Topamax (Topiramate) - Side Effects and Adverse Reactions

ADVERSE REACTIONS

The data described in the following section were obtained using TOPAMAX^® (topiramate) Tablets.

Monotherapy Epilepsy

The adverse events in the controlled trial that occurred most commonly in adults in the 400 mg/day group and at a rate higher than the 50 mg/day group were: paresthesia, weight decrease, somnolence, anorexia, dizziness, and difficulty with memory NOS [see Table 4 ].

The adverse events in the controlled trial that occurred most commonly in children (10 years up to 16 years of age) in the 400 mg/day group and at a rate higher than the 50 mg/day group were: weight decrease, upper respiratory tract infection, paresthesia, anorexia, diarrhea, and mood problems [see Table 5 ].

Approximately 21% of the 159 adult patients in the 400 mg/day group who received topiramate as monotherapy in the controlled clinical trial discontinued therapy due to adverse events. Adverse events associated with discontinuing therapy (≥2%) included depression, insomnia, difficulty with memory (NOS), somnolence, paresthesia, psychomotor slowing, dizziness, and nausea.

Approximately 12% of the 57 pediatric patients in the 400 mg/day group who received topiramate as monotherapy in the controlled clinical trial discontinued therapy due to adverse events. Adverse events associated with discontinuing therapy (≥5%) included difficulty with concentration/attention.

The prescriber should be aware that these data 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 the clinical study. 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.

Table 4: Incidenceof Treatment-Emergent Adverse Events in the Monotherapy Epilepsy Trial in Adults^a Where Rate Was at Least 2% in the 400 mg/day Topiramate Group and Greater Than the Rate in the 50 mg/day Topiramate Group

	TOPAMAX® Dosage (mg/day)
Body System / Adverse Event	50 (N= 160)	400 (N=159)
a 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
Body as a Whole-General Disorders
Asthenia	4	6
Leg Pain	2	3
Chest Pain	1	2
Central & Peripheral Nervous System Disorders
Paresthesia	21	40
Dizziness	13	14
Hypoaesthesia	4	5
Ataxia	3	4
Hypertonia	0	3
Gastro-Intestinal System Disorders
Diarrhea	5	6
Constipation	1	4
Gastritis	0	3
Dry Mouth	1	3
Gastroesophageal Reflux	1	2
Liver and Biliary System Disorders
Gamma-GT Increased	1	3
Metabolic and Nutritional Disorders
Weight Decrease	6	16
Psychiatric Disorders
Somnolence	9	15
Anorexia	4	14
Difficulty with Memory NOS	5	10
Insomnia	8	9
Depression	7	9
Difficulty with Concentration/Attention	7	8
Anxiety	4	6
Psychomotor Slowing	3	5
Mood Problems	2	5
Confusion	3	4
Cognitive Problem NOS	1	4
Libido Decreased	0	3
Reproductive Disorders, Female
Vaginal Hemorrhage	0	3
Red Blood Cell Disorders
Anemia	1	2
Resistance Mechanism Disorders
Infection Viral	6	8
Infection	2	3
Respiratory System Disorders
Bronchitis	3	4
Rhinitis	2	4
Dyspnea	1	2
Skin and Appendages Disorders
Rash	1	4
Pruritus	1	4
Acne	2	3
Special Senses Other, Disorders
Taste Perversion	3	5
Urinary System Disorders
Cystitis	1	3
Renal Calculus	0	3
Urinary Tract Infection	1	2
Dysuria	0	2
Micturition Frequency	0	2

Table 5: Incidence of Treatment-Emergent Adverse Events in the Monotherapy Epilepsy Trial in Children Ages 10 up to 16 Years^a Where Rate Was at Least 5% in the 400 mg/day Topiramate Group and Greater Than the Rate in the 50 mg/day Topiramate Group

	TOPAMAX® Dosage (mg/day)
Body System / Adverse Event	50 (N=57)	400 (N=57)
a 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.
Body as a Whole-General Disorders
Fever	0	9
Central & Peripheral Nervous System Disorders
Paresthesia	2	16
Gastro-Intestinal System Disorders
Diarrhea	5	11
Metabolic and Nutritional Disorders
Weight Decrease	7	21
Psychiatric Disorders
Anorexia	11	14
Mood Problems	2	11
Difficulty with Concentration/Attention	4	9
Cognitive Problems NOS	0	7
Nervousness	4	5
Resistance Mechanism Disorders
Infection Viral	4	9
Infection	2	7
Respiratory System Disorders
Upper Respiratory Tract Infection	16	18
Rhinitis	2	7
Bronchitis	2	7
Sinusitis	2	5
Skin and Appendages Disorders
Alopecia	2	5

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 6 ]. 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 8 ].

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 9 ].

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 (4.0%), 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 (2.0%). 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 6 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 9 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 TOPAMAX^® 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 6: Incidence of Treatment-Emergent Adverse Events in Placebo-Controlled, Add-On Epilepsy Trials in Adults^a,b Where Rate Was > 1% in Any Topiramate Group and Greater Than the Rate in Placebo-Treated Patients

		TOPAMAX® Dosage (mg/day)
Body System / Adverse Eventc	Placebo (N=291)				200-400 (N=183)			600-1,000 (N=414)
a Patients in these add-on trials were receiving 1 to 2 concomitant antiepileptic drugs in addition to TOPAMAX® 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 TOPAMAX® 200-400 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
Page last updated: 2008-04-18