Felbamate (Page 6 of 8)

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 5,400 to 7,200 mg/day for durations between 6 and 51 days. One subject who received 5,400 mg/day as monotherapy for 1 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 Interactionssubsection).

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 3,600 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 1,200 mg/day in divided doses three or four 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 2,400 mg/day based on clinical response and thereafter to 3,600 mg/day if clinically indicated.

Conversion to Monotherapy:

Initiate felbamate at 1,200 mg/day in divided doses three or four times daily. Reduce the dosage of concomitant AEDs by one-third at initiation of felbamate therapy. At week 2, increase the felbamate dosage to 2,400 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 3,600 mg/day and continue to reduce the dosage of other AEDs as clinically indicated.

Adjunctive Therapy:

Felbamate should be added at 1,200 mg/day in divided doses three or four 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 1,200 mg/day increments at weekly intervals to 3,600 mg/day. Most side effects seen during felbamate adjunctive therapy resolve as the dosage of concomitant AEDs is decreased.

Table 6Dosage Table (adults)

	WEEK 1	WEEK 2	WEEK 3
Dosage reduction of Concomitant AEDs	REDUCE original dose by 20 to 33%*	REDUCE original dose by up to an additional 1/3*	REDUCE as clinically indicated
Felbamate Dosage	1,200 mg/day Initial dose	2,400 mg/day Therapeutic dosage range	3,600 mg/day Therapeutic dosage range
*See Adjunctive and Conversion to Monotherapy sections.

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 three or four 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, 400 mg are off-white to pale yellow colored, capsule shaped biconvex tablets, debossed with “10” and “53” separated by breakline on one side and plain on other and are supplied as:

NDC 72578-056-06 in bottles of 30 tablets with child-resistant closures

NDC 72578-056-16 in bottles of 90 tablets with child-resistant closures

NDC 72578-056-01 in bottles of 100 tablets with child-resistant closures

NDC 72578-056-05 in bottles of 500 tablets

NDC 72578-056-77 in cartons of 100 tablets (10 x 10 unit-dose)

Felbamate Tablets USP, 600 mg are light pink to pink colored, capsule shaped biconvex tablets debossed with “10” and “54” separated by breakline on one side and plain on other and are supplied as:

NDC 72578-057-06 in bottles of 30 tablets with child-resistant closures

NDC 72578-057-16 in bottles of 90 tablets with child-resistant closures

NDC 72578-057-01 in bottles of 100 tablets with child-resistant closures

NDC 72578-057-28 in bottles of 180 tablets

NDC 72578-057-05 in bottles of 500 tablets

NDC 72578-057-77 in cartons of 100 tablets (10 x 10 unit-dose)

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

Dispense in tight container.

Manufactured by:

Zydus Lifesciences Ltd.

Matoda, Ahmedabad, India.

Distributed by:

Viona Pharmaceuticals Inc.

Cranford, NJ 07016

Rev.: 07/22

PATIENT/PHYSICIAN ACKNOWLEDGEMENT FORM

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

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

IMPORTANT INFORMATION AND WARNING:

Felbamate, 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 ACKNOWLEDGEMENT:

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 is used to treat certain types of seizures and my physician has told me that I have this type(s) of seizures;
2. INITIALS: __________________________
3. I understand that felbamate is being used because my seizures have not been satisfactorily treated with other antiepileptic drugs;
4. INITIALS: __________________________
5. 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;
6. INITIALS: __________________________
7. 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;
8. INITIALS: __________________________
9. I understand that I should have the recommended blood work before my treatment with felbamate is 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;
10. INITIALS: __________________________
11. If I am currently taking other antiepileptic drugs, I understand that the manufacturer of felbamate recommends that the dosage of these other drugs be decreased by a certain amount when felbamate is started; if my physician determines that this should not be done in my case, he/she has explained the reason(s) for this decision;
12. INITIALS: __________________________
13. 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;
14. INITIALS: __________________________
15. I understand that antiepileptic drugs such as felbamate 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. ____________________.
16. 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 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

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, free of charge, on our website, http://vionausa.com/products/felbamate-tablets-usp/, or may be obtained by calling 1-888-304-5011. Permission to use the above Patient/Physician Acknowledgment Form by photocopy reproduction is also hereby granted by Viona Pharmaceuticals Inc.

Manufactured by:

Zydus Lifesciences Ltd.

Matoda, Ahmedabad, India.

Distributed by:

Viona Pharmaceuticals Inc.

Cranford, NJ 07016

Rev.: 07/22