Topiramate

Topiramate(中文: 托吡酯) 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.

Drug Names

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

How long does it take for topiramate to work?

For EPILEPSY, it can take 1 to 2 weeks. For MIGRAINES, it can take 1 month for migraine attacks to be less frequent. But it can take 2 to 3 months for topiramate to fully work.

Should I take topiramate at night or in the morning?

Topiramate causes drowsiness and fatigue in up to 15% of people taking it. At the start of treatment topiramate may be taken once a day, preferably at night.

Pharmacokinetics

Oral bioavailability	Topiramate is rapidly absorbed after oral doses.
Onset of action	Peak plasma concentrations occur about 2 hours after oral doses.
Metabolism	It is not extensively metabolized in the liver
Elimination half-life	It is excreted chiefly in urine. The mean elimination half-life is about 21 hours. Steady-state concentrations occur after about 4 to 8 days in patients with normal renal function.

How long does topiramate stay in your system?

The elimination half-life of a medication is the time it takes for blood levels of the medication to be reduced by half.

It takes approximately 5.5 x elimination half-life for a medicine to be out of your system.

It can take about 120 hours (5 days) for Topiramate to be out of one’s system.

Drug Management

Monitoring

• Topiramate has been associated with acute myopia with secondary angle-glaucoma. Seek specialist ophthalmological advice if raised intra-ocular pressure occurs.
• Liver and kidney function tests to monitor side effects
• Symptoms and signs suggestive of bone-marrow failure, such as anaemia, bruising or infection.
• Patients with heart failure should be weighed regularly to detect fluid retention.
• Patients with pre-existing cardiac conduction disorders should be carefully monitored.
• changes in mood, the development or worsening depression, and/or any thoughts or behaviour of suicide.

Drug interaction

There are complex interactions between antiepileptics, and toxicity may be enhanced. Plasma monitoring is often advisable with combination therapy.

• As topiramate inhibits carbonic anhydrase, use with other inhibitors of carbonic anhydrase (e.g. acetazolamide) increases the risk of kidney stones
• Topiramate may increase the plasma-levels of phenytoin and increase risk of toxicity
• Topiramate induces CYP3A4 which translating to accelerate metabolism of estrogens. This can reduce the effectiveness of oral contraceptives. Use of alternative birth control methods is recommended.
• Alcohol may cause increased sedation or drowsiness, and increase the risk of having a seizure

Caution

• Avoid abrupt withdrawal (taper off over 2 weeks or longer) unless serious skin reaction occurs
• Used with caution in patients with renal or hepatic impairment
• Avoid in acute porphyria, risk of metabolic acidosis – ensure adequate hydration (especially in strenuous activity or warm environment)

Hepatic impairment

Use with caution in moderate to severe impairment – clearance may be reduced.

Renal impairment

In adults	If creatinine clearance less than 70 mL/minute: Half usual starting and maintenance dose
In children	If estimated creatinine clearance less than 70 mL/minute: Half usual starting and maintenance dose

Pregnancy

• Increased risk if cleft palate if taken in the first trimester of pregnancy.
• The dose should be monitored carefully during pregnancy and after birth, and adjustments made on a clinical basis
• It is recommended that the fetal growth should be monitored

Breast-feeding

Use during breast feeding is not recommended.

Epilepsy and driving

Driving by patients with epilepsy is generally regulated. Also, antiepileptic drugs may produce CNS-related adverse effects, including dizziness and drowsiness, that could impair a patient’s ability to drive a vehicle or operate machinery, particularly during the initial stages of therapy.

FAQ

How should I take the tablet?

Topiramate can be taken with or without food. Swallow your tablets whole with a glass of water, since breaking them may leave a bitter taste. To prevent kidney stones from forming, drink plenty of liquids while taking this medication unless your doctor instructs you otherwise. Topiramate capsules can be swallowed whole or they can be opened and sprinkled on soft food, like porridge.

What should I avoid while taking?

Avoid abruptly discontinue the medication.

Avoid alcohol.

What happen if I overdose?

Contact your primary care doctor. If emergency situation, call 999

What happen if I miss a dose?

Take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.