VIGAFYDE vigabatrin 100 mg/mL Solution
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Anti-epileptic Agent class.
Where does this data come from?
🏭 Manufacturer & labeler
Where does this data come from?
🩺 Clinical
- Vigabatrin is specifically for seizures that haven't responded well to other treatments. It's not a first choice — it's reserved for situations where other options haven't worked,...
- Why is my doctor prescribing this instead of a more common seizure medication?
- Yes, this is a real and serious risk that's important to understand. Vigabatrin can permanently narrow your field of vision — sometimes described as tunnel vision — and in some peo...
- What's this I heard about vision loss? Should I be worried?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Vigabatrin — tap one for details:
Vigabatrin may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.
Where does this data come from?
Ask a licensed pharmacist directly — free, answered by our team.
🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
Where does this data come from?
IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | $24.14 | $3,621.39 / 150 ml |
| Medicare drug plans payPart D · Q2 2026 | $25.34 | $3,800.63 / 150 ml |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Vigafyde 100 mg/mLthis 80789-0003-15 | Upsher-Smith | 1 bottle | — | — | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
The FDA lists approved generic versions of this medicine, but that does not always mean a pharmacy can get one today. Patent rules, launch agreements, supply and pricing can affect when generics actually arrive.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 12576054 ↗ | Drug product | — | Jun 8, 2043 |
| US 12016857 ↗ | Drug product | — | Aug 16, 2039 |
| US 12290499 ↗ | Drug product | — | Oct 17, 2042 |
Is there a generic version of VIGAFYDE 100 MG/ML ORAL SOLN?
The FDA approved a generic — why can’t I get it at my pharmacy yet?
Why do different websites show different generic release dates?
What does “FDA listed” mean?
What does a patent or protection date mean here?
What does “current Orange Book estimate” mean?
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Can a generic come out after the listed dates?
What is the difference between patents and exclusivity?
Why are there multiple patent dates?
Where does this data come from?
🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2025 (Q1-Q4)
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
Where does this data come from?
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 80789-0003-15 You're viewing this | 1 BOTTLE in 1 CARTON (80789-003-15) / 150 mL in 1 BOTTLE | 2024-08-26 | Active |
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | — Not published for this NDC No photo available yet for this listing. |
| Inactive ingredients (structured) | — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available. |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | ✓ Available |
Questions about this listing
Why is there no price listed?
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📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: PERMANENT VISION LOSS VIGAFYDE can cause permanent bilateral concentric visual field constriction, including tunnel vision that can result in disability. In some cases, VIGAFYDE also can damage the central retina and may decrease visual acuity [see Warnings and Precautions ( 5.1 )]. The onset of vision loss from VIGAFYDE 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 VIGAFYDE 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 VIGAFYDE), at least every 3 months during therapy, and about 3 to 6 months after the discontinuation of therapy. Once detected, vision loss due to VIGAFYDE 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 vision loss is documented. Risk of new or worsening vision loss continues as long as VIGAFYDE is used. It is possible that vision loss can worsen despite discontinuation of VIGAFYDE.
Because of the risk of vision loss, VIGAFYDE should be withdrawn from patients with infantile spasms who fail to show substantial clinical benefit within 2 to 4 weeks of initiation, or sooner if treatment failure becomes obvious. Patient response to and continued need for VIGAFYDE should be periodically reassessed. VIGAFYDE 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.
VIGAFYDE 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 VIGAFYDE consistent with clinical objectives [see Dosage and Administration ( 2.1 )]. Because of the risk of permanent vision loss, VIGAFYDE is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Vigabatrin REMS [see Warnings and Precautions ( 5.1 ) ] .
Further information is available at www.vigabatrinREMS.com or call 1 -866-244-8175. WARNING: PERMANENT VISION LOSS See full prescribing information for complete boxed warning. VIGAFYDE can cause permanent bilateral concentric visual field constriction, including tunnel vision that can result in disability.
In some cases, VIGAFYDE may also decrease visual acuity. ( 5.1 ) Risk increases with increasing dose and cumulative exposure, but there is no dose or exposure to VIGAFYDE known to be free of risk of vision loss. ( 5.1 ) Risk of new and worsening vision loss continues as long as VIGAFYDE is used, and possibly after discontinuing VIGAFYDE.
( 5.1 ) Baseline and periodic vision assessment is recommended for patients on VIGAFYDE. However, this assessment cannot always prevent vision damage. ( 5.1 ) VIGAFYDE is available only through a restricted program called the Vigabatrin REMS.
( 5.2 )
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE VIGAFYDE is indicated as monotherapy for the treatment of i nfantile spasms in pediatric patients 1 month to 2 years of age for whom the potential benefits outweigh the potential risk of vision loss. ( 1 ) VIGAFYDE is indicated as monotherapy for the treatment of infantile spasms in pediatric patients 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 )].
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION VIGAFYDE is a concentrated formulation as compared to other vigabatrin products. Verify the strength and the dose of the product prior to prescribing, dispensing, and administering. ( 2.1 ) Administer VIGAFYDE orally or via gastrostomy (G) tube.
Doses administered via gastrojejunal (GJ) tubes must be administered through the G-port. ( 2.1 ) Initiate at a daily dosage of 50 mg/kg (25 mg/kg twice daily); increase total daily dosage every 3 days, in increments of 25 mg/kg/day to 50 mg/kg/day, up to a maximum daily dosage of 150 mg/kg (75 mg/kg twice daily). ( 2.2 )
2.1Important Dosing and Administration Instructions Dosing VIGAFYDE is a solution of 100 mg/mL of vigabatrin. VIGAFYDE is a concentrated solution as compared to other vigabatrin products. Verify strength and the dose of the product prior to prescribing, dispensing, and administering [see Dosage and Administration ( 2.3 )].
VIGAFYDE does not require additional reconstitution or dilution prior to administration. Use the lowest dosage and shortest exposure to VIGAFYDE consistent with clinical objectives [see Warnings and Precautions ( 5.1 )]. The VIGAFYDE dosing regimen depends on weight.
Monitoring of VIGAFYDE plasma concentrations to optimize therapy is not helpful. Administration Administer VIGAFYDE orally or via gastrostomy (G) tube. Doses administered via gastrojejunal (GJ) tubes must be administered through the G-port.
After G-tube administration, flush with water. VIGAFYDE can be given with or without food. A calibrated measuring device is recommended to measure and deliver the prescribed dose accurately.
A household teaspoon or tablespoon is not an adequate measuring device. If a decision is made to discontinue VIGAFYDE, the dose should be gradually reduced [see Dosage and Administration ( 2.4 ) and Warnings and Precautions ( 5.5 )] .
2.2Recommended Dosage for Infantile Spasms The initial daily dosing is 50 mg/kg/day given in two divided doses (25 mg/kg twice daily); subsequent dosing can be titrated by 25 mg/kg/day to 50 mg/kg/day increments every 3 days, up to a maximum of 150 mg/kg/day given in 2 divided doses (75 mg/kg twice daily) [see Use in Specific Populations ( 8.4 )] . Table 1 provides the volume of the 100 mg/mL dosing solution that should be administered as individual doses in infants of various weights. Table 1.
Dosing of VIGAFYDE for Infantile Spasms Weight [kg] Starting Dose 50 mg/kg/day Maximum Dose 150 mg/kg/day 3 75 mg (0.75 mL) twice daily 225 mg (2.25 mL) twice daily 4 100 mg (1 mL) twice daily 300 mg (3 mL) twice daily 5 125 mg (1.25 mL) twice daily 375 mg (3.75 mL) twice daily 6 150 mg (1.5 mL) twice daily 450 mg (4.5 mL) twice daily 7 175 mg (1.75 mL) twice daily 525 mg (5.25 mL) twice daily 8 200 mg (2 mL) twice daily 600 mg (6 mL) twice daily 9 225 mg (2.25 mL) twice daily 675 mg (6.75 mL) twice daily 10 250 mg (2.5 mL) twice daily 750 mg (7.5 mL) twice daily 11 275 mg (2.75 mL) twice daily 825 mg (8.25 mL) twice daily 12 300 mg (3 mL) twice daily 900 mg (9 mL) twice daily 13 325 mg (3.25 mL) twice daily 975 mg (9.75 mL) twice daily 14 350 mg (3.5 mL) twice daily 1,050 mg (10.5 mL) twice daily 15 375 mg (3.75 mL) twice daily 1,125 mg (11.25 mL) twice daily 16 400 mg (4 mL) twice daily 1,200 mg (12 mL) twice daily In patients with infantile spasms, VIGAFYDE 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 [see Warnings and Precautions ( 5.1 )].
2.3Switching Between Other Vigabatrin Products and VIGAFYDE If switching between other vigabatrin products and VIGAFYDE, ensure the correct volume for the correct dosage is prescribed, dispensed, and administered. As compared to other vigabatrin products, VIGAFYDE is a concentrated solution that requires a smaller volume than other vigabatrin products to obtain the…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Oral Solution : 100 mg/mL clear, colorless to light yellow solution with a peppermint odor. Oral Solution : 100 mg/mL ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS None. None ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Abnormal MRI signal changes and intramyelinic edema have been reported in some infants with infantile spasms receiving VIGAFYDE. ( 5.3 , 5.4 ) Withdrawal of AEDs: Taper dose to avoid withdrawal seizures. ( 5.5 ) Anemia: Monitor for symptoms of anemia. ( 5.6 )
5.1Permanent Vision Loss VIGAFYDE can cause permanent vision loss. Because of this risk and because, when it is effective, VIGAFYDE provides an observable symptomatic benefit; patient response and continued need for treatment should be periodically assessed. VIGAFYDE is indicated for treatment in patients 1 month to 2 years of age [see Indications and Usage ( 1 )].
VIGAFYDE is not approved for use in pediatric patients older than 2 years of age or in adults. Based upon adult studies, 30 percent or more of patients can be affected with bilateral concentric visual field constriction ranging in severity from mild to severe. Severe cases may be characterized by tunnel vision to within 10 degrees of visual fixation, which can result in disability.
In some cases, VIGAFYDE also can damage the central retina and may decrease visual acuity. Symptoms of vision loss from VIGAFYDE 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 VIGAFYDE may be more common, more severe, or have more severe functional consequences in infants than in adults cannot be excluded.
The onset of vision loss from VIGAFYDE 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 infantile spasms, VIGAFYDE 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 [see Dosage and Administration ( 2.2 ) and Warnings and Precautions ( 5.5 )]. VIGAFYDE 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 VIGAFYDE has not been well-characterized, but is likely adverse.
VIGAFYDE 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 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 [see Warnings and Precautions ( 5.2 )]. Because vision testing in infants is difficult, vision loss may not be detected until it is severe.
For patients receiving VIGAFYDE, vision assessment is recommended at baseline (no later than 4 weeks after starting VIGAFYDE), at least every 3 months while on therapy, and about 3 to 6 months after the discontinuation of therapy. The diagnostic approach should be individualized for the patient and clinical situation. In cooperative pediatric patients, perimetry is recommended, preferably by automated threshold visual field testing.
Additional testing may also include electrophysiology (e.g., electroretinography [ERG]), retinal imaging (e.g., optical coherence tomography [OCT]), and/or other methods appropriate for the patient. In patients who…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following serious and otherwise important adverse reactions are described elsewhere in labeling: Permanent Vision Loss [see BOXED WARNING and Warnings and Precautions ( 5.1 )] Magnetic Resonance Imaging (MRI) Abnormalities in Infants [see Warnings and Precautions ( 5.3 )] Neurotoxicity [see Warnings and Precautions ( 5.4 )] Withdrawal of Antiepileptic Drugs (AEDs) [see Warnings and Precautions ( 5.5 )] Anemia [see Warnings and Precautions ( 5.6 )] Somnolence and Fatigue [see Warnings and Precautions ( 5.7 )] Peripheral Neuropathy [see Warnings and Precautions ( 5.8 )] Weight Gain [see Warnings and Precautions ( 5.9 )] Edema [see Warnings and Precautions ( 5.10 )] Suicidal Behavior and Ideation with Unapproved use in Adolescents and Adults [see Warnings and Precautions ( 5.11 )] The most common adverse reactions (incidence ˃5% and greater than on placebo) in patients with infantile spasms include somnolence, bronchitis, ear infection, and acute otitis media.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Upsher-Smith Laboratories, LLC at 1-855-899-9180 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Infantile Spasms In a randomized, placebo-controlled study in patients with infantile spasms (IS) with a 5 day double-blind treatment phase (n=40), the adverse reactions that occurred in ≥5% of patients receiving vigabatrin and that occurred more frequently than in placebo patients were somnolence (vigabatrin 45%, placebo 30%), bronchitis (vigabatrin 30%, placebo 15%), ear infection (vigabatrin 10%, placebo 5%), and acute otitis media (vigabatrin 10%, placebo 0%).
In patients with IS, the adverse reactions most commonly associated with vigabatrin treatment discontinuation in ≥1% of patients were infections, status epilepticus, developmental coordination disorder, dystonia, hypotonia, hypertonia, weight gain, and insomnia. In a dose response study of low-dose (18 to 36 mg/kg/day, which is below the recommended starting dose for IS of 50 mg/kg/day) versus high-dose (100 to 148 mg/kg/day) vigabatrin, no clear correlation between dose and incidence of adverse reactions was observed.
The adverse reactions (≥5% in either dose group) are summarized in Table 2. Table 2. Adverse Reactions in a Placebo-Controlled Trial in Patients with Infantile Spasms Body System Adverse Reaction Vigabatrin Low Dose [N=114] % Vigabatrin High Dose [N=108] % Eye Disorders (other than field or acuity changes) Strabismus 5 5 Conjunctivitis 5 2 Gastrointestinal Disorders Vomiting 14 20 Constipation 14 12 Diarrhea 13 12 General Disorders Fever 29 19 Infections Upper respiratory tract infection 51 46 Otitis media 44 30 Viral infection 20 19 Pneumonia 13 11 Candidiasis 8 3 Ear infection 7 14 Gastroenteritis viral 6 5 Sinusitis 5 9 Urinary tract infection 5 6 Influenza 5 3 Croup infectious 5 1 Metabolism & Nutrition Disorders Decreased appetite 9 7 Nervous System Disorders Sedation 19 17 Somnolence 17 19 Status epilepticus 6 4 Lethargy 5 7 Convulsion 4 7 Hypotonia 4 6 Psychiatric Disorders Irritability 16 23 Insomnia 10 12 Re s piratory Disorders Nasal congestion 13 4 Cough 3 8 Skin and Subcutaneous Tissue Disorders Rash 8 11
6.2Postm arketing Experience The following adverse reactions have been identified during postapproval use of vigabatrin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Ear Disorders : Deafness Endocrine Disorders : Delayed puberty Gastrointestinal Disorders : Gastrointestinal hemorrhage, esophagitis General Disorders : Developmental delay, facial edema, malignant hyper…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Decreased phenytoin plasma levels: Dosage adjustment may be needed. ( 7.1 )
7.1Antiepileptic Drugs Phenytoin Although phenytoin dose adjustments are not routinely required, dose adjustment of phenytoin should be considered if clinically indicated, since VIGAFYDE may cause a moderate reduction in total phenytoin plasma levels [see Clinical Pharmacology ( 12.3 )]. Clonazepam VIGAFYDE may moderately increase the C max of clonazepam resulting in an increase of clonazepam-associated adverse reactions [see Clinical Pharmacology ( 12.3 )].
7.2Drug-Laboratory Test Interactions VIGAFYDE decreases alanine transaminase (ALT) and aspartate transaminase (AST) plasma activity in up to 90% of patients. In some patients, these enzymes become undetectable. The suppression of ALT and AST activity by vigabatrin may preclude the use of these markers, especially ALT, to detect early hepatic injury.
VIGAFYDE may increase the amount of amino acids in the urine, possibly leading to a false positive test for certain rare genetic metabolic diseases (e.g., alpha aminoadipic aciduria).
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy VIGAFYDE is indicated for treatment in patients 1 month to 2 years of age [see Indications and Usage ( 1 )]. VIGAFYDE is not approved for use in adolescents and adults. Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AEDs, including VIGAFYDE, during pregnancy.
Encourage women who are taking VIGAFYDE 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 VIGAFYDE 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, VIGAFYDE 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/m 2 ) 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/m 2 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/m 2 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…
🤰 Pregnancy ▾
8.1Pregnancy VIGAFYDE is indicated for treatment in patients 1 month to 2 years of age [see Indications and Usage ( 1 )]. VIGAFYDE is not approved for use in adolescents and adults. Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AEDs, including VIGAFYDE, during pregnancy.
Encourage women who are taking VIGAFYDE 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 VIGAFYDE 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, VIGAFYDE 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/m 2 ) 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/m 2 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/m 2 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 receivin…
🧒 Pediatric Use ▾
8.4Pediatric Use 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 ( 2.2 ) and Clinical Studies ( 14.1 )]. Safety and effectiveness as a 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 ( 14.1 )]. 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 )].
🧓 Geriatric Use ▾
8.5Geriatric Use VIGAFYDE is indicated for treatment in patients 1 month to 2 years of age [see Indications and Usage ( 1 )]. VIGAFYDE is not approved for use in adults. 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. If used in elderly patients, adjustment of dose or frequency of administration should be considered. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.
🆘 Overdosage ▾
10 OVERDOSAGE
10.1Signs, Symptoms, and Laboratory Findings of Overdosage 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.
10.2Management of Overdosage There is no specific antidote for VIGAFYDE 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 VIGAFYDE 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%.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action The precise mechanism of vigabatrin’s anti-seizure effect is unknown, but it is believed to be the result of its action as an irreversible inhibitor of γ-aminobutyric acid transaminase (GABA-T), the enzyme responsible for the metabolism of the inhibitory neurotransmitter GABA. This action results in increased levels of GABA in the central nervous system. No direct correlation between plasma concentration and efficacy has been established.
The duration of drug effect is presumed to be dependent on the rate of enzyme re-synthesis rather than on the rate of elimination of the drug from the systemic circulation.
12.2Pharmacodynamics Effects on Electrocardiogram There is no indication of a QT/QTc prolonging effect of vigabatrin in single doses up to 6.0 g. In a randomized, placebo-controlled, crossover study, 58 healthy subjects were administered a single oral dose of vigabatrin (3 g and 6 g) and placebo. Peak concentrations for 6.0 g vigabatrin were approximately 2-fold higher than the peak concentrations following the 3.0 g single oral dose.
12.3Pharmacokinetics VIGAFYDE is indicated for treatment in patients 1 month to 2 years of age [see Indications and Usage ( 1 )]. VIGAFYDE is not approved for use in adults. Vigabatrin displayed linear pharmacokinetics after administration of single doses ranging from 0.5 g to 4 g, and after administration of repeated doses of 0.5 g and 2.0 g twice daily.
The following PK information (T max , half-life, and clearance) of vigabatrin was obtained from stand-alone PK studies and population PK analyses. Absorption Following oral administration, vigabatrin is essentially completely absorbed. The time to maximum concentration (T max ) is approximately 2.5 hours for infants (5 months to 2 years of age).
There was little accumulation with multiple dosing in adult and pediatric patients. A food effect study involving administration of vigabatrin to healthy volunteers under fasting and fed conditions indicated that the C max was decreased by 33%, T max was increased to 2 hours, and AUC was unchanged under fed conditions. Distribution Vigabatrin does not bind to plasma proteins.
Vigabatrin is widely distributed throughout the body; mean steady-state volume of distribution is
1.1L/kg (CV = 20%). Metabolism and Elimination Vigabatrin is not significantly metabolized; it is eliminated primarily through renal excretion. The terminal half-life of vigabatrin is about 5.7 hours for infants (5 months to 2 years of age).
Following administration of [14] C-vigabatrin to healthy male volunteers, about 95% of total radioactivity was recovered in the urine over 72 hours with the parent drug representing about 80% of this. Vigabatrin induces CYP2C9 but does not induce other hepatic cytochrome P450 enzyme systems. Specific Populations Pediatric The clearance of vigabatrin is
2.4L/hr for infants (5 months to 2 years of age). Gender No gender differences were observed for the pharmacokinetic parameters of vigabatrin in patients. Race No specific study was conducted to investigate the effects of race on vigabatrin pharmacokinetics.
A cross study comparison between 23 Caucasian and 7 Japanese patients who received 1, 2, and 4 g of vigabatrin indicated that the AUC, C max , and half-life were similar for the two populations. However, the mean renal clearance of Caucasians (5.2 L/hr) was about 25% higher than the Japanese (4.0 L/hr). Inter-subject variability in renal clearance was 20% in Caucasians and was 30% in Japanese.
Renal Impairment Mean AUC increased by 30% and the terminal half-life increased by 55% (8.1 hr vs 12.5 hr) in adult patients with mild renal impairment (CLcr from >50 to 80 mL/min) in comparison to normal subjects. Mean AUC increased by two-fold and the terminal half-life increased by two-fold in adult patients with moderate renal impairment (CLcr from >30 to 50 mL/min) in comparison to normal subjects. Mean AUC increased by 4.5-fold and the terminal…
🧬 Mechanism of Action ▾
12.1Mechanism of Action The precise mechanism of vigabatrin’s anti-seizure effect is unknown, but it is believed to be the result of its action as an irreversible inhibitor of γ-aminobutyric acid transaminase (GABA-T), the enzyme responsible for the metabolism of the inhibitory neurotransmitter GABA. This action results in increased levels of GABA in the central nervous system. No direct correlation between plasma concentration and efficacy has been established.
The duration of drug effect is presumed to be dependent on the rate of enzyme re-synthesis rather than on the rate of elimination of the drug from the systemic circulation.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How Supplied VIGAFYDE (vigabatrin) oral solution contains 100 mg/mL vigabatrin. It is a clear, colorless to light yellow, peppermint-flavored solution supplied in a white opaque high-density polyethylene (HDPE) 150 mL bottle in a carton (NDC 80789-003-15).
16.2Storage and Handling Store unopened bottles at room temperature between 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. After opening, store bottle in a refrigerator or at room temperature between 2°C to 30°C (36°F to 86°F). Discard the unused portion 90 days after first opening.
16.1How Supplied VIGAFYDE (vigabatrin) oral solution contains 100 mg/mL vigabatrin. It is a clear, colorless to light yellow, peppermint-flavored solution supplied in a white opaque high-density polyethylene (HDPE) 150 mL bottle in a carton (NDC 80789-003-15).
📦 Storage and Handling ▾
16.2Storage and Handling Store unopened bottles at room temperature between 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. After opening, store bottle in a refrigerator or at room temperature between 2°C to 30°C (36°F to 86°F). Discard the unused portion 90 days after first opening.
📋 Description ▾
11 DESCRIPTION VIGAFYDE (vigabatrin) oral solution is an antiepileptic drug. The chemical name of vigabatrin is (±) 4-amino-5-hexenoic acid, a racemic mixture of R and S isomers. The molecular formula is C 6 H 11 NO 2 and the molecular weight is 129.16.
It has the following structural formula: Vigabatrin is a white to off-white powder which is freely soluble in water, slightly soluble in methyl alcohol, very slightly soluble in ethyl alcohol and chloroform, and insoluble in toluene and hexane. The pH of a 1% aqueous solution is about 6.9. The n-octanol/water partition coefficient of vigabatrin is about 0.011 (log P =-1.96) at physiologic pH.
Vigabatrin melts with decomposition in a 3-degree range within the temperature interval of 171ºC to 176ºC. The dissociation constants (pKa) of vigabatrin are 4 and 9.7 at room temperature (25ºC). Each mL of VIGAFYDE contains 100 mg of vigabatrin.
The inactive ingredients are methylparaben; peppermint flavor; propylparaben; purified water; and sucralose. structural formula for vigabatrin
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise caregivers to read the FDA-approved patient labeling ( Medication Guide and Instructions for Use ). If a patient is switching from vigabatrin powder for oral solution, inform the caregiver that VIGAFYDE is more concentrated (100 mg/mL) compared to reconstituted solutions of vigabatrin powder for oral solution (50 mg/mL), and the volume of solution that should be given to their infant will be lower than previously prescribed. Advise patients to stop using other products that contain vigabatrin.
Administration Instructions for VIGAFYDE Oral Solution Physicians should confirm that caregiver(s) understand how to measure and administer the correct dose of VIGAFYDE oral solution to their infants. Advise caregivers to measure VIGAFYDE with the syringe provided by the pharmacy. A household teaspoon is not an accurate measuring device.
Instruct caregivers that VIGAFYDE should not be diluted prior to dosing. Advise the caregiver that VIGAFYDE may be given orally or via gastrostomy (G) tube. Doses administered via gastrojejunal (GJ) tubes must be administered through the G-port.
If VIGAFYDE will be administered via G-tube, provide instructions to the caregiver(s) as to how to flush the tube after administration. Advise the caregiver to discard any remaining VIGAFYDE 90 days after first opening. Permanent Vision Loss Inform caregivers of the risk of permanent vision loss, particularly loss of peripheral vision, from VIGAFYDE, and the need for monitoring vision [see Warnings and Precautions ( 5.1 )] .
Monitoring of vision, including assessment of visual fields and visual acuity, is recommended at baseline (no later than 4 weeks after starting VIGAFYDE), at least every 3 months while on therapy, and about 3 to 6 months after discontinuation of therapy. In patients for whom vision testing is not possible, treatment may continue without recommended testing according to clinical judgment with appropriate caregiver counseling. Caregivers should be informed that if baseline or subsequent vision is not normal, VIGAFYDE should only be used if the benefits of VIGAFYDE treatment clearly outweigh the risks of additional vision loss.
Advise caregivers that vision testing may be insensitive and may not detect vision loss before it is severe. Also advise caregivers that if vision loss is documented, such loss is irreversible. Ensure that both of these points are understood by caregivers.
Caregivers should be informed that if changes in vision are suspected, they should notify their physician immediately. VIGABATRIN REMS VIGAFYDE is available only through a restricted program called the Vigabatrin REMS [see Warnings and Precautions ( 5.2 )] . Inform caregivers of the following: Patients/caregivers must be enrolled in the program.
VIGAFYDE is only available through pharmacies that are enrolled in the Vigabatrin REMS. MRI Abnormalities in Infants Inform caregiver(s) of the possibility that infants may develop an abnormal MRI signal of unknown clinical significance [see Warnings and Precautions ( 5.3 )] . Withdrawal of VIGAFYDE Therapy Instruct patients and caregivers not to suddenly discontinue VIGAFYDE therapy without consulting with their healthcare provider.
As with all AEDs, withdrawal should normally be gradual [see Warnings and Precautions ( 5.5 )] . Distributed by UPSHER-SMITH LABORATORIES, LLC Maple Grove, MN 55369 VIGAFYDE is a registered trademark of Pyros Pharmaceuticals, Inc. PLEF0427-4-414
💬 Medication Guide ▾
MEDICATION GUIDE VIGAFYDE ® ( VIG- uh-fide ) (vigabatrin) oral solution What is the most important information I should know about VIGAFYDE? VIGAFYDE can cause serious side effects, including: Permanent vision loss Magnetic resonance imaging (MRI) changes in babies with infantile spasms (IS) 1. Permanent vision loss: VIGAFYDE 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, your baby may only be able to see things straight in front of them (sometimes called “tunnel vision”). Your baby may also have blurry vision.
If this happens, it will not get better. Vision loss in babies: Because of the risk of vision loss, VIGAFYDE is used in babies 1 month to 2 years of age with IS only when you and your baby's healthcare provider decide that the possible benefits of VIGAFYDE are more important than the risks. Parents or caregivers are not likely to recognize the symptoms of vision loss in babies until it is severe.
Healthcare providers may not find vision loss in babies until it is severe. It is difficult to test vision in babies, but, to the extent possible, all babies should have their vision tested before starting VIGAFYDE or within 4 weeks after starting VIGAFYDE, and every 3 months after that until VIGAFYDE is stopped. Your baby should also have a vision test about 3 to 6 months after VIGAFYDE is stopped.
Your baby may not be able to be tested. Your baby's healthcare provider will determine if your baby can be tested. If your baby cannot be tested, your baby's healthcare provider may continue prescribing VIGAFYDE, but your baby's healthcare provider will not be able to watch for any vision loss.
Tell your healthcare provider right away if you think that your baby is: not seeing as well as before taking VIGAFYDE. acting differently than normal. Even if your baby’s vision seems fine, it is important to get regular vision tests because damage can happen before your baby acts differently. Even these regular vision exams may not show the damage to your baby’s vision before it is severe and permanent.
Because VIGAFYDE might cause permanent vision loss, it is available to healthcare providers and patients only under a special program called the Vigabatrin Risk Evaluation and Mitigation Strategy (REMS). VIGAFYDE can only be prescribed to people who are enrolled in this program. As part of the Vigabatrin REMS, it is recommended that your baby's healthcare provider test your baby's vision from time to time (periodically) while your baby is being treated with VIGAFYDE, and even after your baby stops treatment.
Your baby's healthcare provider will explain the details of the Vigabatrin REMS to you. For more information, go to www.vigabatrinREMS.com or call 1-866-244-8175. 2.
MRI changes in babies with IS: Brain pictures taken by MRI show changes in some babies after they are given VIGAFYDE. It is not known if these changes are harmful. What is VIGAFYDE?
VIGAFYDE is a prescription medicine used to treat babies 1 month to 2 years of age who have infantile spasms (IS) if you and your baby’s healthcare provider decide the possible benefits of taking VIGAFYDE are more important than the possible risk of vision loss. What should I tell my baby's healthcare provider before starting VIGAFYDE? If you are a parent or caregiver whose baby has IS, before giving VIGAFYDE to your baby, tell your baby's healthcare provider about all of your baby’s medical conditions, including if your baby has or ever had: an allergic reaction to VIGAFYDE, such as hives, itching, or trouble breathing. any vision problems. any kidney problems.
Tell your baby's healthcare provider about all the medicines your baby takes, including prescription and over-the-counter medicines, vitamins, and herbal supplements. VIGAFYDE and other medicines may affect each other causing side effects. How should my baby take VIGAFYDE?
VIGAFYDE com…