1 INDICATIONS AND USAGE Topiramate tablets USP are an antiepileptic (AED) agent indicated for: • Monotherapy epilepsy: Initial monotherapy in patients ≥10 years of age with partial onset or primary generalized tonic-clonic seizures (1.1) • Adjunctive therapy epilepsy: Adjunctive therapy for adults and pediatric patients (2 to 16 years of age) with partial onset seizures or primary generalized tonic-clonic seizures, and in patients ≥2 years of age with seizures associated with Lennox-Gastaut syndrome (LGS) (1.2) 1.1 Monotherapy Epilepsy Topiramate tablets USP are indicated as initial monotherapy in patients 10 years of age and older with partial onset or primary generalized tonic-clonic seizures.

Safety and effectiveness in patients who were converted to monotherapy from a previous regimen of other anticonvulsant drugs have not been established in controlled trials [see Clinical Studies (14.1)].

1.2 Adjunctive Therapy Epilepsy Topiramate tablets USP are indicated as adjunctive therapy for adults and pediatric patients ages 2 to 16 years with partial onset seizures or primary generalized tonic-clonic seizures, and in patients 2 years of age and older with seizures associated with Lennox-Gastaut syndrome [see Clinical Studies (14.2)].

6 ADVERSE REACTIONS The following adverse reactions are 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 most common ( > 10% more frequent than placebo or low dose topiramate in monotherapy) adverse reactions at recommended dosing in adult and pediatric controlled, epilepsy clinical trials were paresthesia, anorexia, weight decrease, speech disorder related speech problem, fatigue, dizziness, somnolence, nervousness, psychomotor slowing, abnormal vision, and fever.

(6) To report SUSPECTED ADVERSE REACTIONS, contact Glenmark Generics Inc., USA at 1(888)721-7115 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical 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 3).

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 topiramate 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 3).

Table 3 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 3: 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) Body System Adverse Reaction 50 400 50 400 (N=74) %* (N=77) %* (N=160) %* (N=159) %* 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 *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 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 4).

Dose-related adverse reactions at dosages of 200 to 1,000 mg/day are shown in Table 6.

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 7).

Table 7 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 (4.0%), 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 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 1000 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 7 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 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 Treatment-Emergent Adverse Reactions in Placebo-Controlled, Add-On Epilepsy Trials in Adults a,b Where Incidence Was > 1% in Any Topiramate Group and Greater Than the Incidence in Placebo-Treated Patients Topiramate Dosage (mg/day) Body System Adverse Reaction c Placebo 200-400 600-1,000 (N=291) (N=183) (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 a Patients in these add-on/adjunctive 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 reaction.

Patients may have reported more than one adverse reaction during the study and can be included in more than one adverse reaction category.

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

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 5).

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 5: Incidence of Treatment-Emergent Adverse Reactions in Study 119 a,b Where Incidence Was ≥ 2% in the Topiramate Group and Greater Than the Rate in Placebo-Treated Patients Topiramate Dosage (mg/day) Body System/ Placebo 200 Adverse Reaction c (N=92) (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 a Patients in these add-on/adjunctive 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 reaction.

Patients may have reported more than one adverse reaction during the study and can be included in more than one adverse reaction category.

c 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.

Table 6: Incidence (%) of Dose-Related Adverse Reactions From Placebo-Controlled, Add-On Trials in Adults With Partial Onset Seizures a Topiramate Dosage (mg/day) Adverse Reaction Placebo 200 400 600-1,000 (N=216) % (N=45) % (N=68) % (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 a Dose-response studies were not conducted for other adult indications or for pediatric indications.

Table 7: Incidence (%) of Treatment-Emergent Adverse Reactions in Placebo-Controlled, Add-On Epilepsy Trials in Pediatric Patients (Ages 2 -16 Years) a,b (Reactions That Occurred in at Least 1% of Topiramate -Treated Patients and Occurred More Frequently in Topiramate -Treated Than Placebo-Treated Patients) Placebo Topiramate Body System/ Adverse Reaction (N=101) % (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 a Patients in these add-on/adjunctive 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 reaction.

Patients may have reported more than one adverse reaction during the study and can be included in more than one adverse reaction category.

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 1/1000 patients; rare occurring in fewer than 1/1000 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.