Topiramate 25 mg Tablet, 30-count
Other active recalls for Topiramate (different manufacturers) — 2 · tap to view
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Centrally acting antiobesity products class.
Where does this data come from?
🏭 Manufacturer & labeler
Where does this data come from?
🩺 Clinical
Topiramate is used to treat certain types of seizures. Topiramate is also used to prevent migraine headaches but not to relieve the pain of migraine headaches when they occur. Topiramate is in a class of medications called anticonvulsants. It works by decreasing abnormal excitement in the brain.
Read the full MedlinePlus article ↗Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Topiramate — tap one for details:
Topiramate may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.
Where does this data come from?
Ask a licensed pharmacist directly — free, answered by our team.
💊 What it looks like
Where does this data come from?
🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
-
UNII OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
-
UNII L06K8R7DQK
A synthetic blue dye approved by the FDA for use in medications and foods. It serves as a colorant to make pills and liquids visually distinct and easier to identify.
-
UNII 0VUT3PMY82
Hypromellose 2910 is a plant-derived thickening agent made from cellulose. In medicines, it forms protective coatings on tablets or capsules, controls how fast the drug releases, and thickens liquid formulations.
-
UNII 0WZ8WG20P6
Hypromellose 2910 is a plant-based cellulose derivative that acts as a thickener, binder, and film-coating agent. It helps control how quickly the medicine dissolves and protects the tablet or capsule from moisture and light.
-
UNII EWQ57Q8I5X
Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
-
UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
-
UNII B697894SGQ
Polyethylene glycol 400 is a clear, thick liquid made from petroleum-derived polymers. It acts as a solvent and humectant in medicines, helping dissolve active ingredients and retain moisture in the formulation.
-
UNII 6OZP39ZG8H
Polysorbate 80 is a synthetic emulsifier derived from sorbitol and oleic acid. It helps mix oil and water-based ingredients together in medications and improves how the product disperses in the body.
-
UNII 5856J3G2A2
A starch-based powder made from potatoes and processed with sodium. It acts as a disintegrant, helping the tablet or capsule break apart quickly in the stomach so the medicine can be absorbed.
-
UNII O8232NY3SJ
A plant-based carbohydrate derived from corn kernels. It acts as a filler to add bulk, a binder to hold ingredients together, and a disintegrant to help the tablet break apart in your stomach for absorption.
-
UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
11 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $0.0808 | $2.42 / 30 tablets |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| topiramate 25 mg 00904-6928-61 | Major | 1 tablet | $0.026 | AB | Availability likely | — |
| Topiramate 25 mg 68084-0342-01 | American | 1 tablet | $0.026 | AB | Availability likely | — |
| Topiramate 25 mg 68462-0108-05 | Glenmark | 500 tablets | $0.026 | AB | Availability likely | — |
| Topiramate 25 mg 69097-0122-03 | Cipla | 60 tablets | $0.026 | AB | Availability likely | — |
| Topiramate 25 mg 76282-0278-10 | EXELAN | 1000 tablets | $0.026 | AB | Availability likely | — |
| topiramate 25 mg 82009-0135-05 | Quallent | 500 tablets | $0.026 | AB | Availability likely | — |
| Topiramate 25 mg 69097-0816-03 | Cipla | 60 tablets | $0.035 | AB | FDA listed | — |
| Topamax 25 mg 50458-0639-65 | Janssen | 60 tablets | $6.576 | AB | Availability likely | — |
| Topiramate 25 mg 00615-8138-39 | NCS | 30 tablets | — | AB | Discontinued | — |
| Topiramate 25 mg 00615-8593-39 | NCS | 30 tablets | — | AB | FDA listed | — |
| topiramate 25 mg 29300-0115-01 | Unichem | 100 tablets | — | AB | FDA listed | — |
| Topiramate 25 mg 31722-0181-05 | Camber | 500 tablets | — | AB | FDA listed | — |
| Topiramate 25 mg 43063-0735-15 | PD-Rx | 15 tablets | — | AB | FDA listed | — |
| Topiramate 25 mg 43063-0998-30 | PD-Rx | 30 tablets | — | AB | FDA listed | — |
| Topiramate 25 mg 47335-0707-08 | Sun | 100 tablets | — | AB | FDA listed | — |
| topiramate 25 mg 50090-2102-00 | A-S | 60 tablets | — | AB | FDA listed | — |
| Topiramate 25 mg 50090-4614-00 | A-S | 60 tablets | — | AB | FDA listed | — |
| topiramate 25 mg 50090-5853-00 | A-S | 60 tablets | — | AB | FDA listed | — |
| Topiramate 25 mg 50090-6827-00 | A-S | 90 tablets | — | AB | FDA listed | — |
| topiramate 25 mg 50090-7067-00 | A-S | 90 tablets | — | AB | FDA listed | — |
| topiramate 25 mg 50268-0806-15 | AvPAK | 1 tablet | — | AB | FDA listed | — |
| topiramate 25 mg 51655-0429-26 | Northwind | 90 tablets | — | AB | FDA listed | — |
| topiramate 25 mg 55154-7146-00 | Cardinal | 1 tablet | — | AB | FDA listed | — |
| topiramate 25 mg 60760-0075-30 | St. | 30 tablets | — | AB | FDA listed | — |
| topiramate 25 mg 60760-0752-60 | St. | 60 tablets | — | AB | FDA listed | — |
| Topiramate 25 mg 62756-0707-08 | Sun | 100 tablets | — | AB | FDA listed | — |
| Topiramate 25 mg 63187-0077-30 | Proficient | 30 tablets | — | AB | FDA listed | — |
| Topiramate 25 mg 63187-0118-30 | Proficient | 30 tablets | — | AB | FDA listed | — |
| Topiramate 25 mg 63187-0773-30 | Proficient | 30 tablets | — | AB | FDA listed | — |
| topiramate 25 mg 65841-0647-01 | Zydus | 100 tablets | — | AB | FDA listed | — |
| Topiramate 25 mg 65862-0171-05 | Aurobindo | 500 tablets | — | AB | FDA listed | — |
| topiramate 25 mg 67046-0375-03 | Coupler | 30 tablets | — | AB | FDA listed | — |
| topiramate 25 mg 67046-1180-03 | Coupler | 30 tablets | — | AB | FDA listed | — |
| Topiramate 25 mgthis 68071-1971-03 | NuCare | 30 tablets | — | AB | FDA listed | — |
| topiramate 25 mg 68071-3660-03 | NuCare | 30 tablets | — | AB | FDA listed | — |
| topiramate 25 mg 68382-0138-01 | Zydus | 100 tablets | — | AB | FDA listed | — |
| topiramate 25 mg 68788-7460-03 | Preferred | 30 tablets | — | AB | FDA listed | — |
| topiramate 25 mg 68788-8817-03 | Preferred | 30 tablets | — | AB | FDA listed | — |
| topiramate 25 mg 70518-0233-00 | REMEDYREPACK | 30 tablets | — | AB | FDA listed | — |
| Topiramate 25 mg 70518-0625-01 | REMEDYREPACK | 30 tablets | — | AB | FDA listed | — |
| topiramate 25 mg 70518-1718-01 | REMEDYREPACK | 1 tablet | — | AB | FDA listed | — |
| topiramate 25 mg 70518-4515-00 | REMEDYREPACK | 120 tablets | — | AB | FDA listed | — |
| topiramate 25 mg 71205-0202-30 | Proficient | 30 tablets | — | AB | FDA listed | — |
| Topiramate 25 mg 71205-0214-30 | Proficient | 30 tablets | — | AB | FDA listed | — |
| topiramate 25 mg 71205-0233-30 | Proficient | 30 tablets | — | AB | FDA listed | — |
| Topiramate 25 mg 71335-0548-00 | Bryant | 28 tablets | — | AB | Discontinued | — |
| topiramate 25 mg 71335-1684-00 | Bryant | 28 tablets | — | AB | FDA listed | — |
| topiramate 25 mg 71335-9727-00 | Bryant | 28 tablets | — | AB | FDA listed | — |
| Topiramate 25 mg 71610-0485-30 | Aphena | 30 tablets | — | AB | FDA listed | — |
| topiramate 25 mg 72162-2480-00 | Bryant | 1000 tablets | — | AB | FDA listed | — |
| Topiramate 25 mg 72789-0471-90 | PD-Rx | 90 tablets | — | AB | FDA listed | — |
| Topiramate 25 mg 72865-0313-10 | XLCare | 1000 tablets | — | AB | FDA listed | — |
| Topiramate 25 mg 76420-0278-30 | Asclemed | 30 tablets | — | AB | FDA listed | — |
| Topiramate 25 mg 80425-0208-02 | Advanced | 30 tablets | — | AB | FDA listed | — |
| Topiramate 25 mg 80425-0288-01 | Advanced | 30 tablets | — | AB | FDA listed | — |
| topiramate 25 mg 80425-0576-01 | Advanced | 30 tablets | — | AB | FDA listed | — |
| Topiramate 25 mg 87441-0079-01 | Unit | 30 tablets | — | AB | FDA listed | — |
| Topiramate 25 mg 70518-2517-00 | REMEDYREPACK | 30 tablets | — | AB | Discontinued | — |
Where does this data come from?
⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 68071-1971-03 You're viewing this | 30 TABLET in 1 BOTTLE (68071-1971-3) | 2017-02-21 | Active |
| 68071-1971-06 | 60 TABLET in 1 BOTTLE (68071-1971-6) | 2017-02-21 | Active |
| 68071-1971-09 | 90 TABLET in 1 BOTTLE (68071-1971-9) | 2017-02-21 | Active |
You're viewing the smallest of 3 pack sizes for this product.
Pack size FAQ
What quantity is in NDC 68071-1971-03?
What is the difference between NDC 68071-1971-03 and NDC 68071-1971-06?
What NDC number is used to bill for this package of Topiramate 25 mg Tablet?
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
Questions about this listing
Why is there no price listed?
Is the NDC printed on the package the same as the 11-digit billing NDC?
What do the three segments of this NDC mean?
Is this package still being marketed?
Does this product come in other package sizes?
Who lists this product with the FDA?
Do I need a prescription for this product?
Where does this data come from?
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Topiramate tablets USP is an antiepileptic (AED) agent indicated for: Monotherapy epilepsy: Initial monotherapy in patients ≥ 2 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 )
1.1Monotherapy Epilepsy Topiramate tablets USP are indicated as initial monotherapy in patients 2 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) ] .
1.2Adjunctive 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) ] .
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION See DOSAGE AND ADMINISTRATION, Epilepsy: Monotherapy and Adjunctive Therapy Use for additional details Initial Dose Titration Recommended Dose Epilepsy monotherapy: children 2to<10years (2.1 ) 25mg/day administered nightly for the first week The dosage should betitratedover5–7 weeks Daily doses in two divided doses based on weight(Table2) Epilepsy monotherapy: adults and pediatric patients≥10years (2.1 ) 50mg/day in two divided doses The dosage should be increased weekly by increments of 50mg for the first 4 weeks then100mgfor weeks 5to6.
400 mg/day in two divided doses Epilepsy adjunctive therapy :adults with partial onset seizures or LGS( 2.1 ) 25to50mg/day The dosage should be increased weekly to an effective dose by incrementsof25to50mg. 200–400 mg/day in two divided doses Epilepsy adjunctive therapy: adults with primary generalized tonic- clonic seizures (2.1 ) 25to50mg/day The dosage should be increased weekly to an effective dose by incrementsof25to50mg. 400 mg/day in two divided doses Epilepsy adjunctive therapy: pediatric Patients with partial onset seizures, primary generalized tonic-clonic seizures or LGS(186 2.1) 25mg/day(or less, based on a range of1to3mg/kg/day) nightly for the first week The dosage should beincreasedat1-or 2-weekintervalsby incrementsof1to3 mg/kg/day(administered in two divided doses).Dose titration should be guided by clinical outcome.
5to9mg/kg/day in two divided doses
2.1Epilepsy It is not necessary to monitor topiramate plasma concentrations to optimize topiramate therapy. On occasion, the addition of topiramate to phenytoin may require an adjustment of the dose of phenytoin to achieve optimal clinical outcome. Addition or withdrawal of phenytoin and/or carbamazepine during adjunctive therapy with topiramate may require adjustment of the dose of topiramate.
Because of the bitter taste, tablets should not be broken. Topiramate tablets USP can be taken without regard to meals. Monotherapy Use Adults and Pediatric Patients 10 Years and Older The recommended dose for topiramate monotherapy in adults and pediatric patients 10 years of age and older is 400 mg/day in two divided doses.
Approximately 58% of patients randomized to 400 mg/day achieved this maximal dose in the monotherapy controlled trial; the mean dose achieved in the trial was 275 mg/day. The dose should be achieved by titration according to the following schedule (Table 1): Table 1: Monotherapy Titration Schedule for Adults and Pediatric Patients 10 years and older Morning Dose Evening Dose Week 1 25 mg 25 mg Week 2 50 mg 50 mg Week 3 75 mg 75 mg Week 4 100 mg 100 mg Week 5 150 mg 150 mg Week 6 200 mg 200 mg Children Ages 2 to <10 Years Dosing of topiramate as initial monotherapy in children 2 to < 10 years of age with partial onset or primary generalized tonic-clonic seizures was based on a pharmacometric bridging approach [see Clinical Studies ( 14.1 ) ] Dosing in patients 2 to <10 years is based on weight.
During the titration period, the initial dose of topiramate should be 25 mg/day administered nightly for the first week. Based upon tolerability, the dosage can be increased to 50 mg/day (25 mg twice daily) in the second week. Dosage can be increased by 25–50 mg/day each subsequent week as tolerated.
Titration to the minimum maintenance dose should be attempted over 5–7 weeks of the total titration period. Based upon tolerability and seizure control, additional titration to a higher dose (up to the maximum maintenance dose) can be attempted at 25–50 mg/day weekly increments. The total daily dose should not exceed the maximum maintenance dose for each range of body weight (Table 2).
Table 2: Monotherapy Target Total Daily Maintenance Dosing for Patients 2 to <10 Years * Administered in two equally divided doses Weight ( kg ) Total Daily Dose ( mg / day ) * Minimum Maintenance Dose Total Daily Dose ( mg / day ) * Maximum Maintenance Dose Up to 11 150 250 12 – 22 200 300 23 – 31 200 350 32 – 38 250 350…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Tablets: 25 mg, 50 mg, 100 mg, and 200 mg Topiramate tablets USP are available in the following strengths and colors: 25 mg, White colored, circular, biconvex film-coated tablets, debossed with "122" on one side and "C" on the other side 50 mg, Light orange colored, circular, biconvex, film-coated tablets, debossed with "123" on one side and "C" on the other side. 100 mg, Orange colored, circular, biconvex, film-coated tablets, debossed with "124" on one side and "Cipla" on the other side.
200 mg, Pink colored, capsule shaped, biconvex, film-coated tablets, debossed with "125" on one side and "Cipla" on other side.
⛔ Contraindications ▾
4 CONTRAINDICATIONS None None
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Acute myopia and secondary angle closure glaucoma: Untreated elevated intraocular pressure can lead to permanent visual loss. The primary treatment to reverse symptoms is discontinuation of topiramate as rapidly as possible ( 5.1 ) Visual field defects: These have been reported independent of elevated intraocular pressure. Consider discontinuation of topiramate ( 5.2 ) Oligohidrosis and hyperthermia: Monitor decreased sweating and increased body temperature, especially in pediatric patients ( 5.3 ) Metabolic acidosis: Baseline and periodic measurement of serum bicarbonate is recommended.
Consider dose reduction or discontinuation of topiramate if clinically appropriate ( 5.4 ) Suicidal behavior and ideation: Antiepileptic drugs increase the risk of suicidal behavior or ideation ( 5.5 ) Cognitive/neuropsychiatric: Topiramate may cause cognitive dysfunction. Patients should use caution when operating machinery including automobiles. Depression and mood problems may occur in epilepsy populations ( 5.6 ) Fetal Toxicity: Topiramate use during pregnancy can cause cleft lip and/or palate ( 5.7 ) Withdrawal of AEDs: Withdrawal of topiramate should be done gradually ( 5.8 ) Hyperammonemia and encephalopathy associated with or without concomitant valproic acid use: Patients with inborn errors of metabolism or reduced mitochondrial activity may have an increased risk of hyperammonemia.
Measure ammonia if encephalopathic symptoms occur ( 5.10 ) Kidney stones: Use with other carbonic anhydrase inhibitors, other drugs causing metabolic acidosis, or in patients on a ketogenic diet should be avoided ( 5.11 ) Hypothermia has been reported with and without hyperammonemia during topiramate treatment with concomitant valproic acid use ( 5.12 )
5.1Acute Myopia and Secondary Angle Closure Glaucoma A syndrome consisting of acute myopia associated with secondary angle closure glaucoma has been reported in patients receiving topiramate. Symptoms include acute onset of decreased visual acuity and/or ocular pain. Ophthalmologic findings can include myopia, anterior chamber shallowing, ocular hyperemia (redness), and increased intraocular pressure.
Mydriasis may or may not be present. This syndrome may be associated with supraciliary effusion resulting in anterior displacement of the lens and iris, with secondary angle closure glaucoma. Symptoms typically occur within 1 month of initiating topiramate therapy.
In contrast to primary narrow angle glaucoma, which is rare under 40 years of age, secondary angle closure glaucoma associated with topiramate has been reported in pediatric patients as well as adults. The primary treatment to reverse symptoms is discontinuation of topiramate as rapidly as possible, according to the judgment of the treating physician. Other measures, in conjunction with discontinuation of topiramate, may be helpful.
Elevated intraocular pressure of any etiology, if left untreated, can lead to serious sequelae including permanent vision loss.
5.2Visual Field Defects Visual field defects (independent of elevated intraocular pressure) have been reported in clinical trials and in post marketing experience in patients receiving topiramate. In clinical trials, most of these events were reversible after topiramate discontinuation. If visual problems occur at any time during topiramate treatment, consideration should be given to discontinuing the drug.
5.3Oligohidrosis and Hyperthermia Oligohidrosis (decreased sweating), infrequently resulting in hospitalization, has been reported in association with topiramate use. Decreased sweating and an elevation in body temperature above normal characterized these cases. Some of the cases were reported after exposure to elevated environmental temperatures.
The majority of the reports have been in pediatric patients. Patients, especially pediatric patients, treated with topiramate should be monitored closely for evidence of decreased sweating and increased body temperature…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS 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 Cipla Ltd, at 1-866-604-3268 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 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 data described in the following sections were obtained using topiramate tablets.
6.1Clinical Trial Experience Monotherapy Epilepsy 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. Increased Risk for Bleeding Topiramate tablets treatment is associated with an increased risk for bleeding. In a pooled analysis of placebo-controlled studies of approved and unapproved indications, bleeding was more frequently reported as an adverse event for topiramate tablets than for placebo (4.5% versus 3.0% in adult patients, and 4.4% versus 2.3% in pediatric patients).
In this analysis, the incidence of serious bleeding events for topiramate tablets and placebo was 0.3% versus 0.2% for adult patients, and 0.4% versus 0% for pediatric patients. Adverse bleeding reactions reported with topiramate tablets ranged from mild epistaxis, ecchymosis, and increased menstrual bleeding to life-threatening hemorrhages. In patients with serious bleeding events, conditions that increased the risk for bleeding were often present, or patients were often taking drugs that cause thrombocytopenia (other antiepileptic drugs) or affect platelet function or coagulation (e.g., aspirin, nonsteroidal anti-inflammatory drugs, selective serotonin reuptake inhibitors, or warfarin or other anticoagulants).
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 a rate higher (≥ 5 %) than in the 50 mg/day group were: paresthesia, weight decrease, anorexia, somnolence, and difficulty with memory (see Table 5 ). 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 oc…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Summary of antiepileptic drug (AED) interactions with topiramate tablets ( 7.1 ) AED Co - administered AED Concentration Topiramate Concentration Phenytoin NCor25%increase a 48%decrease Carbamazepine(CBZ) NC 40%decrease CBZepoxide b NC NE Valproic acid 11%decrease 14%decrease Phenobarbital NC NE Primidone NC NE Lamotrigine NCatTPM dosesupto400 mg/day 13%decrease Oral contraceptives: Decreased contraceptive efficacy and increased breakthrough bleeding should be considered, especially at doses greater than 200 mg/day ( 7.3 ) Metformin is contraindicated with metabolic acidosis, an effect of topiramate tablets ( 7.4 ) Lithium levels should be monitored when co-administered with high-dose topiramate tablets ( 7.5 ) Other carbonic anhydrase inhibitors: Monitor the patient for the appearance or worsening of metabolic acidosis ( 7.6 ) In vitro studies indicate that topiramate does not inhibit enzyme activity for CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, CYP2E1, and CYP3A4/5 isozymes.
In vitro studies indicate that topiramate is a mild inhibitor of CYP2C19 and a mild inducer of CYP3A4. Drug interactions with some antiepileptic drugs, CNS depressants and oral contraceptives are described here. For other drug interactions, please refer to Clinical Pharmacology ( 12.3 ) .
7.1Antiepileptic Drugs Potential interactions between topiramate and standard AEDs were assessed in controlled clinical pharmacokinetic studies in patients with epilepsy. Concomitant administration of phenytoin or carbamazepine with topiramate decreased plasma concentrations of Topiramate by 48% and 40%, respectively when compared to topiramate given alone [see Clinical Pharmacology ( 12.3 ).] Concomitant administration of valproic acid and topiramate tablets has been associated with hyperammonemia with and without encephalopathy.
Concomitant administration of topiramate tablets with valproic acid has also been associated with hypothermia (with and without hyperammonemia) in patients who have tolerated either drug alone. It may be prudent to examine blood ammonia levels in patients in whom the onset of hypothermia has been reported [see Warnings and Precautions ( 5.10 ), ( 5.12 ) or Clinical Pharmacology ( 12.3 )] .
7.2CNS Depressants Concomitant administration of topiramate tablets 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, topiramate tablets should be used with extreme caution if used in combination with alcohol and other CNS depressants.
7.3Oral Contraceptives Exposure to ethinyl estradiol was statistically significantly decreased at doses of 200, 400, and 800 mg/day (18%, 21%, and 30%, respectively) when topiramate tablets was given as adjunctive therapy in patients taking valproic acid. However, norethindrone exposure was not significantly affected. In another pharmacokinetic interaction study in healthy volunteers with a concomitantly administered combination oral contraceptive product containing 1 mg norethindrone (NET) plus 35 mcg ethinyl estradiol (EE), topiramate tablets, given in the absence of other medications at doses of 50 to 200 mg/day, was not associated with statistically significant changes in mean exposure (AUC) to either component of the oral contraceptive.
The possibility of decreased contraceptive efficacy and increased breakthrough bleeding should be considered in patients taking combination oral contraceptive products with topiramate tablets. Patients taking estrogen-containing 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 )].
7.4Metformin Topiramate treatment can frequently cause metabolic acidosis, a condition for which the use of metformin is contraindicated [ see Clinical Pharmacology ( 12.3 )]…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Renal impairment: In renally impaired patients (creatinine clearance less than 70 mL/min/1.73 m 2 ), one-half of the adult dose is recommended ( 2.4 ) Patients undergoing hemodialysis: Topiramate is cleared by hemodialysis. Dosage adjustment is necessary to avoid rapid drops in topiramate plasma concentration during hemodialysis ( 2.6 ) Pregnancy: Increased risk of cleft lip and/or palate. Pregnancy registry available ( 8.1 ).
Nursing mothers: Caution should be exercised when administered to a nursing mother ( 8.3 ) Geriatric use: Dosage adjustment may be necessary for elderly with impaired renal function ( 8.5 )
8.1Pregnancy Pregnancy Category D [see Warnings and Precautions 5.7 ] Topiramate tablets can cause fetal harm when administered to a pregnant woman. Data from pregnancy registries indicate that infants exposed to topiramate in utero have an increased risk for cleft lip and/or cleft palate (oral clefts). When multiple species of pregnant animals received topiramate at clinically relevant doses, structural malformations, including craniofacial defects, and reduced fetal weights occurred in offspring.
Topiramate tablets should be used during pregnancy only if the potential benefit outweighs the potential risk. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus [see Use in Specific Populations ( 8.9 )] . Pregnancy Registry 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.massgeneral.org/aed/ .
Human Data Data from the NAAED Pregnancy Registry (425 prospective topiramate monotherapy-exposed pregnancies) indicate an increased risk of oral clefts in infants exposed during the first trimester of pregnancy. The prevalence of oral clefts among topiramate-exposed infants was 1.2% compared to a prevalence of 0.39% for infants exposed to a reference AED. In infants of mothers without epilepsy or treatment with other AEDs.
The prevalence was 0.12%. For comparison, the Centers for Disease Control and Prevention (CDC) reviewed available data on oral clefts in the United States and found a similar background rate of 0.17%. The relative risk of oral clefts in topiramate-exposed pregnancies in the NAAED Pregnancy Registry was 9.6 (95% Confidence Interval [CI] 4.0 – 23.0) as compared to the risk in a background population of untreated women.
The UK Epilepsy and Pregnancy Register reported a similarly increased prevalence of oral clefts of 3.2% among infants exposed to topiramate monotherapy. The observed rate of oral clefts was 16 times higher than the background rate in the UK, which is approximately 0.2%. Topiramate tablets 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 topiramate tablets should be monitored for metabolic acidosis because of transfer of topiramate to the fetus and possible occurrence of transient metabolic acidosis following birth.
Animal Data Topiramate has demonstrated selective developmental toxicity, including teratogenicity, in multiple animal species at clinically relevant doses. When oral doses of 20, 100, or 500 mg/kg were administered to pregnant mice during…
🆘 Overdosage ▾
10 OVERDOSAGE Overdoses of topiramate tablets 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 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
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action The precise mechanisms by which topiramate exerts its anticonvulsant are unknown; however, preclinical studies have revealed four properties that may contribute to topiramate efficacy for epilepsy. 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.
12.2Pharmacodynamics Topiramate has anticonvulsant activity in rat and mouse maximal electroshock seizure (MES) tests. Topiramate is only weakly effective in blocking clonic seizures induced by the GABA A receptor antagonist, pentylenetetrazole. Topiramate is also effective in rodent models of epilepsy, which include tonic and absence-like seizures in the spontaneous epileptic rat (SER) and tonic and clonic seizures induced in rats by kindling of the amygdala or by global ischemia.
12.3Pharmacokinetics Absorption of topiramate is rapid, with peak plasma concentrations occurring at approximately 2 hours following a 400 mg oral dose. The relative bioavailability of topiramate from the tablet formulation is about 80% compared to a solution. The bioavailability of topiramate is not affected by food.
The pharmacokinetics of topiramate are linear with dose proportional increases in plasma concentration over the dose range studied (200 to 800 mg/day). The mean plasma elimination half-life is 21 hours after single or multiple doses. Steady-state is thus reached in about 4 days in patients with normal renal function.
Topiramate is 15% to 41% bound to human plasma proteins over the blood concentration range of 0.5 to 250 μg/mL. The fraction bound decreased as blood concentration increased. Carbamazepine and phenytoin do not alter the binding of topiramate.
Sodium valproate, at 500 μg/mL (a concentration 5 to 10 times higher than considered therapeutic for valproate) decreased the protein binding of topiramate from 23% to 13%. Topiramate does not influence the binding of sodium valproate. Metabolism and Excretion Topiramate is not extensively metabolized and is primarily eliminated unchanged in the urine (approximately 70% of an administered dose).
Six metabolites have been identified in humans, none of which constitutes more than 5% of an administered dose. The metabolites are formed via hydroxylation, hydrolysis, and glucuronidation. There is evidence of renal tubular reabsorption of topiramate.
In rats, given probenecid to inhibit tubular reabsorption, along with topiramate, a significant increase in renal clearance of topiramate was observed. This interaction has not been evaluated in humans. Overall, oral plasma clearance (CL/F) is approximately 20 to 30 mL/min in adults following oral administration.
Special Populations Renal Impairment The clearance of topiramate was reduced by 42% in moderately renally impaired (creatinine clearance 30 to 69 mL/min/1.73m 2 ) and by 54% in severely renally impaired subjects (creatinine clearance <30 mL/min/1.73m 2 ) compared to normal renal function subjects (creatinine clearance >70 mL/min/1.73m 2 ). Since topiramate is presumed to undergo significant tubular reabsorption, it is uncertain whether this experience can be generalized to all situations of renal impairment. It is conceivable that some forms of renal disease could differentially affect glomerular filtration rate and tubular reabsorption resulting in a clearance of topiramate not predicted by creatinine clearance.
In general, however, use of one-half the usual starting and maintenance dose is recommended in patients with moderate or severe renal impairment [see Dosage and Administration ( 2.4 ) and ( 2.5 ) and Warnings and Precautions ( 5.14 )] . Hemodialysis Topiramate is cleared by hemodia…
🧬 Mechanism of Action ▾
12.1Mechanism of Action The precise mechanisms by which topiramate exerts its anticonvulsant are unknown; however, preclinical studies have revealed four properties that may contribute to topiramate efficacy for epilepsy. 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.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How Supplied Topiramate tablets USP are available in the following strengths and colors: 25 mg, White colored, circular, biconvex film-coated tablets, debossed with "122" on one side and "C" on the other side and are available in Bottles of 30 NDC 68071-1971-3 Bottles of 60 NDC 68071-1971-6 Bottles of 90 NDC 68071-1971-9 PHARMACIST: Dispense in a tight container as defined in the USP. Use child-resistant closure (as required).
16.2Storage and Handling Store at 20°C to 25°C (68°F to 77°F) [See USP controlled room temperature]. Protect from moisture.
16.1How Supplied Topiramate tablets USP are available in the following strengths and colors: 25 mg, White colored, circular, biconvex film-coated tablets, debossed with "122" on one side and "C" on the other side and are available in Bottles of 30 NDC 68071-1971-3 Bottles of 60 NDC 68071-1971-6 Bottles of 90 NDC 68071-1971-9 PHARMACIST: Dispense in a tight container as defined in the USP. Use child-resistant closure (as required).
📦 Storage and Handling ▾
16.2Storage and Handling Store at 20°C to 25°C (68°F to 77°F) [See USP controlled room temperature]. Protect from moisture.
📋 Description ▾
11 DESCRIPTION Topiramate is a sulfamate-substituted monosaccharide. Topiramate tablets USP are available as 25mg, 50 mg and 100 mg circular tablets and 200 mg capsule shaped tablets for oral administration. Topiramate USP 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 339.36. Topiramate is designated chemically as 2,3:4,5Di- O -isopropylidene-ß-D-fructopyranose sulfamate and has the following structural formula: Each tablet, for oral administration, contains 25 mg, 50 mg, 100 mg and 200 mg topiramate and has the following inactive ingredients: hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, pregelatinized starch, sodium starch glycolate and titanium dioxide.
In addition, the 25 mg also contains FD&C Blue #2; the 50 mg and 100 mg also contain red iron oxide and yellow iron oxide; and the 200 mg also contains red iron oxide. topi
💬 Medication Guide ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Eye Disorders Instruct patient taking topiramate tablets should be told to seek immediate medical attention if they experience blurred vision, visual disturbances, or periorbital pain [see Warnings and Precautions Oligohidrosis and Hyperthermia Closely monitor topiramate tablets-treated pateints, especially pediatric patients, for evidence of decreased sweating and increased body temperature, especially in hot weather.
Counsel patient 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 ) and 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 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 Even when taking topiramate tablets other anticonvulsants, some patients with epilepsy will continue to have unpredictable seizures.
Therefore, advise all patients taking topiramate tablets 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 tablets during pregnancy can cause fetal harm, including an increased risk for cleft lip and/or cleft palate (oral clefts), which occur early in pregnancy before many women know they are pregnant. There may also be risks to the fetus from chronic metabolic acidosis with use of Topiramateduring pregnancy [see Warnings and Precautions and Use in Specific Populations . When appropriate, counsel pregnant women and women of childbearing potential about alternative therapeutic options.
This is particularly important when topiramate tablets is considered for a condition not usually associated with permanent injury or death. Advise women of childbearing potential who are not planning a pregnancy to use effective contraception while using topiramate tablets, keeping in mind that there is a potential for decreased contraceptive efficacy when using estrogen-containing birth control with topiramate [see Drug Interactions Encourage pregnant women using topiramate tablets, to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry.
The registry is collecting information about the safety of antiepileptic drugs during pregnancy. To enroll, patients ca…