PharmGKB contains no dosing guidelines for this . To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.
PharmGKB annotates drug labels containing pharmacogenetic information approved by the US Food and Drug Administration (FDA), European Medicines Agency (EMA) and the Pharmaceuticals and Medical Devices Agency, Japan (PMDA). PharmGKB annotations provide a brief summary of the PGx in the label, an excerpt from the label and a downloadable highlighted label PDF file. A list of genes and phenotypes found within the label is mapped to label section headers and listed at the end of each annotation. PharmGKB also attempts to interpret the level of action implied in each label with the "PGx Level" tag.
- FDA Information is gathered from the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels" and from FDA-approved labels brought to our attention. Please note that drugs may be removed from or added to the FDA's Table without our knowledge. We periodically check the Table for changes and update PharmGKB accordingly. Drugs listed on the Table to our knowledge are tagged with the Biomarker icon. A drug label that has been removed from the Table will not have the Biomarker icon but will continue to have an annotation on PharmGKB stating the label has been removed from the FDA's Table. We acquire label PDF files from DailyMed.
- EMA European Public Assessment Reports (EPARs) that contain PGx information were identified from [Article:24433361] and also by searching for drugs for which we have PGx-containing FDA drug labels.
- PMDA Japanese drug label annotation information is sourced from Shimazawa and Ikeda (2013), whose paper provided translations of the pharmacogenetic information contained in PMDA package inserts. The authors selected which PMDA package inserts to examine for PGx information based the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels".
We welcome any information regarding drug labels containing PGx information approved by the FDA, EMA, PMDA or other Medicine Agencies around the world - please contact feedback.
The EMA European Public Assessment Report (EPAR) for imatinib (Glivec) contains pharmacogenetic information regarding the indication of the drug in patients with tumors positive for biomarkers including KIT (CD117), BCR-ABL (Philadelphia chromosome), PDGFR and FIP1L1-PDGFRalpha rearrangements.
Excerpt from the imatinib (Glivec) EPAR:
Glivec is indicated for the treatment of
- adult and paediatric patients with newly diagnosed Philadelphia chromosome (bcr-abl) positive (Ph+) chronic myeloid leukaemia (CML) for whom bone marrow transplantation is not considered as the first line of treatment.
- adult and paediatric patients with Ph+ CML in chronic phase after failure of interferon-alpha therapy, or in accelerated phase or blast crisis.
- adult patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) integrated with chemotherapy.
- adult patients with relapsed or refractory Ph+ ALL as monotherapy.
- adult patients with myelodysplastic/myeloproliferative diseases (MDS/MPD) associated with platelet-derived growth factor receptor (PDGFR) gene re-arrangements.
- adult patients with advanced hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukaemia (CEL) with FIP1L1-PDGFR rearrangement.
Glivec is indicated for
- the treatment of adult patients with Kit (CD 117) positive unresectable and/or metastatic malignant gastrointestinal stromal tumours (GIST).
- the adjuvant treatment of adult patients who are at significant risk of relapse following resection of Kit (CD117)-positive GIST. Patients who have a low or very low risk of recurrence should not receive adjuvant treatment.
This information is highlighted in the following sections:
Therapeutic indications, posology and method of administration, pharmacodynamic properties, package leaflet: information for the user.
The label also states that caution be taken when imatinib is taken concomittantly with CYP3A4 inhibitors and CYP3A4 inducers should be avoided.
For the complete drug label text with sections containing pharmacogenetic information highlighted, see the imatinib EMA drug label.
*Disclaimer: The contents of this page have not been endorsed by the EMA and are the sole responsibility of PharmGKB.
PharmGKB contains no Clinical Variants that meet the highest level of criteria.
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.
|Alternate Symbols: ||CD140b; JTK12; PDGFR1|
|PharmGKB Accession Id:||PA33148|
|Cytogenetic Location:||chr5 : q33.1 - q32|
|GP mRNA Boundary†:||chr5 : 149493402 - 149535422|
|GP Gene Boundary†:||chr5 : 149490402 - 149545422|
PharmGKB Curated Pathways
Pathways created internally by PharmGKB based primarily on literature evidence.
Mechanism of action of sorafenib
Links to non-PharmGKB pathways.
- Down-stream signal transduction - (Reactome via Pathway Interaction Database)
- Nectin adhesion pathway - (Pathway Interaction Database NCI-Nature Curated)
- PDGFR-beta signaling pathway - (Pathway Interaction Database NCI-Nature Curated)
- S1P1 pathway - (Pathway Interaction Database NCI-Nature Curated)
- S1P3 pathway - (Pathway Interaction Database NCI-Nature Curated)
- Signaling by PDGF - (Reactome via Pathway Interaction Database)
- Signaling events mediated by PTP1B - (Pathway Interaction Database NCI-Nature Curated)
Publications related to PDGFRB: 5
The following icons indicate that data of a certain type is available:
- DG Dosing Guideline information is available
- DL Drug Label information is available
- CA High-level Clinical Annotation is available
- VA Variant Annotation is available
- VIP VIP information is available
- PW Pathway is available
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||Combinatorial therapies to overcome B-RAF inhibitor resistance in melanomas. Pharmacogenomics. 2012. Lo Roger S.|
||Targeted cancer therapies in the twenty-first century: lessons from imatinib. Clinical pharmacology and therapeutics. 2010. Stegmeier F, et al.|
||Evolving novel anti-HER2 strategies. The lancet oncology. 2009. Jones Kellie L, et al.|
||Tumor suppressor FUS1 signaling pathway. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 2008. Ji Lin, et al.|
||A quantitative analysis of kinase inhibitor selectivity. Nature biotechnology. 2008. Karaman Mazen W, et al.|