Topiramate

Topiramate is a medication belonging to the second-generation anti-epileptic drugs class. It is primarily used to manage and treat epilepsy and migraine. Additionally, it has received approval for chronic weight management in individuals with a body mass index over 30.

Topiramate (TPM) is a sulfamate-substituted D-fructose derivative. Introduced in 1986, it is considered a breakthrough in epilepsy treatment.

Operates through multiple mechanisms, including blocking voltage-dependent sodium channels, enhancing GABA activity at GABAA receptors, blocking AMPA glutamate receptors, and exhibiting a mild carbonic anhydrase inhibitory effect. Its precise mechanism of action is not fully understood.

Clinical Applications

Used for the management and treatment of epilepsy, including focal and generalized seizures.
Indicated for migraine prophylaxis.
Approved for chronic weight management in individuals with a BMI over 30.

Clinical Evaluation

In a clinical evaluation involving patients with epilepsy, topiramate showed a significantly higher effective rate (93.9%) compared to carbamazepine (77.5%).
In preclinical tests, topiramate demonstrated efficacy as adjuvant therapy, reducing seizure times in adult epilepsy patients.

Contraindications and Caution

Contraindicated in patients with acute porphyrias, risk factors for metabolic acidosis, and risk factors for nephrolithiasis.
Caution is advised in pediatric use or rapid dosage escalation due to potential cognitive impairment, neurotoxicity, and kidney stone formation.

Drug Interactions

Carbamazepine and phenytoin decrease the plasma concentration of topiramate. Dosage adjustments may be necessary.
Concomitant use with alcohol or other CNS depressant drugs is not recommended.

Special Populations

Use with caution in patients with hepatic impairment and in those with impaired renal function.
Pregnancy: Topiramate exposure during the first trimester is associated with an increased risk of major congenital malformations. Careful monitoring and consideration of alternative therapeutic options are recommended.

Pharmacokinetics

Rapidly absorbed orally with a bioavailability of approximately 81%.
Average peak concentration (Cmax) of 1.5 μg/ml is reached within 2 to 3 hours.
Approximately 13% to 17% of the drug binds to plasma proteins.

Additional Applications

Potential efficacy in depression treatment.
Approved by the FDA in combination with phentermine for weight loss.

Metabolism and Elimination

Not extensively metabolized in healthy volunteers (~20%).
Metabolism may increase to 50% in patients receiving enzyme-inducing drugs.
Eliminated chiefly in urine as unchanged drug and metabolites.