Topiramate | Epilepsy clinician handbook
Topiramate has a broad range of seizure efficacy and on the Australian PBS can be considered in treatment for focal onset seizures, primary generalised tonic-clonic seizures, and seizures associated with Lennox Gastaut Syndrome not controlled satisfactorily by other anti-seizure medications.
It has been used in neonates and infants.
Important: Dosing information
Initiation and escalation doses on this webpage are a guide only.
All medications must be individualised based on:
- patient age, weight, co-morbidities
- disease, seizure type, frequency, duration
- medication metabolism, interactions, side-effect profile characteristics.
Further consultation with appropriate formularies or a paediatric neurologist may be required.
Dosing
Commonly used regime
- As monotherapy or add-on therapy, starting dose is 0.5-1mg/kg/day in two divided doses increasing either weekly or fortnightly by 0.5mg-1mg/kg/day to target.
- In certain acute situations such as an epileptic encephalopathy or status epilepticus, initiating dose can be higher (e.g. 2mg/kg/day) and rate of escalation faster. Consultation with Paediatric Neurology may be helpful.
- Maintenance dose range is 3-5mg/kg/day in two divided doses. Some patients may respond to 2mg/kg/day.
- Doses can be increased to 8-9mg/kg/day in selected drug-resistant cases.
- The medication is probably ineffective if there is no improvement in seizures around 7mg/kg/day. Advice from a Paediatric Neurologist may be helpful.
- Maintenance dosage for older children/teenagers is: 100-200mg BD.
- Dosages per kilogram can only be used up to weights of 30-40kgs.
Preparations
- Tablets 25mg, 50mg, 100mg, 200mg
- Topamax Sprinkle Capsule 15mg, 25mg, 50mg
- Tablets or capsule contents can be dissolved to make a liquid form.
- It can be given rectally if a child is fasting.
Monitoring
- Drug level monitoring is not routinely utilized or readily available.
- Blood bicarbonate should be checked within a month as a guide and then at intervals with dose escalation. This is particularly important in the infant.
- Renal ultrasound and urine testing are considered as necessary, particularly if back pain or haematuria
Formulary
Possible side effects
- Marked loss of appetite/loss of weight may occur and require cessation of the drug.
- As topiramate is a carbonic anhydrase inhibitor, metabolic acidosis is a common finding in young infants. Blood bicarbonate levels around 16-18mmol/L are to be expected and usually cause no significant problems. Lower levels may require treatment.
- Nephrocalcinosis can occur and children on long-term treatment or who have other risk factors can be monitored with urine studies and renal ultrasound.
- Reduced sweating may cause heat intolerance which is manageable with simple measures. Care must be taken in warm climates. In the very young heat intolerance can be a more serious side effect and overheating must be avoided.
- Word-finding difficulty and language impairment can occur and are more of a risk with higher doses.
- Sedation can occur but is more common with higher doses.
- Mood disturbance (irritability, agitation, depression) can occur.
- Glaucoma is a contraindication. Advise urgent review if painful eyes develop.
- Rarely, visual field defect is described.
- Paraesthesia and hand tingling can occur but are uncommon.
- All anti-seizure medications are potentially teratogenic and this is often dose related (see section: ASM Prescribing - Pregnancy)
- For a complete list of adverse effects, appropriate formularies should be consulted.
All anti-seizure medications are potentially teratogenic and this is often dose related. For a complete list of adverse effects, appropriate formularies should be consulted.
Interactions and precautions
Precautions
- Topiramate may decrease serum concentrations of oestrogens.
- Topiramate may increase toxicity of sodium valproate.
- Topiramate concentration may be decreased by carbamazepine.
Pregnancy and topiramate
- All anti-seizure medications are potentially teratogenic and this is often dose related
Monitoring
- Drug level monitoring is not routinely utilized or readily available.
- Blood bicarbonate should be checked within a month as a guide and then at intervals with dose escalation. This is particularly important in the infant.
- Renal ultrasound and urine testing are considered as necessary, particularly if back pain or haematuria.
Resources
This information is reviewed annually by the Sydney Children’s Hospitals Network Paediatric Epilepsy NSW working group which includes medical, nursing, and pharmacy representation.