Vigabatrin

Class: Anticonvulsants, Miscellaneous
VA Class: CN400
Chemical Name: (±) 4-amino-5-hexenoic acid
Molecular Formula: C6H11NO2
CAS Number: 60643-86-9
Brands: Sabril

Warning(s)

  • Vision Loss
  • Risk of progressive and permanent bilateral concentric visual field constriction and possible reduced visual acuity.1 2

  • Risk increases with cumulative dosage and duration of use; however, no exposure is known to be without risk.1 2

  • Risk of new and worsening vision loss continues as long as vigabatrin is used and possibly after discontinuance.1 2

  • Periodic vision testing required, but cannot reliably prevent vision damage.1 2 3 (See Vision Loss under Cautions.)

  • Distribution of vigabatrin is restricted.1 2 (See Restricted Distribution Program under Dosage and Administration.)

REMS:

FDA approved a REMS for vigabatrin to ensure that the benefits outweigh the risks. The REMS may apply to one or more preparations of vigabatrin and consists of the following: medication guide, elements to assure safe use, communication plan, and implementation system. See the FDA REMS page () or the ASHP REMS Resource Center (). (See also Restricted Distribution Program under Dosage and Administration.)

Introduction

Anticonvulsant; irreversible inhibitor of GABA transaminase (GABA-T).1 2 6 16 17 18 19 20 21 22 24 25

Uses for Vigabatrin

Infantile Spasms

Management (as monotherapy) of infantile spasms (IS; also known as West's syndrome) in pediatric patients 1 month–2 years of age for whom potential benefits outweigh risk of vision loss.1 3 5 6 7 21 24 25 52 55 58 (See Vision Loss under Boxed Warning and also under Cautions.)

Designated an orphan drug by FDA for this use.5

Slideshow: Flashback: FDA Drug Approvals 2013

Many experts consider hormonal treatments (e.g., corticotropin [ACTH], prednisolone or prednisone, tetracosactide [not commercially available in the US]) and vigabatrin drugs of choice for treatment of IS.7 14 15 21 25 27 28 29 55 58 62 Vigabatrin is particularly effective in treating IS associated with tuberous sclerosis.6 8 14 15 25 27 29 58 62 Additional studies needed to determine optimal management of IS.8 58

Refractory Complex Partial Seizures

Management (in combination with other anticonvulsants) of refractory complex partial seizures (CPS) in adults who have not responded adequately to several alternative treatments.2 16 17 25

Use only in patients in whom potential benefits outweigh risk of vision loss.2 3 21 (See Vision Loss under Boxed Warning and also under Cautions.)

Do not use as first-line therapy.2 52

Vigabatrin Dosage and Administration

General

  • Periodically assess patient's response to and continued need for therapy.1 2 Discontinue treatment if seizure control not apparent after an adequate trial of therapy.1 2 (See Vision Loss under Boxed Warning and also under Cautions.)

  • Avoid abrupt discontinuance; withdraw gradually to minimize potential for increased seizure frequency.1 2 (See Dosage under Dosage and Administration.)

  • Closely monitor for notable changes in behavior that could indicate emergence or worsening of suicidal thoughts or behavior or depression.1 2 3 10 11 12 (See Suicidality Risk under Cautions.)

Restricted Distribution Program

Distribution of vigabatrin is restricted in the US because of the risk of permanent vision loss (see REMS and also see Vision Loss under Boxed Warning and also under Cautions).1 2 3 22 25

Can only prescribe and obtain vigabatrin through the SHARE (Support, Help, And Resources for Epilepsy) program.1 2 22 24

For further information, contact the SHARE program at 888-45-SHARE (888-457-4273) or visit .1 2 38

Administration

Oral Administration

Administer orally (as oral solution for infantile spasms or tablets for refractory complex partial seizures) without regard to meals.1 2 25

Reconstitution

When using the oral solution in infants, instruct parents or caregivers on proper reconstitution, administration, and dosing procedures and confirm their understanding.1

Use only water to dissolve the powder; mix thoroughly with a small spoon or other clean utensil until powder completely dissolves and solution is clear.1 4 Do not mix powder for oral solution with food.1 3 4

Empty entire contents of the appropriate number of packets (500 mg/packet) into a clean, clear cup; dissolve with 10 mL of cold or room-temperature water per packet using the 10-mL oral syringe supplied by manufacturer to yield a final concentration of 50 mg/mL.1 4

For 0–500 mg doses, dissolve 1 packet with 10 mL of water; for 501–1000 mg doses, dissolve 2 packets with 20 mL of water; and for 1–1.5 g doses, dissolve 3 packets with 30 mL of water.1 4

Use an oral syringe to withdraw volume of solution that will provide the appropriate dose; discard any leftover solution.4 Administer immediately following preparation.4

Dosage

Plasma vigabatrin concentrations not directly correlated with efficacy; therapeutic drug monitoring is not useful.1 16 19 21

Pediatric Patients

Infantile Spasms
Oral

Children 1 month–2 years of age: Initially, 50 mg/kg daily, administered in 2 divided doses (as oral solution).1 25 May increase in increments of 25–50 mg/kg daily every 3 days up to a maximum of 150 mg/kg daily.1 25 (See Table 1.)

A spasm-free response often observed within the first 2–4 weeks of therapy; most responses observed within the first 2–3 months.6 7 21 24

Table 1. Vigabatrin Oral Solution (50 mg/mL) Infant Dosing Table.1

Weight (kg)

Starting Dosage (50 mg/kg daily)

Maximum Dosage (150 mg/kg daily)

3

1.5 mL twice daily

4.5 mL twice daily

4

2 mL twice daily

6 mL twice daily

5

2.5 mL twice daily

7.5 mL twice daily

6

3 mL twice daily

9 mL twice daily

7

3.5 mL twice daily

10.5 mL twice daily

8

4 mL twice daily

12 mL twice daily

9

4.5 mL twice daily

13.5 mL twice daily

10

5 mL twice daily

15 mL twice daily

11

5.5 mL twice daily

16.5 mL twice daily

12

6 mL twice daily

18 mL twice daily

13

6.5 mL twice daily

19.5 mL twice daily

14

7 mL twice daily

21 mL twice daily

15

7.5 mL twice daily

22.5 mL twice daily

16

8 mL twice daily

24 mL twice daily

Reduce dosage gradually if discontinuing therapy.1 In a controlled study in patients with infantile spasms, vigabatrin was tapered at a rate of 25–50 mg/kg daily every 3–4 days.1

Adults

Refractory Complex Partial Seizures
Oral

Adjunctive treatment: Initially 1 g daily (given as 500 mg twice daily as tablets).2 25 May increase total daily dosage in 500-mg increments at weekly intervals up to the recommended dosage of 3 g daily (given as 1.5 g twice daily) depending on patient response.2 25

A 6-g daily dosage was not more effective than 3 g daily and was associated with increased adverse effects.2 16

Reduce dosage gradually if discontinuing therapy.2 In clinical studies, vigabatrin was tapered by decreasing the daily dosage by 1 g weekly.2

Prescribing Limits

Pediatric Patients

Infantile Spasms
Oral

Children 1 month–2 years of age: Maximum 150 mg/kg daily.1

Adults

Refractory Complex Partial Seizures
Oral

Although manufacturer does not provide a specific maximum dosage, a 6-g daily dosage was not more effective than 3 g daily and was associated with increased adverse effects.2 16

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.1 2

Renal Impairment

Reduce dosage in adults based on severity of renal impairment (see Table 2).1 2

Table 2. Vigabatrin Dosage Adjustment in Adults with Renal Impairment12

Clcr (mL/min)

Adjusted Dosage Regimen

>50–80 (mild)

Decrease dosage by 25%

>30–50 (moderate)

Decrease dosage by 50%

>10–30 (severe)

Decrease dosage by 75%

Although dosage adjustment in pediatric patients with renal impairment is warranted, specific dosage recommendations for such patients are not available.1 2

Manufacturer does not provide specific dosage recommendations for patients undergoing hemodialysis.1 2 Some clinicians recommend administering vigabatrin following the hemodialysis session.53

Geriatric Patients

Carefully select dosage because of possible decreased renal function.1 2 Consider adjusting dosage or frequency of administration; may respond to a lower maintenance dosage than younger adults.1 2

Cautions for Vigabatrin

Contraindications

  • No known contraindications.1 2

Warnings/Precautions

Warnings

Vision Loss

Risk of visual field defects, including permanent vision loss; may occur at any time during therapy and will not improve after discontinuance.1 2 3 21 22 24 25 34 35 37 52 62 64 65 (See Vision Loss under Boxed Warning.)In adults, manifestations include tunnel vision to within 10 degrees of visual fixation; central retinal vision and visual acuity also may be affected.1 2 23 25 64 Although visual field defects observed in pediatric patients,21 24 26 34 extent of vision loss is poorly characterized.1

Vision testing by a qualified ophthalmic professional required at baseline (≤4 weeks after start of therapy), at least every 3 months during treatment, and 3–6 months following cessation of therapy.1 2 3 22 Perform examinations to the extent possible in children; document such attempts under the SHARE program.1 2 3 If vision testing not possible (e.g., in children), may continue treatment according to clinical judgment after appropriate patient counseling and documentation.1 2 (See Restricted Distribution Program under Dosage and Administration.)

Unless benefits clearly outweigh risks, do not use in patients with, or at high risk of, other types of irreversible vision loss.1 2 Avoid concurrent use with other drugs associated with serious adverse ophthalmic effects (e.g., retinopathy, glaucoma).1 2 (See Drugs Associated with Serious Adverse Ophthalmic Effects under Interactions.)

Periodically reassess patient response to and continued need for therapy.1 2 Discontinue vigabatrin if substantial clinical benefit not evident within 2–4 weeks or within 3 months following therapy initiation in patients with infantile spasms or refractory complex partial seizures, respectively.1 2 If treatment failure becomes obvious earlier, discontinue drug at that time.1 2 (See Vision Loss under Boxed Warning.)

Other Warnings and Precautions

Magnetic Resonance Imaging Abnormalities

Abnormal magnetic resonance imaging (MRI) changes characterized by increased T2 signal and restricted diffusion in a symmetric pattern involving deep gray matter areas of the brain reported in some infants; these specific abnormalities not observed in older children (≥3 years of age) and adults.1 2 3 21 22 23 25 30 31 32 51

MRI abnormalities generally are transient, resolve upon drug discontinuance, and may be dose-dependent.1 2 23 30 31 32 51 In a few patients, the abnormalities resolved despite continued therapy.1 2 31 51 Coincident motor abnormalities reported in some infants; however, causal relationship to drug not established.1 2 23 30 31

Routine MRI surveillance in pediatric patients with infantile spasms generally not recommended since long-term clinical sequelae of MRI changes are unknown.23 24 31 Manufacturer states that routine MRI surveillance is unnecessary in adults.2 If MRI abnormalities are observed, weigh benefits of continued therapy against potential risks of MRI surveillance and possible clinical consequences of the MRI changes.31

Neurotoxicity

Neuropathologic and neurobehavioral changes observed in animals receiving vigabatrin.1 2 22 31 32 33 Neurotoxicity (including convulsions and hypomyelination) observed in rats exposed to vigabatrin during late gestation and the neonatal and juvenile periods of development; relationship of these findings with MRI abnormalities observed in vigabatrin-treated infants unknown.1 2 23 (See Magnetic Resonance Imaging Abnormalities under Cautions.)

Suicidality Risk

Increased risk of suicidality (suicidal ideation or behavior) observed in an analysis of studies using various anticonvulsants in patients with epilepsy, psychiatric disorders (e.g., bipolar disorder, depression, anxiety), and other conditions (e.g., migraine, neuropathic pain); risk in patients receiving anticonvulsants (0.43%) was approximately twice that in patients receiving placebo (0.24%).1 2 10 11 12 Increased suicidality risk was observed ≥1 week after initiation of anticonvulsant therapy and continued through 24 weeks.10 11 Risk was higher for patients with epilepsy compared with those receiving anticonvulsants for other conditions.1 2 10

Closely monitor all patients currently receiving or beginning anticonvulsant therapy for changes in behavior that may indicate emergence or worsening of suicidal thoughts or behavior or depression.1 10 11 12 Anxiety, agitation, hostility, insomnia, and mania may be precursors to emerging suicidality.10

Balance risk of suicidality with risk of untreated illness.1 2 10 Epilepsy and other illnesses treated with anticonvulsants are themselves associated with morbidity and mortality and an increased risk of suicidality.1 2 12 If suicidal thoughts or behavior emerge during anticonvulsant therapy, consider whether these symptoms may be related to the illness itself.1 2 12 (See Advice to Patients.)

Discontinuance of Anticonvulsants

Abrupt withdrawal of anticonvulsants may result in increased seizure frequency in patients with seizure disorders.1 2 Withdraw vigabatrin gradually.1 2

Anemia

Anemia and/or potentially clinically important hematology changes involving hemoglobin, hematocrit, and/or RBC indices reported.1 2

Somnolence and Fatigue

Somnolence and fatigue reported, sometimes requiring discontinuance from clinical trials.1 2

May impair mental and/or physical abilities required to perform potentially hazardous tasks such as driving or operating machinery.1 2 (See Advice to Patients.)

Peripheral Neuropathy

Peripheral neuropathy symptoms reported in adults.1 2 Initial manifestations include numbness or tingling in the toes or feet, signs of reduced distal lower limb vibration or position sensation, and/or progressive loss of reflexes starting at the ankles.1 2

Studies in pediatric patients not adequately designed to assess whether peripheral neuropathy occurs in this population.1 24

Weight Gain

Weight gain reported in adults;1 2 19 22 25 usually was self-limiting in clinical trials,16 but long-term effects of such weight gain not known.1 2 Weight gain not apparently related to occurrence of edema (see Edema under Cautions).1 2

Pediatric clinical studies not adequately designed to evaluate weight gain.1

Edema

Edema reported in adults.1 2 Pediatric clinical studies not adequately designed to determine whether edema occurs in pediatric patients.1

No apparent association between edema and adverse cardiovascular effects (e.g., hypertension, CHF).1 2 Edema not associated with laboratory changes suggesting deterioration of renal or hepatic function.1 2

Laboratory Test Interferences

Decreases plasma ALT and AST activity in ≤90% of patients, sometimes to undetectable levels.1 2 16 May preclude use of these tests, particularly ALT, to detect early hepatic injury.1 2 24

May increase amount of amino acids in the urine, possibly resulting in false positive test results for certain rare genetic metabolic disorders (e.g., alpha aminoadipic aciduria).1 2 56 Consider obtaining urine for metabolic evaluation prior to initiating therapy.56

Specific Populations

Pregnancy

Category C.1 2 25

North American Antiepileptic Drug (NAAED) Pregnancy Registry (for patients) at 888-233-2334 or .1 2

Lactation

Distributed into milk.1 2 44 45 Discontinue nursing or the drug.1 2

Pediatric Use

Indicated as monotherapy in pediatric patients 1 month–2 years of age with infantile spasms for whom potential benefits outweigh the risk of vision loss; safety and efficacy for treating infantile spasms not established outside this age group.1 (See Vision Loss under Boxed Warning and also under Cautions.)

Safety and efficacy for treatment of complex partial seizures in pediatric patients <16 years of age not established;2 risks (e.g., vision loss) generally appear to outweigh benefits of such use.23 (See Vision Loss under Boxed Warningand also under Cautions.)

Abnormal MRI signal changes observed in some infants receiving vigabatrin for infantile spasms.1 2 31 (See Magnetic Resonance Imaging Abnormalities and see also Neurotoxicity under Cautions.)

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.1 2

Moderate to severe sedation and confusion reported in several patients >65 years of age with reduced renal function (Clcr <50 mL/minute).1 2 Other reported clinical experience has not identified differences in response.1 2

Reduced renal function more likely in geriatric patients.1 2 Carefully select dosage; renal function monitoring may also be useful.1 2 (See Geriatric Patients under Dosage and Administration and see also Special Populations under Pharmacokinetics.)

Hepatic Impairment

Pharmacokinetics in patients with hepatic impairment not evaluated.1 2 24

Suppresses ALT and AST activity.1 2 24 (See Laboratory Test Interferences under Cautions.)

Renal Impairment

Decreased clearance; use with caution.1 2 22 24 Adjust dosage and monitor for dose-related adverse effects.1 2 24 (See Renal Impairment under Dosage and Administration and see also Special Populations under Pharmacokinetics.)

Race

Race-related pharmacokinetic differences not specifically evaluated.1 2 Limited data suggest that renal clearance may be lower in Japanese than in Caucasian populations.1 2

Common Adverse Effects

Causes permanent vision damage in a high percentage of patients.1 2 (See Vision Loss under Boxed Warningand also under Cautions.)

Adults with refractory complex partial seizures: fatigue, somnolence, nystagmus, tremor, blurred vision, memory impairment, weight gain, arthralgia, abnormal coordination, confusional state.1 2 16 22 25

Pediatric patients with infantile spasms: somnolence, bronchitis, ear infection, acute otitis media.1 7

Interactions for Vigabatrin

Not extensively metabolized by hepatic CYP isoenzymes.1 2

Induces CYP2C9; does not appear to induce or inhibit other hepatic CYP isoenzymes.1 2 19 24

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Substrates of CYP2C9: potential pharmacokinetic interaction (decreased plasma substrate concentrations).1 19 22 24 25 42

Substrates of other CYP isoenzymes: clinically important interactions unlikely.1 19 22 24 25 42

Drugs Associated with Serious Adverse Ophthalmic Effects

Avoid concurrent use with other drugs associated with serious adverse ophthalmic effects (e.g., retinopathy, glaucoma) unless benefits clearly outweigh risks.1 2 54

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Alcohol

Pharmacokinetic interaction not observed;1 2 24 no evidence of additive CNS depressant effects42

Carbamazepine

Both increased48 49 and decreased plasma carbamazepine concentrations46 49 reported;46 48 49 no apparent effect on plasma vigabatrin concentrations1 2

Monitor plasma carbamazepine concentrations; adjust dosage if necessary46 48 49

Clonazepam

Increased peak plasma concentrations and decreased time to peak concentration of clonazepam; no substantial change in plasma concentrations of vigabatrin1 2

No evidence of additive CNS effects42

Clorazepate

No apparent effect on plasma vigabatrin concentrations2

Felbamate

Slightly increased AUC of vigabatrin; no change in plasma concentrations or AUC of felbamate59 60

Clinically important pharmacokinetic interaction unlikely59 60

Routine dosage adjustments not necessary59 60

Oral contraceptives

No substantial effect on CYP3A4-mediated metabolism of ethinyl estradiol/levonorgestrel;1 2 50 unlikely to affect efficacy of steroid oral contraceptives1 2

Pharmacokinetics of vigabatrin not substantially affected1 2 50

Phenobarbital

Clinically important pharmacokinetic interaction unlikely1 2 16 19

Phenytoin

Decreased total plasma phenytoin concentrations (by 16–20%), probably due to induction of CYP2C91 2 21 22 25 42

Routine phenytoin dosage adjustment not required; adjust dosage if clinically indicated1 2 19

Primidone

Clinically important pharmacokinetic interaction unlikely1 2 16 19

Rufinamide

Slight to moderate decrease in plasma concentrations of rufinamide47

Monitor carefully when initiating or discontinuing either anticonvulsant; adjust rufinamide dosage if necessary47

Tests for ALT and AST activity

Possible suppression of ALT and AST activity1 2

Consider that these tests, particularly ALT, may not be useful for detection of early hepatic injury1 2 24

Tests for amino acids in urine

Possible increased amino acid concentrations in urine; may result in false positive tests for certain rare genetic metabolic disorders (e.g., alpha aminoadipic aciduria)1 2 56

Consider obtaining urine for metabolic evaluation prior to initiating vigabatrin therapy56

Valproic acid

Decreased plasma valproate sodium concentrations,1 2 but no substantial effect on vigabatrin concentrations1 2

Clinically important pharmacokinetic Interaction unlikely 1 2 19 24

Vigabatrin Pharmacokinetics

Absorption

Bioavailability

Rapidly and essentially completely absorbed following oral administration.1 2 21 22 24 Commercially available tablets and oral solution are bioequivalent, with an absolute oral bioavailability of 60–70%.1 2 22

Peak plasma concentrations generally occur within approximately 2.5 hours in infants and 1 hour in older children and adults following oral administration.1 2 22

Little or no accumulation occurs with multiple dosing.1 2 24

Duration

Duration of effect presumed to be dependent on rate of GABA-T resynthesis rather than on rate of drug elimination.1 2 24

Food

Food decreases peak plasma concentrations by 33% and increases time to peak concentrations, but does not affect systemic exposure.1 2 24

Special Populations

Systemic exposure increased by approximately 30%, twofold, and 4.5-fold in adults with mild, moderate, and severe renal impairment, respectively.1 2

Distribution

Extent

Widely distributed.1 2 21 22

Crosses the placenta.44 Distributed into milk,1 2 44 45 probably in small amounts.44

Plasma Protein Binding

Not appreciably bound to plasma proteins.1 2 21 22

Elimination

Metabolism

Not extensively metabolized.1 2 22

Elimination Route

Principally excreted in urine (95% of orally administered dose recovered over 72 hours), with unchanged drug accounting for 80% of the recovered dose.1 21 22

Half-life

Adults: About 7.5 hours.1 2 22 24

Infants: About 5.7 hours.1 2 22 24

Special Populations

In infants and children, clearance is decreased compared with adults.1

In patients with mild, moderate, or severe renal impairment, terminal half-life is increased by 55%, twofold, or 3.5-fold, respectively.1 2

Effect of hemodialysis on clearance not adequately studied.1 2 57 In case reports, hemodialysis reduced plasma concentrations by 40–60%.1 2 53 57

Pharmacokinetics in patients with hepatic impairment not evaluated.1 2

In individuals >65 years of age, renal clearance is reduced by 36% compared with younger individuals.1 2

Stability

Storage

Oral

Powder for Oral Solution

20–25°C.1

Tablets

20–25°C.2

Actions

  • Structural analog of GABA, the primary inhibitory neurotransmitter in the CNS.17 18 20 21 22

  • Exact mechanism of antiseizure effect unknown; thought to be related to preferential and irreversible inhibition of GABA-T, the enzyme responsible for the degradation of GABA, and the resultant increase in GABA concentrations in the CNS.1 2 6 16 17 18 19 20 21 22 24 25

  • Following oral administration, CNS and blood concentrations of GABA increase in a dose-related matter, but there is no direct correlation between plasma concentrations and drug efficacy.1 2 21 22 24 25

  • Highly selective and specific for GABA-T; does not affect other enzymatic pathways in the GABA system.22

  • Commercially available as a racemic mixture of 2 enantiomers; the S enantiomer is pharmacologically active and the R enantiomer is inactive.24 44 57

Advice to Patients

  • Importance of providing patient or caregiver a copy of manufacturer's patient information (medication guide).1 2 (See REMS and also see Restricted Distribution Program under Dosage and Administration.) Importance of patients or caregivers reading the information carefully and discussing questions or concerns with clinician.1 2

  • Risk of permanent vision loss; peripheral vision field loss potentially may interfere with ability to drive.1 2 3 52 Importance of advising patients or caregivers that vision testing, including an assessment of peripheral vision, is required at baseline and periodically during treatment. Importance of patients understanding that visual testing may not prevent the occurrence of visual impairment, but can allow for early detection and intervention.1 2 3 Importance of patients or caregivers notifying a clinician immediately if changes in vision are suspected.1 2 3

  • Importance of taking only as prescribed.1 2 When using oral solution, confirm that caregivers understand instructions for reconstitution and administration of correct dosage to their infants.1

  • Importance of informing caregivers about the possibility of developing abnormal MRI signal changes of unknown clinical importance.1 31

  • Risk of suicidality (anticonvulsants, including vigabatrin, may increase risk of suicidal thoughts or actions in about 1 in 500 people).1 10 12 Importance of patients, family, and caregivers being alert to day-to-day changes in mood, behavior, and actions and immediately informing clinician of any new or worrisome behaviors (e.g., talking or thinking about wanting to hurt oneself or end one’s life, withdrawing from friends and family, becoming depressed or experiencing worsening of existing depression, becoming preoccupied with death and dying, giving away prized possessions).1 10

  • Importance of informing patients or caregivers not to stop vigabatrin therapy without first talking to their clinician since stopping the drug suddenly can cause serious problems, including increased seizures.1 2 3

  • Risk of drowsiness and fatigue.1 2 3 Importance of advising patients not to drive or operate other complex machinery until they have become accustomed to the drug's effects.1 2 3

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illness (e.g., kidney disease, vision problems, depression or other mood disorders) or family history of suicidality or bipolar disorder.1 2 3

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 2 3 Importance of clinicians informing women about the existence of and encouraging enrollment in pregnancy registries (see Pregnancy under Cautions).1 2 3

  • Importance of informing patients or caregivers of other important precautionary information.1 2 3 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Distribution of vigabatrin is restricted.1 2 (See Restricted Distribution Program under Dosage and Administration.)

Vigabatrin

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Powder for oral solution

500 mg

Sabril (available in packets)

Lundbeck

Tablets, film-coated

500 mg

Sabril (scored)

Lundbeck

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions April 3, 2012. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Lundbeck Inc. Sabril (vigabatrin) for oral solution prescribing information. Deerfield, IL; 2010 Feb.

2. Lundbeck Inc. Sabril (vigabatrin) tablets prescribing information. Deerfield, IL; 2010 Feb.

3. Lundbeck Inc. Sabril (vigabatrin) tablet and for oral solution medication guide. Deerfield, IL; 2009 Aug.

4. Lundbeck Inc. Sabril (vigabatrin) for oral solution dosing instructions. Deerfield, IL; 2009 Aug.

5. US Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (PL. 97-414). Rockville, MD; [March 9, 2010]. From FDA web site.

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11. US Food and Drug Administration. FDA News: FDA alerts health care providers to risk of suicidal thoughts and behavior with antiepileptic medications. Rockville, MD; 2008 Jan 31. From the FDA website. Accessed 2010 Mar 12.

12. US Food and Drug Administration. Suicidal behavior and ideation and antiepileptic drugs: update 5/5/2009. Rockville, MD; 2009 May 5. From the FDA website. Accessed 2010 Mar 12.

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18. Hemming K, Maguire MJ, Hutton JL et al. Vigabatrin for refractory partial epilepsy. Cochrane Database of Systematic Reviews 2008, Issue 3. Art. No.: CD007302. DOI: 10.1002/14651858.CD007302.

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20. Beran RG, Berkovic SF, Buchanan N et al. A double-blind, placebo-controlled crossover study of vigabatrin 2 g/day and 3 g/day in uncontrolled partial seizures. Seizure. 1996; 5:259-65. [PubMed 8952010]

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22. Tolman JA, Faulkner MA. Vigabatrin: a comprehensive review of drug properties including clinical updates following recent FDA approval. Expert Opin Pharmacother. 2009; 10:3077-89. [PubMed 19954276]

23. Food and Drug Administration. Center for Drug Evaluation and Research: Application number 20-427: Summary Review. From FDA website http://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/020427s000_SumR.pdf.

24. Lundbeck Inc: Personal communication.

25. Anon. Vigabatrin (Sabril) for epilepsy. Med Lett Drugs Ther. 2010; 52: 14-6.

26. Lux AL, Edwards SW, Hancock E et al. The United Kingdom Infantile Spasms Study comparing vigabatrin with prednisolone or tetracosactide at 14 days: a multicentre, randomised controlled trial. Lancet. 2004; 364:1773-8. [PubMed 15541450]

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