TRILEPTAL SIDE EFFECTS

SIDE EFFECTS

The following serious adverse reactions are described below and elsewhere in the labeling:

• Hyponatremia
• Anaphylactic Reactions and Angioedema
• Cross Hypersensitivity Reaction to Carbamazepine
• Serious Dermatological Reactions
• Suicidal Behavior and Ideation
• Cognitive/Neuropsychiatric Adverse Reactions
• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multi-Organ Hypersensitivity
• Hematologic Events

Clinical Trials 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.

Most Common Adverse Reactions In All Clinical Studies

Adjunctive Therapy/Monotherapy In Adults Previously Treated With Other AEDs

The most common (≥ 10% more than placebo for adjunctive or low dose for monotherapy) adverse reactions with TRILEPTAL: dizziness, somnolence, diplopia, fatigue, nausea, vomiting, ataxia, abnormal vision, headache, nystagmus tremor, and abnormal gait.

Approximately 23% of these 1537 adult patients discontinued treatment because of an adverse reaction. The adverse reactions most commonly associated with discontinuation were: dizziness (6.4%), diplopia (5.9%), ataxia (5.2%),vomiting (5.1%), nausea (4.9%), somnolence (3.8%), headache (2.9%), fatigue (2.1%), abnormal vision (2.1%),tremor (1.8%), abnormal gait (1.7%), rash (1.4%), and hyponatremia (1.0%).

Monotherapy In Adults Not Previously Treated With Other AEDs

The most common (≥ 5%) adverse reactions with TRILEPTAL in these patients were similar to those in previously treated patients.

Approximately 9% of these 295 adult patients discontinued treatment because of an adverse reaction. The adverse reactions most commonly associated with discontinuation were: dizziness (1.7%), nausea (1.7%), rash (1.7%), and headache (1.4%).

Adjunctive Therapy/Monotherapy In Pediatric Patients 4 Years Old And Above Previously Treated With Other AEDs

The most common (≥ 5%) adverse reactions with TRILEPTAL in these patients were similar to those seen in adults.

Approximately 11% of these 456 pediatric patients discontinued treatment because of an adverse reaction. The adverse reactions most commonly associated with discontinuation were: somnolence (2.4%), vomiting (2.0%),ataxia (1.8%), diplopia (1.3%), dizziness (1.3%), fatigue (1.1%), and nystagmus (1.1%).

Monotherapy In Pediatric Patients 4 Years Old And Above Not Previously Treated With Other AEDs

The most common (≥ 5%) adverse reactions with TRILEPTAL in these patients were similar to those in adults.

Approximately 9.2% of 152 pediatric patients discontinued treatment because of an adverse reaction. The adverse reactions most commonly associated (≥ 1%) with discontinuation were rash (5.3%) and maculopapular rash (1.3%).

Adjunctive Therapy/Monotherapy In Pediatric Patients 1 Month To < 4 Years Old Previously Treated Or Not Previously Treated With Other AEDs

The most common (≥ 5%) adverse reactions with TRILEPTAL in these patients were similar to those seen in older children and adults except for infections and infestations which were more frequently seen in these younger children.

Approximately 11% of these 241 pediatric patients discontinued treatment because of an adverse reaction. The adverse reactions most commonly associated with discontinuation were: convulsions (3.7%), status epilepticus(1.2%), and ataxia (1.2%).

Controlled Clinical Studies Of Adjunctive Therapy/Monotherapy In Adults Previously Treated With Other AEDs

Table 3 lists adverse reactions that occurred in at least 2% of adult patients with epilepsy, treated with TRILEPTAL or placebo as adjunctive treatment and were numerically more common in the patients treated with any dose of TRILEPTAL.

Table 4 lists adverse reactions in patients converted from other AEDs to either high-dose TRILEPTAL (2400mg/day) or low-dose (300 mg/day) TRILEPTAL. Note that in some of these monotherapy studies patients who dropped out during a preliminary tolerability phase are not included in the tables.

Table 1: Adverse Reactions in a Controlled Clinical Study of Adjunctive Therapy With TRILEPTAL in Adults

Table 2: Adverse Reactions in Controlled Clinical Studies of Monotherapy With TRILEPTAL in Adults Previously Treated With Other AEDs

Controlled Clinical Study Of Monotherapy In Adults Not Previously Treated With Other AEDs

Table 3 lists adverse reactions in a controlled clinical study of monotherapy in adults not previously treated with other AEDs that occurred in at least 2% of adult patients with epilepsy treated with TRILEPTAL or placebo and were numerically more common in the patients treated with TRILEPTAL.

Table 3: Adverse Reactions in a Controlled Clinical Study of Monotherapy With TRILEPTAL in Adults Not Previously Treated With Other AEDs

Controlled Clinical Studies Of Adjunctive Therapy/Monotherapy In Pediatric Patients Previously Treated With Other AEDs

Table 4 lists adverse reactions that occurred in at least 2% of pediatric patients with epilepsy treated with TRILEPTAL or placebo as adjunctive treatment and were numerically more common in the patients treated with TRILEPTAL.

Table 4: Adverse Reactions in Controlled Clinical Studies of Adjunctive Therapy/Monotherapy With TRILEPTAL in Pediatric Patients Previously Treated With Other AEDs

Other Events Observed In Association With The Administration Of TRILEPTAL

In the paragraphs that follow, the adverse reactions, other than those in the preceding tables or text, that occurred in a total of 565 children and 1574 adults exposed to TRILEPTAL and that are reasonably likely to be related to drug use are presented. Events common in the population, events reflecting chronic illness and events likely to reflect concomitant illness are omitted particularly if minor. They are listed in order of decreasing frequency. Because the reports cite events observed in open label and uncontrolled trials, the role of TRILEPTAL in their causation cannot be reliably determined.

Body as a Whole: fever, malaise, pain chest precordial, rigors, weight decrease

Cardiovascular System: bradycardia, cardiac failure, cerebral hemorrhage, hypertension, hypotension postural, palpitation, syncope, tachycardia

Digestive System: appetite increased, blood in stool, cholelithiasis, colitis, duodenal ulcer, dysphagia, enteritis, eructation, esophagi is, flatulence, gastric ulcer, gingival bleeding, gum hyperplasia, hematemesis, hemorrhage rectum, hemorrhoids, hiccup, mouth dry, pain biliary, pain right hypochondrium, retching, sialoadenitis, stomatitis, stomatitis ulcerative

Hematologic and Lymphatic System: thrombocytopenia

Laboratory Abnormality: gamma-GT increased, hyperglycemia, hypocalcemia, hypoglycemia, hypokalemia, liver enzymes elevated, serum transaminase increased

Musculoskeletal System: hypertonia muscle

Nervous System: aggressive reaction, amnesia, anguish, anxiety, apathy, aphasia, aura, convulsions aggravated, delirium, delusion, depressed level of consciousness, dysphonia, dystonia, emotional lability, euphoria, extra pyramidal disorder, feeling drunk, hemiplegia, hyperkinesia, hyperreflexia, hypoesthesia, hypokinesia, hyporeflexia, hypotonia, hysteria, libido decreased, libido increased, manic reaction, migraine, muscle contractions involuntary, nervousness, neuralgia, oculogyric crisis, panic disorder, paralysis, paroniria, personality disorder, psychosis, ptosis, stupor, tetany

Respiratory System: asthma, dyspnea, epistaxis, laryngismus, pleurisy

Skin and Appendages: acne, alopecia, angioedema, bruising, dermatitis contact, eczema, facial rash, flushing, folliculitis, heat rash, hot flushes, photosensitivity reaction, pruritus genital, psoriasis, purpura, rash erythematous, rash maculopapular, vitiligo, urticaria

Special Senses: accommodation abnormal, cataract, conjunctival hemorrhage, edema eye, hemianopia, mydriasis, otitis externa, photophobia, scotoma, taste perversion, tinnitus, xerophthalmia

Surgical and Medical Procedures: procedure dental oral, procedure female reproductive, procedure musculoskeletal, procedure skin

Urogenital and Reproductive System: dysuria, hematuria, intermenstrual bleeding, leukorrhea, menorrhagia, micturition frequency, pain renal, pain urinary tract, polyuria, priapism, renal calculus

Other: Systemic lupus erythematosus

Laboratory Tests

Serum sodium levels below 125 mmol/L have been observed in patients treated with TRILEPTAL. Experience from clinical trials indicates that serum sodium levels return toward normal when the TRILEPTAL dosage is reduced or discontinued, or when the patient was treated conservatively (e.g., fluid restriction).

Laboratory data from clinical trials suggest that TRILEPTAL use was associated with decreases in T4, without changes in T3 or TSH.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of TRILEPTAL. 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.

Body as a Whole: multi-organ hypersensitivity disorders characterized by features such as rash, fever, lymphadenopathy, abnormal liver function tests, eosinophilia and arthralgia

Cardiovascular System: atrioventricular block

Immune System Disorders: anaphylaxis

Digestive System: pancreatitis and/or lipase and/or amylase increase

Hematologic and Lymphatic Systems: a plastic anemia

Metabolism and Nutrition Disorders: hypothyroidism and syndrome of inappropriate antidiuretic hormone secretion(SIADH)

Skin and Subcutaneous Tissue Disorders: erythema multiforme, Stevens-Johnson syndrome, toxic epidermalnecrolysis , Acute Generalized Exanthematous Pustulosis (AGEP)

Musculoskeletal, Connective Tissue and Bone Disorders: There have been reports of decreased bone mineraldensity, osteoporosis and fractures in patients on long-term therapy with TRILEPTAL.

Injury, Poisoning, and Procedural Complications: fall

Nervous System Disorders: dysarthria

SRC: NLM .