![](media/image1.png){width="5.96875in" height="0.41944444444444445in"}

Top of Form

## Complete Summary

#### GUIDELINE TITLE

Practice advisory: the use of felbamate in the treatment of patients
with intractable epilepsy. Report of the Quality Standards Subcommittee
of the American Academy of Neurology and the American Epilepsy Society.

#### BIBLIOGRAPHIC SOURCE(S)

French J, Smith M, Faught E, Brown L. Practice advisory: the use of
felbamate in the treatment of patients with intractable epilepsy: report
of the Quality Standards Subcommittee of the American Academy of
Neurology and the American Epilepsy Society. Neurology 1999 May
12;52(8):1540-5. \[39 references\]
[PubMed](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10331676)

#### GUIDELINE STATUS

This is the current release of the guideline.

According to the guideline developer, this guideline has been reviewed
and is still considered to be current as of October 2006. This review
involved new literature searches of electronic databases followed by
expert committee review of new evidence that has emerged since the
original publication date.

### COMPLETE SUMMARY CONTENT

 SCOPE\
 METHODOLOGY - including Rating Scheme and Cost Analysis\
 RECOMMENDATIONS\
 EVIDENCE SUPPORTING THE RECOMMENDATIONS\
 BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS\
 QUALIFYING STATEMENTS\
 IMPLEMENTATION OF THE GUIDELINE\
 INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT
CATEGORIES\
 IDENTIFYING INFORMATION AND AVAILABILITY\
 DISCLAIMER

### SCOPE

#### DISEASE/CONDITION(S)

Intractable epilepsy

#### GUIDELINE CATEGORY

Assessment of Therapeutic Effectiveness\
Risk Assessment\
Treatment

#### CLINICAL SPECIALTY

Family Practice\
Internal Medicine\
Neurology\
Pediatrics

#### INTENDED USERS

Physicians

#### GUIDELINE OBJECTIVE(S)

-   To determine the current role of felbamate for treatment of various
    types of epilepsy

-   To provide guidelines to ensure maximum safety and effectiveness
    when the risk/benefit ratio is in favor of the use of felbamate

#### TARGET POPULATION

Patients with intractable epilepsy

#### INTERVENTIONS AND PRACTICES CONSIDERED

Felbamate therapy

#### MAJOR OUTCOMES CONSIDERED

-   Frequency and severity of seizures

-   Frequency of tonic and atonic seizures under felbamate therapy

-   Incidence of side effects during adjunctive therapy and monotherapy
    with felbamate

-   Felbamate interactions with other antiepileptic drugs

-   Incidence of serious idiosyncratic events, including fatalities,
    with felbamate

### METHODOLOGY

#### METHODS USED TO COLLECT/SELECT EVIDENCE

Hand-searches of Published Literature (Primary Sources)\
Hand-searches of Published Literature (Secondary Sources)\
Searches of Electronic Databases\
Searches of Unpublished Data

#### DESCRIPTION OF METHODS USED TO COLLECT/SELECT THE EVIDENCE

A Medline search was performed for articles including the key word
\"felbamate.\" The search was restricted to English language only and
human studies. The search identified 105 articles. The working group
reviewed abstracts of all articles. Of the 105 articles, 54 were
identified as relevant to the topics of efficacy, practice, treatment
guidelines, and side effects.

In addition to the information obtained through the literature search,
each panel member reviewed his or her assigned articles´ reference lists
to determine whether any important articles were missed. Unpublished
data on safety issues were also obtained from Carter Wallace
Pharmaceuticals (Cranbury, New Jersey).

#### NUMBER OF SOURCE DOCUMENTS

54

#### METHODS USED TO ASSESS THE QUALITY AND STRENGTH OF THE EVIDENCE

Weighting According to a Rating Scheme (Scheme Given)

#### RATING SCHEME FOR THE STRENGTH OF THE EVIDENCE

**Quality of evidence ratings**

**Class I**: Well-designed, prospective, blinded, controlled studies

**Class II**: Well-designed clinical studies, such as case control,
cohort studies, etc.

**Class III:** Evidence provided by expert opinion, nonrandomized
historic controls, or case reports of one or more

#### METHODS USED TO ANALYZE THE EVIDENCE

Systematic Review

#### DESCRIPTION OF THE METHODS USED TO ANALYZE THE EVIDENCE

All clinical studies were reviewed in their entirety, including case
reports. Articles were excluded if they reviewed multiple drugs,
discussed only mechanism of action, consisted of news reports, or
summarized previous data without pro-viding new insight or opinion.
Articles were rated as Class I, II, or III (see \"Rating scheme for
strength of the evidence\" above). The 54 articles reviewed could be
classified as follows:

**Class I**: Nine articles, seven related to efficacy and toxicity and
two to pharmacokinetics.

**Class II**: One article related to brain levels of felbamate.

**Class III**: Forty-four articles including case reports, historic
control studies, and reviews with expert opinion.

Studies were assessed for study design, toxicity (dose-dependent and
idiosyncratic), and efficacy, including patient characteristics, seizure
type being treated, and duration of treatment. Reviews were assessed to
determine expert opinion on efficacy, toxicity, and the place of
felbamate in the treatment of various seizure types.

#### METHODS USED TO FORMULATE THE RECOMMENDATIONS

Not stated

#### RATING SCHEME FOR THE STRENGTH OF THE RECOMMENDATIONS

**Definitions for Strength of Recommendations**:

**Standard**: A principle for patient management that reflects a high
degree of clinical certainty (usually this requires Class I evidence
that directly addresses the clinical question, or overwhelming Class II
evidence when circumstances preclude randomized clinical trials).

**Guideline**: A recommendation for patient management that reflects
moderate clinical certainty (usually this requires Class II evidence or
a strong consensus of Class III evidence).

**Practice option**: A strategy for patient management for which the
clinical utility is uncertain (inconclusive or conflicting evidence or
opinion).

**Practice Advisory**: A practice recommendation for emerging and/or
newly approved therapies or technologies based on evidence from at least
one Class I study. The evidence may demonstrate only a modest
statistical effect or limited (partial) clinical response, or
significant cost-benefit questions may exist. Substantial (or potential)
disagreement among practitioners or between payers and practitioners may
exist.

#### COST ANALYSIS

A formal cost analysis was not performed and published cost analyses
were not reviewed.

#### METHOD OF GUIDELINE VALIDATION

External Peer Review\
Internal Peer Review

#### DESCRIPTION OF METHOD OF GUIDELINE VALIDATION

Drafts of the guideline were reviewed by numerous individuals, American
Academy of Neurology sections, and organizations, including the American
Epilepsy Society, the Epilepsy Foundation of America, and the Child
Neurology Society.

The guideline was approved by the American Academy of Neurology Quality
Standards Subcommittee October 17, 1998, by the Practice Committee on
January 23, 1999, and by the Executive Board of the American Academy of
Neurology on February 27, 1999.

### RECOMMENDATIONS

#### MAJOR RECOMMENDATIONS

The quality of evidence ratings, I-III, and the definitions (Standard,
Guideline, Practice Option, Practice Advisory) are defined at the end of
the \"Major Recommendations\" field.

The guideline developers recognize the potential serious side effects
that may exceed those of primary antiepileptic drugs; however, felbamate
can be an effective antiepileptic drug and has important advantages if
used in certain patient populations.

The following recommendations were made as an advisory:

A.  Patients for whom risk/benefit ratio supports use because there is
    Class I evidence for benefit.

    1.  Lennox--Gastaut patients over age 4 unresponsive to primary
        antiepileptic drugs.

    2.  Intractable partial seizures in patients over 18 years of age
        who have failed standard antiepileptic drugs at therapeutic
        levels (monotherapy: data indicate a better risk/benefit ratio
        for felbamate used as monotherapy).

    3.  Patients on felbamate more than 18 months.

B.  Patients for whom the current risk/benefit assessment *does not
    support* the use of felbamate:

    1.  New onset epilepsy in adults or children

    2.  Patients who have experienced significant prior hematologic
        adverse events

    3.  Patients in whom follow-up and compliance will not allow careful
        monitoring

    4.  Patients unable to discuss risks/benefits (i.e., with mental
        retardation, developmental disability) and for whom no parent or
        legal guardian is available to provide consent

C.  Patients in whom risk/benefit ratio is unclear and based on case
    reports and expert opinion (Class III) only, but under certain
    circumstances depending on the nature and severity of the patient´s
    seizure disorder, felbamate use may be appropriate:

    1.  Children with intractable partial epilepsy

    2.  Other generalized epilepsies unresponsive to primary agents

    3.  Patients who experience unacceptable sedative or cognitive side
        effects with traditional antiepileptic drugs.

    4.  Lennox--Gastaut syndrome under age 4 unresponsive to other
        antiepileptic drugs.

**Risk management**

1.  As therapy continues, risk/benefit ratio should be constantly
    assessed.

2.  Patients should be educated as to early signs of potentially serious
    hepatic and hematopoetic side effects. These signs are: easy
    bruising, prolonged excessive bleeding, change in skin color,
    fatigue, fever, change in stool color, change in the color of the
    whites of the eye.

3.  Laboratory monitoring has not been proved efficacious, but the
    manufacturer (Carter-Wallace), in conjunction with the U.S. Food and
    Drug Administration (FDA), suggests liver function tests at baseline
    and every 1 to 2 weeks for the first year of therapy, and also notes
    that complete blood count may identify hematologic changes before
    symptoms occur. There is no evidence that such monitoring will
    prevent adverse outcomes. After the first year, the risk of aplastic
    anemia drops and the need for ongoing laboratory screening is even
    less clear.

4.  Even though individual clinical practice may vary, patients should
    be advised of the manufacturer´s recommendations.

**[Definitions]{.underline}**:

**Quality of evidence ratings**

**Class I**: Well-designed, prospective, blinded, controlled studies.

**Class II**: Well-designed clinical studies, such as case control,
cohort studies, etc.

**Class III**: Evidence provided by expert opinion, nonrandomized
historic controls, or case reports of one or more.

**Definitions**:

**Standard**: A principle for patient management that reflects a high
degree of clinical certainty (usually this requires Class I evidence
that directly addresses the clinical question, or overwhelming Class II
evidence when circumstances preclude randomized clinical trials).

**Guideline**: A recommendation for patient management that reflects
moderate clinical certainty (usually this requires Class II evidence or
a strong consensus of Class III evidence).

**Practice option**: A strategy for patient management for which the
clinical utility is uncertain (inconclusive or conflicting evidence or
opinion).

**Practice Advisory**: A practice recommendation for emerging and/or
newly approved therapies or technologies based on evidence from at least
one Class I study. The evidence may demonstrate only a modest
statistical effect or limited (partial) clinical response, or
significant cost-benefit questions may exist. Substantial (or potential)
disagreement among practitioners or between payers and practitioners may
exist.

#### CLINICAL ALGORITHM(S)

None provided

### EVIDENCE SUPPORTING THE RECOMMENDATIONS

#### TYPE OF EVIDENCE SUPPORTING THE RECOMMENDATIONS

The recommendations are based on a review of the literature. The type of
supporting evidence is identified and graded for the use of felbamate in
the treatment of patients with intractable epilepsy (See \"Major
Recommendations\" field).

Both Class I and Class III evidence was found to support recommendations
for the efficacy of felbamate in various types of epilepsy. Class I
evidence was found for risks for side effects, and Class III evidence
only was found for serious risks of felbamate.

### BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS

#### POTENTIAL BENEFITS

Appropriate use of felbamate in treatment of various types of epilepsy,
taking into account the risks and benefits of treatment

**Subgroups Most Likely to Benefit**:

-   Adults and children over age 4 with Lennox-Gastaut syndrome

-   Adults (over age 18) with intractable partial seizures

#### POTENTIAL HARMS

-   Dose-limiting side effects

    -   Nausea, abdominal distress, anorexia, insomnia, fatigue,
        dizziness, ataxia, cognitive impairment, and weight loss

-   Drug interactions (when used as adjunct therapy), some potentially
    causing toxicity

-   Serious (sometimes fatal) idiosyncratic events

    -   Serious rash, aplastic anemia, and hepatic failure

    -   Stevens-Johnson syndrome and toxic epidermal necrolysis

**Subgroups Most Likely to be Harmed**:

Patients who are being treated with adjunctive therapy or polytherapy,
including phenytoin, valproate, or carbamazepine

### QUALIFYING STATEMENTS

#### QUALIFYING STATEMENTS

This statement is provided as an educational service of the American
Academy of Neurology (AAN). It is based on an assessment of current
scientific and clinical information. It is not intended to include all
possible proper methods of care for a particular neurologic problem or
all legitimate criteria for choosing to use a specific procedure.
Neither is it intended to exclude any reasonable alternative
methodologies. The American Academy of Neurology recognizes that
specific patient care decisions are the prerogative of the patient and
the physician caring for the patient, based on all of the circumstances
involved.

Future research should be performed to determine the following
information:

1.  Potential risk factors that may be associated with the development
    of serious adverse events with felbamate use

2.  Potential for diagnostic testing that would predict susceptibility
    to serious adverse events

The guideline developers recommend that physicians prescribing felbamate
register their patients in the Felbatol Registry so that these goals may
be accomplished. The registry can be contacted at: Felbatol Registry
Program, Wallace Laboratories Data Management Services, PO Box 1001,
Half-Acre Road, Cranbury, New Jersey 08512-0181.

### IMPLEMENTATION OF THE GUIDELINE

#### DESCRIPTION OF IMPLEMENTATION STRATEGY

An implementation strategy was not provided.

### INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT CATEGORIES

#### IOM CARE NEED

Living with Illness

#### IOM DOMAIN

Effectiveness\
Safety

### IDENTIFYING INFORMATION AND AVAILABILITY

#### BIBLIOGRAPHIC SOURCE(S)

French J, Smith M, Faught E, Brown L. Practice advisory: the use of
felbamate in the treatment of patients with intractable epilepsy: report
of the Quality Standards Subcommittee of the American Academy of
Neurology and the American Epilepsy Society. Neurology 1999 May
12;52(8):1540-5. \[39 references\]
[PubMed](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10331676)

#### ADAPTATION

Not applicable: The guideline was not adapted from another source.

#### DATE RELEASED

1999 May (reviewed 2006 Oct)

#### GUIDELINE DEVELOPER(S)

American Academy of Neurology - Medical Specialty Society\
American Epilepsy Society - Disease Specific Society

#### SOURCE(S) OF FUNDING

American Academy of Neurology (AAN)

#### GUIDELINE COMMITTEE

Quality Standards Subcommittee

#### COMPOSITION OF GROUP THAT AUTHORED THE GUIDELINE

*American Academy of Neurology Quality Standards Subcommittee Members*:
Gary Franklin, MD, MPH (Co-chair); Catherine A. Zahn, MD (Co-chair);
Milton Alter, MD, PhD; Stephen Ashwal, MD; John Calverley, MD; Richard
Dubinsky, MD; Jacqueline French, MD; Michael K. Greenberg, MD; Gary
Gronseth, MD; Deborah Hirtz, MD; Robert G. Miller, MD; and James
Stevens, MD

#### FINANCIAL DISCLOSURES/CONFLICTS OF INTEREST

Drs French and Faught have received research support from
Carter--Wallace Pharmaceuticals. Drs French, Faught, and Smith are past
members of a speakers´ bureau supported by Carter-- Wallace. Dr. Faught
has been a consultant for Carter--Wallace.

#### GUIDELINE STATUS

This is the current release of the guideline.

According to the guideline developer, this guideline has been reviewed
and is still considered to be current as of October 2006. This review
involved new literature searches of electronic databases followed by
expert committee review of new evidence that has emerged since the
original publication date.

#### GUIDELINE AVAILABILITY

Electronic copies: A list of American Academy of Neurology (AAN)
guidelines, along with a link to a Portable Document Format (PDF) file
for this guideline, is available at the [AAN Web
site](http://aan.com/go/practice/guidelines).

Print copies: Available from the AAN Member Services Center, (800)
879-1960, or from AAN, 1080 Montreal Avenue, St. Paul, MN 55116.

#### AVAILABILITY OF COMPANION DOCUMENTS

-   Practice statement definitions. St. Paul (MN): American Academy of
    Neurology.

-   Practice statement development. St. Paul (MN): American Academy of
    Neurology.

#### PATIENT RESOURCES

None available

#### NGC STATUS

This summary was completed by ECRI on February 12, 2002. The information
was verified by the guideline developer as of March 29, 2002.

#### COPYRIGHT STATEMENT

This NGC summary is based on the original guideline, which is
copyrighted by the American Academy of Neurology.

### DISCLAIMER

#### NGC DISCLAIMER

The National Guideline Clearinghouse™ (NGC) does not develop, produce,
approve, or endorse the guidelines represented on this site.

All guidelines summarized by NGC and hosted on our site are produced
under the auspices of medical specialty societies, relevant professional
associations, public or private organizations, other government
agencies, health care organizations or plans, and similar entities.

Guidelines represented on the NGC Web site are submitted by guideline
developers, and are screened solely to determine that they meet the NGC
Inclusion Criteria which may be found at
<http://www.guideline.gov/about/inclusion.aspx> .

NGC, AHRQ, and its contractor ECRI Institute make no warranties
concerning the content or clinical efficacy or effectiveness of the
clinical practice guidelines and related materials represented on this
site. Moreover, the views and opinions of developers or authors of
guidelines represented on this site do not necessarily state or reflect
those of NGC, AHRQ, or its contractor ECRI Institute, and inclusion or
hosting of guidelines in NGC may not be used for advertising or
commercial endorsement purposes.

Readers with questions regarding guideline content are directed to
contact the guideline developer.

Bottom of Form

© 1998-2008 National Guideline Clearinghouse

Date Modified: 11/10/2008