Topiramate

Topiramate is a sulphurated fructose. It has multiple modes of action. Topiramate is rapidly absorbed from the gastrointestinal tract. Its binding to blood proteins is negligible, however it is extensively bound to erythrocytes. Dosage and blood topiramate levels are linearly related.

• Topiramate can be given alone or in combination with other drugs for generalised tonic-clonic seizures or partial seizures with or without secondary generalisation.¹
• It can also be used as adjunctive treatment for seizures associated with Lennox-Gastaut syndrome.
• Topiramate is also licensed for migraine prophylaxis under specialist supervision.

• Breast feeding
• Porphyria

• Avoid abrupt withdrawal
• Ensure adequate hydration (especially if predisposition to nephrolithiasis or in strenuous activity or warm environment).
• Pregnancy: topiramate is teratogenic in some animal models and it is not recommended for use in women of childbearing potential.
• Hepatic impairment
• Renal impairment
• Topiramate has been associated with acute myopia with secondary angle-closure glaucoma, typically occurring within 1 month of starting treatment. Choroidal effusions resulting in anterior displacement of the lens and iris have also been reported. The CSM advises that if raised intra-ocular pressure occurs:
  • Seek specialist ophthalmological advice
  • Use appropriate measures to reduce intra-ocular pressure
  • Stop topiramate as rapidly as feasible

Topiramate has minimal interaction with other antiepileptic drugs, although hepatic enzyme inducers accelerate its metabolism. Because of this, topiramate doses may need to be reduced if patients are coming off carbamazepine or phenytoin.

• Most of the acute and dose-related side effects of topiramate are CNS-related. These include dizziness, drowsiness, headaches, irritability, cognitive slowing and speech impairment. These are usually transient and in some patients seem to be related to the dose and rate of titration.
• Nausea, abdominal pain, weight loss, anorexia. Initial weight loss is seen in up to 40% of patients but is usually not a problem.
• Paraesthesia and nephrolithiasis have also been reported.
• Rarely reduced sweating mainly in children, metabolic acidosis.
• As adjunctive therapy:
  • Commonly agitation, ataxia, asthenia, confusion, cognitive impairment, speech disorders, visual disturbances.
  • Also increased salivation, hyperkinesia and personality disorder in children.
  • Less commonly taste disturbances, abnormal gait, incoordination, psychotic reactions including hallucinations, leucopenia.

• Monotherapy
  • Initially 25 mg daily at night for 1 week then increased in steps of 25-50 mg daily at intervals of 1-2 weeks taken in 2 divided doses; usual dose is 100 mg daily in 2 divided doses; maximum dose 400 mg daily.
  • Child 6-16 years: initially 0.5-1 mg/kg daily at night for 1 week then increased in steps of 0.5 mg/kg daily at intervals of 1-2 weeks taken in 2 divided doses; usual dose is 3-6 mg/kg daily in 2 divided doses; maximum dose is 16 mg/kg daily.
• Adjunctive therapy
  • Initially 25 mg daily for 1 week then increased in steps of 25-50 mg daily at intervals of 1-2 weeks taken in 2 divided doses; usual dose is 200-400 mg daily in 2 divided doses; maximum dose is 800 mg daily.
  • Child 2-16 years: initially 25 mg daily at night for one week then increased in steps of 1-3 mg/kg daily at intervals of 1-2 weeks taken in 2 divided doses; recommended dose range is 5-9 mg/kg daily in 2 divided doses; maximum dose is 30 mg/kg daily.
• Migraine prophylaxis
  • Adult and child over 16 years: initially 25 mg daily at night for 1 week then increased in steps of 25 mg daily at intervals of 1 week; usual dose is 50-100 mg daily in 2 divided doses.
• If patient cannot tolerate the recommended titration regimens then smaller steps or longer interval between steps may be used.

• The saturable nature of topiramate binding to erythrocytes results in a concentration-dependent plasma-to-whole-blood level ratio, and therefore monitoring whole blood levels may be more useful than plasma levels.¹
• The current target range is 6-74 mcmol/L.
• Topiramate is measurable in saliva but the relationship between plasma and saliva concentrations has not yet been established.