Topilex 25 mg Uses

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What is Topilex 25 mg?

Topilex 25 mg is a seizure medicine, also called an anticonvulsant. Topilex 25 mg 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 Topilex 25 mg has a higher minimum age (at least 10 years old) when used as the child's only seizure medicine.

The Topilex 25 mg brand of this medicine is also used to prevent migraine headaches in adults and teenagers who are at least 12 years old. Topilex 25 mg will only prevent migraine headaches or reduce the number of attacks. It will not treat a headache that has already begun.

Topilex 25 mg may also be used for purposes not listed in this medication guide.

Topilex 25 mg indications

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Monotherapy Epilepsy

Topilex 25 mg Tablets and Topilex 25 mg 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

Topilex 25 mg Tablets and Topilex 25 mg 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 Topilex 25 mg (Topilex 25 mg) 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

Topilex 25 mg Tablets and Topilex 25 mg capsules (sprinkle) are indicated for adults for the prophylaxis of migraine headache. The usefulness of Topilex 25 mg in the acute treatment of migraine headache has not been studied.

How should I use Topilex 25 mg?

Use Topilex 25 mg 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 Topilex 25 mg extended-release capsules.

Uses of Topilex 25 mg 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 Topilex 25 mg) 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 Topilex 25 mg) 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 Topilex 25 mg 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, Topilex 25 mg is probably effective and may be considered as an alternative agent for the treatment of limb tremor associated with essential tremor.

Topilex 25 mg description

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Topilex 25 mg is a sulfamate-substituted monosaccharide. Topilex 25 mg tablets are available as 50 mg round tablets for oral administration.

Topilex 25 mg is a white crystalline powder with a bitter taste. Topilex 25 mg 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. Topilex 25 mg has the molecular formula C12H21NO8S and a molecular weight of 339.36. Topilex 25 mg 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.

Topilex 25 mg 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 Topilex 25 mg monotherapy in adults and pediatric patients 10 years of age and older is 400 mg orally once daily. Titrate Topilex 25 mg 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 Topilex 25 mg 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 Topilex 25 mg doses above 1,600 mg have not been studied.

In the study of primary generalized tonic-clonic seizures using Topilex 25 mg, 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 Topilex 25 mg 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

Topilex 25 mg 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 Topilex 25 mg concentration to fall below that required to maintain an anti-seizure effect. To avoid rapid drops in Topilex 25 mg plasma concentration during hemodialysis, a supplemental dose of Topilex 25 mg 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 Topilex 25 mg Extended-Release Capsules is recommended.

Dosing Modifications in Patients Taking Phenytoin and/or Carbamazepine

The co-administration of Topilex 25 mg 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 Topilex 25 mg Extended-Release Capsules may require adjustment of the dose of Topilex 25 mg Extended-Release Capsules.

Monitoring for Therapeutic Blood Levels

It is not necessary to monitor Topilex 25 mg plasma concentrations to optimize therapy with Topilex 25 mg Extended-Release Capsules.

Administration Instructions

Topilex 25 mg 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. Topilex 25 mg Extended-Release Capsules can be taken without regard to meals.

Topilex 25 mg interactions

See also:
What other drugs will affect Topilex 25 mg?

Oral Contraceptives

The possibility of decreased contraceptive efficacy and increased breakthrough bleeding should be considered in patients taking combination oral contraceptive products with Topilex 25 mg. 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 Topilex 25 mg decreased plasma concentrations of Topilex 25 mg.

Concomitant administration of valproic acid and Topilex 25 mg has been associated with hyperammonemia with and without encephalopathy. Concomitant administration of Topilex 25 mg 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 Topilex 25 mg does not inhibit enzyme activity for CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, CYP2E1, and CYP3A4/5 isozymes. In vitro studies indicate that immediate-release Topilex 25 mg is a mild inhibitor of CYP2C19 and a mild inducer of CYP3A4. The same drug interactions can be expected with the use of Topilex 25 mg.

CNS Depressants And Alcohol

Topilex 25 mg is a CNS depressant. Concomitant administration of Topilex 25 mg 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 Topilex 25 mg, 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 Topilex 25 mg is given concomitantly with another carbonic anhydrase inhibitor.

Metformin

Topilex 25 mg treatment can frequently cause metabolic acidosis, a condition for which the use of metformin is contraindicated. The concomitant use of Topilex 25 mg and metformin is contraindicated in patients with metabolic acidosis.

Lithium

In patients, there was an observed increase in systemic exposure of lithium following Topilex 25 mg doses of up to 600 mg per day. Lithium levels should be monitored when co-administered with high-dose Topilex 25 mg.

Drug Abuse And Dependence

Controlled Substance

Topilex 25 mg (Topilex 25 mg) extended-release capsule is not a controlled substance.

Abuse

The abuse and dependence potential of Topilex 25 mg has not been evaluated in human studies.

Dependence

Topilex 25 mg has not been systematically studied in animals or humans for its potential for tolerance or physical dependence.

Topilex 25 mg side effects

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What are the possible side effects of Topilex 25 mg?

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

Clinical Trials Experience With Immediate-Release Topilex 25 mg

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

Topilex 25 mg 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 Topilex 25 mg 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 Topilex 25 mg and placebo was 0.3% versus 0.2% for adult patients, and 0.4% versus 0% for pediatric patients.

Adverse bleeding reactions reported with Topilex 25 mg 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 Topilex 25 mg 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 Topilex 25 mg as monotherapy in Study 1 discontinued therapy due to adverse reactions. The most common ( ≥ 2% more frequent than for Topilex 25 mg 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 Topilex 25 mg 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 Topilex 25 mg as monotherapy in Study 1 discontinued therapy due to adverse reactions. The most common ( ≥ 2% more frequent than for Topilex 25 mg 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 Topilex 25 mg Monotherapy Trial with incidence ≥ 2% in any Topilex 25 mg 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 Topilex 25 mg Daily Dosage

Group (mg per day)

50

(N=74) %Reactions that Occurred in at Least 1% of Topilex 25 mg-Treated Patients and Occurred More Frequently in Topilex 25 mg-Treated Than Placebo-Treated Patients

Laboratory Abnormalities

Topilex 25 mg decreases serum bicarbonate.

Immediate-release Topilex 25 mg 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 Topilex 25 mg.

Controlled trials of adjunctive Topilex 25 mg treatment of adults for partial onset seizures showed an increased incidence of markedly decreased serum phosphorus (6% Topilex 25 mg, 2% placebo), markedly increased serum alkaline phosphatase (3% Topilex 25 mg, 1% placebo), and decreased serum potassium (0.4 % Topilex 25 mg, 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 Topilex 25 mg for partial onset seizures.

Topilex 25 mg 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.

Topilex 25 mg treatment with or without concomitant valproic acid (VPA) can cause hyperammonemia with or without encephalopathy.

Clinical Trials Experience With Topilex 25 mg

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 Topilex 25 mg 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 Topilex 25 mg experience.

The safety data presented below are from 249 patients with partial epilepsy on concomitant AEDs who participated in the Topilex 25 mg 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)

Topilex 25 mg (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 Topilex 25 mg, 8.9% of patients who received Topilex 25 mg 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 Topilex 25 mg. 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.

Topilex 25 mg contraindications

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What is the most important information I should know about Topilex 25 mg?

Topilex 25 mg 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 Topilex 25 mg for seizures. Do not start or stop taking Topilex 25 mg 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 Topilex 25 mg without first talking to your doctor, even if you feel fine. You may have increased seizures if you stop using Topilex 25 mg 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 Topilex 25 mg.

Active ingredient matches for Topilex 25 mg:

Topiramate in Austria.


List of Topilex 25 mg substitutes (brand and generic names)

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Unit description / dosage (Manufacturer)Price, USD
Topinmate 25 mg x 500's
Topinmate 100 mg x 500's
25 mg x 10's (Unichem Laboratories Ltd.)$ 0.43
50 mg x 10's (Unichem Laboratories Ltd.)$ 0.79
Topirain 25mg TAB / 10 (Unichem Laboratories Ltd.)$ 0.43
Topirain 50mg TAB / 10 (Unichem Laboratories Ltd.)$ 0.79
Topirain 25 mg Tablet (Unichem Laboratories Ltd.)$ 0.04
Topirain 50 mg Tablet (Unichem Laboratories Ltd.)$ 0.07
TOPIRAIN 25 MG TABLET 1 strip / 10 tablets each (Unichem Laboratories Ltd.)$ 0.55
TOPIRAIN 50 MG TABLET 1 strip / 10 tablets each (Unichem Laboratories Ltd.)$ 1.12
TOPIRAIN tab 25 mg x 10's (Unichem Laboratories Ltd.)$ 0.43
TOPIRAIN tab 50 mg x 10's (Unichem Laboratories Ltd.)$ 0.79
Topirain 25mg TAB / 10 (Unichem Laboratories Ltd.)$ 0.43
Topirain 50mg TAB / 10 (Unichem Laboratories Ltd.)$ 0.79
Topirain 25mg Tablet (Unichem Laboratories Ltd.)$ 0.06
Topirain 50mg Tablet (Unichem Laboratories Ltd.)$ 0.12
TOPIRAM Capsule/ Tablet / 25mg / 10 units (Zydus Neurosciences (Zydus Cadila Healthcare Ltd))$ 0.23
TOPIRAM Capsule/ Tablet / 50mg / 10 units (Zydus Neurosciences (Zydus Cadila Healthcare Ltd))$ 0.43
25 mg x 10's (Zydus Neurosciences (Zydus Cadila Healthcare Ltd))$ 0.23
50 mg x 10's (Zydus Neurosciences (Zydus Cadila Healthcare Ltd))$ 0.43
Topiram 25mg TAB / 10 (Zydus Neurosciences (Zydus Cadila Healthcare Ltd))$ 0.23
Topiram 50mg TAB / 10 (Zydus Neurosciences (Zydus Cadila Healthcare Ltd))$ 0.43
Topiram 50 mg Tablet (Zydus Neurosciences (Zydus Cadila Healthcare Ltd))$ 0.04
Topiram 25 mg Tablet (Zydus Neurosciences (Zydus Cadila Healthcare Ltd))$ 0.02
TOPIRAM 50 MG TABLET 1 strip / 10 tablets each (Zydus Neurosciences (Zydus Cadila Healthcare Ltd))$ 0.76

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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