Bosutinib 500mg tablets
Requires a prescription from a doctor or prescriber
Bosutinib is a 7-alkoxy-3-quinolinecarbonitrile that functions as a potent, dual SRC and ABL tyrosine kinase inhibitor indicated for chronic myelogenous leukemia (CML), specifically Philadelphia chromosome-positive (Ph+) CML.
Safety information for pregnancy and breastfeeding
Pregnancy
Fetal exposure to bosutinib-derived radioactivity during pregnancy was demonstrated in a placental-transfer study in pregnant rats.
Breastfeeding
Always consult your doctor or midwife before taking any medicine during pregnancy or while breastfeeding. Source: DrugBank (CC BY-NC 4.0).
Official documents, adverse reaction reporting, and safety monitoring
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Official medicine documents
Safety monitoring data
Yellow Card reports
The MHRA Yellow Card scheme collects reports of suspected side effects from healthcare professionals and patients. View the Drug Analysis Profile (iDAP) for real-world adverse reaction data.
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Suspected adverse reactions reported for Bosutinib
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Report a side effect
Submit a Yellow Card report to the MHRA
Data from the MHRA Yellow Card scheme. A reported reaction does not necessarily mean the medicine caused it. Contains public sector information licensed under the Open Government Licence v3.0.
EudraVigilance
The European Medicines Agency (EMA) collects suspected adverse reaction reports from across the EU/EEA through the EudraVigilance system. Search for safety data on this medicine.
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Suspected adverse reactions reported for Bosutinib
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EudraVigilance data is published by the European Medicines Agency (EMA). A suspected adverse reaction is not necessarily caused by the medicine.
5 branded products available
MHRA licensed products
View all licensed products for Bosutinib on the MHRA register
Bosulif 500mg tablets
Bosutinib 500mg tablets
Bosutinib 500mg tablets
Bosutinib 500mg tablets
Bosutinib 500mg tablets
WHO defined daily dose (DDD)
400 mg
Not a recommended dose. The DDD is the assumed average maintenance dose per day for a drug used for its main indication in adults. It is a statistical measure used for research and comparison purposes only.
Source: WHO Collaborating Centre for Drug Statistics Methodology, distributed via NHS dm+d BNF mapping files. Contains public sector information licensed under the Open Government Licence v3.0.
Therapeutically similar medicines
Similarity based on WHO Anatomical Therapeutic Chemical (ATC) classification and NHS BNF section grouping. Source data: NHS dm+d via TRUD (OGL v3.0), WHO ATC/DDD Index.
NHS prescribing volume and spending trends
Clinical guidelines and formulary information
British National Formulary
Bosutinib
Source: British National Formulary, NICE. Joint Formulary Committee. Contains public sector information licensed under the Open Government Licence v3.0.
NICE clinical guidance(4)
Bosutinib for previously treated chronic myeloid leukaemia (TA401)
Bosutinib for untreated chronic myeloid leukaemia (terminated appraisal) (TA576)
Asciminib for treating chronic myeloid leukaemia after 2 or more tyrosine kinase inhibitors (TA813)
Ponatinib for treating chronic myeloid leukaemia and acute lymphoblastic leukaemia (TA451)
Source: National Institute for Health and Care Excellence (NICE). Contains public sector information licensed under the Open Government Licence v3.0.
Check stock at pharmacies and supply information
Pharmacy stock checkers
Search for this medicine at major UK pharmacy chains. These links open the retailer's own website — results depend on their current online catalogue.
Supply & product information
Official product databases and supply status monitoring
Pharmacy links redirect to the retailer's own search and do not represent real-time stock levels. emc (electronic medicines compendium) is operated by Datapharm Ltd. Shortage information sourced from NHS Specialist Pharmacy Service (SPS), sps.nhs.uk.
Codes for healthcare professionals and prescribing systems
These codes are used by healthcare IT systems and prescribers to identify this medicine.
NHS UK identifiers
Browse tools
SNOMED CT and dm+d codes from NHS TRUD (Technology Reference data Update Distribution), licensed under the Open Government Licence v3.0. BNF codes from NHS Business Services Authority (NHSBSA). ATC codes from the WHO Collaborating Centre for Drug Statistics Methodology (whocc.no).
Active and completed clinical studies from ClinicalTrials.gov
Source: ClinicalTrials.gov, a database of the U.S. National Library of Medicine (NLM), National Institutes of Health (NIH). Data accessed via ClinicalTrials.gov API v2. Trial information is provided for research purposes and does not constitute medical advice.
Pharmacology and chemical data from DrugBank
Key facts
Drug status
Approved
Major interactions
None known
Half-life
1.7 hours
Mechanism
Bosutinib is a tyrosine kinase inhibitor.
Food interactions
3 warnings
Human targets
11 targets
Data: DrugBank · CC BY-NC 4.0
Pharmacokinetics at a glance
Absorption
200 to 800 mg
Half-life
1.7 hours
[L48355]
Protein binding
94%
[L48355]
Volume of distribution
1230 L
[L48355]
Metabolism
19%
Elimination
91.3%
Clearance
48 L/h
[L48355]
Pharmacokinetic data: DrugBank · CC BY-NC 4.0
Bosutinib was first approved by the FDA in 2012 for the treatment of adult chronic, accelerated, or blast-phase Ph+ CML with resistance or intolerance to prior therapy.[L48436] On September 26, 2023, bosutinib was also approved by the FDA for the treatment of pediatric CML that is newly diagnosed or resistant/intolerant to prior therapy. This approval was based on favorable results obtained from the open-label, randomized, multicenter trial BFORE that showed a significant improvement in major molecular response, defined as a ≤0.1% BCR ABL ratio on an international scale, with bosutinib treatment.[L48441]
[L48355]
Known interactions with other medications. Always consult a healthcare professional.
Showing 50 of 1111 interactions
[L48355]
In an embryo-fetal development study conducted in rabbits, bosutinib was administered orally to pregnant animals during organogenesis at doses of 3, 10, and 30 mg/kg/day. At the maternally-toxic dose of 30 mg/kg/day of bosutinib, there were fetal anomalies (fused sternebrae and 2 fetuses had various visceral observations), and an approximate 6% decrease in fetal body weight.
The dose of 30 mg/kg/day resulted in exposures (AUC) approximately 5.1 and 3.8 times the human exposures at the recommended doses of 400 and 500 mg/day, respectively.
[L48355]
Fetal exposure to bosutinib-derived radioactivity during pregnancy was demonstrated in a placental-transfer study in pregnant rats. In a rat pre-and postnatal development study, bosutinib was administered orally to pregnant animals during the period of organogenesis through lactation day 20 at doses of 10, 30, and 70 mg/kg/day. Reduced number of pups born occurred at greater than or equal to 30 mg/kg/day bosutinib (3.4 and 2.5 times the human exposure at the recommended doses of 400 or 500 mg/day, respectively), and increased incidence of total litter loss and decreased growth of offspring after birth occurred at 70 mg/kg/day bosutinib (6.9 and 5.1 times the human exposure at the recommended doses of 400 or 500 mg/day, respectively).
[L48355]
Experience with bosutinib overdose in clinical studies was limited to isolated cases.
There were no reports of any serious adverse events associated with the overdoses. Patients who take an overdose of BOSULIF should be observed and given appropriate supportive treatment.
[L48355]
Bosutinib was not carcinogenic in rats or transgenic mice. The rat 2-year carcinogenicity study was conducted at bosutinib oral doses up to 25 mg/kg in males and 15 mg/kg in females.
Exposures at these doses were approximately 1.5 times (males) and 3.1 times (females) the human exposure at the 400 mg dose and 1.2 times (males) and 2.4 times (females) exposure in humans at the 500 mg dose. The 6-month RasH2 transgenic mouse carcinogenicity study was conducted at bosutinib oral doses up to 60 mg/kg.
[L48355]
Bosutinib was not mutagenic or clastogenic in a battery of tests, including the bacteria reverse mutation assay (Ames Test), the in vitro assay using human peripheral blood lymphocytes and the micronucleus test in orally treated male mice.
[L48355]
In a rat fertility study, drug-treated males were mated with untreated females or untreated males were mated with drug-treated females. Females were administered the drug from pre-mating through early embryonic development.
The dose of 70 mg/kg/day of bosutinib resulted in reduced fertility in males as demonstrated by 16% reduction in the number of pregnancies. There were no lesions in the male reproductive organs at this dose. This dose of 70 mg/kg/day resulted in exposure (AUC) in male rats approximately 1.5 times and equal to human exposure at the recommended doses of 400 and 500 mg/day, respectively.
Fertility (number of pregnancies) was not affected when female rats were treated with bosutinib. However, there were increased embryonic resorptions at greater than or equal to 10 mg/kg/day of bosutinib (1.6 and 1.2 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 30 mg/kg/day of bosutinib (3.4 and 2.5 times the human exposure at the recommended doses of 400 or 500 mg/day, respectively).
[L48355]
At a single oral dose of 500 mg bosutinib with ketoconazole (a strong CYP3A inhibitor), bosutinib does not prolong the QT interval to any clinically relevant extent.[L48355]
How the body processes this drug — absorption, distribution, metabolism, and elimination
No clinically significant differences in the pharmacokinetics of bosutinib were observed following administration of either the tablet or capsule dosage forms of bosutinib at the same dose, under fed conditions.
[L48355]
The median bosutinib (minimum, maximum) tmax was 6.0 (6.0, 6.0) hours following oral administration of a single oral dose of bosutinib 500 mg with food. The absolute bioavailability was 34% in healthy subjects.
[L48355]
Bosutinib Cmax increased 1.8-fold and AUC increased 1.7-fold when bosutinib tablets were given with a high-fat meal to healthy subjects compared to administration under fasted conditions. Bosutinib Cmax increased 1.6-fold and AUC increased 1.5-fold when bosutinib capsules were given with a high-fat meal to healthy subjects compared to administration under fasted conditions.
The high-fat meal (800-1000 total calories) consisted of approximately 150 protein calories, 250 carbohydrate calories, and 500-600 fat calories.
[L48355]
[L48355]
[L48355]
[L48355]
[L48355]
[L48355]
Proteins and enzymes this drug interacts with in the body
Plays an important role in the regulation of B-cell differentiation, proliferation, survival and apoptosis, and is important for immune self-tolerance. Acts downstream of several immune receptors, including the B-cell receptor, CD79A, CD79B, CD5, CD19, CD22, FCER1, FCGR2, FCGR1A, TLR2 and TLR4. Plays a role in the inflammatory response to bacterial lipopolysaccharide.
Mediates the responses to cytokines and growth factors in hematopoietic progenitors, platelets, erythrocytes, and in mature myeloid cells, such as dendritic cells, neutrophils and eosinophils. Acts downstream of EPOR, KIT, MPL, the chemokine receptor CXCR4, as well as the receptors for IL3, IL5 and CSF2. Plays an important role in integrin signaling.
Regulates cell proliferation, survival, differentiation, migration, adhesion, degranulation, and cytokine release. Involved in the regulation of endothelial activation, neutrophil adhesion and transendothelial migration .
PMID:36932076
Down-regulates signaling pathways by phosphorylation of immunoreceptor tyrosine-based inhibitory motifs (ITIM), that then serve as binding sites for phosphatases, such as PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1, that modulate signaling by dephosphorylation of kinases and their substrates. Phosphorylates LIME1 in response to CD22 activation.
Phosphorylates BTK, CBL, CD5, CD19, CD72, CD79A, CD79B, CSF2RB, DOK1, HCLS1, LILRB3/PIR-B, MS4A2/FCER1B, SYK and TEC. Promotes phosphorylation of SIRPA, PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1. Mediates phosphorylation of the BCR-ABL fusion protein.
Required for rapid phosphorylation of FER in response to FCER1 activation. Mediates KIT phosphorylation. Acts as an effector of EPOR (erythropoietin receptor) in controlling KIT expression and may play a role in erythroid differentiation during the switch between proliferation and maturation.
Depending on the context, activates or inhibits several signaling cascades. Regulates phosphatidylinositol 3-kinase activity and AKT1 activation. Regulates activation of the MAP kinase signaling cascade, including activation of MAP2K1/MEK1, MAPK1/ERK2, MAPK3/ERK1, MAPK8/JNK1 and MAPK9/JNK2.
Mediates activation of STAT5A and/or STAT5B. Phosphorylates LPXN on 'Tyr-72'. Kinase activity facilitates TLR4-TLR6 heterodimerization and signal initiation.
Phosphorylates SCIMP on 'Tyr-107'; this enhances binding of SCIMP to TLR4, promoting the phosphorylation of TLR4, and a selective cytokine response to lipopolysaccharide in macrophages (By similarity). Phosphorylates CLNK (By similarity). Phosphorylates BCAR1/CAS and NEDD9/HEF1 PMID:9020138
Both MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2, leading to their activation and further transduction of the signal within the MAPK/ERK cascade. Activates BRAF in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF dimerization and BRAF activation .
PMID:29433126
Depending on the cellular context, this pathway mediates diverse biological functions such as cell growth, adhesion, survival and differentiation, predominantly through the regulation of transcription, metabolism and cytoskeletal rearrangements. One target of the MAPK/ERK cascade is peroxisome proliferator-activated receptor gamma (PPARG), a nuclear receptor that promotes differentiation and apoptosis.
MAP2K1/MEK1 has been shown to export PPARG from the nucleus. The MAPK/ERK cascade is also involved in the regulation of endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC), as well as in the fragmentation of the Golgi apparatus during mitosis
PMID:16690701
In slow-twitch muscles, is involved in regulation of sarcoplasmic reticulum (SR) Ca(2+) transport and in fast-twitch muscle participates in the control of Ca(2+) release from the SR through phosphorylation of the ryanodine receptor-coupling factor triadin .
PMID:16690701
In the central nervous system, it is involved in the regulation of neurite formation and arborization .
PMID:30184290
It may participate in the promotion of dendritic spine and synapse formation and maintenance of synaptic plasticity which enables long-term potentiation (LTP) and hippocampus-dependent learning. In response to interferon-gamma (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling pathway (By similarity)
Enzymes involved in drug metabolism — important for understanding drug interactions
Proteins that transport this drug across cell membranes
PMID:2897240 PMID:35970996 PMID:8898203 PMID:9038218 PMID:35507548
Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins .
PMID:8898203
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells PMID:2897240 PMID:35970996 PMID:9038218
ATC L01EA04
Chemical identifiers
CAS, UNII, InChI Key and database cross-references
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Chemical identifiers
CAS, UNII, InChI Key and database cross-references
Linked compound data from DrugBank Open Data (CC BY-NC 4.0)
Bosutinib
Additional database identifiers
Drugs Product Database (DPD)
22234
ChemSpider
4486102
BindingDB
4552
PDB
DB8
ZINC
ZINC000022448983
HUGO Gene Nomenclature Committee (HGNC)
HGNC:6735
GeneCards
LYN
GenBank Gene Database
M16038
GenBank Protein Database
307144
Guide to Pharmacology
2060
UniProt Accession
LYN_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:6840
GenAtlas
MAP2K1
GeneCards
MAP2K1
GenBank Gene Database
L05624
GenBank Protein Database
188569
Guide to Pharmacology
2062
UniProt Accession
MP2K1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:6842
GeneCards
MAP2K2
Guide to Pharmacology
2063
UniProt Accession
MP2K2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:6854
GeneCards
MAP3K2
Guide to Pharmacology
2077
UniProt Accession
M3K2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:1463
GeneCards
CAMK2G
GenBank Gene Database
BC034044
GenBank Protein Database
21707842
Guide to Pharmacology
1557
UniProt Accession
KCC2G_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:3697
GeneCards
FGR
Guide to Pharmacology
2024
UniProt Accession
FGR_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:4840
GenAtlas
HCK
GeneCards
HCK
GenBank Gene Database
M16591
GenBank Protein Database
306832
Guide to Pharmacology
2032
UniProt Accession
HCK_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:11719
GeneCards
TEC
Guide to Pharmacology
2238
UniProt Accession
TEC_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:11088
GeneCards
SLK
GenBank Gene Database
AB002804
GenBank Protein Database
1944185
Guide to Pharmacology
2200
UniProt Accession
SLK_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:11283
GenAtlas
SRC
GeneCards
SRC
GenBank Gene Database
AL133293
GenBank Protein Database
10635153
Guide to Pharmacology
2206
UniProt Accession
SRC_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:76
GenAtlas
ABL1
GeneCards
ABL1
GenBank Gene Database
X16416
GenBank Protein Database
28237
Guide to Pharmacology
1923
UniProt Accession
ABL1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2637
GenAtlas
CYP3A4
GeneCards
CYP3A4
GenBank Gene Database
M18907
Guide to Pharmacology
1337
UniProt Accession
CP3A4_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2622
GenAtlas
CYP2C8
GeneCards
CYP2C8
GenBank Gene Database
M17397
Guide to Pharmacology
1325
UniProt Accession
CP2C8_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:40
GenAtlas
ABCB1
GeneCards
ABCB1
GenBank Gene Database
M14758
GenBank Protein Database
307180
Guide to Pharmacology
768
UniProt Accession
MDR1_HUMAN
Patent information
4 active patents, 2 expired
Source: DrugBank · CC BY-NC 4.0. Patent data sourced from national patent offices. Expiry dates may not reflect extensions, regulatory exclusivity periods, or legal challenges.
DrugBank citations
If you use DrugBank data in your research, please cite the following publications: