SABRIL SIDE EFFECTS

SIDE EFFECTS

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

• Permanent Vision Loss
• Magnetic Resonance Imaging (MRI) Abnormalities in Infants
• Neurotoxicity
• Suicidal Behavior and Ideation
• Withdrawal of Antiepileptic Drugs (AEDs)
• Anemia
• Somnolence and Fatigue
• Peripheral Neuropathy
• Weight Gain
• Edema

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 1 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. adjunctive clinical studies of refractory CPS in adults.

Table 1: Adverse Reactions in Pooled, Adjunctive Trials in Adults with Refractory Complex Partial Seizures

Pediatrics 2 To 16 Years Of Age

Table 2 lists adverse reactions from controlled clinical studies of pediatric patients receiving SABRIL or placebo as adjunctive 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 2: Adverse Reactions in Pooled, Adjunctive Trials in Pediatric Patients 3 to 16 Years of Age with Refractory Complex Partial Seizures

Safety of SABRIL for the treatment of refractory CPS in patients 2 years of age is expected to be similar to pediatric patients 3 to 16 years of age.

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 3.

Table 3: Adverse Reactions in a Placebo-Controlled Trial in Patients with Infantile Spasms

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of SABRIL. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably 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), alopecia.

SRC: NLM .