Felbamate (Page 8 of 10)

DRUG ABUSE AND DEPENDENCE

Abuse:

Abuse potential was not evaluated in human studies.

Dependence:

Rats administered felbamate orally at doses 8.3 times the recommended human dose 6 days each week for 5 consecutive weeks demonstrated no signs of physical dependence as measured by weight loss following drug withdrawal on day 7 of each week.

OVERDOSAGE

Four subjects inadvertently received felbamate as adjunctive therapy in dosages ranging from 5400 mg/day to 7200 mg/day for durations between 6 and 51 days. One subject who received 5400 mg/day as monotherapy for one week reported no adverse experiences. Another subject attempted suicide by ingesting 12,000 mg of felbamate in a 12-hour period. The only adverse experiences reported were mild gastric distress and a resting heart rate of 100 bpm. No serious adverse reactions have been reported. General supportive measures should be employed if overdosage occurs. It is not known if felbamate is dialyzable.

DOSAGE AND ADMINISTRATION

Felbamate has been studied as monotherapy and adjunctive therapy in adults and as adjunctive therapy in children with seizures associated with Lennox-Gastaut syndrome. As felbamate is added to or substituted for existing AEDs, it is strongly recommended to reduce the dosage of those AEDs in the range of 20% to 33% to minimize side effects (see Drug Interactions subsection).

Dosage Adjustment in the Renally Impaired:

Felbamate should be used with caution in patients with renal dysfunction. In the renally impaired, starting and maintenance doses should be reduced by one-half (see CLINICAL PHARMACOLOGY/Pharmacokinetics and PRECAUTIONS). Adjunctive therapy with medications which affect felbamate plasma concentrations, especially AEDs, may warrant further reductions in felbamate daily doses in patients with renal dysfunction.

Adults (14 years of age and over)

The majority of patients received 3600 mg/day in clinical trials evaluating its use as both monotherapy and adjunctive therapy.

Monotherapy: (Initial therapy)

Felbamate has not been systematically evaluated as initial monotherapy. Initiate felbamate at 1200 mg/day in divided doses three or 4 times daily. The prescriber is advised to titrate previously untreated patients under close clinical supervision, increasing the dosage in 600 mg increments every 2 weeks to 2400 mg/day based on clinical response and thereafter to 3600 mg/day if clinically indicated.

Conversion to Monotherapy:

Initiate felbamate at 1200 mg/day in divided doses 3 or 4 times daily. Reduce the dosage of concomitant AEDs by one-third at initiation of felbamate therapy. At week 2, increase the felbamate dosage to 2400 mg/day while reducing the dosage of other AEDs up to an additional one-third of their original dosage. At week 3, increase the felbamate dosage up to 3600 mg/day and continue to reduce the dosage of other AEDs as clinically indicated.

Adjunctive Therapy:

Felbamate should be added at 1200 mg/day in divided doses 3 or 4 times daily while reducing present AEDs by 20% in order to control plasma concentrations of concurrent phenytoin, valproic acid, phenobarbital and carbamazepine and its metabolites. Further reductions of the concomitant AEDs dosage may be necessary to minimize side effects due to drug interactions. Increase the dosage of felbamate by 1200 mg/day increments at weekly intervals to 3600 mg/day. Most side effects seen during felbamate adjunctive therapy resolve as the dosage of concomitant AEDs is decreased.

Table 6. Dosage Table (adults)

* See Adjunctive and Conversion to Monotherapy sections.
Dosage reduction of concomitant AEDs	WEEK 1 REDUCE original dose by 20% to 33%*	WEEK 2 REDUCE original dose by up to an additional 1/3	WEEK 3 REDUCE as clinically indicated
Felbamate Dosage	1200 mg/day Initial dose	2400 mg/day Therapeutic dosage range	3600 mg/day Therapeutic dosage range

While the above felbamate conversion guidelines may result in a felbamate 3600 mg/day dose within 3 weeks, in some patients titration to a 3600 mg/day felbamate dose has been achieved in as little as 3 days with appropriate adjustment of other AEDs.

Children with Lennox-Gastaut Syndrome (Ages 2 to 14 years)

Adjunctive Therapy :

Felbamate should be added at 15 mg/kg/day in divided doses 3 or 4 times daily while reducing present AEDs by 20% in order to control plasma levels of concurrent phenytoin, valproic acid, phenobarbital, and carbamazepine and its metabolites. Further reductions of the concomitant AEDs dosage may be necessary to minimize side effects due to drug interactions. Increase the dosage of felbamate by 15 mg/kg/day increments at weekly intervals to 45 mg/kg/day. Most side effects seen during felbamate adjunctive therapy resolve as the dosage of concomitant AEDs is decreased.

HOW SUPPLIED

Felbamate Tablets, USP contain 400 mg or 600 mg of felbamate, USP.

The 400 mg tablet is white to off-white, modified capsule shaped, functionally scored, bisected tablet “FE 400” debossed on bisect side (upper) and “ALV550” on opposite side (bottom) of the tablet. They are available as follows:

NDC 47781-627-01
bottles of 100 tablets

The 600 mg tablet is white to off-white, modified capsule shaped, functionally scored, bisected tablet “FE 600” debossed on bisect side (upper) and “ALV551” on opposite side (bottom) of the tablet. They are available as follows:

NDC 47781-630-01
bottles of 100 tablets

Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]

Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

PHARMACIST: Dispense a Medication Guide with each prescription.

To report SUSPECTED ADVERSE REACTIONS, contact Alvogen, Inc. at 1-866-770-3024 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

PI267-00 Rev. 08/2018

PATIENT/PHYSICIAN ACKNOWLEDGMENT FORM

FELBAMATE TABLETS SHOULD NOT BE USED BY PATIENTS UNTIL THERE HAS BEEN A COMPLETE DISCUSSION OF THE RISKS.

All patients treated with felbamate tablets should acknowledge that they understand the risks and other information about felbamate tablets discussed below, and physicians should acknowledge this discussion.

IMPORTANT INFORMATION AND WARNING:

Felbamate tablets, taken by itself or with other prescription and/or non-prescription drugs, can result in a severe, potentially fatal blood abnormality (“aplastic anemia”) and/or severe, potentially fatal liver damage.

PATIENT ACKNOWLEDGMENT:

Do not sign this form if there is anything you do not understand about the information you have received. Ask your doctor about anything you do not understand before you initial any of the items below or sign this form.

My [My son, daughter, ward ________________________________________’s] treatment with felbamate tablets has been personally explained to me by Dr._____________________________. The following points of information, among others, have been specifically discussed and made clear and I have had the opportunity to ask any questions concerning this information:

1.

I, _______________________________________________________________ (Patient’s Name), understand that felbamate tablets are used to treat certain types of seizures and my physician has told me that I have this type(s) of seizures;

INITIALS: __________________________

2.

I understand that felbamate tablets are being used because my seizures have not been satisfactorily treated with other antiepileptic drugs;

INITIALS: __________________________

3.

I understand that there is a serious risk that I could develop aplastic anemia and/or liver failure, both of which are potentially fatal, by using felbamate tablets;

INITIALS: __________________________

4.

I understand that there are no laboratory tests which will predict if I am at an increased risk for one of the potentially fatal conditions;

INITIALS: __________________________

5.

I understand that I should have the recommended blood work before my treatment with felbamate tablets has begun (baseline) and periodically thereafter as clinical judgement warrants. I understand that although this blood work may help detect if I develop one of these conditions, it may do so only after significant, irreversible and potentially fatal damage has already occurred;

INITIALS: __________________________

6.

If I am currently taking other antiepileptic drugs, I understand that the manufacturer of felbamate tablets recommends that the dosage of these other drugs be decreased by a certain amount when felbamate tablets are started; if my physician determines that this should not be done in my case, he/she has explained the reason(s) for this decision;

INITIALS: __________________________

7.

I understand that I must immediately report any unusual symptoms to Dr. _______________________ and be especially aware of any rashes, easy bruising, bleeding, sore throats, fever, and/or dark urine;

INITIALS: __________________________

8.

I understand that antiepileptic drugs such as felbamate tablets may increase the risk of suicidal thoughts and behavior. I understand that I must immediately report any unusual changes in mood or behavior, symptoms of depression or thoughts about self-harm to Dr. ___________.

INITIALS: __________________________

Patient, Parent, or Guardian

Address

Telephone

PHYSICIAN STATEMENT:

I have fully explained to the patient, ___________________________________________, the nature and purpose of the treatment with felbamate tablets and the potential risks associated with that treatment. I have asked the patient if he/she has any questions regarding this treatment or the risks and have answered those questions to the best of my ability. I also acknowledge that I have read and understand the prescribing information.

_________________________________________________________________________
Physician Date

Acknowledgment Form 627-00 Rev.08/20168

NOTE TO PHYSICIAN:

It is strongly recommended that you retain a signed copy of the Patient/Physician Acknowledgment Form with the patient’s medical records.

SUPPLY OF PATIENT/PHYSICIAN ACKNOWLEDGMENT FORMS:

A supply of “Patient/Physician Acknowledgment” Forms as printed above is available by calling Alvogen, Inc. at 1-866-770-3024. Permission to use the above Patient/Physician Acknowledgment Form by photocopy reproduction is also hereby granted by Alvogen, Inc.