Usage
- Vigabatrin is an anticonvulsant medication primarily prescribed for the treatment of infantile spasms (West Syndrome) in children aged 1 month to 2 years. It is also used as adjunctive therapy for refractory complex partial seizures in adults and children when other treatments have failed.
- Pharmacological classification: Anticonvulsant, GABAergic.
- Mechanism of Action: Vigabatrin irreversibly inhibits gamma-aminobutyric acid transaminase (GABA-T), the enzyme responsible for breaking down GABA in the brain. This leads to increased GABA concentrations, enhancing inhibitory neurotransmission and reducing seizure activity.
Alternate Names
- International/Regional Variations: γ-vinyl GABA
- Brand Names: Sabril, Vigadrone, Vigafyde
How It Works
- Pharmacodynamics: Vigabatrin increases GABA levels in the brain, leading to enhanced inhibitory neurotransmission and a reduction in neuronal excitability. This effect is responsible for its anticonvulsant properties.
- Pharmacokinetics: Vigabatrin is well-absorbed orally, with peak plasma concentrations reached within 1-3 hours. It is not extensively metabolized and is primarily excreted unchanged in the urine. Elimination half-life is approximately 5-8 hours in adults. The renal clearance is reduced in elderly patients.
- Mode of Action: Vigabatrin irreversibly inhibits GABA-T, increasing GABA concentrations in the synaptic cleft.
- Receptor binding, enzyme inhibition, or neurotransmitter modulation: Irreversible inhibition of GABA-T.
- Elimination pathways: Primarily renal excretion.
Dosage
Standard Dosage
Adults:
- Initial dose: 1000 mg/day (500 mg twice daily).
- Maintenance dose: 3000 mg/day (1500 mg twice daily), adjustable based on response and tolerability. Maximum dose generally not exceeding 3000 mg/day.
Children (for infantile spasms):
- Initial dose: 50 mg/kg/day in two divided doses.
- Titration: Increase by 25-50 mg/kg/day every 3 days, as needed.
- Maximum dose: 150 mg/kg/day.
- Children (for refractory complex partial seizures): Similar dosing to adults. Adjustment based on weight and response may be necessary.
Special Cases:
- Elderly Patients: Initiate at the lower end of the dosing range due to reduced renal clearance. Careful monitoring is recommended.
- Patients with Renal Impairment: Dosage adjustments are necessary based on creatinine clearance.
- Mild impairment (CrCl 50-80 mL/min): Reduce dose by 25%.
- Moderate impairment (CrCl 30-50 mL/min): Reduce dose by 50%.
- Severe impairment (CrCl 10-30 mL/min): Reduce dose by 75%.
- Patients with Hepatic Dysfunction: No specific dosage adjustments are typically required.
- Patients with Comorbid Conditions: Exercise caution in patients with a history of psychosis, depression, or behavioral problems.
Clinical Use Cases
Vigabatrin is not typically indicated for intubation, surgical procedures, mechanical ventilation, intensive care unit (ICU) use, or emergency situations like status epilepticus or cardiac arrest.
Dosage Adjustments
Dosage modifications are based on patient-specific factors, including renal impairment as outlined above. Close monitoring and titration are essential for optimizing therapy.
Side Effects
Common Side Effects
- Drowsiness, fatigue, dizziness, headache, tremor, weight gain, nausea, vomiting, blurred vision, and nervousness
Rare but Serious Side Effects
- Permanent vision loss (peripheral visual field defects), suicidal thoughts or behaviors, anemia, MRI abnormalities in infants (especially with high doses), and psychotic symptoms.
Long-Term Effects
- Chronic visual field defects, persistent neurological symptoms
Adverse Drug Reactions (ADR)
- Severe visual field loss, severe psychiatric symptoms, life-threatening hematological abnormalities.
Contraindications
- Hypersensitivity to vigabatrin.
- Pre-existing visual field defects.
- Pregnancy (unless potential benefit outweighs the risk).
Drug Interactions
- Vigabatrin can interact with other antiepileptic drugs, potentially altering their serum levels. Monitor closely when used in combination.
- It is a CYP2C9 inducer and may decrease the levels of drugs metabolized by this enzyme (e.g., phenytoin).
- Interactions with CNS depressants (e.g., alcohol, benzodiazepines) can increase the risk of sedation.
- Certain drugs may exacerbate vigabatrin’s ocular toxicity (e.g., chloroquine, hydroxychloroquine).
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (US FDA), D (Australia).
- Fetal risks: Potential for developmental toxicity, including teratogenic effects. Use only if potential benefits outweigh risks.
- Breastfeeding: Vigabatrin is excreted in breast milk in low concentrations. Exercise caution and monitor the infant for potential adverse effects.
Drug Profile Summary
- Mechanism of Action: Irreversible inhibition of GABA-T, leading to increased GABA levels.
- Side Effects: Drowsiness, fatigue, dizziness, vision loss, psychiatric symptoms.
- Contraindications: Hypersensitivity, pre-existing visual field defects, pregnancy.
- Drug Interactions: Other antiepileptic drugs, CNS depressants, CYP2C9 substrates.
- Pregnancy & Breastfeeding: Use with caution; potential risks to the fetus and nursing infant.
- Dosage: Adults: up to 3000 mg/day; children: individualized based on age, weight, and indication. Adjust for renal impairment.
- Monitoring Parameters: Visual field testing, complete blood counts, liver function tests, neurological assessment.
Popular Combinations
Vigabatrin is often used as adjunctive therapy with other antiepileptic drugs like valproate, lamotrigine, or levetiracetam when monotherapy is insufficient to control seizures. Combinations should be carefully monitored for efficacy and adverse effects.
Precautions
- General Precautions: Baseline visual field testing, complete blood counts, and liver function tests should be obtained. Monitor for neurological and psychiatric symptoms.
- Specific Populations: See above for pregnancy, breastfeeding, children, and elderly.
- Lifestyle Considerations: Avoid alcohol and activities requiring alertness until effects are known.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Vigabatrin?
A: Adults: Start at 1000 mg/day, titrating up to 3000 mg/day as needed. Children: Individualized based on age, weight, and indication, starting at 50 mg/kg/day for infantile spasms. Adjust for renal impairment.
Q2: What is the most serious side effect of Vigabatrin?
A: Permanent vision loss (peripheral visual field defects) is the most significant concern. Regular eye exams are crucial.
Q3: Can Vigabatrin be used during pregnancy?
A: It should only be used if the potential benefits clearly outweigh the risks to the fetus. Discuss risks with the patient.
Q4: How does Vigabatrin work to control seizures?
A: It irreversibly inhibits GABA-T, leading to increased levels of GABA, an inhibitory neurotransmitter in the brain.
Q5: What are the common side effects of Vigabatrin?
A: Drowsiness, fatigue, dizziness, headache, tremor, weight gain, nausea, and blurred vision.
Q6: Are there any specific monitoring requirements for patients on Vigabatrin?
A: Yes, regular visual field testing, blood counts, and liver function tests are essential. Monitor neurological and psychiatric status.
Q7: Can Vigabatrin interact with other medications?
A: Yes, it can interact with other antiepileptic drugs and certain other medications. Review the patient’s medication list carefully.
Q8: How should Vigabatrin be discontinued?
A: Gradually taper the dose to minimize the risk of withdrawal seizures.
Q9: What should be done if a patient experiences vision changes while taking Vigabatrin?
A: Discontinue the drug immediately and refer the patient to an ophthalmologist.
Q10: Is Vigabatrin effective for all types of seizures?
A: It is primarily indicated for infantile spasms and refractory complex partial seizures. Its efficacy may vary depending on the seizure type and individual patient factors.
