A Practitioner’s Guide to Prescribing Felbamate for Adults with Intellectual Disabilities

Abstract

We developed this felbamate guideline using drug prescribing information and reviewing the available literature on relevant neuropsychiatric disorders in populations without intellectual disabilities because of the dearth of available literature on the population with intellectual disabilities. This guideline includes indications, contraindications, assessments prior to and during treatment, dosing with particular focus on dosing modifications required by drug–drug interactions or personal characteristics, and adverse drug reactions. The procedures contained in this guideline may not fully account for all of the possible risks of treatment in this population because of the limited studies available; thus, there will be a need to periodically update this guideline as new information becomes available. Nevertheless, we believe that this guideline provides a useful resource for clinicians who treat epilepsy in adult individuals with intellectual disabilities. A felbamate drug utilization review that summarizes this guideline is described.

Appendix Drug Utilization Review: Felbamate

DRUG UTILIZATION REVIEW CRITERIA				CRITERIA MET
FELBAMATE FOR ADULTS WITH IDs				YES	NO	NA
1) Indication: Check one of the following indications for use
	Patients with epilepsy who respond inadequately to alternative treatments and whose epilepsy is so severe that a substantial risk of aplastic anemia and/or liver failure is deemed acceptable in light of the benefits conferred by its use. Felbamate can be used as either monotherapy or adjunctive therapy in the treatment of partial seizures (with or without generalization) in adults with epilepsy or for treatment of generalized seizures associated with Lennox–Gastaut syndrome.
To meet indication criteria, this indication is present and documented.				‫	‫
2) Dose: Specify current formulation and doses_________________
	Felbamate (Felbutol) is given three to four times/day (Y__ N__) unless otherwise recommended by consultant with expertise in the area (Y__).			‫	‫	‫
	The first anticonvulsive daily dose was ≤1,200 mg (Y__ N__) unless otherwise recommended by consultant with expertise in the area (Y__).			‫	‫	‫
	The maximum antiepileptic dose was ≤3,600 mg/day (Y__ N__) unless otherwise recommended by consultant with expertise in the area (Y__).			‫	‫	‫
	Taking phenytoin__, carbamazepine___. The chart documents the interaction (Y__ N__). The dosage of felbamate may need to be increased when any of these antiepileptic drugs are added; the discontinuation of any of these inducers may need to be followed by a decrease in felbamate dosage.			‫	‫	‫
	Taking other inducers_____________________________. The chart documents the interaction (Y__ N__). The dosage of felbamate may need to be increased when an inducer was added and the discontinuation of the inducer may need to be followed by a decrease in felbamate dosage.			‫	‫	‫
	Taking phenytoin__, phenobarbital__, primidone__, carbamazepine__, valproate__. Felbamate may increase the blood levels of these compounds. The chart documents the interaction (Y__ N__). The dosage of these antiepileptics may need to be decreased when felbamate is added and the discontinuation of felbamate may need to be followed by a dose increase of any of these antiepileptics.			‫	‫	‫
	Taking psychiatric drugs possibly induced by felbamate (e.g., typical antipsychotics___, quetiapine___, ­risperidone___, aripiprazole___, clonazepam___ or alprazolam___). Other________________________ The chart documents the interaction (Y__ N__). The dosage of these drugs may need to be increased when felbamate is added and the discontinuation of felbamate may need to be followed by a decrease in dosage of any of these drugs.			‫	‫	‫
	Taking CYP3A substrates (e.g., some calcium channel blockers, statins, and immunosuppressants). List drugs ___________________________. The chart documents the interaction (Y__ N__). The dosage of these drugs may need to be increased when felbamate is added and the discontinuation of felbamate may need to be followed by a decrease in dosage of any of these drugs.			‫	‫	‫
	Taking oral contraceptives___. The chart documents (Y__ N__) that the oral contraceptive may not be effective.			‫	‫	‫
	Renal impairment____. The chart documents (Y__ N__) the use of lower felbamate doses (decreased by half).			‫	‫	‫
To meet dose criteria, all are Yes or NA.				‫	‫
3) Relative contraindications: Check left boxes of any present.
‫	Pregnancy (Category D) or breast feeding.
‫	History of autoimmune disorders or strong family history of autoimmune disorders that may increase risk of aplastic anemia.
‫	History of hepatic dysfunction or abnormal transaminases.
Answer Yes if none is checked, or if any of the above are checked and rationale is documented in the chart to meet relative contraindication criteria. Answer No if rationale is NOT documented in the chart.				‫	‫
4) Baseline monitoring studies:
‫	Informed consent form from the company was completed.
‫	Weight, height (with body mass index), and waist circumference.
‫	Complete CBC___ with reticulocyte count___ and iron___.
‫	Liver function tests.
‫	Serum concentrations of the concomitantly administered antiepileptics that are usually followed with therapeutic drug monitoring.
‫	If a female patient has potential to be pregnant, a pregnancy test is completed.
Answer Yes (all completed) or No. If information is not available, check NA.				‫	‫	‫
5) Additional baseline monitoring (only when there is history of kidney disturbance or high creatinine level):
‫	Creatinine clearance.
Answer Yes or No. If information is not applicable, check NA.				‫	‫	‫
6) Monthly monitoring studies for first year:
‫	Liver function tests___ and complete CBC___ are monitored every month for the first year.
‫	Weight is monitored every month for the first year.
Answer Yes (all completed) or No. If information is not applicable, check NA.				‫	‫	‫
7) Annual monitoring:
‫	Body mass index and waist circumference.
‫	Liver function tests___ and complete CBC___.
Answer Yes (all completed) or No. If information is not applicable, check NA.				‫	‫	‫
8) Annual monitoring needed only after abnormal results before or after felbamate treatment:
‫	Creatinine clearance.
Answer Yes (completed) or No. If information is not applicable, check NA.				‫	‫	‫
9) Discontinuation:
	Felbamate is or was withdrawn slowly to minimize the potential of increased seizure frequency (Y__ N__). Abrupt withdrawal was justified by a major medical reason (Y__ N__).			‫	‫	‫
10) Adverse drug reactions (ADRs) due to felbamate: Check left boxes to indicate which ADRs are present.
10.1) Common ADRs:
‫	Neurological: Including insomnia, dizziness, headaches, or somnolence.	‫	Gastrointestinal: Nausea or vomiting.
10.2) Relatively uncommon ADRs:
‫	Depression, anxiety, irritability, psychosis, hyperactivity, or aggression.	‫	Other_____________.
10.3) Potentially lethal ADRs:
‫	Aplastic anemia.	‫	Acute liver failure.
‫	Stevens–Johnson syndrome/toxic epidermal necrolysis. Skin rash.	‫	Suicidal ideation or behavior.
10.4) Metabolic syndrome:
‫	Weight loss.
Answer Yes (intervention or benefit/risk discussion after ADRs developed) or No (neither intervention nor benefit/risk discussion after ADRs developed) or NA (no abnormality developed).				‫	‫	‫