Urology Practice Management - October 2014

FOR UROLOGISTS, PRACTICE MANAGERS, FINANCIAL COUNSELORS, AND REIMBURSEMENT SPECIALISTS™

www.UroPracticeManagement.com

OCTOBER 2014

Bringing the Future into the Present: Disaster Planning for the Medical Office

By Mariana S-B Lamb, MS, with contributions from Richard Levine, MD

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very medical practice is at risk for a natural or man-made disaster.

Future events cannot be predicted, but re­ sponses to such events can be. Any medical professional who has worked through a disaster can tell you either how glad they are that the practice had a disaster plan in place, or how they regret the practice was not prepared for such a risk. A serious crisis—fire, weather event, health crisis, or something else—disrupts your business. It threatens income streams, Continued on page 12

VOLUME 3 • NUMBER 5

The Increasing Importance of Patient Portals

By Kurt Ullman, RN, MHA, BSPA

W

ith 2014 marking the first year that Meaningful Use Stage 2 takes effect for some practices, discussions about patient portals and online access to electronic health information—just some of the core objectives required through Stage 2—continue to attract significant

Jeffery attention. Such was Daigrepont, EFPM the case at this year’s American Urological Association Practice Management Conference, where the talk “Adopting an Effective Patient Portal” was featured as one of the key general session presentations.

Continued on page 11

CMS Takes Stock of Federal Health Insurance Marketplace Benefits

By Rosemary Frei, MSc

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s the Centers for Medicare & Medicaid Services (CMS) continues its efforts to ensure that those who are enrolled in the Federal Health Insurance Marketplace (FHIM) meet eligibility requirements, the ripple effects of these efforts may be felt at medical practices nationwide.

In a news release issued on September

15, 2014, the agency stated that 115,000 people who had not submitted sufficient information to clear up data inconsistency issues relating to their citizenship or immigration status “will be receiving notices saying their last day of Federal Marketplace coverage is September 30, 2014.”1 The potential Continued on page 4

S IC T S O N tory a AG or 4 DI b ..1 a

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D te L ests N A gula ed T

© 2014 Engage Healthcare Communications, LLC

G e p IT N to R velo S e TE FDA D

FOR UROLOGISTS, PRACTICE MANAGERS, FINANCIAL COUNSELORS, AND REIMBURSEMENT SPECIALISTS™

Call for Papers

Do you have a practice management story to share

?

In your background as a urology practice manager, it’s likely there’s one business experience—and maybe more—that practice managers across the nation would want to read about.

High-interest topics include: the solution you found to a practice management challenge, reimbursement, your experience with EMR, Medicare audits, a memorable encounter that shaped the way you now run your business and/or practice medicine, or how you successfully integrated ancillary products and services into your practice as a revenue generator.

Send us your ideas!

Submit a 600- to 1500-word original article to Urology Practice Management that your fellow practice managers will want to read.

Submit to: info@the-lynx-group.com UPM_73114

In This Issue

PUBLISHING STAFF Senior Vice President/Group Publisher Nicholas Englezos nenglezos@the-lynx-group.com Vice President, Director of Sales & Marketing Joe Chanley jchanley@the-lynx-group.com Publisher Cristopher Pires cpires@the-lynx-group.com Editorial Directors Dalia Buffery dbuffery@the-lynx-group.com Anne M. Cooper acooper@the-lynx-group.com

Associate Editor Lara J. Lorton Copyeditor Jessica Cheng Editorial Assistant Cara Guglielmon Production Manager Marie RS Borrelli The Lynx Group President/CEO Brian Tyburski Chief Operating Officer Pam Rattananont Ferris Vice President of Finance Andrea Kelly Human Resources Jennine Leale Associate Director, Content Strategy & Development John Welz Director, Quality Control Barbara Marino Quality Control Assistant Theresa Salerno Director, Production & Manufacturing Alaina Pede Director, Creative & Design Robyn Jacobs Creative & Design Assistant Lora LaRocca Director, Digital Media Anthony Romano Web Content Managers David Maldonado Anthony Trevean Digital Programmer Michael Amundsen Meeting & Events Planner Linda Sangenito Senior Project Managers Alyson Bruni Jini Gopalaswamy Project Manager Deanna Martinez Project Coordinator Mike Kodada IT Specialist Carlton Hurdle Executive Administrator Rachael Baranoski Office Coordinator Robert Sorensen Engage Healthcare Communications 1249 South River Road - Ste 202A Cranbury, NJ 08512 phone: 732-992-1880 fax: 732-992-1881

FEATURES Bringing the Future into the Present: Disaster Planning for the Medical Office.............................................................................................1

By Mariana S-B Lamb, MS, with contributions from Richard Levine, MD

The Increasing Importance of Patient Portals......................................................1

By Kurt Ullman, RN, MHA, BSPA

CMS Takes Stock of Federal Health Insurance Marketplace Benefits.............1

By Rosemary Frei, MSc

FDA to Regulate Laboratory-Developed Tests...............................................14

By Rosemary Frei, MSc

Connecting Patients to Resources...................................................................... 20

By Sheryl Riley, RN, OCN, CMCN

Do’s and Don’ts in Physician–Hospital Alignment, Part 3................................ 22

By Max Reiboldt, CPA

Financial Toxicity: The Elephant in the (Side Effect) Room.............................. 24

By Barry D. Brooks, MD

Should You Consider the Interests of Society at Large When Treating the Individual Patient?........................................................................... 26

By Wayne Kuznar

EDITORIAL ADVISORY BOARD Neil Baum, MD Practicing Urologist New Orleans, LA Cheris Craig, MBA, CMPE Chief Administrative Officer Urology of Greater Atlanta, LLC Atlanta, GA Michael deWitt Clayton, MD, FACS Urology Associates of San Luis Obispo, CA Rick Janss, MBA, CMPE Practice Administrator Clinical Urology Associates Gadsden, AL

John McMann, MS Administrator Advanced Urology Specialists, LLC Oxford, FL

James A. Sylora, MD Urologist AUS–Midwest Urology Evergreen Park, IL

Jonathan Oppenheimer, MD, FCAP Medical Director, Chief Pathologist Oppenheimer Urologic Reference Laboratory Nashville, TN

Sean M. Weiss, CCP-P, CCA-P, ACS-EM, CPC, CPC-P Vice President & Chief Compliance Officer DecisionHealth/ Professional Services Gaithersburg, MD

Jonathan Rubenstein, MD Director of Coding and Compliance Chesapeake Urology Baltimore, MD

MISSION STATEMENT Urology healthcare requires providers to focus attention on financial concerns and strategic decisions that affect the bottom line. To continue to provide the high-quality care urology patients deserve, providers must master the ever-changing business of urology. Urology Practice Management offers process solutions for members of the urology care team—medical, surgical, and radiation urologists, as well as executives, administrators, and coders/billers—to assist them in reimbursement, staffing, electronic health records, REMS, and compliance with state and federal regulations.

Urology Practice Management™, ISSN 2374-0752 (print); 2374-0760 (online), is published 6 times a year by Engage Healthcare Communications, LLC, 1249 South River Road, Cranbury, NJ 08512. Copyright © 2014 by Engage Healthcare Communications, LLC. All rights reserved. Urology Practice Management™ is a trademark of Engage Healthcare Communications, LLC. No part of this publication may be reproduced or transmitted in any form or by any means now or hereafter known, electronic or mechanical, including photocopy, recording, or any informational storage and retrieval system, without written permission from the publisher. Printed in the United States of America.

The ideas and opinions expressed in Urology Practice Management™ do not necessarily reflect those of the editorial board, the editors, or the publisher. Publication of an advertisement or other product mentioned in Urology Practice Management™ should not be construed as an endorsement of the product or the manufacturer’s claims. Readers are encouraged to contact the manufacturers about any features or limitations of products mentioned. Neither the editors nor the publisher assume any responsibility for any injury and/or damage to persons or property arising out of or related to any use of the material mentioned in this publication.

POSTMASTER: Correspondence regarding subscriptions or change of address should be directed to CIRCULATION DIRECTOR, Urology Practice Management™, 1249 South River Road, Cranbury, NJ 08512.

Fax: 732-992-1881. Yearly subscription rates: 1 year: $99.00 USD; 2 years: $149.00 USD; 3 years: $199.00 USD.

October 2014

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www.UroPracticeManagement.com

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Insurance & Benefits

CMS Takes Stock of Federal Health…Continued from the cover

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revoking of FHIM benefits to more than 100,000 Americans may make insurance-verification processes at practices even more complex than they already are.

The statement also states that “there are still about 279,000 households with unresolved income-related data-matching issues that haven’t sent in supporting information [to reconcile differences between the households’ applications and those the CMS has on file], representing 363,000 individuals. CMS will send letters starting today to individuals who, if they do not send in supporting documents

by September 30, may see their costs change.…For instance, this may impact the cost of their monthly premium, deductibles, copays, and co-insurance, and even their tax bill or refund during filing season.” 1 These moves are part of CMS’s preparations for the next Marketplace open enrollment period beginning on November 15, 2014. “[CMS] is resolving data-matching issues that occurred during the first year so that its records are accurate before the renewal process begins, and so that consumers have the information they need about their coverage,”1 the news release states.

John V. Cox, DO, Medical Oncologist, Methodist Hospitals of Dallas, TX, and a medical director at Texas Oncology PA, Dallas, said he hopes it will be easy for practices to find out whether their patients’ FHIM coverage remains in place.

“Many plans now have patient coverage information on their computerized systems so you can confirm it right away. So as long as that mechanism remains in place, then practices can use their routine mechanisms to be able to confirm

whether a given patient is covered by the FHIM or not,” said Dr Cox in a phone interview.

“I guess we’re always concerned— oncology, urology, and some other practice types that have high-dollar therapeutics that patients are given in their offices—that we’re not going to be told one day that a patient has coverage, then we provide treatment, and then found out on day 2 or day 3 that that coverage doesn’t exist. No practice can suffer the nonreimbursement for these expensive therapeutics. There’s no margin for error.”

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UROLOGY PRACTICE MANAGEMENT

The potential revoking of FHIM benefits… may make insuranceverification processes at practices even more complex than they already are.

addresses and 52,700 to Texas residents3—who had inconsistencies in their citizenship and/or immigration information. These individuals had not responded to 5 to 7 previous requests via e-mail, phone, and regular mail about inconsistencies. There was a September 5 deadline for submitting information to clear up the data-matching issues, and a September 30 FHIMbenefit cutoff date for people whose submissions had not cleared up the inconsistencies.

September 30 was also the date that costs could change for people who had not cleared up income inconsistencies; CMS also said it had made “numerous previous attempts” to reach these individuals since May 30.1 The news release stated that individuals still can clear up inconsistencies in several ways: by logging into their HealthCare. gov account and selecting their current application to upload their documents, mailing their information to the CMS’s consumer center, or calling the CMS’s call center at 800-318-2596 to see what documents they need to submit and check whether the Federal Marketplace has received their information. l

Rick Rutherford, Director, Practice Management, American Urological Association, is also hoping for the best for urology practice managers.

References “Because the health exchange 1. Centers for Medicare & Medicaid Services. News September 15, 2014. CMS update on coninsurance policies have the 90-day release sumers who have data matching issues. http://cms. grace period for unpaid premiums gov/Newsroom/MediaReleaseDatabase/Press-releases/­ Accessed already in place, this new develop- 2014-Press-releases-items/2014-09-15.html.

September 16, 2014. ment—the termination of coverage 2. Centers for Medicare & Medicaid Services. News August 12, 2014. Federal Health Insurance for lack of citizenship or income-­ release Marketplace: Send in requested documents now to verification documentation—is keep marketplace coverage. www.cms.gov/Newsroom/ just another administrative hassle,” MediaReleaseDatabase/Press-releases/2014-Pressreleases-items/2014-08-12.html. Accessed September Mr Rutherford wrote in an e-mail. 15, 2014.

Centers for Medicare & Medicaid Services.

CMS announced on August 12, 3.

Warning notices generated for citizenship/immigra2014, that its staff had sent out tion data matching issues (Individual Level) by State as of 8/10/14. www.hhs.gov/healthcare/facts/ reminder notices to 310,000 peo- Data factsheets/2014/08/data-matching-map.pdf. Accessed ple2—including 93,800 to Florida September 16, 2014.

October 2014

In mCRPC therapy…

Is there more to the story?

INDICATION ZYTIGA® (abiraterone acetate) in combination with prednisone is indicated for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC).

IMPORTANT SAFETY INFORMATION Contraindications—ZYTIGA® is not indicated for use in women. ZYTIGA® can cause fetal harm (Pregnancy Category X) when administered to a pregnant woman and is contraindicated in women who are or may become pregnant.

Adverse Reactions—The most common adverse reactions (≥10%) are fatigue, joint swelling or discomfort, edema, hot flush, diarrhea, vomiting, cough, hypertension, dyspnea, urinary tract infection, and contusion.

The most common laboratory abnormalities (>20%) are anemia, elevated alkaline phosphatase, hypertriglyceridemia, lymphopenia, hypercholesterolemia, hyperglycemia, elevated AST, hypophosphatemia, elevated ALT, and hypokalemia.

Increased ZYTIGA® Exposures With Food—ZYTIGA® must be taken on an empty stomach. No food should be eaten for at least two hours before the dose of ZYTIGA® is taken and for at least one hour after the dose of ZYTIGA® is taken.

Abiraterone Cmax and AUC0-∞ (exposure) were increased up to 17- and 10-fold higher, respectively, when a single dose of abiraterone acetate was administered with a meal compared to a fasted state.

Adrenocortical Insufficiency (AI)—AI was reported in patients receiving ZYTIGA® in combination with prednisone, after an interruption of daily steroids and/or with concurrent infection or stress. Use caution and monitor for symptoms and signs of AI if prednisone is stopped or withdrawn, if prednisone dose is reduced, or if the patient experiences unusual stress. Symptoms and signs of AI may be masked by adverse reactions associated with mineralocorticoid excess seen in patients treated with ZYTIGA®. Perform appropriate tests, if indicated, to confirm AI. Increased dosages of corticosteroids may be used before, during, and after stressful situations.

Hypertension, Hypokalemia, and Fluid Retention Due to Mineralocorticoid Excess—Use with caution in patients with a history of cardiovascular disease or with medical conditions that might be compromised by increases in blood pressure, hypokalemia, or fluid retention. ZYTIGA® may cause hypertension, hypokalemia, and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition. Safety has not been established in patients with LVEF <50% or New York Heart Association (NYHA) Class III or IV heart failure (in Study 1) or NYHA Class II to IV heart failure (in Study 2) because these patients were excluded from these randomized clinical trials.

Control hypertension and correct hypokalemia before and during treatment. Monitor blood pressure, serum potassium, and symptoms of fluid retention at least monthly. mCRPC=metastatic castration-resistant prostate cancer; AST=aspartate aminotransferase; ALT=alanine aminotransferase.

Please see additional Important Safety Information on the next page.

Please see brief summary of full Prescribing Information on subsequent pages.

For men with mCRPC who progressed on ADT

In a clinical trial, patients had a median overall survival on ZYTIGA® (abiraterone acetate) of…*

More than 1,000 days.

And every day tells a story.

35.3 IMPROVEMENT IN MEDIAN OVERALL SURVIVAL 5.2 MONTHS compared with placebo plus prednisone.

MONTHS MEDIAN OVERALL SURVIVAL FOR ZYTIGA® plus prednisone† vs 30.1 MONTHS with placebo plus prednisone (active compound).‡

Co-primary end point—overall survival: hazard ratio (HR)=0.792; 95% CI: 0.655, 0.956; P=0.0151; prespecified value for statistical significance not reached.

Co-primary end point—radiographic progression-free survival: median not reached for ZYTIGA® plus prednisone vs a median of 8.28 months for placebo plus prednisone. HR=0.425; 95% CI: 0.347, 0.522; P<0.0001.

IMPORTANT SAFETY INFORMATION (cont) Increased ZYTIGA® Exposures With Food—ZYTIGA® must be taken on an empty stomach. No food should be eaten for at least two hours before the dose of ZYTIGA® is taken and for at least one hour after the dose of ZYTIGA® is taken.

Abiraterone Cmax and AUC0-∞ (exposure) were increased up to 17- and 10-fold higher, respectively, when a single dose of abiraterone acetate was administered with a meal compared to a fasted state.

Hepatotoxicity—Monitor liver function and modify, withhold, or discontinue ZYTIGA® dosing as recommended (see Prescribing Information for more information). Measure serum transaminases (ALT and AST) and bilirubin levels prior to starting treatment with ZYTIGA®, every two weeks for the first three months of treatment, and monthly thereafter.

Promptly measure serum total bilirubin, AST, and ALT if clinical symptoms or signs suggestive of hepatotoxicity develop.

Elevations of AST, ALT, or bilirubin from the patient’s baseline should prompt more frequent monitoring. If at any time AST or ALT rise above five times the upper limit of normal (ULN) or the bilirubin rises above three times the ULN, interrupt ZYTIGA® treatment and closely monitor liver function. *Study Design: ZYTIGA®, in combination with prednisone, was evaluated in a phase 3, randomized, double-blind, placebo-controlled, multicenter trial in patients with mCRPC who had not received prior chemotherapy (N=1,088). Patients were using a luteinizing hormone-releasing hormone (LHRH) agonist or were previously treated with orchiectomy. In the ZYTIGA® arm, patients received ZYTIGA® 1,000 mg orally once daily + prednisone 5 mg orally twice daily. In the placebo arm, patients received placebo orally once daily + prednisone 5 mg orally twice daily. In this study, the co-primary efficacy end points were overall survival (OS) and radiographic progression-free survival.

ADT=androgen-deprivation therapy.

Janssen Biotech, Inc. © Janssen Biotech, Inc. 2014 6/14 016819-140612

Please see brief summary of full Prescribing Information on subsequent pages.

B:11.125 in

003307-130924

S:10.375 in

T:10.875 in

Drug Interactions—Based on in vitro data, ZYTIGA® is a substrate of CYP3A4. In a drug interaction trial, co-administration of rifampin, a strong CYP3A4 inducer, decreased exposure of abiraterone by 55%. Avoid concomitant strong CYP3A4 inducers during ZYTIGA® treatment. If a strong CYP3A4 inducer must be co-administered, increase the ZYTIGA® dosing frequency only during the co-administration period [see Dosage and Administration (2.3)]. In a dedicated drug interaction trial, co-administration of ketoconazole, a strong inhibitor of CYP3A4, had no clinically meaningful effect on the pharmacokinetics of abiraterone.

ZYTIGA® is an inhibitor of the hepatic drug-metabolizing enzyme CYP2D6. Avoid co-administration with CYP2D6 substrates with a narrow therapeutic index. If alternative treatments cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate drug. In vitro, ZYTIGA® inhibits CYP2C8. There are no clinical data on the use of ZYTIGA® with drugs that are substrates of CYP2C8. Patients should be monitored closely for signs of toxicity related to the CYP2C8 substrate if used concomitantly with abiraterone acetate.

Use in Specific Populations—Do not use ZYTIGA® in patients with baseline severe hepatic impairment (Child-Pugh Class C). †At a prespecified interim analysis for OS, 37% (200/546) of patients treated with ZYTIGA® plus prednisone compared with 43% (234/542) of patients treated with placebo plus prednisone had died. ‡Prednisone, as a single agent, is not approved for the treatment of prostate cancer.

Learn more today at

www.zytigahcp.com.

Every day tells a story.

ZYTIGA® (abiraterone acetate) Tablets Brief Summary of Prescribing Information.

INDICATIONS AND USAGE ZYTIGA is a CYP17 inhibitor indicated in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer.

CONTRAINDICATIONS Pregnancy: ZYTIGA can cause fetal harm when administered to a pregnant woman. ZYTIGA is not indicated for use in women. ZYTIGA is contraindicated in women who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to the fetus and the potential risk for pregnancy loss [see Use in Specific Populations].

WARNINGS AND PRECAUTIONS Hypertension, Hypokalemia and Fluid Retention Due to Mineralocorticoid Excess: ZYTIGA may cause hypertension, hypokalemia, and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition [see Clinical Pharmacology (12.1) in full Prescribing Information].

In the two randomized clinical trials, grade 3 to 4 hypertension occurred in 2% of patients, grade 3 to 4 hypokalemia in 4% of patients, and grade 3 to 4 edema in 1% of patients treated with ZYTIGA [see Adverse Reactions].

Co-administration of a corticosteroid suppresses adrenocorticotropic hormone (ACTH) drive, resulting in a reduction in the incidence and severity of these adverse reactions. Use caution when treating patients whose underlying medical conditions might be compromised by increases in blood pressure, hypokalemia or fluid retention, e.g., those with heart failure, recent myocardial infarction or ventricular arrhythmia. Use ZYTIGA with caution in patients with a history of cardiovascular disease. The safety of ZYTIGA in patients with left ventricular ejection fraction <50% or New York Heart Association (NYHA) Class III or IV heart failure (in Study 1) or NYHA Class II to IV heart failure (in Study 2) was not established because these patients were excluded from these randomized clinical trials [see Clinical Studies (14) in full Prescribing Information]. Monitor patients for hypertension, hypokalemia, and fluid retention at least once a month. Control hypertension and correct hypokalemia before and during treatment with ZYTIGA. Adrenocortical Insufficiency: Adrenal insufficiency occurred in the two randomized clinical studies in 0.5% of patients taking ZYTIGA and in 0.2% of patients taking placebo. Adrenocortical insufficiency was reported in patients receiving ZYTIGA in combination with prednisone, following interruption of daily steroids and/or with concurrent infection or stress. Use caution and monitor for symptoms and signs of adrenocortical insufficiency, particularly if patients are withdrawn from prednisone, have prednisone dose reductions, or experience unusual stress. Symptoms and signs of adrenocortical insufficiency may be masked by adverse reactions associated with mineralocorticoid excess seen in patients treated with ZYTIGA. If clinically indicated, perform appropriate tests to confirm the diagnosis of adrenocortical insufficiency. Increased dosage of corticosteroids may be indicated before, during and after stressful situations [see Warnings and Precautions].

Hepatotoxicity: In the two randomized clinical trials, grade 3 or 4 ALT or AST increases (at least 5X ULN) were reported in 4% of patients who received ZYTIGA, typically during the first 3 months after starting treatment. Patients whose baseline ALT or AST were elevated were more likely to experience liver test elevation than those beginning with normal values. Treatment discontinuation due to liver enzyme increases occurred in 1% of patients taking ZYTIGA. No deaths clearly related to ZYTIGA were reported due to hepatotoxicity events.

Measure serum transaminases (ALT and AST) and bilirubin levels prior to starting treatment with ZYTIGA, every two weeks for the first three months of treatment and monthly thereafter. In patients with baseline moderate hepatic impairment receiving a reduced ZYTIGA dose of 250 mg, measure ALT, AST, and bilirubin prior to the start of treatment, every week for the first month, every two weeks for the following two months of treatment and monthly thereafter. Promptly measure serum total bilirubin, AST, and ALT if clinical symptoms or signs suggestive of hepatotoxicity develop.

Elevations of AST, ALT, or bilirubin from the patient’s baseline should prompt more frequent monitoring. If at any time AST or ALT rise above five times the ULN, or the bilirubin rises above three times the ULN, interrupt ZYTIGA treatment and closely monitor liver function.

Re-treatment with ZYTIGA at a reduced dose level may take place only after return of liver function tests to the patient’s baseline or to AST and ALT less than or equal to 2.5X ULN and total bilirubin less than or equal to 1.5X ULN [see Dosage and Administration (2.2) in full Prescribing Information].

The safety of ZYTIGA re-treatment of patients who develop AST or ALT greater than or equal to 20X ULN and/or bilirubin greater than or equal to 10X ULN is unknown.

Increased ZYTIGA Exposures with Food: ZYTIGA must be taken on an empty stomach. No food should be consumed for at least two hours before the dose of ZYTIGA is taken and for at least one hour after the dose of ZYTIGA is taken. Abiraterone Cmax and AUC0-∞ (exposure) were increased up to 17and 10-fold higher, respectively, when a single dose of abiraterone acetate was administered with a meal compared to a fasted state. The safety of these increased exposures when multiple doses of abiraterone acetate are taken with food has not been assessed [see Dosage and Administration (2.1) and Clinical Pharmacology (12.3) in full Prescribing Information].

ZYTIGA® (abiraterone acetate) Tablets ADVERSE REACTIONS The following are discussed in more detail in other sections of the labeling: • Hypertension, Hypokalemia, and Fluid Retention due to Mineralocorticoid Excess [see Warnings and Precautions].

• Adrenocortical Insufficiency [see Warnings and Precautions].

• Hepatotoxicity [see Warnings and Precautions].

• Increased ZYTIGA Exposures with Food [see Warnings and Precautions].

Clinical Trial Experience: Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Two randomized placebo-controlled, multicenter clinical trials enrolled patients who had metastatic castration-resistant prostate cancer who were using a gonadotropin-releasing hormone (GnRH) agonist or were previously treated with orchiectomy. In both Study 1 and Study 2 ZYTIGA was administered at a dose of 1,000 mg daily in combination with prednisone 5 mg twice daily in the active treatment arms. Placebo plus prednisone 5 mg twice daily was given to control patients.

The most common adverse drug reactions (≥10%) reported in the two randomized clinical trials that occurred more commonly (>2%) in the abiraterone acetate arm were fatigue, joint swelling or discomfort, edema, hot flush, diarrhea, vomiting, cough, hypertension, dyspnea, urinary tract infection and contusion.

The most common laboratory abnormalities (>20%) reported in the two randomized clinical trials that occurred more commonly (≥2%) in the abiraterone acetate arm were anemia, elevated alkaline phosphatase, hypertriglyceridemia, lymphopenia, hypercholesterolemia, hyperglycemia, elevated AST, hypophosphatemia, elevated ALT and hypokalemia.

Study 1: Metastatic CRPC Following Chemotherapy: Study 1 enrolled 1195 patients with metastatic CRPC who had received prior docetaxel chemotherapy. Patients were not eligible if AST and/or ALT ≥2.5X ULN in the absence of liver metastases. Patients with liver metastases were excluded if AST and/or ALT >5X ULN. Table 1 shows adverse reactions on the ZYTIGA arm in Study 1 that occurred with a ≥2% absolute increase in frequency compared to placebo or were events of special interest. The median duration of treatment with ZYTIGA was 8 months.

Table 1: Adverse Reactions due to ZYTIGA in Study 1 ZYTIGA with Placebo with Prednisone (N=791) Prednisone (N=394) 1 System/Organ Class All Grades Grade 3-4 All Grades Grade 3-4 Adverse reaction % % % % Musculoskeletal and connective tissue disorders Joint swelling/ discomfort2 29.5 4.2 23.4 4.1 Muscle discomfort3 26.2 3.0 23.1 2.3 General disorders Edema4 26.7 1.9 18.3 0.8 Vascular disorders Hot flush 19.0 0.3 16.8 0.3 Hypertension 8.5 1.3 6.9 0.3 Gastrointestinal disorders Diarrhea 17.6 0.6 13.5 1.3 Dyspepsia 6.1 0 3.3 0 Infections and infestations Urinary tract infection 11.5 2.1 7.1 0.5 Upper respiratory tract infection 5.4 0 2.5 0 Respiratory, thoracic and mediastinal disorders Cough 10.6 0 7.6 0 Renal and urinary disorders Urinary frequency 7.2 0.3 5.1 0.3 Nocturia 6.2 0 4.1 0 Injury, poisoning and procedural complications Fractures5 5.9 1.4 2.3 0 Cardiac disorders Arrhythmia6 7.2 1.1 4.6 1.0 Chest pain or chest 7 discomfort 3.8 0.5 2.8 0 Cardiac failure8 2.3 1.9 1.0 0.3

ZYTIGA® (abiraterone acetate) Tablets

ZYTIGA® (abiraterone acetate) Tablets

1 Adverse events graded according to CTCAE version 3.0 2 Includes terms Arthritis, Arthralgia, Joint swelling, and Joint stiffness 3 Includes terms Muscle spasms, Musculoskeletal pain, Myalgia,

Table 3: Adverse Reactions in ≥5% of Patients on the ZYTIGA Arm in Study 2 (continued) ZYTIGA with Placebo with Prednisone (N=542) Prednisone (N=540) System/Organ Class All Grades1 Grade 3-4 All Grades Grade 3-4 Adverse reaction % % % % Renal and urinary disorders Hematuria 10.3 1.3 5.6 0.6 Skin and subcutaneous tissue disorders Rash 8.1 0.0 3.7 0.0 1 Adverse events graded according to CTCAE version 3.0 2 Includes terms Edema peripheral, Pitting edema, and Generalized edema 3 Includes terms Arthritis, Arthralgia, Joint swelling, and Joint stiffness

Musculoskeletal discomfort, and Musculoskeletal stiffness terms Edema, Edema peripheral, Pitting edema, and Generalized edema 5 Includes all fractures with the exception of pathological fracture 6 Includes terms Arrhythmia, Tachycardia, Atrial fibrillation, Supraventricular tachycardia, Atrial tachycardia, Ventricular tachycardia, Atrial flutter, Bradycardia, Atrioventricular block complete, Conduction disorder, and Bradyarrhythmia 7 Includes terms Angina pectoris, Chest pain, and Angina unstable.

Myocardial infarction or ischemia occurred more commonly in the placebo arm than in the ZYTIGA arm (1.3% vs. 1.1% respectively).

8 Includes terms Cardiac failure, Cardiac failure congestive, Left ventricular dysfunction, Cardiogenic shock, Cardiomegaly, Cardiomyopathy, and Ejection fraction decreased 4 Includes

Table 2 shows laboratory abnormalities of interest from Study 1. Grade 3-4 low serum phosphorus (7%) and low potassium (5%) occurred at a greater than or equal to 5% rate in the ZYTIGA arm.

Table 2: Laboratory Abnormalities of Interest in Study 1 Abiraterone (N=791) Placebo (N=394) Laboratory All Grades Grade 3-4 All Grades Grade 3-4 Abnormality (%) (%) (%) (%) Hypertriglyceridemia 62.5 0.4 53.0 0 High AST 30.6 2.1 36.3 1.5 Hypokalemia 28.3 5.3 19.8 1.0 Hypophosphatemia 23.8 7.2 15.7 5.8 High ALT 11.1 1.4 10.4 0.8 High Total Bilirubin 6.6 0.1 4.6 0 Study 2: Metastatic CRPC Prior to Chemotherapy: Study 2 enrolled 1088 patients with metastatic CRPC who had not received prior cytotoxic chemotherapy. Patients were ineligible if AST and/or ALT ≥2.5X ULN and patients were excluded if they had liver metastases.

Table 3 shows adverse reactions on the ZYTIGA arm in Study 2 that occurred with a ≥2% absolute increase in frequency compared to placebo.

The median duration of treatment with ZYTIGA was 13.8 months.

Table 3: Adverse Reactions in ≥5% of Patients on the ZYTIGA Arm in Study 2 ZYTIGA with Placebo with Prednisone (N=542) Prednisone (N=540) System/Organ Class All Grades1 Grade 3-4 All Grades Grade 3-4 Adverse reaction % % % % General disorders Fatigue 39.1 2.2 34.3 1.7 Edema2 25.1 0.4 20.7 1.1 Pyrexia 8.7 0.6 5.9 0.2 Musculoskeletal and connective tissue disorders Joint swelling/ discomfort3 30.3 2.0 25.2 2.0 Groin pain 6.6 0.4 4.1 0.7 Gastrointestinal disorders Constipation 23.1 0.4 19.1 0.6 Diarrhea 21.6 0.9 17.8 0.9 Dyspepsia 11.1 0.0 5.0 0.2 Vascular disorders Hot flush 22.3 0.2 18.1 0.0 Hypertension 21.6 3.9 13.1 3.0 Respiratory, thoracic and mediastinal disorders Cough 17.3 0.0 13.5 0.2 Dyspnea 11.8 2.4 9.6 0.9 Psychiatric disorders Insomnia 13.5 0.2 11.3 0.0 Injury, poisoning and procedural complications Contusion 13.3 0.0 9.1 0.0 Falls 5.9 0.0 3.3 0.0 Infections and infestations Upper respiratory tract infection 12.7 0.0 8.0 0.0 Nasopharyngitis 10.7 0.0 8.1 0.0

Table 4 shows laboratory abnormalities that occurred in greater than 15% of patients, and more frequently (>5%) in the ZYTIGA arm compared to placebo in Study 2. Grade 3-4 lymphopenia (9%), hyperglycemia (7%) and high alanine aminotransferase (6%) occurred at a greater than 5% rate in the ZYTIGA arm.

Table 4: Laboratory Abnormalities in >15% of Patients in the ZYTIGA Arm of Study 2 Abiraterone (N=542) Placebo (N=540) Laboratory Grade 1-4 Grade 3-4 Grade 1-4 Grade 3-4 Abnormality % % % % Hematology Lymphopenia 38.2 8.7 31.7 7.4 Chemistry 1 Hyperglycemia 56.6 6.5 50.9 5.2 High ALT 41.9 6.1 29.1 0.7 High AST 37.3 3.1 28.7 1.1 Hypernatremia 32.8 0.4 25.0 0.2 Hypokalemia 17.2 2.8 10.2 1.7 1Based on non-fasting blood draws Cardiovascular Adverse Reactions: In the combined data for studies 1 and 2, cardiac failure occurred more commonly in patients treated with ZYTIGA compared to patients on the placebo arm (2.1% versus 0.7%).

Grade 3-4 cardiac failure occurred in 1.6% of patients taking ZYTIGA and led to 5 treatment discontinuations and 2 deaths. Grade 3-4 cardiac failure occurred in 0.2% of patients taking placebo. There were no treatment discontinuations and one death due to cardiac failure in the placebo group.

In Study 1 and 2, the majority of arrhythmias were grade 1 or 2. There was one death associated with arrhythmia and one patient with sudden death in the ZYTIGA arms and no deaths in the placebo arms. There were 7 (0.5%) deaths due to cardiorespiratory arrest in the ZYTIGA arms and 3 (0.3%) deaths in the placebo arms. Myocardial ischemia or myocardial infarction led to death in 3 patients in the placebo arms and 2 deaths in the ZYTIGA arms.

Post Marketing Experience The following additional adverse reactions have been identified during post approval use of ZYTIGA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Respiratory, Thoracic and Mediastinal Disorders: non-infectious pneumonitis.

DRUG INTERACTIONS Drugs that Inhibit or Induce CYP3A4 Enzymes: Based on in vitro data, ZYTIGA is a substrate of CYP3A4.

In a dedicated drug interaction trial, co-administration of rifampin, a strong CYP3A4 inducer, decreased exposure of abiraterone by 55%. Avoid concomitant strong CYP3A4 inducers during ZYTIGA treatment. If a strong CYP3A4 inducer must be co-administered, increase the ZYTIGA dosing frequency [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3) in full Prescribing Information].

In a dedicated drug interaction trial, co-administration of ketoconazole, a strong inhibitor of CYP3A4, had no clinically meaningful effect on the pharmacokinetics of abiraterone [see Clinical Pharmacology (12.3) in full Prescribing Information].

Effects of Abiraterone on Drug Metabolizing Enzymes: ZYTIGA is an inhibitor of the hepatic drug-metabolizing enzyme CYP2D6. In a CYP2D6 drug-drug interaction trial, the Cmax and AUC of dextromethorphan (CYP2D6 substrate) were increased 2.8- and 2.9-fold, respectively, when

ZYTIGA® (abiraterone acetate) Tablets

ZYTIGA® (abiraterone acetate) Tablets

dextromethorphan was given with abiraterone acetate 1,000 mg daily and prednisone 5 mg twice daily. Avoid co-administration of abiraterone acetate with substrates of CYP2D6 with a narrow therapeutic index (e.g., thioridazine).

If alternative treatments cannot be used, exercise caution and consider a dose reduction of the concomitant CYP2D6 substrate drug [see Clinical Pharmacology (12.3) in full Prescribing Information].

In vitro, ZYTIGA inhibits CYP2C8. There are no clinical data on the use of ZYTIGA with drugs that are substrates of CYP2C8. However, patients should be monitored closely for signs of toxicity related to the CYP2C8 substrate if used concomitantly with abiraterone acetate.

Patients with Renal Impairment: In a dedicated renal impairment trial, the mean PK parameters were comparable between healthy subjects with normal renal function (N=8) and those with end stage renal disease (ESRD) on hemodialysis (N=8) after a single oral 1,000 mg dose of ZYTIGA. No dosage adjustment is necessary for patients with renal impairment [see Dosage and Administration (2.1) and Clinical Pharmacology (12.3) in full Prescribing Information].

OVERDOSAGE Human experience of overdose with ZYTIGA is limited.

There is no specific antidote. In the event of an overdose, stop ZYTIGA, undertake general supportive measures, including monitoring for arrhythmias and cardiac failure and assess liver function.

Storage and Handling: Store at 20°C to 25°C (68°F to 77°F); excursions permitted in the range from 15°C to 30°C (59°F to 86°F) [see USP controlled room temperature].

Based on its mechanism of action, ZYTIGA may harm a developing fetus.

Therefore, women who are pregnant or women who may be pregnant should not handle ZYTIGA without protection, e.g., gloves [see Use in Specific Populations].

PATIENT COUNSELING INFORMATION See FDA-approved patient labeling (Patient Information) • Patients should be informed that ZYTIGA and prednisone are used together and that they should not interrupt or stop either of these medications without consulting their physician.

• Patients receiving GnRH agonists should be informed that they need to maintain this treatment during the course of treatment with ZYTIGA and prednisone.

• Patients should be informed that ZYTIGA must not be taken with food and that no food should be consumed for at least two hours before the dose of ZYTIGA is taken and for at least one hour after the dose of ZYTIGA is taken. They should be informed that the tablets should be swallowed whole with water without crushing or chewing. Patients should be informed that taking ZYTIGA with food causes increased exposure and this may result in adverse reactions.

• Patients should be informed that ZYTIGA is taken once daily and prednisone is taken twice daily according to their physician’s instructions.

• Patients should be informed that in the event of a missed daily dose of ZYTIGA or prednisone, they should take their normal dose the following day. If more than one daily dose is skipped, patients should be told to inform their physician.

• Patients should be apprised of the common side effects associated with ZYTIGA, including peripheral edema, hypokalemia, hypertension, elevated liver function tests, and urinary tract infection. Direct the patient to a complete list of adverse drug reactions in PATIENT INFORMATION. • Patients should be advised that their liver function will be monitored using blood tests.

• Patients should be informed that ZYTIGA may harm a developing fetus; thus, women who are pregnant or women who may be pregnant should not handle ZYTIGA without protection, e.g., gloves. Patients should also be informed that it is not known whether abiraterone or its metabolites are present in semen and they should use a condom if having sex with a pregnant woman. The patient should use a condom and another effective method of birth control if he is having sex with a woman of child-bearing potential. These measures are required during and for one week after treatment with ZYTIGA.

USE IN SPECIFIC POPULATIONS Pregnancy: Pregnancy Category X [see Contraindications].: ZYTIGA can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals. While there are no adequate and well-controlled studies with ZYTIGA in pregnant women and ZYTIGA is not indicated for use in women, it is important to know that maternal use of a CYP17 inhibitor could affect development of the fetus. Abiraterone acetate caused developmental toxicity in pregnant rats at exposures that were lower than in patients receiving the recommended dose. ZYTIGA is contraindicated in women who are or may become pregnant while receiving the drug. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to the fetus and the potential risk for pregnancy loss. Advise females of reproductive potential to avoid becoming pregnant during treatment with ZYTIGA. In an embryo-fetal developmental toxicity study in rats, abiraterone acetate caused developmental toxicity when administered at oral doses of 10, 30 or 100 mg/kg/day throughout the period of organogenesis (gestational days 6-17). Findings included embryo-fetal lethality (increased post implantation loss and resorptions and decreased number of live fetuses), fetal developmental delay (skeletal effects) and urogenital effects (bilateral ureter dilation) at doses ≥10 mg/kg/day, decreased fetal ano-genital distance at ≥30 mg/kg/day, and decreased fetal body weight at 100 mg/kg/day. Doses ≥10 mg/kg/day caused maternal toxicity. The doses tested in rats resulted in systemic exposures (AUC) approximately 0.03, 0.1 and 0.3 times, respectively, the AUC in patients.

Nursing Mothers: ZYTIGA is not indicated for use in women. It is not known if abiraterone acetate is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from ZYTIGA, a decision should be made to either discontinue nursing, or discontinue the drug taking into account the importance of the drug to the mother.

Pediatric Use: Safety and effectiveness of ZYTIGA in pediatric patients have not been established.

Geriatric Use: Of the total number of patients receiving ZYTIGA in phase 3 trials, 73% of patients were 65 years and over and 30% were 75 years and over. No overall differences in safety or effectiveness were observed between these elderly patients and younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Patients with Hepatic Impairment: The pharmacokinetics of abiraterone were examined in subjects with baseline mild (n=8) or moderate (n=8) hepatic impairment (Child-Pugh Class A and B, respectively) and in 8 healthy control subjects with normal hepatic function. The systemic exposure (AUC) of abiraterone after a single oral 1,000 mg dose of ZYTIGA increased by approximately 1.1-fold and 3.6-fold in subjects with mild and moderate baseline hepatic impairment, respectively compared to subjects with normal hepatic function.

In another trial, the pharmacokinetics of abiraterone were examined in subjects with baseline severe (n=8) hepatic impairment (Child-Pugh Class C) and in 8 healthy control subjects with normal hepatic function. The systemic exposure (AUC) of abiraterone increased by approximately 7-fold and the fraction of free drug increased 2-fold in subjects with severe baseline hepatic impairment compared to subjects with normal hepatic function.

No dosage adjustment is necessary for patients with baseline mild hepatic impairment. In patients with baseline moderate hepatic impairment (ChildPugh Class B), reduce the recommended dose of ZYTIGA to 250 mg once daily. Do not use ZYTIGA in patients with baseline severe hepatic impairment (Child-Pugh Class C). If elevations in ALT or AST >5X ULN or total bilirubin >3X ULN occur in patients with baseline moderate hepatic impairment, discontinue ZYTIGA treatment [see Dosage and Administration (2.1) and Clinical Pharmacology (12.3) in full Prescribing Information].

For patients who develop hepatotoxicity during treatment, interruption of treatment and dosage adjustment may be required [see Dosage and Administration (2.2) in full Prescribing Information, Warnings and Precautions, and Clinical Pharmacology (12.3)] in full Prescribing Information.

Manufactured by: Patheon Inc. Mississauga, Canada Manufactured for: Janssen Biotech, Inc. Horsham, PA 19044 © Janssen Biotech, Inc. 2012 Revised: May 2014 015924-140528

2014 AUA Practice Management Conference

The Increasing Importance of Patient…Continued from the cover During his presentation, Jeffery Daigrepont, EFPM, Senior Vice President at Coker Group, noted that patient portals serve as an important part of practice–patient communication. He advised those who are preparing to implement a portal to take into consideration financial as well as regulatory factors, not just because of Meaningful Use requirements, but also because studies have shown that patients with online access tend to schedule more visits and are more likely to pay their bills.

“The studies we’ve done on patient portals tell us they do a remarkable job at improving collections,” said Mr Daigrepont. “If you can integrate it with a kiosk, that kiosk will never call in sick.

The kiosk works because the portal can actually be there in the waiting room to check in the patient and ask for a copayment.”

“If I’m at home and I want to see a printout of my statement, or if I want to pay online, I can do that,” he continued. “Any time you can make it convenient and easy for people to pay online, they’ll do it.”

Practices should determine the purpose of the portal, he said, such as whether it is a mechanism to facilitate scheduling appointments, or if there will be a back-and-forth exchange of information. Those implementing a portal should put appropriate checks and balances in place to maintain security and address user concerns.

Mr Daigrepont also suggested that prior to finalizing a vendor contract for a patient portal, practices should insist on adding a clause that states the practice is not financially responsible for the portal until it is

adopted by patients. This requires the vendor to partner with the practice in marketing and promoting the site. Otherwise, he stated, “you are paying for something before it is even adopted.”

•

ferrable so that the portal may be transferred to a new owner, and the value of the practice is not diminished if you sell it Demand a perpetual license so you are only paying for actual usage

“The studies we’ve done on patient portals tell us they do a remarkable job at improving collections. If you can integrate it with a kiosk, that kiosk will never call in sick. The kiosk works because the portal can actually be there in the waiting room to check in the patient and ask for a copayment.”

—Jeffery Daigrepont, EFPM

If the vendor is not willing to give you the title to future releases and new versions, this should be considered a deal breaker; some vendors sell a license, discontinue the product, and sell you a new license • Ensure that the vendor cannot disable your system immediately at termination.

“Vendors have become more competitive and are usually willing to give more concessions and be flexible in terms,” said Mr Daigrepont. “Those who are thinking they already signed their contract and it is too late; it isn’t. Every year you have to renew, and that is a perfect opportunity to tighten up a few things.” l

Other suggestions include: • Compose a request for proposal outlining what you are asking for and need • Include acceptance criteria that sets out exactly what has to happen before you start paying the vendor • Hold the vendor responsible for training your staff • Spread out the payment; Mr Daigrepont suggests 20% at signing, and similar payments after successful downloading and system testing, after successful staff training, after the system goes live, and the last 20% 30 days to 45 days after going live, ensuring there are no bugs • Confirm that licenses are trans-

October 2014

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Disaster Planning

Bringing the Future into the Present…Continued from the cover company data, jobs, personal safety, and patient care. Who do you think employees and patients will turn to in an emergency? You, the practice manager. You are the one who your team members expect to have a plan. If you have a good one, then you can help guide your company through a rough spot and get the organization back on its feet. Since you never know when a crisis may strike, the best time to prepare is now.

It is our hope that this article will serve as a guide to inspire you to start writing your plan, or to update or continue to add to the plan you have already developed. The authors will guide you through content to consider and provide checklists and tools to make preparation easier. The article will also focus on the coordination and communication necessary among staff and associates. For a jumpstart to planning, it may also be helpful to visit www. open-central.net to download a free disaster plan checklist.

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and Accountability Act (HIPAA) of 1996. Few people would argue that disaster planning is a waste of time, or that it is not important for maintaining patient safety and continuity of care. It is clearly good business practice to have a plan in place to ensure the financial stability of a practice, even—and especially—in the event of a disaster.

While we cannot control or predict the future, we can plan for it, and we are even required to do so.

Getting Started In 2004, Florida endured 4 hurricanes in a single season, and in 2005, Hurricane Katrina resulted in the displacement of large numbers of hematology/oncology patients, as well as medical practices. A great deal of time and resources were needed to help patients locate hematology/oncology physicians for continuity of care. Some patients had treatments delayed, or did not receive their treatments at all. Unfortunately, this scenario has been repeated throughout numerous disaster events across the country since 2005.

While we cannot control or predict the future, we can plan for it, and we are even required to do so by the Health Insurance Portability

Although it is recognized as important, seen as a sound business practice, and even mandated by federal law, how many oncology practices make disaster planning a priority? It seems to be one of those tasks that gets pushed to the back burner in favor of more immediate, more pressing needs in the office: those with high visibility that confront us daily, those that cannot be set on a back burner. Unfortunately, when a disaster strikes and its fallout is suddenly confronting and challenging us, it is too late to come up with a viable plan to get through.

The most effective plan is developed by a team so that it does not depend solely on 1 person. It will help to designate someone as the disaster plan coordinator to lead the team. Other members to consider are the office manager, information technology manager, human resources manager, and accounts payable/bookkeeper. The makeup of your team may vary depending on the size of your practice.

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Regardless of the titles assumed by those staff members, you will want to make sure that attention is given to the specific tasks discussed below.

The disaster plan coordinator will lead the team. Determine that person’s responsibilities, including oversight, to ensure each of the other team members maintains his or her assignments. Better yet, determine responsibilities with the person to gain buy-in and ownership in developing the plan. Then assign a backup disaster plan coordinator so that not everything is lost if the coordinator becomes unavailable in the event of an emergency.

Before Disaster Hits Below is an outline to guide your planning. Do not let the 10 steps overwhelm you, as you do not need to do them all at once or in order.

Pick and choose where to start, divide them among staff and do some simultaneously, or commit to a set number of hours you will work on the plan each week. Before you know it, you will be checking tasks off your list and feeling good about it.

Ten steps to take before disaster strikes:

1 2

Collect and organize emergency supplies (Table).

Maintain hard copy and electronic lists of important contact information. Keep copies in a secure place offsite. Lists may include business contacts such as your bank, chemotherapy supplier, biohazard waste disposal agency, office supplier, certified public accountant, or attorney. Include the name of the contact person, alternate contact person, product/ service, telephone number, fax number, and e-mail address. The list should also comprise staff, includ-

Disaster Planning

ing name, job description, home address, home telephone number, cell phone number, alternate telephone number, e-mail address, alternate e-mail address, emergency contact person, evacuation zone, initial notification, and subsequent notification.

3

Video and/or photograph your offices, equipment, and furniture inventory. Update it annually, and prior to any anticipated disaster (those with a 24-hour warning or more). Maintain copies both onsite and offsite.

4

Table Emergency Supplies Two flashlights Extra batteries Masking tape First aid kit stocked with aspirin, Tylenol, bandages, scissors, tweezers, antiemetics, adhesive tape, cold compresses, antibiotic ointment, disinfectant, cleaning solutions, burn treatment aloe, gauze, wound closures, safety pins, rubber gloves, saline, mask and CPR mask, sunblock Blood products Blankets and towels Extra clothing Portable radio Bottled water

Back up computer files on a regular basis (ie, financial records, patient clinical records, patient demographic information, business and staff contact information, insurance documents, and accounts payable records). Maintain them onsite and offsite.

Food

5

Summary contact list of all critical vendors and business entities, as discussed in the article

Prepare a script for your office telephone â&#x20AC;&#x153;on holdâ&#x20AC;? message.

This can be e-mailed or faxed to a vendor that can update the script for incoming phone calls as needed.

Can opener Extension cords Disinfectant agents Biohazard container or bag Emergency tools, including crowbar, handsaw, work gloves, goggles, axe, shovel, hard hats, duct tape, folding ladder for rescue operations, hammer, and pliers

Staff telephone list

Determine availability and ability to administer vaccinations for diseases such as polio, tetanus, hepatitis B, and hepatitis C.

as an electronic copy that is accessible through your website. Then, most importantly, make the plan available to all staff members. Conduct training to ensure everyone knows their roles and responsibilities in the event of a disaster. If appropriate, create an organization chart to show the chain of command in the event of a disaster. Update it annually through orientations, training sessions, and/ or emergency drills. The executive director of the practice should review and document the training at least once a year to ensure the plan is current and updated as needed.

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10

6

Establish a central phone number for patients to call, as well as an alternate phone number offsite.

7

Identify alternate physicians and hospitals for patient referral in the event of a disaster (ie, contact county, state, and national medical societies for recommendations on who to include).

8

Train staff. Once you have a written plan, keep a copy of it in a specific place in your office, as well

These are 10 valuable steps to take to prepare for a potential disaster. Remember to involve staff in preparations and preparedness.

Keeping team members informed will facilitate efforts should a disaster strike.

The first in a 2-part series, this article has addressed the importance of disaster planning and how to work with staff members to begin developing a disaster plan.

Watch for the final article in this series, which provides guidance on how to engage patients, with an emphasis on patients sharing responsibility for their care. It will also address what to do when a disaster is imminent and when a disaster strikes. l

Enroll in the Oncology Patient Emergency Network (OPEN) to ensure continuity of patient care.

October 2014

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Testing and Diagnostics

FDA to Regulate Laboratory-Developed Tests

By Rosemary Frei, MSc

T

he US Food and Drug Ad­­ ministration (FDA) recently took initial steps toward regulating laboratory-developed tests (LDTs). Used to select appropriate treatment for individual patients, LDTs are designed, made, and used within a single laboratory,1 and include genetic tests and tests used by clinicians to guide their patients’ treatment.

On July 31, 2014, the FDA announced it would take “impor­ tant steps to ensure that certain tests used by healthcare professionals to

standards for good laboratory practices under the Clinical Laboratory Improvement Amendments,3 and also state laws and accreditation requirements by relevant authorities.

However, with its announcement in mid-July, the FDA indicated it will publish a proposed risk-based oversight framework for LDTs.4 The framework was written, in part, because “the agency has serious concerns regarding the lack of independent review of the evidence of clinical validity of LDTs. Clinical validity is the ability of a diagnostic

“Failure of such tests to perform as intended can lead to patients receiving an inappropriate and potentially harmful treatment or, alternatively, not receiving a treatment that has the potential to benefit them.”

—Richard L. Schilsky, MD

help diagnose and treat patients provide accurate, consistent, and reliable results” by developing a framework for regulation of LDTs.2 Until now, the FDA has opted to “exercise enforcement discretion.”3 LDTs differ from tests sold to users such as hospitals and doctors’ offices; the latter are regulated as medical devices. There are approximately 2000 laboratories that produce LDTs in the United States.

The only standards that laboratories using LDTs have had to comply with are generally accepted

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device to measure or detect the clinical condition for which the device is intended. LDTs that have not been properly clinically validated for their intended use and are used to make critical clinical decisions potentially put patients at risk of missed or incorrect diagnosis, failure to administer appropriate treatment, or administration of potentially harmful treatment with no benefit.”3 The FDA will phase in the requirements over 9 years, beginning with high-risk tests—including those used in the decisions of

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October 2014

which therapy is best for individual patients or to screen for serious conditions such as malignant cancer3—that have the same intended use as an FDA-approved or cleared companion diagnostic test that is already on the market.3 The FDA will continue to exercise enforcement discretion for low-risk tests; these are tests with very few or no possible deleterious consequences of inaccurate results to patients; those aimed at diagnosing rare diseases; those that have no FDAapproved or cleared alternative; or those that are made for laboratories that are within healthcare facilities in which the patients who are being tested are also being treated.3 “Phasing in the requirements is a way not only to give the labs time to come into compliance, but [also so that] we can then adjust, based upon our resources, to provide the appropriate level of oversight,” said Jeffrey Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health, in a media teleconference on the day of the midsummer announcement.3 A few days earlier, a group of 23 pathologists and heads of diagnostic laboratories wrote to the head of the Office of Management and Budget.5 They urged that the FDA “refrain from issuing any draft, proposed, or final guidance document or rule that would purport to regulate LDTs as medical devices.” They expressed concern that, among other points, “FDA regulation of LDTs would stifle innovation, [and] be contrary to public health” due in part to the probable slowdown of test approval “under the rigid, inflexible, and duplicative [proposed] FDA regulatory scheme.”

Richard L. Schilsky, MD, chief

Testing and Diagnostics

medical officer, American Society of Clinical Oncology (ASCO), said the society supports the FDA’s approach, particularly with respect to genomic tests used to guide cancer treatment.

“Failure of such tests to perform as intended can lead to patients receiving an inappropriate and potentially harmful treatment or, alternatively, not receiving a treatment that has the potential to benefit them,” Dr Schilsky wrote in an e-mail. “In contemporary oncology practice, a patient’s treatment options are increasingly driven by detection of molecular abnormalities in the tumor that drive treatment selection. ASCO believes that tests used to detect those

abnormalities must be of the highest quality and thoroughly validated before being offered to doctors and patients. Our patients depend on high-quality tests as much as they depend on carefully studied, safe, and effective drugs to achieve the best possible outcomes.”

On July 31, the FDA also provided to Congress with a draft proposal on its LDT regulation. It also intends to publish a draft version of the LDT guidance this fall,1 and then to gather public comments for 90 days.1 Meanwhile, it has also produced a final guidance on the development, review, and approval or clearance of companion diagnostics, which are all types of tests used to identify patients who will benefit

or be harmed by treatment with a particular drug.2 l

References

1. US Food and Drug Administration. Laboratory developed tests. www.fda.gov/MedicalDevices/ ProductsandMedicalProcedures/InVitroDiagnostics/ ucm407296.htm. Accessed September 11, 2014.

2. US Food and Drug Administration. FDA takes steps to help ensure the reliability of certain diagnostic tests. News release. July 31, 2014. www.fda. gov/NewsEvents/Newsroom/PressAnnouncements/ ucm407321.htm. Accessed September 11, 2014.

3. US Food and Drug Administration. Framework for regulatory oversight of laboratory developed tests (LDTs). July 31, 2014. www.fda.gov/downloads/ MedicalDevices/ProductsandMedicalProcedures/ InVitroDiagnostics/UCM407409.pdf.

Accessed September 11, 2014.

4. US Food and Drug Administration. Transcript of media briefing on companion diagnostic final guidance and proposed risk-based oversight framework for laboratory developed tests. www.fda.gov/down loads/NewsEvents/Newsroom/MediaTranscripts/ UCM408370.pdf. Accessed September 11, 2014.

5. American Clinical Laboratory Association. July 16, 2014. www.acla.com/wp-content/uploads/2014/ 07/Letter-to-OMB-from-Lab-Leaders.pdf. Accessed September 11, 2014.

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www.ValueBasedCancer.com October 2014

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www.UroPracticeManagement.com

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Your Patients, Your Practice…

Helping Your Practice This comprehensive financial assistance program offers ongoing support across the reimbursement spectrum to help you help your patients.

Complete Provider Assistance Benefits verification Prior authorization tracking Regionally dedicated case managers Local access and reimbursement specialists Denied claims assistance Indication XTANDI (enzalutamide) capsules is indicated for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC).

Important Safety Information Contraindications XTANDI (enzalutamide) capsules can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals. XTANDI is not indicated for use in women. XTANDI is contraindicated in women who are or may become pregnant.

Warnings and Precautions In Study 1, conducted in patients with metastatic castration-resistant prostate cancer (CRPC) who previously received docetaxel, seizure occurred in 0.9% of patients who were treated with XTANDI and 0% treated with placebo. In Study 2, conducted in patients with chemotherapy-naïve metastatic CRPC, seizure occurred in 0.1% of patients who were treated with XTANDI and 0.1% treated with placebo. Patients experiencing a seizure were permanently discontinued from therapy and all seizure events resolved. There is no clinical trial experience re-administering XTANDI to patients who experienced a seizure, and limited clinical trial experience in patients with predisposing factors for seizure. Study 1 excluded the use of concomitant medications that may lower threshold, whereas Study 2 permitted the use of these medications.

Because of the risk of seizure associated with XTANDI use, patients should be advised of the risk of engaging in any activity during which sudden loss of consciousness could cause serious harm to themselves or others. Permanently discontinue XTANDI in patients who develop a seizure during treatment.

Adverse Reactions The most common adverse reactions (≥ 10%) reported from the two combined clinical trials that occurred more commonly (≥ 2% over placebo) in the XTANDI-treated patients were asthenia/fatigue, back pain, decreased appetite, constipation, arthralgia, diarrhea, hot flush, upper respiratory tract infection, peripheral edema, dyspnea, musculoskeletal pain, weight decreased, headache, hypertension, and dizziness/ vertigo.

Other Adverse Reactions include: • Laboratory Abnormalities: In the two studies, Grade 1-4 neutropenia occurred in 15% of patients treated with XTANDI (1% Grade 3-4) and in 6% of patients treated with placebo (0.5% Grade 3-4). The incidence of Grade 1-4 thrombocytopenia was 6% of patients treated with XTANDI (0.3% Grade 3-4) and 5% of patients on placebo (0.5% Grade 3-4). Grade 1-4 elevations in ALT occurred in 10% of patients treated with XTANDI (0.2% Grade 3-4) and 16% of patients treated with placebo (0.2% Grade 3-4). Grade 1-4 elevations in bilirubin occurred in 3% of patients treated with XTANDI

We’ve Got You Covered Helping Your Patients Financial assistance is available for patients.* Private Insurance $5000/month copay assistance, up to $12,000/year

Medicare/Medicaid Referrals to Independent Copay Foundations†

Uninsured or Underinsured Free XTANDI® (enzalutamide) capsules

New Patients Awaiting Coverage Decision Free XTANDI through XTANDI Quick Start+™ Program

*Subject to eligibility. Void where prohibited by law. Restrictions may apply. † XTANDI Support SolutionsSM has no control over the decisions made by and does not guarantee support by these independent copay foundations.

To learn more about XTANDI Support Solutions or enroll your patients today:

1-855-8XTANDI (855-898-2634) 8 AM – 8 PM ET

(0.1% Grade 3-4) and 2% of patients treated with placebo (no Grade 3-4).

• Infections: In Study 1, 1% of XTANDI versus 0.3% of placebo patients and in Study 2, 1 patient in each treatment group (0.1%) had an infection resulting in death.

• Falls: In the two studies, falls including fall-related injuries occurred in 9% of XTANDI patients vs 4% treated with placebo. Falls were not associated with loss of consciousness or seizure. Fall-related injuries were more severe in XTANDI patients and included non-pathologic fractures, joint injuries, and hematomas.

• Hypertension: In the two studies, hypertension was reported in 11% of patients receiving XTANDI and 4% of patients receiving placebo. No patients experienced hypertensive crisis. Medical history of hypertension was balanced between arms. Hypertension led to study discontinuation in < 1% of XTANDI or placebo treated patients.

Drug Interactions • Effect of Other Drugs on XTANDI – Administration of strong CYP2C8 inhibitors can increase the plasma exposure to XTANDI. Co-administration of XTANDI with strong CYP2C8 inhibitors should be avoided if possible.

If co-administration of XTANDI cannot be avoided,

XTANDISupportSolutions.com

reduce the dose of XTANDI. Co-administration of XTANDI with strong or moderate CYP3A4 and CYP2C8 inducers may alter the plasma exposure of XTANDI and should be avoided if possible.

• Effect of XTANDI on Other Drugs – XTANDI is a strong CYP3A4 inducer and a moderate CYP2C9 and CYP2C19 inducer in humans. Avoid CYP3A4, CYP2C9 and CYP2C19 substrates with a narrow therapeutic index, as XTANDI may decrease the plasma exposures of these drugs. If XTANDI is co-administered with warfarin (CYP2C9 substrate), conduct additional INR monitoring.

PLEASE SEE BRIEF SUMMARY OF COMPLETE PRESCRIBING INFORMATION ON FOLLOWING PAGES.

XTANDI Support SolutionsSM, a component of Astellas Access ServicesSM 1-855-8XTANDI (1-855-898-2634); Fax 1-855-982-6341; XTANDISupportSolutions.com ©2014 Astellas Pharma US, Inc. All rights reserved. 076-0329-PM 9/14 Printed in USA XTANDI, Astellas, and the flying star logo are trademarks of Astellas Pharma, Inc.

XTANDI® (enzalutamide) capsules for oral use Initial U.S. Approval: 2012 BRIEF SUMMARY OF PRESCRIBING INFORMATION The following is a brief summary. Please see the package insert for full prescribing information.

INDICATIONS AND USAGE

Grade 3 and higher adverse reactions were reported among 47% of XTANDI-treated patients and 53% of placebo-treated patients. Discontinuations due to adverse events were reported for 16% of XTANDI-treated patients and 18% of placebo-treated patients. The most common adverse reaction leading to treatment discontinuation was seizure, which occurred in 0.9% of the XTANDI-treated patients compared to none (0%) of the placebo-treated patients. Table 1 shows adverse reactions reported in Study 1 that occurred at a ≥ 2% higher frequency in the XTANDI arm compared to the placebo arm.

Table 1. Adverse Reactions in Study 1 (cont.)

Respiratory Disorders

Table 1. Adverse Reactions in Study 1

Seizure In Study 1, which enrolled patients who previously received docetaxel, 7 of 800 (0.9%) patients treated with XTANDI experienced a seizure and no patients treated with placebo experienced a seizure. Seizure occurred from 31 to 603 days after initiation of XTANDI. In Study 2, 1 of 871 (0.1%) chemotherapy-naive patients treated with XTANDI and 1 of 844 (0.1%) patients treated with placebo experienced a seizure. Patients experiencing seizure were permanently discontinued from therapy and all seizure events resolved. There is no clinical trial experience readministering XTANDI to patients who experienced seizure.

Limited safety data are available in patients with predisposing factors for seizure because these patients were generally excluded from the trials. These exclusion criteria included a history of seizure, underlying brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain metastases, and brain arteriovenous malformation. Study 1 excluded the use of concomitant medications that may lower the seizure threshold, whereas Study 2 permitted the use of these medications.

Because of the risk of seizure associated with XTANDI use, patients should be advised of the risk of engaging in any activity where sudden loss of consciousness could cause serious harm to themselves or others. Permanently discontinue XTANDI in patients who develop a seizure during treatment.

ADVERSE REACTIONS Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Two randomized clinical trials enrolled patients with metastatic prostate cancer that has progressed on androgen deprivation therapy (GnRH therapy or bilateral orchiectomy), a disease setting that is also defined as metastatic CRPC. In both studies, patients received XTANDI 160 mg orally once daily in the active treatment arm or placebo in the control arm. All patients continued androgen deprivation therapy. Patients were allowed, but not required, to take glucocorticoids.

The most common adverse reactions (≥ 10%) that occurred more commonly (≥ 2% over placebo) in the XTANDI-treated patients from the two randomized clinical trials were asthenia/fatigue, back pain, decreased appetite, constipation, arthralgia, diarrhea, hot flush, upper respiratory tract infection, peripheral edema, dyspnea, musculoskeletal pain, weight decreased, headache, hypertension, and dizziness/vertigo.

Study 1: Metastatic Castration-Resistant Prostate Cancer Following Chemotherapy Study 1 enrolled 1199 patients with metastatic CRPC who had previously received docetaxel. The median duration of treatment was 8.3 months with XTANDI and 3.0 months with placebo. During the trial, 48% of patients on the XTANDI arm and 46% of patients on the placebo arm received glucocorticoids.

0.1

1.3

0.3

26.4

5.3

24.3

4.0

Arthralgia 20.5 Musculoskeletal 15.0 Pain Muscular 9.8 Weakness Musculoskeletal 2.6 Stiffness Gastrointestinal Disorders

2.5

17.3

1.8

1.3

11.5

0.3

Table 2. Adverse Reactions in Study 2

1.5

6.8

1.8

0.3

0.3

0.0

21.8

1.1

17.5

0.3

Hot Flush

20.3

0.0

10.3

0.0

Hypertension

6.4

2.1

2.8

1.3

Grade 1-4a (%)

CONTRAINDICATIONS

WARNINGS AND PRECAUTIONS

3.3

CTCAE v4 Includes asthenia and fatigue.

Includes dizziness and vertigo.

Includes amnesia, memory impairment, cognitive disorder, and disturbance in attention. e Includes nasopharyngitis, upper respiratory tract infection, sinusitis, rhinitis, pharyngitis, and laryngitis. f Includes pneumonia, lower respiratory tract infection, bronchitis, and lung infection.

Study 2: Chemotherapy-naive Metastatic CastrationResistant Prostate Cancer Study 2 enrolled 1717 patients with metastatic CRPC who had not received prior cytotoxic chemotherapy, of whom 1715 received at least one dose of study drug. The median duration of treatment was 17.5 months with XTANDI and 4.6 months with placebo. Grade 3-4 adverse reactions were reported in 44% of XTANDItreated patients and 37% of placebo-treated patients.

Discontinuations due to adverse events were reported for 6% of XTANDI-treated patients and 6% of placebo-treated patients. The most common adverse reaction leading to treatment discontinuation was fatigue/asthenia, which occurred in 1% of patients on each treatment arm. Table 2 includes adverse reactions reported in Study 2 that occurred at a ≥ 2% higher frequency in the XTANDI arm compared to the placebo arm.

XTANDI N = 800

XTANDI is indicated for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC).

Pregnancy XTANDI can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals. XTANDI is not indicated for use in women. XTANDI is contraindicated in women who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to the fetus and the potential risk for pregnancy loss [see Use in Specific Populations (8.1)].

Epistaxis a b c d

General Disorders Asthenic Conditionsb Peripheral Edema

Placebo N = 399

Grade Grade Grade 3-4 1-4 3-4 (%) (%) (%)

50.6

9.0

44.4

9.3

15.4

1.0

13.3

0.8

Musculoskeletal And Connective Tissue Disorders Back Pain

Diarrhea Vascular Disorders

Nervous System Disorders Headache

12.1

0.9

5.5

0.0

Dizzinessc Spinal Cord Compression and Cauda Equina Syndrome Paresthesia Mental Impairment Disordersd Hypoesthesia

9.5

0.5

7.5

0.5

7.4

6.6

4.5

3.8

XTANDI N = 871 Grade 1-4a (%)

Grade 3-4 (%)

Placebo N = 844 Grade 1-4 (%)

Grade 3-4 (%)

General Disorders Asthenic 46.9 3.4 33.0 2.8 Conditionsb Peripheral 11.5 0.2 8.2 0.4 Edema Musculoskeletal And Connective Tissue Disorders Back Pain

28.6

2.5

22.4

3.0

Arthralgia

21.4

1.6

16.1

1.1

Gastrointestinal Disorders

6.6

0.0

4.5

0.0

4.3

0.3

1.8

0.0

4.0

Infections And Infestations Upper Respiratory Tract 10.9 Infectione Lower Respiratory 8.5 Tract And Lung Infectionf Psychiatric Disorders

0.3

1.8

0.0

0.0

6.5

0.3

2.4

4.8

1.3

Insomnia

8.8

0.0

6.0

0.5

Anxiety

6.5

0.3

4.0

0.0

Renal And Urinary Disorders Hematuria

6.9

1.8

4.5

1.0

Pollakiuria

4.8

0.0

2.5

0.0

Injury, Poisoning And Procedural Complications Fall 4.6 0.3 1.3 Non-pathologic 4.0 1.4 0.8 Fractures Skin And Subcutaneous Tissue Disorders

0.0 0.3

Pruritus

3.8

0.0

1.3

0.0

Dry Skin

3.5

0.0

1.3

0.0

Constipation

23.2

0.7

17.3

0.4

Diarrhea

16.8

0.3

14.3

0.4

Vascular Disorders Hot Flush

18.0

0.1

7.8

0.0

Hypertension

14.2

7.2

4.1

2.3

Nervous System Disorders Dizzinessc

11.3

0.3

7.1

0.0

Headache

11.0

0.2

7.0

0.4

Dysgeusia

7.6

0.1

3.7

0.0

5.7

0.0

1.3

0.1

2.1

0.1

0.4

0.0

0.6

8.5

0.6

10.5

0.0

4.7

1.1

5.7

0.0

Mental Impairment Disordersd Restless Legs Syndrome

Respiratory Disorders Dyspneae

11.0

Infections And Infestations Upper Respiratory 16.4 0.0 Tract Infectionf Lower Respiratory Tract And 7.9 1.5 Lung Infectiong Psychiatric Disorders Insomnia

8.2

0.1

Table 2. Adverse Reactions in Study 2 (cont.)

Renal And Urinary Disorders Hematuria

8.8

1.3

5.8

1.3

Injury, Poisoning And Procedural Complications Fall

12.7

1.6

5.3

NonPathological 8.8 2.1 3.0 Fracture Metabolism and Nutrition Disorders Decreased 18.9 0.3 16.4 Appetite

0.7 1.1

0.7

Investigations Weight Decreased

12.4

0.8

8.5

0.2

Reproductive System and Breast Disorders Gynecomastia

3.4

0.0

1.4

0.0

a b c d

CTCAE v4 Includes asthenia and fatigue.

Includes dizziness and vertigo.

Includes amnesia, memory impairment, cognitive disorder, and disturbance in attention. e Includes dyspnea, exertional dyspnea, and dyspnea at rest. f Includes nasopharyngitis, upper respiratory tract infection, sinusitis, rhinitis, pharyngitis, and laryngitis. g Includes pneumonia, lower respiratory tract infection, bronchitis, and lung infection.

Laboratory Abnormalities In the two randomized clinical trials, Grade 1-4 neutropenia occurred in 15% of patients treated with XTANDI (1% Grade 3-4) and in 6% of patients treated with placebo (0.5% Grade 3-4).

The incidence of Grade 1-4 thrombocytopenia was 6% of patients treated with XTANDI (0.3% Grade 3-4) and 5% of patients treated with placebo (0.5% Grade 3-4). Grade 1-4 elevations in ALT occurred in 10% of patients treated with XTANDI (0.2% Grade 3-4) and 16% of patients treated with placebo (0.2% Grade 3-4). Grade 1-4 elevations in bilirubin occurred in 3% of patients treated with XTANDI (0.1% Grade 3-4) and 2% of patients treated with placebo (no Grade 3-4).

Infections In Study 1, 1% of patients treated with XTANDI compared to 0.3% of patients treated with placebo died from infections or sepsis. In Study 2, 1 patient in each treatment group (0.1%) had an infection resulting in death.

Falls and Fall-related Injuries In the two randomized clinical trials, falls including fall-related injuries, occurred in 9% of patients treated with XTANDI compared to 4% of patients treated with placebo. Falls were not associated with loss of consciousness or seizure. Fall-related injuries were more severe in patients treated with XTANDI and included non-pathologic fractures, joint injuries, and hematomas.

Hypertension In the two randomized trials, hypertension was reported in 11% of patients receiving XTANDI and 4% of patients receiving placebo. No patients experienced hypertensive crisis. Medical history of hypertension was balanced between arms. Hypertension led to study discontinuation in < 1% of patients in each arm.

DRUG INTERACTIONS Drugs that Inhibit or Induce CYP2C8 Co-administration of a strong CYP2C8 inhibitor (gemfibrozil) increased the composite area under the plasma concentration-time curve (AUC) of enzalutamide plus N-desmethyl enzalutamide by 2.2-fold in healthy volunteers. Co-administration of XTANDI with strong CYP2C8 inhibitors should be avoided if possible. If co-administration of XTANDI with a strong CYP2C8 inhibitor cannot be avoided, reduce the dose of XTANDI [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)].

The effects of CYP2C8 inducers on the pharmacokinetics of enzalutamide have not been evaluated in vivo.

Co-administration of XTANDI with strong or moderate CYP2C8 inducers (e.g., rifampin) may alter the plasma exposure of XTANDI and should be avoided if possible.

Selection of a concomitant medication with no or minimal CYP2C8 induction potential is recommended [see Clinical Pharmacology (12.3)].

Drugs that Inhibit or Induce CYP3A4 Co-administration of a strong CYP3A4 inhibitor (itraconazole) increased the composite AUC of enzalutamide plus N-desmethyl

enzalutamide by 1.3-fold in healthy volunteers [see Clinical Pharmacology (12.3)].

The effects of CYP3A4 inducers on the pharmacokinetics of enzalutamide have not been evaluated in vivo.

Co-administration of XTANDI with strong CYP3A4 inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine) may decrease the plasma exposure of XTANDI and should be avoided if possible.

Selection of a concomitant medication with no or minimal CYP3A4 induction potential is recommended. Moderate CYP3A4 inducers (e.g., bosentan, efavirenz, etravirine, modafinil, nafcillin) and St. John’s Wort may also reduce the plasma exposure of XTANDI and should be avoided if possible [see Clinical Pharmacology (12.3)].

Effect of XTANDI on Drug Metabolizing Enzymes Enzalutamide is a strong CYP3A4 inducer and a moderate CYP2C9 and CYP2C19 inducer in humans. At steady state, XTANDI reduced the plasma exposure to midazolam (CYP3A4 substrate), warfarin (CYP2C9 substrate), and omeprazole (CYP2C19 substrate). Concomitant use of XTANDI with narrow therapeutic index drugs that are metabolized by CYP3A4 (e.g., alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus and tacrolimus), CYP2C9 (e.g., phenytoin, warfarin) and CYP2C19 (e.g., S-mephenytoin) should be avoided, as enzalutamide may decrease their exposure. If co-administration with warfarin cannot be avoided, conduct additional INR monitoring [see Clinical Pharmacology (12.3)].

USE IN SPECIFIC POPULATIONS Pregnancy - Pregnancy Category X [see Contraindications (4)].

Risk Summary XTANDI can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals. While there are no human data on the use of XTANDI in pregnancy and XTANDI is not indicated for use in women, it is important to know that maternal use of an androgen receptor inhibitor could affect development of the fetus. Enzalutamide caused embryofetal toxicity in mice at exposures that were lower than in patients receiving the recommended dose. XTANDI is contraindicated in women who are or may become pregnant while receiving the drug. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to the fetus and the potential risk for pregnancy loss. Advise females of reproductive potential to avoid becoming pregnant during treatment with XTANDI. Animal Data In an embryo-fetal developmental toxicity study in mice, enzalutamide caused developmental toxicity when administered at oral doses of 10 or 30 mg/kg/day throughout the period of organogenesis (gestational days 6-15). Findings included embryo-fetal lethality (increased post-implantation loss and resorptions) and decreased anogenital distance at ≥ 10 mg/kg/day, and cleft palate and absent palatine bone at 30 mg/kg/day. Doses of 30 mg/kg/day caused maternal toxicity. The doses tested in mice (1, 10 and 30 mg/kg/day) resulted in systemic exposures (AUC) approximately 0.04, 0.4 and 1.1 times, respectively, the exposures in patients. Enzalutamide did not cause developmental toxicity in rabbits when administered throughout the period of organogenesis (gestational days 6-18) at dose levels up to 10 mg/kg/day (approximately 0.4 times the exposures in patients based on AUC).

Nursing Mothers XTANDI is not indicated for use in women. It is not known if enzalutamide is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from XTANDI, a decision should be made to either discontinue nursing, or discontinue the drug taking into account the importance of the drug to the mother.

Pediatric Use Safety and effectiveness of XTANDI in pediatric patients have not been established.

Geriatric Use Of 1671 patients who received XTANDI in the two randomized clinical trials, 75% were 65 and over, while 31% were 75 and over. No overall differences in safety or effectiveness were observed between these patients and younger patients. Other reported clinical

experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Patients with Renal Impairment A dedicated renal impairment trial for XTANDI has not been conducted.

Based on the population pharmacokinetic analysis using data from clinical trials in patients with metastatic CRPC and healthy volunteers, no significant difference in enzalutamide clearance was observed in patients with pre-existing mild to moderate renal impairment (30 mL/min ≤ creatinine clearance [CrCL] ≤ 89 mL/min) compared to patients and volunteers with baseline normal renal function (CrCL ≥ 90 mL/min). No initial dosage adjustment is necessary for patients with mild to moderate renal impairment. Severe renal impairment (CrCL < 30 mL/min) and end-stage renal disease have not been assessed [see Clinical Pharmacology (12.3)].

Patients with Hepatic Impairment A dedicated hepatic impairment trial compared the composite systemic exposure of enzalutamide plus N-desmethyl enzalutamide in volunteers with baseline mild or moderate hepatic impairment (Child-Pugh Class A and B, respectively) versus healthy controls with normal hepatic function.

The composite AUC of enzalutamide plus N-desmethyl enzalutamide was similar in volunteers with mild or moderate baseline hepatic impairment compared to volunteers with normal hepatic function. No initial dosage adjustment is necessary for patients with baseline mild or moderate hepatic impairment. Baseline severe hepatic impairment (Child-Pugh Class C) has not been assessed [see Clinical Pharmacology (12.3)].

OVERDOSAGE In the event of an overdose, stop treatment with XTANDI and initiate general supportive measures taking into consideration the half-life of 5.8 days. In a dose escalation study, no seizures were reported at < 240 mg daily, whereas 3 seizures were reported, 1 each at 360 mg, 480 mg, and 600 mg daily. Patients may be at increased risk of seizure following an overdose.

NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term animal studies have not been conducted to evaluate the carcinogenic potential of enzalutamide.

Enzalutamide did not induce mutations in the bacterial reverse mutation (Ames) assay and was not genotoxic in either the in vitro mouse lymphoma thymidine kinase (Tk) gene mutation assay or the in vivo mouse micronucleus assay.

Based on nonclinical findings in repeat-dose toxicology studies, which were consistent with the pharmacological activity of enzalutamide, male fertility may be impaired by treatment with XTANDI. In a 26-week study in rats, atrophy of the prostate and seminal vesicles was observed at ≥ 30 mg/kg/day (equal to the human exposure based on AUC). In 4-, 13-, and 39-week studies in dogs, hypospermatogenesis and atrophy of the prostate and epididymides were observed at ≥ 4 mg/kg/day (0.3 times the human exposure based on AUC).

Manufactured by: Catalent Pharma Solutions, LLC, St. Petersburg, FL 33716 Manufactured for and Distributed by: Astellas Pharma US, Inc., Northbrook, IL 60062 Marketed by: Astellas Pharma US, Inc., Northbrook, IL 60062 Medivation, Inc., San Francisco, CA 94105 Revised: September 2014 14B006-XTA-BRFS Rx Only © 2014 Astellas Pharma US, Inc. XTANDI® is a registered trademark of Astellas Pharma Inc.

076-0472-PM

Financial Advocacy

Connecting Patients to Resources

By Sheryl Riley, RN, OCN, CMCN

C

20

hanges in our economy and healthcare system (ie, the Affordable Care Act, accountable care organizations, evolving reimbursement models) have given birth to a new member of the healthcare team: the financial advocate. Although many hospitals and large clinics have some form of patient advocates and nurse navigators, not all of these professionals are trained in the complex financial issues inherent to the care of treating a patient with cancer. Furthermore, many professionals are too thinly spread, and see too many patients to develop an expertise in advising on any single disease type.

Cancer is one of those disease processes that is particularly challenging and requires specialized knowledge of the complex nature of diagnosis, copayment, coinsurance, drug assistance, and financial assistance. Most facilities have only one advocate who serves many purposes, which again creates difficulty in being an expert in financial assistance options for patients with one disease type.

I recently attended a conference about financial advocacy.

I was delighted to see so many people from all over the country in attendance. It afforded me the opportunity to speak with as many professionals as possible, and augment my knowledge on the specifics of what they do and how they do it. I had the assumption before attending that financial advocates would be mostly nurses and social workers, but I was mistaken; it was a diverse group. Some of the advocates were laypersons who got involved due to a personal experience and decided to make it a career, while others were nurses and social

workers. Some had degrees in education, finance, or communications. Regardless of everyoneâ&#x20AC;&#x2122;s backgrounds, their common goal was to advocate for patients.

I

I

UROLOGY PRACTICE MANAGEMENT

During the presentation, the speakers acknowledged that the bulk of financial advocacy work is done by laypersons with little or no college education. The highest level of education of the majority of the people employed in this job is a high school diploma; this was both fascinating and reassuring.

The mix of clinical, psychosocial, and nonclinical professionals working together in concert provides the best combination for patients and their families. I had a chance to speak with some of the advocates and was delighted to see how they have embraced the role to become experts in finding resources, reimbursement, and supportive services for patients, providers, and families.

These advocates were particularly engaging, possessed a wealth of knowledge, and were extremely passionate about their work.

In my conversations, I discovered some important information about the number of patients they service and how their services are supported.

October 2014

Advocates were not limited to hospitals and clinics, as large physician practices were jumping on board as well. One aspect that I found particularly fascinating was that some facilities have disease-specific and drug assistance advocates. Only a handful had specific advocates for nonmedical-related expenses and issues. Through these conversations, combined with further research I did after the conference, I discovered that regardless of who is performing the job, there are never enough financial advocates to meet the needs of our patients.

Realities of Patients with Cancer Comprehending a cancer diagnosis is not something anyone wants to deal with, and the cost of care is the last thing that most patients want to wrap their mind around. The cost of having cancer and/or surviving cancer presents many challenges for the patients, caregivers, families, and providers.

Skyrocketing healthcare costs, the price of drugs, plus physician fees and other commodities, such as time off from work, healthcare premiums, copay and coinsurance, possible loss of income, meals, transportation, and other services, can be overwhelming to a person newly diagnosed with cancer.

A survey conducted in 2012 by the Association of Community Cancer Centers, â&#x20AC;&#x153;Cancer Care Trends in Community Cancer Centers,â&#x20AC;? demonstrated that nearly all of respondents reported that they were seeing more patients who needed help with copays and/or coinsurance. Community cancer centers were spending increased time assisting patients with identifying resources to help with costs for medications,

Financial Advocacy

missed work hours, transportation, and more.

A survey conducted by the Association of Oncology Social Work (AOSW) revealed that for more than one half of patients with cancer, treatment costs negatively impact their focus on recovery.

According to the survey, 66% of patients with major financial challenges suffer with depression or anxiety, 29% delay filling prescriptions due to financial pressures, and 22% skip doses. Sixty-three percent of surveyed oncology social workers said financial issues reduce compliance with treatment, and 55% of patients surveyed said the stress of dealing with costs impaired their ability to focus on their recovery. In addition, 40% of patients surveyed had depleted their savings, nearly 30% reported dealing with bill collectors, 54% of those handling a major financial burden said it had become more difficult in the past year to afford treatment, and 68% of responses reported that patients experience financial hardship from the medical bills.

Only 36% of patients have discussed treatment costs with their oncologist, and only 16% of patients and caregivers report that they believe their oncologists even think about the financial implications of the treatments they prescribe. In fact, only about one half of patients feel comfortable speaking with health professionals about financial issues. Too often the physician does not address cost with the patient until after treatment is under way and the patient receives the first bill. This can be devastating to the patient, and hinder the success of treatment by causing incredible stress, anxiety, and depression.

Findings show that at initial diagnosis, nearly all cancer patients consider treatment effectiveness before all other factors when determining their therapy, ranking the

cost of treatment last in their decision-making process. The physicians can supply the knowledge and expertise of care, and financial advisors will help patients navigate through the nonclinical, which is

• 6% of patients sold a home or relocated due to the financial stress, and 3% experienced a home foreclosure.

• 56% of patients were not at all prepared to handle the financial burden of cancer, while only 7% indicated they were completely prepared for it.

Cancer is one of those disease processes that is particularly challenging and requires specialized knowledge of the complex nature of diagnosis, copayment, coinsurance, drug assistance, and financial assistance.

Value of Financial Advisors These numbers tell the story as to why this new emerging profession is so important to the success of cancer treatment. Physicians are faced with many challenges regarding diagnosis, treatment, and care for their patients with cancer, but many do not realize the impact that finances play in patients’ decisions and how it can hinder care. Acknowledgment of this other component to oncology care should assist oncology practices in making the decision to create a position for a financial advocate within their office. It is another salary to pay, but the return on investment is a decrease in the burden on current staff. Current staff members do not have adequate time or resources to provide financial assistance services or reimbursement reduction with the recent increase in underinsured patients.

Physician practices are then faced with balancing a good patient experience with financial concerns. The financial advocate knows how to speak with patients and their families about all the difficult topics, and assist the oncology practice in meeting the growing financial concerns of their patients, streamlining the billing, appeals, denial, verification, and drug assistance or replacement programs. Easing financial concerns have been proven to decrease stress, anxiety, and depression, and help the patient focus on recovery. Financial advocates pay for themselves by giving the oncologist, the patient, and their families peace of mind during a difficult and frightening time. l

just as significant in the patient’s success in fighting, beating, and surviving this complex disease.

Data show that the stress related to finances can impact compliance and potentially present serious consequences. Consider these statistics from the AOSW survey: • Treatment costs negatively impact the ability to focus on recovery for 87% of patients with catastrophic or major financial burdens due to cancer treatment, and 75% of these patients constantly worry about financial issues due to cancer treatment.

• Almost one half (46%) of patients who have experienced a financial burden from their cancer have cut back on necessary expenses such as food to pay for cancer treatment.

• 24% of respondents indicated they suffered a relationship issue in their efforts to afford treatment for cancer.

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Physician–Hospital Alignment Series

Do’s and Don’ts in Physician–Hospital Alignment, Part 3

By Max Reiboldt, CPA, President/CEO, Coker Group, Alpharetta, GA

T

he alignment of physicians with hospitals and health systems can be challenging in today’s healthcare climate, yet interest in alignment continues to expand. In some instances, the necessity of maintaining a strong and diverse medical staff coupled with the threat of losing critical team members and the subsequent closure of a business line may result in hospitals and health systems making decisions and promises they may not otherwise make.

Considering these concerns, this series of articles on physician­–hospital alignments has explored topics relevant to those who are considering a relationship between practices and hospital systems. The first 2 articles in this series discussed pretransactional due diligence, structural design processes, governance, and compensation plans. In this third and final installment, ongoing and posttransactional relationships are explored; accountability, transparency, partnerships, and the use of information technology are discussed in detail.

Ongoing Relationships Once an alignment transaction takes place, the involved parties have to continue to work together.

Sometimes, with the challenges of trying to put a deal together, efforts to provide a fully transparent and accountable posttransaction structure can be overlooked. In order for any such affiliation structure to stand the test of time, there must be a very clear and open process in place for sharing information, data, and overall performance.

Accountability is an impor­

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tant facet of any posttransaction relationship; both parties must be accountable to each other. For example, the employed physi-

Sometimes, with the challenges of trying to put a deal together, efforts to provide a fully transparent and accountable posttransaction structure can be overlooked.

cian must be accountable to his employer. This means everything from normal work performance to equipping oneself to meet the dayto-day responsibilities of the position. However, accountability also applies to the employer. In this case, the employer is often the hospital, and the hospital should realize and buy into the concept that they must fulfill the things they com-

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mitted to during the prealignment discussions. Anything less should result in some form of reconciliation between both parties.

Transparency is also of great importance. Most employees (or physicians who are not fully aligned but significantly tied to a health system) seek some form of transparency. This may manifest as sharing of information and data (including performance) as well as openness in decision-making, not unlike the governance and leadership discussion considered in Part 2 of this series. Thus, an attitude of sharing appropriate information and data is key to building a long-term and sustaining relationship.

Partnering actions are also an important part of the behavior of both parties posttransaction. So much work, effort, and emphasis are placed on getting the deal done that this issue often is overlooked.

Consequently, people start to take others for granted, which inevitably compromises trust, transparency, and accountability. Although true partnering initiatives may not be the legal structure in each arrangement, an attitude of partnering is extremely important for the longterm sustainability of the alignment transaction.

Another key to success in the ongoing relationship posttransaction is the level and degree of information technology (IT) use.

This is related to transparency, but is really much greater than just sharing information. IT in the current healthcare environment is an absolute essential. It is imperative to be able to pull together data from a clinical standpoint that can

Physician–Hospital Alignment Series

be shared over a large number of participating providers. Such forms of clinical integration are critical to the long-term success of both the hospital and the physician going forward. Education is important in this process; that is, teaching and acquainting the physicians with some level of thoroughness relative to what IT is capable of doing as well as the nuances of how best to get information into the system.

When physicians are under great stress to be productive (which can largely be tied to their compensation), the aggravation of working with an IT system that is only partly functional does not create a longterm trusting relationship or success in the alignment strategy.

Building trust and respect, therefore, is a great way to summarize these matters. Understanding roles, keeping accountability well defined, and sharing information through a

transparent mechanism is a sound formula for success as it relates to these alignment structures.

done, inevitably issues will arise that have not been specifically considered. This calls for cooler heads to prevail, with members of management of both the hospital and the physician group sitting down and doing what is best for the entire process. Often, this means reaching a compromised solution, maybe even one that is not quite as preferable to both compromising parties. Nonetheless, compromises are essential in the spirit of working together, now and in the future, postunwind.

Planning for the Unwind Possibilities Although no one likes to talk about the potential for divorce, particularly prior to the marriage, these possibilities must be addressed and well documented prior to consummation of the alignment structure. There are ways to provide the physicians with a “soft landing” in an unwind that does not hurt the hospital, and, in the long run, could be very helpful. This should be the approach of the parties involved.

Moreover, specific unwind protocols and policies should be defined so there are no misunderstandings as to how certain calculations will be completed or other matters resolved relevant to the unwind process. Assuming this has been

Summary Many do’s and don’ts apply to the entire concept of physician–hospital alignments, with variations from the very form or definition of the alignment model to the details of that model. Alignment requires a great deal of planning, expertise, and, in many instances, an independent party to help mediate the process.

If these matters are addressed and appropriate agreements reached and then consistently applied, the chances for a most successful transaction are much enhanced for the hospital, health systems, and the physicians with whom they are aligning. l

KEY POINTS With the challenges of putting a deal together, efforts to provide a fully transparent and accountable post-transaction structure can be overlooked.

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Accountability is an important facet of any post-transaction relationship, and the physician and hospital must be accountable to each other.

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This is the final article in a 3-part series on physician–hospital alignments. To review Part 1 and Part 2 of this series, which appeared in the June 2014 and August 2014 issues of Urology Practice Management, respectively, visit www.uropractice management.com. Click on “Issues” for a drop-down selection of previous journal issues and select the appropriate issue.

Transparency, or an attitude of sharing appropriate information and data, is key to sustaining an alignment relationship.

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An attitude of partnership is also extremely important to sustaining a long-term alignment relationship.

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Effective use of information technology is essential, as is the ability to pull together data from a clinical standpoint that can be shared over a large number of providers.

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Be prepared for issues that may arise from restructuring, and aim for trust, respect, and compromises.

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Urology Practice Management is now available online at: www.UroPracticeManagement.com

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Perspective

Financial Toxicity: The Elephant in the (Side Effect) Room

By Barry D. Brooks, MD, Chair, US Oncology P&T Committee, McKesson Specialty Health, Texas Oncology

W

e have all had that patient—the patient who is prescribed a new targeted therapy and cannot comply with it because it is just too expensive. When asked directly about the reasoning for the noncompliance, the patient suggests that taking the treatment is just too expensive and, in fact, it is cheaper to die.

Financial Toxicity Is a Medical Side Effect In 2013, Zafar, Ubel, and their Duke colleagues, introduced a new term for an important, frequently undisclosed side effect of modern cancer therapy: financial toxicity.1-3 They persuasively argued that financial toxicity should be treated like any medical side effect, because it is as likely as any physical toxicity to cause noncompliance with a prescribed regimen.

I enthusiastically embraced the term and began using it in my everyday lexicon with patients, payers, and my colleagues. Unfortunately, after the 3 publications from the Duke team in 2013, “financial toxicity” has not found its way into publications and essays that focus on the financial burden resulting from increasing copays, coinsurance, and high deductibles introduced in the Affordable Care Act era.

A poignant study by Dusetzina and colleagues published this year reported that commercial patients with chronic myelogenous leukemia (CML) and higher copays were

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70% more likely to abandon therapy than similar patients with lower copays (17% vs 10%, respectively).4

The patients in the highest quartile copay discontinued therapy 70% more often, even though the mean copay differential was only $36 monthly.

Reprinted with permission from ValueBased Cancer Care. 2014;5(7):1,8.

CML is compatible with a normal life expectancy if a patient takes the close to a miracle drug imatinib (Gleevec), but CML is typically lethal within 5 to 6 years if one does not take it.4 Despite this clear clinical benefit, at 6 months, the patients in the highest quartile copay discontinued therapy 70% more often, even though the mean copay differential was only $36 monthly.4 For a drug that offers patients a functional cure, this level of price sensitivity is

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truly surprising. Imatinib is generally well tolerated and was abandoned in these patients for its financial toxicity, not for its gastrointestinal or bone marrow toxicities.

What is the scale of this problem?

In the study by Zafar and colleagues, 42% of the 254 patients reported substantial financial burden.1 To conserve money, “20% took less than the prescribed amount of medication, 19% partially filled prescriptions, and 24% avoided filling prescriptions altogether.”1 Although this study was enriched with patients seeking copay assistance, almost 66% of the patients were not taking their medication as prescribed because of a single, largely unaddressed, side effect: financial toxicity.1 Similarly, a study by Fenn and colleagues concluded that “increased financial burden as a result of cancer care costs is the strongest independent predictor of poor quality of life among cancer survivors.”5 Oncologists often avoid talking about the cost of the treatments that they prescribe, because they lack granular knowledge of an individual patient’s financial burden and the skills needed to negotiate this dimly lit part of oncology practice, preferring to say, “That’s not my job.” Addressing a side effect that caused more than 50% of patients to not take a medication as prescribed would certainly be considered part of an oncologist’s job, if that toxicity were other than financial. The point is that financial toxicity is a medical toxicity: if patients do not take their medication, they cannot benefit from it.

Perspective

Insurance Coverage and Noncompliance Noncompliance is more common with oral oncolytics than other types, because parenteral medications tend to be covered under the more generous medical part of a patient’s insurance, whereas oral medications are frequently covered under the prescription benefit.

Less costly prescriptions at the first and second tiers of benefits usually require a modest copay of $0 to $10 for the first tier and perhaps $20 to $40 for the second tier.

Treatments for cancer are frequently in a third tier, in which benefits switch from a copay (a fixed dollar amount) to coinsurance (a percent of total cost). For example, a postmenopausal patient with breast cancer may have no copay for tamoxifen, a $30 copay for anastrozole, and coinsurance payment of $3000 (total cost $9000) for everolimus (Afinitor).

Oral oncolytics now make up approximately 25% of our therapies for cancer, but more than 50% of new oncology drug approvals are oral medications. Oral oncolytics are never inexpensive, with new ones typically priced at $7000 to $10,000 monthly.

Gone are the days when an oncologist can hand a patient a prescription and then breeze into the next examination room. Instead, oncologists need to wade deeper into the sometimes messy engagement known as the doctor–patient relationship and discuss the financial challenges associated with the treatment being prescribed. If a patient reports that he or she cannot afford a treatment, and if there is no copay assistance available, the oncologist should be willing to discuss less costly alternative therapies.

Prescribing less than the best therapy for a patient is extremely uncomfortable for the majority of oncologists, but we should not let the perfect be the enemy of the good. For example, for many years, I have substituted tamoxifen (Nolvadex) for an aromatase inhibitor in financially challenged patients with postmenopausal luminal A-type breast cancer. The ben-

Medicare, should create a new class of drug coverage for critical oral oncolytics that require only a modest copay.

Although payers acknowledge this decidedly patient-unfriendly aspect of their coverage, no comprehensive programs to address this increasing burden have been put forward. Drug makers are part of this problem as well. Although many companies have good patient-assistance programs, new drugs always cost more than the ones they replace.

When oncologists prescribe costly new regimens, they should begin discussing the potential for financial toxicity just as they discuss the potential for any other unavoidable medical side effect. Perhaps this simple act will begin to draw attention to the proverbial elephant in the room that is responsible for more patients’ poor compliance with prescribed cancer regimens than any other medical side effect.

Patients with cancer can never be cured by a medication they cannot afford to take.

Financial toxicity is everyone’s problem. Having a name for our pain does not remedy the problem, but it is a start. l

Addressing a side effect that caused more than 50% of patients to not take a medication as prescribed would certainly be considered part of an oncologist’s job, if that toxicity were other than financial.

efit of these drugs is very similar, but before the availability of generic options for aromatase inhibitors, the difference in price was approximately 100-fold between the 2 drug classes. In this circumstance, most financially strapped patients have been willing to trade 1% or 2% of clinical benefit for affordability.

However, with a disease such as CML, no inexpensive alternative medication is currently available.

All an oncologist can do in such a case is to help the patient obtain copay assistance. Payers, including

References

1. Zafar SY, Peppercorn JM, Schrag D, et al. The financial toxicity of cancer treatment: a pilot study assessing out-of-pocket expenses and the insured cancer patient’s experience. Oncologist. 2013;18:381-390.

2. Ubel PA, Abernethy AP, Zafar SY. Full disclosure—out-of-pocket costs as side effects. N Engl J Med. 2013;369:1484-1486.

3. Bath C. Disclosing medical costs can help avoid ‘financial toxicity.’ ASCO Post. 2013;4.

4. Dusetzina SB, Winn AN, Abel GA, et al. Cost sharing and adherence to tyrosine kinase inhibitors for patients with chronic myeloid leukemia. J Clin Oncol. 2014;32:306-311.

5. Fenn KM, Evans SB, McCorkle R, et al. Impact of financial burden of cancer on survivors’ quality of life. J Oncol Pract. 2014 May 27 [Epub ahead of print].

Urology Practice Management is now available online at: www.UroPracticeManagement.com

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Defining Value in Oncology

Should You Consider the Interests of Society at Large When Treating the Individual Patient?

Oncologists debate value-based moral questions of patient care

By Wayne Kuznar

Chicago, IL—With finite healthcare resources, do physicians have a duty to serve society broadly by

“Oncology providers are faced with balancing their duties to individual patients and society.”

—Beverly Moy, MD, MPH

amounts to approximately 5% to 11% of the total healthcare budget and is the most rapidly growing segment of healthcare.

The costs of targeted therapy range from $500 to more than $30,000 monthly or per treatment cycle. These ballooning costs in cancer care present an ethical dilemma for oncologists and for society.

Oncologists’ Ethical Dilemmas The professional norm that says that the first and foremost responsibility of oncologists is to do what is best for their patients is eroding in the face of the ever-increasing growth of healthcare costs, said Dr Moy. “Oncology providers are faced with balancing their duties to individual patients and society.”

Reshma Jagsi, MD, DPhil, De­­ partment of Radiation Oncology, University of Michigan, Ann Arbor, argued that physicians’ moral duty to their patients is paramount in

being responsible stewards of those shared resources, or is their obligation to the patients before them incompatible with any rationing?

The balance of duties to patients and to society was the subject of a debate at the 2014 American Society of Clinical Oncology (ASCO) meeting.

Beverly Moy, MD, MPH, Clinical Director of the Breast Oncology Program at Massachusetts General Hospital, Boston, set the stage by noting that therapy for cancer

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any clinical encounter, but in their privileged professional role, they “have an obligation to serve society more broadly.”

Healthcare spending can crowd out other spending that is essential to promote health, she said. The question is not whether to ration resources, but how to ration them.

“Physicians owe it to society to help ensure that resources are allocated in a way that is congruent with broader moral intuitions, as well as to reduce waste to maximize the value of our interventions,” said Dr Jagsi.

“Physician stewardship of society’s scarce resources is best accomplished at the societal level rather than the individual level.”

Physicians must call attention to general areas of waste and develop solutions to improve efficiency, as well as “lead the development of a robust evidence base for the assessment of value, including studies to identify situations of overdiagnosis

“Physicians owe it to society to help ensure that resources are allocated in a way that is congruent with broader moral intuitions, as well as to reduce waste to maximize the value of our interventions.”

—Reshma Jagsi, MD, DPhil

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and overtreatment in healthcare,” she added.

Recent studies on the financial burden of cancer care highlight how prescribing costly care can hurt the individual patient. When strong evidence suggests that clinical benefit is not compromised by a more efficient approach to treatment, physicians have a duty to consider cost, Dr Jagsi advised.

The Choosing Wisely campaign has engaged professional organizations in identifying practices that may represent the inappropriate use of finite societal resources. To this end, ASCO has issued “Top 5” lists of opportunities to improve the quality and value of cancer care, she noted.

Patient-Centered Care The professional ethic of med-

“The existential situation of sickness demands that patients be able to trust that their doctors are applying this public good for their individual benefit, not the physician’s personal benefit or the good of society at large.”

—Daniel P. Sulmasy, MD, PhD icine is patient-centered, countered Daniel P. Sulmasy, MD, PhD, Associate Director of the McLean Center for Clinical Medical Ethics, University of Chicago, in which the goal of the clinical encounter is to promote the good of the individual patient.

Patients must trust that oncologists will do the best for them in light of the available resources.

“Questions of justice might arise regarding the unequal distribution of medical resources across the globe, but such questions are not answered in the immediacy of the bedside encounter, with the individual patient in a particular society,” Dr Sulmasy said.

Economists suggest that medicine is a public good, he said, given the necessity of health for access to many other goods. “The existential situation of sickness demands that patients be able to trust that their doctors are applying this public good for their individual benefit, not the physician’s personal benefit or the good of society at large,” said Dr Sulmasy.

Bedside rationing of care undermines trust, “disrupts the balance between profession, market, and state, and is likely to be idiosyncratic and unjust to individual patients,” he pointed out. l

KEY POINTS With the ever-rising costs of cancer care, oncologists are faced with the dilemma of balancing their duties to individual patients and to society at large

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Patients trust their doctors to treat them on an individual basis, not for the physician’s own benefit or for the good of society

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Patients must trust their oncologists to do the best for them in light of available resources

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With finite healthcare resources, the question is not whether to ration resources, but how to ration them

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Oncologists owe it to society to ensure that resources are allocated, and to reduce waste to maximize value

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Oncologists’ focus should be on reducing healthcare waste, improving efficiency, and developing a strong evidence base to assess value

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ZYTIGA® (abiraterone acetate) Tablets Brief Summary of Prescribing Information.

INDICATIONS AND USAGE ZYTIGA is a CYP17 inhibitor indicated in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer.

CONTRAINDICATIONS Pregnancy: ZYTIGA can cause fetal harm when administered to a pregnant woman. ZYTIGA is not indicated for use in women. ZYTIGA is contraindicated in women who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to the fetus and the potential risk for pregnancy loss [see Use in Specific Populations].

WARNINGS AND PRECAUTIONS Hypertension, Hypokalemia and Fluid Retention Due to Mineralocorticoid Excess: ZYTIGA may cause hypertension, hypokalemia, and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition [see Clinical Pharmacology (12.1) in full Prescribing Information].

In the two randomized clinical trials, grade 3 to 4 hypertension occurred in 2% of patients, grade 3 to 4 hypokalemia in 4% of patients, and grade 3 to 4 edema in 1% of patients treated with ZYTIGA [see Adverse Reactions].

Co-administration of a corticosteroid suppresses adrenocorticotropic hormone (ACTH) drive, resulting in a reduction in the incidence and severity of these adverse reactions. Use caution when treating patients whose underlying medical conditions might be compromised by increases in blood pressure, hypokalemia or fluid retention, e.g., those with heart failure, recent myocardial infarction or ventricular arrhythmia. Use ZYTIGA with caution in patients with a history of cardiovascular disease. The safety of ZYTIGA in patients with left ventricular ejection fraction <50% or New York Heart Association (NYHA) Class III or IV heart failure (in Study 1) or NYHA Class II to IV heart failure (in Study 2) was not established because these patients were excluded from these randomized clinical trials [see Clinical Studies (14) in full Prescribing Information]. Monitor patients for hypertension, hypokalemia, and fluid retention at least once a month. Control hypertension and correct hypokalemia before and during treatment with ZYTIGA. Adrenocortical Insufficiency: Adrenal insufficiency occurred in the two randomized clinical studies in 0.5% of patients taking ZYTIGA and in 0.2% of patients taking placebo. Adrenocortical insufficiency was reported in patients receiving ZYTIGA in combination with prednisone, following interruption of daily steroids and/or with concurrent infection or stress. Use caution and monitor for symptoms and signs of adrenocortical insufficiency, particularly if patients are withdrawn from prednisone, have prednisone dose reductions, or experience unusual stress. Symptoms and signs of adrenocortical insufficiency may be masked by adverse reactions associated with mineralocorticoid excess seen in patients treated with ZYTIGA. If clinically indicated, perform appropriate tests to confirm the diagnosis of adrenocortical insufficiency. Increased dosage of corticosteroids may be indicated before, during and after stressful situations [see Warnings and Precautions].

Hepatotoxicity: In the two randomized clinical trials, grade 3 or 4 ALT or AST increases (at least 5X ULN) were reported in 4% of patients who received ZYTIGA, typically during the first 3 months after starting treatment. Patients whose baseline ALT or AST were elevated were more likely to experience liver test elevation than those beginning with normal values. Treatment discontinuation due to liver enzyme increases occurred in 1% of patients taking ZYTIGA. No deaths clearly related to ZYTIGA were reported due to hepatotoxicity events.

Measure serum transaminases (ALT and AST) and bilirubin levels prior to starting treatment with ZYTIGA, every two weeks for the first three months of treatment and monthly thereafter. In patients with baseline moderate hepatic impairment receiving a reduced ZYTIGA dose of 250 mg, measure ALT, AST, and bilirubin prior to the start of treatment, every week for the first month, every two weeks for the following two months of treatment and monthly thereafter. Promptly measure serum total bilirubin, AST, and ALT if clinical symptoms or signs suggestive of hepatotoxicity develop.

Elevations of AST, ALT, or bilirubin from the patient’s baseline should prompt more frequent monitoring. If at any time AST or ALT rise above five times the ULN, or the bilirubin rises above three times the ULN, interrupt ZYTIGA treatment and closely monitor liver function.

Re-treatment with ZYTIGA at a reduced dose level may take place only after return of liver function tests to the patient’s baseline or to AST and ALT less than or equal to 2.5X ULN and total bilirubin less than or equal to 1.5X ULN [see Dosage and Administration (2.2) in full Prescribing Information].

The safety of ZYTIGA re-treatment of patients who develop AST or ALT greater than or equal to 20X ULN and/or bilirubin greater than or equal to 10X ULN is unknown.

Increased ZYTIGA Exposures with Food: ZYTIGA must be taken on an empty stomach. No food should be consumed for at least two hours before the dose of ZYTIGA is taken and for at least one hour after the dose of ZYTIGA is taken. Abiraterone Cmax and AUC0-∞ (exposure) were increased up to 17and 10-fold higher, respectively, when a single dose of abiraterone acetate was administered with a meal compared to a fasted state. The safety of these increased exposures when multiple doses of abiraterone acetate are taken with food has not been assessed [see Dosage and Administration (2.1) and Clinical Pharmacology (12.3) in full Prescribing Information].

ZYTIGA® (abiraterone acetate) Tablets ADVERSE REACTIONS The following are discussed in more detail in other sections of the labeling: • Hypertension, Hypokalemia, and Fluid Retention due to Mineralocorticoid Excess [see Warnings and Precautions].

• Adrenocortical Insufficiency [see Warnings and Precautions].

• Hepatotoxicity [see Warnings and Precautions].

• Increased ZYTIGA Exposures with Food [see Warnings and Precautions].

Clinical Trial Experience: Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Two randomized placebo-controlled, multicenter clinical trials enrolled patients who had metastatic castration-resistant prostate cancer who were using a gonadotropin-releasing hormone (GnRH) agonist or were previously treated with orchiectomy. In both Study 1 and Study 2 ZYTIGA was administered at a dose of 1,000 mg daily in combination with prednisone 5 mg twice daily in the active treatment arms. Placebo plus prednisone 5 mg twice daily was given to control patients.

The most common adverse drug reactions (≥10%) reported in the two randomized clinical trials that occurred more commonly (>2%) in the abiraterone acetate arm were fatigue, joint swelling or discomfort, edema, hot flush, diarrhea, vomiting, cough, hypertension, dyspnea, urinary tract infection and contusion.

The most common laboratory abnormalities (>20%) reported in the two randomized clinical trials that occurred more commonly (≥2%) in the abiraterone acetate arm were anemia, elevated alkaline phosphatase, hypertriglyceridemia, lymphopenia, hypercholesterolemia, hyperglycemia, elevated AST, hypophosphatemia, elevated ALT and hypokalemia.

Study 1: Metastatic CRPC Following Chemotherapy: Study 1 enrolled 1195 patients with metastatic CRPC who had received prior docetaxel chemotherapy. Patients were not eligible if AST and/or ALT ≥2.5X ULN in the absence of liver metastases. Patients with liver metastases were excluded if AST and/or ALT >5X ULN. Table 1 shows adverse reactions on the ZYTIGA arm in Study 1 that occurred with a ≥2% absolute increase in frequency compared to placebo or were events of special interest. The median duration of treatment with ZYTIGA was 8 months.

Table 1: Adverse Reactions due to ZYTIGA in Study 1 ZYTIGA with Placebo with Prednisone (N=791) Prednisone (N=394) System/Organ Class All Grades1 Grade 3-4 All Grades Grade 3-4 Adverse reaction % % % % Musculoskeletal and connective tissue disorders Joint swelling/ 29.5 discomfort2 4.2 23.4 4.1 Muscle discomfort3 26.2 3.0 23.1 2.3 General disorders Edema4 26.7 1.9 18.3 0.8 Vascular disorders Hot flush 19.0 0.3 16.8 0.3 Hypertension 8.5 1.3 6.9 0.3 Gastrointestinal disorders Diarrhea 17.6 0.6 13.5 1.3 Dyspepsia 6.1 0 3.3 0 Infections and infestations Urinary tract infection 11.5 2.1 7.1 0.5 Upper respiratory tract infection 5.4 0 2.5 0 Respiratory, thoracic and mediastinal disorders Cough 10.6 0 7.6 0 Renal and urinary disorders Urinary frequency 7.2 0.3 5.1 0.3 Nocturia 6.2 0 4.1 0 Injury, poisoning and procedural complications Fractures5 5.9 1.4 2.3 0 Cardiac disorders 6 Arrhythmia 7.2 1.1 4.6 1.0 Chest pain or chest discomfort7 3.8 0.5 2.8 0 Cardiac failure8 2.3 1.9 1.0 0.3

ZYTIGA® (abiraterone acetate) Tablets

ZYTIGA® (abiraterone acetate) Tablets

1 Adverse events graded according to CTCAE version 3.0 2 Includes terms Arthritis, Arthralgia, Joint swelling, and Joint stiffness 3 Includes terms Muscle spasms, Musculoskeletal pain, Myalgia,

Table 3: Adverse Reactions in ≥5% of Patients on the ZYTIGA Arm in Study 2 (continued) ZYTIGA with Placebo with Prednisone (N=542) Prednisone (N=540) 1 System/Organ Class All Grades Grade 3-4 All Grades Grade 3-4 Adverse reaction % % % % Renal and urinary disorders Hematuria 10.3 1.3 5.6 0.6 Skin and subcutaneous tissue disorders Rash 8.1 0.0 3.7 0.0 1 Adverse events graded according to CTCAE version 3.0 2 Includes terms Edema peripheral, Pitting edema, and Generalized edema 3 Includes terms Arthritis, Arthralgia, Joint swelling, and Joint stiffness Table 4 shows laboratory abnormalities that occurred in greater than 15% of patients, and more frequently (>5%) in the ZYTIGA arm compared to placebo in Study 2. Grade 3-4 lymphopenia (9%), hyperglycemia (7%) and high alanine aminotransferase (6%) occurred at a greater than 5% rate in the ZYTIGA arm.

Musculoskeletal discomfort, and Musculoskeletal stiffness terms Edema, Edema peripheral, Pitting edema, and Generalized edema 5 Includes all fractures with the exception of pathological fracture 6 Includes terms Arrhythmia, Tachycardia, Atrial fibrillation, Supraventricular tachycardia, Atrial tachycardia, Ventricular tachycardia, Atrial flutter, Bradycardia, Atrioventricular block complete, Conduction disorder, and Bradyarrhythmia 7 Includes terms Angina pectoris, Chest pain, and Angina unstable.

Myocardial infarction or ischemia occurred more commonly in the placebo arm than in the ZYTIGA arm (1.3% vs. 1.1% respectively).

8 Includes terms Cardiac failure, Cardiac failure congestive, Left ventricular dysfunction, Cardiogenic shock, Cardiomegaly, Cardiomyopathy, and Ejection fraction decreased 4 Includes

Table 2 shows laboratory abnormalities of interest from Study 1. Grade 3-4 low serum phosphorus (7%) and low potassium (5%) occurred at a greater than or equal to 5% rate in the ZYTIGA arm.

Table 2: Laboratory Abnormalities of Interest in Study 1 Abiraterone (N=791) Placebo (N=394) Laboratory All Grades Grade 3-4 All Grades Grade 3-4 Abnormality (%) (%) (%) (%) Hypertriglyceridemia 62.5 0.4 53.0 0 High AST 30.6 2.1 36.3 1.5 Hypokalemia 28.3 5.3 19.8 1.0 Hypophosphatemia 23.8 7.2 15.7 5.8 High ALT 11.1 1.4 10.4 0.8 High Total Bilirubin 6.6 0.1 4.6 0 Study 2: Metastatic CRPC Prior to Chemotherapy: Study 2 enrolled 1088 patients with metastatic CRPC who had not received prior cytotoxic chemotherapy. Patients were ineligible if AST and/or ALT ≥2.5X ULN and patients were excluded if they had liver metastases.

Table 3 shows adverse reactions on the ZYTIGA arm in Study 2 that occurred with a ≥2% absolute increase in frequency compared to placebo.

The median duration of treatment with ZYTIGA was 13.8 months.

Table 3: Adverse Reactions in ≥5% of Patients on the ZYTIGA Arm in Study 2 ZYTIGA with Placebo with Prednisone (N=542) Prednisone (N=540) 1 System/Organ Class All Grades Grade 3-4 All Grades Grade 3-4 Adverse reaction % % % % General disorders Fatigue 39.1 2.2 34.3 1.7 Edema2 25.1 0.4 20.7 1.1 Pyrexia 8.7 0.6 5.9 0.2 Musculoskeletal and connective tissue disorders Joint swelling/ discomfort3 30.3 2.0 25.2 2.0 Groin pain 6.6 0.4 4.1 0.7 Gastrointestinal disorders Constipation 23.1 0.4 19.1 0.6 Diarrhea 21.6 0.9 17.8 0.9 Dyspepsia 11.1 0.0 5.0 0.2 Vascular disorders Hot flush 22.3 0.2 18.1 0.0 Hypertension 21.6 3.9 13.1 3.0 Respiratory, thoracic and mediastinal disorders Cough 17.3 0.0 13.5 0.2 Dyspnea 11.8 2.4 9.6 0.9 Psychiatric disorders Insomnia 13.5 0.2 11.3 0.0 Injury, poisoning and procedural complications Contusion 13.3 0.0 9.1 0.0 Falls 5.9 0.0 3.3 0.0 Infections and infestations Upper respiratory tract infection 12.7 0.0 8.0 0.0 Nasopharyngitis 10.7 0.0 8.1 0.0

Table 4: Laboratory Abnormalities in >15% of Patients in the ZYTIGA Arm of Study 2 Abiraterone (N = 542) Placebo (N = 540) Laboratory Grade 1-4 Grade 3-4 Grade 1-4 Grade 3-4 Abnormality % % % % Hematology Lymphopenia 38.2 8.7 31.7 7.4 Chemistry Hyperglycemia1 56.6 6.5 50.9 5.2 High ALT 41.9 6.1 29.1 0.7 High AST 37.3 3.1 28.7 1.1 Hypernatremia 32.8 0.4 25.0 0.2 Hypokalemia 17.2 2.8 10.2 1.7 1Based on non-fasting blood draws Cardiovascular Adverse Reactions: In the combined data for studies 1 and 2, cardiac failure occurred more commonly in patients treated with ZYTIGA compared to patients on the placebo arm (2.1% versus 0.7%).

Grade 3-4 cardiac failure occurred in 1.6% of patients taking ZYTIGA and led to 5 treatment discontinuations and 2 deaths. Grade 3-4 cardiac failure occurred in 0.2% of patients taking placebo. There were no treatment discontinuations and one death due to cardiac failure in the placebo group.

In Study 1 and 2, the majority of arrhythmias were grade 1 or 2. There was one death associated with arrhythmia and one patient with sudden death in the ZYTIGA arms and no deaths in the placebo arms. There were 7 (0.5%) deaths due to cardiorespiratory arrest in the ZYTIGA arms and 3 (0.3%) deaths in the placebo arms. Myocardial ischemia or myocardial infarction led to death in 3 patients in the placebo arms and 2 deaths in the ZYTIGA arms.

DRUG INTERACTIONS Drugs that Inhibit or Induce CYP3A4 Enzymes: Based on in vitro data, ZYTIGA is a substrate of CYP3A4.

In a dedicated drug interaction trial, co-administration of rifampin, a strong CYP3A4 inducer, decreased exposure of abiraterone by 55%. Avoid concomitant strong CYP3A4 inducers during ZYTIGA treatment. If a strong CYP3A4 inducer must be co-administered, increase the ZYTIGA dosing frequency [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3) in full Prescribing Information].

In a dedicated drug interaction trial, co-administration of ketoconazole, a strong inhibitor of CYP3A4, had no clinically meaningful effect on the pharmacokinetics of abiraterone [see Clinical Pharmacology (12.3) in full Prescribing Information].

Effects of Abiraterone on Drug Metabolizing Enzymes: ZYTIGA is an inhibitor of the hepatic drug-metabolizing enzyme CYP2D6. In a CYP2D6 drug-drug interaction trial, the Cmax and AUC of dextromethorphan (CYP2D6 substrate) were increased 2.8- and 2.9-fold, respectively, when dextromethorphan was given with abiraterone acetate 1,000 mg daily and prednisone 5 mg twice daily. Avoid co-administration of abiraterone acetate with substrates of CYP2D6 with a narrow therapeutic index (e.g., thioridazine).

If alternative treatments cannot be used, exercise caution and consider a dose reduction of the concomitant CYP2D6 substrate drug [see Clinical Pharmacology (12.3) in full Prescribing Information].

ZYTIGA® (abiraterone acetate) Tablets

ZYTIGA® (abiraterone acetate) Tablets

In vitro, ZYTIGA inhibits CYP2C8. There are no clinical data on the use of ZYTIGA with drugs that are substrates of CYP2C8. However, patients should be monitored closely for signs of toxicity related to the CYP2C8 substrate if used concomitantly with abiraterone acetate.

OVERDOSAGE Human experience of overdose with ZYTIGA is limited.

There is no specific antidote. In the event of an overdose, stop ZYTIGA, undertake general supportive measures, including monitoring for arrhythmias and cardiac failure and assess liver function.

Storage and Handling: Store at 20°C to 25°C (68°F to 77°F); excursions permitted in the range from 15°C to 30°C (59°F to 86°F) [see USP controlled room temperature].

Based on its mechanism of action, ZYTIGA may harm a developing fetus.

Therefore, women who are pregnant or women who may be pregnant should not handle ZYTIGA without protection, e.g., gloves [see Use in Specific Populations].

USE IN SPECIFIC POPULATIONS Pregnancy: Pregnancy Category X [see Contraindications].: ZYTIGA can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals. While there are no adequate and well-controlled studies with ZYTIGA in pregnant women and ZYTIGA is not indicated for use in women, it is important to know that maternal use of a CYP17 inhibitor could affect development of the fetus. Abiraterone acetate caused developmental toxicity in pregnant rats at exposures that were lower than in patients receiving the recommended dose. ZYTIGA is contraindicated in women who are or may become pregnant while receiving the drug. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to the fetus and the potential risk for pregnancy loss. Advise females of reproductive potential to avoid becoming pregnant during treatment with ZYTIGA. In an embryo-fetal developmental toxicity study in rats, abiraterone acetate caused developmental toxicity when administered at oral doses of 10, 30 or 100 mg/kg/day throughout the period of organogenesis (gestational days 6-17). Findings included embryo-fetal lethality (increased post implantation loss and resorptions and decreased number of live fetuses), fetal developmental delay (skeletal effects) and urogenital effects (bilateral ureter dilation) at doses ≥10 mg/kg/day, decreased fetal ano-genital distance at ≥30 mg/kg/day, and decreased fetal body weight at 100 mg/kg/day. Doses ≥10 mg/kg/day caused maternal toxicity. The doses tested in rats resulted in systemic exposures (AUC) approximately 0.03, 0.1 and 0.3 times, respectively, the AUC in patients.

Nursing Mothers: ZYTIGA is not indicated for use in women. It is not known if abiraterone acetate is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from ZYTIGA, a decision should be made to either discontinue nursing, or discontinue the drug taking into account the importance of the drug to the mother.

Pediatric Use: Safety and effectiveness of ZYTIGA in pediatric patients have not been established.

Geriatric Use: Of the total number of patients receiving ZYTIGA in phase 3 trials, 73% of patients were 65 years and over and 30% were 75 years and over. No overall differences in safety or effectiveness were observed between these elderly patients and younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Patients with Hepatic Impairment: The pharmacokinetics of abiraterone were examined in subjects with baseline mild (n=8) or moderate (n=8) hepatic impairment (Child-Pugh Class A and B, respectively) and in 8 healthy control subjects with normal hepatic function. The systemic exposure (AUC) of abiraterone after a single oral 1,000 mg dose of ZYTIGA increased by approximately 1.1-fold and 3.6-fold in subjects with mild and moderate baseline hepatic impairment, respectively compared to subjects with normal hepatic function.

No dosage adjustment is necessary for patients with baseline mild hepatic impairment. In patients with baseline moderate hepatic impairment (ChildPugh Class B), reduce the recommended dose of ZYTIGA to 250 mg once daily. If elevations in ALT or AST >5X ULN or total bilirubin >3X ULN occur in patients with baseline moderate hepatic impairment, discontinue ZYTIGA treatment [see Dosage and Administration (2.1) and Clinical Pharmacology (12.3) in full Prescribing Information].

The safety of ZYTIGA in patients with baseline severe hepatic impairment has not been studied. These patients should not receive ZYTIGA. For patients who develop hepatotoxicity during treatment, interruption of treatment and dosage adjustment may be required [see Dosage and Administration (2.2) in full Prescribing Information, Warnings and Precautions, and Clinical Pharmacology (12.3)] in full Prescribing Information.

Patients with Renal Impairment: In a dedicated renal impairment trial, the mean PK parameters were comparable between healthy subjects with normal renal function (N=8) and those with end stage renal disease (ESRD) on hemodialysis (N=8) after a single oral 1,000 mg dose of ZYTIGA. No dosage adjustment is necessary for patients with renal impairment [see Dosage and Administration (2.1) and Clinical Pharmacology (12.3) in full Prescribing Information].

PATIENT COUNSELING INFORMATION See FDA-approved patient labeling (Patient Information) • Patients should be informed that ZYTIGA and prednisone are used together and that they should not interrupt or stop either of these medications without consulting their physician.

• Patients receiving GnRH agonists should be informed that they need to maintain this treatment during the course of treatment with ZYTIGA and prednisone.

• Patients should be informed that ZYTIGA must not be taken with food and that no food should be consumed for at least two hours before the dose of ZYTIGA is taken and for at least one hour after the dose of ZYTIGA is taken. They should be informed that the tablets should be swallowed whole with water without crushing or chewing. Patients should be informed that taking ZYTIGA with food causes increased exposure and this may result in adverse reactions.

• Patients should be informed that ZYTIGA is taken once daily and prednisone is taken twice daily according to their physician’s instructions.

• Patients should be informed that in the event of a missed daily dose of ZYTIGA or prednisone, they should take their normal dose the following day. If more than one daily dose is skipped, patients should be told to inform their physician.

• Patients should be apprised of the common side effects associated with ZYTIGA, including peripheral edema, hypokalemia, hypertension, elevated liver function tests, and urinary tract infection. Direct the patient to a complete list of adverse drug reactions in PATIENT INFORMATION. • Patients should be advised that their liver function will be monitored using blood tests.

• Patients should be informed that ZYTIGA may harm a developing fetus; thus, women who are pregnant or women who may be pregnant should not handle ZYTIGA without protection, e.g., gloves. Patients should also be informed that it is not known whether abiraterone or its metabolites are present in semen and they should use a condom if having sex with a pregnant woman. The patient should use a condom and another effective method of birth control if he is having sex with a woman of child-bearing potential. These measures are required during and for one week after treatment with ZYTIGA. Manufactured by: Patheon Inc. Mississauga, Canada Manufactured for: Janssen Biotech, Inc. Horsham, PA 19044 © Janssen Biotech, Inc. 2012 Revised: September 2013 003185-130920

INDICATION and IMPORTANT SAFETY INFORMATION about ZYTIGA® (abiraterone acetate) INDICATION ZYTIGA® (abiraterone acetate) in combination with prednisone is indicated for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC).

IMPORTANT SAFETY INFORMATION

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Contraindications ZYTIGA® (abiraterone acetate) is not indicated for use in women. ZYTIGA® can cause fetal harm (Pregnancy Category X) when administered to a pregnant woman and is contraindicated in women who are or may become pregnant.

Hypertension, Hypokalemia and Fluid Retention Due to Mineralocorticoid Excess Use with caution in patients with a history of cardiovascular disease or with medical conditions that might be compromised by increases in blood pressure, hypokalemia, or fluid retention. ZYTIGA® may cause hypertension, hypokalemia, and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition. Safety has not been established in patients with LVEF <50% or New York Heart Association (NYHA) Class III or IV heart failure (in Study 1) or NYHA Class II to IV heart failure (in Study 2) because these patients were excluded from these randomized clinical trials. Control hypertension and correct hypokalemia before and during treatment. Monitor blood pressure, serum potassium, and symptoms of fluid retention at least monthly.

Adrenocortical Insufficiency (AI) AI was reported in patients receiving ZYTIGA® in combination with prednisone, after an interruption of daily steroids and/or with concurrent infection or stress. Use caution and monitor for symptoms and signs of AI if prednisone is stopped or withdrawn, if prednisone dose is reduced, or if the patient experiences unusual stress. Symptoms and signs of AI may be masked by adverse reactions associated with mineralocorticoid excess seen in patients treated with ZYTIGA®. Perform appropriate tests, if indicated, to confirm AI. Increased dosages of corticosteroids may be used before, during, and after stressful situations.

Hepatotoxicity Monitor liver function and modify, withhold, or discontinue ZYTIGA® dosing as recommended (see Prescribing Information for more information). Measure serum transaminases [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] and bilirubin levels prior to starting treatment with ZYTIGA®, every two weeks for the first three months of treatment, and monthly thereafter. Promptly measure serum total bilirubin, AST, and ALT if clinical symptoms or signs suggestive of hepatotoxicity develop. Elevations of AST, ALT, or bilirubin from the patient’s baseline should prompt more frequent monitoring. If at any time AST or ALT rise above five times the upper limit of normal (ULN) or the bilirubin rises above three times the ULN, interrupt ZYTIGA® treatment and closely monitor liver function.

Increased ZYTIGA® Exposures with Food ZYTIGA® must be taken on an empty stomach. No food should be eaten for at least two hours before the dose of ZYTIGA® is taken and for at least one hour after the dose of ZYTIGA® is taken. Abiraterone Cmax and AUC0-∞ (exposure) were increased up to 17- and 10- fold higher, respectively, when a single dose of abiraterone acetate was administered with a meal compared to a fasted state.

Adverse Reactions The most common adverse reactions (≥10%) are fatigue, joint swelling or discomfort, edema, hot flush, diarrhea, vomiting, cough, hypertension, dyspnea, urinary tract infection and contusion.

The most common laboratory abnormalities (>20%) are anemia, elevated alkaline phosphatase, hypertriglyceridemia, lymphopenia, hypercholesterolemia, hyperglycemia, elevated AST, hypophosphatemia, elevated ALT and hypokalemia.

Drug Interactions Based on in vitro data, ZYTIGA® is a substrate of CYP3A4. In a drug interaction trial, co-administration of rifampin, a strong CYP3A4 inducer, decreased exposure of abiraterone by 55%. Avoid concomitant strong CYP3A4 inducers during ZYTIGA® treatment. If a strong CYP3A4 inducer must be co-administered, increase the ZYTIGA® dosing frequency only during the co-administration period [see Dosage and Administration (2.3)]. In a dedicated drug interaction trial, co-administration of ketoconazole, a strong inhibitor of CYP3A4, had no clinically meaningful effect on the pharmacokinetics of abiraterone.

ZYTIGA® is an inhibitor of the hepatic drug-metabolizing enzyme CYP2D6. Avoid co-administration with CYP2D6 substrates with a narrow therapeutic index. If alternative treatments cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate drug. In vitro, ZYTIGA® inhibits CYP2C8. There are no clinical data on the use of ZYTIGA® with drugs that are substrates of CYP2C8. Patients should be monitored closely for signs of toxicity related to the CYP2C8 substrate if used concomitantly with abiraterone acetate.

Use in Specific Populations Do not use ZYTIGA® in patients with baseline severe hepatic impairment (Child-Pugh Class C).

Please see Brief Summary of Prescribing Information on adjacent pages. © Janssen Biotech, Inc. 2013

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Our goal is to make access to ZYTIGA®(abiraterone acetate) simple, convenient, and easy.

Support for you:

Support for your patients:

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• Explanation of benefits from a personally-assigned Care Coordinator • Referral to cost support options, including the ZytigaOne™ Instant Savings Program for eligible patients • Upon request, follow-up status calls to those referred for cost support • Coordination with SPP for processing and delivery of medication • Educational materials and personalized prescription reminders, if requested

Take advantage of ZytigaOne™ Support today.

1-855-ZYTIGA-1 (998-4421) Monday–Friday, 8:00 AM–8:00 PM ET ACCESS TO ZYTIGA® SIMPLIFIED FOR YOU AND YOUR PATIENTS More information at ZYTIGAHCP.com

Please see Important Safety Information on back, and Brief Summary of Prescribing Information on adjacent pages.

Patient insurance benefit investigation is provided as a service by The Lash Group, Inc., under contract for Janssen Biotech, Inc. In this regard, The Lash Group, Inc., assists healthcare professionals in the determination of whether treatment could be covered by the applicable third-party payer based on coverage guidelines provided by the payer and patient information provided by the healthcare provider under appropriate authorization following the provider’s exclusive determination of medical necessity.

Importantly, insurance verification is the ultimate responsibility of the provider. Third-party reimbursement is affected by many factors. Therefore, The Lash Group, Inc., and Janssen Biotech make no representation or guarantee that full or partial insurance reimbursement or any other payment will be available. This information is provided as an information service only. While The Lash Group, Inc., tries to provide correct information, it and Janssen Biotech make no representations or warranties, express or implied, as to the accuracy of the information. In no event shall The Lash Group, Inc., or Janssen Biotech or its employees or agents be liable for any damages resulting from or relating to the services. All providers and other users of this information agree that they accept responsibility for the use of this service.

Janssen Biotech assumes no responsibility for, and does not guarantee the quality, scope, or availability of the services including but not limited to reimbursement support services, patient education, and other support services. Each provider, not Janssen Biotech, is responsible for the services they provide. These support services have no independent value to providers apart from the product and are included within the cost of the product. © Janssen Biotech, Inc. 2013

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