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:
- Patients for whom risk/benefit ratio supports use because there is Class I evidence for benefit.
- Lennox–Gastaut patients over age 4 unresponsive to primary antiepileptic drugs.
- 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).
- Patients on felbamate more than 18 months.
- Patients for whom the current risk/benefit assessment does not support the use of felbamate:
- New onset epilepsy in adults or children
- Patients who have experienced significant prior hematologic adverse events
- Patients in whom follow-up and compliance will not allow careful monitoring
- 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
- 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:
- Children with intractable partial epilepsy
- Other generalized epilepsies unresponsive to primary agents
- Patients who experience unacceptable sedative or cognitive side effects with traditional antiepileptic drugs.
- Lennox–Gastaut syndrome under age 4 unresponsive to other antiepileptic drugs.
Risk management
- As therapy continues, risk/benefit ratio should be
constantly assessed.
- 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.
- 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.
- Even though individual clinical practice may vary, patients should be advised of the manufacturer’s recommendations.
Definitions:
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.
