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New Epilepsy Drugs
Another new antiepileptic drug, vigabatrin (Sabril®), received US Food and Drug Administration (FDA) approval in 2009 -- good news for the 30% of patients with treatment-resistant epilepsy. Vigabatrin joined the 11 antiepileptic drugs that have received FDA approval since 1993: felbamate (Felbatol®), gabapentin (Neurontin®), lacosamide (Vimpat®), lamotrigine (Lamictal®), levetiracetam (Keppra®), oxcarbazepine (Trileptal®), pregabalin (Lyrica®), rufinamide (Banzel™), tiagabine (Gabitril®), topiramate (Topamax®), and zonisamide (Zonegran®). All of these drugs offer the potential for seizure control, which must be weighed against their risk for adverse effects. Physicians must be aware of each drug's idiosyncratic side effects, such as hyponatremia with oxcarbazepine, edema with pregabalin, and metabolic acidosis with topiramate. Felbamate was implicated in life-threatening anemia and hepatic failure, for which it received a black box warning. All of these antiepileptic drugs can be prescribed without enrolling patients in a drug surveillance program, except the newest one, vigabatrin.
Irreversible Visual Field Defects and the SHARE program
Because of its substantial risk for permanent visual field defects, vigabatrin can only be prescribed by physicians who participate in the SHARE (Support, Help and Resources for Epilepsy) program (1-800-45-SHARE). The purpose of SHARE is to monitor patients for the development of visual field defects, and to stop the drug as quickly as possible if these develop. The field defects are permanent, but stopping the drug may limit the damage. SHARE is a "risk mitigation program," developed jointly by the company (Lundbeck) and the FDA.
To prescribe vigabatrin, 4 different forms must be completed and returned to the company (www.lundbeckSHARE.com). The first is a "Prescriber Enrollment and Agreement Form," which enlists the physician into the SHARE program. This form requires physicians to agree that they "have experience in treating epilepsy," "know the risks of Sabril treatment, specifically vision loss," "must order and review visual assessment testing at baseline," "counsel patients," "report all serious adverse events" to the FDA and the manufacturer, and make other commitments.
A New Business Partner
Each patient must complete a "Treatment Initiation Form," which includes their personal information, the site of vigabatrin administration (home, hospital, or other facility), and their insurance information. The physician must also complete the form, which requires a National Provider Identifier (NPI) number. The physician must also authorize TheraCom as a "designated agent" and "business associate" for payment purposes.
Sign Here...
If the prescription is for infantile spasms, a "Parent/Legal Guardian-Physician Agreement" must be completed, which requires the parent/legal guardian to sign twice and initial 12 points. If the prescription is for partial complex seizures, a "Patient/Parent/Legal Guardian-Physician Agreement" is required. The patient/parent/legal guardian must sign twice and initial 10 points. Physicians are also required to sign the form for each seizure type.
Not Available in Stores...
After the patient is accepted into the program, all prescriptions must go through the SHARE Call Center. Then the drug is shipped from a specialty pharmacy. Only a 30-day supply is provided at a time. Vigabatrin is not available at community or hospital pharmacies. Patients receive a "Sabril Starter Kit," which includes the necessary forms, a patient diary, medication guide, instructions for mixing the oral solution, and other information.
After the first 30 days of treatment for infantile spasms, a "Treatment Maintenance Form" must be submitted to attest to the necessity of continuing therapy. For patients with infantile spasms, a treatment response should be evident by this time. If infants do not respond by 30 days, keeping them on the drug exposes them to the risk for visual loss with little potential benefit. Subsequently, ophthalmologic evaluations must be submitted every 3 months. Without evidence of these periodic examinations, the company will cease to provide the medication. For patients with refractory partial complex seizures, a treatment maintenance form must be submitted after 90 days.
There is no question that the risk for irreversible visual loss with vigabatrin treatment is substantial and significant. While the SHARE program provides heightened supervision regarding the potential complication of visual loss, it places an additional administrative burden on the physician. The company provides no compensation for the additional paperwork, there is no billing code for the process, and physicians may assume additional liability risk when treating patients with a known retinal toxin.
SHARE and TOUCH
The SHARE program is similar to the TOUCH (Tysabri Outreach Unified Commitment to Health) prescribing program for natalizumab (Tysabri®), which requires physicians, pharmacies, and patients to register to monitor the incidence of progressive multifocal leukoencephalopathy in patients with multiple sclerosis, a life-threatening complication of natalizumab. A potential consequence of programs like SHARE and TOUCH may be to restrict the prescribing of new drugs with harmful idiosyncratic adverse events to relatively few doctors, probably those practicing at specialized centers. If these mandatory drug registries continue to proliferate, it is difficult to imagine how a general neurologist could keep up with the stringent bureaucratic requirements of multiple drug programs. One multiple sclerosis specialist told me that the extra physician time required by the TOUCH program is minimal, as long as he has a trained nurse to help. This solution may be practical, but begs the question of where the money will come from to support additional office staff.
More Referrals to Epilepsy Centers?
If general neurologists cannot manage the burdens of these registry programs, patients who require these treatments will be steered to tertiary centers for epilepsy, multiple sclerosis, and other diseases as new potent, complex, and potentially toxic treatments evolve. Some neurologists may be reluctant to refer and too busy to participate in these programs, making it less likely that their patients will benefit from these new medications. Patients who live far from specialized centers may also be at a disadvantage. For other patients, their need for specialized drugs that require enrollment in a patient registry may spur their neurologists to refer them to a center of excellence.
Conclusions
For the 30% of patients with drug-resistant epilepsy, referral to an epilepsy center for vigabatrin will have the added benefit of a comprehensive evaluation and consideration for the ketogenic diet, vagus nerve stimulator, epilepsy surgery, and other specialized treatment. It will be important to assess how programs like SHARE and TOUCH affect the dynamics of neurologic practice and treatment outcomes.
Dr. Wilner is the author of Epilepsy: 199 Answers (A Doctor Responds to His Patients' Questions), 3rd ed, and writes "Neuro Notes," a bimonthly community blog for Medscape.com. Dr. Wilner's writings can be followed at: www.twitter.com/drwilner
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