Hospital Pharmacy - April 2012 - (Page 270)

Hosp Pharm 2012;47(4):270–274 2012 Ó Thomas Land Publishers, Inc. www.thomasland.com doi: 10.1310/hpj4704-270 Cancer Chemotherapy Update Drug Monographs: Crizotinib and Ruxolitinib Ashley Chasick, PharmDp; Dominic A. Solimando, Jr, MA, FAPhA, FASHP, BCOP; and J. Aubrey Waddell, PharmD, FAPhA, BCOP The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A. Solimando, Jr., President, Oncology Pharmacy Services, Inc., 4201 Wilson Blvd #110-545, Arlington, VA 22203, email: OncRxSvc@aol.com; or J. Aubrey Waddell, Professor, University of Tennessee College of Pharmacy; Oncology Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander Parkway, Maryville, TN 37804, e-mail: waddfour@charter.net. Name: Crizotinib Synonyms: L01XE16, PF-02341066, Xalkori MECHANISM OF ACTION Crizotinib is a tyrosine kinase inhibitor with activity against anaplastic lymphoma kinase (ALK) and c-Met tyrosine kinases. Crizotinib inhibits ALK and c-Met tyrosine kinases, resulting in decreased cell proliferation and survival. Approximately 3% to 5% of non-small cell lung cancer patients carry an ALK rearrangement. The exact role of the c-Met inhibition is unknown. PHARMACOKINETICS Crizotinib has moderate oral absorption with 43% bioavailability following the administration of a single 250 mg dose. Absorption is modestly affected by food; administration with a high-fat meal reduced the area under the time versus concentration curve (AUC) and maximum concentration (Cmax) by 14%. Crizoitinib has a large volume of distribution (1772 L) and is 91% protein-bound. Metabolism occurs predominantly in the liver by CYP3A4/5 enzymes. The mean plasma terminal half-life (t1) is 42 hours. Sixty-three percent and 22% 2 of the administered dose is recovered in feces and urine, respectively, with 53% and 2.3% as unchanged drug, respectively. The apparent clearance of crizotinib was lower at steady state (60 L/h) after 250 mg twice daily than after a single 250 mg oral dose (100 L/h). This difference is likely due to autoinhibition of CYP3A by crizotinib after multiple dosing. Selected therapeutic regimens of crizotinib appear in Table 1. PREPARATION A. Follow institutional policies for handling hazardous medications when dispensing crizotinib. B. Crizotinib is available as 200 mg and 250 mg capsules. STABILITY Crizotinib should be stored at controlled room temperature (20°C to 25°C [68°F to 77°F]). ADMINISTRATION A. Crizotinib is given orally (PO), usually twice daily, with or without food. B. The manufacturer recommends that crizotinib be dispensed in the original container and the capsules not be opened, crushed, or dissolved. C. Patients should avoid grapefruit and grapefruit juice while taking crizotinib. *Dr. Chasick is an Oncology Pharmacy Specialty Resident (PGY-2), Hematology-Oncology Pharmacy Service, Department of Pharmacy, Walter Reed National Military Medical Center, Bethesda, Maryland. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or reflections the views of the US Department of the Army, Department of the Navy, or the Department of Defense. 270 Volume 47, April 2012 http://www.thomasland.com

Table of Contents for the Digital Edition of Hospital Pharmacy - April 2012

Hospital Pharmacy - April 2012
Editorial
ISMP Medication Error Report Analysis
ISMP Adverse Drug Reactions
Cancer Chemotherapy Update
Off-Label Drug Uses
Original Article
Symptomatic Bradycardia, Syncope, and Prolonged Qtc Interval Associated With Dronedarone Therapy
Extended Stability of Magnesium Sulfate Infusions Prepared in Polyolefin Bags
Formulary Drug Reviews
Continuing Education Case Study Quiz (0.15 CEU)
Current FDA-Related Drug Information
Pharmacy Automation and Technology
Director’s Forum
Hospital Pharmacy Pulse
Index to Advertisers

Hospital Pharmacy - April 2012

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