FDA prescribing information, side effects and uses. Refractory Complex Partial Seizures(CPS) Sabril is indicated as adjunctive therapy for adults and pediatric patients 1. Sabril is not indicated as a first line agent for complex partial seizures. Infantile Spasms(IS)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 . Patients with impaired renal function require dose adjustment . Sabril tablets and powder for oral solution are bioequivalent. Either tablet or powder can be used for CPS. Powder for oral solution should be used for IS; tablets should not be used for IS because of difficulty in the administration of tablets to infants and young children. Monitoring of Sabril plasma concentrations to optimize therapy is not helpful. Administration. Sabril is given orally with or without food. Sabril powder for oral solution should be mixed with water prior to administration . Total daily dose may be increased in 5. The recommended dose of Sabril in adults is 3. Treatment should be initiated at a total daily dose of 5. Patients weighing more than 6. Table 1. Pediatric CPS Dosing Recommendations. Body Weight. 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 . Infant Dosing Table Weight. Physicians should confirm that patients or caregiver(s) understand how to mix Sabril powder with water and administer the correct daily dose. Empty the entire contents of each 5. L of cold or room temperature water per packet. Administer the resulting solution using the 1. L oral syringe supplied with the medication. The concentration of the final solution is 5. Andrew Wilner discusses the FDA's approval of vigabatrin (Sabril. While the SHARE program provides heightened supervision. L. Table 3 below describes how many packets and how many milliliters (m. L) of water will be needed to prepare each individual dose. Number of Sabril Packets and m. L of Water Needed for Each Individual Dose. Individual Dose . Each individual dose should be prepared and used immediately. Discard any unused portion of the solution after administering the correct dose. DOSAGE FORMS AND STRENGTHSTablet: 5. OV 1. 11 on the other. Because of this risk and because, when it is effective, Sabril provides an observable symptomatic benefit; patient response and continued need for treatment should be periodically assessed. Based upon adult studies, 3. Severe cases may be characterized by tunnel vision to within 1. In some cases, Sabril also can damage the central retina and may decrease visual acuity. 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. Because assessing vision may be difficult in infants and children, the frequency and extent of vision loss is poorly characterized in these patients. For this reason, the understanding of the risk is primarily based on the adult experience. The possibility that vision loss from Sabril may be more common, more severe, or have more severe functional consequences in infants and children than in adults cannot be excluded. 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. 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. In patients with refractory complex partial seizures, Sabril 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 . 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 . The interaction of other types of irreversible vision damage with vision damage from Sabril has not been well- characterized, but is likely adverse. 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. Monitoring of Vision. SABRIL PRIOR APPROVAL REQUEST. Send completed form to: Service Benefit Plan Prior Approval P.O. Box 52080 MC 139 Phoenix, AZ 85072-2080. Are the patient and prescriber enrolled in the SHARE REMS program? The Sabril REMS program, formerly known as SHARE, has been changed after the FDA determined that some of the program’s requirements are no longer necessary to ensure that the benefits of Sabril outweigh the risks. Learn more about the SABRIL SABRIL is only available through pharmacies that are enrolled in the SHARE REMS Program. As part of the SABRIL REMS Program, it is recommended that your healthcare provider test you (or your child’s) vision from time. Find patient medical information for Sabril oral on WebMD including its uses, side effects and safety, interactions, pictures, warnings and user ratings. Sabril (Vigabatrin) Tablets Drug Safety Labeling Changes, June 2016, September 2015, October 2013. Monitoring of vision by an ophthalmic professional with expertise in visual field interpretation and the ability to perform dilated indirect ophthalmoscopy of the retina is recommended . Because vision testing in infants is difficult, vision loss may not be detected until it is severe. For patients receiving Sabril, vision assessment is recommended at baseline (no later than 4 weeks after starting Sabril), at least every 3 months while on therapy, and about 3- 6 months after the discontinuation of therapy. In patients who cannot be tested, treatment may continue according to clinical judgment, with appropriate patient counseling. Because of variability, results from ophthalmic monitoring must be interpreted with caution, and repeat assessment is recommended if results are abnormal or uninterpretable. Repeat assessment in the first few weeks of treatment is recommended to establish if, and to what degree, reproducible results can be obtained, and to guide selection of appropriate ongoing monitoring for the patient. The onset and progression of vision loss from Sabril is unpredictable, and it may occur or worsen precipitously between assessments. Once detected, vision loss due to Sabril is not reversible. It is expected that even with frequent monitoring, some Sabril patients will develop severe vision loss. Consider drug discontinuation, balancing benefit and risk, if vision loss is documented. It is possible that vision loss can worsen despite discontinuation of Sabril. Sabril REMS Program. Sabril is available only through a restricted distribution program called the Sabril REMS Program, because of the risk of permanent vision loss. Notable requirements of the Sabril 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 periodic monitoring of vision, and reporting any event suggestive of vision loss to Lundbeck. Patients must enroll in the program. In a retrospective epidemiologic study in infants with IS (N=2. In the study above, in post marketing experience, and in published literature reports, these changes generally resolved with discontinuation of treatment. In a few patients, the lesion resolved despite continued use. The relationship between these findings and the abnormal MRI findings in infants treated with vigabatrin for infantile spasms is unknown . In a blinded review of MRI images obtained in prospective clinical trials in patients with refractory CPS 3 years and older (N=6. MRI signal changes between vigabatrin treated and placebo treated patients. For adults treated with Sabril, routine MRI surveillance is unnecessary as there is no evidence that vigabatrin causes MRI changes in this population. Neurotoxicity. Vacuolation, characterized by fluid accumulation and separation of the outer layers of myelin, has been observed in brain white matter tracts in adult and juvenile rats and adult mice, dogs, and possibly monkeys following administration of vigabatrin. This lesion, referred to as intramyelinic edema (IME), was seen in animals at doses within the human therapeutic range. A no- effect dose was not established in rodents or dogs. In the rat and dog, vacuolation was reversible following discontinuation of vigabatrin treatment, but, in the rat, pathologic changes consisting of swollen or degenerating axons, mineralization, and gliosis were seen in brain areas in which vacuolation had been previously observed. Decreased myelination and evidence of oligodendrocyte injury were additional findings in the brains of vigabatrin- treated rats. An increase in apoptosis was seen in some brain regions following vigabatrin exposure during the early postnatal period. Administration of vigabatrin to juvenile dogs produced vacuolar changes in the brain gray matter (including the septal nuclei, hippocampus, hypothalamus, thalamus, cerebellum, and globus pallidus). Neurobehavioral effects of vigabatrin were not assessed in the juvenile dog. These effects in young animals occurred at doses lower than those producing neurotoxicity in adult animals and were associated with plasma vigabatrin levels substantially lower than those achieved clinically in infants and children . Studies of the effects of vigabatrin on MRI and EP in adult epilepsy patients have demonstrated no clear- cut abnormalities . 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. Pooled analyses of 1. AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1. CI: 1. 2, 2. 7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 1. AED treated patients was 0. There were four suicides in drug treated patients in the trials and none in placebo treated patients, but the number is too small to allow any conclusion about drug effect on suicide. The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 2. The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. Archives
December 2016
Categories |