Sabril Tablets

Tablet: 500 mg: white, oval, film-coated, biconvex, scored on one side, and debossed with OV 111 on the other.   

Powder for Oral Solution: 500 mg packets of a white to off-white granular powder.

10.1       Signs, 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.

10.2       Management of Overdosage

There is no specific antidote for SABRIL 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 SABRIL 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%.

14.1        Complex Partial Seizures

Adults

The effectiveness of SABRIL as adjunctive therapy in adult patients was established in two U.S. multicenter, double-blind, placebo-controlled, parallel-group clinical studies. A total of 357 adults (age 18 to 60 years) with complex partial seizures, with or without secondary generalization were enrolled (Studies 1 and 2). Patients were required to be on an adequate and stable dose of an anticonvulsant, and have a history of failure on an adequate regimen of carbamazepine or phenytoin. Patients had a history of about 8 seizures per month (median) for about 20 years (median) prior to entrance into the study. These studies were not capable by design of demonstrating direct superiority of SABRIL over any other anticonvulsant added to a regimen to which the patient had not adequately responded. Further, in these studies patients had previously been treated with a limited range of anticonvulsants.

The primary measure of efficacy was the patient’s reduction in mean monthly frequency of complex partial seizures plus partial seizures secondarily generalized at end of study compared to baseline.

Study 1

Study 1 (N=174) was a randomized, double-blind, placebo-controlled, dose-response study consisting of an 8-week baseline period followed by an 18-week treatment period. Patients were randomized to receive placebo or 1, 3, or 6 g/day vigabatrin administered twice daily. During the first 6 weeks following randomization, the dose was titrated upward beginning with 1 g/day and increasing by 0.5 g/day on days 1 and 5 of each subsequent week in the 3 g/day and 6 g/day groups, until the assigned dose was reached.

Results for the primary measure of effectiveness, reduction in monthly frequency of complex partial seizures, are shown in Table 8. The 3 g/day and 6 g/day dose groups were statistically significantly superior to placebo, but the 6 g/day dose was not superior to the 3 g/day dose.

Figure 1 presents the percentage of patients (X-axis) with a percent reduction in seizure frequency (responder rate) from baseline to the maintenance phase at least as great as that represented on the Y-axis. A positive value on the Y-axis indicates an improvement from baseline (i.e., a decrease in complex partial seizure frequency), while a negative value indicates a worsening from baseline (i.e., an increase in complex partial seizure frequency). Thus, in a display of this type, a curve for an effective treatment is shifted to the left of the curve for placebo. The proportion of patients achieving any particular level of reduction in complex partial seizure frequency was consistently higher for the SABRIL 3 and 6 g/day groups compared to the placebo group. For example, 51% of patients randomized to SABRIL 3 g/day and 53% of patients randomized to SABRIL 6 g/day experienced a 50% or greater reduction in seizure frequency, compared to 9% of patients randomized to placebo. Patients with an increase in seizure frequency >100% are represented on the Y-axis as equal to or greater than -100%.

Figure 1. Percent Reduction from Baseline in Seizure Frequency

Study 2

Study 2 (N=183 randomized, 182 evaluated for efficacy) was a randomized, double-blind, placebo-controlled, parallel study consisting of an 8-week baseline period and a 16-week treatment period. During the first 4 weeks following randomization, the dose of vigabatrin was titrated upward beginning with 1 g/day and increased by 0.5 g/day on a weekly basis to the maintenance dose of 3 g/day.

Results for the primary measure of effectiveness, reduction in monthly complex partial seizure frequency, are shown in Table 9. Vigabatrin 3 g/day was statistically significantly superior to placebo in reducing seizure frequency.

Figure 2 presents the percentage of patients (X-axis) with a percent reduction in seizure frequency (responder rate) from baseline to the maintenance phase at least as great as that represented on the Y-axis. A positive value on the Y-axis indicates an improvement from baseline (i.e., a decrease in complex partial seizure frequency), while a negative value indicates a worsening from baseline (i.e., an increase in complex partial seizure frequency). Thus, in a display of this type, a curve for an effective treatment is shifted to the left of the curve for placebo. The proportion of patients achieving any particular level of reduction in seizure frequency was consistently higher for the SABRIL 3 g/day group compared to the placebo group. For example, 39% of patients randomized to SABRIL (3 g/day) experienced a 50% or greater reduction in complex partial seizure frequency, compared to 21% of patients randomized to placebo. Patients with an increase in seizure frequency >100% are represented on the Y-axis as equal to or greater than -100%.

Figure 2. Percent Reduction from Baseline in Seizure Frequency

For both studies, there was no difference in the effectiveness of vigabatrin between male and female patients. Analyses of age and race were not possible as nearly all patients were between the ages of 18 to 65 and Caucasian.

Pediatric patients 10 to 16 years of age

SABRIL was studied in three double-blind, placebo-controlled, parallel-group studies in 269 patients who received SABRIL and 104 patients who received placebo. No individual study was considered adequately powered to determine efficacy in pediatric patients age 10 years and above. The data from all three pediatric studies were pooled and used in a pharmacometric bridging analysis using weight-normalized doses to establish efficacy and determine appropriate dosing. All three studies were randomized, double-blind, placebo-controlled, parallel-group, adjunctive-treatment studies in patients aged 3-16 years with uncontrolled complex partial seizures with or without secondary generalization. The study period included a 6 to 10 week baseline phase and a 14 to 17 week treatment phase (composed of a titration and maintenance period).

The pharmacometric bridging approach consisted of defining a weight-normalized dose-response, and showing that a similar dose-response relationship exists between pediatric patients and adult patients when SABRIL was given as adjunctive therapy for complex partial seizures. Dosing recommendations in pediatric patients 10 to 16 years of age were derived from simulations utilizing these pharmacometric dose-response analyses [see Dosage and Administration (2.2)].

14.2        Infantile Spasms

The effectiveness of SABRIL as monotherapy was established for infantile spasms in two multicenter controlled studies. Both studies were similar in terms of disease characteristics and prior treatments of patients and all enrolled infants had a confirmed diagnosis of infantile spasms.

Study 1

Study 1 (N=221) was a multicenter, randomized, low-dose high-dose, parallel-group, partially-blind (caregivers knew the actual dose but not whether their child was classified as low or high dose; EEG reader was blinded but investigators were not blinded) study to evaluate the safety and efficacy of vigabatrin in patients <2 years of age with new-onset infantile spasms. Patients with both symptomatic and cryptogenic etiologies were studied. The study was comprised of two phases. The first phase was a 14 to 21 day partially-blind phase in which patients were randomized to receive either low-dose (18-36 mg/kg/day) or high-dose (100-148 mg/kg/day) vigabatrin. Study drug was titrated over 7 days, followed by a constant dose for 7 days. If the patient became spasm-free on or before day 14, another 7 days of constant dose was administered. The primary efficacy endpoint of this study was the proportion of patients who were spasm-free for 7 consecutive days beginning within the first 14 days of vigabatrin therapy. Patients considered spasm-free were defined as those patients who remained free of spasms (evaluated according to caregiver response to direct questioning regarding spasm frequency) and who had no indication of spasms or hypsarrhythmia during 8 hours of CCTV EEG recording (including at least one sleep-wake-sleep cycle) performed within 3 days of the seventh day of spasm freedom and interpreted by a blinded EEG reader. Seventeen patients in the high-dose group achieved spasm freedom compared with 8 patients in the low dose group. This difference was statistically significant (p=0.0375). Primary efficacy results are shown in Table 10.

Study 2

Study 2 (N=40) was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study consisting of a pre-treatment (baseline) period of 2-3 days, followed by a 5-day double-blind treatment phase during which patients were treated with vigabatrin (initial dose of 50 mg/kg/day with titration allowed to 150 mg/kg/day) or placebo. The primary efficacy endpoint in this study was the average percent change in daily spasm frequency, assessed during a pre-defined and consistent 2-hour window of evaluation, comparing baseline to the final 2 days of the 5-day double-blind treatment phase. No statistically significant differences were observed in the average frequency of spasms using the 2-hour evaluation window. However, a post-hoc alternative efficacy analysis, using a 24-hour clinical evaluation window found a statistically significant difference in the overall percentage of reductions in spasms between the vigabatrin group (68.9%) and the placebo group (17.0%) (p=0.030).

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.  The 38/68 infants in the study who had responded to vigabatrin therapy (complete cessation of spasms and hypsarrhythmia) continued vigabatrin therapy for a total duration of 6 months therapy. The 38 infants who responded were then followed for an additional 18 months after discontinuation of vigabatrin to determine their clinical outcome. A post hoc analysis indicated no observed recurrence of infantile spasms in any of these 38 infants. 

Advise patients and caregivers to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

Administration Instructions for SABRIL Powder for Oral Solution

Physicians should confirm that caregiver(s) understand how to mix SABRIL for Oral Solution and to administer the correct dose to their infants [see Dosage and Administration (2.5)].

Permanent Vision Loss
Inform patients and caregivers of the risk of permanent vision loss, particularly loss of peripheral vision, from SABRIL, 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 SABRIL), at least every 3 months while on therapy, and about 3-6 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 patient or caregiver counseling. Patients or caregivers should be informed that if baseline or subsequent vision is not normal, SABRIL should only be used if the benefits of SABRIL treatment clearly outweigh the risks of additional vision loss.

Advise patients and caregivers that vision testing may be insensitive and may not detect vision loss before it is severe. Also advise patients and caregivers that if vision loss is documented, such loss is irreversible. Ensure that both of these points are understood by patients and caregivers.

Patients and caregivers should be informed that if changes in vision are suspected, they should notify their physician immediately.

Vigabatrin REMS Program
SABRIL is available only through a restricted program called the Vigabatrin REMS Program [see Warnings and Precautions (5.2)]. Inform patients/caregivers of the following:

• Patients must be enrolled in the program.
• SABRIL is only available through pharmacies that are enrolled in the Vigabatrin REMS Program.

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)].

Suicidal Thinking and Behavior
Counsel patients, their caregiver(s), and families that AEDs, including SABRIL, may increase the risk of suicidal thoughts and behavior. Also advise patients and caregivers of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts of self-harm. Behaviors of concern should be reported immediately to healthcare providers [see Warnings and Precautions (5.5)].

Use in Pregnancy
Instruct patients to notify their physician if they become pregnant or intend to become pregnant during therapy, and to notify their physician if they are breast feeding or intend to breast feed during therapy [see Use in Specific Populations (8.1, 8.3)].

Encourage patients to enroll in the NAAED Pregnancy Registry if they become pregnant. This registry is collecting information about the safety of antiepileptic drugs during pregnancy. To enroll, patients can call the toll free number 1-888-233-2334. Information on the registry can also be found at the website http://www.aedpregnancyregistry.org/[see Use in Specific Populations (8.1)].

Withdrawal of SABRIL Therapy
Instruct patients and caregivers not to suddenly discontinue SABRIL therapy without consulting with their healthcare provider. As with all AEDs, withdrawal should be gradual [see Warnings and Precautions (5.6)].

Manufactured by: Patheon
Cincinnati, OH  45237, U.S.A.

For:  Lundbeck
Deerfield, IL  60015, U.S.A.

SABRIL is a registered trademark of Lundbeck

MEDICATION GUIDE

SABRIL®(SAY-bril) 
(vigabatrin)
Tablets

SABRIL®(SAY-bril) 
(vigabatrin)
Powder for oral solution

What is the most important information I should know about SABRIL?

SABRIL can cause serious side effects, including:

• Permanent vision loss
• Magnetic resonance imaging (MRI) changes in babies with infantile spasms (IS)
• Risk of suicidal thoughts or actions

1. Permanent vision loss:  

SABRIL can damage the vision of anyone who takes it. People who take SABRIL do not lose all of their vision, but some people can have severe loss particularly to their ability to see to the side when they look straight ahead (peripheral vision). With severe vision loss, you may only be able to see things straight in front of you (sometimes called “tunnel vision”). You may also have blurry vision. If this happens, it will not get better.

• Vision loss and use of SABRIL in adults and children 10 years and older: Because of the risk of vision loss, SABRIL is used to treat complex partial seizures (CPS) only in people who do not respond well enough to several other medicines.

Tell your healthcare provider right away if you (or your child):

• might not be seeing as well as before starting SABRIL

• start to trip, bump into things, or are more clumsy than usual
• are surprised by people or things coming in front of you that seem to come out of nowhere
  
• These changes can mean that you (or your child) have damage to your vision.
• It is recommended that your healthcare provider test your (or your child’s) vision (including peripheral vision) and visual acuity (ability to read an eye chart) before you (or your child) start SABRIL or within 4 weeks after starting SABRIL, and at least every 3 months after that until SABRIL is stopped. It is also recommended that you (or your child) have a vision test about 3 to 6 months after SABRIL is stopped.
• Some people are not able to complete testing of vision. Your healthcare provider will determine if you (or your child) can be tested. If you (or your child) cannot complete vision testing, your healthcare provider may continue prescribing SABRIL, but your healthcare provider will not be able to watch for any vision loss you (or your child) may get.
• Even if your vision (or your child’s vision) seems fine, it is important that you get these regular vision tests because vision damage can happen before you (or your child) notice any changes.
• These vision tests cannot prevent the vision damage that can happen with SABRIL, but they do allow the healthcare provider to decide if you (or your child) should stop SABRIL if vision has gotten worse, which usually will lessen further damage.
• If you do not have these vision tests regularly, your healthcare provider may stop prescribing SABRIL.
• If you drive and your vision is damaged by SABRIL, driving might be more dangerous, or you may not be able to drive safely at all. Talk about this with your healthcare provider.
• Vision loss in babies: Because of the risk of vision loss, SABRIL is used in babies 1 month to 2 years of age with infantile spasms (IS) only when you and your healthcare provider decide that the possible benefits of SABRIL 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 SABRIL or within 4 weeks after starting SABRIL, and every 3 months after that until SABRIL is stopped. Your baby should also have a vision test about 3 to 6 months after SABRIL is stopped.
  • Your baby may not be able to be tested. Your healthcare provider will determine if your baby can be tested. If your baby cannot be tested, your healthcare provider may continue prescribing SABRIL, but your 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 SABRIL
• 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 serious and permanent.

• Because SABRIL 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) program. SABRIL can only be prescribed to people who are enrolled in this program. As part of the Vigabatrin REMS Program, it is recommended that your healthcare provider test you (or your child’s) vision from time to time (periodically) while you (or your child) are being treated with SABRIL, and even after you (or your child) stop treatment. Your healthcare provider will explain the details of the Vigabatrin REMS program to you. For more information, go to www.vigabatrinREMS.com or call 1-866-244-8175.

2. Magnetic resonance imaging (MRI) changes in babies with infantile spasms:

Brain pictures taken by magnetic resonance imaging (MRI) show changes in some babies after they are given SABRIL. It is not known if these changes are harmful.

3. Risk of suicidal thoughts or actions:  

Like other antiepileptic drugs, SABRIL may cause suicidal thoughts or actions in a very small number of people, about 1 in 500 people taking it. Call a healthcare provider right away if you or your child have any of these symptoms, especially if they are new, worse, or worry you:

• thoughts about suicide or dying
• attempts to commit suicide
• new or worse depression
• new or worse anxiety
• feeling agitated or restless
• panic attacks
• trouble sleeping (insomnia)
• new or worse irritability
• acting aggressive, being angry, or violent
• acting on dangerous impulses
• an extreme increase in activity and talking (mania)
• other unusual changes in behavior or mood

Suicidal thoughts or actions can be caused by things other than medicines. If you or your child have suicidal thoughts or actions, your healthcare provider may check for other causes.

How can I watch for early symptoms of suicidal thoughts and actions?

• Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings.
• Keep all follow-up visits with your healthcare provider as scheduled.
• Call your healthcare provider between visits as needed, especially if you are worried about symptoms.

• Do not stop SABRIL without first talking to a healthcare provider.

• Stopping SABRIL suddenly can cause serious problems. Stopping a seizure medicine suddenly can cause seizures that will not stop (status epilepticus) in people who are being treated for seizures.  

What is SABRIL?

• SABRIL is a prescription medicine used along with other treatments to treat adults and children 10 years and older with complex partial seizures (CPS) if:
  ○   The CPS does not respond well enough to several other treatments, and         
  ○   You and your healthcare provider decide the possible benefit of taking SABRIL is more important than the risk of vision loss.
  SABRIL should not be the first medicine used to treat CPS.
• SABRIL is also used to treat babies 1 month to 2 years of age who have infantile spasms (IS) if you and your healthcare provider decide the possible benefits of taking SABRIL are more important than the possible risk of vision loss.

What should I tell my healthcare provider before starting SABRIL?

If you or your child has CPS, before taking SABRIL tell your healthcare provider if you or your child have or had:

• depression, mood problems or suicidal thoughts or behavior
• an allergic reaction to SABRIL, such as hives, itching, or trouble breathing
• any vision problems
• any kidney problems
• low red blood cell counts (anemia)
• any nervous or mental illnesses, such as depression, thoughts of suicide, or attempts at suicide
• any other medical conditions
• are breastfeeding or planning to breastfeed. SABRIL can pass into breast milk and may harm your baby. Talk to your healthcare provider about the best way to feed your baby if you take SABRIL.
• are pregnant or plan to become pregnant. It is not known if SABRIL will harm your unborn baby. You and your healthcare provider will have to decide if you should take SABRIL while you are pregnant.

Pregnancy Registry:

If you become pregnant while taking SABRIL, talk to your healthcare provider about registering with the North American Antiepileptic Drug Pregnancy Registry. You can enroll in this registry by calling 1-888-233-2334. The purpose of this registry is to collect information about the safety of antiepileptic medicine during pregnancy.

If you are a parent or caregiver whose baby has IS, before giving SABRIL to your baby, tell the healthcare provider about all of your baby’s medical conditions, including if your baby has or ever had:

• an allergic reaction to SABRIL, such as hives, itching, or trouble breathing
• any vision problems
• any kidney problems

Tell your healthcare provider about all the medicines you or your child take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. SABRIL and other medicines may affect each other causing side effects.

How should I take SABRIL?

• SABRIL comes as tablets or powder for oral solution. 
• You or your child will receive SABRIL from a specialty pharmacy.
• Take SABRIL exactly as your healthcare provider tells you to. SABRIL is usually taken 2 times each day.
• SABRIL may be taken with or without food.
• Before starting to take SABRIL, talk to your healthcare provider about what you or your child should do if a SABRIL dose is missed.
• If you or your child are taking SABRIL for CPS and the seizures do not improve enough within 3 months, your healthcare provider will stop prescribing SABRIL.
• If your child is taking SABRIL for IS and the seizures do not improve within 2 to 4 weeks, your healthcare provider will stop prescribing SABRIL.
• Do not stop taking SABRIL suddenly. This can cause serious problems. Stopping SABRIL or any seizure medicine suddenly can cause seizures that will not stop (status epilepticus) in people who are being treated for seizures. You should follow your healthcare provider’s instructions on how to stop taking SABRIL.
• Tell your healthcare provider right away about any increase in seizures when SABRIL treatment is being stopped. Before your child starts taking SABRIL, speak to your child’s healthcare provider about what to do if your baby misses a dose, vomits, spits up, or only takes part of the dose of SABRIL.
• Do not stop taking SABRIL without talking to your healthcare provider. If SABRIL improves your (or your child’s) seizures, you and your healthcare provider should talk about whether the benefit of taking SABRIL is more important than the risk of vision loss, and decide if you (or your child) will continue to take SABRIL.
• If you are giving SABRIL powder for oral solution to your child, it can be given to your baby at the same time with their meal. SABRIL for oral solution powder should be mixed with water only.
• See “Instructions for Use” for detailed information about how to mix and give SABRIL powder for oral solution to your baby the right way.

What should I avoid while taking SABRIL?

SABRIL causes sleepiness and tiredness. Adults taking SABRIL should not drive, operate machinery, or perform any hazardous task, unless you and your healthcare provider have decided that you can do these things safely.

What are the possible side effects of SABRIL?

SABRIL can cause serious side effects, including:  

• See “What is the most important information I should know about SABRIL?”
• sleepiness and tiredness. See “What should I avoid while taking SABRIL?”
• SABRIL may cause your baby to be sleepy. Sleepy babies may have a harder time suckling and feeding, or may be irritable.
• weight gain that happens without swelling

The following serious side effects happen in adults. It is not known if these side effects also happen in babies who take SABRIL. 

• low red blood cell counts (anemia)
• nerve problems. Symptoms of a nerve problem can include numbness and tingling in your toes or feet. It is not known if nerve problems will go away after you stop taking SABRIL.
• swelling

If you or your child has CPS, SABRIL may make certain types of seizures worse. Tell your healthcare provider right away if your (or your child's) seizures get worse. 

The most common side effects of SABRIL in adults include:

• problems walking or feeling uncoordinated
• feeling dizzy
• shaking (tremor)
• joint pain
• memory problems and not thinking clearly
• eye problems: blurry vision, double vision and eye movements that you cannot control

The most common side effects of SABRIL in children 10 to 16 years of age include:

• weight gain
• upper respiratory tract infection
• tiredness
• aggression
• Also expect side effects like those seen in adults

If you are giving SABRIL to your baby for IS:

SABRIL may make certain types of seizures worse. You should tell your baby’s healthcare provider right away if your baby’s seizures get worse. Tell your baby’s healthcare provider if you see any changes in your baby’s behavior.

The most common side effects of SABRIL in babies include:

• sleepiness - SABRIL may cause your baby to be sleepy. Sleepy babies may have a harder time suckling and feeding, or may be irritable.
• swelling in the bronchial tubes (bronchitis)
• ear infection
• irritability

Tell your healthcare provider if you or your child have any side effect that bothers you or that does not go away. These are not all the possible side effects of SABRIL.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store SABRIL?

• Store Sabril Tablets and SABRIL packets at room temperature, between 68ºF to 77ºF (20ºC to 25ºC).
• Keep Sabril Tablets and SABRIL powder in the container they come in.

Keep SABRIL and all medicines out of the reach of children.

General information about the safe and effective use of SABRIL.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. You can ask your pharmacist or healthcare provider for information about SABRIL that is written for health professionals. Do not use SABRIL for a condition for which it was not prescribed. Do not give SABRIL to other people, even if they have the same symptoms that you have. It may harm them.

What are the ingredients in SABRIL?
Active Ingredient: vigabatrin
Inactive Ingredients:

• Tablets: hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycols, povidone, sodium starch glycolate, and titanium dioxide
• Powder for oral solution: povidone

Marketed by: Lundbeck, Deerfield, IL 60015, U.S.A. SABRIL is a registered trademark of Lundbeck 

For more information, go to www.SABRIL.net or call 1-866-402-8520.

This Medication Guide has been approved by the U.S. Food and Drug Administration.                              Revised: 04/2017                       

PRINCIPAL DISPLAY PANEL
NDC 67386-111-01
Sabril®
(vigabatrin) Tablets
500 mg
DISPENSE THE ENCLOSED MEDICATION
GUIDE WITH EACH PRESCTIPTION.
Rx only
100 Tablets

INFANTILE SPASMS:
1 month to 2 years of age:
-Initial dose: 25 mg/kg twice daily
-Titration: The dose may be titrated by 25 to 50 mg/kg/day increments every 3 days up to a maximum of 150 mg/kg/day in 2 divided doses (75 mg/kg twice daily)

Comments:
-This drug can be taken with or without food.
-In clinical studies, this drug was tapered by decreasing the daily dose 25 to 50 mg/kg every 3 to 4 days.
-In patients with infantile spasms, 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 than 2 to 4 weeks, treatment should be discontinued at that time.

COMPLEX PARTIAL SEIZURES IN CHILDREN 10 TO 16 YEARS OF AGE:
-Body weight 25 to 60 kg:
Initial dose: 250 mg orally twice a day
Titration: The total daily dose may be increased in 500 mg increments at weekly intervals depending on response
Maintenance dose: 1000 mg orally twice a day
-Body weight greater than 60 kg:
Patients weighing more than 60 kg should be dosed according to adult recommendations

Comments:
-This drug can be taken with or without food.
-In clinical studies in pediatric patients with complex partial seizures, this drug was tapered by decreasing the daily dose by one-third every week for 3 weeks.
-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.

Uses:
-As monotherapy for pediatric patients who are 1 month to 2 years of age with infantile spasms (IS) and for whom the potential benefits outweigh the risk of vision loss.
-For children 10 years of age and older as adjunctive therapy for refractory complex partial seizures (CPS) who have inadequately responded to several alternative treatments and for whom the potential benefits outweigh the risk of vision loss (this drug is not indicated as a first line agent for complex partial seizures)

Infants with renal impairment: Data not available

Patients 10 years of age and older and adults:
-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%

Data not available

Administration advice:
-This drug may be given with or without food.
-If a decision is made to discontinue therapy, the dose should be gradually reduced.

Reconstitution/preparation techniques:
-The powder for oral solution should be mixed with water prior to administration.
-Consult the manufacturer product information for reconstitution instructions.

General:
-Therapy should only be initiated by a specialist (in epileptology, neurology or pediatric neurology) and follow-up arranged under their supervision.
-Use the lowest dosage and shortest exposure consistent with clinical objectives.
-The dosing regimen depends on the indication, age group, weight, and dosage form (tablets or powder for oral solution).
-Tablets and powder for oral solution are bioequivalent. Either tablet or powder can be used for Refractory Complex Partial Seizures (CPS). Powder for oral solution should be used for Infantile Spasms (IS); tablets should not be used for IS because of difficulty in the administration of tablets to infants and young children.

Patient advice:
-Patients should be fully apprised of the risk of permanent vision loss.