Vigabatrin (Sabril) for treatment-resistant epilepsy now available in US

Vigabatrin (Sabril) poses the high risk of permanent vision loss

Vigabatrin (Sabril) to treat treatment-resistant epilepsy is now available in US, but no through drug stores and pharmacies but directly from Lundbeck because of the high risk of vision loss associated with the drug.

Vigabatrin (Sabril) tablets and powder for oral solution are now available for prescribing in the United States, announced Lundbeck Inc, a wholly owned subsidiary of Copenhagen, Denmark-based H. Lundbeck A/S.

Vigabatrin (Sabril) was approved by the U.S. Food and Drug Administration as monotherapy for pediatric patients one month to two years of age with infantile spasms (IS) for whom the potential benefits outweigh the potential risk of vision loss in August 2009.The disorder can be difficult to treat because of the frequency of seizures.

Vigabatrin (Sabril) was also approved for adult use in combination with other treatments for refractory complex partial seizures (CPS) that have not responded adequately to previous drug therapies and for whom the potential benefits outweigh the risk of vision loss.1, 2 It is not indicated as a first line agent for CPS.

While Sabril is not for everyone confronting these challenging epilepsies, we are so pleased to be able to make this therapy available in the U.S. for the patients who need it,” said Jeffrey S. Aronin, CEO, Lundbeck Inc. The tireless work of our employees, the epilepsy community and the FDA made this day possible. Above all, we are gratified to be able to bring an important new treatment option to patients who can benefit from having approved alternatives to consider.

Vigabatrin (Sabril) causes permanent bilateral concentric visual field constriction in 30 percent or more of patients that ranges in severity from mild to severe, including tunnel vision to within 10 degrees of visual fixation and can result in disability.

Vigabatrin (Sabril) also can damage the central retina and may decrease visual acuity, in some cases.

Vigabatrin (Sabril) causes permanent vision loss in infants, children and adults.  The onset is unpredictable and can occur within weeks of starting treatment, or sooner, or at any time during treatment, even after months or years.

Because of the risk of permanent vision loss, Sabril is available through an FDA-mandated Risk Evaluation and Mitigation Strategy (REMS), which specifies elements to manage the risk of permanent vision loss including a special restricted distribution program called SHARE (Support Help and Resources for Epilepsy), required vision testing, a patient registry, and mandatory benefit-risk assessments. The Sabril REMS was a critical component in receiving US FDA approval.

“Because these are truly challenging types of epilepsies, it’s important that physicians, patients and their families have therapy options available to them and the information they need to make an informed treatment decision,” stated Michael C. Smith, M.D., Director, Rush Epilepsy Center and Rush University Medical Center in Chicago and a member of the Professional Advisory Board of the Epilepsy Foundation of America.

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.

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.

What are Complex Partial Seizures?

There are three million Americans affected by epilepsy3 and approximately 35 percent have CPS, the single largest seizure type, which originates from a single region of the brain and can cause impaired consciousness.

Despite the availability of many antiepileptic drugs, approximately 30 to 36 percent of adults with CPS continue to have seizures.5,6 Sabril provides a new and valuable add-on treatment option for adult CPS patients who have not responded to several alternative treatments and are considered ‘refractory’ to treatment.

Given the potential benefit compared to the risk of permanent vision loss, it is expected that only a small percentage of refractory CPS patients will initiate and maintain treatment with Sabril as add-on therapy.

Vigabatrin (Sabril) is an oral antiepileptic drug developed in the United States by Lundbeck Inc.  Sabril is available in two formulations—in 500 mg tablets for use as add-on therapy for adults with refractory CPS and in 500 mg packets of powder for oral solution for infants with IS.

The precise mechanism of Sabril’s antiseizure effect is unknown, but is believed to be the result of its action as an irreversible inhibitor of gamma-aminobutyric acid transaminase (GABA-T), the enzyme responsible for the metabolism of the inhibitory neurotransmitter GABA.

This action results in increased levels of GABA in the central nervous system.  No direct correlation between plasma concentration and efficacy has been established.  The duration of drug effect is presumed to be dependent on the rate of enzyme re-synthesis rather than on the rate of elimination of the drug from the systemic circulation.

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).