Pradox Adverse Reactions

Adverse events are reported for placebo-controlled trials of adjunctive therapy in adult and pediatric patients. Unless otherwise noted, the percen­tages refer to incidence in epilepsy trials.
Note: A wide range of dosages were studied; incidence of adverse events was frequently lower in the pediatric population studied.
>10%: Central nervous system: Somnolence (15% to 29%), dizziness (4% to 25%; dose dependent), fatigue (9% to 16%; dose-dependent), nervousness (9% to 18%), ataxia (6% to 16%), psychomotor slowing (3% to 13%; dose dependent), speech problems (2% to 13%), mem­ory difficulties (2% to 12%), behavior problems (children 11%), confusion (4% to 11%).
Endocrine and metabolic: Serum bicarbonate decreased (dose related: 7% to 67%; marked reductions [to <17 mEq/L] 1% to 11%).
Gastrointestinal: Anorexia (4% to 24%; dose dependent), nausea (6% to 10%; migraine trial: 9% to 14%).
Neuromuscular and skeletal: Paresthesia (1% to 11%; migraine trial: 35% to 51%).
Ocular: Abnormal vision (2% to 13%).
Respiratory: Upper respiratory infection (migraine trial: 12% to 14%).
Miscellaneous: Injury (14%).
1% to 10%: Cardiovascular: Chest pain (2% to 4%), edema (2%), hypertension (1% to 2%), bradycardia (1%), pallor (1%), syncope (1%).
Central nervous system: Difficulty concentrating (5% to 10%), aggressive reactions (2% to 9%), depression (5% to 9%; dose dependent, insomnia (4% to 8%), mood problems (≤6%), abnormal coordination (4%), agitation (3%), cognitive problems (3%), emotional lability (3%), anxiety (2% to 3%; dose dependent), hypoesthesia (2%; migraine trial: 6% to 8%), stupor (2%), vertigo (2%), fever (migraine trial: 1% to 2%), apathy (1%), hallucination (1%), neurosis (1%), psychosis (1%), seiz­ure (1%), suicide attempt (1%).
Dermatologic: Pruritus (migraine trial: 2% to 4%), skin disorder (2% to 3%); alopecia (2%), dermatitis (2%), hypertrichosis (2%), rash erythematous (1% to 2%), eczema (1%), seborrhea (1%), skin discoloration (1%).
Endocrine and metabolic: Breast pain (4%), hot flashes (1% to 2%), libido decreased (<1% to 2%), menstrual irregularities (1% to 2%), hypoglycemia (1%), acidosis (hyperchloremia, nonanion gap), metabolic.
Gastrointestinal: Weight loss (4% to 9%), dyspepsia  (2% to 7%), abdominal pain (5% to 6%), salivation increased (6%), constipation (4% to 5%), gastroenteritis (2% to 3%), vomiting (migraine trial: 1% to 3%), diarrhea (2%; migraine trial: 9% to 11%), dysgeusia (2%; migraine trial: 8% to 15%), xerostomia (2%), loss of taste (migraine trial: <2%), appetite increased, (1%), dyspha­gia, (1%), fecal incontinence (1%), flatulence (1%), GERD (1%), gingivitis (1%), glossitis (1%), gum hyperplasia (1%), weight gain (1%).
Genitourinary: Incontinence (2% to 4%), UTI (2%), premature ejaculation (migraine trial: ≤3%), cystitis (2%), leukorrhea (2%), impotence (1%), nocturia (1%).
Hematologic: Purpura (8%), leukopenia (2%), anemia (1%), hematoma (1%), prothrombin time increased (1%), thrombocytopenia (1%).
Neuromuscular and skeletal: Tremor (3% to 9%), gait abnormal (3% to 8%), arthraglia (migraine trial: 1% to 7%), weakness (6%), hyperkinesia (5%), back pain (1% to 5%), involuntary muscle contractions (2%; migraine trial: 2% to 4%), leg cramps (2%), leg pain (2%), myaglia (2%), hyporeflexia (2%), rigors (1%), skeletal pain (1%).
Ocular: Diplopia (1% to 10%), nystagmus (10%), conjunctivitis (1%), lacrimation abnormal (1%), myopia (1%).
Otic: Hearing decreased (2%), tinnitus (2%), otitis media (migraine trial: 1% to 2%).
Renal: Hematuria (2%), renal calculus (migraine trial ≤2%).
Respiratory: Rhinitis (4% to 7%), pharyngitis (6%), sinus­itis (5%; migraine trial: 6% to 10%), pneumonia (5%), epistaxis (2%·to 4%), cough (migraine trial: 2% to 4%), bronchitis (migraine trial: 3%), dyspnea (migraine trial: 1% to 3%).
Miscellaneous: Viral infection (2% to 7%: migraine trial: 3% to 4%), flu-like syndrome (3%), allergy (2%), infection (2%), thirst (2%), body odor (1%), diaphoresis (1%), moniliasis (1%).
<1% (Limited to important or life-threatening): Angina, apraxia, AV block, bone marrow depression, deep vein thrombosis, dehydration, delirium, delusion, diabetes mellitus, dyskinesia, eosinophilia, erythema multiforme, euphoria, granulocytopenia, hepatic failure, hepatitis, hyperammonemia/encephalopathy (with or without val­proate therapy), hyperthermia (severe), hypokalernia, hypotension, lymphadenopathy, lymphopenia, maculop­athy, manic reaction, neuropathy, oligohydrosis, pancreatitis, pancytopenia, paranoid reaction, pemphigus, photosensitivity, pulmonary embolism, renal tubular acidosis, Stevens-Johnson syndrome, suicidal behavior, suicide, suicidal ideation, syndrome of acute myopia/secondary angle-closure  glaucoma, tongue edema, toxic epidermal necrolysis.