Actions of Topilex 200 mg in details
Pharmacology: Pharmacodynamics: Mechanism of Action: The precise mechanisms by which Topilex 200 mg exerts its anticonvulsant and migraine prophylaxis effects are unknown; however, preclinical studies have revealed four properties that may contribute to Topilex 200 mg's efficacy for epilepsy and migraine prophylaxis. Electrophysiological and biochemical evidence suggests that Topilex 200 mg, at pharmacologically relevant concentrations, blocks voltage dependent sodium channels, augments the activity of the neurotransmitter gamma-aminobutyrate at some subtypes of the GABAA receptor, antagonizes the AMPA/kainate subtype of the glutamate receptor, and inhibits the carbonic anhydrase enzyme, particularly isozymes II and IV.
Topilex 200 mg has anticonvulsant activity in rat and mouse maximal electroshock seizure (MES) tests. Topilex 200 mg is only weakly effective in blocking clonic seizures induced by the GABAA receptor antagonist, pentylenetetrazole. Topilex 200 mg is also effective in rodent models of epilepsy, which include tonic and absence-like seizures in the spontaneous epileptic rat (SER) and tonic and clonic seizures induced in rats by kindling of the amygdala or by global ischemia.
Pharmacokinetics: Absorption and Distribution: Absorption of Topilex 200 mg is rapid, with peak plasma concentrations occurring at approximately 2 hours following a 400 mg oral dose. The relative bioavailability of Topilex 200 mg from the tablet formulation is about 80% compared to a solution. The bioavailability of Topilex 200 mg is not affected by food.
The pharmacokinetics of Topilex 200 mg are linear with dose proportional increases in plasma concentration over the dose range studied (200 to 800 mg/day). The mean plasma elimination half-life is 21 hours after single or multiple doses. Steady state is thus reached in about 4 days in patients with normal renal function. Topilex 200 mg is 15 to 41 % bound to human plasma proteins over the blood concentration range of 0.5 to 250 μg/mL. The fraction bound decreased as blood concentration increased. Carbamazepine and phenytoin do not alter the binding of Topilex 200 mg. Sodium valproate, at 500 μg/mL (a concentration 5 to 10 times higher than considered therapeutic for valproate) decreased the protein binding of Topilex 200 mg from 23 to 13%. Topilex 200 mg does not influence the binding of sodium valproate.
Metabolism and Excretion: Topilex 200 mg is not extensively metabolized and is primarily eliminated unchanged in the urine (approximately 70% of an administered dose). Six metabolites have been identified in humans, none of which constitutes more than 5% of an administered dose. The metabolites are formed via hydroxylation, hydrolysis and glucuronidation. There is evidence of renal tubular re-absorption of Topilex 200 mg. In rats, given probenecid to inhibit tubular reabsorption, along with Topilex 200 mg, a significant increase in renal clearance of Topilex 200 mg was observed. This interaction has not been evaluated in humans. Overall, oral plasma clearance (CL/F) is approximately 20 to 30 mL/minute in humans following oral administration.
How should I take Topilex 200 mg?
Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.
Topilex 200 mg can be taken with or without food.
Do not crush, chew, or break a Topilex 200 mg tablet. Swallow it whole. The Trokendi XR extended-release capsule must be swallowed whole. Do not break or open.
The Topilex 200 mg and Topilex 200 mg Sprinkle Capsule can be swallowed whole. Or you may open the capsule and sprinkle the medicine into a spoonful of applesauce or other soft food. Swallow right away without chewing. Do not save the mixture for later use. Discard the empty capsule.
Carefully follow the swallowing instructions for your medicine.
While using Topilex 200 mg, you may need frequent blood tests.
Drink plenty of liquids while you are taking Topilex 200 mg, to prevent kidney stones or an electrolyte imbalance.
Do not stop using Topilex 200 mg suddenly, even if you feel fine. Stopping suddenly may cause increased seizures. Follow your doctor's instructions about tapering your dose.
Call your doctor if your seizures get worse or you have them more often while taking Topilex 200 mg.
Any medical care provider who treats you should know that you take seizure medication.
Store at cool room temperature away from moisture, light, and high heat. Keep the bottle tightly closed when not in use.
Topilex 200 mg administration
Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results.
Topilex 200 mg can be taken with or without food. The Topilex 200 mg tablet should be swallowed whole. It has a bitter taste when chewed or broken.
You may open the Topilex 200 mg capsule and sprinkle the medicine into a spoonful of applesauce or other soft food to make swallowing easier. Swallow right away without chewing. Do not save the mixture for later use. Discard the empty capsule.
Drink plenty of liquids while you are taking Topilex 200 mg. This will lower your risk of having kidney stones or an electrolyte imbalance. Call your doctor if you have ongoing vomiting or diarrhea. You can easily become dehydrated while taking this medication.
If you need surgery, tell the surgeon ahead of time that you are using Topilex 200 mg. You may need to stop using the medicine for a short time.
Do not stop using Topilex 200 mg without first talking to your doctor, even if you feel fine. You may have increased seizures if you stop using Topilex 200 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 200 mg. To be sure this medication is not causing harmful effects, your blood may need to be tested often. Your kidney or liver function may also need to be tested. Visit your doctor regularly.
Wear a medical alert tag or carry an ID card stating that you take Topilex 200 mg. Any medical care provider or dentist who treats you should know that you are taking a seizure medication.
Store at room temperature away from moisture and heat. Keep the bottle tightly closed when not in use.
Topilex 200 mg pharmacology
Mechanism of Action
The precise mechanisms by which Topilex 200 mg exerts its anticonvulsant effects are unknown; however, preclinical studies have revealed four properties that may contribute to Topilex 200 mg's efficacy for epilepsy. Electrophysiological and biochemical evidence suggests that Topilex 200 mg, at pharmacologically relevant concentrations, blocks voltage-dependent sodium channels, augments the activity of the neurotransmitter gamma-aminobutyrate at some subtypes of the GABA-A receptor, antagonizes the AMPA/kainate subtype of the glutamate receptor, and inhibits the carbonic anhydrase enzyme, particularly isozymes II and IV.
Pharmacodynamics
Topilex 200 mg has anticonvulsant activity in rat and mouse maximal electroshock seizure (MES) tests. Topilex 200 mg is only weakly effective in blocking clonic seizures induced by the GABA-A receptor antagonist, pentylenetetrazole. Topilex 200 mg is also effective in rodent models of epilepsy, which include tonic and absence-like seizures in the spontaneous epileptic rat (SER) and tonic and clonic seizures induced in rats by kindling of the amygdala or by global ischemia.
Pharmacokinetics
Absorption and Distribution
The pharmacokinetics of Topilex 200 mg Extended-Release Capsules are linear with dose proportional increases in plasma concentration when administered as a single oral dose over the range of 50 mg to 1,400 mg. At 25 mg, the pharmacokinetics of Topilex 200 mg Extended-Release Capsules are nonlinear, possibly due to the binding of Topilex 200 mg to carbonic anhydrase in red blood cells.
Topilex 200 mg Extended-Release Capsules sprinkled on a spoonful of soft food is bioequivalent to the intact capsule formulation.
Following a single 200 mg oral dose of Topilex 200 mg Extended-Release Capsules, peak plasma concentrations (Tmax) occurred approximately 20 hours after dosing. Steady-state was reached in about 5 days following daily dosing of Topilex 200 mg Extended-Release Capsules in subjects with normal renal function, with a Tmax of approximately 6 hours.
At steady-state, the plasma exposure (AUC0-24hr, Cmax, and Cmin) of Topilex 200 mg from Topilex 200 mg Extended-Release Capsules administered once daily and the immediate-release Topilex 200 mg tablets administered twice-daily were shown to be bioequivalent. Fluctuation of Topilex 200 mg plasma concentrations at steady-state for Topilex 200 mg Extended-Release Capsules administered once daily was approximately 40% in healthy subjects, compared to approximately 53% for immediate-release Topilex 200 mg.
Compared to the fasted state, high-fat meal had no effect on bioavailability (AUC and Cmax) but delayed the Tmax by approximately 4 hours following a single dose of Topilex 200 mg Extended-Release Capsules. Topilex 200 mg Extended-Release Capsules can be taken without regard to meals.
Topilex 200 mg is 15% to 41% bound to human plasma proteins over the blood concentration range of 0.5 mcg/mL to 250 mcg/mL. The fraction bound decreased as blood concentration increased.
Carbamazepine and phenytoin do not alter the binding of immediate-release Topilex 200 mg. Sodium valproate, at 500 mcg/mL (a concentration 5 to 10 times higher than considered therapeutic for valproate) decreased the protein binding of immediate-release Topilex 200 mg from 23% to 13%. Immediate-release Topilex 200 mg does not influence the binding of sodium valproate.
Metabolism and Excretion
Topilex 200 mg is not extensively metabolized and is primarily eliminated unchanged in the urine (approximately 70% of an administered dose). Six metabolites have been identified in humans, none of which constitutes more than 5% of an administered dose. The metabolites are formed via hydroxylation, hydrolysis, and glucuronidation. There is evidence of renal tubular reabsorption of Topilex 200 mg. In rats, given probenecid to inhibit tubular reabsorption, along with Topilex 200 mg, a significant increase in renal clearance of Topilex 200 mg was observed. This interaction has not been evaluated in humans. Overall, oral plasma clearance (CL/F) is approximately 20 mL/min to 30 mL/min in adults following oral administration. The mean effective half-life of Topilex 200 mg Extended-Release Capsules is approximately 56 hours. Steady-state is reached in about 5 days after dosing with Topilex 200 mg Extended-Release Capsules in subjects with normal renal function.
Specific Populations
Renal Impairment
The clearance of Topilex 200 mg was reduced by 42% in subjects with moderate renal impairment (creatinine clearance 30 to 69 mL/min/1.73 m2) and by 54% in subjects with severe renal impairment (creatinine clearance less than 30 mL/min/1.73 m2) compared to subjects with normal renal function (creatinine clearance greater than70 mL/min/1.73 m2). Since Topilex 200 mg is presumed to undergo significant tubular reabsorption, it is uncertain whether this experience can be generalized to all situations of renal impairment. It is conceivable that some forms of renal disease could differentially affect glomerular filtration rate and tubular reabsorption resulting in a clearance of Topilex 200 mg not predicted by creatinine clearance. In general, however, use of one-half the usual starting and maintenance dose is recommended in patients with creatinine clearance less than 70 mL/min/1.73 m2.
Hemodialysis
Topilex 200 mg is cleared by hemodialysis. Using a high-efficiency, counterflow, single pass-dialysate hemodialysis procedure, Topilex 200 mg dialysis clearance was 120 mL/min with blood flow through the dialyzer at 400 mL/min. This high clearance (compared to 20 mL/min to 30 mL/min total oral clearance in healthy adults) will remove a clinically significant amount of Topilex 200 mg from the patient over the hemodialysis treatment period. Therefore, a supplemental dose may be required.
Hepatic Impairment
In subjects with hepatic impairment, the clearance of Topilex 200 mg may be decreased; the mechanism underlying the decrease is not well understood.
Age, Gender and Race
The pharmacokinetics of Topilex 200 mg in elderly subjects (65 to 85 years of age, N=16) were evaluated in a controlled clinical study. The elderly subject population had reduced renal function (creatinine clearance [-20%]) compared to young adults. Following a single oral 100 mg dose, maximum plasma concentration for elderly and young adults was achieved at approximately 1 to 2 hours. Reflecting the primary renal elimination of Topilex 200 mg, Topilex 200 mg plasma and renal clearance were reduced 21% and 19%, respectively, in elderly subjects, compared to young adults. Similarly, Topilex 200 mg half-life was longer (13%) in the elderly. Reduced Topilex 200 mg clearance resulted in slightly higher maximum plasma concentration (23%) and AUC (25%) in elderly subjects than observed in young adults. Topilex 200 mg clearance is decreased in the elderly only to the extent that renal function is reduced. Because of this, dosage adjustment may be necessary.
Clearance of Topilex 200 mg in adults was not affected by gender or race.
Pediatric Pharmacokinetics
Pharmacokinetics of immediate-release Topilex 200 mg were evaluated in patients ages 2 years to less than 16 years. Patients received either no or a combination of other antiepileptic drugs. A population pharmacokinetic model was developed on the basis of pharmacokinetic data from relevant Topilex 200 mg clinical studies. This dataset contained data from 1217 subjects including 258 pediatric patients aged 2 years to less than 16 years (95 pediatric patients less than 10 years of age).
Pediatric patients on adjunctive treatment exhibited a higher oral clearance (L/h) of Topilex 200 mg compared to patients on monotherapy, presumably because of increased clearance from concomitant enzyme-inducing antiepileptic drugs. In comparison, Topilex 200 mg clearance per kg is greater in pediatric patients than in adults and in young pediatric patients (down to 2 years) than in older pediatric patients. Consequently, the plasma drug concentration for the same mg/kg/day dose would be lower in pediatric patients compared to adults and also in younger pediatric patients compared to older pediatric patients. Clearance was independent of dose.
As in adults, hepatic enzyme-inducing antiepileptic drugs decrease the steady state plasma concentrations of Topilex 200 mg.
Drug-Drug Interaction Studies
Antiepileptic Drugs
Potential interactions between immediate-release Topilex 200 mg and standard AEDs were assessed in controlled clinical pharmacokinetic studies in patients with epilepsy. The effects of these interactions on mean plasma AUCs are summarized in Table 9. Interaction of Topilex 200 mg Extended-Release Capsules and standard AEDs is not expected to differ from the experience with immediate-release Topilex 200 mg products.
In Table 9, the second column (AED concentration) describes what happened to the concentration of the AED listed in the first column when Topilex 200 mg was added. The third column (Topilex 200 mg concentration) describes how the co-administration of a drug listed in the first column modified the concentration of Topilex 200 mg in experimental settings when Topilex 200 mg was given alone.
In addition to the pharmacokinetic interaction described in the above table, concomitant administration of valproic acid and Topilex 200 mg has been associated with hyperammonemia with and without encephalopathy and hypothermia.
CNS Depressants or Alcohol
Concomitant administration of Topilex 200 mg and alcohol or other CNS depressant drugs has not been evaluated in clinical studies.
Oral Contraceptives
In a pharmacokinetic interaction study in healthy volunteers with a concomitantly administered combination oral contraceptive product containing 1 mg norethindrone (NET) plus 35 mcg ethinyl estradiol (EE), Topilex 200 mg, given in the absence of other medications at doses of 50 to 200 mg per day, was not associated with statistically significant changes in mean exposure (AUC) to either component of the oral contraceptive. In another study, exposure to EE was statistically significantly decreased at doses of 200, 400, and 800 mg per day (18%, 21%, and 30%, respectively) when given as adjunctive therapy in patients taking valproic acid. In both studies, Topilex 200 mg (50 mg per day to 800 mg per day) did not significantly affect exposure to NET. Although there was a dose-dependent decrease in EE exposure for doses between 200 to 800 mg per day, there was no significant dose-dependent change in EE exposure for doses of 50 to 200 mg per day. The clinical significance of the changes observed is not known. The possibility of decreased contraceptive efficacy and increased breakthrough bleeding should be considered in patients taking combination oral contraceptive products with Topilex 200 mg Extended-Release Capsules. 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.
Digoxin
In a single-dose study, serum digoxin AUC was decreased by 12% with concomitant Topilex 200 mg administration. The clinical relevance of this observation has not been established.
Hydrochlorothiazide
A drug-drug interaction study conducted in healthy volunteers evaluated the steady-state pharmacokinetics of hydrochlorothiazide (HCTZ) (25 mg every 24 hours) and Topilex 200 mg (96 mg every 12 hours) when administered alone and concomitantly. The results of this study indicate that Topilex 200 mg Cmax increased by 27% and AUC increased by 29% when HCTZ was added to Topilex 200 mg. The clinical significance of this change is unknown. The addition of HCTZ to Topilex 200 mg Extended-Release Capsules therapy may require an adjustment of the Topilex 200 mg Extended-Release Capsules dose. The steady-state pharmacokinetics of HCTZ were not significantly influenced by the concomitant administration of Topilex 200 mg. Clinical laboratory results indicated decreases in serum potassium after Topilex 200 mg or HCTZ administration, which were greater when HCTZ and Topilex 200 mg were administered in combination.
Metformin
Topilex 200 mg treatment can frequently cause metabolic acidosis, a condition for which the use of metformin is contraindicated. Topilex 200 mg Extended-Release Capsules are expected to exhibit the same degree of metabolic acidosis as Topilex 200 mg.
A drug-drug interaction study conducted in healthy volunteers evaluated the steady-state pharmacokinetics of metformin (500 mg every 12 hr) and Topilex 200 mg in plasma when metformin was given alone and when metformin and Topilex 200 mg (100 mg every 12 hr) were given simultaneously. The results of this study indicated that the mean metformin Cmax and AUC0-12h increased by 17% and 25%, respectively, when Topilex 200 mg was added. Topilex 200 mg did not affect metformin tmax. The clinical significance of the effect of Topilex 200 mg on metformin pharmacokinetics is not known.
Oral plasma clearance of Topilex 200 mg appears to be reduced when administered with metformin. The clinical significance of the effect of metformin on Topilex 200 mg Extended-Release Capsules pharmacokinetics is unclear.
Pioglitazone
A drug-drug interaction study conducted in healthy volunteers evaluated the steady-state pharmacokinetics of Topilex 200 mg and pioglitazone when administered alone and concomitantly. A 15% decrease in the AUCτ,ss of pioglitazone with no alteration in Cmax,ss was observed. This finding was not statistically significant. In addition, a 13% and 16% decrease in Cmax,ss and AUCτ,ss respectively, of the active hydroxy-metabolite was noted as well as a 60% decrease in Cmax,ss and AUCτ,ss of the active keto-metabolite. The clinical significance of these findings is not known.
When Topilex 200 mg Extended-Release Capsules are added to pioglitazone therapy or pioglitazone is added to Topilex 200 mg Extended-Release Capsules therapy, careful attention should be given to the routine monitoring of patients for adequate control of their diabetic disease state.
Glyburide
A drug-drug interaction study conducted in patients with type 2 diabetes evaluated the steady-state pharmacokinetics of glyburide (5 mg per day) alone and concomitantly with Topilex 200 mg (150 mg per day). There was a 22% decrease in Cmax and 25% reduction in AUC24 for glyburide during Topilex 200 mg administration. Systemic exposure (AUC) of the active metabolites, 4-trans-hydroxy glyburide (M1) and 3-cis-hydroxyglyburide (M2), was also reduced by 13% and 15%, reduced Cmax by 18% and 25%, respectively. The steady-state pharmacokinetics of Topilex 200 mg were unaffected by concomitant administration of glyburide.
Lithium
In patients, the pharmacokinetics of lithium were unaffected during treatment with Topilex 200 mg at doses of 200 mg per day; however, there was an observed increase in systemic exposure of lithium (27% for Cmax and 26% for AUC) following Topilex 200 mg doses up to 600 mg per day. Lithium levels should be monitored when co-administered with high-dose Topilex 200 mg Extended-Release Capsules.
Haloperidol
The pharmacokinetics of a single dose of haloperidol (5 mg) were not affected following multiple dosing of Topilex 200 mg (100 mg every 12 hr) in 13 healthy adults (6 males, 7 females).
Amitriptyline
There was a 12% increase in AUC and Cmax for amitriptyline (25 mg per day) in 18 normal subjects (9 males, 9 females) receiving 200 mg per day of Topilex 200 mg. Some subjects may experience a large increase in amitriptyline concentration in the presence of Topilex 200 mg Extended-Release Capsules and any adjustments in amitriptyline dose should be made according to the patient's clinical response and not on the basis of plasma levels.
Sumatriptan
Multiple dosing of Topilex 200 mg (100 mg every 12 hrs) in 24 healthy volunteers (14 males, 10 females) did not affect the pharmacokinetics of single-dose sumatriptan either orally (100 mg) or subcutaneously (6 mg).
Risperidone
When administered concomitantly with Topilex 200 mg at escalating doses of 100, 250, and 400 mg per day, there was a reduction in risperidone systemic exposure (16% and 33% for steady-state AUC at the 250 and 400 mg per day doses of Topilex 200 mg). No alterations of 9-hydroxyrisperidone levels were observed. Coadministration of Topilex 200 mg 400 mg per day with risperidone resulted in a 14% increase in Cmax and a 12% increase in AUC12 of Topilex 200 mg. There were no clinically significant changes in the systemic exposure of risperidone plus 9- hydroxyrisperidone or of Topilex 200 mg; therefore, this interaction is not likely to be of clinical significance.
Propranolol
Multiple dosing of Topilex 200 mg (200 mg per day) in 34 healthy volunteers (17 males, 17 females) did not affect the pharmacokinetics of propranolol following daily 160 mg doses. Propranolol doses of 160 mg per day in 39 volunteers (27 males, 12 females) had no effect on the exposure to Topilex 200 mg at a dose of 200 mg per day of Topilex 200 mg.
Dihydroergotamine
Multiple dosing of Topilex 200 mg (200 mg per day) in 24 healthy volunteers (12 males, 12 females) did not affect the pharmacokinetics of a 1 mg subcutaneous dose of dihydroergotamine. Similarly, a 1 mg subcutaneous dose of dihydroergotamine did not affect the pharmacokinetics of a 200 mg per day dose of Topilex 200 mg in the same study.
Diltiazem
Co-administration of diltiazem (240 mg) with Topilex 200 mg (150 mg per day) resulted in a 10% decrease in Cmax and 25% decrease in diltiazem AUC, 27% decrease in Cmax and 18% decrease in des-acetyl diltiazem AUC, and no effect on N-desmethyl diltiazem. Co-administration of Topilex 200 mg with diltiazem resulted in a 16% increase in Cmax and a 19% increase in AUC12 of Topilex 200 mg.
Venlafaxine
Multiple dosing of Topilex 200 mg (150 mg per day) in healthy volunteers did not affect the pharmacokinetics of venlafaxine or O-desmethyl venlafaxine. Multiple dosing of venlafaxine (150 mg) did not affect the pharmacokinetics of Topilex 200 mg.
Other Carbonic Anhydrase Inhibitors
Concomitant use of Topilex 200 mg Extended-Release Capsules, 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. Therefore, if Topilex 200 mg Extended-Release Capsules are given concomitantly with another carbonic anhydrase inhibitor, the patient should be monitored for the appearance or worsening of metabolic acidosis.
Drug/Laboratory Tests Interactions
There are no known interactions of Topilex 200 mg Extended-Release Capsules with commonly used laboratory tests.
Relative Bioavailability of Topilex 200 mg Extended-Release Capsules Compared to Immediate-Release Topilex 200 mg in Healthy Volunteers
Topilex 200 mg Extended-Release Capsules, taken once daily, provides similar steady-state Topilex 200 mg concentrations to immediate-release Topilex 200 mg taken every 12 hours, when administered at the same total daily dose. In a healthy volunteer, multiple-dose crossover study, the 90% CI for the ratios of AUC0-24, Cmax and Cmin, as well as partial AUC (the area under the concentration-time curve from time 0 to time p (post dose)) for multiple time points were within the 80 to 125% bioequivalence limits, indicating no clinically significant difference between the two formulations. In addition, the 90% CI for the ratios of Topilex 200 mg plasma concentration at each of multiple time points over 24 hours for the two formulations were within the 80 to 125% bioequivalence limits, except for the initial time points before 3 hours and at 8 hours post-dose, which is not expected to have a significant clinical impact.
The effects of switching between Topilex 200 mg Extended-Release Capsules and immediate-release Topilex 200 mg were also evaluated in the same multiple-dose, crossover, comparative bioavailability study. In healthy subjects switched from immediate-release Topilex 200 mg given every 12 hours to Topilex 200 mg Extended-Release Capsules given once daily, similar concentrations were maintained immediately after the formulation switch. On the first day following the switch, there were no significant differences in AUC0-24, Cmax, and Cmin, as the 90% CI for the ratios were contained within the 80 to 125% equivalence limits.
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).
- NCIt. "Topiramate: NCI Thesaurus (NCIt) provides reference terminology for many systems. It covers vocabulary for clinical care, translational and basic research, and public information and administrative activities.". https://ncit.nci.nih.gov/ncitbrowser... (accessed September 17, 2018).
- EPA DSStox. "Topiramate: DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology.". https://comptox.epa.gov/dashboard/ds... (accessed September 17, 2018).
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Information checked by Dr. Sachin Kumar, MD Pharmacology
