Generic Name

Vigabatrin

Mechanism

Vigabatrin irreversibly inhibits the enzyme GABA transaminase, the principal catabolic route for γ‑aminobutyric acid (GABA) in the central nervous system.
• Result: Prolonged elevation of intracellular GABA, enhancing inhibitory neurotransmission.
• Clinical impact: Suppression of epileptiform activity, especially in infantile spasms and Lennox‑Gastaut syndrome.

Pharmacokinetics

• Absorption: Rapid and complete after oral dosing; peak plasma concentration (~2 h).
• Distribution: High protein binding (~90 %); extensive CNS penetration.
• Metabolism: No significant hepatic metabolism; excreted unchanged.
• Elimination: Primarily renal (≈70 % unchanged in urine). Half‑life: 7–20 h, varies with dose & age.
• Special populations: No dose adjustment required for hepatic impairment; caution in renal dysfunction.

Indications

• Primary: Refractory infantile spasms; first‑line therapy when drug‑sparing window available.
• Off‑label & adjunctive:
• Lennox‑Gastaut syndrome.
• Lennox‑Gastaut‑like syndromes with status epilepticus.
• Intractable focal seizures in adults (limited data).

Contraindications

• Contraindications:
• Known hypersensitivity to vigabatrin or any excipient.
• Pre‑existing retinal disease or severe visual impairment.
• Warnings:
• Retinal toxicity: Dose‑dependent, irreversible visual field loss, especially in infants. Requires baseline & periodic ophthalmologic evaluation.
• Pregnancy category Category C: Animal studies showed embryo‑fetal harm; use only if benefits outweigh risks.
• Possible increase in seizure frequency at initiation; titrate gradually.

Dosing

• Administration: Oral capsules/tablets; can be taken with food to reduce GI upset.
• Special notes: Maintain consistent dosing schedule; avoid abrupt discontinuation.

Adverse Effects

• Common (>10 %):
• Side‑effects: Visual disturbances (color desaturation, reduced brightness).
• Gastro‑intestinal: Nausea, vomiting, constipation.
• Neurologic: Drowsiness, dizziness, ataxia.
• Serious (>1 %):
• Retinal toxicity: Progressive central visual field loss; can become permanent.
• Seizure exacerbation at initiation.
• Rare: Respiratory depression, hypotension, hypersensitivity reactions.

Monitoring

• Baseline:
• Complete ophthalmologic exam (visual fields, color vision, ERG).
• Serum creatinine & eGFR.
• Baseline EEG (in infants with spasms).
• Ongoing:
• Visual field testing: Every 3–6 months (or sooner if symptoms).
• EEG: At least quarterly, or earlier if clinical status changes.
• Serum creatinine: Every 3–6 months.
• Patient diary: For seizure frequency, visual changes, GI symptoms.
• Discontinuation criteria: Progressive visual field loss >20 % (central), lasting >3 months.

Clinical Pearls

• Infantile Spasms “Gold Standard”: Vigabatrin is the only FDA‑approved oral agent for infantile spasms; early treatment (within 4 weeks of onset) improves long‑term cognitive outcomes.
• Retinal Toxicity Timing: Most visual field loss occurs within the first 6 months; diligent screening can prevent irreversible loss.
• Dosing Differential: Children require higher mg/kg doses due to faster metabolism; adults often tolerate higher absolute doses without increased toxicity.
• Drug Interaction: Co‑administration with other antiepileptics (e.g., carbamazepine, valproate) does not require dose adjustment but may amplify CNS depression.
• Pregnancy Consideration: If pregnancy is anticipated, consider alternative treatment; otherwise, proceed with rigorous ophthalmologic monitoring.
• Switching Strategies: If retinal toxicity emerges, washout and transition to alternative GABAergic agents (e.g., topiramate, ethosuximide) is generally safe but watch for rebound seizures.

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• *References:*

1. L. M. CRobb & W. S. Bawden, *Pharmacology for Clinical Diabetology*, 5th ed.

2. A. Benson, *Epileptology Review*, 2021.

3. FDA label: Vigabatrin (Sabril), 2023.