VIGABATRIN for solution

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

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

Available from:

Amneal Pharmaceuticals NY LLC

INN (International Name):

VIGABATRIN

Composition:

VIGABATRIN 500 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Vigabatrin for oral solution 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)] . Vigabatrin for oral solution is not indicated as a first line agent for complex partial seizures. Vigabatrin for oral solution 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 vigabatrin, during pregnancy. Encourage women who are taking vigabatrin 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 vigabatrin in pregnant women. Limited available data from case reports and cohort studies pertaining to vigabatrin 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, vigabatrin 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% to 4% and 15% to 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 to 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 vigabatrin 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 vigabatrin, observe for any potential adverse effects [see Warnings and Precautions (5.1, 5.3, 5.4, 5.8)] . The safety and effectiveness of vigabatrin 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 vigabatrin 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 vigabatrin 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 to 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 to 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)] . Vigabatrin (vye ga’ ba trin) for oral solution Read this Instructions for Use before your child starts taking vigabatrin for oral solution and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your child’s medical condition or treatment. Talk to your healthcare provider if you have any questions about the right dose of medicine to give your child or how to mix it. Important Note:    - Vigabatrin for oral solution comes in a packet - Each packet contains 500 mg of vigabatrin for oral solution powder - V igabatrin for oral solution powder must be mixed with water only. The water may be cold or at room temperature. - Your healthcare provider will tell you: - how many packets of vigabatrin for oral solution you will need for each dose - how many milliliters (mL) of water to use to mix one dose of vigabatrin for oral solution - how many milliliters (mL) of the powder and water mixture you will need for each dose of medicine - Vigabatrin for oral solution should be given right away after it is mixed - Use the oral syringes, provided by the pharmacy, to measure and give the correct dose. Do not use a household teaspoon or tablespoon. Supplies you will need to mix 1 dose of v igabatrin for oral solution: - The number of packets of vigabatrin for oral solution needed for each dose - 2 clean cups: 1 for mixing and 1 for water. The cup used for mixing vigabatrin for oral solution should be clear so you can see if the powder is dissolved - Water to mix with the vigabatrin for oral solution powder - One small 3 mL oral syringe and one large 10 mL oral syringe which are provided by the pharmacy - Small spoon or other clean utensil to stir the mixture - Scissors Oral syringe detail Step 1: Start with 1 of the empty cups and the total number of packets you will need for 1 dose. Step 2: Before you open the packet, tap it to settle all the powder to the bottom of the packet. Step 3: Use a pair of scissors to cut open the vigabatrin for oral solution packet along the dotted line. Step 4: Empty the entire contents of the vigabatrin for oral solution packet into 1 of the clean empty cups (see Figure A). Figure A - Repeat steps 2 to 4 above to open all of the packets needed for 1 dose of vigabatrin for oral solution. Step 5: Take the second cup and fill it half way with water (see Figure B). Do not mix vigabatrin for oral solution with anything other than water. Figure B - You will use the larger oral syringe (10 mL) to draw up the water needed to mix with the powder from the packets. You will need 10 mL of water for each packet of v igabatrin for oral solution. For example: - If you are using 1 packet of vigabatrin for oral solution, you will need to use 10 mL of water (fill the 10 mL oral syringe 1 time) - If you are using 2 packets of vigabatrin for oral solution, you will need to use 20 mL of water (fill the 10 mL oral syringe 2 times) - If you are using 3 packets of vigabatrin for oral solution, you will need to use 30 mL of water (fill the 10 mL oral syringe 3 times) Step 6: Use the 10 mL oral syringe to draw up 10 mL of water. To do this, put the tip of the oral syringe all the way into the water in your cup. Then pull the plunger up towards you until the edge of the white plunger is at the 10 mL line on the barrel of the oral syringe (see Figure C). Figure C - If you see bubbles of air in the oral syringe after drawing up the water, turn the oral syringe so the tip is pointing up (see Figure D). The air will move to the top of the oral syringe. Pull the plunger back towards you and then push it back gently into the oral syringe to get rid of the bubbles. Tiny bubbles are normal. Figure D Step 7: Check the oral syringe to make sure it is filled with water up to the 10 mL line (see Figure E). Figure E Step 8: Get the second cup that contains the vigabatrin for oral solution needed for your dose. Step 9: Hold the 10 mL oral syringe that is filled with water with the tip pointing down over the vigabatrin for oral solution. Step 10: Slowly push the oral syringe plunger all the way down to empty the water from the oral syringe straight into the cup containing the vigabatrin for oral solution (see Figure F). Figure F Repeat steps 6 through 10 until all of the water that is needed to mix 1 dose of v igabatrin for oral solution has been added to the cup containing the powder. Step 11: Stir the mixture with the small spoon or other clean utensil until the solution is clear (see Figure G). This means that all of the powder is dissolved and ready for use. Figure G - To give a dose of vigabatrin for oral solution to your child, you should use the oral syringe to draw up the total number of mLs of the mixture that your healthcare provider tells you to. - If you are giving 3 mL or less of the mixture, use the smaller 3 mL oral syringe. - If you are giving more than 3 mL of the mixture, use the larger 10 mL oral syringe (this is the oral syringe that you just used to add the water). Step 12: Put the tip of the oral syringe all the way into the mixture. Pull the plunger up towards you to draw up the mixture. Stop when the edge of the white plunger lines up with markings on the barrel of the oral syringe that matches the number of mLs of mixture your healthcare provider told you to give (see Figure H). Figure H - If you see bubbles of air in the oral syringe after drawing up the mixture, turn the oral syringe so the tip is pointing up (see Figure I). The air will move to the top of the oral syringe. Pull the plunger back towards you and then gently push it back in the oral syringe in order to get rid of the bubbles. Tiny bubbles are normal. Figure I Step 13: Place the tip of the oral syringe into your child’s mouth and point the oral syringe towards either cheek (see Figure J). Push on the plunger slowly, a small amount at a time, until all of the mixture in the oral syringe is given. Figure J - If the dose you are giving your child is more than 10 mLs, repeat steps 12 and 13 until you give the total dose of mixture prescribed by your healthcare provider. Step 14: Throw away any mixture that is left over. Do not save or reuse any leftover mixture. Step 15: Wash the oral syringes and mixing cups in warm water. To clean the oral syringes, remove the plunger by gently pulling it straight out of the barrel. The barrel and plunger can be hand washed with soap and water, rinsed, and allowed to dry. This Instructions for Use has been approved by the U.S. Food and Drug Administration. Distributed by: Amneal Pharmaceuticals LLC Bridgewater, NJ 08807 Rev. 01-2020-03

Product summary:

Vigabatrin for oral solution USP, 500 mg packets contain a white to off-white granular powder. They are available as follows: Carton of 50 packets:                                     NDC 69238-1425-5 (Single Packet:                                                NDC 69238-1425-1) The oral syringes are provided separately by the pharmacy. Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].

Authorization status:

Abbreviated New Drug Application

Patient Information leaflet

Amneal Pharmaceuticals NY LLC
----------
MEDICATION GUIDE
Dispense with Medication Guide available at:
documents.amneal.com/mg/vigabatrinoralsolution.pdf
Vigabatrin (vye ga’ ba trin) for Oral Solution, USP
What is the most important information I should know about vigabatrin
for oral solution?
Vigabatrin for oral solution 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:
Vigabatrin for oral solution 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 vigabatrin for oral solution in adults and
children 2 years and older:
Because of the risk of vision loss, vigabatrin for oral solution 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 vigabatrin for oral
solution.
•
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
vigabatrin for oral solution or within 4 weeks after starting
vigabatrin for oral solution, and at
least every 3 months after that until vigabatrin for oral solution is
stopped. It is also recommended
that you (or your chi

Summary of Product characteristics

VIGABATRIN- VIGABATRIN FOR SOLUTION
AMNEAL PHARMACEUTICALS NY LLC
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
VIGABATRIN FOR ORAL
SOLUTION SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
VIGABATRIN FOR ORAL
SOLUTION.
VIGABATRIN FOR ORAL SOLUTION
INITIAL U.S. APPROVAL: 2009
WARNING: PERMANENT VISION LOSS
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
VIGABATRIN CAN CAUSE PERMANENT BILATERAL CONCENTRIC VISUAL FIELD
CONSTRICTION,
INCLUDING TUNNEL VISION THAT CAN RESULT IN DISABILITY. IN SOME CASES,
VIGABATRIN MAY
ALSO DECREASE VISUAL ACUITY (5.1).
RISK INCREASES WITH INCREASING DOSE AND CUMULATIVE EXPOSURE, BUT THERE
IS NO DOSE
OR EXPOSURE TO VIGABATRIN KNOWN TO BE FREE OF RISK OF VISION LOSS
(5.1).
RISK OF NEW AND WORSENING VISION LOSS CONTINUES AS LONG AS VIGABATRIN
IS USED, AND
POSSIBLY AFTER DISCONTINUING VIGABATRIN (5.1).
BASELINE AND PERIODIC VISION ASSESSMENT IS RECOMMENDED FOR PATIENTS ON
VIGABATRIN.
HOWEVER, THIS ASSESSMENT CANNOT ALWAYS PREVENT VISION DAMAGE (5.1).
VIGABATRIN IS AVAILABLE ONLY THROUGH A RESTRICTED PROGRAM CALLED THE
VIGABATRIN REMS
PROGRAM (5.2).
INDICATIONS AND USAGE
Vigabatrin for oral solution 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;
vigabatrin for oral solution 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 1,000 mg/day (500 mg
twice daily); increase total daily
dose weekly in 500 mg/day increments, to the recommended dose of 3,000
mg/day (1,500 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 dose