SABRIL- vigabatrin tablet, film coated

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

VIGABATRIN (UNII: GR120KRT6K) (VIGABATRIN - UNII:GR120KRT6K)

Available from:

Lundbeck Pharmaceuticals LLC

INN (International Name):

VIGABATRIN

Composition:

VIGABATRIN 500 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

SABRIL is indicated as adjunctive therapy for adults and pediatric patients 2 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 [see Warnings and Precautions (5.1)] . SABRIL is not indicated as a first line agent for complex partial seizures. 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 [see Warnings and Precautions (5.1) ]. None. Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AEDs, including SABRIL, during pregnancy. Encourage women who are taking SABRIL during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. This can be done by calling the toll-free number 1-888-233-2334 or visiting the website, http://www.aedpregnancyregistry.org/ . This must be done by the patient herself. Risk Summary There are no adequate data on the developmental risk associated with the use of SABRIL in pregnant women. Limited available data from case reports and cohort studies pertaining to SABRIL use in pregnant women have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. However, based on animal data, SABRIL use in pregnant women may result in fetal harm. When administered to pregnant animals, vigabatrin produced developmental toxicity, including an increase in fetal malformations and offspring neurobehavioral and neurohistopathological effects, at clinically relevant doses. In addition, developmental neurotoxicity was observed in rats treated with vigabatrin during a period of postnatal development corresponding to the third trimester of human pregnancy (see Data) . In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data Administration of vigabatrin (oral doses of 50 to 200 mg/kg/day) to pregnant rabbits throughout the period of organogenesis was associated with an increased incidence of malformations (cleft palate) and embryofetal death; these findings were observed in two separate studies. The no-effect dose for adverse effects on embryofetal development in rabbits (100 mg/kg/day) is approximately 1/2 the maximum recommended human dose (MRHD) of 3 g/day on a body surface area (mg/m2 ) basis. In rats, oral administration of vigabatrin (50, 100, or 150 mg/kg/day) throughout organogenesis resulted in decreased fetal body weights and increased incidences of fetal anatomic variations. The no-effect dose for adverse effects on embryo-fetal development in rats (50 mg/kg/day) is approximately 1/5 the MRHD on a mg/m2 basis. Oral administration of vigabatrin (50, 100, 150 mg/kg/day) to rats from the latter part of pregnancy through weaning produced long-term neurohistopathological (hippocampal vacuolation) and neurobehavioral (convulsions) abnormalities in the offspring. A no-effect dose for developmental neurotoxicity in rats was not established; the low-effect dose (50 mg/kg/day) is approximately 1/5 the MRHD on a mg/m2 basis. In a published study, 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 fetal malformations (including cleft palate) was observed at both doses. Oral administration of vigabatrin (5, 15, or 50 mg/kg/day) 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. The no-effect dose for developmental neurotoxicity in juvenile rats (5 mg/kg/day) was associated with plasma vigabatrin exposures (AUC) less than 1/30 of those measured in pediatric patients receiving an oral dose of 50 mg/kg. Risk Summary Vigabatrin is excreted in human milk. The effects of SABRIL on the breastfed infant and on milk production are unknown. Because of the potential for serious adverse reactions from vigabatrin in nursing infants, breastfeeding is not recommended. If exposing a breastfed infant to SABRIL, observe for any potential adverse effects [see Warnings and Precautions (5.1, 5.3, 5.4, 5.8)] . The safety and effectiveness of SABRIL as adjunctive treatment of refractory complex partial seizures in pediatric patients 2 to 16 years of age have been established and is supported by three double-blind, placebo-controlled studies in patients 3 to 16 years of age, adequate and well-controlled studies in adult patients, pharmacokinetic data from patients 2 years of age and older, and additional safety information in patients 2 years of age [see Clinical Pharmacology (12.3) and Clinical Studies (14.1)]. The dosing recommendation in this population varies according to age group and is weight-based [see Dosage and Administration (2.2)]. Adverse reactions in this pediatric population are similar to those observed in the adult population [see Adverse Reactions (6.1)] . The safety and effectiveness of SABRIL as monotherapy for pediatric patients with infantile spasms (1 month to 2 years of age) have been established [see Dosage and Administration (2.3) and Clinical Studies (14.2)] . Safety and effectiveness as adjunctive treatment of refractory complex partial seizures in pediatric patients below the age of 2 and as monotherapy for the treatment of infantile spasms in pediatric patients below the age of 1 month have not been established. Duration of therapy for infantile spasms was evaluated in a post hoc analysis of a Canadian Pediatric Epilepsy Network (CPEN) study of developmental outcomes in infantile spasms patients. This analysis suggests that a total duration of 6 months of vigabatrin therapy is adequate for the treatment of infantile spasms. However, prescribers must use their clinical judgment as to the most appropriate duration of use [see Clinical Studies (14.2)].   Abnormal MRI signal changes and Intramyelinic Edema (IME) in infants and young children being treated with SABRIL have been observed [see Warnings and Precautions (5.3, 5.4)] . Juvenile Animal Toxicity Data Oral administration of vigabatrin (5, 15, or 50 mg/kg/day) 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 gray matter vacuolation, decreased myelination, and retinal dysplasia) abnormalities. The no-effect dose for developmental neurotoxicity in juvenile rats (the lowest dose tested) was associated with plasma vigabatrin exposures (AUC) substantially less than those measured in pediatric patients at recommended doses. In dogs, oral administration of vigabatrin (30 or 100 mg/kg/day) during selected periods of juvenile development (postnatal days 22-112) produced neurohistopathological abnormalities (brain gray matter vacuolation). Neurobehavioral effects of vigabatrin were not assessed in the juvenile dog. A no-effect dose for neurohistopathology was not established in juvenile dogs; the lowest effect dose (30 mg/kg/day) was associated with plasma vigabatrin exposures lower than those measured in pediatric patients at recommended doses [see Warnings and Precautions (5.4)]. Clinical studies of vigabatrin did not include sufficient numbers of patients aged 65 and over to determine whether they responded differently from younger patients. Vigabatrin is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Oral administration of a single dose of 1.5 g of vigabatrin  to elderly (≥65 years) patients with reduced creatinine clearance (<50 mL/min) was associated with moderate to severe sedation and confusion in 4 of 5 patients, lasting up to 5 days. The renal clearance of vigabatrin was 36% lower in healthy elderly subjects (≥65 years) than in young healthy males. Adjustment of dose or frequency of administration should be considered. Such patients may respond to a lower maintenance dose [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3 )] . Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Dose adjustment, including initiating treatment with a lower dose, is necessary in pediatric patients 2 years of age and older and adults with mild (creatinine clearance >50 to 80 mL/min), moderate (creatinine clearance >30 to 50 mL/min) and severe (creatinine clearance >10 to 30 mL/min) renal impairment [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3)] . Vigabatrin is not a controlled substance. Vigabatrin did not produce adverse events or overt behaviors associated with abuse when administered to humans or animals. It is not possible to predict the extent to which a CNS active drug will be misused, diverted, and/or abused once marketed. Consequently, physicians should carefully evaluate patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of vigabatrin (e.g., incrementation of dose, drug-seeking behavior). Following chronic administration of vigabatrin to animals, there were no apparent withdrawal signs upon drug discontinuation.  However, as with all AEDs, vigabatrin should be withdrawn gradually to minimize increased seizure frequency [see Warnings and Precautions (5.6)] .

Product summary:

SABRIL 500 mg tablets are white, film-coated, oval, biconvex, scored on one side, and debossed with OV 111 on the other. They are supplied as bottles of 100 (NDC 67386-111-01). SABRIL for oral solution is available as 500 mg packets containing a white to off-white granular powder. They are supplied in packages of 50 (NDC 67386-211-65). The oral syringes are provided separately by the pharmacy. Store at 20°C to 25°C (68°F to 77°F).  See USP controlled room temperature.

Authorization status:

New Drug Application

Patient Information leaflet

SABRIL- VIGABATRIN TABLET, FILM COATED
Lundbeck Pharmaceuticals LLC
----------
MEDICATION GUIDE
SABRIL®(SAY-bril)
(vigabatrin)
tablets
SABRIL®(SAY-bril)
(vigabatrin)
for oral solution
What is the most important information I should know about SABRIL?
SABRIL can cause serious side effects, including:
•
Permanent vision loss
•
Magnetic resonance imaging (MRI) changes in babies with infantile
spasms (IS)
•
Risk of suicidal thoughts or actions
1. Permanent vision loss:
SABRIL can damage the vision of anyone who takes it. Some people can
have severe loss particularly to
their ability to see to the side when they look straight ahead
(peripheral vision). With severe vision loss,
you may only be able to see things straight in front of you (sometimes
called “tunnel vision”). You may
also have blurry vision. If this happens, it will not get better.
•
Vision loss and use of SABRIL in adults and children 2 years and
older: Because of the risk of
vision loss, SABRIL is used to treat complex partial seizures (CPS)
only in people who do not
respond well enough to several other medicines.
Tell your healthcare provider right away if you (or your child):
•
might not be seeing as well as before starting SABRIL.
•
start to trip, bump into things, or are more clumsy than usual.
•
are surprised by people or things coming in front of you that seem to
come out of nowhere.
•
These changes can mean that you (or your child) have damage to your
vision.
•
It is recommended that your healthcare provider test your (or your
child’s) vision (including
peripheral vision) and visual acuity (ability to read an eye chart)
before you (or your child) start
SABRIL or within 4 weeks after starting SABRIL, and at least every 3
months after that until
SABRIL is stopped. It is also recommended that you (or your child)
have a vision test about 3 to 6
months after SABRIL is stopped. Your vision loss may get worse after
you stop taking Sabril.
•
Some people are not able to complete testing of vision. Your
healthcare provider will d

Summary of Product characteristics

SABRIL- VIGABATRIN TABLET, FILM COATED
LUNDBECK PHARMACEUTICALS LLC
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
SABRIL SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR SABRIL.
SABRIL (VIGABATRIN) TABLETS, FOR ORAL USE
SABRIL (VIGABATRIN) FOR ORAL SOLUTION
INITIAL U.S. APPROVAL: 2009
WARNING: PERMANENT VISION LOSS
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
SABRIL CAN CAUSE PERMANENT BILATERAL CONCENTRIC VISUAL FIELD
CONSTRICTION, INCLUDING
TUNNEL VISION THAT CAN RESULT IN DISABILITY. IN SOME CASES, SABRIL MAY
ALSO DECREASE
VISUAL ACUITY (5.1).
RISK INCREASES WITH INCREASING DOSE AND CUMULATIVE EXPOSURE, BUT THERE
IS NO DOSE
OR EXPOSURE TO SABRIL KNOWN TO BE FREE OF RISK OF VISION LOSS (5.1).
RISK OF NEW AND WORSENING VISION LOSS CONTINUES AS LONG AS SABRIL IS
USED, AND
POSSIBLY AFTER DISCONTINUING SABRIL (5.1).
BASELINE AND PERIODIC VISION ASSESSMENT IS RECOMMENDED FOR PATIENTS ON
SABRIL.
HOWEVER, THIS ASSESSMENT CANNOT ALWAYS PREVENT VISION DAMAGE (5.1).
SABRIL IS AVAILABLE ONLY THROUGH A RESTRICTED PROGRAM CALLED THE
VIGABATRIN
REMS PROGRAM (5.2).
INDICATIONS AND USAGE
SABRIL is indicated for the treatment of:
Refractory Complex Partial Seizures as adjunctive therapy in patients
2 years of age and older who
have responded inadequately to several alternative treatments; SABRIL
is not indicated as a first line
agent (1.1)
Infantile Spasms - monotherapy in infants 1 month to 2 years of age
for whom the potential benefits
outweigh the potential risk of vision loss (1.2)
DOSAGE AND ADMINISTRATION
Refractory Complex Partial Seizures
Adults (17 years of age and older): Initiate at 1000 mg/day (500 mg
twice daily); increase total daily
dose weekly in 500 mg/day increments, to the recommended dose of 3000
mg/day (1500 mg twice
daily) (2.2)
Pediatric (2 to 16 years of age): The recommended dosage is based on
body weight and administered
as two divided doses (2.2)
The dosage may be increased in weekly intervals, depending