Topiramate

Topiramate may be found in some form under the following brand names:

• Qudexy XR

• Topamax

• Topiragen

• Trokendi

Topiramate may cause eye problems. Serious eye problems include:

• any sudden decrease in vision with or without eye pain and redness
• a blockage of fluid in the eye causing increased pressure in the eye (secondary angle closure glaucoma)

These eye problems can lead to permanent loss of vision if not treated. You should call your healthcare provider right away if you have any new eye symptoms.

Topiramate may cause decreased sweating and increased body temperature (fever). People, especially children, should be watched for signs of decreased sweating and fever, especially in hot temperatures. Some people may need to be hospitalized for this condition. Call your healthcare provider right away if you have a fever or decreased sweating.

Topiramate can increase the level of acid in your blood (metabolic acidosis). If left untreated, metabolic acidosis can cause brittle or soft bones (osteoporosis, osteomalacia, osteopenia), kidney stones, can slow the rate of growth in children, and may possibly harm your baby if you are pregnant. Metabolic acidosis can happen with or without symptoms.

Sometimes people with metabolic acidosis will:

• feel tired
• not feel hungry (loss of appetite)
• feel changes in heartbeat
• have trouble thinking clearly

Your healthcare provider should do a blood test to measure the level of acid in your blood before and during your treatment with topiramate. If you are pregnant, you should talk to your healthcare provider about whether you have metabolic acidosis.

Topiramate may cause suicidal thoughts or actions in a very small number of people, about 1 in 500.

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

Do not stop topiramate without first talking to a healthcare provider.

• Stopping topiramate suddenly can cause serious problems.
• Suicidal thoughts or actions can be caused by things other than medicines. If you have suicidal thoughts or actions, your healthcare provider may check for other causes.

Watch for early symptoms of suicidal thoughts and actions.

• 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.

Topiramate can harm your unborn baby (see "Pregnant Section").

• Do not drink alcohol while taking topiramate. Topiramate and alcohol can affect each other causing side effects such as sleepiness and dizziness.
• Do not drive a car or operate heavy machinery until you know how topiramate affects you. Topiramate can slow your thinking and motor skills, and may affect vision.

Medicines can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of topiramate there are no specific foods that you must exclude from your diet when receiving topiramate.

If you take too much topiramate, call your local Poison Control Center or seek emergency medical attention right away.

Topiramate is used alone or together with other medicines to help treat certain types of seizures (eg, partial seizures, tonic-clonic seizures, or Lennox-Gastaut syndrome). topiramate will not cure epilepsy and will only work to control seizures for as long as you continue to take it. It is also used to help prevent migraine headaches.

topiramate is available only with your doctor's prescription.

Take topiramate only as directed by your doctor. Do not use more of it, do not use it more often, and do not use it for a longer time than your doctor ordered.

topiramate comes with a Medication Guide. Read and follow the instructions carefully. Ask your doctor if you have any questions.

Topiramate may be taken with or without food.

Swallow the Trokendi XR™ extended-release capsule whole. Do not open, crush, or chew the capsule.

Avoid drinking alcohol with Qudexy® XR or Topamax®, or avoid for 6 hours before and 6 hours after taking the Trokendi XR™ capsule.

Swallow the tablet whole. Do not break, crush, or chew it. The tablet may taste bitter if it is held in the mouth or chewed.

The Topamax® sprinkle capsule or Qudexy® XR extended-release capsule may be swallowed whole or opened and sprinkled on a small amount (1 teaspoon) of soft food like applesauce. Swallow the food mixture immediately without chewing. Do not store the mixture for use at a later time.

Drink extra water with topiramate to help prevent kidney stones.

Dosing

The dose of topiramate will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of topiramate. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (extended-release capsules):
  • For seizures (taken with other medicines):
    • Adults—At first, 25 to 50 milligrams (mg) once a day. Your doctor may adjust the dose as needed. However, the dose is usually not more than 400 mg per day.
    • Children—
      • Qudexy®:
        • Children 2 years of age and older—Dose is based on body weight and must be determined by your doctor. The usual starting dose is 25 milligrams (mg) once a day in the evening. Your doctor may adjust the dose as needed. However, the dose is usually not more than 5 to 9 mg per kilogram (kg) of body weight per day.
        • Children younger than 2 years of age—Use is not recommended.
      • Trokendi™:
        • Children 6 years of age and older—At first, 25 milligrams (mg) once a day in the evening. Your doctor may adjust the dose as needed. However, the dose is usually not more than 5 to 9 mg per kilogram (kg) of body weight per day.
        • Children younger than 6 years of age—Use is not recommended.
  • For seizures (taken alone):
    • Qudexy®:
      • Adults and children 10 years of age and older—At first, 50 milligrams (mg) once a day. Your doctor may increase the dose as needed. However, the dose is usually not more than 400 mg per day.
      • Children 2 to 10 years of age—Dose is based on body weight and must be determined by your doctor. The starting dose is usually 25 mg once a day, in the evening. Your doctor may increase the dose as needed and tolerated. However, the dose is usually not more than 400 mg per day.
      • Children younger than 2 years of age—Use and dose must be determined by your doctor.
    • Trokendi™:
      • Adults and children 10 years of age and older—At first, 50 milligrams (mg) once a day. Your doctor may adjust the dose as needed. However, the dose is usually not more than 400 mg per day.
      • Children younger than 10 years of age—Use and dose must be determined by your doctor.
  • For migraine headaches:
    • Adults and children 12 years of age and older—At first, 25 milligrams (mg) once a day. Your doctor may adjust the dose as needed. However, the dose is usually not more than 100 mg per day.
    • Children younger than 12 years of age—Use and dose must be determined by your doctor.
• For oral dosage forms (capsules or tablets):
  • For seizures (taken with other medicines):
    • Adults and children 17 years of age and older—At first, 25 or 50 milligrams (mg) once a day. Your doctor may adjust the dose as needed. However, the dose is usually not more than 400 mg per day.
    • Children 2 to 16 years of age—Dose is based on body weight and must be determined by your child's doctor. The starting dose is usually 25 milligrams (mg) once a day in the evening. The doctor may adjust the dose as needed.
    • Children younger than 2 years of age—Use and dose must be determined by your doctor.
  • For seizures (taken alone):
    • Adults and children 10 years of age and older—At first, 50 milligrams (mg) per day, divided and taken as 2 doses. Your doctor may adjust the dose as needed. However, the dose is usually not more than 400 mg per day.
    • Children 2 to less than 10 years of age—Dose is based on body weight and must be determined by your child's doctor. The starting dose is usually 25 milligrams (mg) once a day in the evening. The doctor may adjust the dose as needed. However, the dose is usually not more than 250 to 400 mg per day.
    • Children younger than 2 years of age—Use and dose must be determined by your doctor.
  • For migraine headaches:
    • Adults and children 12 years of age and older—At first, 25 milligrams (mg) once a day in the evening. Your doctor may adjust the dose as needed. However, the dose is usually not more than 100 mg per day.
    • Children younger than 12 years of age—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of topiramate, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

If you miss a dose or forget to use your medicine, use it as soon as you can. If your next regular dose of Topamax® capsule or tablet is less than 6 hours away, wait until then to use the medicine and skip the missed dose.

If you miss more than 1 dose of Topamax® capsule or tablet, contact your doctor for instructions about how to re-start it.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

It is very important that your doctor check your or your child's progress at regular visits to see if the medicine is working properly. Blood tests may be needed to check for unwanted effects.

Using topiramate while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant. If you think you have become pregnant while using topiramate, tell your doctor right away.

Birth control pills containing estrogen may not work properly if you take them with topiramate. To keep from getting pregnant, use an additional form of birth control together with your birth control pill. If you have any questions about this, check with your doctor or pharmacist.

topiramate may cause vision changes, clumsiness or unsteadiness, dizziness, drowsiness, or trouble with thinking or speaking. Make sure you know how you or your child react to topiramate before you drive, use machines, climb in high places, swim, or do anything else that could be dangerous if you are not alert, well-coordinated, or able to think or see well.

topiramate will add to the effects of alcohol and other CNS depressants (medicines that make you drowsy or less alert). Some examples of CNS depressants are antihistamines or medicine for hay fever, allergies, or colds, prescription pain medicines, or sleep medicines. Check with your doctor before taking any of these medicines while you or your child are using topiramate.

Check with your doctor immediately if you or your child have changes in vision or pain around the eyes during and after treatment with topiramate. Your doctor may want your eyes to be checked by an ophthalmologist (eye doctor).

topiramate may make you sweat less which will cause your body temperature to increase. Use extra care not to become overheated during exercise or hot weather with topiramate. Overheating may result in heat stroke and hot baths or saunas may make you dizzy or feel faint.

Topiramate may cause some people to be agitated, irritable, or display other abnormal behaviors. It may also cause some people to have suicidal thoughts and tendencies or to become more depressed. If you, your child, or your caregiver notice any of these side effects, tell your doctor right away.

topiramate may cause nausea, muscle tremors, breathing problems, eating problems, fast heartbeats, restlessness, and abdominal or stomach pain. Tell your doctor right away if you or your child have any of these symptoms. You might have a serious condition called metabolic acidosis (too much acid in the blood).

topiramate may cause slow growth. For children, the doctor will need to keep track of height and weight to make sure that the child is growing properly.

Do not suddenly stop taking topiramate without checking first with your doctor. Stopping the medicine suddenly may cause your seizures to return or to occur more often. Your doctor may want you or your child to gradually reduce the amount you are taking before stopping it completely.

Check with your doctor right away if you or your child are having unusual drowsiness, dullness, tiredness, weakness, feelings of sluggishness, mental depression or anxiety, nightmares or unusually vivid dreams, or vomiting. These may be symptoms of a serious condition called hyperammonemic encephalopathy.

Check with your doctor right away if you or your child have sudden back pain, abdominal or stomach pain, pain while urinating, or bloody or dark urine. These may be symptoms of kidney stones.

Tell your doctor if your or your child's skin feels like it is burning, crawling, itching, or if you have numbness, prickling, "pins and needles", or tingling feeling after using topiramate.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Any vision problems, especially blurred vision, double vision, eye pain, or rapidly decreasing vision
• burning, prickling, or tingling sensations
• clumsiness or unsteadiness
• confusion
• continuous, uncontrolled back-and-forth or rolling eye movements
• dizziness
• drowsiness
• eye redness
• generalized slowing of mental and physical activity
• increased eye pressure
• memory problems
• menstrual changes
• menstrual pain
• nervousness
• speech or language problems
• trouble in concentrating or paying attention
• unusual tiredness or weakness

• Abdominal or stomach pain
• fever, chills, or sore throat
• lessening of sensations or perception
• loss of appetite
• mood or mental changes, including aggression, agitation, apathy, irritability, and mental depression
• red, irritated, or bleeding gums
• weight loss

• Blood in the urine
• decrease in sexual performance or desire
• difficult or painful urination
• frequent urination
• hearing loss
• loss of bladder control
• lower back or side pain
• nosebleeds
• pale skin
• red or irritated eyes
• ringing or buzzing in the ears
• skin rash or itching
• swelling
• trouble breathing

• Blistering, peeling, or loosening of the skin
• blisters in the mouth
• blisters on the trunk, scalp, or other areas
• bloating
• clay-colored stools
• constipation
• cough
• diarrhea
• increased rate of breathing
• joint or muscle pain
• pain or tenderness in upper abdomen or stomach
• red skin lesions, often with a purple center
• sores, ulcers, or white spots in the mouth or on the lips
• yellow eyes or skin

Get emergency help immediately if any of the following symptoms of overdose occur:

• Decreased awareness or responsiveness
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• severe sleepiness
• unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Breast pain in women
• tremors

• Back pain
• chest pain
• constipation
• heartburn
• hot flushes
• increased sweating
• leg pain

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Pregnancy

Pregnancy Category D [see Warnings and Precautions (5.7)]

Topiramate can cause fetal harm when administered to a pregnant woman. Data from pregnancy registries indicate that infants exposed to Topiramate in utero have an increased risk for cleft lip and/or cleft palate (oral clefts) and for being small for gestational age. When multiple species of pregnant animals received Topiramate at clinically relevant doses, structural malformations, including craniofacial defects, and reduced fetal weights occurred in offspring. Topiramate should be used during pregnancy only if the potential benefit outweighs the potential risk. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus [see Use in Specific Populations (8.8)].

Pregnancy Registry

Patients should be encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry if they become pregnant. This registry is collecting information about the safety of antiepileptic drugs during pregnancy. To enroll, patients can call the toll-free number 1-888-233-2334. Information about the North American Drug Pregnancy Registry can be found at http://www.aedpregnancyregistry.org/.

Human Data

Data from pregnancy registries indicate an increased risk of oral clefts in infants exposed to Topiramate during the first trimester of pregnancy. In the NAAED pregnancy registry, the prevalence of oral clefts among Topiramate-exposed infants (1.1%) was higher than the prevalence of infants exposed to a reference AED (0.36%) or the prevalence of infants in mothers without epilepsy and without exposure to AEDs (0.12%). It was also higher than the background prevalence in United States (0.17%) as estimated by the Centers for Disease Control and Prevention (CDC). The relative risk of oral clefts in Topiramate-exposed pregnancies in the NAAED Pregnancy Registry was 9.6 (95% Confidence Interval [CI] 4.0 to 23.0) as compared to the risk in a background population of untreated women. The UK Epilepsy and Pregnancy Register reported a prevalence of oral clefts among infants exposed to Topiramate monotherapy (3.2%) that was 16 times higher than the background rate in the UK (0.2%).

Data from the NAAED pregnancy registry and a population-based birth registry cohort indicate that exposure to Topiramate in utero is associated with an increased risk of small for gestational age (SGA) newborns (birth weight <10th percentile). In the NAAED pregnancy registry, 19.7% of Topiramate-exposed newborns were SGA compared to 7.9% of newborns exposed to a reference AED and 5.4% of newborns of mothers without epilepsy and without AED exposure. In the Medical Birth Registry of Norway (MBRN), a population-based pregnancy registry, 25% of newborns in the Topiramate monotherapy exposure group were SGA compared to 9 % in the comparison group unexposed to AEDs. The long term consequences of the SGA findings are not known.

Topiramate treatment can cause metabolic acidosis [see Warnings and Precautions (5.4)]. The effect of Topiramate-induced metabolic acidosis has not been studied in pregnancy; however, metabolic acidosis in pregnancy (due to other causes) can cause decreased fetal growth, decreased fetal oxygenation, and fetal death, and may affect the fetus' ability to tolerate labor. Pregnant patients should be monitored for metabolic acidosis and treated as in the nonpregnant state [see Warnings and Precautions (5.4)]. Newborns of mothers treated with Topiramate should be monitored for metabolic acidosis because of transfer of Topiramate to the fetus and possible occurrence of transient metabolic acidosis following birth.  

Animal Data

Topiramate has demonstrated selective developmental toxicity, including teratogenicity, in multiple animal species at clinically relevant doses. When oral doses of 20, 100, or 500 mg/kg were administered to pregnant mice during the period of organogenesis, the incidence of fetal malformations (primarily craniofacial defects) was increased at all doses. The low dose is approximately 0.2 times the recommended human dose (RHD) 400 mg/day on a mg/m2 basis. Fetal body weights and skeletal ossification were reduced at 500 mg/kg in conjunction with decreased maternal body weight gain.

In rat studies (oral doses of 20, 100, and 500 mg/kg or 0.2, 2.5, 30, and 400 mg/kg), the frequency of limb malformations (ectrodactyly, micromelia, and amelia) was increased among the offspring of dams treated with 400 mg/kg (10 times the RHD on a mg/m2 basis) or greater during the organogenesis period of pregnancy. Embryotoxicity (reduced fetal body weights, increased incidence of structural variations) was observed at doses as low as 20 mg/kg (0.5 times the RHD on a mg/m2 basis). Clinical signs of maternal toxicity were seen at 400 mg/kg and above, and maternal body weight gain was reduced during treatment with 100 mg/kg or greater.

In rabbit studies (20, 60, and 180 mg/kg or 10, 35, and 120 mg/kg orally during organogenesis), embryo/fetal mortality was increased at 35 mg/kg (2 times the RHD on a mg/m2 basis) or greater, and teratogenic effects (primarily rib and vertebral malformations) were observed at 120 mg/kg (6 times the RHD on a mg/m2 basis). Evidence of maternal toxicity (decreased body weight gain, clinical signs, and/or mortality) was seen at 35 mg/kg and above.

When female rats were treated during the latter part of gestation and throughout lactation (0.2, 4, 20, and 100 mg/kg or 2, 20, and 200 mg/kg), offspring exhibited decreased viability and delayed physical development at 200 mg/kg (5 times the RHD on a mg/m2 basis) and reductions in pre- and/or postweaning body weight gain at 2 mg/kg (0.05 times the RHD on a mg/m2 basis) and above. Maternal toxicity (decreased body weight gain, clinical signs) was evident at 100 mg/kg or greater.

In a rat embryo/fetal development study with a postnatal component (0.2, 2.5, 30, or 400 mg/kg during organogenesis; noted above), pups exhibited delayed physical development at 400 mg/kg (10 times the RHD on a mg/m2 basis) and persistent reductions in body weight gain at 30 mg/kg (1 times the RHD on a mg/m2 basis) and higher.

Labor and Delivery

Although the effect of Topiramate on labor and delivery in humans has not been established, the development of Topiramate-induced metabolic acidosis in the mother and/or in the fetus might affect the fetus' ability to tolerate labor [see Use in Specific Populations (8.1)].

Nursing Mothers

Limited data on 5 breastfeeding infants exposed to Topiramate showed infant plasma Topiramate levels equal to 10 to 20% of the maternal plasma level. The effects of this exposure on infants are unknown. Caution should be exercised when administered to a nursing woman.

Pediatric Use

Adjunctive Treatment for Partial Onset Epilepsy in Pediatric Patients 1 to 24 months

Safety and effectiveness in patients below the age of 2 years have not been established for the adjunctive therapy treatment of partial onset seizures, primary generalized tonic-clonic seizures, or seizures associated with Lennox-Gastaut syndrome. In a single randomized, double-blind, placebo-controlled investigational trial, the efficacy, safety, and tolerability of Topiramate oral liquid and sprinkle formulations as an adjunct to concurrent antiepileptic drug therapy in pediatric patients 1 to 24 months of age with refractory partial onset seizures were assessed. After 20 days of double-blind treatment, Topiramate (at fixed doses of 5, 15, and 25 mg/kg/day) did not demonstrate efficacy compared with placebo in controlling seizures.

In general, the adverse reaction profile for Topiramate in this population was similar to that of older pediatric patients, although results from the above controlled study and an open-label, long-term extension study in these pediatric patients 1 to 24 months old suggested some adverse reactions/toxicities (not previously observed in older pediatric patients and adults; i.e., growth/length retardation, certain clinical laboratory abnormalities, and other adverse reactions/toxicities that occurred with a greater frequency and/or greater severity than had been recognized previously from studies in older pediatric patients or adults for various indications.

These very young pediatric patients appeared to experience an increased risk for infections (any Topiramate dose 12%, placebo 0%) and of respiratory disorders (any Topiramate dose 40%, placebo 16%). The following adverse reactions were observed in at least 3% of patients on Topiramate and were 3% to 7% more frequent than in patients on placebo: viral infection, bronchitis, pharyngitis, rhinitis, otitis media, upper respiratory infection, cough, and bronchospasm. A generally similar profile was observed in older pediatric patients [see Adverse Reactions (6)].

Topiramate resulted in an increased incidence of patients with increased creatinine (any Topiramate dose 5%, placebo 0%), BUN (any Topiramate dose 3%, placebo 0%), and protein (any Topiramate dose 34%, placebo 6%), and an increased incidence of decreased potassium (any Topiramate dose 7%, placebo 0%). This increased frequency of abnormal values was not dose-related. Creatinine was the only analyte showing a noteworthy increased incidence (Topiramate 25 mg/kg/day 5%, placebo 0%) of a markedly abnormal increase. The significance of these findings is uncertain.

Topiramate treatment also produced a dose-related increase in the percentage of patients who had a shift from normal at baseline to high/increased (above the normal reference range) in total eosinophil count at the end of treatment. The incidence of these abnormal shifts was 6 % for placebo, 10% for 5 mg/kg/day, 9% for 15 mg/kg/day, 14% for 25 mg/kg/day, and 11% for any Topiramate dose. There was a mean dose-related increase in alkaline phosphatase. The significance of these findings is uncertain.

Topiramate produced a dose-related increased incidence of hyperammonemia [see Warnings and Precautions (5.9)].

Treatment with Topiramate for up to 1 year was associated with reductions in Z SCORES for length, weight, and head circumference [see Warnings and Precautions (5.4), Adverse Reactions (6)].

In open-label, uncontrolled experience, increasing impairment of adaptive behavior was documented in behavioral testing over time in this population. There was a suggestion that this effect was dose-related. However, because of the absence of an appropriate control group, it is not known if this decrement in function was treatment-related or reflects the patient's underlying disease (e.g., patients who received higher doses may have more severe underlying disease) [see Warnings and Precautions (5.6)].

In this open-label, uncontrolled study, the mortality was 37 deaths/1000 patient years. It is not possible to know whether this mortality rate is related to Topiramate treatment, because the background mortality rate for a similar, significantly refractory, young pediatric population (1 to 24 months) with partial epilepsy is not known.

Monotherapy Treatment in Partial Onset Epilepsy in Patients <2 Years Old

Safety and effectiveness in patients below the age of 2 years have not been established for the monotherapy treatment of epilepsy.

Migraine Prophylaxis in Pediatric Patients 12 to 17 Years of Age

Safety and effectiveness of Topiramate in the prophylaxis of migraine was studied in 5 double-blind, randomized, placebo-controlled, parallel-group trials in a total of 219 pediatric patients, at doses of 50 to 200 mg/day, or 2 to 3 mg/kg/day. These comprised a fixed dose study in 103 pediatric patients 12 to 17 years of age [see Clinical Studies (14.3)], a flexible dose (2 to 3 mg/kg/day), placebo-controlled study in 157 pediatric patients 6 to 16 years of age (including 67 pediatric patients 12 to 16 years of age), and a total of 49 pediatric patients 12 to 17 years of age in 3 studies of migraine prophylaxis primarily in adults. Open-label extension phases of 3 studies enabled evaluation of long-term safety for up to 6 months after the end of the double-blind phase.

Efficacy of Topiramate for migraine prophylaxis in pediatric patients 12 to 17 years of age is demonstrated for a 100 mg daily dose in Study 12 [see Clinical Studies (14.3)]. Efficacy of Topiramate (2 to 3 mg/kg/day) for migraine prophylaxis was not demonstrated in a placebo-controlled trial of 157 pediatric patients (6 to 16 years of age) that included treatment of 67 pediatric patients (12 to 16 years of age) for 20 weeks.

In the pediatric trials (12 to 17 years of age) in which patients were randomized to placebo or a fixed daily dose of Topiramate, the most common adverse reactions with Topiramate that were seen at an incidence higher (≥5%) than in the placebo group were: paresthesia, upper respiratory tract infection, anorexia, and abdominal pain [see Adverse Reactions (6)].  

The most common cognitive adverse reaction in pooled double-blind studies in pediatric patients 12 to 17 years of age was difficulty with concentration/attention [see Warnings and Precautions (5.6)].

Markedly abnormally low serum bicarbonate values indicative of metabolic acidosis were reported in Topiramate-treated pediatric migraine patients [see Warnings and Precautions (5.4)].

In Topiramate-treated pediatric patients (12 to 17 years of age) compared to placebo-treated patients, abnormally increased results were more frequent for creatinine, BUN, uric acid, chloride, ammonia, total protein, and platelets. Abnormally decreased results were observed with Topiramate vs placebo treatment for phosphorus and bicarbonate [see Warnings and Precautions (5.12)].

Notable changes (increases and decreases) from baseline in systolic blood pressure, diastolic blood pressure, and pulse were observed occurred more commonly in pediatric patients treated with Topiramate compared to pediatric patients treated with placebo [see Clinical Pharmacology (12.2)].

Migraine Prophylaxis in Pediatric Patients 6 to 11 Years of Age

Safety and effectiveness in pediatric patients below the age of 12 years have not been established for the prophylaxis treatment of migraine headache.

In a double-blind study in 90 pediatric patients 6 to 11 years of age (including 59 Topiramate-treated and 31 placebo patients), the adverse reaction profile was generally similar to that seen in pooled double-blind studies of pediatric patients 12 to 17 years of age. The most common adverse reactions that occurred in Topiramate-treated pediatric patients 6 to 11 years of age, and at least twice as frequently than placebo, were gastroenteritis (12% Topiramate, 6% placebo), sinusitis (10% Topiramate, 3% placebo), weight loss (8% Topiramate, 3% placebo) and paresthesia (7% Topiramate, 0% placebo). Difficulty with concentration/attention occurred in 3 Topiramate-treated patients (5%) and 0 placebo-treated patients.

The risk for cognitive adverse reaction was greater in younger patients (6 to 11 years of age) than in older patients (12 to 17 years of age) [see Warnings and Precautions (5.6)].

Juvenile Animal Studies

When Topiramate (30, 90, or 300 mg/kg/day) was administered orally to rats during the juvenile period of development (postnatal days 12 to 50), bone growth plate thickness was reduced in males at the highest dose, which is approximately 5 to 8 times the maximum recommended pediatric dose (9 mg/kg/day) on a body surface area (mg/m2) basis.

Geriatric Use

In clinical trials, 3% of patients were over age 60. No age-related differences in effectiveness or adverse effects were evident. However, clinical studies of Topiramate did not include sufficient numbers of subjects age 65 and over to determine whether they respond differently than younger subjects. Dosage adjustment may be necessary for elderly with age-related renal impairment (creatinine clearance rate <70 mL/min/1.73 m2) resulting in reduced clearance [see Dosage and Administration (2.5), Clinical Pharmacology (12.3)].

Renal Impairment

The clearance of Topiramate is reduced in patients with moderate (creatinine clearance 30 to 69 mL/min/1.73 m2) and severe (creatinine clearance <30 mL/min/1.73 m2) renal impairment. A dosage adjustment is recommended in patients with moderate or severe renal impairment [see Dosage and Administration (2.5), Clinical Pharmacology (12.3)].

Patients Undergoing Hemodialysis

Topiramate is cleared by hemodialysis at a rate that is 4 to 6 times greater than in a normal individual. A dosage adjustment may be required [see Dosage and Administration (2.6), Clinical Pharmacology (12.3)].

Women of Childbearing Potential

Data from pregnancy registries indicate that infants exposed to Topiramate in utero have an increased risk for cleft lip and/or cleft palate (oral clefts) [see Warnings and Precautions (5.7), Use in Specific Populations (8.1)]. Consider the benefits and the risks of Topiramate when prescribing this drug to women of childbearing potential, particularly when Topiramate is considered for a condition not usually associated with permanent injury or death. Because of the risk of oral clefts to the fetus, which occur in the first trimester of pregnancy before many women know they are pregnant, all women of childbearing potential should be apprised of the potential hazard to the fetus from exposure to Topiramate. If the decision is made to use Topiramate, women who are not planning a pregnancy should use effective contraception [see Drug Interactions (7.3)]. Women who are planning a pregnancy should be counseled regarding the relative risks and benefits of Topiramate use during pregnancy, and alternative therapeutic options should be considered for these patients.

Topiramate, USP is a sulfamate-substituted monosaccharide. Topiramate Tablets USP are available as 25 mg, 50 mg, 100 mg, and 200 mg round tablets for oral administration.

Topiramate, USP is a white to off white powder. It is freely soluble in dichloromethane.

Topiramate, USP has the molecular formula C12H21NO8S and a molecular weight of 339.37. Topiramate, USP is designated chemically as 2,3:4,5-Di-O-isopropylidene-β-D-fructopyranose sulfamate and has the following structural formula:

Topiramate Tablets USP contain the following inactive ingredients: hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, pregelatinized starch, polyethylene glycol, polysorbate 80, purified water, sodium starch glycolate, and titanium dioxide. The 50 mg tablets also contain FD&C yellow# 6 and iron oxide yellow for color. The 100 mg and 200 mg tablets also contain iron oxide red and iron oxide yellow for color.

(toe PYRE a mate)

• Qudexy XR
• Topamax
• Topamax Sprinkle
• Topiragen [DSC]
• Trokendi XR

Anticonvulsant activity may be due to a combination of potential mechanisms: Blocks neuronal voltage-dependent sodium channels, enhances GABA(A) activity, antagonizes AMPA/kainate glutamate receptors, and weakly inhibits carbonic anhydrase.

Absorption

Good, rapid; immediate release formulation is unaffected by food. A single Trokendi XR dose with a high-fat meal increased the Cmax by 37% and shortened the Tmax to approximately 8 hours; this effect is significantly reduced following repeat administrations. A single Qudexy XR dose with a high-fat meal delayed the Tmax by 4 hours.

Distribution

Vd: 0.6 to 0.8 L/kg

Metabolism

Minor amounts metabolized in liver via hydroxylation, hydrolysis, and glucuronidation; there is evidence of renal tubular reabsorption; percentage of dose metabolized in liver and clearance are increased in patients receiving enzyme inducers (eg, carbamazepine, phenytoin)

Excretion

Urine (~70% as unchanged drug); may undergo renal tubular reabsorption

Clearance:

Not receiving concomitant enzyme inducers or valproic acid:

Neonates (full-term) with hypothermia: 13.4 mL/kg/hour (Fillipi 2009)

Infants and Children 9 months to <4 years: 46.5 mL/kg/hour (range: 30.5 to 70.9 mL/kg/hour) (Mikaeloff 2004)

Children 4 to 17 years: 27.6 mL/kg/hour (Rosenfeld 1999)

Receiving concomitant enzyme inducers:

Neonates (full-term) with hypothermia: 17.9 mL/kg/hour (Fillipi 2009)

Infants and Children 9 months to <4 years: 85.4 mL/kg/hour (range: 46.2 to 135 mL/kg/hour) (Mikaeloff 2004)

Children and Adolescents 4 to 17 years: 60.6 mL/kg/hour (Rosenfeld 1999)

Receiving valproic acid: Infants and Children 9 months to <4 years: 49.6 mL/kg/hour (range: 26.6 to 60.2 mL/kg/h) (Mikaeloff 2004)

Adults: 20 to 30 mL/minute

Time to Peak

Immediate release:

Neonates (full-term) with hypothermia: 3.8 hours (Fillipi 2009)

Infants and Children 9 months to <4 years: 3.7 hours (range: 1.5 to 10.2 hours) (Mikaeloff 2004)

Children 4 to 17 years: Mean range: 1 to 2.8 hours (Rosenfeld 1999)

Adults: 2 hours; range: 1.4 to 4.3 hours

Extended release: Qudexy XR: ~20 hours; Trokendi XR: ~24 hours

Half-Life Elimination

Immediate release:

Not receiving concomitant enzyme inducers or valproic acid:

Neonates (full-term) with hypothermia: ~43 hours (Fillipi 2009)

Infants and Children 9 months to <4 years: 10.4 hours (range: 8.5 to 15.3 hours) (Mikaeloff 2004)

Children 4 to 7 years: Mean range: 7.7 to 8 hours (Rosenfeld 1999)

Children 8 to 11 years: Mean range: 11.3 to 11.7 hours (Rosenfeld 1999)

Children and Adolescents 12 to 17 years: Mean range: 12.3 to 12.8 hours (Rosenfeld 1999)

Receiving concomitant enzyme inducers (eg, carbamazepine, phenytoin, phenobarbital):

Neonates (full-term) with hypothermia: 26.5 hours (Fillipi 2009)

Infants and Children 9 months to <4 years: 6.5 hours (range: 3.75 to 10.2 hours) (Mikaeloff 2004)

Children and Adolescents 4 to 17 years: 7.5 hours (Rosenfeld 1999)

Receiving valproic acid: Infants and Children 9 months to 4 years: 9.2 hours (range: 7.23 to 12 hours) (Mikaeloff 2004)

Adults: 19 to 23 hours (mean: 21 hours)

Adults with renal impairment: 59 ± 11 hours

Extended release: Qudexy XR: ~56 hours; Trokendi XR: ~31 hours

Protein Binding

15% to 41% (inversely related to plasma concentrations)

Half-life elimination is longer. Plasma and renal clearance were reduced 21% and 19%, respectively. Reduced clearance resulted in slightly higher Cmax (23% for immediate release; 30% for Trokendi XR) and AUC (25% for immediate release; 44% for Trokendi XR). Topiramate clearance is decreased only to the extent that renal function is reduced. Tmax for Trokendi XR is shorter (16 hours).

Administer without regard to meals. Administer the immediate release formulation in divided doses. It is not recommended to crush, break, or chew immediate release tablets due to bitter taste. Swallow extended release (ER) and sprinkle capsules whole. Sprinkle capsules and Qudexy XR capsules may also be opened to sprinkle the entire contents on a small amount (~1 teaspoon) of soft food; swallow immediately and do not chew. Do not store drug/food mixture for future use. Do not sprinkle Trokendi XR capsules on food, chew, or crush. Avoid alcohol use with Trokendi XR capsules within 6 hours prior to and 6 hours after administration.

Alcohol (Ethyl): May enhance the CNS depressant effect of Topiramate. Alcohol (Ethyl) may increase the serum concentration of Topiramate. This applies specifically to use with the extended-release topiramate capsules (Trokendi XR). Also, topiramate concentrations may be subtherapeutic in the later portion of the dosage interval. Management: Concurrent use of alcohol within 6 hours of ingestion of extended-release topiramate (Trokendi XR) is contraindicated. Any use of alcohol with topiramate should be avoided when possible and should only be undertaken with extreme caution. Avoid combination

Alpha-/Beta-Agonists (Indirect-Acting): Carbonic Anhydrase Inhibitors may increase the serum concentration of Alpha-/Beta-Agonists (Indirect-Acting). Monitor therapy

Amantadine: Carbonic Anhydrase Inhibitors may increase the serum concentration of Amantadine. Monitor therapy

Amitriptyline: Topiramate may enhance the CNS depressant effect of Amitriptyline. Topiramate may increase serum concentrations of the active metabolite(s) of Amitriptyline. Topiramate may increase the serum concentration of Amitriptyline. Monitor therapy

Amphetamines: Carbonic Anhydrase Inhibitors may decrease the excretion of Amphetamines. Monitor therapy

Analgesics (Opioid): CNS Depressants may enhance the CNS depressant effect of Analgesics (Opioid). Management: Avoid concomitant use of opioid analgesics and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Anticholinergic Agents: May enhance the adverse/toxic effect of Topiramate. Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

CarBAMazepine: May decrease the serum concentration of Topiramate. Consider therapy modification

Carbonic Anhydrase Inhibitors: May enhance the adverse/toxic effect of other Carbonic Anhydrase Inhibitors. The development of acid-base disorders with concurrent use of ophthalmic and oral carbonic anhydrase inhibitors has been reported. Management: Avoid concurrent use of different carbonic anhydrase inhibitors if possible. Monitor patients closely for the occurrence of kidney stones and with regards to severity of metabolic acidosis. Avoid combination

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy

Contraceptives (Estrogens): Topiramate may decrease the serum concentration of Contraceptives (Estrogens). Contraceptive failure is possible. Management: Risk appears greatest for higher topiramate doses (200 mg/day or greater). Some have recommended using at least 50 mcg/day of ethinyl estradiol, but the effectiveness of this is unclear. Consider a nonhormonal form of contraception. Consider therapy modification

Contraceptives (Progestins): Topiramate may decrease the serum concentration of Contraceptives (Progestins). Management: Caution patients that this combination may be associated with reduced contraceptive effectiveness. Consider adding an additional (non-hormonal) contraceptive method. Consider therapy modification

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification

Flecainide: Carbonic Anhydrase Inhibitors may increase the serum concentration of Flecainide. Monitor therapy

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification

Fosphenytoin: May decrease the serum concentration of Topiramate. Topiramate may increase the serum concentration of Fosphenytoin. Monitor therapy

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Lithium: Topiramate may increase the serum concentration of Lithium. Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Loop Diuretics: May enhance the hypokalemic effect of Topiramate. Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mefloquine: May diminish the therapeutic effect of Anticonvulsants. Mefloquine may decrease the serum concentration of Anticonvulsants. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of convulsions. Monitor anticonvulsant concentrations and treatment response closely with concurrent use. Consider therapy modification

Memantine: Carbonic Anhydrase Inhibitors may increase the serum concentration of Memantine. Monitor therapy

MetFORMIN: Topiramate may enhance the adverse/toxic effect of MetFORMIN. Monitor therapy

Methenamine: Carbonic Anhydrase Inhibitors may diminish the therapeutic effect of Methenamine. Management: Consider avoiding this combination. Monitor for decreased therapeutic effects of methenamine if used concomitant with a carbonic anhydrase inhibitor. Consider therapy modification

Methotrimeprazine: May enhance the CNS depressant effect of CNS Depressants. CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

Mianserin: May diminish the therapeutic effect of Anticonvulsants. Monitor therapy

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Orlistat: May decrease the serum concentration of Anticonvulsants. Monitor therapy

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Phenytoin: Topiramate may increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Topiramate. Monitor therapy

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy

Primidone: Carbonic Anhydrase Inhibitors may enhance the adverse/toxic effect of Primidone. Specifically, osteomalacia and rickets. Carbonic Anhydrase Inhibitors may decrease the serum concentration of Primidone. Monitor therapy

QuiNIDine: Carbonic Anhydrase Inhibitors may decrease the excretion of QuiNIDine. Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Salicylates: May enhance the adverse/toxic effect of Carbonic Anhydrase Inhibitors. Salicylate toxicity might be enhanced by this same combination. Management: Avoid these combinations when possible.Dichlorphenamide use with high-dose aspirin as contraindicated. If another combination is used, monitor patients closely for adverse effects. Tachypnea, anorexia, lethargy, and coma have been reported. Consider therapy modification

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Thiazide and Thiazide-Like Diuretics: May enhance the hypokalemic effect of Topiramate. Thiazide and Thiazide-Like Diuretics may increase the serum concentration of Topiramate. Management: Monitor for increased topiramate levels/adverse effects (e.g., hypokalemia) with initiation/dose increase of a thiazide diuretic. Closely monitor serum potassium concentrations with concomitant therapy. Topiramate dose reductions may be necessary. Consider therapy modification

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Ulipristal: Topiramate may decrease the serum concentration of Ulipristal. Avoid combination

Valproate Products: Topiramate may enhance the adverse/toxic effect of Valproate Products. Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification

Commonly reported side effects of topiramate include: anxiety, ataxia, confusion, diarrhea, diplopia, dizziness, drowsiness, dysphasia, fatigue, lack of concentration, memory impairment, nausea, nervousness, paresthesia, psychomotor disturbance, speech disturbance, depression, visual disturbance, weight loss, dysgeusia, mood changes, and anorexia. Other side effects include: arthralgia, and asthenia. See below for a comprehensive list of adverse effects.

IMMEDIATE RELEASE MONOTHERAPY:
For adults with partial onset seizures or primary generalized tonic-clonic seizures: 400 mg orally daily in 2 divided doses
The dose should be achieved by titration:
Week 1: 25 mg orally in the AM and 25 mg orally in the PM
Week 2: 50 mg orally in the AM and 50 mg orally in the PM
Week 3: 75 mg orally in the AM and 75 mg orally in the PM
Week 4: 100 mg orally in the AM and 100 mg orally in the PM
Week 5: 150 mg orally in the AM and 150 mg orally in the PM
Week 6: 200 mg orally in the AM and 200 mg orally in the PM

IMMEDIATE RELEASE ADJUNCTIVE THERAPY:
17 years of age and older with partial onset seizures, primary generalized tonic-clonic seizures, or Lennox-Gastaut Syndrome:
-Partial onset seizures or Lennox-Gastaut Syndrome: 200 to 400 mg orally daily in 2 divided doses
-Primary generalized tonic-clonic seizures: 400 mg orally daily in 2 divided doses
-Therapy should be initiated at 25 to 50 mg orally daily followed by titration to an effective dose in increments of 25 to 50 mg orally daily every week. Titrating in increments of 25 mg per day every week may delay the time to reach an effective dose.
-Doses above 400 mg daily have not been shown to improve responses in dose-response studies in adults with partial onset seizures. Daily doses above 1600 mg have not been studied.
-In the study of primary generalized tonic-clonic seizures, the initial titration rate was slower than in previous studies. The assigned dose was reached at the end of 8 weeks.

EXTENDED-RELEASE MONOTHERAPY:
For adults with partial onset seizures or primary generalized tonic-clonic seizures:
400 mg orally once a day
The dose should be achieved by titration:
Week 1: 50 mg once a day
Week 2: 100 mg once a day
Week 3: 150 mg once a day
Week 4: 200 mg once a day
Week 5: 300 mg once a day
Week 6: 400 mg once a day

EXTENDED-RELEASE ADJUNCTIVE THERAPY:
17 years and older with partial onset seizures, primary generalized tonic-clonic seizures, or Lennox-Gastaut Syndrome:
-Partial onset seizures or Lennox-Gastaut Syndrome: 200 to 400 mg orally once a day
-Primary generalized tonic-clonic seizures: 400 mg orally once a day
-Therapy should be initiated at 25 to 50 mg orally once a day followed by titration to an effective dose in increments of 25 to 50 mg every week.
-Daily doses above 1600 mg have not been studied.
-In the study of primary generalized tonic-clonic seizures, the assigned dose was reached at the end of 8 weeks.

Comments:
-This drug may be taken without regard to meals.
-The addition of this drug to phenytoin may require an adjustment of the dose of phenytoin to achieve optimal clinical outcome; addition or withdrawal of phenytoin and/or carbamazepine during adjunctive therapy with this drug may require adjustment of the dose of this drug.

Uses:
-Initial monotherapy for patients with partial onset or primary generalized tonic-clonic seizures
-Adjunctive therapy for patients with partial onset seizures or primary generalized tonic-clonic seizures, and in patients with seizures associated with Lennox-Gastaut syndrome (LGS)

12 years of age and older:
IMMEDIATE RELEASE:
100 mg daily in 2 divided doses
The dose should be achieved by titration:
Week 1: No dose in the AM and 25 mg orally in the PM
Week 2: 25 mg orally in the AM and 25 mg orally in the PM
Week 3: 25 mg orally in the AM and 50 mg orally in the PM
Week 4: 50 mg orally in the AM and 50 mg orally in the PM

12 years of age and older:
EXTENDED-RELEASE:
100 mg orally once a day
The dose should be achieved by titration:
Week 1: 25 mg orally once a day
Week 2: 50 mg orally once a day
Week 3: 75 mg orally once a day
Week 4: 1000 mg orally once a day

Comments:
-This drug may be taken without regard to meals.
-Longer intervals between dose adjustments may be appropriate.

Use: For adults and adolescents 12 years of age and older for the prophylaxis of migraine headache

• Topiramate reduces the frequency and duration of seizures and is used in the treatment of certain types of epilepsy. It also prevents the development of migraine headaches.
• Experts aren't sure exactly how topiramate works in either epilepsy or to prevent migraines but research suggests it dampens down excessive nerve firing, enhances the actions of GABA, and blocks the effects of other chemical messengers.
• Topiramate belongs to the class of medicines known as carbonic anhydrase inhibitors or carbonic anhydrase inhibitor anticonvulsants. It may also be called an anticonvulsant.

• Can be taken with or without food.
• Tablets have a bitter taste; do not break.
• Topiramate is usually started at a low dosage and then titrated up slowly until an effective dose is reached (experts suggest increasing by 25 mg/day every week). Your doctor will explain this to you.
• Topiramate should be discontinued slowly to minimize the potential for seizures unless a rapid withdrawal is justified. Dosage should be titrated up slowly until effective dose is achieved (experts suggest increasing by 25mg/day every week).
• Seek urgent medical attention if you develop eye pain, blurred vision or visual disturbances while taking topiramate.
• Also, report any changes in mood or the development of depression or suicidal thoughts to your doctor.
• Discontinue slowly to minimize the potential for seizures, unless rapid withdrawal has been advised by your doctor.
• Keep up your fluid intake and avoid dehydration as topiramate can increase the risk of kidney stones developing. Topiramate may also make you sweat less or give you a fever. Contact your doctor if your fever does not go away, you develop abdominal pain with or without vomiting, or you are unable to sweat.
• Do not drive or operate machinery or perform other hazardous tasks if topiramate makes you dizzy or drowsy. Alcohol can potentiate these effects so should be avoided.
• Extended-release topiramate (Trokendi XR) should not be used in children aged less than ten when used as the sole medication, or less than six when used in addition to other anticonvulsants.
• Topiramate should not be taken during pregnancy or while breastfeeding.