Results
INDICATIONS
- Adjunct for neuroprotection against hypoxic-ischemic encephalopathy (HIE): Combined frequency of mortality and severe neurological disability at 18 to 24 months of age was not reduced when topiramate was added to whole-body hypothermia in a randomized pilot study of 44 asphyxiated term-newborns with HIE. The dosage of topiramate was 10 mg/kg/day orally via orogastric tube once daily for the first 3 days of life. No adverse effects were related to topiramate. Topiramate has been safely used, in concert with deep or mild hypothermia, for HIE in fullterm newborns (n=27). An initial dose of 5 mg/kg (by orogastric tube) was started at initiation of hypothermia, followed by doses of either 5 mg/kg or 3 mg/kg given on days 2 and 3
- Seizure disorders: The addition of topiramate controlled or reduced acute seizure activity in 4 of 6 term infants having a variety of seizure syndromes refractory to phenobarbital or phenobarbital + phenytoin in a retrospective review of use in term newborns (n=6). At follow-up (5 to 11.5 months), 5 of 6 patients were seizure-free on topiramate monotherapy. Of these 5 patients, 4 received topiramate 10 mg/kg/day; the remaining patient received 3 mg/kg/day.
FDA APPROVED INDICATION
- Immediate-release: Indicated for partial-onset or primary generalized tonic-clonic seizures in patients 2 years or older (initial monotherapy) and ages 2 years or older (adjunctive therapy). Indicated for seizures associated with Lennox-Gastaut syndrome in patients 2 years or older. Indicated for the prophylaxis of migraine headache in adolescents 12 years or older. The efficacy of topiramate in the acute treatment of migraine has not been studied.
- Extended-release: Indicated as initial monotherapy for partial-onset or primary generalized tonic-clonic seizures in patients 2 years or older (Qudexy® XR) and 6 years or older (Trokendi XR™). Indicated as an adjunct for seizures associated with Lennox-Gastaut syndrome, partial-onset, or primary generalized tonic-clonic seizures in patients 6 years or older (Trokendi XR™) and 2 years or older (Qudexy® XR). Also indicated for the prophylaxis of migraine headache in adolescent patients 12 years or older.
CONTRAINDICATIONS/PRECAUTIONS
Acute myopia, associated with secondary angle-closure glaucoma, has been reported with topiramate, generally within the first month of use. Hyperthermia and decreased sweating have been reported, especially in pediatric patients. Metabolic acidosis has been reported, with an increased risk in patients with conditions or therapies that predispose to acidosis (eg, renal disease, severe respiratory disorders, status epilepticus, diarrhea, ketogenic diet, or certain drugs). In patients with or without a history of seizures, topiramate should be gradually withdrawn to minimize the potential for seizures or increased seizure frequency. Hyperammonemia with or without encephalopathy may occur with topiramate with or without concomitant valproic acid
ADVERSE EFFECTS
When used for neuroprotection in concert with hypothermia for hypoxic-ischemic encephalopathy (n=27), mild and reversible acidosis was seen in patients receiving deep hypothermia (DH); metabolic acidosis was not seen with mild hypothermia (MH). In addition, short-course topiramate did not cause acid-base imbalance, nephrolithiasis, or ophthalmological concerns. When used for seizure disorders, 3 of 6 term infants had a weight of less than the fifth percentile, however, these patients also had poor oromotor control
ADMINISTRATION
Sprinkle Capsules: May be opened and the sprinkles mixed with water to be administered via orogastric tube. Use mixture immediately. Do not store opened capsules for future use. The National Institute for Occupational Safety and Health (NIOSH) recommends the use of single gloves by anyone handling intact tablets or capsules or administering from a unit-dose package. n the preparation of tablets or capsules, including cutting, crushing, or manipulating, or the handling of uncoated tablets, NIOSH recommends the use of double gloves and a protective gown. Prepare in a ventilated control device, if possible. Use respiratory protection if not prepared in a control device. During administration, wear single gloves, and wear eye/face protection if the formulation is hard to swallow or if the patient may resist, vomit, or spit up.
MONITORING
Monitor for hyperthermia and decreased sweating, especially in hot weather. Measure serum bicarbonate levels at baseline and periodically during treatment. Seizures or increased seizure frequency should be monitored in patients with or without a history of epilepsy if rapid withdrawal of topiramate therapy is required. Examination of ammonia levels is recommended in any patient experiencing unexplained lethargy, vomiting, or changes in mental status, which may be indicative of hyperammonemia with or without encephalopathy