Sabril

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

>10%

Weight gain, children (47%)

Permanent bilateral concentric visual field constriction (>30%)

Fatigue (28%)

Somnolence (24%)

Headache (18%)

Weight gain, adults (17%)

Dizziness (15%)

Convulsion (11%)

Hyperactivity, in children (11%)

1-10%

Nasopharyngitis (10%)

Weight increased (10%)

Upper respiratory tract infection (10%)

Visual field defect (9%)

Depression (8%)

Tremor (7%)

Nystagmus (7%)

Nausea (7%)

Diarrhea (7%)

Memory impairment (7%)

Insomnia (7%)

Irritability (7%)

Coordination abnormal (7%)

Vision blurred (6%)

Diplopia (6%)

Vomiting (6%)

Influenza (6%)

Pyrexia (6%)

Rash (6%)

Postmarketing Reports

Birth defects: Congenital cardiac defects, congenital external ear anomaly, congenital hemangioma, congenital hydronephrosis, congenital male genital malformation, congenital oral malformation, congenital vesicoureteric reflux, dentofacial anomaly, dysmorphism, fetal anticonvulsant syndrome, hamartomas, hip dysplasia, limb malformation, limb reduction defect, low set ears, renal aplasia, retinitis pigmentosa, supernumerary nipple, talipes

Ear disorders: Deafness

Endocrine disorders: Delayed puberty

Gastrointestinal disorders: Gastrointestinal hemorrhage, esophagitis

General disorders: Developmental delay, facial edema, malignant hyperthermia, multiorgan failure

Hepatobiliary disorders: Cholestasis

Nervous system disorders: Dystonia, encephalopathy, hypertonia, hypotonia, muscle spasticity, myoclonus, optic neuritis

Psychiatric disorders: Acute psychosis, apathy, delirium, hypomania, neonatal agitation, psychotic disorder

Respiratory disorders: Laryngeal edema, pulmonary embolism, respiratory failure, stridor

Skin and subcutaneous tissue disorders: Angioedema, maculopapular rash, pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis

Vision disorders: Permanent vision loss

Sabril is a prescription medication used in combination with other treatments to treat adults with complex partial seizures. Sabril is also used to treat babies with infantile spasms.

Sabril belongs to a group of drugs called anti-epileptics. It works by decreasing abnormal activity in the brain.

This medication comes in tablet and solution form. It is usually taken twice daily with or without food.

Common side effects of Sabril include headache, sleepiness, fatigue and dizziness.

This medication may cause drowsiness. Do not drive or operate heavy machinery until you know how Sabril affects you.

• Lundbeck, LLC

If you are an adult with complex partial seizures, before taking Sabril tell your doctor if you 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.

Before giving Sabril your baby, tell the doctor 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 doctor about all the medicines you or your baby take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Sabril and other medicines may affect each other causing side effects.

Vigabatrin is an anti-epileptic medicine, also called an anticonvulsant.

Vigabatrin is used in combination with other medications to treat complex partial seizures in adults and children who are at least 10 years old. The powder form of vigabatrin is used to treat infantile spasms in babies and children between the ages of 1 month and 2 years.

Vigabatrin can cause serious side effects and should be used only by people who have been unable to control their seizures with several other medications.

Vigabatrin may also be used for purposes not listed in this medication guide.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Call your doctor for instructions if your baby is taking vigabatrin and misses a dose, takes only part of a dose, or spits up or vomits after taking the medicine.

• 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 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 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

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

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Distribution of vigabatrin is restricted.1 71 (See Restricted Distribution Program under Dosage and Administration.)

1.1       Refractory Complex Partial Seizures (CPS) 

Sabril is indicated as adjunctive therapy for adults and pediatric patients 10 years of age and older 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 [see Warnings and Precautions (5.1)]. Sabril is not indicated as a first line agent for complex partial seizures.

1.2       Infantile Spasms (IS)

Sabril is indicated as monotherapy for pediatric patients with infantile spasms 1 month to 2 years of age for whom the potential benefits outweigh the potential risk of vision loss [see Warnings and Precautions (5.1)].

The following serious and otherwise important adverse reactions are described elsewhere in labeling:

• Permanent Vision Loss [see BOXED WARNING and Warnings and Precautions (5.1)]
• Magnetic Resonance Imaging (MRI) Abnormalities in Infants [see Warnings and Precautions (5.3)]
• Neurotoxicity [see Warnings and Precautions (5.4)]
• Suicidal Behavior and Ideation [see Warnings and Precautions (5.5)]
• Withdrawal of Antiepileptic Drugs (AEDs) [see Warnings and Precautions (5.6)]
• Anemia [see Warnings and Precautions (5.7)]
• Somnolence and Fatigue [see Warnings and Precautions (5.8)]
• Peripheral Neuropathy [see Warnings and Precautions (5.9)]
• Weight Gain [see Warnings and Precautions (5.10)]
• Edema [see Warnings and Precautions (5.11)]

6.1       Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In U.S. and primary non-U.S. clinical studies of 4,079 Sabril treated patients, the most common (≥5%) adverse reactions associated with the use of Sabril in combination with other AEDs were headache, somnolence, fatigue, dizziness, convulsion, nasopharyngitis, weight gain, upper respiratory tract infection, visual field defect, depression, tremor, nystagmus, nausea, diarrhea, memory impairment, insomnia, irritability, abnormal coordination, blurred vision, diplopia, vomiting, influenza, pyrexia, and rash.

The adverse reactions most commonly associated with Sabril treatment discontinuation in ≥1% of patients were convulsion and depression.

In patients with infantile spasms, the adverse reactions most commonly associated with Sabril treatment discontinuation in ≥1% of patients were infections, status epilepticus, developmental coordination disorder, dystonia, hypotonia, hypertonia, weight gain, and insomnia.

Refractory Complex Partial Seizures
Adults 
Table 5 lists the adverse reactions that occurred in ≥2% and more than one patient per Sabril treated group and that occurred more frequently than in placebo patients from 2 U.S. add-on clinical studies of refractory CPS in adults. 

Pediatrics 10 to 16 years of age
Table 6 lists adverse reactions from controlled clinical studies of pediatric patients receiving Sabril or placebo as add-on therapy for refractory complex partial seizures.  Adverse reactions that are listed occurred in at least 2% of Sabril treated patients and more frequently than placebo. The median Sabril dose was 49.4 mg/kg (range of 8.0 – 105.9 mg/kg).

Infantile Spasms
In a randomized, placebo-controlled IS study with a 5 day double-blind treatment phase (n=40), the adverse reactions that occurred in >5% of patients receiving Sabril and that occurred more frequently than in placebo patients were somnolence (Sabril 45%, placebo 30%), bronchitis (Sabril 30%, placebo 15%), ear infection (Sabril 10%, placebo 5%), and acute otitis media (Sabril 10%, placebo 0%).

In a dose response study of low-dose (18-36 mg/kg/day) versus high-dose (100-148 mg/kg/day) Sabril, no clear correlation between dose and incidence of adverse reactions was observed. The adverse reactions (≥5% in either dose group) are summarized in Table 7.

6.2       Post Marketing Experience

The following adverse reactions have been reported during post approval use of Sabril worldwide. All adverse reactions that are not listed above as adverse reactions reported in clinical trials, that are not relatively common in the population and are not too vague to be useful are listed in this section. These reactions are reported voluntarily from a population of uncertain size; therefore, it is not possible to estimate their frequency or establish a causal relationship to drug exposure. Adverse reactions are categorized by system organ class.

Birth Defects: Congenital cardiac defects, congenital external ear anomaly, congenital hemangioma, congenital hydronephrosis, congenital male genital malformation, congenital oral malformation, congenital vesicoureteric reflux, dentofacial anomaly, dysmorphism, fetal anticonvulsant syndrome, hamartomas, hip dysplasia, limb malformation, limb reduction defect, low set ears, renal aplasia, retinitis pigmentosa, supernumerary nipple, talipes

Ear Disorders: Deafness

Endocrine Disorders: Delayed puberty

Gastrointestinal Disorders: Gastrointestinal hemorrhage, esophagitis

General Disorders: Developmental delay, facial edema, malignant hyperthermia, multi-organ failure

Hepatobiliary Disorders: Cholestasis

Nervous System Disorders: Dystonia, encephalopathy, hypertonia, hypotonia, muscle spasticity, myoclonus, optic neuritis, dyskinesia

Psychiatric Disorders: Acute psychosis, apathy, delirium, hypomania, neonatal agitation, psychotic disorder

Respiratory Disorders: Laryngeal edema, pulmonary embolism, respiratory failure, stridor

Skin and Subcutaneous Tissue Disorders: Angioedema, maculo-papular rash, pruritus, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) 

9.1       Controlled Substance

Vigabatrin is not a controlled substance.

9.2       Abuse

Vigabatrin did not produce adverse events or overt behaviors associated with abuse when administered to humans or animals. It is not possible to predict the extent to which a CNS active drug will be misused, diverted, and/or abused once marketed. Consequently, physicians should carefully evaluate patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of vigabatrin (e.g., incrementation of dose, drug-seeking behavior).

9.3       Dependence

Following chronic administration of vigabatrin to animals, there were no apparent withdrawal signs upon drug discontinuation.  However, as with all AEDs, vigabatrin should be withdrawn gradually to minimize increased seizure frequency [see Warnings and Precautions (5.6)].

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%.

16.1       How Supplied

Sabril 500 mg tablets are white, film-coated, oval, biconvex, scored on one side, and debossed with OV 111 on the other. They are supplied as bottles of 100 (NDC 67386-111-01).

Sabril 500 mg packets contain a white to off-white granular powder. They are supplied in packages of 50 (NDC 67386-211-65).

16.2       Storage and Handling

Store at 20 to 25°C (68 to 77°F).  See USP controlled room temperature.

Before you take Sabril, tell your doctor if you have any vision problems, such as retinitis or glaucoma. Some people taking Sabril have developed mild to severe vision problems. Vision loss caused by vigabatrin may be permanent, and you must have eye exams on a regular basis while taking this medication.

To be sure Sabril is not causing harmful effects on your vision, you will need a thorough eye exam when you start taking the medication and then every 3 months during treatment. If you ever stop taking Sabril, you may still need to have eye exams every 3 to 6 months after your treatment ends. Do not miss any follow-up visits to your doctor.

Anyone taking Sabril can develop vision problems that could get worse, even after you stop using this medicine. The more you take Sabril, the more likely you are to develop severe vision problems.

Some people have thoughts about suicide while taking seizure medication. Stay alert to changes in your mood or symptoms. Report any new or worsening symptoms to your doctor.

Other drugs may interact with vigabatrin, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

A decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother. Excreted into human milk: Yes (in low concentrations) Comments: -The effects in the nursing infant are unknown.

Limited information indicates that maternal doses of this drug up to 2000 mg daily produce low levels in milk and would not be expected to cause any adverse effects in breastfed infants, especially if the infant is older than 2 months. Until more data are available, this drug should only be used with careful monitoring during breastfeeding.