What is topiramate, and how does it work (mechanism of action)?

Topiramate is an oral drug that is used to prevent the seizures of epilepsy. It is an anti-epileptic or anti-seizure drug. It is used primarily among patients who are not controlled by other anti-epileptic drugs. About 1 in 4 Americans diagnosed with epilepsy has seizures that resist treatment with other anti-epileptic drugs. Topiramate also prevents migraine headaches.

Seizures are due to the abnormal activity (“firing”) of nerves in the brain, and the abnormal activity spreads to smaller or larger portions of the brain. Although topiramate’s exact mechanism of action is unknown, scientific studies suggest that it may alter neurotransmitters within the brain. Neurotransmitters are chemicals that nerves manufacture and use to communicate with other nearby nerves. By altering the production or action of the neurotransmitters, topiramate may suppress the abnormal activity of the nerves in the brain that cause the seizures or may prevent the abnormal activity from spreading to other nerves. Other studies suggest that topiramate may suppress the nerves directly (i.e., not by altering neurotransmitters) and make them less likely to fire. The FDA approved topiramate as a tablet in 1997. The sprinkle capsules were approved in October 1998.

What brand names are available for topiramate?

Topamax, Qudexy XR, Topamax Sprinkle, Topiragen, Trokendi XR

Is topiramate available as a generic drug?

GENERIC AVAILABLE: Yes

Do I need a prescription for topiramate?

Yes

What are the side effects of topiramate?

The most common side effects of topiramate are:

Other important side effects include:

  • increased ammonia levels,
  • metabolic acidosis,
  • kidney stones,
  • decreased sweating, and
  • increased body temperature.

What is the dosage for topiramate?

  • Most commonly, topiramate immediate release tablets and sprinkles are started in low doses, 25 or 50 mg per day, and then increased slowly by 25 to 50 mg per week until an effective daily dose is reached for treatment of seizures. For children 10 years or older and adults the dose may be increased by 100 mg in week 5 and 6 when topiramate is used alone. This slow approach to treatment reduces side effects. The recommended final adult dose is 200-400 mg administered as two divided doses daily.
  • In children, the starting dose is up to 25 mg (1 to 3 mg/kg/day), taken nightly for the first week. The dose is then increased at 1 or 2 week intervals by 1 to 3 mg/kg/day administered in two divided doses. The target dose is 5 to 9 mg/kg per day in two divided doses.
  • Migraine is treated 25 mg nightly for the first week then increased by 25 mg weekly up to a maximum dose of 100 mg administered in two divided doses.
  • Patients should maintain an adequate fluid intake in order to minimize the risk of kidney stones.
  • The recommended dose for extended release capsules is 200-400 mg once daily.

Which drugs or supplements interact with topiramate?

The following medications, when taken with topiramate, increase the risk of kidney stones and metabolic acidosis: acetazolamide (Diamox), dorzolamide (Trusopt), methazolamide (Neptazane), dichlorphenamide (Daranide).

Carbamazepine (Tegretol) and phenytoin (Dilantin) markedly decrease the amount of topiramate in the body by increasing its elimination from the body. As a result, topiramate may lose effectiveness unless doses are increased.

Combining valproic acid (Depakote, Depakote ER, Depakene, Depacon, Stavzor) with topiramate may increase the blood ammonia levels and cause hypothermia.

Topiramate may decrease the amount of estrogen in the body in women taking oral contraceptives, possibly increasing the chances of unwanted pregnancy and breakthrough bleeding.

Patients with seizure disorders taking anticonvulsant medications, including topiramate, may develop nerve toxicity from a chemical, 4′-O-methylpyridoxine, found as a contaminant in some ginkgo preparations.

Topiramate may cause metabolic acidosis. Metformin (Glucophage) is contraindicated in patients with metabolic acidosis.

Topiramate may increase lithium (Eskalith, Lithobid) levels at higher doses.

Is topiramate safe to take if I’m pregnant or breastfeeding?

Topiramate has been associated with cleft palate in newborns whose mothers used topiramate during the first trimester of pregnancy.

Topiramate is excreted in human milk at levels 10% to 20% the levels in the mother’s blood.

What else should I know about topiramate?

What preparations of topiramate are available?
  • Tablets: 25, 50, 100, 200 mg
  • Sprinkle capsules: 15 and 25 mg
  • Capsule (Extended Release): 25, 50, 100, 150, 200 mg
How should I keep topiramate stored?
  • Topiramate tablets should be stored at room temperature, 15 C to 30 C (59F to 86 F).
  • Sprinkle capsules should be stored at or below 25 C (77 F).

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Medically Reviewed on 6/26/2019

References

Reference: FDA Prescribing Information