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Disclaimer: CME certification for these activities has expired. All information is pertinent to the timeframe in which it was released.


Understanding the Ramifications of Switching Among AEDs: A 2008 Clinical Update


GOAL
To provide neurologists with up-to-date information on the ramifications of switching among antiepileptic drugs.

TARGET AUDIENCE
This activity is designed for neurologists. No prerequisites required.

LEARNING OBJECTIVES
At the conclusion of this activity, the participant should be able to:

  • Describe the US Food and Drug Administration's standards and requirements for generic drugs and the positions of national societies.
  • List the challenges and concerns regarding substitution with generic antiepileptic drugs (AEDs) in terms of bioequivalence, narrow therapeutic index, and risk versus benefit.
  • Analyze historical and newer data on the effects of switching among AEDs, in addition to patient and clinician experiential research to justify a possible switch to a generic.
  • Compare and contrast current issues in AED substitution, including future research, epilepsy management, quality of life, risk of breakthrough seizures, and alteration of brand drugs.

The Johns Hopkins University School of Medicine takes responsibility for the content, quality, and scientific integrity of this CME activity.

ACCREDITATION STATEMENT
The Johns Hopkins University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT
The Johns Hopkins University School of Medicine designates this educational activity for a maximum of 2 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

The estimated time to complete this educational activity: 2 hours.

After reading this monograph, participants may receive credit by completing the CME test, evaluation, and receiving a score of 70% or higher.

Release date: July 15, 2008. Expiration date: July 15, 2010.

DISCLAIMER STATEMENT
The opinions and recommendations expressed by faculty and other experts whose input is included in this program are their own. This enduring material is produced for educational purposes only. Use of The Johns Hopkins University School of Medicine name implies review of educational format, design, and approach. Please review the complete prescribing information of specific drugs or combinations of drugs, including indications, contraindications, warnings, and adverse effects, before administering pharmacologic therapy to patients.

This program is supported by an educational grant from Ortho-McNeil Neurologics, administered by Ortho-McNeil Janssen Scientific Affairs.

Full Disclosure Policy Affecting CME Activities:
As a provider accredited by the Accreditation Council for Continuing Medical Education (ACCME), it is the policy of The Johns Hopkins University School of Medicine to require the disclosure of the existence of any significant financial interest or any other relationship a faculty member or a sponsor has with the manufacturer(s) of any commercial product(s) discussed in an educational presentation. The Course Directors and Participating Faculty reported the following:

COURSE DIRECTORS

Adam L. Hartman, MD
Assistant Professor of Neurology and Pediatrics
John M. Freeman Pediatric Epilepsy Center
Department of Neurology
The Johns Hopkins Medical Institutions
Baltimore, Maryland
Dr Hartman reports having no financial or advisory relationships with corporate organizations related to this activity.

Stephanie J. Phelps, PharmD, BCPS
Professor of Clinical Pharmacy and Pediatrics
The University of Tennessee Health Science Center
Memphis, Tennessee
Dr Phelps reports serving as a consultant for Harris Interactive through a grant from GlaxoSmithKline.

Eileen P. Vining, MD
Professor of Neurology and Pediatrics
Director of the John M. Freeman Pediatric Epilepsy Center
Department of Neurology
The Johns Hopkins Medical Institutions
Baltimore, Maryland
Dr Vining reports having no financial or advisory relationships with corporate organizations related to this activity.

PARTICIPATING FACULTY

Gail D. Anderson, PhD
Professor
Department of Pharmacy
University of Washington
Seattle, Washington
Dr Anderson reports having no financial or advisory relationships with corporate organizations related to this activity.

Michel J. Berg, MD
Associate Professor of Neurology
Medical Director, Strong Epilepsy Center
Department of Neurology
University of Rochester Medical Center
Rochester, New York
Dr Berg reports serving as a consultant for Harris Interactive through a grant from GlaxoSmithKline.

William R. Garnett, PharmD
Professor of Pharmacy and Neurology
Virginia Commonwealth University
Medical College of Virginia
School of Pharmacy
Richmond, Virginia
Dr Garnett reports receiving grants/research support from Ovation; receiving honoraria from R&R Health Communications; and serving on the speakers' bureau for Abbott Laboratories and UCB Pharma.

Notice: The audience is advised that an article in this CME activity contains reference(s) to unlabeled or unapproved uses of drugs or devices.

Dr Garnett–possible mention of off-label drugs.
Dr Hartman–may discuss pediatric uses for antiepileptic drugs.
Dr Phelps–many antiepileptic drugs are off-label in children and may be discussed.
Dr Vining–many antiepileptic drugs are off-label in children.

All other faculty have indicated that they have not referenced unlabeled/unapproved uses of drugs or devices.

Johns Hopkins Advanced Studies in Medicine provides disclosure information from contributing authors, lead presenters, and participating faculty. Johns Hopkins Advanced Studies in Medicine does not provide disclosure information from authors of abstracts and poster presentations. The reader shall be advised that these contributors may or may not maintain financial relationships with pharmaceutical companies.

Understanding the Ramifications of Switching Among AEDs: A 2008 Clinical Update
Adam L. Hartman, MD,* Stephanie J. Phelps, PharmD, BCPS, and Eileen P. Vining, MD

In the next 2 years, the patents will expire for most antiepileptic drugs (AEDs) used to treat people with epilepsy. Many AEDs will be available in generic formulation for the first time.  Around the same time, the latest generation of new AEDs will begin to arrive on the US market. Neurologists and other healthcare professionals who care for those with epilepsy and individuals who make formulary decisions will be faced with a multitude of questions.  Unfortunately, there are very little data to guide decisions regarding what is best for an individual patient.  It is in light of these rapid, but important changes in therapeutic options that we assembled this monograph. 

Although the US Food and Drug Administration (FDA) has provided several guidelines addressing safety and efficacy of approved generic drugs, the debates about patient safety have continued among healthcare professionals and managed care providers.1-3

The debate over generic substitution of AEDs is multifaceted and consists of several complicating factors. The discussion frequently centers on the known pharmacoeconomic benefits compared to the unknown potential of altered clinical outcomes. Given escalating healthcare costs, the initial consideration of generic substitution is largely an economic one. Regardless, the final decision is significantly influenced by everyone's assessment of the benefit-to-risk ratio of a generic compared to a brand AED. For those with epilepsy, the risk to benefit includes the all-or-nothing definition of successful treatment.1 The unknown effect of generic substitution on seizure control is a major concern for those with epilepsy because the consequences of a single seizure may dramatically impact an individual's quality of life (eg, eliminating driving privileges and employment ramifications).

Further complicating the discussions are misconceptions and misinformation about the FDA approval process of both brand and generic medications and regulatory standards for generic AEDs.

The aim of this issue of Johns Hopkins Advanced Studies in Medicine is to provide clear, concrete answers to common questions about generic and brand- name AEDs. We also hope to provide a context and perspective of how these decisions on substitution are made, by both physicians and pharmacists, given the clinical experiential history of generic substitution. With this background, we hope to make the current discussion a more informed one, with healthcare providers aware of the unique issues that affect the pharmacology of AEDs and public policy affecting people with epilepsy.

We have assembled a faculty with an extensive yet broad background in treating epilepsy and facing the challenges of the generic-versus-brand debate. The issue opens with an article by Michel J. Berg, MD, who walks us through the FDA standards for generic drugs and reviews the official positions on this subject assumed by leading medical organizations. Among these groups, the debate continues, and he discusses ways that such clinical equipoise can be resolved. As he succinctly concludes, "Either the FDA has not sufficiently convinced healthcare providers of the interchangeability of approved drugs or the equivalency issues have not yet been adequately addressed by the FDA." Next, William R. Garnett, PharmD, sheds light on the many facets of this debate by outlining the different stakeholders (physician, patient, pharmacist, payer, and pharmaceutical manufacturer) and their positions and sometimes competing interests. Importantly, he notes that, with a lack of hard data for each of the stakeholder's positions, "there is currently more emotion than science" when it comes to the decision of switching to generic from brand-name AEDs. Gail D. Anderson, PhD, then provides a historical perspective of generic switching of the older AEDs, and discusses the cost considerations and financial implications of switching for both older and newer AEDs. Finally, we also conducted a roundtable discussion to more directly address some of the most common questions and concerns that impact both physicians and pharmacists who treat patients with epilepsy. These questions and topics include the concept of an individualized therapeutic index, the validity of the FDA's position, interchangeability of newer versus older AEDs, substitution in patients at the extremes of age (ie, pediatric and elderly patients), the effect of adherence on substitution and vice versa, the role of branded generics, and the type of data needed to allay concerns about generic substitution of AEDs. A summary of those discussions is provided here.

Numerous influential forces will create increasing pressure to resolve these questions: a presidential election in November 2008 and a greater interest in reforming healthcare; a rapidly growing Medicare population that can take advantage of the Part D prescription drug benefit; the 10% of US expenditures on healthcare attributable to prescription drugs; the potential for hundreds of millions of dollars in annual savings by switching to generic drugs for Medicaid patients alone; and national "big-box stores" and grocery chains selling generic drugs at very low prices. Note that all of these forces are financial, yet the clinician ultimately must balance cost considerations (including the patient's budget) with safety and efficacy. It is our hope that this monograph provides the information necessary to help clinicians optimize each patient's epilepsy treatment.

REFERENCES

1. Wolf P. Should newly diagnosed epilepsy be treated with generics? Neurology. 2008;4:176-177.
2. Johannessen SI, Landmark CJ. Value of therapeutic drug monitoring in epilepsy. Expert Rev Neurother. 2008;8:929-939.
3. Sipkoff M. The epilepsy battle in the war between brands and generics. Manag Care. 2008;17:24-27.

*Assistant Professor of Neurology and Pediatrics, John M. Freeman Pediatric Epilepsy Center, Department of Neurology, The Johns Hopkins Medical Institutions, Baltimore, Maryland.
†Professor of Clinical Pharmacy and Pediatrics, The University of Tennessee Health Science Center, Memphis, Tennessee.
‡Professor of Neurology and Pediatrics, Director of the John M. Freeman Pediatric Epilepsy Center, Department of Neurology, The Johns Hopkins Medical Institutions, Baltimore, Maryland.
Address correspondence to: Adam L. Hartman, MD, Assistant Professor of Neurology and Pediatrics, John M. Freeman Pediatric Epilepsy Center, Department of Neurology, The Johns Hopkins Medical Institutions, 600 North Wolfe Street, Meyer 2-147, Baltimore, MD 21287. E-mail: ahartma2@jhmi.edu.

The content in this monograph was developed with the assistance of a staff medical writer. Each author had final approval of his or her article and all its contents.





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