MOBILE VIEW  | 
Adult Dosing


Normal Dosage

    Oral route
      Complex partial epileptic seizure, Refractory; Adjunct
        a) Initial dosage: 500 mg orally twice daily [1]
        b) Dosage titration: Increase dose in 500-mg/day increments at weekly intervals [1].
        c) Maximum dosage: 3000 mg/day [1]
        d) Duration: Periodically reassess patient response and the need for continued treatment. Due to the risk of vision loss, therapy should be discontinued in patients who fail to demonstrate significant clinical benefit within 3 months of initiation, or sooner if treatment failure is evident [1].
        e) Discontinuing therapy: Gradual tapering of the dose is recommended. In clinical studies, vigabatrin was tapered by decreasing the daily dose by 1000 mg/day on a weekly basis until discontinued [1].
    The oral solution and the tablet formulation are bioequivalent [1].

Dosage in Renal Failure

    A) CrCl greater than 50 to 80 mL/min: Decrease dose by 25% [1].
    B) CrCl greater than 30 to 50 mL/min: Decrease dose by 50% [1].
    C) CrCl greater than 10 to 30 mL/min: Decrease dose by 75% [1].

Pediatric Dosing


Normal Dosage

    Oral route
    Complex partial epileptic seizure, Refractory; Adjunct
    West syndrome
      Complex partial epileptic seizure, Refractory; Adjunct
        a) 10 to 16 Years and 25 to 60 kg
        1) Initial dosage: 250 mg orally twice daily [1]
        2) Dosage titration: Increase dose in 500-mg/day increments at weekly intervals [1].
        3) Maintenance dose: 1000 mg twice daily [1]
        4) Duration: Periodically reassess patient response and the need for continued treatment. Due to the risk of vision loss, therapy should be discontinued in patients who fail to demonstrate significant clinical benefit within 3 months of initiation, or sooner if treatment failure is evident [1].
        5) Discontinuing therapy: Gradual tapering of the dose is recommended. In a clinical study of pediatric patients, vigabatrin was tapered by decreasing the daily dose by one-third on a weekly basis until discontinued [1].
        b) 10 to 16 Years and Greater Than 60 kg
        1) Initial dosage: 500 mg orally twice daily [1]
        2) Dosage titration: Increase dose in 500-mg/day increments at weekly intervals [1].
        3) Maximum dosage: 3000 mg/day [1]
        4) Duration: Periodically reassess patient response and the need for continued treatment. Due to the risk of vision loss, therapy should be discontinued in patients who fail to demonstrate significant clinical benefit within 3 months of initiation, or sooner if treatment failure is evident [1].
        5) Discontinuing therapy: Gradual tapering of the dose is recommended. In a clinical study of pediatric patients, vigabatrin was tapered by decreasing the daily dose by one-third on a weekly basis until discontinued [1].
        c) 17 years and Older
        1) Initial dosage: 500 mg orally twice daily [1]
        2) Dosage titration: Increase dose in 500-mg/day increments at weekly intervals [1].
        3) Maximum dosage: 3000 mg/day [1]
        4) Duration: Periodically reassess patient response and the need for continued treatment. Due to the risk of vision loss, therapy should be discontinued in patients who fail to demonstrate significant clinical benefit within 3 months of initiation, or sooner if treatment failure is evident [1].
        5) Discontinuing therapy: Gradual tapering of the dose is recommended. In a clinical study of pediatric patients, vigabatrin was tapered by decreasing the daily dose by one-third on a weekly basis until discontinued [1].
      West syndrome
        a) 1 Month to 2 Years
        1) Initial dosage: 50 mg/kg/day orally in 2 divided doses (25 mg/kg twice daily) [1]
        2) Dosage titration: Titrate by 25 to 50 mg/kg/day increments every 3 days [1]
        3) Maximum dosage: 150 mg/kg/day in 2 divided doses (75 mg/kg twice daily) [1]
        4) Duration: Periodically reassess patient response and the need for continued treatment. Due to the risk of vision loss, therapy should be discontinued in patients who fail to demonstrate significant clinical benefit within 2 to 4 weeks of initiation, or sooner if treatment failure is evident [1].
        5) Discontinuing therapy: Do not suddenly discontinue therapy; gradual tapering of the dose is recommended. In a clinical study, the daily dose was decreased by 25 to 50 mg/kg every 3 to 4 days [1].
        b) Infant Dosing Table
        1) The following table provides the volumes to be administered as individual doses in infants of various weights [1]:
        Weight (kg)Starting Dose50 mg/kg/dayMaximum Dose150 mg/kg/day
        31.5 mL twice daily4.5 mL twice daily
        42 mL twice daily6 mL twice daily
        52.5 mL twice daily7.5 mL twice daily
        63 mL twice daily9 mL twice daily
        73.5 mL twice daily10.5 mL twice daily
        84 mL twice daily12 mL twice daily
        94.5 mL twice daily13.5 mL twice daily
        105 mL twice daily15 mL twice daily
        115.5 mL twice daily16.5 mL twice daily
        126 mL twice daily18 mL twice daily
        136.5 mL twice daily19.5 mL twice daily
        147 mL twice daily21 mL twice daily
        157.5 mL twice daily22.5 mL twice daily
        168 mL twice daily24 mL twice daily

    The oral solution and the tablet formulation are bioequivalent [1].

Dosage in Renal Failure

    A) CrCl greater than 50 to 80 mL/min: Decrease dose by 25% [1].
    B) CrCl greater than 30 to 50 mL/min: Decrease dose by 50% [1].
    C) CrCl greater than 10 to 30 mL/min: Decrease dose by 75% [1].

Fda Approved Uses


Complex partial epileptic seizure, Refractory; Adjunct

    FDA Labeled Indication
    1) Overview
    FDA Approval: Adult, yes; Pediatric, yes (10 years or older )
    Efficacy: Adult, Evidence favors efficacy; Pediatric, Evidence favors efficacy
    Recommendation: Adult, Class IIb; Pediatric, Class IIb
    Strength of Evidence: Adult, Category B; Pediatric, Category B


    2) Summary:
    Indication
    Vigabatrin is indicated as adjunctive therapy for patients with refractory complex partial seizures who have inadequately responded to several alternative treatments and for whom the potential benefits outweigh the risk of vision loss. Vigabatrin is not indicated as first-line therapy for complex partial seizures [1].

    Evidence (Adult)
    Efficacy was established in 2 randomized, double-blind clinical trials (N=357) with treatment durations of 16 to 18 weeks. A 50% or greater reduction in seizure frequency was achieved in approximately 39% to 51% of patients receiving 3 g/day compared with 9% to 21% of patients receiving placebo [1]. Anticonvulsant efficacy was maintained for up to 5 years in long-term studies [3][4][5][6][7][8]. If loss of seizure control occurs, it is generally seen during the first 2 years of therapy [3].

    Evidence (Pediatric)
    Pooled data from 3 randomized, double-blind, placebo-controlled studies (N=373) with treatment durations of 14 to 17 weeks were used to establish efficacy and appropriate dosing. No individual study was adequately powered to determine efficacy of vigabatrin in patients 10 years or older [1]. Both single-blind (Luna et al, 1989) [9] and open-label, multicenter studies [10] demonstrated efficacy with a 75% to 100% reduction in seizures in approximately 25% of children and adolescents who were treated with mean daily doses of 40 to 85 mg/kg; some children received doses as high as 600 mg/kg/day. Efficacy was generally maintained with long-term therapy (up to 4 years) in responding children [9].

West syndrome

    FDA Labeled Indication
    1) Overview
    FDA Approval: Adult, no; Pediatric, yes (1 month to 2 years of age, powder for oral solution)
    Efficacy: Pediatric, Evidence favors efficacy
    Recommendation: Pediatric, Class IIb
    Strength of Evidence: Pediatric, Category B


    2) Summary:
    Indication
    Vigabatrin is indicated as monotherapy for infantile spasms in patients for whom the potential benefits outweigh the potential risk of vision loss [1].

    Evidence
    Efficacy was established in 2 randomized controlled studies. Patients (N=221) received either low-dose (18 to 36 mg/kg/day) or high-dose (100 to 148 mg/kg/day) therapy; 68.2% in the high-dose group were spasm-free for 7 consecutive days at any time period during the study and remained spasm-free compared with 51.8% in the low-dose group. Relapse rates for the 25 primary responders who were spasm-free within the first 14 days of therapy were 11.8% in the high-dose group and 25% in the low-dose group, with a mean time to relapse of 162 days and 45 days, respectively. The relapse rate for the 39 patients who became spasm free for 7 consecutive days was 22.8%, with 71.8% becoming spasm free again [2]. Post hoc analysis of the 5-day treatment phase in a second study (N=40) showed a significant 68.9% reduction in spasms with vigabatrin (50 mg/kg/day, with titration to 150 mg/kg/day) vs 17% with placebo when a 24-hour evaluation window was used [1].

Off Labeled Uses

Route of administration

administrationSection


A) Preparation
1) General Information
a) The National Institute for Occupational Safety and Health (NIOSH) recommends the use of single gloves by anyone handling intact tablets or capsules or administering from a unit-dose package [11].
b) In the preparation of tablets or capsules, including cutting, crushing, or manipulating, or the handling of uncoated tablets, NIOSH recommends the use of double gloves and a protective gown. Prepare in a ventilated control device, if possible. Use respiratory protection if not prepared in a control device. During administration, wear single gloves, and wear eye/face protection if the formulation is hard to swallow or if the patient may resist, vomit, or spit up [11].
c) NIOSH recommends the use of double gloves and a protective gown by anyone handling a hazardous oral liquid or any hazardous drug via a feeding tube. Prepare in a control device, if possible. Use respiratory, eye, and face protection if not done in a control device. During administration, eye/face protection is needed if the patient may resist, or if there is potential to vomit or spit up [11].
2) Oral route
a) Preparation (Powder For Oral Solution)
1) Prepare and use each individual dose immediately [1].
2) Empty contents of each 500-mg packet into clean cup and dissolve with 10 mL of cold or room temperature water; final concentration is 50 mg/mL. The following table provides guidelines for the preparation of the powder for oral solution with the number of packages and mL of water used for each individual dose [1]:
Each Individual Dose (Prepared and Given Twice Daily)Number of PacketsNumber of mL of Water for Dissolving
0 to 500 mg1 packet10 mL
501 to 1000 mg2 packets20 mL
1001 to 1500 mg3 packets30 mL

3) (Powder for oral solution) Discard any unused portion of the prepared solution after administration [1].
b) Administration
1) Take with or without food [1].
2) Administer the prepared powder for oral solution with the supplied 10 mL oral syringe [1].
B) Oral route
1) Solution/Tablet
a) Store at controlled room temperature between 20 and 25 degrees C (68 and 77 degrees F) [16][26].

Comparative efficacy


Baclofen

    Spasticity
      a) Vigabatrin in mean doses of 2.2 grams daily was as effective as baclofen (mean, 37 milligrams daily) in treating spasticity associated with multiple sclerosis or spinal cord lesions in a preliminary, double-blind, placebo-controlled study involving 30 patients [108].

Carbamazepine

    Seizure
      a) Time to withdrawal for lack of efficacy or adverse events did not differ in newly diagnosed epileptic patients who received carbamazepine (n=226) or vigabatrin (n=220) in a double-blind, randomized, monotherapy study (p=0.318) [109]. However, patients treated with carbamazepine were more likely to withdraw sooner than vigabatrin patients, especially in the first 4 to 6 months of therapy. The total daily dose of vigabatrin was 1 gram (g) during the first 6 weeks after randomization. Vigabatrin dose was increased to 2 g as an initial maintenance dose with a dose range from 1.5 g to 4 g daily. The initial daily dose of carbamazepine was 200 milligrams (mg) followed by an increase to 600 mg after 6 weeks. Maintenance doses of carbamazepine ranged from 400 mg to 1600 mg per day. No treatment differences between treatment groups were observed throughout the study. After 12 months of double-blind therapy, 107 vigabatrin and 116 carbamazepine patients had achieved 6 months of remission. The time to first seizure was significantly less for vigabatrin patients compared to carbamazepine patients (p=0.0003). Twenty-three vigabatrin and 9 carbamazepine patients withdrew from the study solely due to lack of therapeutic effect (p=0.0298). Drowsiness, fatigue, and headache were reported by more than 20% of patients with no differences between the two treatment groups observed.. Adverse events in the psychiatric system were reported significantly more often in vigabatrin patients (25%) compared to carbamazepine patients (15%; p less than 0.05). Likewise, more patients treated with vigabatrin experienced weight gain (11%) compared to those treated with carbamazepine (5%; p less than 0.05). Carbamazepine patients experienced significantly more adverse events in the skin and appendages system (23%) compared to vigabatrin patients (14%; p less than 0.05). A decrease in white-cell counts, uric acid and bilirubin and an increase in alkaline phosphatase were observed in carbamazepine patients.
      b) Preliminary results from an open-label comparative trial (n=34) suggested the potential superiority of carbamazepine monotherapy over vigabatrin monotherapy in patients with newly diagnosed epilepsy [110]. In this study, 5 patients treated with vigabatrin 50 milligrams/kilogram/day were considered non- responders; 1 of these patients subsequently failed to respond to carbamazepine. None of the patients treated with carbamazepine (plasma levels of 35 micromol/L) were considered non-responders. However, 3 carbamazepine-treated patients discontinued therapy due to hypersensitivity reactions.
      c) Carbamazepine monotherapy was compared to vigabatrin monotherapy in patients with newly-diagnosed partial and/or generalized tonic-clonic seizures [111]. Sixty percent of patients (n=50) were considered successfully treated in both groups; however, significantly more patients were totally seizure free while receiving carbamazepine. Vigabatrin therapy resulted in fewer side effects that resulted in discontinuation of therapy. Vigabatrin monotherapy may be an alternative to carbamazepine or other standard antiepileptic drugs in cases where patients are intolerant of toxic or cognitive side effects.

Cosyntropin

    West syndrome
      a) Hormonal treatments, including either PREDNISOLONE or COSYNTROPIN, were superior to VIGABATRIN for inhibition of spasms in 2- to 12-month-old infants with INFANTILE SPASMS, according to the randomized, open-label UKISS trial (n=107). UKISS (United Kingdom Infantile Spasms Study) enrolled infants diagnosed with infantile spasms and who had hypsarrhythmic (or similar) electroencephalograms. Using a 1:1:2 ratio, enrollees were randomized to prednisolone (n=30), cosyntropin (n=25), or vigabatrin (n=52). Prednisolone was given as 10 milligrams (mg) orally 4 times a day for 2 weeks (dose increased to 20 mg 3 times daily after 1 week (wk) if spasms continued); cosyntropin was given as 0.5 mg (40 international units (IU)) intramuscularly on alternate days for 2 wk (dose increased to 0.75 mg (60 IU) on alternate days after 1 wk if spasms continued). Prednisolone- and cosyntropin-treated infants were switched to a dose-tapering regimen after 2 wk. Vigabatrin was given as 50 mg/kilogram (kg) orally in 2 divided doses daily for the first 2 doses, followed by 100 mg/kg/day after 24 hours (hr); if spasms continued, the dose was increased to 150 mg/kg/day after 4 days. At endpoint (after day 14 of the trial), spasms had ceased by days 13 and 14 (primary endpoint) in 40 infants (73%) given hormones (prednisolone, 21; cosyntropin, 19) compared with 28 infants (54%) who received vigabatrin (difference 19%; 95% confidence interval 1% to 36%; p=0.043). Number of consecutive days free of spasms totalled 9 and 2.5 for the hormonal and vigabatrin groups, respectively (p=0.038). Resolution of hypsarrhythmia occurred in 81% and 56% of those treated with hormones and vigabatrin, respectively (p=0.024). Adverse effects were reported in similar proportions in the hormonal and vigabatrin groups, with irritability and increased appetite more common in the hormonal group and drowsiness more common in the vigabatrin group. There were no detectable differences in response between infants receiving prednisolone and cosyntropin; however, the trial was not powered to compare the 2 hormonal agents [112].

Prednisolone

    West syndrome
      a) Hormonal treatments, including either prednisoLONE or COSYNTROPIN, were superior to VIGABATRIN for inhibition of spasms in 2- to 12-month-old infants with INFANTILE SPASMS, according to the randomized, open-label UKISS trial (n=107). UKISS (United Kingdom Infantile Spasms Study) enrolled infants diagnosed with infantile spasms and who had hypsarrhythmic (or similar) electroencephalograms. Using a 1:1:2 ratio, enrollees were randomized to prednisoLONE (n=30), cosyntropin (n=25), or vigabatrin (n=52). PrednisoLONE was given as 10 milligrams (mg) orally 4 times a day for 2 weeks (dose increased to 20 mg 3 times daily after 1 week (wk) if spasms continued); cosyntropin was given as 0.5 mg (40 international units (IU)) intramuscularly on alternate days for 2 wk (dose increased to 0.75 mg (60 IU) on alternate days after 1 wk if spasms continued). PrednisoLONE- and cosyntropin-treated infants were switched to a dose-tapering regimen after 2 wk. Vigabatrin was given as 50 mg/kilogram (kg) orally in 2 divided doses daily for the first 2 doses, followed by 100 mg/kg/day after 24 hours (hr); if spasms continued, the dose was increased to 150 mg/kg/day after 4 days. At endpoint (after day 14 of the trial), spasms had ceased by days 13 and 14 (primary endpoint) in 40 infants (73%) given hormones (prednisoLONE, 21; cosyntropin, 19) compared with 28 infants (54%) who received vigabatrin (difference 19%; 95% confidence interval 1% to 36%; p=0.043). Number of consecutive days free of spasms totalled 9 and 2.5 for the hormonal and vigabatrin groups, respectively (p=0.038). Resolution of hypsarrhythmia occurred in 81% and 56% of those treated with hormones and vigabatrin, respectively (p=0.024). Adverse effects were reported in similar proportions in the hormonal and vigabatrin groups, with irritability and increased appetite more common in the hormonal group and drowsiness more common in the vigabatrin group. There were no detectable differences in response between infants receiving prednisoLONE and cosyntropin; however, the trial was not powered to compare the 2 hormonal agents [112].

Role in Therapy


A) Complex Partial Seizures, Refractory
1) Vigabatrin is indicated as adjunctive therapy for adult and pediatric patients, 10 years or older, with refractory complex partial seizures who have inadequately responded to several alternative treatments (ie, valproic acid, primidone, carbamazepine, phenobarbital, phenytoin) and for whom the potential benefits outweigh the risk of vision loss. It is not indicated as first line therapy for complex partial seizures. The efficacy of vigabatrin as adjunctive therapy in adult patients (18 to 60 years old) with complex partial seizures (with or without secondary generalization) was established in 2 multicenter, double-blind, placebo-controlled, parallel-group clinical trials (n=357) [12]. Anticonvulsant efficacy maintained for up to 5 years in long-term studies, primarily involving patients with previously refractory partial seizures [3][4][5][6][7][8].
B) West Syndrome (Infantile Spasms)
1) Vigabatrin is indicated as monotherapy for pediatric patients (1 month to 2 years of age) with infantile spasms for whom the potential benefits outweigh the potential risk of vision loss. Efficacy of vigabatrin for infantile spasms was established in 2 multicenter, controlled studies (n=221 in one study [2], and n=40 in another study [13]). In clinical studies, vigabatrin has shown a 50% to 70% spasm cessation rate (Pellock, 1998) [106][107].