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

Blond woman with glasses at picnic

Frequently asked questions

About Trokendi XR

Trokendi XR (topiramate) is a prescription medicine used:

  • to prevent migraine headaches in adults and adolescents 12 years and older
  • to treat certain types of seizures (partial onset seizures and primary generalized tonic-clonic seizures) in people 6 years and older
  • with other medicines to treat certain types of seizures (partial onset seizures, primary generalized tonic-clonic seizures, and seizures associated with Lennox-Gastaut syndrome) in adults and children 6 years and older

Before taking Trokendi XR (topiramate), tell your healthcare provider about all your medical conditions, including if you:

  • have or have had depression, mood problems, or suicidal thoughts or behavior
  • have kidney problems, kidney stones, or are getting kidney dialysis
  • have a history of metabolic acidosis (too much acid in the blood)
  • have liver problems
  • have weak, brittle, or soft bones (osteomalacia, osteoporosis, osteopenia, or decreased bone density)
  • have lung or breathing problems
  • have eye problems, especially glaucoma
  • have diarrhea
  • have a growth problem
  • are on a diet high in fat and low in carbohydrates, which is called a ketogenic diet
  • are having surgery
  • are pregnant or plan to become pregnant
  • are breastfeeding. Trokendi XR (topiramate) passes into your breast milk. It is not known if the Trokendi XR that passes into breast milk can cause other serious harm to your baby. Talk to your healthcare provider about the best way to feed your baby if you take Trokendi XR

Tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. Trokendi XR (topiramate) and other medicines may affect each other, causing side effects. Especially, tell your healthcare provider if you take:

  • valproic acid (such as DEPAKENE® or DEPAKOTE®)
  • any medicines that impair or decrease your thinking, concentration, or muscle coordination
  • birth control pills. Trokendi XR (topiramate) may make your birth control pills less effective. Tell your healthcare provider if your menstrual bleeding changes while you are taking birth control pills and Trokendi XR (topiramate)
  • Take Trokendi XR (topiramate) capsules whole. Do not sprinkle Trokendi XR on food, or break, crush, dissolve, or chew Trokendi XR (topiramate) capsules before swallowing
  • If you cannot swallow Trokendi XR (topiramate) capsules whole, tell your healthcare provider. You may need a different medicine
  • Take Trokendi XR (topiramate) exactly as prescribed
  • Your healthcare provider may change your dose. Do not change your dose without talking to your healthcare provider
  • Do not stop taking Trokendi XR (topiramate) without talking to your healthcare provider. Stopping Trokendi XR (topiramate) suddenly may cause serious problems. If you have epilepsy and you stop taking Trokendi XR (topiramate) suddenly, you may have seizures that do not stop. Your healthcare provider will tell you how to slowly stop taking Trokendi XR (topiramate)
  • Talk to your healthcare provider on what you should do if you miss a dose
  • Do not drink alcohol within 6 hours prior to and 6 hours after taking Trokendi XR (topiramate) capsules. Trokendi XR (topiramate) and alcohol can cause serious side effects, such as severe sleepiness and dizziness and an increase in seizures.
  • Do not drive a car or operate heavy machinery until you know how Trokendi XR (topiramate) affects you. Trokendi XR (topiramate) can slow your thinking and motor skills, and may affect vision

Trokendi XR (topiramate) can harm your unborn baby.

  • If you take Trokendi XR (topiramate) during pregnancy, your baby has a higher risk for birth defects called cleft lip and cleft palate. These defects can begin early in pregnancy, even before you know you are pregnant
  • Also, if you take Trokendi XR (topiramate) during pregnancy, your baby may be smaller than expected at birth. The long-term effects of this are not known
  • There may be other medicines to treat your condition that have a lower chance of birth defects
  • All women of childbearing age should talk to their healthcare providers about using other possible treatments instead of Trokendi XR (topiramate). If the decision is made to use Trokendi XR (topiramate), you should use effective birth control (contraception) unless you are planning to become pregnant. You should talk to your healthcare provider about the best kind of birth control to use while you are taking Trokendi XR (topiramate)
  • Tell your healthcare provider right away if you become pregnant while taking Trokendi XR (topiramate). You and your healthcare provider should decide if you will continue to take Trokendi XR (topiramate) while you are pregnant
  • Metabolic acidosis may have harmful effects on your baby. Talk to your healthcare provider if Trokendi XR (topiramate) has caused metabolic acidosis during your pregnancy
  • Pregnancy Registry: If you become pregnant while taking Trokendi XR (topiramate), talk to your healthcare provider about registering with the North American Antiepileptic Drug Pregnancy Registry. You can enroll in this registry by calling 1-888-233-2334. The purpose of this registry is to collect information about the safety of Trokendi XR (topiramate) and other antiepileptic drugs during pregnancy

Trokendi XR (topiramate) may cause serious side effects, including:

  • High blood ammonia levels. High ammonia in the blood can affect your mental activities, slow your alertness, make you feel tired, or cause vomiting. This has happened when Trokendi XR (topiramate) is taken with a medicine called valproic acid (DEPAKENE® and DEPAKOTE®)
  • Kidney stones. Drink plenty of fluids when taking Trokendi XR (topiramate) to decrease your chances of getting kidney stones
  • Low body temperature. Taking Trokendi XR (topiramate) when you are also taking valproic acid may cause a drop in body temperature to less than 95°F, feeling tired, confusion, or coma
  • Effects on thinking and alertness. Trokendi XR (topiramate) may affect how you think, and may cause confusion, problems with concentration, attention, memory, or speech. Trokendi XR (topiramate) may cause depression or mood problems, tiredness, and sleepiness
  • Dizziness or loss of muscle coordination

Call your prescriber right away if you have any of these symptoms. These are not all the possible side effects of Trokendi XR (topiramate). Please see the Patient Medication Guide or talk to your healthcare provider for more information about possible side effects of Trokendi XR (topiramate).

Call a healthcare provider right away if you have any of these symptoms, especially if they are new, worse, or worry you:

  • thoughts about suicide or dying
  • attempts to commit suicide
  • new or worse depression
  • new or worse anxiety
  • feeling agitated or restless
  • panic attacks
  • trouble sleeping (insomnia)
  • new or worse irritability
  • acting aggressive, being angry or violent
  • acting on dangerous impulses
  • an extreme increase in activity and talking (mania)
  • other unusual changes in behavior or mood
  • if you have any new eye symptoms, including any new problems with your vision
  • if a high fever, a fever that does not go away, or decreased sweating develops
  • Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings
  • Keep all follow-up visits with your healthcare provider as scheduled
  • Call your healthcare provider between visits as needed, especially if you are worried about symptoms
  • Store Trokendi XR (topiramate) capsules at room temperature between 59°F to 86°F (15°C to 30°C)
  • Keep Trokendi XR (topiramate) in a tightly closed container
  • Keep Trokendi XR (topiramate) dry and away from moisture and light
  • Keep Trokendi XR (topiramate) and all medicines out of the reach of children and pets

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