IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

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

WARNINGS & PRECAUTIONS

• 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.

• Immediate-release topiramate monotherapy demonstrated significant decrease in bone mineral density (BMD) measured in lumbar spine and in total body less head in a one year active controlled study in pediatric patients. Although decreases in BMD occurred across all pediatric age subgroups, patients 6 to 9 years of age were most commonly affected. Decreased BMD in the lumbar spine was correlated with decreased serum bicarbonate, which commonly occurs with topiramate treatment and reflects metabolic acidosis, a known cause of increased bone resorption

• Immediate-release topiramate monotherapy demonstrated negative effects on growth (height and weight) among pediatric patients in a one-year active controlled study. Negative effects on growth were seen across all immediate-release topiramate age subgroups. Growth of children receiving prolonged TROKENDI XR® therapy should be carefully monitored.

• Serious skin reactions (Stevens-Johnson Syndrome [SJS] and Toxic Epidermal Necrolysis [TEN]) have been reported in patients receiving topiramate. Trokendi XR should be discontinued at the first sign of a rash, unless the rash is clearly not drug related. If signs or symptoms suggest SJS/TEN, use of this drug should not be resumed and alternative therapy should be considered. Inform patients about the signs of serious skin reactions.

• 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. An increase in urinary calcium and decrease in urinary citrate was observed in immediate-release topiramate-treated pediatric patients in a one-year active-controlled study. Increased ratio of urinary calcium/citrate increases the risk of kidney stones and/or nephrocalcinosis.

• 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.

DOSING GUIDELINES & CONSIDERATIONS

• 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.

ADVERSE REACTIONS

• 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 the preventive treatment of migraine 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%).

INDICATION

• 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 for oral use

hcp-otherindications-hero

Other indications

In addition to migraine prevention, Trokendi XR is indicated as initial monotherapy in patients 6 years of age and older with partial-onset or primary generalized tonic-clonic seizures and as adjunctive therapy in patients 6 years of age and older with partial-onset, primary generalized tonic-clonic seizures, or seizures associated with Lennox-Gastaut syndrome.1

Most patients in a conversion study preferred Trokendi XR2

In a conversion study, 93.4% of patients with epilepsy who had been taking a stable dose of immediate-release topiramate for a minimum of 1 month prior to study entry preferred Trokendi XR.2

Primary endpoint:

Bioavailability of extended-release topiramate vs. TPM-IR

Secondary endpoint:

Included patient preference

Conversion study enrolled adult male and female patients receiving a stable dose of TPM-IR for a minimum of 1 month prior to study entry

Patients received TPM-IR for 2 weeks at their current dose

At day 14, samples were drawn for PK analysis, and patients were then switched to the equivalent dose of Trokendi XR given once daily, with PK samples drawn following the first dose

Patients then received Trokendi XR for 2 weeks at the same daily dose
 

As this study design employed only 1 sequence of TPM-IR to Trokendi XR, evaluation of effect of sequence (if any) on PK endpoints, as in standard crossover designs, was not possible2

At day 28, patient preference was determined through questions that were then documented in case report forms. Questions included:

Was the assessment done?

 Yes  No

Which treatment did you prefer?

 Once a day  Twice a day

Trokendi XR was shown to be bioequivalent to TPM-IR.

Abbreviations: PK, pharmacokinetic; TPM-IR, immediate-release topiramate.
 

Seamlessly convert your patients to once-daily Trokendi XR2

Example of same-day conversion for patients switching to once-a-day Trokendi XR (topiramate) from twice-daily Topamax (topiramate)1,3

Twice daily

Topamax

100 mg

Once daily

Trokendi XR

200 mg

Tablets and capsule shown are not actual size. Recommended dose of Trokendi XR as adjunctive therapy in adults with partial-onset seizures is 200-400 mg/day.

Dosage and administration for new patients starting Trokendi XR1

Initial dose

Titration

Recommended dose

Monotherapy Partial-onset or primary generalized tonic-clonic seizures

Adults and pediatric patients 10 years and older

Initial dose

50 mg orally once daily

Recommended dose

400 mg once daily

Titration

Increase dose weekly by increments of 50 mg for the first 4 weeks then 100 mg for weeks 5 to 6

Pediatric patients 6 years to under 10

Initial dose

25 mg/day nightly for the first week

Recommended dose

Daily doses based on weight

Titration

Titrate over 5 to 7 weeks

Adjunctive therapy in epilepsy

Adults ≥17 years with partial-onset seizures or LGS

Initial dose

25 mg to 50 mg orally once daily

Recommended dose

200 mg to 400 mg once daily

Titration

Increase dose weekly by increments of 25 mg to 50 mg to achieve an effective dose

Adults ≥17 years with primary generalized tonic-clonic seizures

Initial dose

25 mg to 50 mg orally once daily

Recommended dose

400 mg once daily

Titration

Increase dose weekly to an effective dose by increments of 25 mg to 50 mg

Pediatric patients 6 years and older with partial-onset seizures, primary generalized tonic-clonic seizures, or LGS

Initial dose

25 mg once at nighttime (based on a range of 1 mg/kg to 3 mg/kg once daily) for the first week

Recommended dose

5 mg/kg to 9 mg/kg once daily

Titration

Increase dosage at 1- or 2-week intervals by increments of 1 mg/kg to 3 mg/kg; dose titration should be guided by clinical outcome

Abbreviation: LGS, Lennox-Gastaut syndrome.

Patient savings

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

GET CO-PAY CARD

Trokendi XR® (topiramate) co-pay savings card
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RESOURCES

TERMS AND CONDITIONS

*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.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

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

WARNINGS & PRECAUTIONS

• 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.

• Immediate-release topiramate monotherapy demonstrated significant decrease in bone mineral density (BMD) measured in lumbar spine and in total body less head in a one year active controlled study in pediatric patients. Although decreases in BMD occurred across all pediatric age subgroups, patients 6 to 9 years of age were most commonly affected. Decreased BMD in the lumbar spine was correlated with decreased serum bicarbonate, which commonly occurs with topiramate treatment and reflects metabolic acidosis, a known cause of increased bone resorption

• Immediate-release topiramate monotherapy demonstrated negative effects on growth (height and weight) among pediatric patients in a one-year active controlled study. Negative effects on growth were seen across all immediate-release topiramate age subgroups. Growth of children receiving prolonged TROKENDI XR® therapy should be carefully monitored.

• Serious skin reactions (Stevens-Johnson Syndrome [SJS] and Toxic Epidermal Necrolysis [TEN]) have been reported in patients receiving topiramate. Trokendi XR should be discontinued at the first sign of a rash, unless the rash is clearly not drug related. If signs or symptoms suggest SJS/TEN, use of this drug should not be resumed and alternative therapy should be considered. Inform patients about the signs of serious skin reactions.

• 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. An increase in urinary calcium and decrease in urinary citrate was observed in immediate-release topiramate-treated pediatric patients in a one-year active-controlled study. Increased ratio of urinary calcium/citrate increases the risk of kidney stones and/or nephrocalcinosis.

• 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.

DOSING GUIDELINES & CONSIDERATIONS

• 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.

ADVERSE REACTIONS

• 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 the preventive treatment of migraine 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%).

INDICATION

• 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 for oral use

REFERENCES

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

2. Data on file. Supernus Pharmaceuticals, Inc.

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