General Information

Trokendi XR is an extended-release formulation of topiramate, an anticonvulsant.

Trokendi XR is specifically indicated as initial monotherapy in patients 10 years of age and older with partial onset or primary generalized tonic-clonic seizures and adjunctive therapy in patients 6 years of age and older with partial onset or primary generalized tonic-clonic seizures. Trokendi XR is also indicated as adjunctive therapy in patients 6 years of age and older with seizures associated with Lennox-Gastaut syndrome.

Mechanism of Action

Trokendi XR is an extended-release formulation of topiramate, an anticonvulsant. The precise mechanisms by which topiramate exerts its anticonvulsant effects are unknown; however, preclinical studies have revealed four properties that may contribute to topiramate's efficacy for epilepsy. Electrophysiological and biochemical evidence suggests that topiramate, at pharmacologically relevant concentrations, blocks voltage-dependent sodium channels, augments the activity of the neurotransmitter gamma-aminobutyrate at some subtypes of the GABA-A receptor, antagonizes the AMPA/kainate subtype of the glutamate receptor and inhibits the carbonic anhydrase enzyme.

Side Effects

Adverse events associated with the use of Topamax XR may include, but are not limited to, the following:

• paresthesia
• anorexia
• weight decrease
• fatigue
• dizziness
• somnolence
• nervousness
• psychomotor slowing
• difficulty with memory
• difficulty with concentration/attention
• cognitive problems
• confusion
• mood problems
• fever
• infection
• flushing

Dosing/Administration

Trokendi XR is supplied as a capsule for oral administration. The recommended dose regimen is as follows:
Monotherapy use
Adults and pediatrics 10 years and older with partial onset or primary generalized tonic-clonic seizures: 400 mg orally once daily. Titrate Trokendi XR according to the following schedule:
Week 1 50 mg once daily
Week 2 100 mg once daily
Week 3 150 mg once daily
Week 4 200 mg once daily
Week 5 300 mg once daily
Week 6 400 mg once daily

Adjunctive therapy use
Adults (17 years of age and older) - partial onset seizures, primary generalized tonic-clonic seizures or Lennox-Gastaut syndrome: partial onset seizures or Lennox-Gastaut syndrome - 200 mg to 400 mg orally once daily; primary generalized tonic-clonic seizures - 400 mg orally once daily. Initiate therapy at 25 mg to 50 mg once daily followed by titration to an effective dose in increments of 25 mg to 50mg every week.

Pediatrics (ages 6 years to 16 years) - partial onset seizures, primary generalized tonic-clonic seizures or Lennox-Gastaut syndrome: approximately 5 mg/kg to 9 mg/kg orally once daily. Begin titration at 25 mg once daily (based on a range of 1 mg/kg/day to 3 mg/kg/day) given nightly for the first week. Subsequently, increase the dosage at one- or two­-week intervals by increments of 1 mg/kg to 3 mg/kg to achieve optimal clinical response.

Clinical Trial Results

The FDA approval of Trokendi XR was based on studies using an immediate-release formulation of topiramate and the demonstration of the pharmacokinetic equivalence of Trokendi XR to immediate-release topiramate through the analysis of concentrations and cumulative AUCs at multiple time points.