QUDEXY

Contraindications (4) 3/2026 Waenings and Precautions (5.7) 8/2026 Warnings and Precautions (5.12, 5.14) 3/2026

1 INDICATIONS AND USAGE QUDEXY XR is indicated for: Epilepsy: initial monotherapy for the treatment of partial-onset or primary generalized tonic-clonic seizures in patients 2 years of age and older ( 1.1 ); adjunctive therapy for the treatment of partial-onset seizures, primary generalized tonic-clonic seizures, or seizures associated with Lennox-Gastaut Syndrome in patients 2 years of age and older ( 1.2 ) Preventive treatment of migraine in patients 12 years of age and older ( 1.3 ) 1.1 Monotherapy Epilepsy QUDEXY XR is indicated as initial monotherapy for the treatment of partial-onset or primary generalized tonic-clonic seizures in patients 2 years of age and older. 1.2 Adjunctive Therapy Epilepsy QUDEXY XR is indicated as adjunctive therapy for the treatment of partial-onset seizures, primary generalized tonic-clonic seizures, and seizures associated with Lennox-Gastaut Syndrome in patients 2 years of age and older. 1.3 Migraine QUDEXY XR is indicated for the preventive treatment of migraine in patients 12 years of age and older.

2 DOSAGE AND ADMINISTRATION QUDEXY XR initial dose, titration, and recommended maintenance dose varies by indication and age group. See Full Prescribing Information for recommended dosage, and dosing considerations in patients with renal impairment, geriatric patients, and patients undergoing hemodialysis ( 2.1 , 2.2 , 2.3 , 2.4 , 2.5 , 2.6 ) Capsules may be swallowed whole or opened and sprinkled on a spoonful of soft food ( 2.6 ) 2.1 Dosing in Monotherapy Epilepsy Adults and Pediatric Patients 10 Years of Age and Older The recommended dose for QUDEXY XR monotherapy in adults and pediatric patients 10 years of age and older is 400 mg orally once daily. Titrate QUDEXY XR according to the following schedule (see Table 1 ). Table 1: Monotherapy Titration Schedule for Adults and Pediatric Patients 10 Years of Age and Older QUDEXY XR Once Daily Dose Week 1 50 mg Week 2 100 mg Week 3 150 mg Week 4 200 mg Week 5 300 mg Week 6 400 mg Pediatric Patients 2 to 9 Years of Age Dosing in patients 2 to 9 years of age is based on weight. During the titration period, the initial dose of QUDEXY XR is 25 mg/day nightly for the first week. Based upon tolerability, the dosage can be increased to 50 mg/day in the second week. Dosage can be increased by 25 mg to 50 mg once daily each subsequent week, as tolerated. Titration to the minimum maintenance dose should be attempted over 5 to 7 weeks. Based upon tolerability and clinical response, additional titration to a higher dose (up to the maximum maintenance dose) can be attempted at 25 mg to 50 mg once daily weekly increments. The total daily dose should not exceed the maximum maintenance dose for each range of body weight (see Table 2 ). Table 2: Monotherapy Target Total Daily Maintenance Dosing for Patients 2 to 9 Years of Age Weight (kg) Total Daily Dose (mg/day) Minimum Maintenance Dose Total Daily Dose (mg/day) Maximum Maintenance Dose Up to 11 150 250 12 to 22 200 300 23 to 31 200 350 32 to 38 250 350 Greater than 38 250 400 2.2 Dosing in Adjunctive Therapy Epilepsy Adults (17 Years of Age and Older) The recommended total daily dose of QUDEXY XR as adjunctive therapy in adults with partial-onset seizures or Lennox-Gastaut Syndrome is 200 mg to 400 mg orally once daily, and with primary generalized tonic-clonic seizures is 400 mg orally once daily. Initiate therapy at 25 mg to 50 mg once daily followed by titration to an effective dose in increments of 25 mg to 50 mg every week. Titrating in increments of 25 mg/day every week may delay the time to reach an effective dose. Doses above 400 mg/day have not been shown to improve responses in adults with partial-onset seizures. Pediatric Patients 2 to 16 Years of Age The recommended total daily dose of QUDEXY XR as adjunctive therapy for pediatric patients 2 to 16 years of age with partial-onset seizures, primary generalized tonic-clonic seizures, or seizures associated with Lennox-Gastaut syndrome is approximately 5 mg/kg to 9 mg/kg orally once daily. Begin titration at 25 mg once daily (or less, based on a range of 1 mg/kg/day to 3 mg/kg/day) given nightly for the first week. Subsequently, increase the dosage at 1- or 2-week intervals by increments of 1 mg/kg/day to 3 mg/kg/day to achieve optimal clinical response. Dose titration should be guided by clinical outcome. The total daily dose should not exceed 400 mg/day. 2.3 Dosing for the Preventive Treatment of Migraine The recommended total daily dose of QUDEXY XR as treatment for the preventive treatment of migraine in patients 12 years of age and older is 100 mg once daily. The recommended titration rate for QUDEXY XR for the preventive treatment of migraine is as follows: Table 3: Preventive Treatment of Migraine Titration Schedule for Patients 12 Years of Age and Older QUDEXY XR Once Daily Dose Week 1 25 mg Week 2 50 mg Week 3 75 mg Week 4 100 mg Dose and titration rate should be guided by clinical outcome. If required, longer intervals between dose adjustment can be used. 2.4 Dosing in Patien …

3 DOSAGE FORMS AND STRENGTHS QUDEXY XR (topiramate) extended-release capsules are available in the following strengths and colors: 25 mg: light pink and grey capsules, printed with "UPSHER-SMITH" on the cap in black ink and "25 mg" on the body in black ink 50 mg: golden yellow and grey capsules, printed with "UPSHER-SMITH" on the cap in black ink and "50 mg" on the body in black ink 100 mg: reddish brown and grey capsules, printed with "UPSHER-SMITH" on the cap in black ink and "100 mg" on the body in black ink 150 mg: pale yellow and grey capsules, printed with "UPSHER-SMITH" on the cap in black ink and "150 mg" on the body in black ink 200 mg: brown and grey capsules, printed with "UPSHER-SMITH" on the cap in white ink and "200 mg" on the body in black ink Extended-release capsules: 25 mg, 50 mg, 100 mg, 150 mg, and 200 mg ( 3 )

4 CONTRAINDICATIONS QUDEXY XR is contraindicated in patients with a history of hypersensitivity reaction to topiramate, QUDEXY XR, or any of the inactive ingredients of QUDEXY XR. Anaphylaxis and angioedema have occurred with topiramate [see Warnings and Precautions (5.14) ]. History of hypersensitivity reaction to topiramate, QUDEXY XR, or any of the inactive ingredients of QUDEXY XR (4, 5.13)

6 ADVERSE REACTIONS 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) ] Cardiac Rhythm and Conduction Abnormalities [see Warnings and Precautions (5.7 )] Decrease in Bone Mineral Density [see Warnings and Precautions (5.10) ] Negative Effects on Growth (Height and Weight) [see Warnings and Precautions (5.11) ] Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan • Hypersensitivity Reactions [see Warnings and Precautions (5.12) ] Serious Skin Reactions [see Warnings and Precautions (5.13) ] Anaphylaxis and Angioedema [see Warnings and Precautions (5.14) ] Hyperammonemia and Encephalopathy (Without and With Concomitant Valproic Acid Use [see Warnings and Precautions (5.15) ] Kidney Stones [see Warnings and Precautions (5.16) ] Hypothermia with Concomitant Valproic Acid Use [see Warnings and Precautions (5.17) ] The data described in section 6.1 were obtained using immediate-release topiramate tablets. Epilepsy : The most common (≥10% more frequent than placebo or low-dose topiramate) adverse reactions in adult and pediatric patients were: paresthesia, anorexia, weight loss, speech disorders/related speech problems, fatigue, dizziness, somnolence, nervousness, psychomotor slowing, abnormal vision and fever ( 6.1 ) Migraine : Most common (≥5% more frequent than placebo) adverse reactions in adult and pediatric patients were: paresthesia, anorexia, weight loss, difficulty with memory, taste perversion, diarrhea, hypoesthesia, nausea, abdominal pain and upper respiratory tract infection ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Upsher-Smith Laboratories, LLC at 1-855-899-9180 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience with Immediate-Release Topiramate Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Monotherapy Epilepsy Adults 16 Years of Age and Older The most common adverse reactions in the controlled trial (Study 1) that occurred in adults in the 400 mg/day topiramate group and at an incidence higher (≥ 10%) than in the 50 mg/day group were: paresthesia, weight loss, and anorexia (see Table 5 ) . Approximately 21% of the 159 adult patients in the 400 mg/day group who received topiramate as monotherapy in Study 1 discontinued therapy due to adverse reactions. The most common (≥ 2% more frequent than low-dose 50 mg/day topiramate) adverse reactions causing discontinuation were difficulty with memory, fatigue, asthenia, insomnia, somnolence, and paresthesia. Pediatric Patients 6 to 15 Years of Age The most common adverse reactions in the controlled trial (Study 1) that occurred in pediatric patients in the 400 mg/day topiramate group and at an incidence higher (≥ 10%) than in the 50 mg/day group were fever and weight loss (see Table 5 ). 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 in the 50 mg/day group) adverse reactions resulting in discontinuation in this trial were difficulty with concentration/attention, fever, flushing, and confusion. Table 5 represents the incidence of adverse reactions occurring in at least 3% of the adult and pediatric patients treated with 400 mg/day immediate-releas …

7 DRUG INTERACTIONS Oral contraceptives: decreased contraceptive efficacy and increased breakthrough bleeding, especially at doses greater than 200 mg per day ( 7.4 ) Monitor lithium levels if lithium is used with high-dose QUDEXY XR ( 7.7 ) 7.1 Antiepileptic Drugs Concomitant administration of phenytoin or carbamazepine with topiramate resulted in a clinically significant decrease in plasma concentrations of topiramate when compared to topiramate given alone. A dosage adjustment may be needed [see Clinical Pharmacology (12.3) ] . Concomitant administration of valproic acid and topiramate has been associated with hypothermia and hyperammonemia with and without encephalopathy. Examine blood ammonia levels in patients in whom the onset of hypothermia has been reported [see Warnings and Precautions (5.12 , 5.14) , Clinical Pharmacology (12.3) ]. 7.2 Other Carbonic Anhydrase Inhibitors Concomitant use of topiramate, a carbonic anhydrase inhibitor, with any other carbonic anhydrase inhibitor (e.g., zonisamide or acetazolamide) may increase the severity of metabolic acidosis and may also increase the risk of kidney stone formation. Patients should be monitored for the appearance or worsening of metabolic acidosis when QUDEXY XR is given concomitantly with another carbonic anhydrase inhibitor [see Clinical Pharmacology (12.3) ]. 7.3 CNS Depressants Concomitant administration of topiramate and alcohol or other CNS depressant drugs has not been evaluated in clinical studies. Because of the potential of topiramate to cause CNS depression, as well as other cognitive and/or neuropsychiatric adverse reactions, QUDEXY XR should be used with extreme caution if used in combination with alcohol and other CNS depressants. 7.4 Contraceptives The possibility of decreased contraceptive efficacy and increased breakthrough bleeding may occur in patients taking contraceptive products with QUDEXY XR. Patients taking estrogen-containing or progestin-only contraceptives should be asked to report any change in their bleeding patterns. Contraceptive efficacy can be decreased even in the absence of breakthrough bleeding [see Clinical Pharmacology (12.3) ] . 7.5 Hydrochlorothiazide (HCTZ) Topiramate C max and AUC increased when HCTZ was added to immediate-release topiramate. The clinical significance of this change is unknown. The addition of HCTZ to QUDEXY XR may require a decrease in the QUDEXY XR dose [see Clinical Pharmacology (12.3) ] . 7.6 Pioglitazone A decrease in the exposure of pioglitazone and its active metabolites were noted with the concurrent use of pioglitazone and immediate-release topiramate in a clinical trial. The clinical relevance of these observations is unknown; however, when QUDEXY XR is added to pioglitazone therapy or pioglitazone is added to QUDEXY XR therapy, careful attention should be given to the routine monitoring of patients for adequate control of their diabetic disease state [see Clinical Pharmacology (12.3) ] . 7.7 Lithium An increase in systemic exposure of lithium following topiramate doses of up to 600 mg/day can occur. Lithium levels should be monitored when co-administered with high-dose QUDEXY XR [see Clinical Pharmacology (12.3) ] . 7.8 Amitriptyline Some patients may experience a large increase in amitriptyline concentration in the presence of QUDEXY XR and any adjustments in amitriptyline dose should be made according to the patient's clinical response and not on the basis of plasma levels [see Clinical Pharmacology (12.3) ] .

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), such as QUDEXY XR, during pregnancy. Patients should be encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry if they become pregnant. This registry is collecting information about the safety of antiepileptic drugs during pregnancy. To enroll, patients can call the toll-free number 1-888-233-2334. Information about the North American Drug Pregnancy Registry can be found at http://www.aedpregnancyregistry.org/. Risk Summary QUDEXY XR can cause fetal harm when administered to a pregnant woman. Data from pregnancy registries indicate that infants exposed to topiramate in utero have increased risk of major congenital malformations, including but not limited to cleft lip and/or cleft palate (oral clefts), and of being small for gestational age (SGA) [see Human Data ]. SGA has been observed at all doses and appears to be dose-dependent. The prevalence of SGA is greater in infants of women who received higher doses of topiramate during pregnancy. In addition, the prevalence of SGA in infants of women who continued topiramate use until later in pregnancy is higher compared to the prevalence in infants of women who stopped topiramate use before the third trimester. In multiple animal species, topiramate demonstrated developmental toxicity, including increased incidences of fetal malformations, in the absence of maternal toxicity at clinically relevant doses [see Animal Data ] . All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2% to 4% and 15% to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Consider the benefits and risks of topiramate when prescribing this drug to women of childbearing potential, particularly when topiramate is considered for a condition not usually associated with permanent injury or death. Because of the risk of oral clefts to the fetus, which occur in the first trimester of pregnancy before many women know they are pregnant, all women of childbearing potential should be informed of the potential risk to the fetus from exposure to topiramate. Women who are planning a pregnancy should be counseled regarding the relative risks and benefits of topiramate use during pregnancy, and alternative therapeutic options should be considered for these patients. Labor or Delivery Although the effect of topiramate on labor and delivery in humans has not been established, the development of topiramate-induced metabolic acidosis in the mother and/or in the fetus might affect the fetus' ability to tolerate labor . QUDEXY XR treatment can cause metabolic acidosis [see Warnings and Precautions (5.4) ]. The effect of topiramate-induced metabolic acidosis has not been studied in pregnancy; however, metabolic acidosis in pregnancy (due to other causes) can cause decreased fetal growth, decreased fetal oxygenation, and fetal death, and may affect the fetus' ability to tolerate labor. Pregnant patients should be monitored for metabolic acidosis and treated as in the nonpregnant state [see Warnings and Precautions (5.4) ]. Newborns of mothers treated with QUDEXY XR should be monitored for metabolic acidosis because of transfer of topiramate to the fetus and possible occurrence of transient metabolic acidosis following birth. Based on limited information, topiramate has also been associated with pre-term labor and premature delivery. Data Human Data Data from pregnancy registries indicate an increased risk of major congenital malformations, including but not limited to oral clefts in infants exposed to …

12.1 Mechanism of Action The precise mechanisms by which topiramate exerts its anticonvulsant and preventive migraine effects are unknown; however, preclinical studies have revealed four properties that may contribute to topiramate's efficacy for epilepsy and the preventive treatment of migraine. Electrophysiological and biochemical evidence suggests that topiramate, at pharmacologically relevant concentrations, blocks voltage-dependent sodium channels, augments the activity of the neurotransmitter gamma-aminobutyrate at some subtypes of the GABA-A receptor, antagonizes the AMPA/kainate subtype of the glutamate receptor, and inhibits the carbonic anhydrase enzyme, particularly isozymes II and IV.

11 DESCRIPTION Topiramate, USP, is a sulfamate-substituted monosaccharide. QUDEXY XR (topiramate) extended-release capsules 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 is a white to off-white powder. Topiramate is freely soluble in polar organic solvents such as acetonitrile and acetone; and very slightly soluble to practically insoluble in non-polar organic solvents such as hexanes. 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: QUDEXY XR (topiramate) extended-release capsules contain beads of topiramate in a capsule. The inactive ingredients are microcrystalline cellulose, hypromellose 2910, ethylcellulose, diethyl phthalate. In addition, the capsule shells for all strengths contain hypromellose 2910, titanium dioxide, black iron oxide, red iron oxide and/or yellow iron oxide, black pharmaceutical ink, and white pharmaceutical ink (200 mg only). Chemical Structure

10 OVERDOSAGE 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 to 24 hours followed by full recovery after 3 to 4 days. Similar signs, symptoms, and clinical consequences are expected to occur with overdosage of QUDEXY XR. Therefore, in the event of QUDEXY XR overdose, QUDEXY XR 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.

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied QUDEXY ® XR (topiramate) extended-release capsules contain beads of topiramate in a capsule and are available in the following strengths and colors: 25 mg: light pink and grey capsules, printed with "UPSHER-SMITH" on the cap in black ink and "25 mg" on the body in black ink. 25 mg capsules are supplied in the following package configurations: Bottles of 30 with desiccant and a child-resistant closure, NDC 0245-1071-30 Bottles of 90 with desiccant and a child-resistant closure, NDC 0245-1071-90 50 mg: golden yellow and grey capsules, printed with "UPSHER-SMITH" on the cap in black ink and "50 mg" on the body in black ink. 50 mg capsules are supplied in the following package configurations: Bottles of 30 with desiccant and a child-resistant closure, NDC 0245-1072-30 Bottles of 90 with desiccant and a child-resistant closure, NDC 0245-1072-90 100 mg: reddish brown and grey capsules, printed with "UPSHER-SMITH" on the cap in black ink and "100 mg" on the body in black ink. 100 mg capsules are supplied in the following package configurations: Bottles of 30 with desiccant and a child-resistant closure, NDC 0245-1074-30 Bottles of 90 with desiccant and a child-resistant closure, NDC 0245-1074-90 150 mg: pale yellow and grey capsules, printed with "UPSHER-SMITH" on the cap in black ink and "150 mg" on the body in black ink. 150 mg capsules are supplied in the following package configurations: Bottles of 30 with desiccant and a child-resistant closure, NDC 0245-1075-30 Bottles of 90 with desiccant and a child-resistant closure, NDC 0245-1075-90 200 mg: brown and grey capsules, printed with "UPSHER-SMITH" on the cap in white ink and "200 mg" on the body in black ink. 200 mg capsules are supplied in the following package configurations: Bottles of 30 with desiccant and a child-resistant closure, NDC 0245-1073-30 Bottles of 90 with desiccant and a child-resistant closure, NDC 0245-1073-90 16.2 Storage and Handling QUDEXY XR (topiramate) extended-release capsules should be stored in a tightly closed container at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Protect from moisture.