Topiramaat Apotex Uses

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What is Topiramaat Apotex?

Topiramaat Apotex is a seizure medicine, also called an anticonvulsant. Topiramaat Apotex 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 Topiramaat Apotex has a higher minimum age (at least 10 years old) when used as the child's only seizure medicine.

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

Topiramaat Apotex may also be used for purposes not listed in this medication guide.

Topiramaat Apotex indications

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Monotherapy Epilepsy

Topiramaat Apotex Tablets and Topiramaat Apotex 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

Topiramaat Apotex Tablets and Topiramaat Apotex 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 Topiramaat Apotex (Topiramaat Apotex) 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

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

How should I use Topiramaat Apotex?

Use Topiramaat Apotex 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 Topiramaat Apotex extended-release capsules.

Uses of Topiramaat Apotex 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 Topiramaat Apotex) 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 Topiramaat Apotex) 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 Topiramaat Apotex 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, Topiramaat Apotex is probably effective and may be considered as an alternative agent for the treatment of limb tremor associated with essential tremor.

Topiramaat Apotex description

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

Topiramaat Apotex is a white crystalline powder with a bitter taste. Topiramaat Apotex 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. Topiramaat Apotex has the molecular formula C12H21NO8S and a molecular weight of 339.36. Topiramaat Apotex 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.

Topiramaat Apotex 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 Topiramaat Apotex monotherapy in adults and pediatric patients 10 years of age and older is 400 mg orally once daily. Titrate Topiramaat Apotex 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 Topiramaat Apotex 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 Topiramaat Apotex doses above 1,600 mg have not been studied.

In the study of primary generalized tonic-clonic seizures using Topiramaat Apotex, 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 Topiramaat Apotex 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

Topiramaat Apotex 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 Topiramaat Apotex concentration to fall below that required to maintain an anti-seizure effect. To avoid rapid drops in Topiramaat Apotex plasma concentration during hemodialysis, a supplemental dose of Topiramaat Apotex 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 Topiramaat Apotex Extended-Release Capsules is recommended.

Dosing Modifications in Patients Taking Phenytoin and/or Carbamazepine

The co-administration of Topiramaat Apotex 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 Topiramaat Apotex Extended-Release Capsules may require adjustment of the dose of Topiramaat Apotex Extended-Release Capsules.

Monitoring for Therapeutic Blood Levels

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

Administration Instructions

Topiramaat Apotex 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. Topiramaat Apotex Extended-Release Capsules can be taken without regard to meals.

Topiramaat Apotex interactions

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What other drugs will affect Topiramaat Apotex?

Oral Contraceptives

The possibility of decreased contraceptive efficacy and increased breakthrough bleeding should be considered in patients taking combination oral contraceptive products with Topiramaat Apotex. 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 Topiramaat Apotex decreased plasma concentrations of Topiramaat Apotex.

Concomitant administration of valproic acid and Topiramaat Apotex has been associated with hyperammonemia with and without encephalopathy. Concomitant administration of Topiramaat Apotex 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 Topiramaat Apotex does not inhibit enzyme activity for CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, CYP2E1, and CYP3A4/5 isozymes. In vitro studies indicate that immediate-release Topiramaat Apotex is a mild inhibitor of CYP2C19 and a mild inducer of CYP3A4. The same drug interactions can be expected with the use of Topiramaat Apotex.

CNS Depressants And Alcohol

Topiramaat Apotex is a CNS depressant. Concomitant administration of Topiramaat Apotex 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 Topiramaat Apotex, 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 Topiramaat Apotex is given concomitantly with another carbonic anhydrase inhibitor.

Metformin

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

Lithium

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

Drug Abuse And Dependence

Controlled Substance

Topiramaat Apotex (Topiramaat Apotex) extended-release capsule is not a controlled substance.

Abuse

The abuse and dependence potential of Topiramaat Apotex has not been evaluated in human studies.

Dependence

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

Topiramaat Apotex side effects

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What are the possible side effects of Topiramaat Apotex?

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

Clinical Trials Experience With Immediate-Release Topiramaat Apotex

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

Topiramaat Apotex 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 Topiramaat Apotex 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 Topiramaat Apotex and placebo was 0.3% versus 0.2% for adult patients, and 0.4% versus 0% for pediatric patients.

Adverse bleeding reactions reported with Topiramaat Apotex 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 Topiramaat Apotex 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 Topiramaat Apotex as monotherapy in Study 1 discontinued therapy due to adverse reactions. The most common ( ≥ 2% more frequent than for Topiramaat Apotex 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 Topiramaat Apotex 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 Topiramaat Apotex as monotherapy in Study 1 discontinued therapy due to adverse reactions. The most common ( ≥ 2% more frequent than for Topiramaat Apotex 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 Topiramaat Apotex Monotherapy Trial with incidence ≥ 2% in any Topiramaat Apotex 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 Topiramaat Apotex Daily Dosage

Group (mg per day)

50

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

Laboratory Abnormalities

Topiramaat Apotex decreases serum bicarbonate.

Immediate-release Topiramaat Apotex 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 Topiramaat Apotex.

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

Topiramaat Apotex 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.

Topiramaat Apotex treatment with or without concomitant valproic acid (VPA) can cause hyperammonemia with or without encephalopathy.

Clinical Trials Experience With Topiramaat Apotex

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 Topiramaat Apotex 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 Topiramaat Apotex experience.

The safety data presented below are from 249 patients with partial epilepsy on concomitant AEDs who participated in the Topiramaat Apotex 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)

Topiramaat Apotex (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 Topiramaat Apotex, 8.9% of patients who received Topiramaat Apotex 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 Topiramaat Apotex. 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.

Topiramaat Apotex contraindications

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What is the most important information I should know about Topiramaat Apotex?

Topiramaat Apotex 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 Topiramaat Apotex for seizures. Do not start or stop taking Topiramaat Apotex 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 Topiramaat Apotex without first talking to your doctor, even if you feel fine. You may have increased seizures if you stop using Topiramaat Apotex 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 Topiramaat Apotex.

Active ingredient matches for Topiramaat Apotex:

Topiramate in Netherlands.


List of Topiramaat Apotex substitutes (brand and generic names)

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Unit description / dosage (Manufacturer)Price, USD
Tablet; Oral; Topiramate 100 mg (Actavis)
Tablet; Oral; Topiramate 200 mg (Actavis)
Tablet; Oral; Topiramate 25 mg (Actavis)
Tablet; Oral; Topiramate 50 mg (Actavis)
Capsule; Oral; Topiramate 15 mg (Actavis)
Capsule; Oral; Topiramate 25 mg (Actavis)
Capsule; Oral; Topiramate 50 mg (Actavis)
Tablet, Film-Coated; Oral; Topiramate 100 mg (Actavis)
Tablet, Film-Coated; Oral; Topiramate 200 mg (Actavis)
Tablet, Film-Coated; Oral; Topiramate 25 mg (Actavis)
Tablet, Film-Coated; Oral; Topiramate 50 mg (Actavis)
Tablet, Film-Coated; Oral; Topiramate 300 mg (Actavis)
Tablet, Film-Coated; Oral; Topiramate 400 mg (Actavis)

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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