Vigabatrin is a prescription antiepileptic drug (AED) used to treat certain types of seizures. Marketed under the brand name Sabril, the medication works by altering the balance of specific chemical messengers in the central nervous system to decrease the likelihood of seizures. Due to its profile of potential side effects, Vigabatrin is generally reserved for situations where other treatments have proven ineffective.
Therapeutic Applications
Vigabatrin is approved by the U.S. Food and Drug Administration (FDA) for specific and limited patient populations. Its primary indication is as monotherapy for infantile spasms (IS), also known as West Syndrome, in infants between one month and two years of age. Infantile spasms are a severe form of epilepsy that can cause significant developmental harm, making effective treatment urgent.
The medication is also indicated as adjunctive therapy for adults and children two years of age and older who suffer from refractory complex partial seizures (CPS). Refractory seizures are treatment-resistant, having responded inadequately to alternative antiepileptic drugs. Vigabatrin is added to a patient’s existing medication regimen, as it is not a first-line treatment.
FDA approval requires that the potential benefits of seizure control outweigh the risk of permanent vision loss. Consequently, its use is restricted to patients whose seizures pose a greater threat to health and development than the drug’s potential side effects.
How Vigabatrin Works
Vigabatrin’s action is linked to Gamma-Aminobutyric Acid (GABA), the central nervous system’s primary inhibitory neurotransmitter. GABA dampens the excitability of nerve cells, helping to prevent the uncontrolled electrical activity that triggers seizures.
Vigabatrin is a structural analog of GABA, but it does not directly bind to GABA receptors. Instead, it targets the enzyme responsible for breaking down GABA, called GABA transaminase (GABA-T). Vigabatrin acts as an irreversible inhibitor of GABA-T, permanently deactivating the enzyme.
This inhibition prevents the normal metabolic breakdown of GABA in the brain. The resulting effect is a sustained increase in the concentration of GABA available in the synapses (junctions between nerve cells). This elevated GABA level enhances the brain’s overall inhibitory activity, which raises the seizure threshold and suppresses irregular electrical discharges.
Safety Profile and Adverse Effects
Vigabatrin’s safety profile is dominated by a severe, irreversible adverse effect that carries an FDA Boxed Warning. The primary risk is Vigabatrin-Associated Vision Loss (VAVL), which involves permanent bilateral concentric visual field constriction. This results in a narrowing of the patient’s peripheral vision, often described as “tunnel vision,” and can lead to significant disability.
The risk of vision loss increases with both daily dosage and total cumulative exposure. No dose or duration of use is known to be entirely free of this risk. The onset is unpredictable and may occur weeks or years after starting treatment, potentially worsening even after the medication is stopped.
Patients may also experience common adverse effects, including somnolence, fatigue, dizziness, and weight gain. Other serious, less frequent adverse reactions include MRI signal changes and intramyelinic edema, particularly in infants. Peripheral neuropathy and suicidal behavior or ideation are also possible risks.
Required Monitoring and Administration
Due to the risk of permanent vision loss, Vigabatrin is only available through a restricted distribution system mandated by the FDA, known as the Vigabatrin Risk Evaluation and Mitigation Strategy (REMS) Program. The REMS program ensures that healthcare providers and patients are informed of the risks and that monitoring procedures are followed to ensure benefits outweigh risks.
Before treatment begins, patients must undergo a baseline ophthalmologic assessment, including visual field testing, to identify pre-existing visual defects. Throughout treatment, regular visual assessments are required, typically every three months, to monitor for developing field defects.
The mandatory vision testing cannot prevent damage but is intended for the early detection of visual field constriction. If vision loss is documented, the prescribing physician must weigh the risks and benefits to determine if the drug should be discontinued. Monitoring must continue for three to six months after cessation, as vision loss can progress even after the medication is stopped.
Vigabatrin is administered orally (tablets or powder for oral solution) and is typically taken twice daily. Treatment initiation involves gradual dose titration to the target therapeutic dose. Prescribers and the dispensing pharmacy must both be certified within the REMS program to ensure adherence to safety protocols.