Chemical: Drug
crizotinib

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 crizotinib and ALK,ROS1
  2. Annotation of EMA Label for crizotinib and ALK
  3. Annotation of PMDA Label for crizotinib and ALK
  4. Annotation of HCSC Label for crizotinib and ALK

last updated 03/15/2017

1. Annotation of FDA Label for crizotinib and ALK,ROS1

Testing required

Summary

The FDA-approved drug label for crizotinib (XALKORI) states that it is indicated for treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are ALK-positive as detected by an FDA-approved test, and for patients with metastatic NSCLC whose tumors are ROS1-positive.

There's more of this label. Read more.


last updated 10/25/2013

2. Annotation of EMA Label for crizotinib and ALK

Testing required

Summary

The EMA European Public Assessment Report (EPAR) requires testing of ALK prior to treatment with crizotinib, indicated for patients with ALK-positive advanced non-small cell lung cancer.

There's more of this label. Read more.


3. Annotation of PMDA Label for crizotinib and ALK

Testing required

Summary

Crizotinib is indicated for the treatment of patients with non-small cell lung cancer. The PMDA package insert for crizotinib states positive confirmation of the ALK fusion gene is necessary prior to treatment.

There's more of this label. Read more.


4. Annotation of HCSC Label for crizotinib and ALK

Testing required

Summary

The product monograph for crizotinib (XALKORI) states that it is indicated for patients with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non-small cell lung cancer.

There's more of this label. Read more.


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.

? = 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 crizotinib

Gene ? Variant?
(147)
Alternate Names ? Chemicals ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available No VIP available VA ABCB1 *2 (PMID: 11503014) N/A N/A N/A
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 147

Overview

Generic Names
  • crizotinib
Trade Names
  • Xalkori
Brand Mixture Names

PharmGKB Accession Id

PA165946122

Type(s):

Drug

Metabolite(s):

Description

Crizotinib is an inhibitor of receptor tyrosine kinases including ALK, Hepatocyte Growth Factor Receptor (HGFR, c-Met), and Recepteur d'Origine Nantais (RON).

Source: PharmGKB

Indication

Crizotinib is indicated for the treatment of ALK-positive Non-Small-Cell Lung Carcinoma (NSCLC) and ROS1-positive NSCLC.

Source: PharmGKB [Article:27328934] [Article:23386065]

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Chemical Properties

Chemical Formula

C21H22Cl2FN5O

Source: PubChem Compound

Canonical SMILES

C[C@H](C1=C(C=CC(=C1Cl)F)Cl)OC2=C(N=CC(=C2)C3=CN(N=C3)C4CCNCC4)N

Source: PubChem Compound

Average Molecular Weight

450.336683

Source: PubChem Compound

Monoisotopic Molecular Weight

449.118544

Source: PubChem Compound

IUPAC Names

  • 3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-(1-piperidin-4-ylpyrazol-4-yl)pyridin-2-amine

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
ALK [PMID: 26654422] (source: PharmGKB )
ROS1 [PMID: 27328934] (source: PharmGKB )
No related drugs are available.

Curated Information ?

Publications related to crizotinib: 15

No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Pharmacokinetic profiles of significant adverse events with crizotinib in Japanese patients with ABCB1 polymorphism. Cancer science. 2016. Fujiwara Yutaka, 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 in the treatment of lung cancer: an update. Pharmacogenomics. 2015. Morales-Espinosa Daniela, 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 next-generation ALK inhibitors. Current opinion in oncology. 2015. Pall Georg. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Novel targeted therapies for resistant ALK-rearranged non-small-cell lung cancer: ceritinib and beyond. OncoTargets and therapy. 2015. Kanaan Zeyad, 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
In vitro assessment of time-dependent inhibitory effects on CYP2C8 and CYP3A activity by fourteen protein kinase inhibitors. Drug metabolism and disposition: the biological fate of chemicals. 2014. Filppula Anne M, 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
Clinical Implementation of Germline Cancer Pharmacogenetic Variants during the Next-Generation Sequencing Era. Clinical pharmacology and therapeutics. 2013. Gillis Nancy K, 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
Pharmacogenetics and pharmacogenomics: a bridge to individualized cancer therapy. Pharmacogenomics. 2013. Weng Liming, 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
Pharmacogenetics and pharmacogenomics: role of mutational analysis in anti-cancer targeted therapy. The pharmacogenomics journal. 2012. Savonarola A, 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
ROS1 as a 'druggable' receptor tyrosine kinase: lessons learned from inhibiting the ALK pathway. Expert review of anticancer therapy. 2012. Ou Sai-Hong Ignatius, 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
Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer. Clinical cancer research : an official journal of the American Association for Cancer Research. 2012. Doebele Robert C, 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
Crizotinib-resistant mutants of EML4-ALK identified through an accelerated mutagenesis screen. Chemical biology & drug design. 2011. Zhang Sen, 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
ALK mutations conferring differential resistance to structurally diverse ALK inhibitors. Clinical cancer research : an official journal of the American Association for Cancer Research. 2011. Heuckmann Johannes M, 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
Crizotinib: a novel and first-in-class multitargeted tyrosine kinase inhibitor for the treatment of anaplastic lymphoma kinase rearranged non-small cell lung cancer and beyond. Drug design, development and therapy. 2011. Ou Sai-Hong Ignatius. PubMed

LinkOuts

PubChem Compound:
11626560

Clinical Trials

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

No trials loaded.

NURSA Datasets

provided by nursa.org

No NURSA datasets available.

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Sources for PharmGKB drug information: DrugBank, PubChem.