What is Topilex?
Topilex is a seizure medicine, also called an anticonvulsant. Topilex 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 has a higher minimum age (at least 10 years old) when used as the child's only seizure medicine.
The Topilex brand of this medicine is also used to prevent migraine headaches in adults and teenagers who are at least 12 years old. Topilex will only prevent migraine headaches or reduce the number of attacks. It will not treat a headache that has already begun.
Topilex may also be used for purposes not listed in this medication guide.
Topilex indications
Monotherapy Epilepsy
Topilex Tablets and Topilex 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 Tablets and Topilex 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 (Topilex) 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 Tablets and Topilex capsules (sprinkle) are indicated for adults for the prophylaxis of migraine headache. The usefulness of Topilex in the acute treatment of migraine headache has not been studied.
How should I use Topilex?
Use Topilex extended-release capsules as directed by your doctor. Check the label on the medicine for exact dosing instructions.
- Topilex extended-release capsules comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Topilex extended-release capsules refilled.
- Take Topilex extended-release capsules by mouth with or without food.
- Swallow Topilex extended-release capsules whole. Do not sprinkle on food, break, crush, chew, open, or dissolve before swallowing. If you cannot swallow Topilex extended-release capsules whole, talk to your doctor. You may need a different medicine.
- Drinking extra fluids while you are taking Topilex extended-release capsules is recommended. Doing so may help to prevent kidney stones from forming. Check with your doctor for instructions.
- Do not suddenly stop taking Topilex extended-release capsules. Suddenly stopping Topilex extended-release capsules may increase the risk of seizures. If you need to stop Topilex extended-release capsules, your doctor will gradually lower your dose.
- If you miss a dose of Topilex extended-release capsules, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once. Contact your doctor if you miss more than 1 dose of Topilex extended-release capsules.
Ask your health care provider any questions you may have about how to use Topilex extended-release capsules.
Uses of Topilex in details
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) 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) 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 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 is probably effective and may be considered as an alternative agent for the treatment of limb tremor associated with essential tremor.
Topilex description
Topilex is a sulfamate-substituted monosaccharide. Topilex tablets are available as 50 mg round tablets for oral administration.
Topilex is a white crystalline powder with a bitter taste. Topilex 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 has the molecular formula C12H21NO8S and a molecular weight of 339.36. Topilex 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 dosage
Monotherapy Use
Adults and Pediatric Patients 10 Years and Older with Partial Onset or Primary Generalized Tonic-Clonic Seizures
The recommended dose for Topilex monotherapy in adults and pediatric patients 10 years of age and older is 400 mg orally once daily. Titrate Topilex 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 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 doses above 1,600 mg have not been studied.
In the study of primary generalized tonic-clonic seizures using Topilex, 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 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 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 concentration to fall below that required to maintain an anti-seizure effect. To avoid rapid drops in Topilex plasma concentration during hemodialysis, a supplemental dose of Topilex may be required. The actual adjustment should take into account the:
- duration of dialysis period
- clearance rate of the dialysis system being used
- effective renal clearance of Topilex in the patient being dialyzed.
Laboratory Testing Prior to Treatment Initiation
Measurement of baseline and periodic serum bicarbonate during treatment with Topilex Extended-Release Capsules is recommended.
Dosing Modifications in Patients Taking Phenytoin and/or Carbamazepine
The co-administration of Topilex 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 Extended-Release Capsules may require adjustment of the dose of Topilex Extended-Release Capsules.
Monitoring for Therapeutic Blood Levels
It is not necessary to monitor Topilex plasma concentrations to optimize therapy with Topilex Extended-Release Capsules.
Administration Instructions
Topilex 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 Extended-Release Capsules can be taken without regard to meals.
Topilex interactions
See also:
What other drugs will affect Topilex?
Oral Contraceptives
The possibility of decreased contraceptive efficacy and increased breakthrough bleeding should be considered in patients taking combination oral contraceptive products with Topilex. 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 decreased plasma concentrations of Topilex.
Concomitant administration of valproic acid and Topilex has been associated with hyperammonemia with and without encephalopathy. Concomitant administration of Topilex 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 does not inhibit enzyme activity for CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, CYP2E1, and CYP3A4/5 isozymes. In vitro studies indicate that immediate-release Topilex is a mild inhibitor of CYP2C19 and a mild inducer of CYP3A4. The same drug interactions can be expected with the use of Topilex.
CNS Depressants And Alcohol
Topilex is a CNS depressant. Concomitant administration of Topilex 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, 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 is given concomitantly with another carbonic anhydrase inhibitor.
Metformin
Topilex treatment can frequently cause metabolic acidosis, a condition for which the use of metformin is contraindicated. The concomitant use of Topilex and metformin is contraindicated in patients with metabolic acidosis.
Lithium
In patients, there was an observed increase in systemic exposure of lithium following Topilex doses of up to 600 mg per day. Lithium levels should be monitored when co-administered with high-dose Topilex.
Drug Abuse And Dependence
Controlled Substance
Topilex (Topilex) extended-release capsule is not a controlled substance.
Abuse
The abuse and dependence potential of Topilex has not been evaluated in human studies.
Dependence
Topilex has not been systematically studied in animals or humans for its potential for tolerance or physical dependence.
Topilex side effects
See also:
What are the possible side effects of Topilex?
The following adverse reactions are discussed in more detail in other sections of the labeling:
- Acute Myopia and Secondary Angle Closure Glaucoma
- Visual Field Defects
- Oligohydrosis and Hyperthermia
- Metabolic Acidosis
- Suicidal Behavior and Ideation
- Cognitive/Neuropsychiatric Adverse Reactions
- Fetal Toxicity
- Hyperammonemia and Encephalopathy
- Kidney Stones
- Hypothermia with Concomitant Valproic Acid Use
- Paresthesia
Clinical Trials Experience With Immediate-Release Topilex
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 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 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 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 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 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 as monotherapy in Study 1 discontinued therapy due to adverse reactions. The most common ( ≥ 2% more frequent than for Topilex 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 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 as monotherapy in Study 1 discontinued therapy due to adverse reactions. The most common ( ≥ 2% more frequent than for Topilex 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 Monotherapy Trial with incidence ≥ 2% in any Topilex 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 Daily Dosage Group (mg per day) | |
| 50 (N=74) %Reactions that Occurred in at Least 1% of Topilex-Treated Patients and Occurred More Frequently in Topilex-Treated Than Placebo-Treated Patients |
Laboratory Abnormalities
Topilex decreases serum bicarbonate.
Immediate-release Topilex 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.
Controlled trials of adjunctive Topilex treatment of adults for partial onset seizures showed an increased incidence of markedly decreased serum phosphorus (6% Topilex, 2% placebo), markedly increased serum alkaline phosphatase (3% Topilex, 1% placebo), and decreased serum potassium (0.4 % Topilex, 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 for partial onset seizures.
Topilex 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 treatment with or without concomitant valproic acid (VPA) can cause hyperammonemia with or without encephalopathy.
Clinical Trials Experience With Topilex
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 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 experience.
The safety data presented below are from 249 patients with partial epilepsy on concomitant AEDs who participated in the Topilex 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 (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, 8.9% of patients who received Topilex 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. 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 contraindications
See also:
What is the most important information I should know about Topilex?
Topilex 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 for seizures. Do not start or stop taking Topilex 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 without first talking to your doctor, even if you feel fine. You may have increased seizures if you stop using Topilex 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.
Active ingredient matches for Topilex:
Topiramate in Austria, Bulgaria, Estonia, Latvia, Lithuania, Romania, Slovakia.
List of Topilex substitutes (brand and generic names) | Sort by popularity |
| Unit description / dosage (Manufacturer) | Price, USD |
| Topilept (Czech Republic, Netherlands) | |
| Topilex 100 mg (Austria) | |
| Topilex 200 mg (Austria) | |
| Topilex 25 mg (Austria) | |
| Topilex 50 mg (Austria) | |
| Topimark (Bulgaria, Czech Republic, Estonia, Latvia, Lithuania) | |
| Topimate 100 | |
| Topimatil (Poland) | |
| Topimax (Costa Rica, Denmark, Dominican Republic, El Salvador, Finland, Guatemala, Honduras, Iceland, Nicaragua, Norway, Panama, Sweden) | |
| Topimax Lyfjaver (Iceland) | |
| Topimax Singad Pharma (Denmark) | |
| Topimol (Turkey) | |
| Topimylan (Spain) | |
| Topina (Japan) | |
| Topina 10% (Japan) | |
| Topinitial (Poland) | |
| Topinmate (Taiwan) | |
| Topinmate 25 mg x 500's | |
| Topinmate 100 mg x 500's | |
| Topira (Croatia (Hrvatska), South Korea) | |
| Topira-Q (Germany) | |
| Topiragamma (Germany) | |
| Topiragen | |
| Topiragis (Czech Republic) | |
| TOPIRAIN (India) | |
| 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 (India) | |
| 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 |
See 963 substitutes for Topilex | |
References
- 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).
- PubChem. "topiramate". https://pubchem.ncbi.nlm.nih.gov/com... (accessed September 17, 2018).
- DrugBank. "topiramate". http://www.drugbank.ca/drugs/DB00273 (accessed September 17, 2018).
Reviews
The results of a survey conducted on ndrugs.com for Topilex are given in detail below. The results of the survey conducted are based on the impressions and views of the website users and consumers taking Topilex. We implore you to kindly base your medical condition or therapeutic choices on the result or test conducted by a physician or licensed medical practitioners.User reports
Consumer reported useful
No survey data has been collected yetConsumer reported price estimates
No survey data has been collected yetConsumer reported time for results
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Information checked by Dr. Sachin Kumar, MD Pharmacology
