The right topiramate dose may help you do more for migraine patients


Significant reductions in migraine frequency begin at 100-mg daily dose1-3

Study overview1,2:
Two multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trials evaluating the efficacy of immediate-release topiramate (TPM-IR) in the prophylactic treatment of migraine. Study 1 was conducted in the United States; Study 2 was conducted in the United States and Canada. Trial design was identical, enrolling patients 12 to 65 years of age with a history of migraine, with or without aura, for at least 6 months, according to IHS diagnostic criteria. Patients experiencing cluster, basilar, ophthalmoplegic, hemiplegic, or transformed migraine were excluded.

Patients experiencing 3 to 12 migraines over a 28-day prospective baseline phase were randomized to TPM-IR 50 mg/day, 100 mg/day, 200 mg/day, or placebo and treated for 26 weeks (8-week titration period; 18-week maintenance period).

Treatment was initiated at 25 mg/day for 1 week, then daily dose was increased by 25-mg increments weekly until reaching the assigned target dose or maximum tolerated dose (administered twice daily).

Treatment efficacy was assessed by the reduction in migraine frequency, as measured by the change in 4-week migraine rate (migraine classified by IHS criteria) from the baseline phase to double-blind treatment period in each TPM-IR treatment group, compared to placebo, in the ITT population.

Abbreviations: IHS, International Headache Society; ITT, intent-to-treat; TPM-IR, immediate-release topiramate.

Primary endpoint: Mean reduction from baseline (5.5 migraines per 28 days) in migraine frequency1-4

*Active treatment group was statistically different than placebo group in both studies.

NSNot statistically significant.

The 200-mg/day dose group was also statistically different than placebo. Mean reduction from baseline: Study 1 (n=112): 2.2; Study 2 (n=117): 2.4 (P<0.001 for both).

Have you asked your patients how they are doing on immediate-release topiramate?

Explore how once-daily Trokendi XR may be the right topiramate medication for your patients.3,5

All-day delivery of migraine prevention treatment3,5

Once-daily Trokendi XR is bioequivalent to twice-daily Topamax® (topiramate)—24-hour mean steady state plasma concentration-time profiles3,5

Primary endpoint3

Relative bioavailability of Trokendi XR and Topamax at steady state.

Study design3

Phase 1, single-center, multiple-dose, single-blind, randomized, crossover PK study of Trokendi XR (200 mg once daily) and Topamax (100 mg twice daily) in 39 healthy adults.

Subjects were titrated to a 200-mg/day dose of either Trokendi XR or Topamax over 3 weeks.

Following titration, subjects were maintained on 200 mg/day for 10 days.

Following a 32-day washout period, subjects crossed over to alternate treatment.

Ratio Trokendi XR to Topamax (90% CI) AUC0-24 97% (94%-100%) | Cmax 88% (85%-91%) | Cmin 100% (96%-104%)

Fluctuation in plasma concentration of Trokendi XR was ~26% for healthy subjects compared to ~40% for subjects taking TPM-IR.3,5

Abbreviations: CI, confidence interval; PK, pharmacokinetic; Q12H, every 12 hours; QD, daily; TPM-IR, immediate-release topiramate.

It’s important for patients to have

steady, 24-hour delivery3,5

Trokendi XR is designed and approved to be prescribed once daily; immediate-release topiramate is not.4,5

Simulated fluctuation of topiramate concentration at steady state was approximately6:

• 18% for patients with epilepsy taking once-daily Trokendi XR 200 mg

• 64% for patients with epilepsy taking once-daily TPM-IR 200 mg

Abbreviations: AED, anti-epileptic drug; PK, pharmacokinetic; TPM-IR, immediate-release topiramate.

Population PK modeling and once-daily dosing simulation based on bioavailability in patients with epilepsy*,3,6

*Randomized, controlled trials have not explored the consequences of dosing irregularities for an extended-release AED and its twice-daily counterpart. Because they can be powerful predictive tools, population PK modeling and simulation were used to compare the potential PK consequences of dosing irregularities during steady state AED treatment with once-daily Trokendi XR and twice-daily TPM-IR. In addition, simulations compared once-daily dosing of Trokendi XR and TPM-IR to address the perception that, due to the long half-life of topiramate, once-daily dosing produces relatively constant topiramate concentrations, regardless of formulation.6

Patient savings

Help your eligible patients save with a $0 co-pay savings card.

Trokendi XR® (topiramate) co-pay savings card



*This offer is good for commercially insured and cash-paying patients purchasing Trokendi XR® (topiramate) extended-release capsules and may not be used for any other product. Maximum benefits apply. This offer is not valid for prescriptions purchased under Medicaid, Medicare, or other federal or state programs (such as medical assistance programs). Offer not valid where prohibited by law, taxed, or restricted. It is not transferable and may not be combined with any other offer. The amount of the rebate cannot exceed the patient’s actual out-of-pocket expenses. Offer must be presented along with a valid prescription for Trokendi XR® at the time of purchase. By enrolling into this program you are consenting to the collection and use of certain personal information including your phone number and/or email address and elements of pharmacy claim information. This information will be collected and used by service providers of Supernus Pharmaceuticals, Inc. (“Supernus”), in order to administer this program. This information is not provided to Supernus directly. If you do not consent, please do not enroll into the program. If you require additional assistance, please call 1-866-398-0833. Supernus reserves the right to rescind, revoke, or amend this offer without notice at any time.



Trokendi XR is contraindicated in patients with recent alcohol use (within 6 hours prior to and 6 hours after Trokendi XR use).


• A syndrome consisting of acute myopia associated with secondary angle closure glaucoma has been reported in patients receiving topiramate. Symptoms can include acute onset of decreased visual acuity and/or ocular pain, myopia, anterior chamber shallowing, ocular hyperemia, and increased intraocular pressure. Symptoms typically occur within 1 month of initiating topiramate therapy. The primary treatment to reverse symptoms is discontinuation of Trokendi XR as rapidly as possible. Elevated intraocular pressure of any etiology, if left untreated, can lead to serious sequelae including permanent vision loss.

• Visual field defects (independent of elevated intraocular pressure) have been reported in patients receiving topiramate. In clinical trials, most events were reversible after topiramate discontinuation. If problems occur at any time during topiramate treatment, consider discontinuation of the drug.

• Oligohydrosis resulting in hospitalization has been reported in some cases in association with topiramate use. The majority of reports have been in pediatric patients. Patients, especially pediatric patients, should be monitored closely for evidence of decreased sweating and increased body temperature, especially in hot weather. Caution should be used when Trokendi XR is prescribed with other drugs that predispose patients to heat-related disorders.

• Hyperchloremic, non-anion gap, metabolic acidosis has been reported in adults and pediatric patients treated with topiramate. This metabolic acidosis is caused by renal bicarbonate loss due to the inhibitory effect of topiramate on carbonic anhydrase. Conditions that predispose patients to acidosis may be additive to the bicarbonate-lowering effects of topiramate. Although Trokendi XR is not approved for children under 6 years of age, a study of topiramate as adjunctive treatment in patients under 2 produced metabolic acidosis of a notably greater magnitude than in older children and adults. Measurement of baseline and periodic serum bicarbonate during topiramate treatment is recommended. If metabolic acidosis develops and persists, consideration should be given to reducing the dose or discontinuing topiramate. The incidence of persistent decreases in serum bicarbonate in placebo-controlled trials with immediate-release topiramate for adults for prophylaxis of migraine was higher than in the epilepsy controlled trials, and higher in adolescents than adults.

• In vitro data show that, in the presence of alcohol, the pattern of topiramate release from Trokendi XR capsules is significantly altered. Alcohol use should be completely avoided within 6 hours prior to and 6 hours after Trokendi XR administration.

• Antiepileptic drugs (AEDs) increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED, including Trokendi XR for any indication, should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Anyone prescribing Trokendi XR must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Many illnesses for which antiepileptic drugs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during Trokendi XR treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.

• Immediate-release topiramate can cause, and therefore Trokendi XR is expected to cause cognitive/neuropsychiatric adverse reactions. In adults, the most frequent of these can be classified into three general categories: cognitive-related dysfunction, psychiatric/ behavioral disturbances, and somnolence or fatigue.

• Topiramate can cause fetal harm when administered to a pregnant woman. Use during pregnancy and data from pregnancy registries indicate that infants exposed to topiramate in utero can have increased risk of cleft lip and/or cleft palate, and for being small for gestational age. Trokendi XR should only be used during pregnancy if the potential benefit outweighs the potential risk. Patients should be informed of the potential hazard to the fetus. Diarrhea and somnolence have been reported in breastfed infants whose mothers receive topiramate.

• Antiepileptic drugs, including Trokendi XR, should be gradually withdrawn to minimize the potential for seizures or increased seizure frequency.

• Hyperammonemia with and without encephalopathy has been observed in post-marketing reports in patients who were taking topiramate with or without concomitant valproic acid (VPA); hyperammonemia appears more common when used concomitantly with VPA. Although Trokendi XR is not indicated for use in infants or toddlers, topiramate with concomitant VPA produced a dose-related increase in hyperammonemia in this population.

• The concomitant use of Trokendi XR with any other drug producing metabolic acidosis, or potentially in patients on a ketogenic diet, may increase the risk of kidney stone formation and should therefore be avoided.

• Hypothermia has been reported in association with topiramate use with concomitant valproic acid (VPA) both in the presence and in the absence of hyperammonemia. Consideration should be given to stopping topiramate or valproate in patients who develop hypothermia; clinical management should include examination of blood ammonia levels.

• Topiramate is a CNS depressant. Concomitant administration of topiramate with other CNS depressant drugs can result in significant CNS depression. Patients should be watched carefully when Trokendi XR is coadministered with other CNS depressant drugs.


• Refer to the Trokendi XR DOSAGE AND ADMINISTRATION section of the full prescribing information for recommended dosing guidelines for Trokendi XR.

• 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.

• In patients undergoing hemodialysis, to avoid rapid drops in topiramate plasma concentration, a supplemental dose of topiramate may be required. The actual adjustment should take into account the duration of dialysis period, clearance rate of the dialysis system being used, and the effective renal clearance of topiramate in the patient being dialyzed.

• Trokendi XR can be taken without regard to meals. Swallow capsule whole and intact. Do not sprinkle on food, chew, or crush.


• Trokendi XR has not been studied in a randomized, placebo-controlled phase 3 clinical study; however, it is expected that Trokendi XR would produce a similar adverse reaction profile as that of immediate-release topiramate. See the ADVERSE REACTIONS section of the Trokendi XR full prescribing information for further adverse reaction rates from the clinical trials conducted under widely varying conditions.

• In migraine prophylaxis trials of 100 mg immediate-release topiramate, the most common adverse reactions in adults that were higher than placebo were paresthesia (51% v 6%, 100 mg/day v placebo), anorexia (15% v 6%), upper respiratory tract infection (14% v 12%), weight decrease (9% v 1%), taste perversion (8% v 1%), diarrhea (11% v 4%), difficulty with memory (7% v 2%), hypoaesthesia (7% v 2%), nausea (13% v 8%), and abdominal pain (6% v 5%).


• Trokendi XR (topiramate) extended-release capsules are indicated for prophylaxis of migraine headaches in patients 12 years of age and older.

Please refer to the full Prescribing Information and Medication Guide for additional important information on Trokendi XR.

Trokendi XR (topiramate) extended-release capsules 


1. Silberstein SD, Neto W, Schmitt J, Jacobs D; MIGR-001 Study Group. Topiramate in migraine prevention: results of a large controlled trial. Arch Neurol. 2004,614(4):490-495.

2. Brandes JL, Saper JR, Diamond M; MIGR-002 Study Group. Topiramate in migraine prevention: results of a large controlled trial. JAMA. 2004;291(8):965-973. 

3. Data on file. Supernus Pharmaceuticals, Inc.

4. Topamax. Package insert. Janssen Pharmaceuticals, Inc; May 2019.

5. Trokendi XR. Package insert. Supernus Pharmaceuticals, Inc; April 2020.

6. Brittain ST, Wheless JW. Pharmacokinetic simulations of topiramate plasma concentrations following dosing irregularities with extended-release vs. immediate-release formulations. Epilepsy Behav. 2015;52(Pt A):31-36.