Vigabatrin

129.16

129.16

270-929-6

DTXSID4041153

Crystals from acetone/water|White to off-white powder

N03AG04|N - Nervous system

63.3 Ų

-2.16 (LogP)|log Kow = -2.16|log Kow = -1.96 at physiologic pH|0.1

1.064±0.06 g/cm3

209 °C

277.7±28.0 °C(Predicted)

Freely soluble in water|Slightly soluble in methanol, alcohol; very slightly soluble in ethyl alchol and chloroform; insoluble in toluene and hexane|9.66e+01 g/L

Keep container tightly closed in a dry and well-ventilated place.|Store at 20 to 25 °C (68 to 77 °F).

4.18X10-8 mm Hg at 25 °C (est)

LD50 oral in rat: 3gm/kg

4.36±0.10

4 and 9.7|pKa1 = 4 (carboxylic acid); pKa2 = 9.7 (primary amine) at 25 °C

A racemate consisting of two enantiomers

3

36/37/38

26-36

MP7745000

Xi

Stable under recommended storage conditions.

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.|Product: Offer surplus and non-recyclable solutions to a licensed disposal company; Contaminated packaging: Dispose of as unused product.

Incompatible materials: Strong oxidizing agents.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including vigabatrin, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

|Warning|H315 (97.5%): Causes skin irritation [Warning Skin corrosion/irritation]|P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 40 companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Eye/face protection: Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).|Skin protection: Handle with gloves.|Body Protection: Choose body protection in relation to its type, to the concentration and amount of dangerous substances, and to the specific work-place.|Respiratory protection: Respiratory protection is not required. Where protection from nuisance levels of dusts are desired, use type N95 (US) or type P1 (EN 143) dust masks. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.|Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Avoid breathing dust. Environmental precautions: Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Avoid breathing dust.|SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.|Precautions for safe handling: Avoid formation of dust and aerosols. Further processing of solid materials may result in the formation of combustible dusts. The potential for combustible dust formation should be taken into consideration before additional processing occurs. Provide appropriate exhaust ventilation at places where dust is formed.|Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.|Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

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.|IDENTIFICATION AND USE: Vigabatrin is a structural analog of gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the CNS. Vigabatrin is commercially available as a racemic mixture of 2 enantiomers; the S enantiomer is pharmacologically active and the R enantiomer is inactive. HUMAN STUDIES: Visual field defects, including permanent vision loss, have been reported in infants, children, and adults receiving vigabatrin. Based on clinical studies in adults, bilateral concentric visual field constriction ranging in severity from mild to severe may occur in 30% or more of patients receiving the drug. Severe cases may be characterized by tunnel vision to within 10 degrees of visual fixation, which can lead to disability. In some cases, vigabatrin can also damage the central retina and decrease visual acuity. Coma, unconsciousness, and/or drowsiness were described in the majority of cases of vigabatrin overdose. Other less commonly reported symptoms included vertigo, psychosis, apnea or respiratory depression, bradycardia, agitation, irritability, confusion, headache, hypotension, abnormal behavior, increased seizure activity, status epilepticus, and speech disorder. These symptoms resolved with supportive care. ANIMAL STUDIES: Vigabatrin showed no carcinogenic potential in mouse or rat when given in the diet at doses up to 150 mg/kg/day for 18 months (mouse) or at doses up to 150 mg/kg/day for 2 years (rat). Vigabatrin (300 or 450 mg/kg) was administered by intraperitoneal injection to a mutant mouse strain on a single day during organogenesis (day 7, 8, 9, 10, 11, or 12). An increase in malformations (including cleft palate) was observed at both doses. In rats, oral administration of vigabatrin (50, 100, or 150 mg/kg) throughout organogenesis resulted in decreased fetal body weights and increased incidences of fetal anatomic variations. Oral administration of vigabatrin (50, 100, 150 mg/kg) to rats from the latter part of pregnancy through weaning produced long-term neurohistopathological (hippocampal vacuolation) and neurobehavioral (convulsions) abnormalities in the offspring. Administration of vigabatrin (oral doses of 50 to 200 mg/kg) to pregnant rabbits throughout the period of organogenesis was associated with an increased incidence of malformations (cleft palate) and embryo-fetal death; these findings were observed in two separate studies. No adverse effects on male or female fertility were observed in rats at oral doses up to 150 mg/kg/day. Oral administration of vigabatrin (5, 15, or 50 mg/kg) to young rats during the neonatal and juvenile periods of development (postnatal days 4-65) produced neurobehavioral (convulsions, neuromotor impairment, learning deficits) and neurohistopathological (brain vacuolation, decreased myelination, and retinal dysplasia) abnormalities in treated animals. The early postnatal period in rats is generally thought to correspond to late pregnancy in humans in terms of brain development. Vigabatrin was negative in in vitro (Ames, CHO/HGPRT mammalian cell forward gene mutation, chromosomal aberration in rat lymphocytes) and in in vivo (mouse bone marrow micronucleus) assays.

In controlled clinical trials, addition of vigabatrin to standard anticonvulsant therapy was reported to cause an immediate and marked decrease in serum enzyme levels that could be reproduced by simply mixing vigabatrin with plasma. In some instances, markedly raised serum ALT levels were found to rapidly fall into the normal range with treatment. Vigabatrin inhibits GABA transaminase and is thus suspected of also being an inhibitor of alanine and aspartate aminotransferase, accounting for its unusual effects on liver associated enzymes. In prelicensure clinical trials, there were no reports of serum enzyme elevations during treatment and no instances of clinically apparent liver injury. After its general availability, however, there have been isolated case reports of severe liver injury and hepatitis associated with vigabatrin use. The onset of injury was 3 to 10 months after starting vigabatrin and was largely hepatocellular. One case resulted in rapid death from liver failure and a second worsened despite stopping and ultimately required a course of immunosuppression with prednisone and azathioprine (Case 1). Thus, clinically apparent liver injury from vigabatrin may occur and can be severe, but is rare.

Sabril may moderately increase the Cmax of clonazepam resulting in an increase of clonazepam-associated adverse reactions.|Based on population pharmacokinetic modeling, concurrent administration of vigabatrin and rufinamide appears to be associated with a slight to moderate decrease in mean steady-state plasma concentrations of rufinamide (ranging from a decrease of approximately 14-15% in adults to a decrease of approximately 30% in children). Although the clinical importance of this potential interaction remains to be established, some clinicians recommend careful patient monitoring when either anticonvulsant is initiated or discontinued; rufinamide dosage adjustment should be considered if clinically necessary.|In controlled clinical studies, concomitant administration of phenytoin and vigabatrin resulted in moderate reductions (averaging 16-20%) in total plasma phenytoin concentrations, probably due to induction of CYP2C9. In a pharmacokinetic study evaluating a possible interaction between vigabatrin and phenytoin, mean plasma phenytoin concentrations fell by 23% during the fifth week of concurrent administration. Such reductions may be of little clinical importance, and phenytoin dosage adjustments are not routinely required; however, phenytoin dosage adjustment should be considered if clinically indicated.|In a study in healthy individuals, concomitant administration of vigabatrin (1.5 g twice daily) with clonazepam (0.5 mg) did not affect plasma concentrations of vigabatrin; however, mean peak plasma clonazepam concentrations increased by 30% and mean time to peak clonazepam concentrations decreased by 45%, which may increase the risk of clonazepam-associated adverse effects. In another study in healthy individuals, vigabatrin did not appear to potentiate the CNS effects of clonazepam during concurrent administration.|For more Interactions (Complete) data for Vigabatrin (7 total), please visit the HSDB record page.

Unless the benefits clearly outweigh the risks, vigabatrin should not be used in patients with, or at high risk of, other types of irreversible vision loss. The interaction of other types of irreversible vision damage with vigabatrin-associated vision damage has not been well characterized, but is expected to be adverse.

Vigabatrin does not bind to plasma proteins.

Vigabratin's production and administration as a medication(1) may result in its release to the environment through various waste streams(SRC).

/MILK/ Vigabatrin is /an/ antiepileptic medication consisting of a racemic mixture of 50% active S enantiomer and 50% inactive R enantiomer. Since patients suffering from epilepsy may become pregnant, it is important to understand the extent of placental transfer of such medication. During steady-state, vigabatrin enantiomer concentrations were measured in maternal and umbilical blood and in breast milk of two patients. The concentration ratios from the umbilical vein to maternal plasma were R:0.068, S:0.16; 4 hr 25 min after drug administration (case 1) and R: 1.39, S: 0.91; 9h after drug administration (case 2). The milk: plasma concentration ratio was lower than 1 at pre dose sampling in both cases, as well as 3 and 6 h post dose in one case. An estimate of the maximum amount of R and S enantiomers of vigabatrin that a suckling infant would ingest in a day is 3.6% and 1% of the weight-adjusted daily dose respectively. These results would suggest a slow placental transfer of the vigabatrin enantiomers and that the quantity ingested through milk is small.

Vigabatrin 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.|Kigabeq is indicated in infants and children from 1 month to less than 7 years of age for:Treatment in monotherapy of infantile spasms (West's syndrome).Treatment in combination with other antiepileptic medicinal products for patients with resistant partial epilepsy (focal onset seizures) with or without secondary generalisation, that is where all other appropriate medicinal product combinations have proved inadequate or have not been tolerated.|Treatment of epilepsy

Vigabatrin is a GABA derivative that is used in combination with other agents as therapy of refractory complex partial seizures and as monotherapy for infantile spasms. Vigabatrin is associated with a paradoxical decrease in serum enzyme levels during therapy, explained by its direct inhibition of aminotransferase activity. Vigabatrin has not been convincingly linked to cases of clinically apparent liver injury, but was linked to a fatal case of Reye syndrome in a child with severe developmental delay.

Anticonvulsants

Anticonvulsants; Enzyme Inhibitors; GABA Agents|/CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. Vigabatrin is included in the database.|Sabril is indicated as adjunctive therapy for adults and pediatric patients 10 years of age and older with refractory complex partial seizures who have inadequately responded to several alternative treatments and for whom the potential benefits outweigh the risk of vision loss. Sabril is not indicated as a first line agent for complex partial seizures. /Included in US product label/|Sabril is indicated as monotherapy for pediatric patients with infantile spasms 1 month to 2 years of age for whom the potential benefits outweigh the potential risk of vision loss. /Included in US product label/

/BOXED WARNING/ WARNING: PERMANENT VISION LOSS. Sabril can cause permanent bilateral concentric visual field constriction, including tunnel vision that can result in disability. In some cases, Sabril also can damage the central retina and may decrease visual acuity. The onset of vision loss from Sabril is unpredictable, and can occur within weeks of starting treatment or sooner, or at any time after starting treatment, even after months or years. Symptoms of vision loss from Sabril are unlikely to be recognized by patients or caregivers before vision loss is severe. Vision loss of milder severity, while often unrecognized by the patient or caregiver, can still adversely affect function. The risk of vision loss increases with increasing dose and cumulative exposure, but there is no dose or exposure known to be free of risk of vision loss. Vision assessment is recommended at baseline (no later than 4 weeks after starting Sabril), at least every 3 months during therapy, and about 3 to 6 months after the discontinuation of therapy. Once detected, vision loss due to Sabril is not reversible. It is expected that, even with frequent monitoring, some patients will develop severe vision loss. Consider drug discontinuation, balancing benefit and risk, if visual loss is documented. Risk of new or worsening vision loss continues as long as Sabril is used. It is possible that vision loss can worsen despite discontinuation of Sabril. Because of the risk of vision loss, Sabril should be withdrawn from patients with refractory complex partial seizures who fail to show substantial clinical benefit within 3 months of initiation and within 2-4 weeks of initiation for patients with infantile spasms, or sooner if treatment failure becomes obvious. Patient response to and continued need for Sabril should be periodically reassessed. Sabril should not be used in patients with, or at high risk of, other types of irreversible vision loss unless the benefits of treatment clearly outweigh the risks. Sabril should not be used with other drugs associated with serious adverse ophthalmic effects such as retinopathy or glaucoma unless the benefits clearly outweigh the risks. Use the lowest dosage and shortest exposure to Sabril consistent with clinical objectives. Because of the risk of permanent vision loss, Sabril is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Vigabatrin REMS Program|Visual field defects, including permanent vision loss, have been reported in infants, children, and adults receiving vigabatrin. Based on clinical studies in adults, bilateral concentric visual field constriction ranging in severity from mild to severe may occur in 30% or more of patients receiving the drug. Severe cases may be characterized by tunnel vision to within 10 degrees of visual fixation, which can lead to disability. In some cases, vigabatrin can also damage the central retina and decrease visual acuity. Because vision assessment may be difficult in infants and children, the frequency and extent of vision loss is poorly characterized in such patients; therefore, the understanding of the risk is mainly based on adult experience with the drug. The possibility that vigabatrin-induced vision loss may be more common, more severe, or have more functional consequences in infants and children than in adults cannot be excluded.|The onset and progression of vision loss with vigabatrin are unpredictable and can occur within weeks of beginning treatment or sooner or at any time after starting therapy, even after months or years. In addition, vision loss may develop or worsen precipitously between vision assessments. Symptoms of vigabatrin-associated vision loss are unlikely to be recognized by patients or caregivers before the impairment is severe. Vision loss of milder severity that is often unrecognized by the patient or caregiver can still adversely affect function. Once detected, vigabatrin-induced visual field defects are irreversible and will not improve even after the drug is discontinued. In addition, it is possible that further impairment of vision may occur following drug discontinuance. Risk of vision loss increases with increasing dosages and cumulative exposure to vigabatrin; however, no dosage or exposure to the drug is known to be free of the risk of vision loss. Some studies have suggested that smoking, age, and male gender are possible risk factors for developing visual field defects.|In patients with infantile spasms, vigabatrin therapy should be withdrawn if a substantial clinical benefit is not observed within 2-4 weeks of initiating the drug. If, in the clinical judgment of the prescribing clinician, evidence of treatment failure becomes obvious earlier than 2-4 weeks, vigabatrin treatment should be discontinued at that time.|For more Drug Warnings (Complete) data for Vigabatrin (25 total), please visit the HSDB record page.

Vigabatrin is an antiepileptic agent chemically unrelated to other anticonvulsants. Vigabatrin 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.

Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. (See all compounds classified as Enzyme Inhibitors.)|Drugs used to prevent SEIZURES or reduce their severity. (See all compounds classified as Anticonvulsants.)|Substances used for their pharmacological actions on GABAergic systems. GABAergic agents include agonists, antagonists, degradation or uptake inhibitors, depleters, precursors, and modulators of receptor function. (See all compounds classified as GABA Agents.)

Absorption following oral administration is essentially complete. The T_max is approximately 2.5 hours in infants (5m - 2y) and 1 hour in all other age groups.|Approximately 95% of the drug is eliminated in the urine within 72 hours of administration, of which ~80% is unchanged parent drug.|Vigabatrin is widely distributed throughout the body with a mean steady-state volume of distribution of 1.1 L/kg.|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.|Drug transporters in various tissues, such as intestine, kidney, liver and brain, are recognized as important mediators of absorption, distribution, metabolism and excretion of drug substances. This review gives a current status on the transporter(s) mediating the absorption, distribution, metabolism and excretion properties of the anti-epileptic drug substance vigabatrin. For orally administered drugs, like vigabatrin, the absorption from the intestine is a prerequisite for the bioavailability. Therefore, transporter(s) involved in the intestinal absorption of vigabatrin in vitro and in vivo are discussed in detail. Special focus is on the contribution of the proton-coupled amino acid transporter 1 (PAT1) for intestinal vigabatrin absorption. Furthermore, the review gives an overview of the pharmacokinetic parameters of vigabatrin across different species and drug-food and drug-drug interactions involving vigabatrin.|The aims were to determine blood-brain barrier penetration and brain extracellular pharmacokinetics for the anticonvulsant vigabatrin (VGB; gamma-vinyl-gamma-aminobutyric acid) in brain extracellular fluid and plasma from severe traumatic brain injury (TBI) patients, and to measure the response of gamma-aminobutyric acid (GABA) concentration in brain extracellular fluid. Severe TBI patients (n = 10) received VGB (0.5 g enterally, every 12 hr). Each patient had a cerebral microdialysis catheter; two patients had a second catheter in a different region of the brain. Plasma samples were collected 0.5 hr before and 2, 4 and 11.5 hr after the first VGB dose. Cerebral microdialysis commenced before the first VGB dose and continued through at least three doses of VGB. Controls were seven severe TBI patients with microdialysis, without VGB. After the first VGB dose, the maximum concentration of VGB (Cmax) was 31.7 (26.9-42.6) umol/L (median and interquartile range for eight patients) in plasma and 2.41 (2.03-5.94) umol/L in brain microdialysates (nine patients, 11 catheters), without significant plasma-brain correlation. After three doses, median Cmax in microdialysates increased to 5.22 (4.24-7.14) umol/L (eight patients, 10 catheters). Microdialysate VGB concentrations were higher close to focal lesions than in distant sites. Microdialysate GABA concentrations increased modestly in some of the patients after VGB administration. Vigabatrin, given enterally to severe TBI patients, crosses the blood-brain barrier into the brain extracellular fluid, where it accumulates with multiple dosing. Pharmacokinetics suggest delayed uptake from the blood.|/MILK/ Vigabatrin distributes into milk, probably in small amounts.|The aim of the study was to investigate the intestinal transport mechanisms responsible for vigabatrin absorption in rats by developing a population pharmacokinetic (PK) model of vigabatrin oral absorption. The PK model was used to investigate whether vigabatrin absorption was carrier-mediated and if the proton-coupled amino acid transporter 1 (PAT1) was involved in the absorption processes. Vigabatrin (0.3-300 mg/kg) was administered orally or intravenously to Sprague Dawley rats in the absence or presence of PAT1-ligands l-proline, l-tryptophan or sarcosine. The PK profiles of vigabatrin were described by mechanistic non-linear mixed effects modelling, evaluating PAT1-ligands as covariates on the PK parameters with a full covariate modelling approach. The oral absorption of vigabatrin was adequately described by a Michaelis-Menten type saturable absorption. Using a Michaelis constant of 32.8 mM, the model estimated a maximal oral absorption rate (Vmax) of 64.6mmol/min and dose-dependent bioavailability with a maximum of 60.9%. Bioavailability was 58.5-60.8% at 0.3-30 mg/kg doses, but decreased to 46.8% at 300 mg/kg. Changes in oral vigabatrin PK after co-administration with PAT1-ligands was explained by significant increases in the apparent Michaelis constant. Based on the mechanistic model, a high capacity low affinity carrier is proposed to be involved in intestinal vigabatrin absorption. PAT1-ligands increased the Michaelis constant of vigabatrin after oral co-administration indicating that this carrier could be PAT1.|For more Absorption, Distribution and Excretion (Complete) data for Vigabatrin (10 total), please visit the HSDB record page.

Vigabatrin is not metabolized to any significant extent.|Vigabatrin is not significantly metabolized ... .

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.|The terminal half-life of vigabatrin is about 5.7 hours for infants (5 months - 2 years), 9.5 hours for children (10 years - 16 years), and 10.5 hours for adults.

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. Vigabatrin 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).|Vigabatrin is a structural analog of gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the CNS. Although the exact mechanism of vigabatrin's antiseizure effect is unknown, it is thought to be related to the drug's action as a preferential and irreversible inhibitor of GABA transaminase (GABA-T), which is the enzyme responsible for the degradation of GABA and the resultant increase in GABA concentrations in the CNS. Vigabatrin is commercially available as a racemic mixture of 2 enantiomers; the S enantiomer is pharmacologically active and the R enantiomer is inactive.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/|There is no specific antidote for Sabril overdose. Standard measures to remove unabsorbed drug should be used, including elimination by emesis or gastric lavage. Supportive measures should be employed, including monitoring of vital signs and observation of the clinical status of the patient. In an in vitro study, activated charcoal did not significantly adsorb vigabatrin. The effectiveness of hemodialysis in the treatment of Sabril overdose is unknown. In isolated case reports in renal failure patients receiving therapeutic doses of vigabatrin, hemodialysis reduced vigabatrin plasma concentrations by 40% to 60%.|For more Antidote and Emergency Treatment (Complete) data for Vigabatrin (8 total), please visit the HSDB record page.

/SIGNS AND SYMPTOMS/ Visual field defects, including permanent vision loss, have been reported in infants, children, and adults receiving vigabatrin. Based on clinical studies in adults, bilateral concentric visual field constriction ranging in severity from mild to severe may occur in 30% or more of patients receiving the drug. Severe cases may be characterized by tunnel vision to within 10 degrees of visual fixation, which can lead to disability. In some cases, vigabatrin can also damage the central retina and decrease visual acuity. Because vision assessment may be difficult in infants and children, the frequency and extent of vision loss is poorly characterized in such patients; therefore, the understanding of the risk is mainly based on adult experience with the drug. The possibility that vigabatrin-induced vision loss may be more common, more severe, or have more functional consequences in infants and children than in adults cannot be excluded.|/SIGNS AND SYMPTOMS/ Confirmed and/or suspected vigabatrin overdoses have been reported during clinical trials and in post marketing surveillance. No vigabatrin overdoses resulted in death. When reported, the vigabatrin dose ingested ranged from 3 g to 90 g, but most were between 7.5 g and 30 g. Nearly half the cases involved multiple drug ingestions including carbamazepine, barbiturates, benzodiazepines, lamotrigine, valproic acid, acetaminophen, and/or chlorpheniramine. Coma, unconsciousness, and/or drowsiness were described in the majority of cases of vigabatrin overdose. Other less commonly reported symptoms included vertigo, psychosis, apnea or respiratory depression, bradycardia, agitation, irritability, confusion, headache, hypotension, abnormal behavior, increased seizure activity, status epilepticus, and speech disorder. These symptoms resolved with supportive care.|/CASE REPORTS/ Vigabatrin is an irreversible inhibitor of gamma-aminobutyrate (Gaba) aminotransferase, producing an increase in Gaba concentrations in the brain. It may prove to be an important drug in the treatment of refractory epilepsy, but would be payed attention to behavioral changes noted in association with vigabatrin treatment. Behavior disturbances, as psychosis, associated to vigabatrin /have/ been described in adult patients, ... are uncommon in childhood. We report a case of acute psychosis occurred in a child in treatment with vigabatrin.|/CASE REPORTS/ Vigabatrin is an effective antiepileptic drug (AED) typically used in the treatment of refractory partial seizures and infantile spasms. Its use, however, is limited due to the concern of retinal toxicity and subsequent visual field defects. ... We describe a case of vigabatrin toxicity that illustrates electroretinographic (ERG) changes occur before imaging and visual field deterioration. Decrease in maximal ERG b: a ratio was observed before thinning of the retinal nerve fiber layer (RNFL) on optical coherence tomography (OCT).|For more Human Toxicity Excerpts (Complete) data for Vigabatrin (17 total), please visit the HSDB record page.

gamma Vinyl GABA

Table: Vigabatrin Preparations [Table#8453]

HPLC determination in plasma and urine.

Human drugs -> Kigabeq -> EMA Drug Category|Antiepileptics -> Human pharmacotherapeutic group|Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients