Drug Interaction:
Drug interactions-
One of the major advantages of vigabatrin is the fact it not does appear to be metabolised
by the liver, nor influence hepatic metabolism.Therefore the typical drug interactions
observed with traditional anticonvulsants are not seen with vigabatrin.
However,vigabatrin was shown to decrease pheytoin (eg Dilatin) levels by 20% to 30%
in clinical trials. No mechanism of action could account for the decreased levels, therefore
phenytoin levels should be monitored if vigabatrin is added.
Vigabatrin does not appear to interact with phenobarbital, primidone, carbamazepine,
(eg.Tergretol) or valproate (eg Depakene) to any clinically significant degree
Indication:
Proprietary Name- Sabril
Established Name - Vigabatrin - Anticonvulsant - Anti-epiletic drug
Applicant- Lundbeck inc.
Indication-
Refractory Complex Partial seizures in adults
Dosage-
50mg twice daily
Approved by FDA 21-8-2009 (Ref- FDA approved List- 2009)
Seizures
Summary-
Vigabatrin appears to be effective in the treatment of complex partial seizures,
less effective for primary generalized seizures and not effective ( and may even
worsen) absence of myoclonic seizures.
The dosing range is from 1 to 4g/day in adults, with 2 to 3g appearing to be the
most optimal and a dose of 50 to 150mg/kg /day for children ,
Side effects are minimal and mild and there seems to be a lack of clinically significant
drug interactions , except that observed with phehytoin.
Vigabatrin is already available in Europe. An aniticipated approval date is unknown.
Adverse Reaction:
Side effects-
Vegabatrin appears to be well tolerated with minimal side effects and when they do occur,
they are mild. In a trial of 254 patients who received vigabatrin from 12 months to > 2 years,
up to 75% of patients reported no side effects.
Data from pooled studies indicate that the most common sides effects are rare.
Somnolence, fatigue, irritatability, dizziness, headache, depression, confusion, poor
concentration, abdominal pain, anorexia,( some trials have reported weight gain).
In some studies involving children, the main side effects observed were agitation
and insomnia, with a similar number of patients reporting a lack of side effects(75%)
Pharmacology/ Pharmacokinetics:
Pharmacology-
Vigabartin is a second generation antiepileptic which appears to exert its mechansim
of action via increasing brain GABA metabolism. These effects on GABA appears to
be dose related.
Vigabatrin has an S(+) enantiomer that inhibits GABA-T , whereas the R(-) enantomier
has no almost no effect. Vigabatrins mechanism of action may also be attributed to its
ability to decrease excitation-related amino-acids, asparate, glutamate and glutamine
concentrations in the brain but these same changes do not occur in the CSF
Pharmacokinetics-
Although the exact bioavailability of vigabatrin is not known, following oral admininstration
about 80% of the dose is recovered in the urine. In healthy volunteers its absorption was
rapid and peak plasma concentrations occurred within the first 2 hours. When vigabatrin
was administered with food, it appropiate bioavailability was 92% +/- 11%.
Vigabatrin has a volume of distribution of about 0.8L/kg, is not bound to plasma proteins
and distributes into the CSF . The drug does not appear to be metabolized by the liver,
or influence hepatic metabolism.
The elimination half life observed in 24 volunteers was approximately 7 hours and does
not appear to be significantly affected by single or multiple dosing , and appears to be
similar in both adults and children. Dosing adjustments may be necessary in patients with
patients with renal impairment (Ccr less than 60ml/min) and in the elderly.
Clinical trials-
When traditional antiepileptic therapies including add on treatments are used, up to 25%
of patients still experience seizures. The studies examining the efficacy of vigabatrin as
an antiepileptic mediation were primarily add-on trials in patients with resistent epilepsy,
Reductions in seizure frequency have been observed in patients with partial and complex
partial seizures, but reductions have been observed less frequently with primarily
generalized seizures, and no reductions( and worsening ) of absence of myoclonic seizures
In a meta-analysis of nine European trials , of the patients with complex partial seizures,
72% showed a decrease a > 25% decrease in seizure frequency over 7 to 12 week period.
When combining all clinical trials, ( including European studies) examining the efficacy of
vigabratin in treatment of resistent partial complex epilepsy, between 33% and 61% of patients experienced a >50% reduction in seizure freqency at doses between 1 and 4g/day
The use of vigabatrin in doses ranging from 50 to 150mg/day has also been studied as an
add-on therapy in children with partial, generalized ,Lennox-Gaustaut Syndrome and
West syndrome. Results appear to those similar to adults, children with partial seizures
appear to respond better with rates between 38% and 49% of patients experiencing
between a 50 to 100 reduction in seizure freqency.
Vigabratin has also been examined in the use of intractable infantile spasms and was
found to be effective in reducing spasms > 50% in patients (71%) with complete relief
of spams in 16 patients (38%) . Caution should be used in the interpretation of these
rsults since great variability can occur in the incidence of infantile seizures over time
Manufacturer Details