in pregnant women to inform the drug-associated risk . In animal reproduction studies conducted in rats and rabbits , oral administration of bosutinib caused adverse developmental outcomes . Administration of bosutinib to rats prior to fertilization until gestation day ( GD ) 7 caused increased embryonic resorptions at maternal exposures ( AUC ) approximately 0.5 and 0.4 times the human exposure at the recommended doses of 400 and 500 mg / day , respectively , and decreased implantations and reduced number of viable embryos at maternal exposures approximately 1.8 and 1.3 times the human exposure at the recommended doses of 400 or 500 mg / day , respectively . Administration of bosutinib to pregnant rabbits during organogenesis caused adverse developmental outcomes including fetal anomalies and reduced fetal body weights at maternal exposures ( AUC ) approximately 2.3 and 1.7 times the human exposure at the recommended doses of 400 or 500 mg / day , respectively . Advise pregnant women of the potential risk to a fetus . Lactation : No data are available regarding the presence of bosutinib or its metabolites in human milk or its effects on a breastfed child or on milk production . However , bosutinib is present in the milk of lactating rats . Because of the potential for serious adverse reactions in a nursing child , breastfeeding is not recommended during treatment with BOSULIF and for at least 1 month after the last dose .
Females and Males of Reproductive Potential : Based on findings from animal studies , BOSULIF can cause fetal harm when administered to a pregnant woman . Females of reproductive potential should have a pregnancy test prior to starting treatment with BOSULIF . Advise females of reproductive potential to use effective contraception ( methods that result in less than 1 % pregnancy rates ) during treatment with BOSULIF and for at least 1 month after the last dose . The risk of infertility in females or males of reproductive potential has not been studied in humans . Based on findings from animal studies , BOSULIF may cause reduced fertility in females and males of reproductive potential .
Pediatric Use : The safety and efficacy of BOSULIF in patients less than 18 years of age have not been established .
Geriatric Use : In the single-arm study in patients with CML who were resistant or intolerant to prior therapy of BOSULIF in patients with Ph + CML , 20 % were age 65 and over and 4 % were 75 and over . No overall differences in safety or effectiveness were observed between these patients and younger patients , and other reported clinical experience has not identified differences in responses between the elderly and younger patients , but greater sensitivity of some older individuals cannot be ruled out .
Renal Impairment : Reduce the BOSULIF starting dose in patients with moderate ( creatinine clearance
[ CL cr ] 30 to 50 mL / min , estimated by Cockcroft-Gault ( C-G )) and severe ( CL cr less than 30 mL / min , C-G ) renal impairment at baseline . For patients who have declining renal function while on BOSULIF who cannot tolerate the starting dose , follow dose adjustment recommendations for toxicity . BOSULIF has not been studied in patients undergoing hemodialysis .
Hepatic Impairment : Reduce the BOSULIF dosage in patients with hepatic impairment ( Child-Pugh A , B , or C ).
PATIENT COUNSELING INFORMATION See FDA-approved patient labeling . Dosing and Administration : Instruct patients to take BOSULIF exactly as prescribed , not to change their dose or to stop taking BOSULIF unless they are told to do so by their doctor . If patients miss a dose beyond 12 hours , they should be advised to take the next scheduled dose at its regular time . A double dose should not be taken to make up for any missed dose . Advise patients to take BOSULIF with food . Patients should be advised : “ Do not crush , break , or cut tablet . Do not touch or handle crushed or broken tablets .” Gastrointestinal Problems : Advise patients that they may experience diarrhea , nausea , vomiting , abdominal pain , or blood in their stools with BOSULIF and to seek medical attention promptly for these symptoms . Low Blood Cell Counts : Advise patients of the possibility of developing low blood cell counts and to immediately report fever , any suggestion of infection , or signs or symptoms suggestive of bleeding or easy bruising . Liver Problems : Advise patients of the possibility of developing liver function abnormalities and to immediately report jaundice . Fluid Retention : Advise patients of the possibility of developing fluid retention ( swelling , weight gain , or shortness of breath ) and to seek medical attention promptly if these symptoms arise . Renal Problems : Advise patients of the possibility of developing renal problems and to immediately report frequent urination , polyuria , or oliguria . Other Adverse Reactions : Advise patients that they may experience other adverse reactions such as respiratory tract infections , rash , fatigue , loss of appetite , headache , dizziness , back pain , arthralgia , or pruritus with BOSULIF and to seek medical attention if symptoms are significant . There is a possibility of anaphylactic shock . Embryofetal Toxicity : Advise females to inform their healthcare provider if they are pregnant or become pregnant . Inform female patients of the risk to a fetus and potential loss of the pregnancy . Advise females of reproductive potential to use effective contraception during treatment and for 1 month after receiving the last dose of BOSULIF . Advise lactating women not to breastfeed during treatment with BOSULIF and for at least 1 month after the last dose . Drug Interactions : Advise patients that BOSULIF and certain other medicines , including over-the-counter medications or herbal supplements ( such as St . John ’ s wort ), can interact with each other and may alter the effects of BOSULIF .
Rx only This brief summary is based on BOSULIF Prescribing Information LAB-0443-10.0 , revised December 2017 .
© 2018 Pfizer Inc . All rights reserved . January 2018
Thrombocytopenia includes the following preferred terms: Platelet count decreased, Thrombocytopenia. 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