Topiramate

Topiramate is a prescription medication used to treat Partial-Onset or Primary Generalized Tonic-Clonic Seizures, Lennox-Gastaut Syndrome, and Migraine Headaches.

• Topiramate is available under the following different brand names: Topamax, Trokendi XR, Qudexy XR, Eprontia

Adult dosage

Tablet (Topamax)

• 25mg
• 50mg
• 100mg
• 200mg

Capsule, Sprinkle (Topamax Sprinkle)

• 15mg
• 25mg

Capsule, extended-release

• 25mg (Trokendi XR, Qudexy XR)
• 50mg (Trokendi XR, Qudexy XR)
• 100mg (Trokendi XR, Qudexy XR)
• 150mg (Qudexy XR)
• 200mg (Trokendi XR, Qudexy XR)

Oral solution

• 25mg/mL (Eprontia)

Partial-Onset or Primary Generalized Tonic-Clonic Seizures

Adult dosage

Monotherapy

• Topamax, Topamax Sprinkles, Eprontia: 25 mg orally every 12 hours initially; may increase by 50 mg/day at weekly intervals to 200 mg orally every 12 hours
• Trokendi XR, Qudexy XR: 50 mg orally once daily initially; may increase by 50 mg/day at weekly intervals for first 4 weeks, then 100 mg/day for weeks 5 to 6; target dose is 200-400 mg/day for partial-onset seizures and 400 mg/day for generalized seizures

Adjunct therapy

• Topamax, Topamax Sprinkles, Eprontia: 25-50 mg/day orally initially; increase by 25-50 mg/day at weekly intervals to 100-200 mg every 12 hours for partial-onset seizures and 200 mg every 12 hours
• Trokendi XR, Qudexy XR: 25-50 mg orally once daily initially; increase by 25-50 mg/day at weekly intervals to achieve effective dose; not to exceed 200-400 mg/day

Pediatric dosage

Monotherapy (Topamax, Topamax Sprinkles, Eprontia)

• Children younger than 2 years of age: Safety and efficacy not established
• Children 2 years to 10 years of age: 25 mg orally before bedtime for 1 week
  • Titrate dose over 5-7 weeks to target daily maintenance dose (weight based) and divide into a twice-daily dosing schedule
• Children aged 2 to 10 years weight-based maintenance dosing
  • Weighing at least 11 kg: 150 mg/day minimum; 250 mg/day maximum
  • Weighing 12-22 kg: 200 mg/day minimum; 300 mg/day maximum
  • Weighing 23-31 kg: 200 mg/day minimum; 350 mg/day maximum
  • Weighing 32-38 kg: 250 mg/day minimum; 350 mg/day maximum
  • Weighing over 38 kg: 250 mg/day minimum; 400 mg/day maximum
• Children 10 years or older: 25 mg orally twice daily initially
  • Titrate by increments of 50 mg/week up to 200 mg every 12 hours

Monotherapy (Trokendi XR)

• Children 6 years or younger: Safety and efficacy not established
• Children 6-10 years of age, initial dosing:
  • 25 mg/day nightly for the first week; based upon tolerability
  • May increase to 50 mg/day in the second week and then increased by 25-50 mg/day each subsequent week as tolerated
• Children 6-10 years of age, weight-based maintenance dosing
  • Minimum and maximum weight-based maintenance dosage ranges are listed below
  • Weighing at least 11 kg: 150-250 mg/day
  • Weighing 12-22 kg: 200-300 mg/day
  • Weighing 23-31 kg: 200-350 mg/day
  • Weighing 32-38 kg: 250-350 mg/day
  • Weighing over 38 kg: 250-400 mg/day
• Children 10 years or older: 
  • 50 mg orally once daily initially; may increase by 50 mg/week for first 4 weeks, then 100 mg/week for weeks 5 to 6; target dose is 400 mg orally once daily
  • Week 1: 50 mg/day
  • Week 2: 100 mg/day
  • Week 3: 150 mg/day
  • Week 4: 200 mg/day
  • Week 5: 300 mg/day
  • Week 6: 400 mg/day

Monotherapy (Qudexy XR)

• Children 2 years of age: Safety and efficacy not established
• For children aged 2 to 10 years of age, initial dosing
  • 25 mg orally at bedtime initially during the first week; based upon tolerability,
  • May increase to 50 mg/day in the second week, and then increased by 25-50 mg/day each subsequent week, as tolerated
  • Titration to the minimum maintenance dose should be attempted over 5-7 weeks
  • Based upon tolerability and clinical response, additional titration to a higher dose (up to the maximum maintenance dose) can be attempted in weekly increments by 25-50 mg/day, up to the maximum recommended maintenance dose for each range of body weight
• For children aged 2 to 10 years of age, weight-based maintenance dosing
  • Weighing at least 11 kg: 150 mg/day (minimum); 250 mg/day (maximum)
  • Weighing 12-22 kg: 200 mg/day (minimum); 300 mg/day (maximum)
  • Weighing 23-31 kg: 200 mg/day (minimum); 350 mg/day (maximum)
  • Weighing 32-38 kg: 250 mg/day (minimum); 350 mg/day (maximum)
  • Weighing over 38 kg: 250 mg/day (minimum); 400 mg/day (maximum)
• Children aged 10 years or older: 
  • 50 mg orally once daily initially
  • Titrate to target dose by increasing 50 mg/week for first 4 weeks, and then 100 mg/week for weeks 5 to 6
  • The target dose is 400 mg orally once daily

Adjunctive therapy (Topamax, Topamax Sprinkles, Eprontia)

• Children younger than 2 years of age: Safety and efficacy not established
• Children 2-16 years: 25 mg orally at bedtime initially for the first week (based on 1-3 mg/kg/day); increase dose by 1-3 mg/kg/day orally divided every 12 hours at 1-2 week intervals to 5-9 mg/kg/day divided every 12 hours  
• Children older than 17 years: 25-50 mg/day orally initially; increase by 25-50 mg/day at weekly intervals to 100-200 mg every 12 hours for partial-onset seizures and 200 mg every 12 hours for generalized tonic/clonic seizures

Adjunctive therapy (Trokendi XR)

• Children younger than 6 years of age: Safety and efficacy not established
• Children 6 years: 25 mg orally at bedtime initially for the first week (based on 1-3 mg/kg/day); increase dose by 1-3 mg/kg once daily at 1-2 week intervals to 5-9 mg/kg once daily

Adjunctive therapy (Qudexy XR)

• Children younger than 2 years of age: Safety and efficacy not established
• Children 2 years of age: 25 mg orally at bedtime initially for the first week (based on 1-3 mg/kg/day); increase dose by 1-3 mg/kg once daily at 1-2 week intervals to 5-9 mg/kg once daily

Lennox-Gastaut Syndrome

Adult dosage

• Topamax, Topamax Sprinkles, Eprontia: 25-50 mg/day orally initially; increase by 25-50 mg/day at weekly intervals to 100-200 mg every 12 hours
• Trokendi XR, Qudexy XR: 25-50 mg orally once daily initially; increase by 25-50 mg/day at weekly intervals to achieve effective dose; not to exceed 200-400 mg/day

Pediatric dosage

Adjunctive therapy (Topamax, Topamax Sprinkles, Eprontia)

• Children younger than 2 years of age: Safety and efficacy not established
• Children aged 2-16 years: 25 mg orally at bedtime initially for the first week (based on 1-3 mg/kg/day); increase dose by 1-3 mg/kg/day orally divided every 12 hours at 1-2 week intervals to 5-9 mg/kg/day divided every 12 hours
• Children aged 17 years or older: 25-50 mg/day orally initially; increase by 25-50 mg/day at weekly intervals to 100-200 mg every 12 hours for partial-onset seizures and 200 mg every 12 hours for generalized tonic/clonic seizures

Adjunctive therapy (Trokendi XR)

• Children younger than 6 years: Safety and efficacy not established
• Children 6 years of age or older: 25 mg orally at bedtime initially for the first week (based on 1-3 mg/kg/day); increase dose by 1-3 mg/kg once daily at 1-2 week intervals to 5-9 mg/kg once daily

Adjunctive therapy (Qudexy XR)

• Children younger than 2 years of age: Safety and efficacy not established
• Children 2 years or older: 25 mg orally at bedtime initially for the first week (based on 1-3 mg/kg/day); increase dose by 1-3 mg/kg once daily at 1-2 week intervals to 5-9 mg/kg once daily

Migraine Headache

Adult dosage

Topamax, Epronita

• Titrate over 4 weeks to achieve a dose of 50 mg orally twice daily
• Week 1: 25 mg orally in the evening
• Week 2: 25 mg orally twice daily
• Week 3: 25 mg in the morning and 50 mg in the evening
• Week 4: 50 mg orally twice daily

Qudexy XR or Trokendi XR

• Titrate over 4 weeks to achieve a dose of 100 mg/day
• Week 1: 25 mg orally once daily
• Week 2: 50 mg orally once daily
• Week 3: 75 mg orally once daily
• Week 4: 100 mg orally once daily

Pediatric dosage

• Children younger than 12 years of age: Safety and efficacy not established
• Children 12 years of age or older: 

Topamax, Eprontia

• Titrate over 4 weeks to achieve a dose of 50 mg orally twice daily
• Week 1: 25 mg orally at bedtime
• Week 2: 25 mg orally twice daily
• Week 3: 25 mg orally in the morning and 50 mg at bedtime
• Week 4: 50 mg orally twice daily

Qudexy XR or Trokendi XR

• Titrate over 4 weeks to achieve a dose of 100 mg/day
• Week 1: 25 mg orally once daily
• Week 2: 50 mg orally once daily
• Week 3: 75 mg orally once daily
• Week 4: 100 mg orally once daily 

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”.

Common side effects of Topiramate include:

• dizziness, 
• drowsiness, 
• tiredness, 
• slow reactions, 
• problems with speech or memory, 
• abnormal vision, 
• numbness or tingling in arms and legs, 
• decreased sensation (especially in the skin), 
• nervousness, 
• nausea, 
• diarrhea, 
• stomach pain, 
• loss of appetite, 
• fever, 
• weight loss, 
• stuffy nose, 
• sneezing, 
• sore throat, and
• changes in sense of taste

Serious side effects of Topiramate include:

• hives, 
• difficulty breathing, 
• swelling of the face or throat, 
• fever, 
• sore throat, 
• burning eyes, 
• skin pain, 
• red or purple skin rash with blistering and peeling, 
• mood or behavior changes, 
• anxiety, 
• panic attacks, 
• trouble sleeping, 
• impulsive behavior, 
• irritableness, 
• agitation, 
• hostility, 
• aggression, 
• restlessness, 
• hyperactivity (mentally or physically), 
• depression, 
• thoughts of self-harm, 
• skin rash (no matter how mild), 
• vision problems, 
• blurred vision, 
• eye pain or redness, 
• sudden vision loss (can be permanent if not treated quickly), 
• confusion, 
• problems with thinking or memory, 
• trouble concentrating, 
• problems with speech, 
• decreased sweating, 
• high fever, 
• hot and dry skin, 
• severe pain in the side or lower back, 
• painful or difficult urination, 
• irregular heartbeats, 
• tiredness, 
• loss of appetite, 
• trouble thinking, 
• shortness of breath, 
• vomiting, 
• unexplained weakness, and
• lightheadedness

Rare side effects of Topiramate include:

• none

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them.  Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first

• Topiramate has severe interactions with no other drugs. 
• Topiramate has serious interactions with at least 24 other drugs. 
• Topiramate has moderate interactions with at least 268 other drugs.
• Topiramate has minor interactions with at least 76 other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drugs interactions. Therefore, before using this drug, tell your doctor or pharmacist of all the drugs you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Contraindications

• Hypersensitivity 
• Extended-release: Within 6 hours of alcohol intake; patients with metabolic acidosis that are taking metformin concomitantly 

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Topiramate?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Topiramate?”

Cautions

• Maintain adequate fluid intake due to kidney stone risk
• Use caution with alcohol use
• Monitor closely for decreased sweating and increased body temperature; oligohydrosis reported with use; monitor during strenuous exercise
• Concomitant use of drugs that predispose patients to heat-related disorders (such as carbonic anhydrase inhibitors and anticholinergics)
• Coadministration with valproic acid increases the risk of hyperammonemia (with or without encephalopathy)
• Risk of the hyperchloremic, non-anion gap, metabolic acidosis; especially if concomitant renal disease, severe respiratory disorder, status epilepticus, diarrhea, surgery, ketogenic diet, or drugs predisposing to acidosis; if metabolic acidosis develops and persists, consideration should be given to reducing the dose or discontinuing therapy (using dose tapering); if the decision is made to continue patients on therapy in face of persistent acidosis, alkali treatment should be considered
• Visual field defects reported independent of elevated IOP; reversible upon discontinuation
• Rapid titration rate, dose, and higher initial dose associated with a higher incidence of the neuropsychiatric disorder in both epilepsy and migraine patients; also associated with higher incidences of cognitive-related dysfunction
• Monitor serum bicarbonate at baseline and then periodically; may also monitor serum chloride, ammonia, and phosphorus
• When discontinuing the drug, gradually withdraw to decrease the risk of seizure or increased seizure frequency
• Increased risk in suicidal thoughts/behavior reported; monitor patients for notable changes in behavior and notify a healthcare provider if symptoms occur
• Use caution when operating heavy machinery
• Hypothermia reported with and without hyperammonemia during topiramate treatment with concomitant valproic acid use; consideration should be given to stopping topiramate or valproate in patients who develop hypothermia
• Hyperammonemia with or without encephalopathy with monotherapy or in combination with valproic acid reported in patients that have tolerated each drug alone; the risk may increase in patients with inborn errors of metabolism or decreased hepatic mitochondrial activity; monitor for vomiting, lethargy, or unusual changes in mental status; in some patients, hyperammonemia can be asymptomatic
• Infants exposed to topiramate in utero may have an increased risk for cleft lip and/or cleft palate (oral clefts) and for being small for gestational age
• Women of childbearing potential who are not planning a pregnancy should use effective contraception because of risks to the fetus of oral clefts and of being small for gestational age

Skin reactions

• Serious skin reactions (Stevens-Johnson Syndrome [SJS] and Toxic Epidermal Necrolysis [TEN]) were reported in patients receiving therapy
• Therapy should be discontinued at the first sign of a rash unless the rash is 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 signs of serious skin reactions

Glaucoma syndrome

• A syndrome consisting of acute myopia associated with secondary angle-closure glaucoma was reported in patients receiving the drug
• Symptoms include acute onset of decreased visual acuity and/or ocular pain
• Ophthalmologic findings can include some or all of the following: myopia, mydriasis, anterior chamber shallowing, ocular hyperemia (redness), choroidal detachments, retinal pigment epithelial detachments, macular striae, and increased intraocular pressure
• This syndrome may be associated with supraciliary effusion resulting in anterior displacement of the lens and iris, with secondary angle-closure glaucoma
• Symptoms typically occur within 1 month of initiating therapy; in contrast to primary narrow-angle glaucoma, which is rare under 40 years of age, secondary angle-closure glaucoma associated with topiramate has been reported in pediatric patients as well as adults
• The primary treatment to reverse symptoms is the discontinuation of therapy as rapidly as possible, according to the judgment of the treating physician; other measures, in conjunction with discontinuation of therapy, may be helpful

Pregnancy and Lactation

• There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to drugs during pregnancy; to enroll, patients can call the toll-free number 1-888-233-2334. Information about North American Drug Pregnancy Registry can be found at http://www.aedpregnancyregistry.org/
• Topiramate can cause fetal harm when administered to a pregnant woman; data from pregnancy registries indicate that infants exposed to topiramate in utero have increased risk for cleft lip and/or cleft palate (oral clefts) and for being small for gestational age
• In multiple animal species, topiramate demonstrated developmental toxicity, including teratogenicity, in the absence of maternal toxicity at clinically relevant doses
• Consider benefits and risks of topiramate when prescribing 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 occurs in the first trimester of a pregnancy before many women know they are pregnant, all women of childbearing potential should be informed of the potential risk to the fetus from exposure to topiramate; women who are planning a pregnancy should be counseled regarding relative risks and benefits of topiramate use during pregnancy; alternative therapeutic options should be considered for these patients
• Although the effect of topiramate on labor and delivery in humans has not been established, the development of topiramate-induced metabolic acidosis in mother and/or in fetus might affect the fetus’ ability to tolerate labor; 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 nonpregnant state; 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

Lactation

• Topiramate is excreted in human milk; effects of topiramate exposure in breastfed infants or on milk production are unknown; developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for extended-release formulation and any potential adverse effects on the breastfed infant from the extended-release formulation or the underlying maternal condition