Vigabatrin
Mechanism :
Vigabatrin is an irreversible inhibitor of gamma- aminobutyric acid transaminase (GABA-T), the enzyme responsible for the catabolism of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the brain. The mechanism of action of vigabatrin is attributed to irreversible enzyme inhibition of GABA-T, and consequent increased levels of the inhibitory neurotransmitter, GABA.
Indication :
- Infantile spasm
- Partial seizures with secondary GTC as adjunct if not controlled by other antiepileptic combination
Contraindications :
Contraindicated in pregnancy and lactation and in patients with a known hypersensitivity to vigabatrin or to any components of the product. Can exacerbate myoclonic and absence seizures. Caution in psychosis or behavioural problems. Cautionary use in children with pre-existing visual field defects. Formal assessment of visual fields (perimetry) should be undertaken in all children with a cognitive age of 9 years and above before the drug is started and every 6 months while receiving the drug. Reduce dose in renal failure.
Dosing :
PO
Resistant partial epilepsy with or without secondary generalisation:
As an adjunct; Initially, 30-40 mg/kg daily, followed by the following maintenance dose:
10-15 kg: 0.5-1 g/day.
15-30 kg: 1-1.5 g/day.
30-50 kg: 1.5-3 g/day.
>50 kg: 2-3 g/day.
Doses to be administered once or twice daily.
Infantile spasms:
In children as monotherapy: 50 mg/kg daily, adjust according to response over 7 days. Maximum dose: 150 mg/kg daily in 1-2 divided doses.
Adverse Effect :
Dose dependent side-effects include somnolence, dizziness, headache, nervousness, depression, memory disturbances, hyperactivity, diplopia, aggression, irritability, hypo- or hypertonia. Chronic adverse effects include increased appetite and weight gain, peripheral constriction of visual fields.
Interaction :
May gradually reduce plasma phenytoin levels.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | Give 50% of normal dose and titrate to response |
| 10-20 | Give 50% of normal dose and titrate to response |
| <10 | Give 25% of normal dose and titrate to response |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Unknown dialysability. Dose as for GFR<10 mL/min |
| HD | Dialysed. Dose as for GFR<10 mL/min |
| HDF/High flux | Dialysed. Dose as for GFR<10 mL/min |
| CAV/VVHD | Unknown dialysability. Dose as for GFR=10–20 mL/min |
Hepatic Dose :
No dose adjustment recommended.