Crizotinib

Crizotinib
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Stefano Giannoni [2]

Disclaimer

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Overview

Crizotinib is a tyrosine kinase inhibitor that is FDA approved for the treatment of metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive. Common adverse reactions include vision disorders, nausea, diarrhea, vomiting, constipation, edema, elevated transaminases, and fatigue.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

There is limited information regarding Crizotinib FDA-Labeled Indications and Dosage (Adult) in the drug label.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Crizotinib in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Crizotinib in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Crizotinib FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Crizotinib in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Crizotinib in pediatric patients.

Contraindications

There is limited information regarding Crizotinib Contraindications in the drug label.

Warnings

There is limited information regarding Crizotinib Warnings' in the drug label.

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Crizotinib Clinical Trials Experience in the drug label.

Postmarketing Experience

There is limited information regarding Crizotinib Postmarketing Experience in the drug label.

Drug Interactions

There is limited information regarding Crizotinib Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There is no FDA guidance on usage of Crizotinib in women who are pregnant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Crizotinib in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Crizotinib during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Crizotinib in women who are nursing.

Pediatric Use

There is no FDA guidance on the use of Crizotinib in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Crizotinib in geriatric settings.

Gender

There is no FDA guidance on the use of Crizotinib with respect to specific gender populations.

Race

There is no FDA guidance on the use of Crizotinib with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Crizotinib in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Crizotinib in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Crizotinib in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Crizotinib in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Crizotinib Administration in the drug label.

Monitoring

There is limited information regarding Crizotinib Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Crizotinib and IV administrations.

Overdosage

There is limited information regarding Crizotinib overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Crizotinib Pharmacology in the drug label.

Mechanism of Action

There is limited information regarding Crizotinib Mechanism of Action in the drug label.

Structure

There is limited information regarding Crizotinib Structure in the drug label.

Pharmacodynamics

There is limited information regarding Crizotinib Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Crizotinib Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Crizotinib Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Crizotinib Clinical Studies in the drug label.

How Supplied

There is limited information regarding Crizotinib How Supplied in the drug label.

Storage

There is limited information regarding Crizotinib Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Crizotinib Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Crizotinib interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Crizotinib Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Crizotinib Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

Crizotinib

File:Crizotinib structure.svg
Clinical data
Trade names	Xalkori
Synonyms	PF-02341066 1066
MedlinePlus	a612018
[[Regulation of therapeutic goods |Template:Engvar data]]	US FDA: Crizotinib
Pregnancy category	US: D (Evidence of risk)
Routes of administration	Oral
ATC code	L01XE16 (WHO)
Legal status
Legal status	US: ℞-only
Pharmacokinetic data
Elimination half-life	46 hours
Identifiers
IUPAC name 3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-(1-piperidin-4-ylpyrazol-4-yl)pyridin-2-amine
CAS Number	877399-52-5 N
PubChem CID	11626560
DrugBank	DB08700 Y
ChemSpider	9801307 Y
UNII	53AH36668S
KEGG	D09731 Y
ChEMBL	ChEMBL601719 Y
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C21H22Cl2FN5O
Molar mass	450.337 g/mol
3D model (JSmol)	Interactive image
SMILES C1(=C(C=CC(=C1[C@H](OC2=C(N=CC(=C2)C3=C[N](N=C3)C4CCNCC4)N)C)Cl)F)Cl
InChI InChI=1S/C21H22Cl2FN5O/c1-12(19-16(22)2-3-17(24)20(19)23)30-18-8-13(9-27-21(18)25)14-10-28-29(11-14)15-4-6-26-7-5-15/h2-3,8-12,15,26H,4-7H2,1H3,(H2,25,27)/t12-/m1/s1 Y Key:KTEIFNKAUNYNJU-GFCCVEGCSA-N Y
NY (what is this?)  (verify)

WikiDoc Resources for Crizotinib
Articles
Most recent articles on Crizotinib Most cited articles on Crizotinib Review articles on Crizotinib Articles on Crizotinib in N Eng J Med, Lancet, BMJ
Media
Powerpoint slides on Crizotinib Images of Crizotinib Photos of Crizotinib Podcasts & MP3s on Crizotinib Videos on Crizotinib
Evidence Based Medicine
Cochrane Collaboration on Crizotinib Bandolier on Crizotinib TRIP on Crizotinib
Clinical Trials
Ongoing Trials on Crizotinib at Clinical Trials.gov Trial results on Crizotinib Clinical Trials on Crizotinib at Google
Guidelines / Policies / Govt
US National Guidelines Clearinghouse on Crizotinib NICE Guidance on Crizotinib NHS PRODIGY Guidance FDA on Crizotinib CDC on Crizotinib
Books
Books on Crizotinib
News
Crizotinib in the news Be alerted to news on Crizotinib News trends on Crizotinib
Commentary
Blogs on Crizotinib
Definitions
Definitions of Crizotinib
Patient Resources / Community
Patient resources on Crizotinib Discussion groups on Crizotinib Patient Handouts on Crizotinib Directions to Hospitals Treating Crizotinib Risk calculators and risk factors for Crizotinib
Healthcare Provider Resources
Symptoms of Crizotinib Causes & Risk Factors for Crizotinib Diagnostic studies for Crizotinib Treatment of Crizotinib
Continuing Medical Education (CME)
CME Programs on Crizotinib
International
Crizotinib en Espanol Crizotinib en Francais
Business
Crizotinib in the Marketplace Patents on Crizotinib
Experimental / Informatics
List of terms related to Crizotinib

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]

Overview

Crizotinib (Xalkori, Pfizer), is an ALK (anaplastic lymphoma kinase) and ROS1 (c-ros oncogene1, receptor tyrosine kinase) inhibitor, approved for treatment of some non-small cell lung carcinoma (NSCLC) in the US and some other countries, and undergoing clinical trials testing its safety and efficacy in anaplastic large cell lymphoma, neuroblastoma, and other advanced solid tumors in both adults and children.

Mechanism of action

File:2xp2.png

Human anaplastic lymphoma kinase in complex with crizotinib. PDB 2xp2

Crizotinib has an aminopyridine structure, and functions as a protein kinase inhibitor by competitive binding within the ATP-binding pocket of target kinases. About 4% of patients with non-small cell lung carcinoma have a chromosomal rearrangement that generates a fusion gene between EML4 ('echinoderm microtubule-associated protein-like 4') and ALK ('anaplastic lymphoma kinase'), which results in constitutive kinase activity that contributes to carcinogenesis and seems to drive the malignant phenotype. The kinase activity of the fusion protein is also inhibited by crizotinib. Patients with this gene fusion are typically younger non-smokers who do not have mutations in either the epidermal growth factor receptor gene (EGFR) or in the K-ras gene. The number of new cases of ALK-fusion NSLC is about 9,000 per year in the U.S. and about 45,000 worldwide.

ALK mutations are also thought to be important in driving the malignant phenotype in about 15% of cases of neuroblastoma, a rare form of peripheral nervous system cancer that occurs almost exclusively in very young children.

Crizotinib also inhibits the c-Met/Hepatocyte growth factor receptor (HGFR) tyrosine kinase, which is involved in the oncogenesis of a number of other histological forms of malignant neoplasms.

Crizotinib is currently thought to exert its effects through modulation of the growth, migration, and invasion of malignant cells. Other studies suggest that crizotinib may also act via inhibition of angiogenesis in malignant tumors.

Clinical trials

Crizotinib caused tumors to shrink or stabilize in 90% of 82 patients carrying the ALK fusion gene. Tumors shrank at least 30% in 57% of people treated. Most had adenocarcinoma, and had never smoked or were former smokers. They had undergone treatment with an average of three other drugs prior to receiving crizotinib, and only 10% were expected to respond to standard therapy. They were given 250 mg crizotinib twice daily for a median duration of six months. Approximately 50% of these patients suffered at least one side effect, such as nausea, vomiting, or diarrhea. Some responses to crizotinib have lasted up to 15 months.

A phase 3 trial, PROFILE 1007, compares crizotinib to standard second line chemotherapy (pemetrexed or taxotere) in the treatment of ALK-positive NSCLC. Additionally, a phase 2 trial, PROFILE 1005, studies patients meeting similar criteria who have received more than one line of prior chemotherapy.

On August 26, 2011, the U.S. Food and Drug Administration approved crizotinib (Xalkori) to treat certain late-stage (locally advanced or metastatic) non-small cell lung cancers that express the abnormal anaplastic lymphoma kinase (ALK) gene. Approval required a companion molecular test for the EML4-ALK fusion.

Crizotinib is also being tested in clinical trials of advanced disseminated anaplastic large-cell lymphoma, and neuroblastoma.