These highlights do not include all the information needed to use TOPIRAMATE TABLETS safely and effectively. See full prescribing information for TOPIRAMATE TABLETS. TOPIRAMATE tablets, for oral use Initial U.S. Approval: 1996

1 INDICATIONS AND USAGE

Indications & Usage Section

2 DOSAGE AND ADMINISTRATION

Dosage & Administration Section

3 DOSAGE FORMS AND STRENGTHS

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)

4 CONTRAINDICATIONS

Contraindications Section

Topiramate is contraindicated in patients with a history of hypersensitivity reaction to topiramate, topiramate tablet or any of the inactive ingredients of topiramate tablet. Anaphylaxis and angioedema have occurred [see Warnings and Precautions (5.13) ]

5 WARNINGS AND PRECAUTIONS

Warnings And Precautions Section

6 ADVERSE REACTIONS

Adverse Reactions Section

The following serious adverse reactions are discussed in more detail in other sections of the labeling: Acute Myopia and Secondary Angle Closure Glaucoma [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)] Decrease of Bone Mineral Density [see Warnings and Precautions (5.9)] Negative Effects on Growth (Height and Weight) [see Warnings and Precautions (5.10)] Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity Reactions [ see Warnings and Precautions (5.11) ] Serious Skin Reactions [see Warnings and Precautions (5.12)] Anaphylaxis and Angioedema [see Warnings and Precautions (5.13)] Hyperammonemia and Encephalopathy (Without and With Concomitant Valproic Acid [VPA] Use) [see Warnings and Precautions (5.14)] Kidney Stones [see Warnings and Precautions (5.15)] Hypothermia with Concomitant Valproic Acid (VPA) Use [see Warnings and Precautions (5.16)] The data described in the following sections were obtained using topiramate tablets.

7 DRUG INTERACTIONS

Drug Interactions Section

8 USE IN SPECIFIC POPULATIONS

Use In Specific Populations Section

10 OVERDOSAGE

Overdosage Section

Overdoses of topiramate have been reported. Signs and symptoms included convulsions, drowsiness, speech disturbance, blurred vision, diplopia, impaired mentation, 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 overdoses involving topiramate. Topiramate overdose has resulted in severe metabolic acidosis [see Warnings and Precautions (5.4)]. A patient who ingested a dose of topiramate between 96 and 110 g was admitted to a hospital with a coma lasting 20 to 24 hours followed by full recovery after 3 to 4 days. In the event of overdose, topiramate should be discontinued and general supportive treatment given until clinical toxicity has been diminished or resolved. Hemodialysis is an effective means of removing topiramate from the body.

11 DESCRIPTION

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 C 12 H 21 NO 8 S 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: Topiramate tablets, USP contain the following inactive ingredients: anhydrous lactose, microcrystalline cellulose, pregelatinized maize starch, sodium starch glycolate type A potato, 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

12 CLINICAL PHARMACOLOGY

Clinical Pharmacology Section

13 NON-CLINICAL TOXICOLOGY

Nonclinical Toxicology Section

14 CLINICAL STUDIES

Clinical Studies Section

The studies described in the following sections were conducted using topiramate tablets.

16 HOW SUPPLIED/STORAGE AND HANDLING

How Supplied Section

17 PATIENT COUNSELING INFORMATION

Information For Patients Section

Advise the patient to read the FDA-approved patient labeling (Medication Guide). Eye Disorders Instruct patients taking topiramate tablets to seek immediate medical attention if they experience blurred vision, visual disturbances, or periorbital pain [see Warnings and Precautions (5.1, 5.2)]. Oligohidrosis and Hyperthermia Closely monitor topiramate-treated patients, especially pediatric patients, for evidence of decreased sweating and increased body temperature, especially in hot weather. Counsel patients to contact their healthcare professionals immediately if they develop a high or persistent fever, or decreased sweating [see Warnings and Precautions (5.3)]. Metabolic Acidosis Warn patients about the potential significant risk for metabolic acidosis that may be asymptomatic and may be associated with adverse effects on kidneys (e.g., kidney stones, nephrocalcinosis), bones (e.g., osteoporosis, osteomalacia, and/or rickets in children), and growth (e.g., growth delay/retardation) in pediatric patients, and on the fetus [see Warnings and Precautions (5.4), Use in Specific Populations (8.1)]. Suicidal Behavior and Ideation Counsel patients, their caregivers, and families that AEDs, including topiramate tablets, may increase the risk of suicidal thoughts and behavior, and advise of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior or the emergence of suicidal thoughts, or behavior or thoughts about self-harm. Instruct patients to immediately report behaviors of concern to their healthcare providers [see Warnings and Precautions (5.5)]. Interference with Cognitive and Motor Performance Warn patients about the potential for somnolence, dizziness, confusion, difficulty concentrating, or visual effects, and advise patients not to drive or operate machinery until they have gained sufficient experience on topiramate tablets to gauge whether it adversely affects their mental performance, motor performance, and/or vision [see Warnings and Precautions (5.6)]. Even when taking topiramate or other anticonvulsants, some patients with epilepsy will continue to have unpredictable seizures. Therefore, advise all patients taking topiramate for epilepsy to exercise appropriate caution when engaging in any activities where loss of consciousness could result in serious danger to themselves or those around them (including swimming, driving a car, climbing in high places, etc.). Some patients with refractory epilepsy will need to avoid such activities altogether. Discuss the appropriate level of caution with patients, before patients with epilepsy engage in such activities. Fetal Toxicity Inform pregnant women and women of childbearing potential that use of topiramate during pregnancy can cause fetal harm. Topiramate increases the risk of major congenital malformations, including but not limited to cleft lip and/or cleft palate (oral clefts), which occur early in pregnancy before many women know they are pregnant. Also inform patients that infants exposed to topiramate monotherapy in utero may be SGA [see Use in Specific Populations (8.1)]. There may also be risks to the fetus from chronic metabolic acidosis with use of topiramate during pregnancy [see Warnings and Precautions (5.7), Use in Specific Populations (8.1)]. When appropriate, counsel pregnant women and women of childbearing potential about alternative therapeutic options. Advise women of childbearing potential who are not planning a pregnancy to use effective contraception while using topiramate, keeping in mind that there is a potential for decreased contraceptive efficacy when using estrogen-containing or progestin-only contraceptives with topiramate [see Drug Interactions (7.4)]. Encourage pregnant women using topiramate, to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. The registry is collecting information about the safety of antiepileptic drugs during pregnancy [see Use in Specific Populations (8.1)]. Decrease in Bone Mineral Density Inform the patient or caregiver that long-term treatment with topiramate tablets can decrease bone formation and increase bone resorption in children [see Warnings and Precautions (5.9)]. Negative Effects on Growth (Height and Weight) Discuss with the patient or caregiver that long-term topiramate tablets treatment may attenuate growth as reflected by slower height increase and weight gain in pediatric patients [see Warnings and Precautions (5.10)]. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity Reactions Instruct patients that a fever associated with other organ system involvement (rash, lymphadenopathy, etc.) may be drug-related. Advise patients to report such reactions to a healthcare provider immediately [see Warnings and Precautions (5.11)]. Serious Skin Reactions Inform patients about the signs of serious skin reactions. Instruct patients to immediately inform their healthcare provider at the first appearance of skin rash [see Warnings and Precautions (5.12)]. Anaphylaxis and Angioedema Inform patients about the signs and symptoms of hypersensitivity reactions such as anaphylaxis and angioedema, which can occur with topiramate. Advise patients to seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions [see Warnings and Precautions (5.13)]. Hyperammonemia and Encephalopathy Warn patients about the possible development of hyperammonemia with or without encephalopathy. Although hyperammonemia may be asymptomatic, clinical symptoms of hyperammonemic encephalopathy often include acute alterations in level of consciousness and/or cognitive function with lethargy and/or vomiting. This hyperammonemia and encephalopathy can develop with topiramate treatment alone or with topiramate treatment with concomitant valproic acid (VPA). Instruct patients to contact their physician if they develop unexplained lethargy, vomiting, or changes in mental status [see Warnings and Precautions (5.14)]. Kidney Stones Instruct patients, particularly those with predisposing factors, to maintain an adequate fluid intake in order to minimize the risk of kidney stone formation [see Warnings and Precautions (5.15)]. Instructions for a Missing Dose Instruct patients that if they miss a single dose of topiramate, it should be taken as soon as possible. However, if a patient is within 6 hours of taking the next scheduled dose, tell the patient to wait until then to take the usual dose of topiramate, and to skip the missed dose. Tell patients that they should not take a double dose in the event of a missed dose. Advise patients to contact their healthcare provider if they have missed more than one dose. Distributed by: Sun Pharmaceutical Industries, Inc. Cranbury, NJ 08512 Manufactured by: Sun Pharmaceutical Industries Ltd. Survey No. 1012, Dadra-396 193, U.T. of D & NH and Daman & Diu, India.

MEDICATION GUIDE

SPL MEDGUIDE SECTION

MEDICATION GUIDE Topiramate Tablets, USP ( toe pir' a mate) What is the most important information I should know about topiramate tablet? Topiramate tablets may cause eye problems. Serious eye problems include: any sudden decrease in vision with or without eye pain and redness. a blockage of fluid in the eye causing increased pressure in the eye (secondary angle closure glaucoma). These eye problems can lead to permanent loss of vision if not treated. You should call your healthcare provider right away if you have any new eye symptoms, including any new problems with your vision. Topiramate tablet may cause decreased sweating and increased body temperature (fever). People, especially children, should be watched for signs of decreased sweating and fever, especially in hot temperatures. Some people may need to be hospitalized for this condition. If a high fever, a fever that does not go away, or decreased sweating develops, call your healthcare provider right away. Topiramate tablet can increase the level of acid in your blood (metabolic acidosis). If left untreated, metabolic acidosis can cause brittle or soft bones (osteoporosis, osteomalacia, osteopenia), kidney stones, can slow the rate of growth in children, and may possibly harm your baby if you are pregnant. Metabolic acidosis can happen with or without symptoms. Sometimes people with metabolic acidosis will: feel tired not feel hungry (loss of appetite) feel changes in heartbeat have trouble thinking clearly Your healthcare provider should do a blood test to measure the level of acid in your blood before and during your treatment with topiramate tablets. If you are pregnant, you should talk to your healthcare provider about whether you have metabolic acidosis. Like other antiepileptic drugs, topiramate tablet may cause suicidal thoughts or actions in a very small number of people, about 1 in 500. Call a healthcare provider right away if you have any of these symptoms, especially if they are new, worse, or worry you: thoughts about suicide or dying attempts to commit suicide new or worse depression new or worse anxiety feeling agitated or restless panic attacks trouble sleeping (insomnia) new or worse irritability acting aggressive, being angry, or violent acting on dangerous impulses an extreme increase in activity and talking (mania) other unusual changes in behavior or mood Do not stop topiramate tablets w ithout first talking to a healthcare provider. Stopping topiramate tablets suddenly can cause serious problems. Suicidal thoughts or actions can be caused by things other than medicines. If you have suicidal thoughts or actions, your healthcare provider may check for other causes. How can I watch for early symptoms of suicidal thoughts and actions? Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings. Keep all follow-up visits with your healthcare provider as scheduled. Call your healthcare provider between visits as needed, especially if you are worried about symptoms. Topiramate can harm your unborn baby. If you take topiramate tablets during pregnancy, your baby has a higher risk for birth defects including cleft lip and cleft palate. These defects can begin early in pregnancy, even before you know you are pregnant. Birth defects may happen even in children born to women who are not taking any medicines and do not have other risk factors. There may be other medicines to treat your condition that have a lower chance of birth defects. All women of childbearing age should talk to their healthcare providers about using other possible treatments instead of topiramate tablets. If the decision is made to use topiramate tablets, you should use effective birth control (contraception) unless you are planning to become pregnant. You should talk to your doctor about the best kind of birth control to use while you are taking topiramate tablets. Tell your healthcare provider right away if you become pregnant while taking topiramate. You and your healthcare provider should decide if you will continue to take topiramate tablets while you are pregnant. If you take topiramate during pregnancy, your baby may be smaller than expected at birth. The long-term effects of this are not known. Talk to your healthcare provider if you have questions about this risk during pregnancy. Metabolic acidosis may have harmful effects on your baby. Talk to your healthcare provider if topiramate tablets have caused metabolic acidosis during your pregnancy. Pregnancy Registry: If you become pregnant while taking topiramate tablets, talk to your healthcare provider about registering with the North American Antiepileptic Drug Pregnancy Registry. You can enroll in this registry by calling 1-888-233-2334. The purpose of this registry is to collect information about the safety of topiramate and other antiepileptic drugs during pregnancy. Topiramate tablets may decrease the density of bones when used over a long period. Topiramate tablets may slow height increase and weight gain in children and adolescents when used over a long period. W hat is topiramate tablet? Topiramate tablet is prescription medicine used: to treat certain types of seizures (partial-onset seizures and primary generalized tonic-clonic seizures) in adults and children 2 years and older, with other medicines to treat certain types of seizures (partial-onset seizures, primary generalized tonic-clonic seizures, and seizures associated with Lennox-Gastaut syndrome) in adults and children 2 years and older, to prevent migraine headaches in adults and adolescents 12 years and older. Who should not take topiramate tablet? Do not take topiramate tablet if you are allergic to topiramate, topiramate tablet or any of the ingredients in topiramate tablet. See the end of this Medication Guide for a complete list of ingredients in topiramate tablet. Before taking topiramate tablets, tell your healthcare provider about all of your medical conditions, including if you: have or have had depression, mood problems, or suicidal thoughts or behavior. have kidney problems, have kidney stones, or are getting kidney dialysis. have a history of metabolic acidosis (too much acid in the blood). have liver problems. have weak, brittle, or soft bones (osteomalacia, osteoporosis, osteopenia, or decreased bone density). have lung or breathing problems. have eye problems, especially glaucoma. have diarrhea. have a growth problem. are on a diet high in fat and low in carbohydrates, which is called a ketogenic diet. are having surgery. are pregnant or plan to become pregnant. are breastfeeding or plan to breastfeed. Topiramate passes into breast milk. Breastfed babies may be sleepy or have diarrhea. It is not known if the topiramate that passes into breast milk can cause other serious harm to your baby. Talk to your healthcare provider about the best way to feed your baby if you take topiramate tablets. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Topiramate and other medicines may affect each other causing side effects. Especially tell your healthcare provider if you take: Valproic acid (such as DEPAKENE* or DEPAKOTE*). any medicines that impair or decrease your thinking, concentration, or muscle coordination. birth control that contains hormones (such as pills, implants, patches or injections). Topiramate tablets may make your birth control less effective. Tell your healthcare provider if your menstrual bleeding changes while you are using birth control and topiramate tablets. Ask your healthcare provider if you are not sure if your medicine is listed above. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist each time you get a new medicine. Do not start a new medicine without talking with your healthcare provider. How should I take topiramate tablets? Take topiramate tablets exactly as presc...

PRINCIPAL DISPLAY PANEL-25 mg

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

NDC 47335-707-86 Topiramate Tablets, USP 25 mg PHARMACIST: Dispense with Medication Guide to each patient. Rx only 60 Tablets SUN PHARMA

PRINCIPAL DISPLAY PANEL-50 mg

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

NDC 47335-710-86 Topiramate Tablets, USP 50 mg PHARMACIST: Dispense with Medication Guide to each patient. Rx only 60 Tablets SUN PHARMA

PRINCIPAL DISPLAY PANEL-100 mg

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

NDC 47335-711-86 Topiramate Tablets, USP 100 mg PHARMACIST: Dispense with Medication Guide to each patient. Rx only 60 Tablets SUN PHARMA

PRINCIPAL DISPLAY PANEL-200 mg

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

NDC 47335-712-86 Topiramate Tablets, USP 200 mg Rx only PHARMACIST: Dispense with Medication Guide to each patient. 60 Tablets SUN PHARMA