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Vigabatrin can cause permanent vision loss. Because of this risk and because, when it is effective, Vigabatrin provides an observable ymptomatic benefit; patient response and continued need for treatment should be periodically assessed.
In patients with refractory complex partial seizures, Vigabatrin should be withdrawn if a substantial clinical benefit is not observed within 3 months of initiating treatment. If, in the clinical judgment of the prescriber, evidence of treatment failure becomes obvious earlier than 3 months, treatment should be discontinued at that time.
In patients with infantile spasms, Vigabatrin should be withdrawn if a substantial clinical benefit is not observed within 2 to 4 weeks. If, in the clinical judgment of the prescriber, evidence of treatment failure becomes obvious earlier than 2 to 4 weeks, treatment should be discontinued at that time.
Vigabatrin 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. The interaction of other types of irreversible vision damage with vision damage from Vigabatrin has not been well-characterized, but is likely adverse.
Vigabatrin 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.
Vigabatrin is available only through a restricted distribution program called the Vigabatrin REMS Program, because of the risk of ermanent vision loss.
Notable requirements of the Vigabatrin REMS Program include the following:
•Prescribers must be certified by enrolling in the program, agreeing to counsel patients on the risk of vision loss and the need for eriodic monitoring of vision, and reporting any event suggestive of vision loss to Lundbeck.
•Patients must enroll in the program.
•Pharmacies must be certified and must only dispense to patients authorized to receive Vigabatrin.
Abnormal MRI signal changes characterized by increased T2 signal and restricted diffusion in a symmetric pattern involving the halamus, basal ganglia, brain stem, and cerebellum have been observed in some infants treated with vigabatrin.
For adults treated with Vigabatrin, routine MRI surveillance is unnecessary as there is no evidence that vigabatrin causes MRI changes in this population.
Administration of vigabatrin to female rats during pregnancy and lactation at doses below those used clinically resulted in ippocampal vacuolation and convulsions in the mature offspring.
Antiepileptic drugs (AEDs), including Vigabatrin, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.
Anyone considering prescribing Vigabatrin or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.
Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers.
As with all AEDs, Vigabatrin should be withdrawn gradually. However, if withdrawal is needed because of a serious adverse event, rapid discontinuation can be considered. Patients and caregivers should be told not to suddenly discontinue Vigabatrin therapy. In controlled clinical studies in adults with complex partial seizures, Vigabatrin was tapered by decreasing the daily dose 1000 mg/day on a weekly basis until discontinued.
In a controlled study in pediatric patients with complex partial seizures, Vigabatrin was tapered by decreasing the daily dose by one third every week for three weeks.
In a controlled clinical study in patients with infantile spasms, Vigabatrin was tapered by decreasing the daily dose at a rate of 25-50 mg/kg every 3-4 days.
In North American controlled trials in adults, 6% of patients (16/280) receiving Vigabatrin and 2% of patients (3/188) receiving placebo had adverse events of anemia and/or met criteria for potentially clinically important hematology changes involving hemoglobin, hematocrit, and/or RBC indices. Across U.S. controlled trials, there were mean decreases in hemoglobin of about 3% and 0% in Vigabatrin and placebo-treated patients, respectively, and a mean decrease in hematocrit of about 1% in Vigabatrin-treated patients compared to a mean gain of about 1% in patients treated with placebo.
In controlled and open-label epilepsy trials in adults and pediatric patients, 3 Vigabatrin patients (0.06%, 3/4855) discontinued for anemia and 2 Vigabatrin patients experienced unexplained declines in hemoglobin to below 8 g/dL and/or hematocrit below 24%.
Vigabatrin causes somnolence and fatigue. Patients should be advised not to drive a car or operate other complex machinery until they are familiar with the effects of Vigabatrin on their ability to perform such activities.
Vigabatrin causes symptoms of peripheral neuropathy in adults. Pediatric clinical trials were not designed to assess symptoms of eripheral neuropathy, but observed incidence of symptoms based on pooled data from controlled pediatric studies appeared similar for pediatric patients on vigabatrin and placebo.
In all epilepsy trials, 0.6% (31/4855) of Vigabatrin patients discontinued for weight gain. The long term effects of Vigabatrin related weight gain are not known. Weight gain was not related to the occurrence of edema.
Vigabatrin causes edema in adults. Pediatric clinical trials were not designed to assess edema, but observed incidence of edema-based pooled data from controlled pediatric studies appeared similar for pediatric patients on vigabatrin and placebo.
from FDA，2021.10
