Modification for Anticonvulsant Used for Seizures; Weighing Risks

On June 21, 2016, the FDA announced the approval of a supplemental New Drug Application (sNDA) modifying the risk evaluation and mitigation strategy (REMS) for Sabril. The FDA determined that, although the risk of vision loss with Sabril still exists, requiring submission of OAFs as an element of the REMS is no longer necessary to ensure the benefits of Sabril outweigh its risks. Prescribers should continue to follow the vision monitoring recommendations described in the prescribing information for Sabril. As a condition of certification in the REMS, prescribers must agree to ensure that periodic visual monitoring is conducted as described in the product label.


Sabril (vigabatrin), an anticonvulsant medication, was approved on August 21, 2009 for use as monotherapy in infants one month to two years of age who suffer from infantile spasms, a form of epilepsy. Infantile spasms are associated with a poor prognosis that includes neurodevelopmental regression and a significant mortality rate. Sabril is also approved for use in combination with other medications for refractory partial complex seizures in patients ten years of age and older who have responded inadequately to several alternative treatments.


Sabril was approved with a risk evaluation and mitigation strategy (REMS) to ensure that the benefits of Sabril outweigh the risks of vision loss and of suicidal thoughts and behaviors. Sabril can cause permanent bilateral concentric visual field constriction, including tunnel vision that can result in disability. In some cases, it also can damage the central retina and may decrease visual acuity. Since approval, the REMS has required periodic visual monitoring results to be documented through submission of ophthalmologic assessment forms (OAFs).


The FDA is also modifying the REMS to remove additional education requirements about the risk of suicidal thoughts and behaviors because this risk is adequately communicated in the Warnings and Precautions section and the Medication Guide of the current FDA-approved prescribing information.


In addition, the FDA is eliminating the patient registry as an element of the REMS because the related postmarketing study is a better mechanism for further characterizing and assessing the risk of vision loss associated with Sabril.


Finally, the REMS is being modified to allow for inpatient pharmacy certification in order to alleviate delays in initiating treatment with Sabril and interruptions in treatment during hospitalizations.


In the modified Sabril REMS:


  • Health care professionals who prescribe Sabril, must still be specially certified. As a condition of certification, prescribers must counsel patients and caregivers about the risks associated with Sabril, complete the Patient/Parent/Legal Guardian-Physician Agreement Form for each patient, and ensure that periodic visual monitoring, as described in the Prescribing Information, is performed on an ongoing basis for each patient.
  • Pharmacies that dispense Sabril must be specially certified. The pharmacy enrollment form has been revised to provide a clear pathway for inpatient pharmacies to become certified. This action is intended to alleviate delays in initiating treatment and to allow for the continuation of treatment with Sabril during a patient’s hospitalization.
  • Patients must sign a Patient/Parent/Legal Guardian-Physician Agreement Form to become enrolled in the Sabril REMS Program, indicating that they have been counseled by their prescriber regarding the risk of vision loss and the need for periodic visual monitoring based on the recommendations in the Prescribing Information.


See the FDA Postmarket Drug Safety Information


See also Medical Law Perspectives, May 2013 Report: Drugs, Dosage, and Damage: Physician Liability for Prescribing or Administering Medication