Topiramate

Introduction

Topiramate is a medication used to treat epilepsy and prevent migraines. For epilepsy this includes treatment for generalized or focal seizures. It is also used as adjunctive treatment for seizures associated with Lennox-Gastaut syndrome.

Generic Name 藥名	HA Code 藥物代碼	Classification藥物分類
Topiramate Tablet 25 mg	TOPI01	P1S1S3
Topiramate Tablet 50 mg	TOPI01	P1S1S3
Topiramate Tablet 100 mg	TOPI03	P1S1S3

Mechanism of Action

Anticonvulsant medication. It inhibits the sodium channels, calcium channels, GABA-A receptors, and carbonic anhydrase isoenzymes, contributing to the antiseizure effects.

Dosage

For both adjunctive and monotherapy of epilepsy

By mouth ADULT: Initial dose of 25 to 50 mg at night for 1 week; then Increased by increments of 25 or 50 mg at intervals of 1 to 2 weeks until the effective dose is reached. Daily doses of more than 25 mg should be taken in 2 divided doses. The usual daily dose for adjunctive therapy is 200 to 400 mg When used as monotherapy, usual doses range from 100 mg daily to a maximum of 500 mg daily. For monotherapy, CHILD 6 – 17 years: Initially 0.5 -1 mg/kg at night for the first week, Increased thereafter by 0.5 – 1 mg/kg every 1 or 2 weeks, to an initial target dose of 100 mg (about 2 mg/kg) daily in 2 divided doses. As adjunctive therapy, CHILD form 2 years of age: 1 – 3 mg/kg once daily (maximum 25 mg). This is given as a single dose at night for 1 week, then Increased by 1 to 3 mg/kg every 1 or 2 weeks until the effective dose is reached. About 5 to 9 mg/kg daily is usually required.

Migraine prophylaxis

By mouth ADULT: Initially 25 mg once daily at night for 1 week, then Increased in steps of 25 mg every 1 week. Usual dose 50 – 100 mg daily in 2 divided doses Maximum 200 mg per day

As with other antiepileptics, withdrawal of topiramate therapy should be made gradually to avoid precipitating an increase in the frequency of seizures. The daily dose should be decreased by 50 to 100 mg at weekly intervals.

Side Effects

Adverse drug reactions associated with the use of topiramate include:

Very Common (>10% incidence)	Dizziness, Diarrhoea Depression Fatigue Somnolence Paraesthesia – e.g. pins and needles
Common (1-10% incidence)	alopecia Blurred vision, diplopia, nystagmus Cognitive impairment Confusion constipation Impaired concentration Impaired coordination Impaired speech Muscle twitching, muscular weakness, myalgia Dysuria Rash, pruritus Suicidal ideation
Rare (<0.1% of incidence)	Hepatic failure, hepatitis Periorbital oedema Raynaud’s syndrome Stevens-Johnson syndrome Angle closure glaucoma

Topiramate has been associated with acute myopia with secondary angle-closure glaucoma, typically occurring within 1 month of starting treatment. STOP topiramate may halt the progression of the ocular damage and may reverse the visual impairment.

Overdose

Topiramate has been deemed the primary substance that led to fatal overdoses in cases due to polydrug exposure. Therapeutic plasma levels are usually less than 10 mg/L, but can range from 10- 150 mg/L in overdose patients. Symptoms of overdose include:

• Agitation
• Speech problems
• Blurred vision, double vision
• Loss of consciousness and coma
• Shortness of breath; fast, shallow breathing
• Pounding or irregular heartbeat
• Bone pain
• Seizures

No antidote is available. Treatment is entirely supportive