Drug/Small Molecule:
dasatinib

PharmGKB contains no dosing guidelines for this drug/small molecule. To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.

PharmGKB gathers information regarding PGx on FDA drug labels from the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels", and from FDA-approved FDA and EMA-approved (European Medicines Agency) EMA labels brought to our attention. Excerpts from the label and downloadable highlighted label PDFs are manually curated by PharmGKB.

Please note that some drugs may have been removed from or added to the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels" without our knowledge. We periodically check the table for additions to this table and update PharmGKB accordingly.

There is currently no such list for European drug labels - we are working with the EMA to establish a list of European Public Assessment Reports (EPAR)s that contain PGx information. We are constructing this list by initially searching for drugs for which we have PGx-containing FDA drug labels - of these 44 EMA EPARs were identified and are being curated for pgx information.

We welcome any information regarding drug labels containing PGx information approved by the FDA, EMA or other Medicine Agencies around the world - please contact feedback.


last updated 10/25/2013

FDA Label for dasatinib and ABL1, BCR

This label is on the FDA Biomarker List
Genetic testing required

Summary

The FDA-approved drug label for dasatinib (SPRYCEL) notes that it is intended for adults with Philadelphia chromosome-positive chronic myeloid leukemia (CML) or acute lymphoblastic leukemia (Ph+ ALL) and resistance or intolerance to prior therapy.

Annotation

The FDA-approved drug label for dasatinib (SPRYCEL) states that the drug is indicated for treatment of adults with Philadelphia chromosome-positive chronic myeloid leukemia (CML) or acute lymphoblastic leukemia with resistance or intolerance to prior therapy. Dasatinib is a protein kinase inhibitor whose substrates include the BCR-ABL kinase encoded by the Philadelphia chromosome.

Excerpt from the dasatinib (SPRYCEL) drug label:

SPRYCEL is a kinase inhibitor indicated for the treatment of newly diagnosed adults with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase...adults with chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib...[or] adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the dasatinib drug label.

*Disclaimer: The contents of this page have not been endorsed by the FDA and are the sole responsibility of PharmGKB.

Full label available at DailyMed

Genes and/or phenotypes found in this label

  • Neoplasms
    • Warnings section, Adverse reactions section
    • source: PHONT
  • ABL1
    • Clinical pharmacology section, efficacy
    • source: FDA Label
  • BCR
    • Clinical pharmacology section, efficacy
    • source: FDA Label
  • CYP1A2
    • Clinical pharmacology section
    • source: FDA Label
  • CYP2A6
    • Clinical pharmacology section
    • source: FDA Label
  • CYP2B6
    • Clinical pharmacology section
    • source: FDA Label
  • CYP2C19
    • Clinical pharmacology section
    • source: FDA Label
  • CYP2C8
    • Clinical pharmacology section
    • source: FDA Label
  • CYP2C9
    • Clinical pharmacology section
    • source: FDA Label
  • CYP2D6
    • Clinical pharmacology section
    • source: FDA Label
  • CYP2E1
    • Clinical pharmacology section
    • source: FDA Label
  • CYP3A4
    • Dosage & administration section, Drug interactions section, Clinical pharmacology section, metabolism/PK
    • source: FDA Label
  • FMO3
    • Clinical pharmacology section, metabolism/PK
    • source: FDA Label

European Medicines Agency (EMA) Label for dasatinib and ABL1, BCR

Genetic testing required

Summary

The EMA European Public Assessment Report (EPAR) highlights information regarding the indication of Dasatinib (Sprycel) in patients with Philadelphia chromosome positive (Ph+) chronic myelogenous leukaemia or acute lymphoblastic leukaemia.

Annotation

Excerpt from the Dasatinib (Sprycel) EPAR:

SPRYCEL is indicated for the treatment of adult patients with:

  • newly diagnosed Philadelphia chromosome positive (Ph+) chronic myelogenous leukaemia (CML) in the chronic phase.
  • chronic, accelerated or blast phase CML with resistance or intolerance to prior therapy including
    imatinib mesilate.
  • Ph+ acute lymphoblastic leukaemia (ALL) and lymphoid blast CML with resistance or
    intolerance to prior therapy.

This information is highlighted in the following sections:
Therapeutic indications, package leaflet: information for the user.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the Dasatinib EMA drug label.

*Disclaimer: The contents of this page have not been endorsed by the EMA and are the sole responsibility of PharmGKB.


Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

? = Mouse-over for quick help

This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Gene?
BCR-ABL Quantitation; ABL Kinase Domain Sequencing BCR-ABL (reciprocal translocation involving chromosomes 9 and 22, t(9,22)(q34, q11))

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

Gene ? Variant?
(138)
Alternate Names / Tag SNPs ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available No Clinical Annotations available VA
rs1061018 13590574A>G, 42159T>C, 623T>C, 89042853A>G, Phe208Ser
A > G
Missense
Phe208Ser
No VIP available No Clinical Annotations available VA
rs121913459 1001C>T, 133748283C>T, 164016C>T, 525223C>T, 944C>T, Thr315Ile, Thr334Ile
C > T
Missense
Thr315Ile
No VIP available No Clinical Annotations available VA
rs2231137 13608835C>T, 23898G>A, 34G>A, 89061114C>T, ABCG2:V12M, Val12Met
C > T
Missense
Val12Met
No VIP available No Clinical Annotations available VA
rs2231142 13600044G>T, 32689C>A, 421C>A, 89052323G>T, ABCG2: Q141K, ABCG2:421C>A, ABCG2:Q141K, ABCG2:c.421C>A, Gln141Lys, rs2231142
G > T
Missense
Gln141Lys
No VIP available No Clinical Annotations available VA
rs41282401 13583887C>G, 48846G>C, 886G>C, 89036166C>G, Asp296His
C > G
Missense
Asp296His
No VIP available No Clinical Annotations available VA
rs45605536 13566391C>T, 1582G>A, 66342G>A, 89018670C>T, Ala528Thr
C > T
Missense
Ala528Thr
No VIP available No Clinical Annotations available VA
rs58818712 13566399A>C, 1574T>G, 66334T>G, 89018678A>C, Leu525Arg
A > C
Missense
Leu525Arg
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • BMS-354825
  • dasatinib
Trade Names
  • Sprycel
Brand Mixture Names

PharmGKB Accession Id:
PA162372878

Description

Dasatinib is an oral dual BCR/ABL and Src family tyrosine kinase inhibitor approved for use in patients with chronic myelogenous leukemia (CML). The main targets of Dasatinib, are BCRABL, SRC, Ephrins and GFR.

Source: Drug Bank

Indication

For the treatment of adults with chronic, accelerated, or myeloid or lymphoid blast phase chronic myeloid leukemia with resistance or intolerance to prior therapy. Also indicated for the treatment of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia with resistance or intolerance to prior therapy.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Dasatinib, at nanomolar concentrations, inhibits the following kinases: BCR-ABL, SRC family (SRC, LCK, YES, FYN), c-KIT, EPHA2, and PDGFRbeta. Based on modeling studies, dasatinib is predicted to bind to multiple conformations of the ABL kinase. In vitro, dasatinib was active in leukemic cell lines representing variants of imatinib mesylate sensitive and resistant disease. Dasatinib inhibited the growth of chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) cell lines overexpressing BCR-ABL. Under the conditions of the assays, dasatinib was able to overcome imatinib resistance resulting from BCR-ABL kinase domain mutations, activation of alternate signaling pathways involving the SRC family kinases (LYN, HCK), and multi-drug resistance gene overexpression.

Source: Drug Bank

Pharmacology

Dasatinib is an oral dual BCR/ABL and Src family tyrosine kinase inhibitor

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Dasatinib is extensively metabolized in humans, primarily by the cytochrome P450 enzyme 3A4

Source: Drug Bank

Protein Binding

96%

Source: Drug Bank

Half-Life

The overall mean terminal half-life of dasatinib is 3-5 hours.

Source: Drug Bank

Toxicity

Acute overdose in animals was associated with cardiotoxicity.

Source: Drug Bank

Route of Elimination

Dasatinib is extensively metabolized in humans, primarily by the cytochrome P450 enzyme 3A4. Elimination is primarily via the feces.

Source: Drug Bank

Volume of Distribution

  • 2505 L

Source: Drug Bank

Chemical Properties

Chemical Formula

C22H26ClN7O2S

Source: Drug Bank

Isomeric SMILES

Cc1cccc(c1NC(=O)c2cnc(s2)Nc3cc(nc(n3)C)N4CCN(CC4)CCO)Cl

Source: OpenEye

Canonical SMILES

CC1=NC(NC2=NC=C(S2)C(=O)NC2=C(C)C=CC=C2Cl)=CC(=N1)N1CCN(CCO)CC1

Source: Drug Bank

Average Molecular Weight

488.006

Source: Drug Bank

Monoisotopic Molecular Weight

487.155721508

Source: Drug Bank

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

Drug Targets

Gene Description
ABL1 (source: Drug Bank)
ABL2 (source: Drug Bank)
EPHA2 (source: Drug Bank)
FYN (source: Drug Bank)
KIT (source: Drug Bank)
LCK (source: Drug Bank)
PDGFRB (source: Drug Bank)
SRC (source: Drug Bank)
STAT5B (source: Drug Bank)
YES1 (source: Drug Bank)

Drug Interactions

Drug Description
dasatinib Possible decreased levels of dasatinib (source: Drug Bank)
dasatinib Omeprazole may decrease the serum level of dasatinib. (source: Drug Bank)
dasatinib Possible decreased levels of dasatinib (source: Drug Bank)
dasatinib Pantoprazole may decrease the serum level of dasatinib. (source: Drug Bank)
dasatinib Decreased levels/efficacy of ddasatinib (source: Drug Bank)
dasatinib Phenobarbital may decrease the serum level and efficacy of dasatinib. (source: Drug Bank)
dasatinib Decreased levels/efficacy of dasatinib (source: Drug Bank)
dasatinib Phenytoin may decrease the serum level and efficacy of dasatinib. (source: Drug Bank)
dasatinib Possible decreased levels of dasatinib (source: Drug Bank)
dasatinib Rabeprazole may decrease the serum level of dasatinib. (source: Drug Bank)
dasatinib Possible decreased levels of dasatinib (source: Drug Bank)
dasatinib Ranitidine may decrease the serum level of dasatinib. (source: Drug Bank)
dasatinib Decreased levels/efficacy of dasatinib (source: Drug Bank)
dasatinib Rifampin may decrease the serum level and efficacy of dasatinib. (source: Drug Bank)
dasatinib Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution. (source: Drug Bank)
dasatinib Increased levels/toxicity of dasatinib (source: Drug Bank)
dasatinib Telithromycin may reduce clearance of Dasatinib. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Dasatinib if Telithromycin is initiated, discontinued or dose changed. (source: Drug Bank)
dasatinib May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration. (source: Drug Bank)
dasatinib May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration. (source: Drug Bank)
dasatinib Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration. (source: Drug Bank)
dasatinib Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution. (source: Drug Bank)
dasatinib Additive QTc prolongation may occur. Voriconazole, a strong CYP3A4 inhibitor, may also increase the serum concentration of dasatinib by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dasatinib if voriconazole is initiated, discontinued or dose changed. (source: Drug Bank)
dasatinib Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP). (source: Drug Bank)
dasatinib Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated. (source: Drug Bank)
dasatinib Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP). (source: Drug Bank)

Curated Information ?

EvidenceDisease
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Leukemia
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Neoplasms
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Recurrence

Publications related to dasatinib: 8

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Interaction of the Efflux Transporters ABCB1 and ABCG2 With Imatinib, Nilotinib, and Dasatinib. Clinical pharmacology and therapeutics. 2014. Eadie L N, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Single-nucleotide polymorphisms of ABCG2 increase the efficacy of tyrosine kinase inhibitors in the K562 chronic myeloid leukemia cell line. Pharmacogenetics and genomics. 2014. Skoglund Karin, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Challenges in pharmacogenetics. European journal of clinical pharmacology. 2013. Cascorbi Ingolf, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenomics as a risk mitigation strategy for chemotherapeutic cardiotoxicity. Pharmacogenomics. 2013. Jensen Brian C, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Pharmacokinetics of Dasatinib for Philadelphia- Positive Acute Lymphocytic Leukemia with Acquired T315I mutation. Journal of hematology & oncology. 2012. Takahashi Naoto, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Chemotherapeutic agents circumvent emergence of dasatinib-resistant BCR-ABL kinase mutations in a precise mouse model of Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 2011. Boulos Nidal, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Systematic review of pharmacoeconomic studies of pharmacogenomic tests. Pharmacogenomics. 2010. Beaulieu Mathieu, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Evolving novel anti-HER2 strategies. The lancet oncology. 2009. Jones Kellie L, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0003-0527-11
DrugBank:
DB01254
ChEBI:
49375
KEGG Drug:
D03658
PubChem Compound:
3062316
PubChem Substance:
10061134
46505143
BindingDB:
13216
ChemSpider:
2323020
Therapeutic Targets Database:
DAP000004
FDA Drug Label at DailyMed:
4764f37b-c9e6-4ede-bcc2-8a03b7c521df

Clinical Trials

These are trials that mention dasatinib and are related to either pharmacogenetics or pharmacogenomics.

Common Searches

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Sources for PharmGKB drug information: DrugBank, Open Eye Scientific Software.