Usual Adult Dose for Epilepsy

Initial dose: 500 mg orally twice a day

• Increase in 500 mg increments at weekly intervals based on response

Maintenance dose: 1500 mg orally twice a day

Comments:

• Use the lowest dose and shortest exposure consistent with clinical objectives.
• In clinical studies, a dose of 6000 mg/day did not show additional benefit but was associated with an increased incidence of adverse events.
• In patients with refractory complex partial seizures, this drug should be withdrawn if a substantial clinical benefit is not observed within 3 months of initiating treatment; if evidence of treatment failure becomes obvious earlier than 3 months, treatment should be discontinued at that time.
• This drug is not indicated as a first line agent for complex partial seizures.

Use: As an adjunct for refractory complex partial seizures in patients who have inadequately responded to several alternative treatments and for whom the potential benefits outweigh the risk of vision loss.

Usual Pediatric Dose for Infantile Spasms

1 month to 2 years of age:
Initial dose: 25 mg/kg orally twice daily

• Dose may be titrated in 25 to 50 mg/kg/day increments every 3 days

Maximum dose: 150 mg/kg/day in 2 divided doses (75 mg/kg twice daily)

Comments:

• Use the lowest dose and shortest exposure consistent with clinical objectives.
• This drug should be withdrawn if a substantial clinical benefit is not observed within 2 to 4 weeks of initiating treatment; if evidence of treatment failure becomes obvious earlier, treatment should be discontinued at that time.

Use:

• As monotherapy for pediatric patients who are 1 month to 2 years of age with infantile spasms and for whom the potential benefits outweigh the risk of vision loss.

Usual Pediatric Dose for Epilepsy

10 to 16 years; weight 25 to 60 kg:
Initial dose: 250 mg orally twice a day

• Increase in 500 mg increments at weekly intervals based on response

Maintenance dose: 1000 mg orally twice a day

10 to 16 years; weight greater than 60 kg and patients 17 years or older:
Initial dose: 500 mg orally twice a day

• Increase in 500 mg increments at weekly intervals based on response

Maintenance dose: 1500 mg orally twice a day

Comments:

• Use the lowest dose and shortest exposure consistent with clinical objectives.
• In clinical studies in adults, a dose of 6000 mg/day did not show additional benefit but was associated with an increased incidence of adverse events.
• In patients with refractory complex partial seizures, this drug should be withdrawn if a substantial clinical benefit is not observed within 3 months of initiating treatment; if evidence of treatment failure becomes obvious earlier than 3 months, treatment should be discontinued at that time.
• This drug is not indicated as a first line agent for complex partial seizures.

Use: As an adjunct for refractory complex partial seizures in patients who have inadequately responded to several alternative treatments and for whom the potential benefits outweigh the risk of vision loss.

Renal Dose Adjustments

Infants with renal impairment: Data not available

10 years of age and older:

• Mild renal impairment (CrCl 50 to 80 mL/min): Decrease dose by 25%
• Moderate renal impairment (CrCl 31 to 50 mL/min): Decrease dose by 50%
• Severe renal impairment (CrCl 10 to 30 mL/min): Decrease dose by 75%

Liver Dose Adjustments

Data not available

Dose Adjustments

Elderly: Dose selection should be cautious; renal function monitoring should be considered

Plasma concentration monitoring to optimize therapy is not recommended

Drug Discontinuation:

• If symptomatic relief is not obtained, this drug should be discontinued
• In patients with refractory complex partial seizures, this drug should be withdrawn if a substantial clinical benefit is not observed within 3 months of initiating treatment or if evidence of treatment failure becomes obvious earlier, treatment should be discontinued at that time.
• In patients with infantile spasm, if a substantial clinical benefit is not observed within 2 to 4 weeks of initiating treatment or if evidence of treatment failure becomes obvious earlier, treatment should be discontinued at that time.

Drug Withdrawal:
As with all antiepileptic drugs, this drug should be withdrawn gradually, the following recommendations are based on clinical trials:

• Adults: Decrease by 1000 mg/day weekly
• Older pediatric patients: Decreased by one-third of the daily dose weekly
• Infantile spasms: 25 to 50 mg/kg every 3 to 4 days

Precautions

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for Vigabatrin. It includes elements to assure safe use and an implementation system. For additional information: www.accessdata.fda.gov/scripts/cder/rems/index.cfm

US BOXED WARNING: PERMANENT VISION LOSS:

• This drug can cause permanent bilateral concentric visual field constriction, including tunnel vision that can result in disability. In some cases, damage to the central retina and decreased visual acuity may occur.
• The onset of vision loss 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 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 initiating therapy), at least every 3 months during therapy, and about 3 to 6 months after the discontinuation of therapy.
• Once detected, vision loss 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 if this drug is used. It is possible that vision loss can worsen despite discontinuation of therapy.
• Because of the risk of vision loss, therapy should be withdrawn from patients with refractory complex partial seizures who fail to show substantial clinical benefit within 3 months of initiation and within 2 to 4 weeks of initiation for patients with infantile spasms, or sooner if treatment failure becomes obvious. Patient response to and continued need for therapy should be periodically reassessed.
• This drug 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.
• This drug 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 this drug consistent with clinical objectives.
• Because of the risk of permanent vision loss, this drug is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS).

CONTRAINDICATIONS:

• None

• Safety and efficacy have not been established in pediatric patients less than 10 years of age with refractory complex partial seizures.
• Safety and efficacy as monotherapy for pediatric patients with infantile spasms (1 month to 2 years of age) have been established.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available; isolated reports in patients with renal failure on hemodialysis have shown a 40% to 60% reduction in vigabatrin plasma concentrations

Other Comments

Administration advice:

• Take orally twice a day with or without food
• Tablets and powder for oral solution are bioequivalent
• Oral solution should be mixed with water prior to administration

Reconstitution/preparation techniques:
Oral Solution:

• Empty entire contents of 500 mg packet into clean cup and dissolve in 10 mL of cold or room temperature water; multiple packets may be needed to obtain dose
• The resulting concentration should be 50 mg/mL which should be administered using an oral syringe
• Consult manufacturer product information for infant dosing tables

General:

• Due to risk of vision loss, this drug is only available through the Vigabatrin REMS program.
• Use the lowest dosage and shortest exposure consistent with clinical objectives.

Monitoring:

• Vision should be monitored by an ophthalmic professional with expertise in visual field interpretation; vision testing in infants is difficult and must be individualized.
• Asses visual fields and visual acuity at baseline (no later than 4 weeks after starting therapy) and at least every 3 months on therapy, and at 3 to 6 months after discontinuation; in adults and 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 appropriate methods; because of variability, results from ophthalmic monitoring must be interpreted with caution, and repeat assessment is recommended if results are abnormal or uninterruptible.
• Monitor for emergence of worsening symptoms of depression, unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts of self-harm.
• Monitor for symptoms of anemia
• Monitor for neurotoxicity
• Consider renal function monitoring, especially in geriatric patients

Patient advice:

• Read the US FDA-approved patient labeling (Medication Guide and Instructions for Use).
• Patients should be fully apprised of the risk of permanent vision loss.
• Patients should understand that this drug causes somnolence and fatigue; they should be advised not to drive or operate other hazardous machinery until they understand how this drug effects their ability to perform such activities.

Frequently asked questions

• How long does vigabatrin (Sabril) take to work?
• What is the vigabatrin REMS Program?