Vigabatrinum
Vigabatrinum Uses, Dosage, Side Effects, Food Interaction and all others data.
Vigabatrinum is an analog of gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the central nervous system, used in the treatment of refractory seizures and infantile spasms. It irreversibly inhibits the enzyme responsible for GABA metabolism, thereby increasing levels of circulating GABA. Although administered as a racemic mixture, only the S(+) enantiomer is pharmacologically active.
It was first introduced as an antiepileptic agent in the United Kingdom in 1989 and was used extensively until 1997, when an association with vision loss became apparent. Its use is now generally reserved for patients who have failed alternative therapies, and its US approval by the FDA in 2009 mandated the creation of a drug registry to monitor patients for visual deficits.
Vigabatrinum is an antiepileptic agent chemically unrelated to other anticonvulsants. Vigabatrinum prevents the metabolism of GABA by irreversibly inhibiting GABA transaminase (GABA-T). As vigabatrin is an irreversible inhibitor of gamma-aminobutyric acid transaminase (GABA-T), its duration of effect is thought to be dependent on the rate of GABA-T re-synthesis rather than on the rate of drug elimination.
| Trade Name | Vigabatrinum |
| Availability | Prescription only |
| Generic | Vigabatrin |
| Vigabatrin Other Names | Gamma vinyl GABA, gamma-Vinyl GABA, Vigabatrin, Vigabatrina, Vigabatrine, Vigabatrinum, Vinyl gamma-aminobutyric acid |
| Related Drugs | Sabril, Rapamune, gabapentin, clonazepam, lamotrigine, diazepam, pregabalin, Lyrica, topiramate, levetiracetam |
| Type | |
| Formula | C6H11NO2 |
| Weight | Average: 129.157 Monoisotopic: 129.078978601 |
| Protein binding | Vigabatrin does not bind to plasma proteins. |
| Groups | Approved |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Vigabatrinum is an irreversible GABA transaminase inhibitor used as an adjunct therapy to treat refractory complex partial seizures in patients ≥2 years unresponsive to alternatives. May also be used as monotherapy to treat infantile spasms in infants 1 month to 2 years.
Vigabatrinum is indicated as adjunctive therapy in the treatment of refractory complex partial seizures in patients 2 years of age and older who have had inadequate responses to multiple previous treatments (i.e. not to be used for first-line therapy). It is also indicated as monotherapy in the treatment of infantile spasms in patients between 1 month and 2 years of age for whom the potential benefits outweigh the risk of vision loss.
Vigabatrinum is also used to associated treatment for these conditions: Infantile Spasms (IS), Refractory Complex partial seizures
How Vigabatrinum works
Gamma-aminobutyric acid (GABA) is the major inhibitory transmitter throughout the central nervous system, and the potentiation of GABAergic neurotransmission is therefore a crucial mechanism through which antiepileptic agents may combat the pathologic excitatory neurotransmission seen in epilepsy. Vigabatrinum increases concentrations of GABA in the central nervous system by irreversibly inhibiting the enzymes responsible for its metabolism to succinic semialdehyde: gamma-aminobutyric acid transaminase (GABA-T).
Toxicity
The oral LD50 of vigabatrin in mice and rats is 2830 mg/kg and 3100 mg/kg, respectively. Symptoms of overdose tend to involve significant CNS depression - e.g. coma, unconsciousness, and/or drowsiness - with less common symptoms including neurologic disorders (e.g. seizure activity, speech disorder, headache) and psychiatric sequelae (e.g. psychosis, agitation, abnormal behaviour, confusion).
In cases of overdose, symptoms generally resolve with symptomatic and supportive care. Standard measures to remove unabsorbed drug may be employed (e.g. gastric lavage), although an in vitro study found that activated charcoal did not significantly absorb vigabatrin. Although vigabatrin is not protein-bound, the effectiveness of hemodialysis in drug removal during overdose is unknown - isolated reports of patients in renal failure undergoing hemodialysis who were receiving therapeutic doses of vigabatrin note a reduction in vigabatrin plasma concentrations of 40-60% following dialysis.
Food Interaction
- Take with or without food.
- Take with plain water. Only mix vigabatrin oral solution powder with plain water.
[Moderate] GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents.
Use in combination may result in additive central nervous system depression and
MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol.
Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.
Vigabatrinum Drug Interaction
Moderate: levetiracetam, lithium, pregabalin, clobazam, topiramate, valproic acid, cetirizineUnknown: fluticasone nasal, arginine, levocarnitine, cysteine, polyethylene glycol 3350, acetaminophen, acetaminophen, thiamine, cyanocobalamin, pyridoxine, cholecalciferol, phytonadione, menaquinone
Vigabatrinum Disease Interaction
Major: vision lossModerate: suicidal tendency, neurotoxicity, peripheral neuropathy
Volume of Distribution
Vigabatrinum is widely distributed throughout the body with a mean steady-state volume of distribution of 1.1 L/kg.
Elimination Route
Absorption following oral administration is essentially complete. The Tmax is approximately 2.5 hours in infants (5m - 2y) and 1 hour in all other age groups.
Half Life
The terminal half-life of vigabatrin is approximately 5.7 hours for infants (5m - 2y), 6.8 hours for children (3y - 9y), 9.5 hours for adolescents (10y - 16y), and 10.5 h for adults.
Clearance
The oral clearance of vigabatrin is 2.4 L/h for infants (5m - 2y), 5.1 L/h for children (3y - 9y), 5.8 L/h for adolescents (10y - 16y), and 7 L/h for adults.
Elimination Route
Approximately 95% of the drug is eliminated in the urine within 72 hours of administration, of which ~80% is unchanged parent drug.
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