applied therpeutics the clinical use of drugs

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Eleventh edition

Copyright © 2018 Wolters Kluwer.

Copyright © 2013, 2009, 2005 by LIPPINCOTT WILLIAMS & WILKINS, a WOLTERS KLUWER business All

rights reserved. This book is protected by copyright. No part of this book may be reproduced or transmitted in any

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Printed in China

Library of Congress Cataloging-in-Publication Data

Names: Zeind, Caroline S., editor. | Carvalho, Michael G., editor.

Title: Applied therapeutics : the clinical use of drugs / [edited by]

Caroline S. Zeind, Michael G. Carvalho.

Other titles: Applied therapeutics for clinical pharmacists.

Description: Eleventh edition. | Philadelphia : Wolters Kluwer Health, [2018]

| Includes bibliographical references and index.

Identifiers: LCCN 2017045052 | eISBN 9781496396075 | VST 9781496396082

Subjects: | MESH: Drug Therapy

Classification: LCC RM262 | NLM WB 330 | DDC 615.5/8—dc23 LC record available at

https://lccn.loc.gov/2017045052

This work is provided “as is,” and the publisher disclaims any and all warranties, express or implied, including any

warranties as to accuracy, comprehensiveness, or currency of the content of this work.

This work is no substitute for individual patient assessment based upon healthcare professionals’ examination of

each patient and consideration of, among other things, age, weight, gender, current or prior medical conditions,

medication history, laboratory data and other factors unique to the patient. The publisher does not provide medical

advice or guidance and this work is merely a reference tool. Healthcare professionals, and not the publisher, are

solely responsible for the use of this work including all medical judgments and for any resulting diagnosis and

treatments.

Given continuous, rapid advances in medical science and health information, independent professional verification

of medical diagnoses, indications, appropriate pharmaceutical selections and dosages, and treatment options should

be made and healthcare professionals should consult a variety of sources. When prescribing medication, healthcare

professionals are advised to consult the product information sheet (the manufacturer’s package insert)

accompanying each drug to verify, among other things, conditions of use, warnings and side effects and identify

any changes in dosage schedule or contraindications, particularly if the medication to be administered is new,

infrequently used or has a narrow therapeutic range. To the maximum extent permitted under applicable law, no

responsibility is assumed by the publisher for any injury and/or damage to persons or property, as a matter of

products liability, negligence law or otherwise, or from any reference to or use by any person of this work.

LWW.com

p. iv

The editors wish to express their sincere thanks to Dr. Mary

Anne Koda-Kimble and Dr. Lloyd Young who created

Applied Therapeutics, the gold standard textbook used in

the teaching of patient-centered drug therapeutics. Their

vision and legendary contributions have inspired

generations of health profession students, faculty, and

clinicians. We are grateful to the past editors and current

editorial team and contributors, as well as faculty

colleagues and clinicians across the globe for their

tremendous dedication to their patients and their

communities. They have shaped and inspired the next

generation of health care professionals through innovative

teaching, mentoring, and dissemination of their scholarship.

Finally, we wish to thank our families for their patience and

understanding as we embarked on this journey and

completed this eleventh edition of the textbook.

p. v

It has been over forty years since the first edition of Applied Therapeutics: The

Clinical Use of Drugs was published, and the landscape of health care has changed

dramatically. While we have seen tremendous scientific and technologic

advancements transform personalized medicine, we also realize the significant

challenges that we face within our increasingly complex health care delivery system.

More than ever, we are in need of health professionals who are able to think

critically and to utilize problem-solving skills to improve patient outcomes.

Approximately four decades later, the founding principle for this textbook—a

patient-centric, case-based approach to learning—remains the cornerstone of health

professions education. Our authors present approximately 900 patient cases that

stimulate the reader to integrate and apply therapeutic principles in the context of

specific clinical situations. Health profession students and practitioners gain a

glimpse into the minds of clinicians as they work to assess and solve therapeutic

problems and develop their own critical-thinking and problem-solving skills.

Readers familiar with past editions of the book will notice that the overall design

of the book is consistent with the tenth edition, which incorporates a Core Principles

section at the beginning of each chapter, providing the most important “take home”

information from the chapter. Each Core Principle is mapped to specific cases within

the chapter where the principle is discussed in detail. Key references and websites

are listed at the end of each chapter, whereas the full reference lists for each chapter

have been moved online.

Building upon the excellent foundation of case-based learning provided in

previous editions, the eleventh edition has incorporated changes to meet the evolving

educational needs of health profession educators and students across the globe. The

editors and contributors have utilized the five Institute of Medicine (IOM) core

competencies as a broad framework for proposing case studies and questions within

the textbook: patient-centered care; interdisciplinary teams; evidence-based practice;

quality improvement; and informatics. In addition, the Accreditation Council for

Pharmacy Education (ACPE) Accreditation Standards 2016, the Center for the

Advancement of Pharmacy Education (CAPE) Educational Outcomes, and the North

American Pharmacist Licensure Examination (NAPLEX) revised competency

statements have served as road maps for the editorial team and contributors in

designing the eleventh edition.

Featuring contributions from more than 200 experienced clinicians, every chapter

has been revised and updated to reflect our ever-changing knowledge of drugs and

the application of this knowledge to the individualized therapy of patients. Content

within several sections has been extensively reorganized, with new chapters

introduced to expand important topics. Among these are seven new chapters within

the General Principles, Immunologic Disorders, Rheumatic and Musculoskeletal

Diseases, Neurologic Disorders, Psychiatric Disorders & Substance Abuse, and

Hematology and Oncology sections. Of particular note are featured new chapters in

the General Principles section on Drug Interactions, Pharmacogenomics and

Personalized Medicine, and Interprofessional Education and Practice. In addition, a

chapter has been redesigned to focus on Care of the Critically Ill Adult, which now

complements the chapter on Care of the Critically Ill Child.

Given the importance of incorporating Interprofessional Education (IPE) within

the didactic, practicum, and clinical settings, we have added an array of IPE case

studies prepared by contributors that are representative of various sections of the

textbook. These IPE cases, along with answer guides, will be available for

instructors on the textbook’s website (see the “Additional Resources” section).

We welcome your feedback as we undertake planning for the next edition. The

authors have drawn on information from the literature, current standards, and their

own clinical experiences to share the process involved in making sound and

thoughtful therapeutic decisions. However, it remains the responsibility of every

practitioner to evaluate the appropriateness of a particular opinion in the context of

the actual clinical situation, bearing in mind any recent developments in the field. We

strongly urge students and practitioners to consult several appropriate information

sources when working with new and unfamiliar drugs.

p. vi

We are deeply indebted to the many dedicated people who have given of themselves

to complete the eleventh edition of Applied Therapeutics: The Clinical Use of Drugs.

We are grateful to our contributing authors who have worked tirelessly to provide the

highest quality of work, while balancing numerous responsibilities as educators,

clinicians, and researchers. We are grateful for the exceptional work of our twentysix section editors, who provided critical feedback necessary both in the

organizational structure of the textbook and in the individual editing of chapters;

without their dedication and support, this edition would not be possible. In

particular, we wish to recognize those returning section editors as they have been a

guiding force for the eleventh edition: Drs. Jean M. Nappi, Timothy J. Ives, Marcia

L. Buck, Judith L. Beizer, and Myrna Y. Munar. We sincerely thank the past editorial

team of Applied Therapeutics, with special thanks to Dr. Brian K. Alldredge and Dr.

B. Joseph Guglielmo for their guidance and support and contributions to the eleventh

edition. We would also like to thank Facts and Comparisons for allowing us to use

their data for the construction of some of our tables.

The team from Wolters Kluwer, Matt Hauber, Andrea Vosburgh, and Annette

Ferran, deserve special recognition for their efforts. Their exceptional patience,

attention to detail, and guidance have been critical to the success of this project. We

sincerely thank Tara Slagle (project management) and Samson Premkumar

(production) for their assistance in completing this edition. Most importantly, we

wish to acknowledge the love, understanding, and unwavering support of our spouses

and families. They selflessly gave to us early mornings, late nights, weekends, and

vacation time that we spent writing and editing.

Consistent with past editions, we continue to dedicate our work to our students

who inspire us and to the many patients we have been privileged to care for and who

have taught us invaluable lessons. We also dedicate the eleventh edition to those

clinicians and educators who have served as pioneering leaders and role models in

the delivery of patient-centered care using team-based approaches.

p. vii

The eleventh edition of Applied Therapeutics: The Clinical Use of Drugs includes

additional resources for both instructors and students, available on the book’s

companion website at http://thepoint.lww.com/AT11e.

STUDENT RESOURCES

Students who have purchased Applied Therapeutics: The Clinical Use of Drugs,

Eleventh Edition have access to the following additional resources for each chapter:

A full online reference list for that chapter

INSTRUCTOR RESOURCES

Approved adopting instructors will be given access to the following additional

resources:

Interprofessional Education (IPE) Case Studies and Answer Guides

Each chapter will map which NAPLEX competency statements are addressed within

it, which will be a helpful resource for instructors.

p. viii

Michael C. Angelini, PharmD, MA, BCPP

Associate Professor of Pharmacy Practice

School of Pharmacy–Boston

MCPHS University

Boston, Massachusetts

Judith L. Beizer, PharmD, CGP, FASCP

Clinical Professor

Department of Clinical Pharmacy Practice

College of Pharmacy & Allied Health Professions

St. John’s University

Jamaica, New York

Marcia L. Buck, PharmD, FCCP, FPPAG

Professor

Department of Pediatrics

School of Medicine

Clinical Coordinator, Pediatrics

Department of Pharmacy

University of Virginia

Charlottesville, Virginia

Michael G. Carvalho, PharmD, BCPP

Assistant Dean of Interprofessional Education

Professor and Chair

Department of Pharmacy Practice

School of Pharmacy–Boston

MCPHS University

Boston, Massachusetts

Judy W. Cheng, PharmD, MPH, BCPS, FCCP

Professor of Pharmacy Practice

School of Pharmacy–Boston

MCPHS University

Boston, Massachusetts

R. Rebecca Couris, PhD, RPh

Professor of Nutrition Science and Pharmacy Practice

Department of Pharmacy Practice, School of Pharmacy–Boston

MCPHS University

Boston, Massachusetts

Steven Gabardi, PharmD, BCPS, FAST, FCCP

Abdominal Organ Transplant Clinical Specialist & Program Director PGY-2 Organ Transplant Pharmacology

Residency

Brigham and Women’s Hospital

Departments of Transplant Surgery/Pharmacy/Renal Division

Assistant Professor of Medicine

Harvard Medical School

Boston, Massachusetts

Jennifer D. Goldman, BS, PharmD, CDE, BC-ADM, FCCP

Professor of Pharmacy Practice

School of Pharmacy–Boston

MCPHS University

Boston, Massachusetts

Christy S. Harris, PharmD, BCPS, BCOP

Associate Professor of Pharmacy Practice

School of Pharmacy–Boston

MCPHS University

Boston, Massachusetts

Timothy R. Hudd, PharmD, AE-C

Associate Professor of Pharmacy Practice

School of Pharmacy–Boston

MCPHS University

Boston, Massachusetts

Timothy J. Ives, PharmD, MPH, FCCP, BCPS

Professor

Eshelman School of Pharmacy

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina

Susan Jacobson, MS, EdD, RPh

Associate Professor of Pharmacy Practice

School of Pharmacy–Boston

MCPHS University

Boston, Massachusetts

Maria D. Kostka-Rokosz, PharmD

Assistant Dean of Academic Affairs

Professor of Pharmacy Practice

School of Pharmacy–Boston

MCPHS University

Boston, Massachusetts

Trisha LaPointe, PharmD, BCPS

Associate Professor of Pharmacy Practice

School of Pharmacy–Boston

MCPHS University

Boston, Massachusetts

Michele Matthews, PharmD, CPE, BCACP

Associate Professor of Pharmacy Practice

School of Pharmacy–Boston

MCPHS University

Boston, Massachusetts

p. ix

p. x

Susan L. Mayhew, PharmD, BCNSP, FASHP

Professor and Dean

Appalachian College of Pharmacy

Oakwood, Virginia

William W. McCloskey, BA, BS, PharmD

Professor and Vice-Chair

Department of Pharmacy Practice

School of Pharmacy–Boston

MCPHS University

Boston, Massachusetts

Myrna Y. Munar, PharmD

Associate Professor

Department of Pharmacy Practice

College of Pharmacy

Oregon State University

Oregon Health and Science University

Portland, Oregon

Jean M. Nappi, PharmD, FCCP, BCPS AQ-Cardiology

Professor

Clinical Pharmacy and Outcome Sciences

South Carolina College of Pharmacy

Medical University of South Carolina

Charleston, South Carolina

Kamala M. Nola, PharmD, MS

Professor and Vice-Chair

Department of Pharmacy Practice

Lipscomb University College of Pharmacy

Nashville, Tennessee

Dorothea C. Rudorf, PharmD, MS

Professor of Pharmacy Practice

School of Pharmacy–Boston

MCPHS University

Boston, Massachusetts

Carrie A. Sincak, PharmD, BCPS, FASHP

Assistant Dean for Clinical Affairs and Professor

Department of Pharmacy Practice

Midwestern University Chicago College of Pharmacy

Downers Grove, Illinois

Timothy E. Welty, PharmD, FCCP

Professor

Department of Pharmacy Practice

University of Kansas School of Pharmacy

Lawrence, Kansas

G. Christopher Wood, PharmD, FCCP, FCCM, BCPS

Associate Professor of Clinical Pharmacy

University of Tennessee Health Science Center

College of Pharmacy

Memphis, Tennessee

Kathy Zaiken, PharmD

Professor of Pharmacy Practice

School of Pharmacy–Boston

MCPHS University

Boston, Massachusetts

Caroline S. Zeind, PharmD

Associate Provost for Academic and International Affairs

Chief Academic Officer

Worcester, Massachusetts and Manchester, New Hampshire Campuses

Professor of Pharmacy Practice

Academic Affairs

MCPHS University

Boston, Massachusetts

p. x

Steven R. Abel, PharmD, FASHP

Professor of Pharmacy Practice

Associate Provost for Engagement

Purdue University

West Lafayette, Indiana

Jessica L. Adams, PharmD, BCPS, AAHIVP

Assistant Professor of Clinical Pharmacy

HIV and Infectious Diseases Specialist

Department of Pharmacy Practice and Pharmacy Administration

Philadelphia College of Pharmacy

University of the Sciences

Philadelphia, Pennsylvania

Brian K. Alldredge, PharmD

Professor and Vice Provost

University of California–San Francisco

San Francisco, California

Mary G. Amato, PharmD, MPH, BCPS

Professor of Pharmacy Practice

School of Pharmacy–Boston

MCPHS University

Boston, Massachusetts

Jaime E. Anderson, PharmD, BCOP

Oncology Clinical Pharmacy Specialist

MD Anderson Medical Center

University of Texas

Houston, Texas

Michael C. Angelini, PharmD, MA, BCPP

Associate Professor of Pharmacy Practice

School of Pharmacy–Boston

MCPHS University

Boston, Massachusetts

Albert T. Bach, PharmD

Assistant Professor of Pharmacy Practice

School of Pharmacy

Chapman University

Irvine, California

Jennifer H. Baggs, PharmD, BCPS, BCNSP

Clinical Assistant Professor

University of Arizona

Tucson, Arizona

David T. Bearden, PharmD

Clinical Professor and Chair

Department of Pharmacy Practice

Clinical Assistant Director

Department of Pharmacy Services

College of Pharmacy

Oregon State University

Oregon Health and Science University

Portland, Oregon

Sandra Benavides, PharmD, FCCP, FPPAG

Professor

Assistant Dean for Programmatic Assessment and Accreditation

Interim Chair

Department of Clinical and Administrative Sciences

Larkin Health Sciences Institute College of Pharmacy

Paul M. Beringer, PharmD, FASHP, FCCP

Associate Professor

Department of Clinical Pharmacy

University of Southern California

Los Angeles, California

Snehal H. Bhatt, PharmD, BCPS

Associate Professor of Pharmacy Practice

School of Pharmacy–Boston

MCPHS University

Clinical Pharmacist

Beth Israel Deaconess Medical Center

Boston, Massachusetts

Jeff F. Binkley, PharmD, BCNSP, FASHP

Administrative Director of Pharmacy

Maury Regional Medical Center and Affiliates

Columbia, Tennessee

Marlo Blazer, PharmD, BCOP

Assistant Director

Xcenda, an AmerisourceBergen Company

Columbus, Ohio

KarenBeth H. Bohan, PharmD, BCPS

Professor and Founding Chair

Department of Pharmacy Practice

School of Pharmacy and Pharmaceutical Sciences

Binghamton University

Binghamton, New York

Suzanne G. Bollmeier, PharmD, BCPS, AE-C

Professor of Pharmacy Practice

School of Pharmacy–Boston

St. Louis College of Pharmacy

St. Louis, Missouri

p. xi

p. xii

Laura M. Borgelt, PharmD, BCPS

Associate Dean of Administration and Operations

Professor

Departments of Clinical Pharmacy and Family Medicine

University of Colorado Anschutz Medical Campus

Skaggs School of Pharmacy

Aurora, Colorado

Jolene R. Bostwick, PharmD, BCPS, BCPP

Clinical Associate Professor

Department of Clinical, Social, and Administrative Sciences

University of Michigan College of Pharmacy

Ann Arbor, Michigan

Nicole J. Brandt, PharmD, MBA, CGP, BCPP, FASCP

Executive Director

Peter Lamy Center on Drug Therapy and Aging

Professor

University of Maryland School of Pharmacy

Baltimore, Maryland

Marcia L. Buck, PharmD, FCCP, FPPAG

Professor

Department of Pediatrics

School of Medicine

Clinical Coordinator, Pediatrics

Department of Pharmacy

University of Virginia

Charlottesville, Virginia

Deanna Buehrle, PharmD