Dosing and uses of Topamax, Trokendi XR Qudexy XR (topiramate)
Adult dosage forms and strengths
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)
Partial-Onset or Primary Generalized Tonic-Clonic Seizures
Monotherapy
- Topamax, Topamax Sprinkles: 25 mg PO q12hr initially; may increase by 50 mg/day at weekly intervals to 200 mg PO q12hr
- Trokendi XR, Qudexy XR: 50 mg PO qDay 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
Adjunctive therapy
- Topamax, Topamax Sprinkles: 25-50 mg/day PO initially; increase by 25-50 mg/day at weekly intervals to 100-200 mg q12hr for partial onset seizures and 200 mg q12hr
- Trokendi XR, Qudexy XR: 25-50 mg PO qDay initially; increase by 25-50 mg/day at weekly intervals to achieve effective dose; not to exceed 200-400 mg/day
Lennox-Gastaut Syndrome
Indicated as adjunctive therapy for seizures associated with Lennox-Gastaut syndrome (LGS)
Topamax, Topamax Sprinkles: 25-50 mg/day PO initially; increase by 25-50 mg/day at weekly intervals to 100-200 mg q12hr
Trokendi XR, Qudexy XR: 25-50 mg PO qDay initially; increase by 25-50 mg/day at weekly intervals to achieve effective dose; not to exceed 200-400 mg/day
Migraine Headache (Topamax)
Indicated for prophylaxis of migraine headache
Titrate over 4 wk to achieve a dose of 50 mg PO BId
Week 1: 25 mg PO qHs
Week 2: 25 mg PO BId
Week 3: 25 mg PO in the morning and 50 mg Hs
Week 4: 50 mg PO BId
Guide dose/titration rate by clinical outcome; if needed, use longer intervals between dose adjustments
Dosage modifications
Renal impairment
- CrCl <70 mL/min: Reduce dose by 50%
- Hemodialysis: Cleared by hemodialysis at rate 4-6 times greater than normal; prolonged period of dialysis may decrease topiramate serum concentrations
Hepatic impairment
- Clearance may decrease; monitor
Cluster Headache (Off-label)
Prophylaxis
Initial: 25 mg PO qDay for 7 days
Increase by 25 mg/day every week to no more than 200 mg/day
Alcoholism (Off-label)
Initial: 25 mg PO qDay week 1
May increase to maximum 300 mg/day by weeks 5-14; may divide 300 mg dose q8hr (case reports)
Maintenance: 200 mg/day divided q12hr or 300 mg/day divided q8hr
Injectable topiramate (Orphan)
Orphan designation for Captisol-enabled topiramate injection for the treatment of partial onset or primary generalized tonic-clonic seizures in hospitalized patients with epilepsy or those being treated in an emergency care setting who are unable to take oral topiramate
Orphan sponsor
- Ligand Pharmaceuticals, Inc.; 11119 North Torrey Pines Road, Suite 200; La Jolla, CA 92037
Pediatric dosage forms and strengths
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)
Partial-Onset or Primary Generalized Tonic-Clonic Seizures
Monotherapy (Topamax, Topamax Sprinkles)
- <2 years: Safety and efficacy not established
- 2 to <10 years: 25 mg PO qHS for 1 week; titrate dose over 5-7 weeks to target daily maintenance dose (weight based) and divide into q12hr dosing schedule
- Weight-based dosing
- Up to 11 kg: 150 mg/day minimum; 250 mg/day maximum
- 12-22 kg: 200 mg/day minimum; 300 mg/day maximum
- 23-31 kg: 200 mg/day minimum; 350 mg/day maximum
- 32-38 kg: 250 mg/day minimum; 350 mg/day maximum
- >38 kg: 250 mg/day minimum; 400 mg/day maximum
- ≥10 years
- 25 mg PO q12hr initially
- Titrate by increments of 50 mg/week up to 200 mg q12hr
Monotherapy (Trokendi XR)
- <6 years: Safety and efficacy not established
- 6-10 years
- 25 mg/day nightly for the first week; based upon tolerability, the dosage can be increased to 50 mg/day in the second week, and then increased by 25-50 mg/day each subsequent week as tolerated
- Minimum and maximum weight based maintenance dosage ranges listed below
- ≤11 kg: 150-250 mg/day
- 12-22 kg: 200-300 mg/day
- 23-31 kg: 200-350 mg/day
- 32-38 kg: 250-350 mg/day
- ≥38 kg: 250-400 mg/day
- ≥10 years
- 50 mg PO qDay 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 PO qDay
- 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)
- <2 years: Safety and efficacy not established
- 2 to <10 years
- 25 mg PO qHS initially during the first week; based upon tolerability, the dosage can be increased 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
- Up to 11 kg: 150 mg/day (minimum); 250 mg/day (maximum)
- 12-22 kg: 200 mg/day (minimum); 300 mg/day (maximum)
- 23-31 kg: 200 mg/day (minimum); 350 mg/day (maximum)
- 32-38 kg: 250 mg/day (minimum); 350 mg/day (maximum)
- >38 kg: 250 mg/day (minimum); 400 mg/day (maximum)
- ≥10 years
- 50 mg PO qDay initially
- Titrate to target dose by increasing 50 mg/week for first 4 weeks, and then 100 mg/week for weeks 5 to 6
- Ttarget dose is 400 mg PO qDay
Adjunctive therapy (Topamax, Topamax Sprinkles)
- <2 years: Safety and efficacy not established
- 2-16 years: 25 mg PO qHS initially for first week (based on 1-3 mg/kg/day); increase dose by 1-3 mg/kg/day PO divided q12hr at 1-2 week intervals to 5-9 mg/kg/day divided q12hr
- ≥17 years: 25-50 mg/day PO initially; increase by 25-50 mg/day at weekly intervals to 100-200 mg q12hr for partial onset seizures and 200 mg q12hr for generalized tonic/clonic seizures
Adjunctive therapy (Trokendi XR)
- <6 years: Safety and efficacy not established
- ≥6 years: 25 mg PO qHS initially for 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)
- <2 years: Safety and efficacy not established
- ≥2 years: 25 mg PO qHS initially for 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
Adjunctive therapy (Topamax, Topamax Sprinkles)
- <2 years: Safety and efficacy not established
- 2-16 years: 25 mg PO qHS initially for first week (based on 1-3 mg/kg/day); increase dose by 1-3 mg/kg/day PO divided q12hr at 1-2 week intervals to 5-9 mg/kg/day divided q12hr
- ≥17 years: 25-50 mg/day PO initially; increase by 25-50 mg/day at weekly intervals to 100-200 mg q12hr for partial onset seizures and 200 mg q12hr for generalized tonic/clonic seizures
Adjunctive therapy (Trokendi XR)
- <6 years: Safety and efficacy not established
- ≥6 years: 25 mg PO qHS initially for 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)
- <2 years: Safety and efficacy not established
- ≥2 years: 25 mg PO qHS initially for 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 (Topamax)
Indicated for prophylaxis of migraine headache
<12 years: Safety and efficacy not established
Guide dose/titration rate by clinical outcome; if needed, use longer intervals between dose adjustments
≥12 years
- Titrate over 4 wk to achieve a dose of 50 mg PO BID
- Week 1: 25 mg PO qHS
- Week 2: 25 mg PO BID
- Week 3: 25 mg PO in the morning and 50 mg HS
- Week 4: 50 mg PO BID
Dosage modifications
Renal impairment
- CrCl <70 mL/min: Reduce dose by 50%
- Hemodialysis: Cleared by hemodialysis at rate 4-6 times greater than normal; prolonged period of dialysis may decrease topiramate serum concentrations
Topamax, Trokendi XR Qudexy XR (topiramate) adverse (side) effects
>10%
Decrease in serum bicarbonate (7-67%)
Dizziness (4-29%)
Fatigue (9-16%)
Ataxia (6-16%)
Nervousness (9-18%)
Paresthesia (1-11%)
Psychomotor slowing (3-13%)
Abnormal vision (2-13%)
Anorexia (4-24%)
Confusion (4-11%)
Decreased memory (2-12%)
Nausea (6-10%)
Speech disorder (2-13%)
Injury (14%)
1-10%
Abdominal pain (6-10%)
Weight loss (4-9%)
Diplopia (1-10%)
Mood problems (<6%)
Pharyngitis (6%)
Tremor (3-9%)
Abnormal gait (3-8%)
Apathy (1%)
Asthenia (1-5%)
Dry mouth (2%)
Menorrhagia (1-2%)
Skin disorder (2-3%)
Taste change (2%)
Edema (2%)
Hypertension (1-2%)
Syncope (1%)
Bradycardia (1%)
Pallor (1%)
<1%
Angina
Erythema
Hepatic failure
Hyperthermia
Hypokalemia
Neuropathy
Toxic epidermal necrolysis
Warnings
Contraindications
Hypersensitivity
Extended release: Within 6 hr of alcohol intake; patients with metabolic acidosis that are taking metformin concomitantly
Cautions
Maintain adequate fluid intake due to kidney stone risk
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 risk of hyperammonemia (with or without encephalopathy)
Risk of 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
Risks of acute myopia and secondary angle-closure glaucoma (discontinue immediately if vision problems)
Visual field defects reported independent of elevated IOP; reversible upon discontinuation
Risk of neuropsychiatric disorder; rapid titration rate and higher initial dose were associated with higher incidence
Monitor serum bicarbonate at baseline and then periodically; may also monitor serum chloride, ammonia, and phosphorus
When discontinuing drug, gradually withdraw to decrease risk of seizure or increased seizure frequency
Increased risk in suicidal thoughts/behavior reported; monitor patients for notable changes in behavior and notify 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
Hyperammonemia with or without encephalopathy with monotherapy or in combination with valproic acid reported in patients that have tolerated each drug alone; 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
Pregnancy and lactation
Pregnancy category: d
Cleft lip and cleft palate observed in newborns whose mothers had taken topiramate during first trimester of pregnancy; prevalence of oral clefts was 1.4%, compared with 0.38-0.55% with other antiepileptic drugs (AEDs) and 0.07% with no AED exposure
Lactation: Excreted in milk; use caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Topamax, Trokendi XR Qudexy XR (topiramate)
Mechanism of action
Mechanism unknown; may inhibit neuronal voltage-dependent sodium channels and may enhance the neurotransmitter inhibitory activity of gamma-aminobutyric acid (GABA)
Weak carbonic anhydrase inhibitor
Absorption
Bioavailability: 80%
Peak serum time: 1-4 hr (IR); 24 hr (ER))
Distribution
Protein bound: 13-17% (IR); 15-41% (ER)
Metabolism
Hepatic (30%); 70% unchanged
Enzyme induced: CYP3A4 (weak)
Enzyme inhibited: CYP2C19 (weak)
Elimination
Half-life: 21 hr (IR); 31 hr (ER)
Dialyzable: Yes
Total body clearance: 20-30 mL/min; 50% higher in pediatric patients
Excretion: Urine (70-80%)
Administration
Oral Administration
Can be taken without regard to meals
Trokendi Xr
- Swallow capsule whole and intact
- Do not sprinkle on food, chew, or crush
Qudexy XR, Topamax Sprinkle Capsules
- Capsules may be swallowed whole or may be administered by carefully opening the capsule and sprinkling the entire contents on a small amount (teaspoon) of soft food
- This drug/food mixture should be swallowed immediately and not chewed or crushed
- Do not store drug/food mixture for further use
