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Trokendi XR

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Trokendi XR

Trokendi XR

Trokendi XR Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

Trokendi XR (topiramate) Extended-release is a sulfamate-substituted monosaccharide used as initial monotherapy in patients 10 years of age and older with partial onset or primary generalized tonic-clonic seizures and adjunctive therapy in patients 6 years of age and older with partial onset or primary generalized tonic-clonic seizures. Common side effects include tingling sensations, dizziness, diarrhea, weight loss, sleepiness, memory problems, insomnia, depression, difficulty concentrating, anxiety, and infections. A small percent of patients may experience suicidal ideation. If you have thoughts of suicide, tell your doctor immediately.

The recommended dose for Trokendi XR monotherapy in adults and pediatric patients 10 years of age and older is 400 mg orally once daily. Trokendi XR may interact with alcohol, oral contraceptives, antiepileptic drugs, CNS depressants, carbonic anhydrase inhibitors, metformin, and lithium. Tell your doctor all medications and supplements you use. Trokendi XR may harm a fetus. Use of birth control is recommended while using this drug. Since Trokendi XR may affect hormonal birth control, discuss forms of birth control with your doctor. It is unknown if Trokendi XR could harm a nursing infant and caution should be used. Consult your doctor before breastfeeding. Antiepileptic drugs including Trokendi XR should be gradually withdrawn to minimize the potential for seizures or increased seizure frequency.

Our Trokendi XR (topiramate) Extended-release Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What is Prescribing information?

The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.

Trokendi XR FDA Prescribing Information: Side Effects
(Adverse Reactions)

SIDE EFFECTS

The following adverse reactions are discussed in more detail in other sections of the labeling:

The data described in the following sections were obtained using immediate-release topiramate tablets in studies of patients with epilepsy. Trokendi XR™ has not been studied in a randomized, placebo-controlled Phase III clinical study in the epilepsy patient population. However, it is expected that Trokendi XR™ would produce a similar adverse reaction profile as immediate-release topiramate.

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 clinical practice.

Adverse Reactions Observed in Monotherapy Trial

Adults 17 Years and Older

The adverse reactions in the controlled trial (Study 1) that occurred most commonly in adults in the 400 mg per day group (incidence greater than or equal to 5%) and at a rate higher than the 50 mg per day group were paresthesia, weight decrease, somnolence, anorexia, dizziness, and difficulty with memory (see Table 2) [see Clinical Studies].

Approximately 21% of the 159 adult patients in the 400 mg per day group who received topiramate as monotherapy in Study 1 discontinued therapy due to adverse reactions. The most common (greater than or equal to 2% more frequent than low-dose 50 mg per day topiramate) adverse reactions causing discontinuation in this trial were difficulty with memory, fatigue, asthenia, insomnia, somnolence and paresthesia.

Pediatric Patients 10 Years to 16 Years of Age

The adverse reactions in the controlled trial (Study 1) that occurred most commonly in children (10 years up to 16 years of age) in the 400 mg per day topiramate group (incidence greater than or equal to 5%) and at a rate higher than in the 50 mg per day group were weight decrease, upper respiratory tract infection, paresthesia, anorexia, diarrhea, and mood problems (see Table 3) [see Clinical Studies].

Approximately 12% of the 57 pediatric patients in the 400 mg per day group who received topiramate as monotherapy in the controlled clinical trial discontinued therapy due to adverse reactions. The most common (greater than 5%) adverse reactions resulting in discontinuation in this trial were difficulty with concentration/attention.

Table 2: Incidence of Treatment-Emergent Adverse Reaction in the Monotherapy Epilepsy Trial in Adultsa Where Incidence Was at Least 2% in the 400 mg/day Immediate-Release Topiramate Group and Greater Than the Rate in the 50 mg/day Immediate-Release Topiramate Group

Body System/ Adverse Reaction Immediate release topiramate Dosage (mg/day)
50
(N 160)
400
(N 159)
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
Hypoasthesia 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
Gastroesophogeal 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
Pychomotor 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
aValues represent the percentage of patients reporting a given adverse reaction. Patients may have reported more than one adverse reaction during the study and can be included in more than one adverse reaction category

Table 3: Incidence of Treatment-Emergent Adverse Reactions in the Monotherapy Epilepsy Trial in Pediatric Patients (Ages 10 up to 16 Years)a Where Incidence Was at Least 5% in the 400 mg/day Immediate-Release Topiramate Group and Greater than the Rate in the 50mg/day Immediate-Release Topiramate Group

Body System/ Adverse Reaction Immediate release topiramate Dosage (mg/day)
50
(N 57)
400
(N 57)
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 Problem 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
aValues 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

Adverse Reactions Observed in Adjunctive Therapy Epilepsy Trials

The most commonly observed adverse reactions associated with the use of topiramate at dosages of 200 to 400 mg per 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, ataxia, speech disorders and related speech problems, psychomotor slowing, abnormal vision, difficulty with memory, paresthesia and diplopia [see Table 4] [see Clinical Studies]. The most common dose-related adverse reactions at dosages of 200 mg to 1,000 mg per day were: fatigue, nervousness, difficulty with concentration or attention, confusion, depression, anorexia, language problems, anxiety, mood problems, and weight decrease [see Table 6].

Adverse reactions associated with the use of topiramate at dosages of 5 mg/kg/day 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 7].

In controlled clinical trials in adults, 11% of patients receiving topiramate 200 to 400mg per day as adjunctive therapy discontinued due to adverse reactions. This rate appeared to increase at dosages above 400mg per 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 per day. None of the pediatric patients who received topiramate adjunctive therapy at 5 mg/kg/day to 9 mg/kg/day in controlled clinical trials discontinued due to adverse reactions.

Approximately 28% of the 1757 adults with epilepsy who received topiramate at dosages of 200 mg to 1,600 mg per day in clinical studies discontinued treatment because of adverse reactions; an individual patient could have reported more than one adverse reaction. These adverse reactions 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 reactions. Adverse reactions 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 4 lists adverse reactions that occurred in at least 1% of adults treated with 200 to 400 mg per 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 reactions during the first eight weeks of these trials no longer experienced them by their last visit. Table 7 lists adverse reactions that occurred in at least 1% of pediatric patients treated with 5 mg/kg to 9 mg/kg topiramate in controlled trials that were numerically more common than in patients treated with placebo.

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

Other adverse reactions that occurred in more than 1% of adults treated with 200 mg 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 4: Incidence of Adverse Reactions in Placebo-Controlled, Adjunctive Epilepsy Trials in Adultsa,b,c

Body System/Adverse Reactionc Topiramate Dosage(mg per day)
Placebo
(N=291)
200-400
(N=183)
600-1,000
(N=414)
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 I
Musculo-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 liability 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 1
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 Senses 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
aPatients in these adjunctive trials were receiving 1 to 2 concomitant antiepileptic drugs in addition to topiramate or placebo
bValues represent the percentage of patients reporting a given reaction. Patient may have reported more than one adverse reaction during the study and can be included in more than one adverse reaction category.
cAdverse reactions reported by at least 1% of patients in the topiramate 200 mg to 400 mg per day group and more common than in the placebo group

Adverse Reactions Observed in Adjunctive Therapy Trial in Adults with Partial Onset Seizures (Study 7)

Study 7 was a randomized, double-blind, adjunctive, placebo-controlled, parallel group study with 3 treatment arms: 1) placebo; 2) topiramate 200 mg per day with a 25 mg per day starting dose, increased by 25 mg per day each week for 8 weeks until the 200 mg per day maintenance dose was reached; and 3) topiramate 200 mg per day with a 50 mg per day starting dose, increased by 50 mg per day each week for 4 weeks until the 200 mg per day maintenance dose was reached. All patients were maintained on concomitant carbamazepine with or without another concomitant antiepileptic drug.

The incidence of adverse reactions (Table 5) did not differ significantly between the 2 topiramate regimens. Because the frequencies of adverse reactions reported in this study were markedly lower than those reported in the previous epilepsy studies, they cannot be directly compared with data obtained in other studies.

Table 5: Incidence of Adverse Reactions in Study 7a,b,c

Body System/Adverse Reactionc TopiramateDosage (mg per day)
Placebo
(N=92)
200
(N=171)
Body as a Whole-General Disorders
Fatigue 4 9
Chest pain 1 2
Cardiovasular Disorders, General
Hypertension 0 2
Central & Peripheral Nervous System Disorders
Paresthesia 2 9
Dizziness 4 7
Tremor 2 3
Hypoesthesia 0 2
Leg cramps 0 2
Language problems 0 2
Gastro-intestinal System Disorders
Abdominal pain 3 5
Constipation 0 4
Diarrhea 1 2
Dyspepsia 0 2
Dry mouth 0 2
Hearing and Vestibular Disorders
Tinnitus 0 2
Metabolic and Nutritional Disorders
Weight decrease 4 8
Psychiatric Disorders
Somnolence 9 15
Anorexia 7 9
Nervousness 2 9
Difficulty with concentration/attention 0 5
Insomnia 3 4
Difficulty with memory 1 2
Aggressive reaction 0 2
Respiratory System Disorders
Rhinitis 0 4
Urinary System Disorders
Cystitis 0 2
Vision Disorder
Diplopia 0 2
Vision abnormal 0 2
aPatients in these adjunctive trials were receiving 1 to 2 concomitant antiepileptic drugs in addition to topiramate or placebo
bValues represent the percentage of patients reporting a given adverse reaction. Patients may have reported more than one adverse reaction during the study and can be included in more than one adverse reaction category
cAdverse reactions reported by at least 2% of patients in the topiramate 200 mg per day group and more common than in the placebo group

Table 6: Incidence (%) of Dose-Related Adverse Reactions From Placebo-Controlled, Adjunctive Trials in Adults With Partial Onset Seizures (Studies 2 through 7)a

Adverse Reaction (Topiramate) Dosage (mg per day)
Placebo
(N=216)
200
(N=45)
400
(N=68)
600-1,000
(N=414)
Fatigue 13 11 12 30
Nervousness 7 13 18 19
Difficulty with concentration/attention 1 7 9 14
Confusion 4 9 10 14
Depression 6 9 7 13
Anorexia 4 4 6 12
Language Problems < 1 2 9 10
Anxiety 6 2 3 10
Mood Problems 2 0 6 9
Weight Decrease 3 4 9 13
aDose-response studies were not conducted for other adult indications or for pediatric indications

Table 7: Incidence (%) of Adverse Reaction in Placebo-Controlled, Adjunctive Epilepsy Trial in Pediatric Patients (Ages 2 Years to 16 Years)a,b,c (Study 8)

Body System/Adverse Reaction Placebo
(N=101)
Topiramate
(N=98)
Body as a Whole-General Disorders
Fatigue 5 16
Injury 13 14
Allergic reaction 1 2
Back pain 0 1
Pallor 0 1
Cardiovascular Disorders, General
Hypertension 0 1
Central & Peripheral Nervous System Disorders
Gait abnormal 5 8
Ataxia 2 6
Hyperkinesia 4 5
Dizziness 2 4
Speech disorders/Related speech problems 2 4
Hyporeflexia 0 2
Convulsions grand mal 0 1
Fecal incontinence 0 1
Paresthesia 0 1
Gastro-Intestinal System Disorders
Nausea 5 6
Saliva increased 4 6
Constipation 4 5
Gastroenteritis 2 3
Dysphagia 0 1
Flatulence 0 1
Gastroesophageal reflux 0 1
Glossitis 0 1
Gum hyperplasia 0 1
Heart Rate and Rhythm Disorders
Bradycardia 0 1
Metabolic and Nutritional Disorders
Weight decrease 1 9
Thirst 1 2
Hypoglycemia 0 1
Weight increase 0 1
Platelet, Bleeding & Clotting Disorders
Purpura 4 8
Epistaxis 1 4
Hematoma 0 1
Prothrombin increased 0 1
Thrombocytopenia 0 1
Psychiatric Disorders
Somnolence 16 26
Anorexia 15 24
Nervousness 7 14
Personality disorder (Behavior Problems) 9 11
Difficulty with concentration/attention 2 10
Aggressive reaction 4 9
Insomnia 7 8
Difficulty with memory 0 5
Confusion 3 4
Psychomotor slowing 2 3
Appetite increased 0 1
Neurosis 0 1
Reproductive Disorders, Female
Leukorrhea 0 2
Resistance Mechanism Disorders
Infection viral 3 7
Respiratory System Disorders
Pneumonia 1 5
Respiratory disorder 0 1
Skin and Appendages Disorders
Skin Disorder 2 3
Alopecia 1 2
Dermatitis 0 2
Hypertrichosis 1 2
Rash erythematous 0 2
Eczema 0 1
Seborrhea 0 1
Skin discoloration 0 1
Urinary System Disorders
Urinary incontinence 2 4
Nocturia 0 1
Vision Disorders
Eye abnormality 1 2
Vision abnormal 1 2
Diplopia 0 1
Lacrimation abnormal 0 1
Myopia 0 1
White Cell and RES Disorders
Leukopenia 0 2
aPatients in these adjunctive trials were receiving 1 to 2 concomitant antiepileptic drugs in addition to topiramate or placebo
bValues represent the percentage of patients reporting a given adverse reaction. Patients may have reported more than one adverse reaction during the study and can be included in more than one adverse reaction category
cReactions that Occurred in at Least 1% of Topiramate-Treated Patients and Occurred More Frequently in Topiramate-Treated Than Placebo-Treated Patients

Laboratory Abnormalities

Topiramate decreases serum bicarbonate [see WARNINGS AND PRECAUTIONS]

Immediate-release topiramate treatment was associated with changes in several clinical laboratory analytes in randomized, double-blind, placebo-controlled studies. Similar effects should be anticipated with use of Trokendi XR™.

Controlled trials of adjunctive topiramate treatment of adults for partial onset seizures showed an increased incidence of markedly decreased serum phosphorus (6% topiramate, 2% placebo), markedly increased serum alkaline phosphatase (3% topiramate, 1% placebo), and decreased serum potassium (0.4 % topiramate, 0.1 % placebo). The clinical significance of these abnormalities has not been clearly established.

Changes in several clinical laboratory results (increased creatinine, BUN, alkaline phosphatase, total protein, total eosinophil count and decreased potassium) have been observed in a clinical investigational program in very young (2 years and younger) pediatric patients who were treated with adjunctive topiramate for partial onset seizures [see Use In Specific Populations].

Topiramate treatment produced a dose-related increased shift in serum creatinine from normal at baseline to an increased value at the end of 4 months treatment in adolescent patients (ages 12 years to 16 years) in a double-blind, placebo-controlled study. The incidence of these abnormal shifts was 4% for placebo, 4% for 50 mg, and 18% for 100 mg.

Topiramate treatment with or without concomitant valproic acid (VPA) can cause hyperammonemia with or without encephalopathy [see WARNINGS AND PRECAUTIONS].

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of topiramate. 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. The listing is alphabetized: bullous skin reactions (including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis), hepatic failure (including fatalities), hepatitis, maculopathy, pancreatitis, and pemphigus.

Read the entire FDA prescribing information for Trokendi XR (Topiramate Extended-release Capsules) »

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Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


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