Chemical: Drug
lapatinib

PharmGKB contains no prescribing info for this . Contact us to report known genotype-based dosing guidelines, or if you are interested in developing guidelines.


Annotated Labels

  1. Annotation of FDA Label for lapatinib and ERBB2
  2. Annotation of FDA Label for lapatinib and HLA-DQA1,HLA-DRB1
  3. Annotation of EMA Label for lapatinib and ERBB2,HLA-DQA1,HLA-DRB1
  4. Annotation of PMDA Label for lapatinib and ERBB2,HLA-DQA1,HLA-DRB1
  5. Annotation of HCSC Label for lapatinib and ERBB2,HLA-DQA1,HLA-DRB1

last updated 03/21/2016

1. Annotation of FDA Label for lapatinib and ERBB2

Testing required

Summary

Lapatinib (TYKERB) is indicated for patients with breast cancer whose tumors overexpress HER2 (ERBB2). The FDA-approved drug label for lapatinib notes that the HLA-DQA1*02:01 and HLA-DRB1*07:01 alleles have been associated with hepatotoxicity in individuals received the drug, but does not discuss genetic testing for these alleles.

There's more of this label. Read more.


last updated 03/21/2016

2. Annotation of FDA Label for lapatinib and HLA-DQA1,HLA-DRB1

Actionable PGx

Summary

Lapatinib (TYKERB) is indicated for patients with breast cancer whose tumors overexpress HER2 (ERBB2). The FDA-approved drug label for lapatinib notes that the HLA-DQA1*02:01 and HLA-DRB1*07:01 alleles have been associated with hepatotoxicity in individuals received the drug, but does not discuss genetic testing for these alleles.

There's more of this label. Read more.


last updated 10/27/2013

3. Annotation of EMA Label for lapatinib and ERBB2,HLA-DQA1,HLA-DRB1

Testing required

Summary

The EMA European Public Assessment Report (EPAR) for lapatinib (Tyverb) contains pharmacogenetic information regarding the indication of the drug in HER2+ (ERBB2) breast cancer, and that HER2 status should be determined using an accurate technique. It also contains pharmacogenetic information regarding an increased risk of drug-induced hepatotoxicity in patients carrying the DQA1*02:01 or DRB1*07:01 HLA alleles.

There's more of this label. Read more.


4. Annotation of PMDA Label for lapatinib and ERBB2,HLA-DQA1,HLA-DRB1

Testing required

Summary

The PMDA package insert for lapatinib states that it is indicated for individuals with breast cancer whose tumors overexpress HER2. It also contains information about the risk of severe liver injury in patients with the HLA-DQA1*02:01 or HLA-DRB1*07:01 variants.

There's more of this label. Read more.


5. Annotation of HCSC Label for lapatinib and ERBB2,HLA-DQA1,HLA-DRB1

Testing required

Summary

The product monograph for lapatinib (TYKERB) states that it is indicated for patients with metastatic breast cancer whose tumours overexpress HER2. It also notes that those with the HLA-DQA1*02:01 and HLA-DRB1*07:01 alleles have an increased risk of lapatinib-associated hepatotoxicity. The product monograph does not comment on genotyping for the HLA alleles.

There's more of this label. Read more.


PharmGKB contains no Clinical Variants that meet the highest level of criteria.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

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

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.

List of all variant annotations for lapatinib

Gene ? Variant?
(147)
Alternate Names ? Chemicals ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available CA VA HLA-DQA1 *02:01 N/A N/A N/A
No VIP available CA VA HLA-DRB1 *07:01:01:01 N/A N/A N/A
No VIP available No Clinical Annotations available VA
rs9344 NC_000011.10:g.69648142G>A, NC_000011.9:g.69462910G>A, NG_007375.1:g.12038G>A, NM_053056.2:c.723G>A, NP_444284.1:p.Pro241=, XM_006718653.2:c.747G>A, XP_006718716.1:p.Pro249=, rs1131451, rs11557586, rs17295377, rs17349816, rs17359282, rs17852153, rs2227951, rs3191361, rs59807553, rs603965
G > A
SNP
P241P
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 147

Overview

Generic Names
  • FMM
  • GW 572016
  • GW572016
  • Lapatinib ditosylate
  • Lapatinib tosilate hydrate
  • lapatinib
Trade Names
  • Tycerb
  • Tykerb
Brand Mixture Names

PharmGKB Accession Id

PA152241907

Type(s):

Drug

Other Vocabularies

Chemical Properties

SMILES

CS(=O)(=O)CCNCC1=CC=C(O1)C2=CC3=C(C=C2)N=CN=C3NC4=CC(=C(C=C4)OCC5=CC(=CC=C5)F)Cl

Source: PubChem

InChI String

InChI=1S/C29H26ClFN4O4S/c1-40(36,37)12-11-32-16-23-7-10-27(39-23)20-5-8-26-24(14-20)29(34-18-33-26)35-22-6-9-28(25(30)15-22)38-17-19-3-2-4-21(31)13-19/h2-10,13-15,18,32H,11-12,16-17H2,1H3,(H,33,34,35)

Source: PubChem

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. EGFR Inhibitor Pathway, Pharmacodynamics
    Model non-tissue specific cancer cell displaying genes that may be involved in the treatment using epidermal growth factor receptor specific tyrosine kinase inhibitors or monoclonal antibodies.

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
EGFR (source: Drug Bank )
ERBB2 (source: Drug Bank )

Drug Interactions

Interaction Description
tamsulosin - lapatinib Lapatinib, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Lapatinib is initiated, discontinued, or dose changed. (source: Drug Bank )
tamsulosin - lapatinib Lapatinib, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Lapatinib is initiated, discontinued, or dose changed. (source: Drug Bank )
telithromycin - lapatinib Telithromycin may reduce clearance of Lapatinib. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Lapatinib if Telithromycin is initiated, discontinued or dose changed. (source: Drug Bank )
thiothixene - lapatinib 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 )
thiothixene - lapatinib 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 )
tolterodine - lapatinib Lapatinib may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity. (source: Drug Bank )
tolterodine - lapatinib Lapatinib may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity. (source: Drug Bank )
topotecan - lapatinib The p-glycoprotein inhibitor, Lapatinib, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided. (source: Drug Bank )
toremifene - lapatinib 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 )
tramadol - lapatinib Lapatinib may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. (source: Drug Bank )
trazodone - lapatinib The CYP3A4 inhibitor, Lapatinib, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Lapatinib is initiated, discontinued or dose changed. (source: Drug Bank )
trazodone - lapatinib The CYP3A4 inhibitor, Lapatinib, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Lapatinib is initiated, discontinued or dose changed. (source: Drug Bank )
trimipramine - lapatinib Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution. (source: Drug Bank )
voriconazole - lapatinib Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of lapatinib by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of lapatinib if voriconazole is initiated, discontinued or dose changed. (source: Drug Bank )
vorinostat - lapatinib 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 )
ziprasidone - lapatinib Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated. (source: Drug Bank )
zuclopenthixol - lapatinib 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 ?

Publications related to lapatinib: 29

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The role of germline variants in chemotherapy outcome in brain tumors: a systematic review of pharmacogenetic studies. Pharmacogenomics. 2017. Klumpers Marije J, 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
Targeting therapeutic liabilities engendered by PIK3R1 mutations for cancer treatment. Pharmacogenomics. 2016. Cheung Lydia Wt, 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
Pharmacogenomic agreement between two cancer cell line data sets. Nature. 2015. Cancer Cell Line Encyclopedia Consortium, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Comprehensive genome-wide evaluation of lapatinib-induced liver injury yields a single genetic signal centered on known risk allele HLA-DRB1*07:01. The pharmacogenomics journal. 2015. Parham L R, 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
De novo resistance biomarkers to anti-HER2 therapies in HER2-positive breast cancer. Pharmacogenomics. 2015. Madrid-Paredes Adela, 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
T Cell-Mediated Hypersensitivity Reactions to Drugs. Annual review of medicine. 2014. Pavlos Rebecca, 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
PIK3CA mutations are associated with lower rates of pathologic complete response to anti-human epidermal growth factor receptor 2 (her2) therapy in primary HER2-overexpressing breast cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2014. Loibl Sibylle, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Prospective validation of HLA-DRB1*07:01 allele carriage as a predictive risk factor for lapatinib-induced liver injury. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2014. Schaid Daniel J, 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
EMA Initiatives and Perspectives on Pharmacogenomics. British journal of clinical pharmacology. 2014. Ehmann Falk, 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
Inconsistency in large pharmacogenomic studies. Nature. 2013. Haibe-Kains Benjamin, 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
Emerging landscape of oncogenic signatures across human cancers. Nature genetics. 2013. Ciriello Giovanni, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
PharmGKB summary: very important pharmacogene information for the epidermal growth factor receptor. Pharmacogenetics and genomics. 2013. Hodoglugil Ugur, 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
Genetic characterization to improve interpretation and clinical management of hepatotoxicity caused by tyrosine kinase inhibitors. Pharmacogenomics. 2013. Spraggs Colin F, 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
Activating HER2 mutations in HER2 gene amplification negative breast cancer. Cancer discovery. 2013. Bose Ron, 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
Predictive Genetic Testing for Drug-Induced Liver Injury: Considerations of Clinical Utility. Clinical pharmacology and therapeutics. 2012. Alfirevic A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
The Cyclin D1 (CCND1) A870G polymorphism predicts clinical outcome to lapatinib and capecitabine in HER2-positive metastatic breast cancer. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2012. Labonte M J, 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
Lapatinib-induced liver injury characterized by class II HLA and Gilbert's syndrome genotypes. Clinical pharmacology and therapeutics. 2012. Spraggs C F, 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
Positive interaction between lapatinib and capecitabine in human breast cancer models: study of molecular determinants. Fundamental & clinical pharmacology. 2011. Chefrour Mohamed, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
HER2-amplified breast cancer: mechanisms of trastuzumab resistance and novel targeted therapies. Expert review of anticancer therapy. 2011. Gajria Devika, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
HLA-DQA1*02:01 is a major risk factor for lapatinib-induced hepatotoxicity in women with advanced breast cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2011. Spraggs Colin F, 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
Pharmacogenomic contribution to drug response. Cancer journal (Sudbury, Mass.). 2011. Watson Roshawn G, 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
Targeted cancer therapies in the twenty-first century: lessons from imatinib. Clinical pharmacology and therapeutics. 2010. Stegmeier F, 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
The dual EGFR/HER-2 tyrosine kinase inhibitor lapatinib sensitizes colon and gastric cancer cells to the irinotecan active metabolite SN-38. International journal of cancer. Journal international du cancer. 2009. LaBonte Melissa J, 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
Grb7 upregulation is a molecular adaptation to HER2 signaling inhibition due to removal of Akt-mediated gene repression. PloS one. 2010. Nencioni Alessio, 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
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Beyond trastuzumab: overcoming resistance to targeted HER-2 therapy in breast cancer. Current cancer drug targets. 2009. Bedard Philippe L, 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
MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science (New York, N.Y.). 2007. Engelman Jeffrey A, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0173-0752-00
DrugBank:
DB01259
PDB:
FMM
ChEBI:
49603
KEGG Drug:
D04024
PubChem Compound:
208908
PubChem Substance:
14911387
46507141
BindingDB:
5445
ChemSpider:
181006
HET:
FMM
Therapeutic Targets Database:
DCL000344
FDA Drug Label at DailyMed:
63319b01-cad6-4d0a-c39b-938fa951a808

Clinical Trials

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

No trials loaded.

NURSA Datasets

provided by nursa.org

No NURSA datasets available.

Common Searches

Search PubMed
Search Medline Plus
Search PubChem
Search CTD

Sources for PharmGKB drug information: DrugBank, PubChem.