Topiramate - Zydus Pharmaceuticals USA Inc. | Zydus Worldwide DMCC | Zydus Lifesciences Limited

1 INDICATIONS AND USAGE

INDICATIONS & USAGE SECTION

2 DOSAGE AND ADMINISTRATION

DOSAGE & ADMINISTRATION SECTION

3 DOSAGE FORMS AND STRENGTHS

DOSAGE FORMS & STRENGTHS SECTION

Topiramate extended-release capsules, USP are available in the following strengths and colors: 25 mg: white to off white pellets filled in size "4" cellulose capsules with flesh opaque cap printed with "1039" in black ink and a white opaque body. 50 mg: white to off white pellets filled in size "2" cellulose capsules with ivory opaque cap printed with "1040" in black ink and a white opaque body. 100 mg: white to off white pellets filled in size "1" cellulose capsules with medium orange opaque cap printed with "1041" in black ink and a white opaque body. 150 mg: white to off white pellets filled in size "0" cellulose capsules with white opaque cap printed with "1042" in black ink and a white opaque body. 200 mg: white to off white pellets filled in size "00" cellulose capsules with light green opaque cap printed with "1043" in black ink and a white opaque body.

4 CONTRAINDICATIONS

CONTRAINDICATIONS SECTION

Topiramate extended-release capsules is contraindicated in patients with a history of hypersensitivity reaction to topiramate, Topiramate extended-release capsules, or any of the inactive ingredients of topiramate extended-release capsules. Anaphylaxis and angioedema have occurred with topiramate [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 )] Oligohydrosis 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 in 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 Use [see Warnings and Precautions ( 5.14 )] Kidney Stones [see Warnings and Precautions ( 5.15 )] Hypothermia with Concomitant Valproic Acid Use [see Warnings and Precautions ( 5.16 )] The data described in section 6.1 were obtained using immediate-release 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 immediate-release topiramate between 96 g and 110 g was admitted to a hospital with a coma lasting 20 hours to 24 hours followed by full recovery after 3 days to 4 days. Similar signs, symptoms, and clinical consequences are expected to occur with overdosage of topiramate extended-release capsules. Therefore, in the event of topiramate extended-release capsules overdose, topiramate extended-release capsules 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 extended-release capsules, USP are available as 25 mg, 50 mg, 100 mg, 150 mg, and 200 mg capsules for oral administration as whole capsules or opened and sprinkled onto a spoonful of soft food. Topiramate, USP is a white to off white crystalline powder. Topiramate is freely soluble in dichloromethane. Topiramate has the molecular formula C 12 H 21 NO 8 S and a molecular weight of 339.4. Topiramate is designated chemically as 2,3:4,5-Di-O-isopropylidene-β-D-fructopyranose sulfamate and has the following structural formula: Each topiramate extended-release capsule, USP contains extended-release pellets of topiramate in a capsule. Each capsule contains active ingredient topiramate USP, 25 mg or 50 mg or 100 mg or 150 mg or 200 mg and following inactive ingredients: ethyl cellulose, hydroxypropyl cellulose, hypromellose, microcrystalline cellulose, polyethylene glycol, talc and triethyl citrate. Each capsule shell contains hypromellose and titanium dioxide. Additionally, each 25 mg capsule shell contains red iron oxide, 50 mg capsule shell contains yellow iron oxide, 100 mg capsule shell contains black iron oxide, red iron oxide and yellow iron oxide and 200 mg capsule shell contains black iron oxide and yellow iron oxide. The capsule is imprinted with black pharmaceutical ink and contains following inactive ingredients: ferrosoferric oxide, potassium hydroxide, propylene glycol, purified water and shellac. FDA approved dissolution test specifications differ from USP.

12 CLINICAL PHARMACOLOGY

CLINICAL PHARMACOLOGY SECTION

13 NON-CLINICAL TOXICOLOGY

NONCLINICAL TOXICOLOGY SECTION

14 CLINICAL STUDIES

CLINICAL STUDIES SECTION

16 HOW SUPPLIED/STORAGE AND HANDLING

HOW SUPPLIED SECTION

17 PATIENT COUNSELING INFORMATION

INFORMATION FOR PATIENTS SECTION

Advise patients to read the FDA-approved patient labeling (Medication Guide). Administration Instructions Counsel patients to swallow topiramate extended-release capsules whole or carefully open and sprinkle the entire contents on a spoonful of soft food. This drug/food mixture should be swallowed immediately and not chewed. Do not store drug/food mixture for future use [see Dosage and Administration ( 2.6 )] . Eye Disorders Advise patients taking topiramate extended-release capsules to seek immediate medical attention if they experience blurred vision, visual disturbances or periorbital pain [see Warnings and Precautions ( 5.1 and 5.2 )] . Oligohydrosis and Hyperthermia Closely monitor topiramate extended-release capsules-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 , 8.4 )]. Suicidal Behavior and Ideation Counsel patients, their caregivers, and families that AEDs, including topiramate extended-release capsules, may increase the risk of suicidal thoughts and behavior and they should be advised 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, 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, visual effects, and advise patients not to drive or operate machinery until they have gained sufficient experience on topiramate extended-release capsules to gauge whether it adversely affects their mental performance, motor performance, and/or vision [see Warnings and Precautions ( 5.6 )] . Even when taking topiramate extended-release capsules, or other anticonvulsants, some patients with epilepsy will continue to have unpredictable seizures. Therefore, advise all patients taking topiramate extended-release capsules 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 extended-release capsules during pregnancy can cause fetal harm. Topiramate extended-release capsules increased 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 small for their gestational age. There may also be risks to the fetus from chronic metabolic acidosis with use of topiramate extended-release capsules during pregnancy [see Warnings and Precautions ( 5.4 , 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 extended-release capsules, 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 extended-release capsules 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 extended-release capsules 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 extended-release capsules 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 extended-release capsules. 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 )] . Hypothermia Counsel patients that topiramate extended-release capsules can cause a reduction in body temperature, which can lead to alterations in mental status. If they note such changes, they should call their health care professional and measure their body temperature. Patients taking concomitant valproic acid should be specifically counseled on this potential adverse reaction [see Warnings and Precautions ( 5.16 )] . Medication Guide available at www.zydususa.com/medguides or call 1-877-993-8779.

SPL UNCLASSIFIED SECTION

SPL UNCLASSIFIED SECTION

Manufactured by: Zydus Lifesciences Ltd. Ahmedabad, India Distributed by: Zydus Pharmaceuticals (USA) Inc. Pennington, NJ 08534 Rev.: 04/26

SPL MEDGUIDE SECTION

SPL MEDGUIDE SECTION

MEDICATION GUIDE Topiramate (toe pir' a mate) Extended-Release Capsules, USP for oral use What is the most important information I should know about topiramate extended-release capsules? Topiramate extended-release capsules 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 extended-release capsules 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 you have a high fever, a fever that does not go away, or decreased sweating develops, call your healthcare provider right away. Topiramate extended-release capsules 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 extended-release capsules. If you are pregnant, you should talk to your healthcare provider about whether you have metabolic acidosis. Like other antiepileptic drugs, topiramate extended-release capsules 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: o thoughts about suicide or dying o feeling agitated or restless o acting aggressive, being angry, or violent o attempts to commit suicide o panic attacks o acting on dangerous impulses o new or worse depression o trouble sleeping (insomnia) o an extreme increase in activity and talking (mania) o new or worse anxiety o new or worse irritability o other unusual changes in behavior or mood Do not stop topiramate extended-release capsules without first talking to a healthcare provider. Stopping topiramate extended-release capsules 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 extended-release capsules can harm your unborn baby. If you take topiramate extended-release capsules 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 extended-release capsules. If the decision is made to use topiramate extended-release capsules, you should use effective birth control (contraception) unless you are planning to become pregnant. You should talk to your healthcare provider about the best kind of birth control to use while you are taking topiramate extended-release capsules. Tell your healthcare provider right away if you become pregnant while taking topiramate extended-release capsules. You and your healthcare provider should decide if you will continue to take topiramate extended-release capsules while you are pregnant. If you take topiramate extended-release capsules 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 any questions about this risk during pregnancy. Metabolic acidosis may have harmful effects on your baby. Talk to your healthcare provider if topiramate extended-release capsules have caused metabolic acidosis during your pregnancy. Pregnancy Registry: If you become pregnant while taking topiramate extended-release capsules, 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 extended-release capsules and other antiepileptic drugs during pregnancy. Topiramate extended-release capsules may decrease the density of bones when used over a long period. Topiramate extended-release capsules may slow height increase and weight gain in children and adolescents when used over a long period. What are topiramate extended-release capsules? Topiramate extended-release capsules are a prescription medicine used: to treat certain types of seizures (partial-onset seizures and primary generalized tonic-clonic seizures) in adults and children 2 years of age 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 of age and older, to prevent migraine headaches in adults and adolescents 12 years of age and older. Who should not take topiramate extended-release capsules ? Do not take topiramate extended-release capsules if you are allergic to topiramate, topiramate extended-release capsules, or any of the ingredients in topiramate extended-release capsules. See the end of this Medication Guide for a complete list of ingredients in topiramate extended-release capsules. What should I tell my healthcare provider before taking topiramate extended-release capsules? Before taking topiramate extended-release capsules, 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, 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 extended-release capsules. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Topiramate extended-release capsules and other medicines may affect each other causing side effects. Especially tell your healthcare provider if yo...

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

NDC 70710-1039-3 Topiramate extended-release Capsules USP, 25 mg Rx only 30 Capsules Zydus NDC 70710-1040-3 Topiramate extended-release Capsules USP, 50 mg Rx only 30 Capsules Zydus NDC 70710-1041-3 Topiramate extended-release Capsules USP, 100 mg Rx only 30 Capsules Zydus NDC 70710-1042-3 Topiramate extended-release Capsules USP, 150 mg Rx only 30 Capsules Zydus NDC 70710-1043-3 Topiramate extended-release Capsules USP, 200 mg Rx only 30 Capsules Zydus