Topiramat acis Uses

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What is Topiramat acis?

Topiramat acis is a seizure medicine, also called an anticonvulsant. Topiramat acis is used to treat seizures in adults and children who are at least 2 years old. Trokendi XR is for use in adults and children who are at least 6 years old.

Extended-release Topiramat acis has a higher minimum age (at least 10 years old) when used as the child's only seizure medicine.

The Topiramat acis brand of this medicine is also used to prevent migraine headaches in adults and teenagers who are at least 12 years old. Topiramat acis will only prevent migraine headaches or reduce the number of attacks. It will not treat a headache that has already begun.

Topiramat acis may also be used for purposes not listed in this medication guide.

Topiramat acis indications

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Monotherapy Epilepsy

Topiramat acis Tablets and Topiramat acis capsules (sprinkle) 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.

Adjunctive Therapy Epilepsy

Topiramat acis Tablets and Topiramat acis capsules (sprinkle) 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.

Additional pediatric use information for patients ages 12 to 17 years is approved for Janssen Pharmaceuticals, Inc.'s Topiramat acis (Topiramat acis) Tablets and Sprinkle Capsules. However, due to Janssen Pharmaceuticals, Inc.'s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

Migraine

Topiramat acis Tablets and Topiramat acis capsules (sprinkle) are indicated for adults for the prophylaxis of migraine headache. The usefulness of Topiramat acis in the acute treatment of migraine headache has not been studied.

How should I use Topiramat acis?

Use Topiramat acis extended-release capsules as directed by your doctor. Check the label on the medicine for exact dosing instructions.

Ask your health care provider any questions you may have about how to use Topiramat acis extended-release capsules.

Uses of Topiramat acis in details

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Use: Labeled Indications

Migraine (prevention): Prophylaxis of migraine headache in patients ≥12 years of age

Seizures: Monotherapy or adjunctive therapy in patients ≥2 years of age (immediate release and Topiramat acis) or ≥6 years of age (Trokendi XR) with focal (partial) onset or primary generalized tonic-clonic seizures; adjunctive therapy in patients ≥2 years of age (immediate release and Topiramat acis) or ≥6 years of age (Trokendi XR only) with seizures associated with Lennox-Gastaut syndrome

Off Label Uses

Antipsychotic-induced weight gain

Data from multiple meta-analyses with varying degrees of heterogeneity support the use of Topiramat acis in promoting modest weight loss and preventing weight gain associated with second-generation antipsychotics in patients with schizophrenia (evidence is more limited in patients with bipolar disorder).

Based on the American Academy of Neurology practice parameter for the treatment of essential tremor, Topiramat acis is probably effective and may be considered as an alternative agent for the treatment of limb tremor associated with essential tremor.

Topiramat acis description

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Topiramat acis is a sulfamate-substituted monosaccharide. Topiramat acis tablets are available as 50 mg round tablets for oral administration.

Topiramat acis is a white crystalline powder with a bitter taste. Topiramat acis 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. Topiramat acis has the molecular formula C12H21NO8S and a molecular weight of 339.36. Topiramat acis is designated chemically as 2,3:4,5-Di-O-isopropylidene-ß-D-fructopyranose sulfamate.

Excipients/Inactive Ingredients: Microcrystalline cellulose Ph. Eur., mannitol Ph. Eur., sodium starch glycolate Type A Ph. Eur., pregelatinized starch L.M.Ph. Eur., crospovidone Ph. Eur., povidone Ph. Eur., magnesium stearate Ph. Eur., carnauba wax Ph. Eur., acetone Ph. Eur., opadry II white OY-LS-28908, opadry yellow 02H2229, ethyl alcohol Ph. Eur., purified water Ph. Eur.

Topiramat acis dosage

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Monotherapy Use

Adults and Pediatric Patients 10 Years and Older with Partial Onset or Primary Generalized Tonic-Clonic Seizures

The recommended dose for Topiramat acis monotherapy in adults and pediatric patients 10 years of age and older is 400 mg orally once daily. Titrate Topiramat acis Extended-Release Capsules according to the following schedule:

Adjunctive Therapy Use

Adults (17 Years of Age and Older) - Partial Onset Seizures, Primary Generalized Tonic-Clonic Seizures, or Lennox-Gastaut Syndrome

The recommended total daily dose of Topiramat acis Extended-Release Capsules as adjunctive therapy in adults with partial onset seizures or Lennox-Gastaut Syndrome is 200 mg to 400 mg orally once daily. The recommended total dose for adults 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. Daily Topiramat acis doses above 1,600 mg have not been studied.

In the study of primary generalized tonic-clonic seizures using Topiramat acis, the assigned dose was reached at the end of 8 weeks.

Pediatric Patients (Ages 2 Years to 16 Years) - Partial Onset Seizures, Primary Generalized Tonic-Clonic Seizures, or Lennox-Gastaut Syndrome

The recommended total daily dose of Topiramat acis Extended-Release Capsules as adjunctive therapy for pediatric patients 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 (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 to 3 mg/kg to achieve optimal clinical response. Dose titration should be guided by clinical outcome. If required, longer intervals between dose adjustments can be used.

In the study of primary generalized tonic-clonic seizures, the assigned dose of 6 mg/kg once daily was reached at the end of 8 weeks.

Dose Modifications in Patients with Renal Impairment

In patients with renal impairment (creatinine clearance less than 70 mL/min/1.73 m2), one-half of the usual adult dose is recommended. Such patients will require a longer time to reach steady-state at each dose.

Prior to dosing, obtain an estimated creatinine clearance (CrCl) in patients at high risk for renal insufficiency (e.g., older patients, or those with diabetes mellitus, hypertension, or autoimmune disease). CrCl can be estimated using the following equation (multiply by 0.85 for women):

Dosage Modifications in Patients Undergoing Hemodialysis

Topiramat acis is cleared by hemodialysis at a rate that is 4 to 6 times greater than in patients with normal renal function. Accordingly, a prolonged period of dialysis may cause Topiramat acis concentration to fall below that required to maintain an anti-seizure effect. To avoid rapid drops in Topiramat acis plasma concentration during hemodialysis, a supplemental dose of Topiramat acis may be required. The actual adjustment should take into account the:

Laboratory Testing Prior to Treatment Initiation

Measurement of baseline and periodic serum bicarbonate during treatment with Topiramat acis Extended-Release Capsules is recommended.

Dosing Modifications in Patients Taking Phenytoin and/or Carbamazepine

The co-administration of Topiramat acis Extended-Release Capsules with 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 Topiramat acis Extended-Release Capsules may require adjustment of the dose of Topiramat acis Extended-Release Capsules.

Monitoring for Therapeutic Blood Levels

It is not necessary to monitor Topiramat acis plasma concentrations to optimize therapy with Topiramat acis Extended-Release Capsules.

Administration Instructions

Topiramat acis Extended-Release Capsules may be swallowed whole or may be administered by carefully opening the capsule and sprinkling the entire contents on a small amount (teaspoon) of soft food. This drug/food mixture should be swallowed immediately and not chewed or crushed. Do not store drug/food mixture for further use. Topiramat acis Extended-Release Capsules can be taken without regard to meals.

Topiramat acis interactions

See also:
What other drugs will affect Topiramat acis?

Oral Contraceptives

The possibility of decreased contraceptive efficacy and increased breakthrough bleeding should be considered in patients taking combination oral contraceptive products with Topiramat acis. 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.

Antiepileptic Drugs

Concomitant administration of phenytoin or carbamazepine with Topiramat acis decreased plasma concentrations of Topiramat acis.

Concomitant administration of valproic acid and Topiramat acis has been associated with hyperammonemia with and without encephalopathy. Concomitant administration of Topiramat acis 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.

Numerous AEDs are substrates of the CYP enzyme system. In vitro studies indicate that Topiramat acis does not inhibit enzyme activity for CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, CYP2E1, and CYP3A4/5 isozymes. In vitro studies indicate that immediate-release Topiramat acis is a mild inhibitor of CYP2C19 and a mild inducer of CYP3A4. The same drug interactions can be expected with the use of Topiramat acis.

CNS Depressants And Alcohol

Topiramat acis is a CNS depressant. Concomitant administration of Topiramat acis with other CNS depressant drugs or alcohol can result in significant CNS depression. Concomitant use of alcohol should be avoided.

Other Carbonic Anhydrase Inhibitors

Concomitant use of Topiramat acis, a carbonic anhydrase inhibitor, with any other carbonic anhydrase inhibitor (e.g., zonisamide, acetazolamide or dichlorphenamide), 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 Topiramat acis is given concomitantly with another carbonic anhydrase inhibitor.

Metformin

Topiramat acis treatment can frequently cause metabolic acidosis, a condition for which the use of metformin is contraindicated. The concomitant use of Topiramat acis and metformin is contraindicated in patients with metabolic acidosis.

Lithium

In patients, there was an observed increase in systemic exposure of lithium following Topiramat acis doses of up to 600 mg per day. Lithium levels should be monitored when co-administered with high-dose Topiramat acis.

Drug Abuse And Dependence

Controlled Substance

Topiramat acis (Topiramat acis) extended-release capsule is not a controlled substance.

Abuse

The abuse and dependence potential of Topiramat acis has not been evaluated in human studies.

Dependence

Topiramat acis has not been systematically studied in animals or humans for its potential for tolerance or physical dependence.

Topiramat acis side effects

See also:
What are the possible side effects of Topiramat acis?

The following adverse reactions are discussed in more detail in other sections of the labeling:

Clinical Trials Experience With Immediate-Release Topiramat acis

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.

Increased Risk for Bleeding

Topiramat acis 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 Topiramat acis 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 Topiramat acis and placebo was 0.3% versus 0.2% for adult patients, and 0.4% versus 0% for pediatric patients.

Adverse bleeding reactions reported with Topiramat acis 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).

Adverse Reactions Observed in Monotherapy Trial

Patients 16 Years and Older

The adverse reactions in the monotherapy controlled trial (Study 1) that occurred most commonly in adults in the 400 mg per day Topiramat acis group and at an incidence ≥ 5% higher than the 50 mg per day group were paresthesia, weight decrease, somnolence, anorexia, and difficulty with memory.

Approximately 21% of the 159 adult patients in the 400 mg per day group who received Topiramat acis as monotherapy in Study 1 discontinued therapy due to adverse reactions. The most common ( ≥ 2% more frequent than for Topiramat acis 50 mg per day) adverse reactions causing discontinuation in this trial were difficulty with memory, fatigue, asthenia, insomnia, somnolence and paresthesia.

Pediatric Patients 6 to less than 16 Years of Age

The adverse reactions in Study 1 that occurred most commonly in pediatric patients in the 400 mg per day Topiramat acis group and at an incidence ≥ 5% higher than in the 50 mg per day group were fever, weight decrease, mood problems, cognitive problems, infection, flushing, and paresthesia.

Approximately 14% of the 77 pediatric patients in the 400 mg per day group who received Topiramat acis as monotherapy in Study 1 discontinued therapy due to adverse reactions. The most common ( ≥ 2% more frequent than for Topiramat acis 50 mg per day) adverse reactions resulting in discontinuation in this trial were difficulty with concentration/attention, fever, flushing, and confusion.

Table 4: Adverse Reactions in the Immediate-Release Topiramat acis Monotherapy Trial with incidence ≥ 2% in any Topiramat acis group and incidence in the 400 mg per day group greater than in the 50 mg per day group

Body System/ Adverse Reaction Age Group
Pediatric(6 to ≥ 16 Years) Adult(Age ≥ 16 Years)
Immediate-release Topiramat acis Daily Dosage

Group (mg per day)

50

(N=74) %Reactions that Occurred in at Least 1% of Topiramat acis-Treated Patients and Occurred More Frequently in Topiramat acis-Treated Than Placebo-Treated Patients

Laboratory Abnormalities

Topiramat acis decreases serum bicarbonate.

Immediate-release Topiramat acis treatment was associated with changes in several clinical laboratory analytes in randomized, double-blind, placebo-controlled studies. Similar effects should be anticipated with use of Topiramat acis.

Controlled trials of adjunctive Topiramat acis treatment of adults for partial onset seizures showed an increased incidence of markedly decreased serum phosphorus (6% Topiramat acis, 2% placebo), markedly increased serum alkaline phosphatase (3% Topiramat acis, 1% placebo), and decreased serum potassium (0.4 % Topiramat acis, 0.1 % placebo).

Changes in several clinical laboratory analytes (i.e., increased creatinine, BUN, alkaline phosphatase, total protein, total eosinophil count and decreased potassium) have been observed in a clinical investigational program in very young (2 years and younger) pediatric patients who were treated with adjunctive Topiramat acis for partial onset seizures.

Topiramat acis treatment produced a dose-related increased shift in serum creatinine from normal at baseline to an increased value at the end of 4 months treatment in adolescent patients (ages 12 years to 16 years) in a double-blind, placebo-controlled study. The incidence of these abnormal shifts was 4% for placebo, 4% for 50 mg, and 18% for 100 mg.

Topiramat acis treatment with or without concomitant valproic acid (VPA) can cause hyperammonemia with or without encephalopathy.

Clinical Trials Experience With Topiramat acis

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. In the Topiramat acis study, a dose of 200 mg per day was administered to a limited number of patients; therefore, these results cannot be directly compared to immediate-release Topiramat acis experience.

The safety data presented below are from 249 patients with partial epilepsy on concomitant AEDs who participated in the Topiramat acis study.

Table 9 displays the incidence of treatment-emergent adverse reactions that occurred in ≥ 2% of patients and numerically greater than placebo.

Table 9: Incidence ( ≥ 2%) of Treatment-Emergent Adverse Reactions in Placebo-Controlled Adjunctive Therapy Clinical Trial in Patients With Partial Onset Seizures

Body System/ Adverse Reaction Placebo

(N=125)

Topiramat acis (200 mg)

(N=124)

General Disorders
Fatigue 5 6
Asthenia 1 2
Irritability 1 2
Nervous System Disorders
Somnolence 2 12
Dizziness 6 7
Paresthesia 2 7
Aphasia 0 2
Dysarthria 1 2
Memory impairment 1 2
Psychiatric Disorder
Psychomotor retardation 0 2
Cardiovascular Disorders, General
Hypertension 1 3
Metabolic and Nutritional Disorders
Weight decrease 0 7
Decreased appetite 2 4
Anorexia 1 2

In the controlled clinical study using Topiramat acis, 8.9% of patients who received Topiramat acis and 4.0% who received placebo discontinued as a result of treatment-emergent adverse reactions.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Topiramat acis. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The listing is alphabetized: bullous skin reactions (including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis), hepatic failure (including fatalities), hepatitis, maculopathy, pancreatitis, and pemphigus.

Topiramat acis contraindications

See also:
What is the most important information I should know about Topiramat acis?

Topiramat acis may cause harm to an unborn baby, but having a seizure during pregnancy could harm both the mother and the baby. Tell your doctor right away if you become pregnant while taking Topiramat acis for seizures. Do not start or stop taking Topiramat acis during pregnancy without your doctor's advice.

Seek emergency medical attention if you have a sudden change in vision or pain around or behind the eyes. These may be early signs of a serious and permanent side effect on your vision.

Do not stop using Topiramat acis without first talking to your doctor, even if you feel fine. You may have increased seizures if you stop using Topiramat acis suddenly. You may need to use less and less before you stop the medication completely.

Contact your doctor if your seizures get worse or you have them more often while taking Topiramat acis.

Active ingredient matches for Topiramat acis:

Topiramate in Germany.


List of Topiramat acis substitutes (brand and generic names)

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Unit description / dosage (Manufacturer)Price, USD
Tablet; Oral; Topiramate 100 mg
Tablet; Oral; Topiramate 200 mg
Tablet; Oral; Topiramate 25 mg
Tablet; Oral; Topiramate 50 mg
Capsule; Oral; Topiramate 15 mg
Capsule; Oral; Topiramate 25 mg
Topiramate 200 mg tablet$ 8.32
Topamax 200 mg tablet$ 7.68
Topiramate 100 mg tablet$ 7.11
Topamax 100 mg tablet$ 6.31
Topamax 50 mg tablet$ 5.96
Topiramate 50 mg tablet$ 5.21
Topiramate 25 mg Sprinkle Capsule$ 3.04
Topiramate 25 mg tablet$ 2.61
Topiramate 99.7% powder$ 2.59
Topiramate 15 mg Sprinkle Capsule$ 2.52
Topamax 25 mg tablet$ 2.46
Co Topiramate 200 mg Tablet$ 2.08
Mylan-Topiramate 200 mg Tablet$ 2.08
Novo-Topiramate 200 mg Tablet$ 2.08
Phl-Topiramate 200 mg Tablet$ 2.08
Pms-Topiramate 200 mg Tablet$ 2.08
Ratio-Topiramate 200 mg Tablet$ 2.08
Sandoz Topiramate 200 mg Tablet$ 2.08
Topamax Sprinkle 25 mg Capsule$ 1.35
Sandoz Topiramate 100 mg Tablet$ 1.31
Co Topiramate 100 mg Tablet$ 1.31
Mylan-Topiramate 100 mg Tablet$ 1.31
Novo-Topiramate 100 mg Tablet$ 1.31
Phl-Topiramate 100 mg Tablet$ 1.31
Pms-Topiramate 100 mg Tablet$ 1.31
Ratio-Topiramate 100 mg Tablet$ 1.31
Topamax Sprinkle 15 mg Capsule$ 1.29
Pms-Topiramate 50 mg Tablet$ 1.05
Co Topiramate 25 mg Tablet$ 0.69
Mylan-Topiramate 25 mg Tablet$ 0.69
Novo-Topiramate 25 mg Tablet$ 0.69
Phl-Topiramate 25 mg Tablet$ 0.69
Pms-Topiramate 25 mg Tablet$ 0.69
Ratio-Topiramate 25 mg Tablet$ 0.69
Sandoz Topiramate 25 mg Tablet$ 0.69
Topiramate tablet 200 mg (Sivem Pharmaceuticals Ulc (Canada))
Topiramate tablet 25 mg (Sanis Health Inc (Canada))
Topiramate capsule, extended release 100 mg/1 (REMEDYREPACK INC. (US))
Topiramate capsule, extended release 200 mg/1 (Upsher Smith Laboratories, Inc. (US))
Topiramate tablet 100 mg (Sanis Health Inc (Canada))
Topiramate capsule, extended release 25 mg/1 (Upsher Smith Laboratories, Inc. (US))
Topiramate capsule, extended release 150 mg/1 (Upsher Smith Laboratories, Inc. (US))
Topiramate capsule, extended release 50 mg/1 (Upsher Smith Laboratories, Inc. (US))
Topiramate tablet 50 mg (Sivem Pharmaceuticals Ulc (Canada))
Topiramate tablet, film coated 50 mg/1 (Rebel Distributors Corp (US))
Topiramate tablet, film coated 25 mg/1 (Sun Pharma Global FZE (US))
Topiramate tablet 25 mg/1 (Unit Dose Services (US))
Topiramate tablet, film coated 100 mg/1 (REMEDYREPACK INC. (US))
Topiramate tablet, coated 25 mg/1 (Hangzhou Minsheng Binjiang Pharmaceutical CO., Ltd (US))
Topiramate tablet, film coated 200 mg/1 (Sun Pharmaceutical Industries Limited (US))
Topiramate capsule, coated pellets 15 mg/1 (Teva Pharmaceuticals Usa, Inc. (US))
Topiramate tablet 50 mg/1 (Preferred Pharmaceuticals, Inc. (US))
Topiramate tablet 100 mg/1 (REMEDYREPACK INC. (US))
Topiramate tablet 200 mg/1 (Torrent Pharmaceuticals Limited (US))
Topiramate capsule, coated pellets 25 mg/1 (Cadila Healthcare Limited (US))
Topiramate tablet, coated 200 mg/1 (Upsher Smith Laboratories, Inc. (US))
Topiramate tablet, coated 100 mg/1 (Upsher Smith Laboratories, Inc. (US))
Topiramate tablet, coated 50 mg/1 (Hangzhou Minsheng Binjiang Pharmaceutical CO., Ltd (US))
Topiramate tablet 200 1/1 (Cipla USA Inc. (US))
Topiramate tablet 25 meq/1 (Cipla USA Inc. (US))

References

  1. DailyMed. "TOPIRAMATE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
  2. PubChem. "topiramate". https://pubchem.ncbi.nlm.nih.gov/com... (accessed September 17, 2018).
  3. DrugBank. "topiramate". http://www.drugbank.ca/drugs/DB00273 (accessed September 17, 2018).

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