What is Vigabatrin?
Vigabatrin is an antiepileptic drug primarily used to manage infantile spasms, spasms in tuberous sclerosis complex, and refractory complex partial seizures. This medication functions as an irreversible inhibitor of GABA transaminase, increasing GABA levels in the brain, which helps control seizure activity. Indications include infantile spasms and cases of epilepsy that do not respond to other treatments. Vigabatrin is associated with significant adverse effects, including visual field defects, which have led to an FDA-issued box warning. Due to these risks, routine visual monitoring is essential during treatment.
In addition to adverse effects, vigabatrin’s various pharmacokinetic features may necessitate dose adjustments in patients with certain conditions. Contraindications, drug interactions, and recommended monitoring are among the topics discussed in this activity. A collaborative, interprofessional healthcare team approach is critical to ensuring the safe and effective management of patients receiving vigabatrin. The team must adhere to evidence-based guidelines and adjust treatment as needed to mitigate adverse effects while maximizing seizure control.
Vigabatrin Indications
Vigabatrin was first synthesized in 1974 as a treatment for seizures. Clinical trials started in Europe in 1979 and the United States in 1980. These trials led to the approval of vigabatrin for the general public in the UK in 1989. Initially, the drug was most commonly prescribed for infantile spasms and refractory complex partial seizures.
However, officials raised concerns about its safety in 1997 despite its efficacy, citing the increased incidence of peripheral vision loss in patients receiving vigabatrin. After a series of studies, the FDA approved vigabatrin in 2009 for the treatment of infantile spasms as a single drug and refractory complex partial seizures as an additional drug to other anti-epileptic drugs.
Given the potential risks of visual loss, the approval comes with a supplemental “Risk Evaluation and Mitigation Strategy.” The International Tuberous Sclerosis Complex (TSC) Consensus Group recommends vigabatrin as the first-line therapy for treating infantile spasms associated with tuberous sclerosis complex.
A systematic review and meta-analysis found that vigabatrin is less effective than hormonal monotherapy (ACTH or steroids) for treating infantile epileptic spasms syndrome in patients with non-tuberous sclerosis complex etiologies. However, vigabatrin is more effective for infantile epileptic spasms syndrome in patients with tuberous sclerosis complex (TSC), making it the first-line medication for these patients.
FDA-Approved Indications
The FDA has approved vigabatrin for the treatment of infantile epileptic spasms syndrome and refractory complex partial seizures.
Off-Label Uses
A systematic review suggests that vigabatrin may reduce seizure frequency in adults with drug-resistant focal epilepsy. Vigabatrin is more effective for infantile epileptic spasms syndrome in patients with tuberous sclerosis complex (TSC), making it the first-line medication for these patients. Caution is advised when considering vigabatrin due to its risk-benefit considerations.
Vigabatrin FDA Label
Vigafyde (vigabatrin) FDA Label
Download the Vigafyde label below or visit: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=217684
Sabril (vigabatrin) FDA Label
Download the Sabril label below or visit: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=022006
Vigabatrin Mechanism of Action
Vigabatrin is an irreversible inhibitor of gamma-amino-butyric acid transaminase (GABA-T), an enzyme that degrades GABA, an inhibitory neurotransmitter. Vigabatrin is structurally similar to GABA, with an extra vinyl group. This similarity allows vigabatrin to act as a substrate for GABA-T, freeing GABA in the synaptic cleft. The concentration of GABA increases in the brain, which aids in terminating seizure activity. In addition to inhibiting GABA-T, vigabatrin also prevents the neuronal uptake of GABA and stimulates its release into the synapse. Some studies have demonstrated that vigabatrin enhances the action of the inhibitory neurotransmitter glutamine, which researchers suggest enhances its anticonvulsant effect.
Pharmacokinetics
Absorption: Complete absorption occurs after oral administration. Peak plasma concentrations are achieved in approximately 1 hour.
Distribution: Vigabatrin does not bind to plasma proteins and is widely distributed. The drug exhibits negligible plasma protein binding.
Metabolism: Vigabatrin is a mild inducer of CYP2C9, undergoes minimal hepatic metabolism, and is primarily excreted unchanged through the kidneys.
Excretion: Approximately 95% of vigabatrin is excreted unchanged in the urine.
Vigabatrin Dosage Forms and Strengths
Vigabatrin is available as a tablet for adults and older children, as a ready-to-use liquid solution for infants and younger children, and as an oral powder. Tablets and sachets of powder are available in 500 mg doses. The ready-to-use liquid solution is available in a 100 mg/mL concentration. The powder for oral solution requires dissolving 500 mg of vigabatrin in 10 mL of water to achieve a 50 mg/mL concentration.
Vigabatrin Brands
Vigabatrin is available as Vigafyde in a ready-to-use liquid dosage form.
Vigabatrin is available as Sabril in a tablet and powder for oral solution dosage form.
Benefits of Vigafyde (vigabatrin liquid) vs Sabril (vigabatrin powder)
If you are considering vigabatrin for your child, talk to your doctor about the risks and benefits of each formulation. Your doctor can help you decide which formulation is best for your child. The benefits of liquid vigabatrin over vigabatrin powder are highlighted below:
- Convenience: Vigafyde is ready to use, while the powder needs to be mixed with water before each dose. This can be more convenient for caregivers, especially when traveling or in situations where mixing the powder may be difficult.
- Accuracy: Studies have shown that caregivers are more likely to give the correct dose of vigabatrin when using the ready-to-use liquid formulation compared to the powder. This is because there is less room for error when mixing the liquid.
- Reduced risk of contamination: The powder formulation may be more susceptible to contamination, while the ready-to-use liquid is sterile and less likely to be contaminated.
It is important to note that both Vigafyde ready-to-use liquid and vigabatrin powder are effective in treating infantile spasms. The choice between the two formulations depends on individual needs and preferences.
Vigabatrin Stability
Vigabatrin is available in three formulations: tablets, a powder for oral solution, and a ready-to-use liquid solution, each with distinct stability profiles. According to the prescribing information, vigabatrin tablets remain stable until their expiration date when stored at controlled room temperature, offering long-term stability without the need for preparation. However, vigabatrin powder, once reconstituted with water, must be used immediately, with any unused portion discarded due to potential degradation or microbial growth in the absence of preservatives. In contrast, the vigabatrin liquid solution (Vigafyde) maintains stability for 90 days after the bottle is opened, providing a significant advantage over the powder in terms of shelf life post-opening. The liquid formulation’s 90-day post-opening stability reduces waste, simplifies storage, and supports consistent dosing for patients requiring ongoing treatment, making it more practical than the powder, which demands frequent preparation and immediate use.
Latest Vigabatrin Research
Liquid Medication Dosing Errors: Comparison of a Ready-to-Use Vigabatrin Solution to Reconstituted Solutions of Vigabatrin Powder for Oral Solution
Abstract
Introduction
Vigabatrin (VGB) is intended for use by caregivers of infants (1 month to 2 years old) diagnosed with infantile spasms (IS). Commercially available vigabatrin powders require caregiver reconstitution prior to oral administration. This study compared the ability of caregivers to accurately provide a targeted dose of vigabatrin using a ready-to-use (RTU) vigabatrin oral solution (VGB-RTU solution) and SABRIL® (vigabatrin) powder for oral solution, Lundbeck LLC, (vigabatrin powder) without instruction from a healthcare professional.
Methods
A crossover comparative usability study with 30 lay users (15 caregivers with vigabatrin powder experience and 15 oral-syringe/medication preparation naïve users) which required users to deliver a single dose of both VGB-RTU surrogate solution and vigabatrin powder to a sample collection bottle was performed. Doses were measured analytically with a primary endpoint to deliver doses within ± 10% of the target dose of 1125 mg.
Results
All 30 participants administered VGB-RTU solution doses within ± 5% of the target, while only 23/30 of the vigabatrin powder doses were within ± 10%. All naïve users delivered vigabatrin doses using VGB-RTU solution within ± 5% of the target; whereas only 13/15 delivered doses within ± 10% for vigabatrin powder. All experienced vigabatrin users delivered calculated vigabatrin doses using VGB-RTU solution within ± 3%; whereas only 10/15 delivered doses within ± 10% for vigabatrin powder. Users were equally able to accurately deliver the prescribed volumes of both products. Calculated doses of VGB-RTU solution (mg) were significantly less variable (p < 0.0001) and more accurate (p < 0.01) than doses of vigabatrin powder.
Conclusion
Caregivers delivered more accurate and less variable doses of the ready-to-use solution compared to solutions prepared from vigabatrin powders for oral solution. These differences were shown to be due to caregiver errors in reconstituting vigabatrin powders for oral solution.
Download the study below or visit: https://link.springer.com/article/10.1007/s12325-024-03089-0
The PREVeNT Trial
The PREVeNT study found that early vigabatrin treatment delayed the onset and reduced the overall prevalence of infantile spasms in TSC infants. However, the seizure prevention was not seen for other seizure types, including focal seizures, that are highly prevalent in this population. PREVeNT, similarly to EPISTOP, reported a reduced incidence of infantile spasms up to 24 months of age.
Download the study below or visit: https://pubmed.ncbi.nlm.nih.gov/37638552
EPISTOP Trial
Infantile spasms are seen in 50 to 70% of children with TSC, and are associated with both drug-resistance and intellectual disability. Importantly, in EPISTOP, none of the children who received preventive treatment developed infantile spasms throughout the 2-year course of the study, in contrast to 10 of 25 (40%) receiving conventional treatment.
Download the study below or visit: https://pmc.ncbi.nlm.nih.gov/articles/PMC7898885
Vigabatrin Risk Evaluation and Mitigation Strategy (REMS)
A REMS is a strategy to manage known or potential serious risks associated with a drug product, and is required by the Food and Drug Administration (FDA) to ensure the benefits of a drug outweigh its risks. The vigabatrin black box warning alerts healthcare providers and patients to the serious risk of permanent vision loss, specifically bilateral concentric visual field constriction, which can lead to tunnel vision or disability and may occur unpredictably during treatment. The REMS (Risk Evaluation and Mitigation Strategy) program is a mandatory safety protocol requiring prescriber certification, patient enrollment, and regular vision monitoring to ensure the drug’s benefits outweigh its risks. This program also restricts vigabatrin dispensing to certified pharmacies and mandates periodic vision assessments to manage and mitigate the risk of vision impairment.
Specifically, the current goals and purpose of the Vigabatrin REMS is to mitigate vision loss associated with vigabatrin by:
- Ensuring that healthcare providers are educated about the risk of vision loss, the need to counsel patients about the risk, and the need for periodic visual monitoring
- Ensuring that vigabatrin is dispensed only to patients with documentation that they are informed about the risk of vision loss associated with vigabatrin and the need for periodic visual monitoring
You can learn more about the Vigabatrin REMS here: https://www.vigabatrinrems.com/
Support Groups for Infantile Spasms
- Infantile Spasms Action Network (ISAN) – https://infantilespasms.org
- Epilepsy Foundation – https://www.epilepsy.com/programs/family-services
- Infantile Spasms Community Facebook – https://www.facebook.com/groups/infantilespasmscommunity
- Epilepsy Alliance America – https://epilepsyallianceamerica.org/programs-services/support-groups
- r/infantilespasms Reddit – https://www.reddit.com/r/infantilespasms
Support Groups for Tuberous Sclerosis Complex (TSC)
- Tuberous Sclerosis Alliance (TSC Alliance) – https://www.tscalliance.org/find-support/community-support-network
- Tuberous Sclerosis Association (TSA) – https://tuberous-sclerosis.org/
- TSC Alliance Tuberous Sclerosis Complex Facebook – https://www.facebook.com/groups/TS.Alliance.Online.Discussion.Group
- r/TuberousSclerosisComp Reddit – https://www.reddit.com/r/TuberousSclerosisComp/
Sources:
https://www.ncbi.nlm.nih.gov/books/NBK557579
https://link.springer.com/article/10.1007/s12325-024-03089-0
https://en.wikipedia.org/wiki/Vigabatrin
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a88ac1b4-e2c9-45c0-b321-4785902172e3
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8d3d6316-33ab-41e8-9485-4495c218be56
Note: This is for informational purposes only. For medical advice or diagnosis, consult a professional.