TOPIRAMATE (Page 7 of 11)

Adjunctive Therapy Epilepsy

The most commonly observed adverse events associated with the use of topiramate at dosages of 200 to 400 mg/day in controlled trials in adults with partial onset seizures, primary generalized tonic-clonic seizures, or Lennox-Gastaut syndrome, that were seen at greater frequency in topiramate-treated patients and did not appear to be dose-related were: somnolence, dizziness, ataxia, speech disorders and related speech problems, psychomotor slowing, abnormal vision, difficulty with memory, paresthesia and diplopia [see Table 7]. The most common dose-related adverse events at dosages of 200 to 1,000 mg/day were: fatigue, nervousness, difficulty with concentration or attention, confusion, depression, anorexia, language problems, anxiety, mood problems, and weight decrease [see Table 9].

Adverse events associated with the use of topiramate at dosages of 5 to 9 mg/kg/day in controlled trials in pediatric patients with partial onset seizures, primary generalized tonic-clonic seizures, or Lennox-Gastaut syndrome, that were seen at greater frequency in topiramate-treated patients were: fatigue, somnolence, anorexia, nervousness, difficulty with concentration/attention, difficulty with memory, aggressive reaction, and weight decrease [see Table 10].

In controlled clinical trials in adults, 11% of patients receiving topiramate 200 to 400 mg/day as adjunctive therapy discontinued due to adverse events. This rate appeared to increase at dosages above 400 mg/day. Adverse events associated with discontinuing therapy included somnolence, dizziness, anxiety, difficulty with concentration or attention, fatigue, and paresthesia and increased at dosages above 400 mg/day. None of the pediatric patients who received topiramate adjunctive therapy at 5 to 9 mg/kg/day in controlled clinical trials discontinued due to adverse events.

Approximately 28% of the 1,757 adults with epilepsy who received topiramate at dosages of 200 to 1,600 mg/day in clinical studies discontinued treatment because of adverse events; an individual patient could have reported more than one adverse event. These adverse events were: psychomotor slowing (4%), difficulty with memory (3.2%), fatigue (3.2%), confusion (3.1%), somnolence (3.2%), difficulty with concentration/attention (2.9%), anorexia (2.7%), depression (2.6%), dizziness (2.5%), weight decrease (2.5%), nervousness (2.3%), ataxia (2.1%), and paresthesia (2%). Approximately 11% of the 310 pediatric patients who received topiramate at dosages up to 30 mg/kg/day discontinued due to adverse events. Adverse events associated with discontinuing therapy included aggravated convulsions (2.3%), difficulty with concentration/attention (1.6%), language problems (1.3%), personality disorder (1.3%), and somnolence (1.3%).

Incidence in Epilepsy Controlled Clinical Trials — Adjunctive Therapy – Partial Onset Seizures, Primary Generalized Tonic-Clonic Seizures, and Lennox-Gastaut Syndrome

Table 7 lists treatment-emergent adverse events that occurred in at least 1% of adults treated with 200 to 400 mg/day topiramate in controlled trials that were numerically more common at this dose than in the patients treated with placebo. In general, most patients who experienced adverse events during the first eight weeks of these trials no longer experienced them by their last visit. Table 10 lists treatment-emergent adverse events that occurred in at least 1% of pediatric patients treated with 5 to 9 mg/kg topiramate in controlled trials that were numerically more common than in patients treated with placebo.

The prescriber should be aware that these data were obtained when topiramate was added to concurrent antiepileptic drug therapy and cannot be used to predict the frequency of adverse events in the course of usual medical practice where patient characteristics and other factors may differ from those prevailing during clinical studies. Similarly, the cited frequencies cannot be directly compared with data obtained from other clinical investigations involving different treatments, uses, or investigators. Inspection of these frequencies, however, does provide the prescribing physician with a basis to estimate the relative contribution of drug and non-drug factors to the adverse event incidences in the population studied.

Other Adverse Events Observed During Double-Blind Epilepsy Adjunctive Therapy Trials

Other events that occurred in more than 1% of adults treated with 200 to 400 mg of topiramate in placebo-controlled epilepsy trials but with equal or greater frequency in the placebo group were: headache, injury, anxiety, rash, pain, convulsions aggravated, coughing, fever, diarrhea, vomiting, muscle weakness, insomnia, personality disorder, dysmenorrhea, upper respiratory tract infection, and eye pain.

Table 7: Incidence of Treatment-Emergent Adverse Events in Placebo-Controlled, Add-On Epilepsy Trials in Adultsa,b Where Rate Was > 1% in Any Topiramate Group and Greater Than the Rate in Placebo-Treated Patients
Topiramate Dosage (mg/day)
Body System /Adverse Eventc Placebo(N=291) 200 to 400(N=183) 600 to 1,000(N=414)

a Patients in these add-on trials were receiving 1 to 2 concomitant antiepileptic drugs in addition to topiramate or placebo.

b Values represent the percentage of patients reporting a given adverse event. Patients may have reported more than one adverse event during the study and can be included in more than one adverse event category.

c Adverse events reported by at least 1% of patients in the topiramate 200 to 400 mg/day group and more common than in the placebo group are listed in this table.

Body as a Whole-General Disorders
Fatigue 13 15 30
Asthenia 1 6 3
Back Pain 4 5 3
Chest Pain 3 4 2
Influenza-Like Symptoms 2 3 4
Leg Pain 2 2 4
Hot Flushes 1 2 1
Allergy 1 2 3
Edema 1 2 1
Body Odor 0 1 0
Rigors 0 1 <1
Central & Peripheral Nervous System Disorders
Dizziness 15 25 32
Ataxia 7 16 14
Speech Disorders/Related Speech Problems 2 13 11
Paresthesia 4 11 19
Nystagmus 7 10 11
Tremor 6 9 9
Language Problems 1 6 10
Coordination Abnormal 2 4 4
Hypoaesthesia 1 2 1
Gait Abnormal 1 3 2
Muscle Contractions Involuntary 1 2 2
Stupor 0 2 1
Vertigo 1 1 2
Gastro-Intestinal System Disorders
Nausea 8 10 12
Dyspepsia 6 7 6
Abdominal Pain 4 6 7
Constipation 2 4 3
Gastroenteritis 1 2 1
Dry Mouth 1 2 4
Gingivitis <1 1 1
GI Disorder <1 1 0
Hearing and Vestibular Disorders
Hearing Decreased 1 2 1
Metabolic and Nutritional Disorders
Weight Decrease 3 9 13
Muscle-Skeletal System Disorders
Myalgia 1 2 2
Skeletal Pain 0 1 0
Platelet, Bleeding, & Clotting Disorders
Epistaxis 1 2 1
Psychiatric Disorders
Somnolence 12 29 28
Nervousness 6 16 19
Psychomotor Slowing 2 13 21
Difficulty with Memory 3 12 14
Anorexia 4 10 12
Confusion 5 11 14
Depression 5 5 13
Difficulty with Concentration/Attention 2 6 14
Mood Problems 2 4 9
Agitation 2 3 3
Aggressive Reaction 2 3 3
Emotional Lability 1 3 3
Cognitive Problems 1 3 3
Libido Decreased 1 2 <1
Apathy 1 1 3
Depersonalization 1 1 2
Reproductive Disorders, Female
Breast Pain 2 4 0
Amenorrhea 1 2 2
Menorrhagia 0 2 1
Menstrual Disorder 1 2 1
Reproductive Disorders, Male
Prostatic Disorder <1 2 0
Resistance Mechanism Disorders
Infection 1 2 1
Infection Viral 1 2 <1
Moniliasis <1 1 0
Respiratory System Disorders
Pharyngitis 2 6 3
Rhinitis 6 7 6
Sinusitis 4 5 6
Dyspnea 1 1 2
Skin and Appendages Disorders
Skin Disorder <1 2 1
Sweating Increased <1 1 <1
Rash Erythematous <1 1 <1
Special Sense Other, Disorders
Taste Perversion 0 2 4
Urinary System Disorders
Hematuria 1 2 <1
Urinary Tract Infection 1 2 3
Micturition Frequency 1 1 2
Urinary Incontinence <1 2 1
Urine Abnormal 0 1 <1
Vision Disorders
Vision Abnormal 2 13 10
Diplopia 5 10 10
White Cell and RES Disorders
Leukopenia 1 2 1

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2020. All Rights Reserved.