Vigabatrin Oral Solution

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

• Permanent Vision Loss [see BOXED WARNING and WARNINGS AND PRECAUTIONS]
• Magnetic Resonance Imaging (MRI) Abnormalities in Infants [see WARNINGS AND PRECAUTIONS]
• Neurotoxicity [see WARNINGS AND PRECAUTIONS]
• Suicidal Behavior and Ideation [see WARNINGS AND PRECAUTIONS]
• Withdrawal of Antiepileptic Drugs (AEDs) [see WARNINGS AND PRECAUTIONS]
• Anemia [see WARNINGS AND PRECAUTIONS]
• Somnolence and Fatigue [see WARNINGS AND PRECAUTIONS]
• Peripheral Neuropathy [see WARNINGS AND PRECAUTIONS]
• Weight Gain [see WARNINGS AND PRECAUTIONS]
• Edema [see WARNINGS AND PRECAUTIONS]

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

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.

Table 5: Adverse Reactions in Pooled, Add-On Trials in Adults with Refractory Complex Partial Seizures

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).

Table 6: Adverse Reactions in Pooled, Add-On Trials in Pediatric Patients 10 to 16 Years of Age with Refractory Complex Partial Seizures

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.

Table 7: Adverse Reactions in a Placebo-Controlled Trial in Patients with Infantile Spasms

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)

Before you take vigabatrin, tell your doctor if you have any vision problems, such as retinitis or glaucoma. Some people taking vigabatrin 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 vigabatrin 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 vigabatrin, 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.

Tell your doctor about all other medications you use.

You may have thoughts about suicide while taking vigabatrin. Your doctor will need to check your progress at regular visits. Call your doctor at once if you have any new or worsening symptoms such as: mood or behavior changes, depression, or thoughts about suicide or hurting yourself.

Vigabatrin is available only under a special program called SHARE. You must be registered in the program and sign documents stating that you understand the risks and benefits of taking this medication and that you agree to have vision exams on a regular basis while you are taking vigabatrin.

• Electroencephalogram (EEG)
• MRI (Magnetic Resonance Imaging Scan)
• Seizure (Epilepsy)
• Seizures Symptoms and Types

• If you have an allergy to vigabatrin or any other part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you are breast-feeding or plan to breast-feed.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take vigabatrin oral solution with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Side effects that you should report to your doctor or health care professional as soon as possible:

• allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
• changes in vision such as blurred vision, double vision or eye movements you cannot control
• fever or infection
• joint pain
• memory problems
• numbness or tingling in feet or toes
• seizures
• suicidal thoughts or other mood changes
• tremors
• unusually weak or tired

Side effects that usually do not require medical attention (Report these to your doctor or health care professional if they continue or are bothersome.):

• constipation
• diarrhea
• dizziness
• drowsiness
• headache
• nausea
• tiredness
• weight gain