TOPIRAMATE- topiramate tablet, film coated 
TOPIRAMATE- topiramate tablet 
DirectRX

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TOPIRAMATE

INDICATIONS & USAGE SECTION

DOSAGE & ADMINISTRATION SECTION

DOSAGE FORMS & STRENGTHS SECTION

Topiramate tablets, USP are available as debossed, film-coated, circular tablets in the following strengths and colors:
25 mg white (coded "S" on one side; "707" on the other)
50 mg yellow (coded "S" on one side; "710" on the other)
100 mg yellow (coded "S" on one side; "711" on the other)
200 mg brown (coded "S" on one side; "712" on the other)

WARNINGS AND PRECAUTIONS SECTION

ADVERSE REACTIONS SECTION

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

Acute Myopia and Secondary Angle Closure [see Warnings and Precautions ( 5.1)]
Visual Field Defects [see Warnings and Precautions ( 5.2)]
Oligohidrosis and Hyperthermia [see Warnings and Precautions ( 5.3)]
Metabolic Acidosis [see Warnings and Precautions ( 5.4)]
Suicidal Behavior and Ideation [see Warnings and Precautions ( 5.5)]
Cognitive/Neuropsychiatric Adverse Reactions [see Warnings and Precautions ( 5.6)]
Fetal Toxicity [see Warnings and Precautions ( 5.7) and Use in Specific Populations ( 8.1)]
Withdrawal of Antiepileptic Drugs (AEDs) [see Warnings and Precautions ( 5.8)]
Sudden Unexplained Death in Epilepsy (SUDEP) [see Warnings and Precautions ( 5.9)]
Hyperammonemia and Encephalopathy (Without and With Concomitant Valproic Acid [VPA] Use [see Warnings and Precautions ( 5.10)]
Kidney Stones [see Warnings and Precautions ( 5.11)]
Hypothermia with Concomitant Valproic Acid (VPA) Use [see Warnings and Precautions ( 5.12)]
Paresthesia [see Warnings and Precautions ( 5.13)]

The data described in thefollowing sections were obtained using topiramate tablets.

6.1Clinical Trials Experience


Because clinical trials are conducted under widely varying conditions, the incidence of adverse reactions observed in the clinical trials of a drug cannot be directly compared to the incidence of adverse reactions in the clinical trials of another drug, and may not reflect the incidence of adverse reactions observed in practice.




Monotherapy Epilepsy

Adults ≥16 Years

The adverse reactions in the controlled trial that occurred most commonly in adults in the 400 mg/day topiramate group and at an incidence higher (> 5 %) than in the 50 mg/day group were: paresthesia, weight decrease, anorexia, somnolence, and difficulty with memory (see Table 4).

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 reactions.

The most common (> 2% more frequent than low-dose 50 mg/day topiramate) adverse reactions causing discontinuation in this trial were difficulty with memory, fatigue, asthenia, insomnia, somnolence, and paresthesia.

Pediatric Patients 6 to <16 Years of Age

The adverse reactions in the controlled trial that occurred most commonly in pediatric patients in the 400 mg/day topiramante group and at an incidence higher (> 5%) than in the 50 mg/day group were fever, weight decrease, mood problems, cognitive problems, infection, flushing, and paresthesia (see Table 4). Table 4 also presents the incidence of adverse reactions occurring in at least 2% of adult and pediatric patients treated with 400 mg/day topiramate and occurring with greater incidence than 50 mg/day topiramate.






Approximately 14 % of the 77 pediatric patients in the 400 mg/day group who received topiramate as monotherapy in the controlled clinical trial discontinued therapy due to adverse reactions. The most common (> 2% more frequent than low-dose 50 mg/day topiramate) adverse reactions resulting in discontinuation in this trial were difficulty with concentration/attention, fever, flushing, and confusion.






Table 4: Incidence (%) of Treatment-Emergent Adverse Reactions in Monotherapy Epilepsy Where the Incidence Was at Least 2% in Any Topiramate Group and the Incidence in the 400 mg/day Topiramate Group Was Greater Than the Incidence in the 50 mg/day Topiramate Group for Adults (≥16 Years) and Pediatric (6 to <16 Years) Patients in Study Topiramate-EPMN-106
Age Group
Pediatric (6 to <16 Years) Adult (Age ≥16 Years)
Topiramate Daily Dosage Group (mg/day)
50 400 50 400
Body System

Adverse Reaction (N=74)

% * (N=77)

% * (N=160)

% * (N=159)

% *
*Percentages calculated with the number of subjects in each group as denominator †N with Female Reproductive Disorders – Incidence calculated relative to the number of females; Pediatric TPM 50 mg n=40; Pediatric TPM 400 mg n=33; Adult TPM 50 mg n=84; TPM 400 mg n=80
Body as a Whole - General Disorders
Asthenia 0 3 4 6
Chest pain 1 2
Fever 1 12
Leg pain 2 3
Central & Peripheral Nervous System Disorders
Ataxia 3 4
Dizziness 13 14
Hypertonia 0 3
Hypoesthesia 4 5
Muscle contractions involuntary 0 3
Paresthesia 3 12 21 40
Vertigo 0 3
Gastro-Intestinal System Disorders
Constipation 1 4
Diarrhea 8 9
Gastritis 0 3
Gastroesophageal reflux 1 2
Dry mouth 1 3
Liver and Biliary System Disorders
Gamma-GT increased 1 3
Metabolic and Nutritional Disorders
Weight decrease 7 17 6 17
Platelet, Bleeding & Clotting Disorders
Epistaxis 0 4
Psychiatric Disorders
Anorexia 4 14
Anxiety 4 6
Cognitive problems 1 6 1 4
Confusion 0 3
Depression 0 3 7 9
Difficulty with

concentration/attention 7 10 7 8
Difficulty with memory 1 3 6 11
Insomnia 8 9
Libido decreased 0 3
Mood problems 1 8 2 5
Personality disorder (behavior problems) 0 3
Psychomotor slowing 3 5
Somnolence 10 15
Red Blood Cell Disorders
Anemia 1 3
Reproductive Disorders, Female †
Intermenstrual Bleeding 0 3
Vaginal Hemorrhage 0 3
Resistance Mechanism Disorders
Infection 3 8 2 3
Infection viral 3 6 6 8
Respiratory System Disorders
Bronchitis 1 5 3 4
Dyspnea 1 2
Rhinitis 5 6 2 4
Sinusitis 1 4
Upper respiratory tract infection 16 18
Skin and Appendages Disorders
Acne 2 3
Alopecia 1 4 3 4
Pruritus 1 4
Rash 3 4 1 4
Special Senses Other, Disorders
Taste perversion 3 5
Urinary System Disorders
Cystitis 1 3
Dysuria 0 2
Micturition frequency 0 3 0 2
Renal calculus 0 3
Urinary incontinence 1 3
Urinary tract infection 1 2
Vascular (Extracardiac) Disorders
Flushing 0 5






Adjunctive Therapy Epilepsy

The most commonly observed adverse reactions associated with the use of topiramate at dosages of 200 to 400 mg/day (recommended dose range) in controlled trials in adults with partial onset seizures, primary generalized tonic-clonic seizures, or Lennox-Gastaut syndrome, that were seen at an incidence higher (≥ 5%) than in the placebo group were : somnolence, weight decrease, anorexia, dizziness, ataxia, speech disorders and related speech problems, language problems, psychomotor slowing, confusion, abnormal vision, difficulty with memory, paresthesia, diplopia, nervousness, and asthenia (see Table 5). Dose-related adverse reactions at dosages of 200 to 1,000 mg/day are shown in Table 7.

The most commonly observed adverse reactions 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 an incidence higher (≥ 5%) than in the placebo group were : fatigue, somnolence, anorexia, nervousness, difficulty with concentration/attention, difficulty with memory, aggressive reaction, and weight decrease (see Table 8). Table 8 also presents the incidence of adverse reactions occurring in at least 1% of pediatric patients treated with topiramate and occurring with greater incidence than placebo.

In controlled clinical trials in adults, 11% of patients receiving topiramate 200 to 400 mg/day as adjunctive therapy discontinued due to adverse reactions. This rate appeared to increase at dosages above 400 mg/day. Adverse reactions 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 reactions.

Approximately 28% of the 1757 adults with epilepsy who received topiramate at dosages of 200 to 1,600 mg/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%), 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 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 5 lists the incidence of adverse reactions that occurred in at least 1% of adults treated with 200 to 400 mg/day topiramate (and also higher daily dosing of 600 mg to 1,000 mg) in controlled trials and that was numerically greater with topiramate than 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 8 lists the incidence of treatment-emergent adverse reactions that occurred in at least 1% of pediatric patients treated with 5 to 9 mg/kg topiramate in controlled trials and that was numerically greater than the incidence 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 reactions 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 reaction incidences in the population studied.

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 5: Incidence of Treatment-Emergent Adverse Reactions in Placebo-Controlled, Add-On Epilepsy Trials in Adults * † Where Incidence Was > 1% in Any Topiramate Group and Greater Than the Incidence in Placebo-Treated Patients
*Patients in these add-on/ adjunctive trials were receiving 1 to 2 concomitant antiepileptic drugs in addition to topiramate or placebo. †Values 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. ‡Adverse reactions 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.









TopiramateDosage (mg/day)



Body System/



Adverse Reaction ‡



Placebo



(N=291)



200 to 400



(N=183)



600 to 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



Hypoesthesia



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






Incidence in Study 119 – Add-On Therapy– Adults with Partial Onset Seizures

Study 119 was a randomized, double-blind, add-on/adjunctive, placebo-controlled, parallel group study with 3 treatment arms: 1) placebo; 2) topiramate 200 mg/day with a 25 mg/day starting dose, increased by 25 mg/day each week for 8 weeks until the 200 mg/day maintenance dose was reached; and 3) topiramate 200 mg/day with a 50 mg/day starting dose, increased by 50 mg/day each week for 4 weeks until the 200 mg/day maintenance dose was reached. All patients were maintained on concomitant carbamazepine with or without another concomitant antiepileptic drug.

The most commonly observed adverse reactions associated with the use of topiramate that were seen at an incidence higher (≥ 5%) than in the placebo group were: paresthesia, nervousness, somnolence, difficulty with concentration/attention, and fatigue (see Table 6). Because these topiramate treatment difference incidence (topiramate % - Placebo %) of many 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 6: Incidence of Treatment-Emergent Adverse Reactions in Study 119 * † Where Incidence Was ≥ 2% in the Topiramate Group and Greater Than the Rate in Placebo-Treated Patients
*Patients in these add-on/adjunctive trials were receiving 1 to 2 concomitant antiepileptic drugs in addition to topiramate or placebo. †Values 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. ‡Adverse reactions reported by at least 2% of patients in the topiramate 200 mg/day group and more common than in the placebo group are listed in this table.









Topiramate Dosage (mg/day)



Body System/



Adverse Reaction ‡



Placebo (N=92)



200



(N=171)



Body as a Whole-General Disorders



Fatigue



4



9



Chest pain



1



2



Cardiovascular 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 Disorders



Diplopia



0



2



Vision abnormal



0



2










Table 7: Incidence (%) of Dose-Related Adverse Reactions From Placebo-Controlled, Add-On Trials in Adults With Partial Onset Seizures *
*Dose-response studies were not conducted for other adult indications or for pediatric indications.





Topiramate Dosage (mg/day)







Adverse Reaction



Placebo



(N = 216)

%

200



(N = 45)

%

400



(N = 68)

%

600 to 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






Table 8: Incidence (%) of Treatment-Emergent Adverse Reactions in Placebo-Controlled, Add-On Epilepsy Trials in Pediatric Patients (Ages 2 to 16 Years) *, † (Reactions That Occurred in at Least 1% of Topiramate-Treated Patients and Occurred More Frequently in Topiramate-Treated Than Placebo-Treated Patients)
*Patients in these add-on/ adjunctive trials were receiving 1 to 2 concomitant antiepileptic drugs in addition to topiramate or placebo. †Values 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.
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




Other Adverse Reactions Observed During All Epilepsy Clinical Trials

Topiramate has been administered to 2246 adults and 427 pediatric patients with epilepsy during all clinical studies, only some of which were placebo-controlled. During these studies, all adverse reactions were recorded by the clinical investigators using terminology of their own choosing. To provide a meaningful estimate of the proportion of individuals having adverse reactions, similar types of reactions were grouped into a smaller number of standardized categories using modified WHOART dictionary terminology. The frequencies presented represent the proportion of patients who experienced a reaction of the type cited on at least one occasion while receiving topiramate. Reported reactions are included except those already listed in the previous tables or text, those too general to be informative, and those not reasonably associated with the use of the drug.

Reactions are classified within body system categories and enumerated in order of decreasing frequency using the following definitions: frequent occurring in at least 1/100 patients; infrequent occurring in 1/100 to 1/1,000 patients; rare occurring in fewer than 1/1,000 patients.

Autonomic Nervous System Disorders: Infrequent: vasodilation.

Body as a Whole: Frequent: syncope. Infrequent: abdomen enlarged. Rare: alcohol intolerance.

Cardiovascular Disorders, General: Infrequent: hypotension, postural hypotension, angina pectoris.

Central & Peripheral Nervous System Disorders: Infrequent: neuropathy, apraxia, hyperesthesia, dyskinesia, dysphonia, scotoma, ptosis, dystonia, visual field defect, encephalopathy, EEG abnormal. Rare: upper motor neuron lesion, cerebellar syndrome, tongue paralysis.

Gastrointestinal System Disorders: Infrequent: hemorrhoids, stomatitis, melena, gastritis, esophagitis. Rare: tongue edema.

Heart Rate and Rhythm Disorders: Infrequent: AV block.

Liver and Biliary System Disorders: Infrequent: SGPT increased, SGOT increased.

Metabolic and Nutritional Disorders: Infrequent: dehydration, hypocalcemia, hyperlipemia, hyperglycemia, xerophthalmia, diabetes mellitus. Rare: hypernatremia, hyponatremia, hypocholesterolemia, creatinine increased.

Musculoskeletal System Disorders: Frequent: arthralgia. Infrequent: arthrosis.

Neoplasms: Infrequent: thrombocythemia. Rare: polycythemia.

Platelet, Bleeding, and Clotting Disorders: Infrequent: gingival bleeding, pulmonary embolism.

Psychiatric Disorders: Frequent: impotence, hallucination, psychosis, suicide attempt. Infrequent: euphoria, paranoid reaction, delusion, paranoia, delirium, abnormal dreaming. Rare: libido increased, manic reaction.



Red Blood Cell Disorders: Frequent: anemia. Rare: marrow depression, pancytopenia.

Reproductive Disorders, Male: Infrequent: ejaculation disorder, breast discharge.

Skin and Appendages Disorders: Infrequent: urticaria, photosensitivity reaction, abnormal hair texture. Rare: chloasma.



Special Senses Other, Disorders: Infrequent: taste loss, parosmia.

Urinary System Disorders: Infrequent: urinary retention, face edema, renal pain, albuminuria, polyuria, oliguria.



Vascular (Extracardiac) Disorders: Infrequent: flushing, deep vein thrombosis, phlebitis. Rare: vasospasm.



Vision Disorders: Frequent: conjunctivitis. Infrequent: abnormal accommodation, photophobia, strabismus. Rare: mydriasis, iritis.

White Cell and Reticuloendothelial System Disorders: Infrequent: lymphadenopathy, eosinophilia, lymphopenia, granulocytopenia. Rare: lymphocytosis.





6.2 Postmarketing and Other Experience

In addition to the adverse experiences reported during clinical testing of topiramate, the following adverse experiences have been reported worldwide in patients receiving topiramate post-approval.

These adverse experiences have not been listed above and data are insufficient to support an estimate of their incidence or to establish causation. 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.

DRUG INTERACTIONS SECTION

USE IN SPECIFIC POPULATIONS SECTION

DRUG ABUSE AND DEPENDENCE SECTION

OVERDOSAGE SECTION

Overdoses of topiramate have been reported. Signs and symptoms included convulsions, drowsiness, speech disturbance, blurred vision, diplopia, mentation impaired, lethargy, abnormal coordination, stupor, hypotension, abdominal pain, agitation, dizziness and depression. The clinical consequences were not severe in most cases, but deaths have been reported after poly-drug overdoses involving topiramate.

Topiramate overdose has resulted in severe metabolic acidosis [see Warnings and Precautions (5.4)].

A patient who ingested a dose between 96 g and 110 g topiramate was admitted to a hospital with a coma lasting 20 to 24 hours followed by full recovery after 3 to 4 days.

In acute topiramate overdose, if the ingestion is recent, the stomach should be emptied immediately by lavage or by induction of emesis. Activated charcoal has been shown to adsorb topiramate in vitro. Treatment should be appropriately supportive. Hemodialysis is an effective means of removing topiramate from the body.

DESCRIPTION SECTION

Topiramate is a sulfamate-substituted monosaccharide. Topiramate tablets are available as 25 mg, 50 mg, 100 mg, and 200 mg round tablets for oral administration.

Topiramate is a white crystalline powder with a bitter taste. Topiramate USP is most soluble in alkaline solutions containing sodium hydroxide or sodium phosphate and having a pH of 9 to 10. It is freely soluble in acetone, chloroform, dimethylsulfoxide, and ethanol. The solubility in water is 9.8 mg/mL. Its saturated solution has a pH of 6.3. Topiramate has the molecular formula C12H21NO8S and a molecular weight of 339.37. Topiramate is designated chemically as 2,3:4,5-­Di-O-isopropylidene-β-D-fructopyranose sulfamate and has the following structural formula:

chemical-structure

Topiramate tablets, USP contain the following inactive ingredients: anhydrous lactose, microcrystalline cellulose, pregelatinized maize starch, sodium starch glycolate, magnesium stearate, polyvinyl alcohol, titanium dioxide, polyethylene glycol and talc.

In addition, individual tablets contain:

50 mg tablets: iron oxide yellow

100 mg tablets: iron oxide yellow, and D&C Yellow # 10 Aluminum Lake

200 mg tablets: iron oxide red, lecithin (soya), and iron oxide black

CLINICAL PHARMACOLOGY SECTION

NONCLINICAL TOXICOLOGY SECTION

CLINICAL STUDIES SECTION

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

823

369

TOPIRAMATE 
topiramate tablet, film coated
Product Information
Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:61919-823(NDC:62756-712)
Route of AdministrationORAL
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
TOPIRAMATE (UNII: 0H73WJJ391) (TOPIRAMATE - UNII:0H73WJJ391) TOPIRAMATE200 mg
Inactive Ingredients
Ingredient NameStrength
ANHYDROUS LACTOSE (UNII: 3SY5LH9PMK)  
CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)  
STARCH, CORN (UNII: O8232NY3SJ)  
SODIUM STARCH GLYCOLATE TYPE A POTATO (UNII: 5856J3G2A2)  
MAGNESIUM STEARATE (UNII: 70097M6I30)  
POLYVINYL ALCOHOL (UNII: 532B59J990)  
TITANIUM DIOXIDE (UNII: 15FIX9V2JP)  
POLYETHYLENE GLYCOL, UNSPECIFIED (UNII: 3WJQ0SDW1A)  
TALC (UNII: 7SEV7J4R1U)  
FERRIC OXIDE RED (UNII: 1K09F3G675)  
LECITHIN, SOYBEAN (UNII: 1DI56QDM62)  
FERROSOFERRIC OXIDE (UNII: XM0M87F357)  
Product Characteristics
ColorbrownScoreno score
ShapeROUND (circular) Size12mm
FlavorImprint Code S;712
Contains    
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:61919-823-6060 in 1 BOTTLE; Type 0: Not a Combination Product01/01/2015
2NDC:61919-823-3030 in 1 BOTTLE; Type 0: Not a Combination Product01/01/2015
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
ANDAANDA09027801/01/2015
TOPIRAMATE 
topiramate tablet
Product Information
Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:61919-369(NDC:69097-123)
Route of AdministrationORAL
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
TOPIRAMATE (UNII: 0H73WJJ391) (TOPIRAMATE - UNII:0H73WJJ391) TOPIRAMATE50 mg
Inactive Ingredients
Ingredient NameStrength
FERRIC OXIDE RED (UNII: 1K09F3G675)  
POLYETHYLENE GLYCOL 400 (UNII: B697894SGQ)  
HYPROMELLOSE 2910 (3 MPA.S) (UNII: 0VUT3PMY82)  
FERRIC OXIDE YELLOW (UNII: EX438O2MRT)  
MAGNESIUM STEARATE (UNII: 70097M6I30)  
TITANIUM DIOXIDE (UNII: 15FIX9V2JP)  
POLYSORBATE 80 (UNII: 6OZP39ZG8H)  
LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X)  
STARCH, CORN (UNII: O8232NY3SJ)  
CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)  
SODIUM STARCH GLYCOLATE TYPE A POTATO (UNII: 5856J3G2A2)  
HYPROMELLOSE 2910 (6 MPA.S) (UNII: 0WZ8WG20P6)  
Product Characteristics
ColororangeScoreno score
ShapeROUNDSize7mm
FlavorImprint Code 123;C
Contains    
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:61919-369-6060 in 1 BOTTLE; Type 0: Not a Combination Product05/12/2020
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
ANDAANDA07634305/12/2020
Labeler - DirectRX (079254320)
Establishment
NameAddressID/FEIBusiness Operations
DirectRX079254320repack(61919-823, 61919-369)

Revised: 5/2020
Document Id: a5762b8d-02f8-225b-e053-2a95a90aea65
Set id: 2082548c-371c-4c98-98a6-effe0a9bd2a4
Version: 4
Effective Time: 20200512
 
DirectRX