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Therapeutic Classification: anticonvulsants

• Partial-onset seizures (as monotherapy or adjunctive therapy).
• Primary generalized tonic-clonic seizures (as monotherapy or adjunctive therapy).
• Seizures due to Lennox-Gastaut syndrome (as adjunctive therapy).
• Prevention of migraine headache.

Unlabeled Uses:

• Adjunct in treatment of bipolar disorder.
• Infantile spasms.

• Action may be due to:
  • Blockade of sodium channels in neurons,
  • Enhancement of gamma-aminobutyrate, an inhibitory neurotransmitter,
  • Prevention of activation of excitatory receptors.

• Decreased incidence of seizures.
• Decreased incidence/severity of migraine headache.

Absorption: 80% absorbed following oral administration.

Distribution: Minimally distributed to tissues.

Metabolism/Excretion: Not extensively metabolized. 70% excreted unchanged in urine.

Half-life: Immediate release: 21 hr; Extended release: 31 hr.

(plasma concentrations†)

†After single dose.

Contraindicated in:

• Hypersensitivity
• Recent alcohol use (within 6 hr before and after use of extended-release product)
• Metabolic acidosis (on metformin) (with extended-release product only).

Use Cautiously in:

• All patients (may ↑ risk of suicidal thoughts/behaviors)
• Renal impairment (dose ↓ recommended if CCr <70 mL/min/1.73 m²)
• Hepatic impairment
• Dehydration
• Patients predisposed to metabolic acidosis
• Sulfa allergy
• Women of reproductive potential
• OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk
• Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant
• Pedi: Safety and effectiveness not established in children <2 yr (immediate-release) and <6 yr (extended-release); children are more prone to oligohydrosis, hyperthermia, metabolic acidosis, ↓ bone mineral density, and ↓ growth
• Geri: Consider age-related ↓ in renal/hepatic impairment, concurrent disease states and drug therapy in older adults.

Derm: oligohydrosis (↑ in children), STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS.

EENT: abnormal vision, diplopia, nystagmus, ↑ intraocular pressure, acute myopia/secondary angle closure glaucoma, mydriasis, ocular pain, ocular redness, retinal detachment, visual field defects.

Endo: ↓growth (children).

F and E: hyperchloremic metabolic acidosis.

GI: nausea, abdominal pain, anorexia, constipation, dry mouth, hyperammonemia.

GU: kidney stones.

Hemat: BLEEDING, leukopenia.

Metab: weight loss, hyperthermia (↑ in children).

MS: ↓bone mineral density (↑ in children).

Neuro: ataxia, cognitive disorders, dizziness, drowsiness, fatigue, impaired concentration/memory, nervousness, paresthesia, psychomotor slowing, sedation, speech problems, aggressive reaction, agitation, anxiety, confusion, depression, encephalopathy, malaise, mood problems, SEIZURES, SUICIDAL THOUGHTS, tremor.
Misc: fever.

Drug-Drug:

• Alcohol use within 6 hr before or after use of Trokendi XR may significantly alter topiramate levels; use during this time frame contraindicated
• Phenytoin, carbamazepine, or valproic acid may ↓ levels and effectiveness.
• May ↑ levels and the risk of toxicity of phenytoin, amitriptyline, or lithium.
• May ↓ levels and effectiveness of hormonal contraceptives, risperidone, or valproic acid.
• ↑risk of CNS depression with alcohol or other CNS depressants.
• Carbonic anhydrase inhibitors (e.g. acetazolamide or zonisamide) may ↑ risk of metabolic acidosis and kidney stones.
• Concurrent use with valproic acid may ↑ risk of hyperammonemia, encephalopathy, and hypothermia.
• ↑risk of bleeding with aspirin, clopidogrel, ticagrelor, prasugrel, warfarin, dabigatran, rivaroxaban, apixaban, edoxaban, NSAIDs, or SSRIs.

Epilepsy (monotherapy)

• PO (Adults and Children 10 yr): Immediate-release: 25 mg twice daily initially, gradually ↑ at weekly intervals to 200 mg twice daily over a 6-wk period; Extended-release (Qudexy XR or Trokendi XR): 50 mg once daily initially, gradually ↑ at weekly intervals to 400 mg once daily over a 6-wk period.
• PO (Children 2–<10 yr [6–<10 yr for Trokendi XR] and >38 kg): Immediate-release: 25 mg once daily in the evening initially, gradually ↑ at weekly intervals to 125 mg twice daily over a 5–7-wk period; if needed may continue to titrate dose on a weekly basis up to 200 mg twice daily; Extended-release (Qudexy XR or Trokendi XR): 25 mg once daily for 1 wk, then ↑ to 50 mg once daily for 1 wk, then ↑ by 25–50 mg/day at weekly intervals over a 5–7-wk period to target dose of 250–400 mg once daily.
• PO (Children 2–<10 yr [6–<10 yr for Trokendi XR] and 32–38 kg): Immediate-release: 25 mg once daily in the evening initially, gradually ↑ at weekly intervals to 125 mg twice daily over a 5–7-wk period; if needed, may continue to titrate dose on a weekly basis up to 175 mg twice daily; Extended-release (Qudexy XR or Trokendi XR): 25 mg once daily for 1 wk, then ↑ to 50 mg once daily for 1 wk, then ↑ by 25–50 mg/day at weekly intervals over a 5–7-wk period to target dose of 250–350 mg once daily.
• PO (Children 2–<10 yr [6–<10 yr for Trokendi XR] and 23–31 kg): Immediate-release: 25 mg once daily in the evening initially, gradually ↑ at weekly intervals to 100 mg twice daily over a 5–7-wk period; if needed; may continue to titrate dose on a weekly basis up to 175 mg twice daily; Extended-release (Qudexy XR or Trokendi XR): 25 mg once daily for 1 wk, then ↑ to 50 mg once daily for 1 wk, then ↑ by 25–50 mg/day at weekly intervals over a 5–7-wk period to target dose of 200–350 mg once daily.
• PO (Children 2–<10 yr [6–<10 yr for Trokendi XR] and 12–22 kg): Immediate-release: 25 mg once daily in the evening initially, gradually ↑ at weekly intervals to 100 mg twice daily over a 5–7-wk period; if needed, may continue to titrate dose on a weekly basis up to 150 mg twice daily; Extended-release (Qudexy XR or Trokendi XR): 25 mg once daily for 1 wk, then ↑ to 50 mg once daily for 1 wk, then ↑ by 25–50 mg/day at weekly intervals over a 5–7-wk period to target dose of 200–300 mg once daily.
• PO (Children 2–<10 yr [6–<10 yr for Trokendi XR] and 11 kg): Immediate-release: 25 mg once daily in the evening initially, gradually ↑ at weekly intervals to 75 mg twice daily over a 5–7-wk period; if needed, may continue to titrate dose on a weekly basis up to 125 mg twice daily; Extended-release (Qudexy XR or Trokendi XR): 25 mg once daily for 1 wk, then ↑ to 50 mg once daily for 1 wk, then ↑ by 25–50 mg/day at weekly intervals over a 5–7-wk period to target dose of 150–250 mg once daily.

Epilepsy (adjunctive therapy)

• PO (Adults and Children 17 yr): Immediate-release: 25–50 mg/day initially, ↑ by 25–50 mg/day at weekly intervals up to 200–400 mg/day in 2 divided doses (200–400 mg/day in 2 divided doses for partial seizures or Lennox-Gastaut syndrome and 400 mg/day in 2 divided doses for primary generalized tonic-clonic seizures); Extended-release (Qudexy XR or Trokendi XR): 25–50 mg once daily initially, ↑ by 25–50 mg/day at weekly intervals up to 200–400 mg once daily (for partial seizures or Lennox-Gastaut syndrome) and 400 mg once daily (for primary generalized tonic-clonic seizures).
• PO (Children 2–16 yr): Immediate-release and extended-release (Qudexy XR): 25 mg once daily at night initially for first wk, ↑ at 1–2 wk intervals by 1–3 mg/kg/day up to 5–9 mg/kg/day in 2 divided doses.
• PO (Children 6–16 yr): Extended-release (Trokendi XR): 25 mg once daily at night initially for first wk, ↑ at 1–2 wk intervals by 1–3 mg/kg/day up to 5–9 mg/kg/day given once daily at night.

Migraine Prevention

• PO (Adults and Children 12 yr): Immediate-release: 25 mg at night initially, ↑ by 25 mg/day at weekly intervals up to target dose of 100 mg/day in 2 divided doses; Extended-release (Qudexy XR): 25 mg once daily initially, ↑ by 25 mg/day at weekly intervals up to target dose of 100 mg once daily.

(Generic available)

• Immediate-release tablets: 25 mg; 50 mg; 100 mg; 200 mg;
• Extended-release capsules (Qudexy XR): 25 mg; 50 mg; 100 mg; 150 mg; 200 mg;
• Extended-release capsules (Trokendi XR): 25 mg; 50 mg; 100 mg; 200 mg;
• Oral solution (mixed berry flavor): 25 mg/mL;
• Sprinkle capsules: 15 mg; 25 mg;
• In combination with: phentermine (Qsymia). See Appendix [not included in this PDA edition]

• Monitor closely for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.
• Pedi: Monitor growth rate (height and weight) in pediatric patients; may have negative effects on height and weight.
• Seizures: Assess location, duration, and characteristics of seizure activity.
• Migraines: Assess pain location, intensity, duration, and associated symptoms (photophobia, phonophobia, nausea, vomiting) during migraine attack. Monitor frequency and intensity of pain on pain scale.
• Bipolar Disorder: Assess mental status (mood, orientation, behavior) and cognitive abilities before and periodically during therapy.

• Monitor CBC with differential and platelet count before therapy to determine baseline levels and periodically during therapy. Frequently causes anemia.
  • Monitor hepatic function periodically during therapy. May cause ↑ AST and ALT levels.
  • Evaluate serum bicarbonate prior to and periodically during therapy. Monitor for signs and symptoms of metabolic acidosis (hyperventilation, fatigue, anorexia, cardiac arrhythmias, stupor). If metabolic acidosis occurs, dosing taper or discontinuation may be necessary.

• Implement seizure precautions.
  • Do not confuse Topamax with Toprol XL.
• PO: May be administered without regard to meals.
  • DNC: Do not break/crush tablets because of bitter taste.
  • Contents of the sprinkle capsules can be sprinkled on a small amount (teaspoon) of soft food, such as applesauce, custard, ice cream, oatmeal, pudding, or yogurt. To open, hold the capsule upright so that you can read the word "TOP." Carefully twist off the clear portion of the capsule. It may be best to do this over the small portion of the food onto which you will be pouring the sprinkles. Sprinkle the entire contents of the capsule onto the food. Be sure the patient swallows the entire spoonful of the sprinkle/food mixture immediately without chewing. Follow with fluids immediately to make sure all of the mixture is swallowed. Never store a sprinkle/food mixture for use at another time.
  • A 6 mg/mL oral suspension may be compounded by pharmacy for pediatric patients.
  • DNC: Swallow extended-release capsules (Trokendi XR) whole; do not sprinkle on food, break, crush, dissolve, or chew.
  • DNC: Swallow extended-release capsules (Qudexy XR) whole; may be opened and sprinkled on soft food; do not crush or chew. Swallow immediately; do not save for later.

• Instruct patient to take topiramate exactly as directed. Take missed doses as soon as possible but not just before next dose; do not double doses. Notify health care professional if more than 1 dose is missed. Medication should be gradually discontinued to prevent seizures and status epilepticus. Instruct patient to read the Medication Guide before starting and with each Rx refill in case of changes.
• May cause decreased sweating and increased body temperature. Advise patients, especially parents of pediatric patients, to provide adequate hydration and monitoring, especially during hot weather.
• May cause dizziness, drowsiness, confusion, and difficulty concentrating. Caution patients to avoid driving or other activities requiring alertness until response to medication is known.
• Advise patient to maintain a fluid intake of 2000–3000 mL of fluid/day to prevent the formation of kidney stones.
• Instruct patient to notify health care professional immediately if periorbital pain or blurred vision occur. Medication should be discontinued if ocular symptoms occur. May lead to permanent loss of vision.
• Advise patient and family to notify health care professional if thoughts about suicide or dying, attempts to commit suicide; new or worse depression; new or worse anxiety; feeling very agitated or restless; panic attacks; trouble sleeping; new or worse irritability; acting aggressive; being angry or violent; acting on dangerous impulses; an extreme increase in activity and talking; other unusual changes in behavior or mood; or rash occur.
• Inform patients that topiramate may cause encephalopathy. If signs and symptoms (unexplained lethargy, vomiting, changes in mental status) occur, notify health care professional.
• Caution patient to make position changes slowly to minimize orthostatic hypotension.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
• Advise patient not to take alcohol or other CNS depressants concurrently with this medication. Avoid alcohol 6 hr before and 6 hr after taking Trokendi XR.
• Instruct patient to notify health care professional of medication regimen before treatment or surgery.
• Advise patient to use sunscreen and wear protective clothing to prevent photosensitivity reactions.
• May cause fetal harm. Infants exposed to topiramate during pregnancy are at increased risk for cleft lip and/or cleft palate and for being small for gestational age. Advise patient to use a nonhormonal form of contraception while taking topiramate; may make hormonal contraceptives less effective. Notify health care professional if pregnancy is planned or suspected or if breastfeeding. If pregnancy occurs, encourage patient to enroll in the North American Drug Pregnancy Registry by calling 1-888-233-2334 or online at www.aedpregnancyregistry.org/.
• Advise patient to carry identification describing disease and medication regimen at all times.

• Absence or reduction of seizure activity.
• Decrease in incidence and severity of migraine headaches.
• Remission of manic symptoms.

Eprontia, Qudexy XR, Topamax, Topamax Sprinkle, Trokendi XR