What is the use of Topamax (Topiramate)?

From the Guidelines

Topamax (generic name: topiramate) is a medication that can be used for weight loss, particularly when combined with phentermine, with a recommended starting dose of 3.75 mg/23 mg daily for 14 days, followed by a maintenance dose of 7.5 mg/46 mg daily, and potentially escalating to 15 mg/92 mg daily for optimal efficacy, as supported by the most recent and highest quality study 1.

Key Considerations

• The medication should be used with caution in patients with a history of cardiovascular disease or uncontrolled hypertension, and avoided in patients with untreated hyperthyroidism or those taking monoamine oxidase inhibitors 1.
• Female patients with child-bearing potential should be counseled on the risks of teratogenicity and consistent use of reliable contraception while using phentermine-topiramate ER, with monitoring of serum bicarbonate levels and periodic pregnancy tests 1.
• Common side effects include paresthesia, xerostomia, constipation, headache, and cognitive impairment, with more serious risks including topiramate's teratogenic effects and potential for seizures or metabolic acidosis 1.

Dosage and Administration

• The recommended dosage of phentermine-topiramate ER is 3.75 mg/23 mg daily for 14 days, followed by 7.5 mg/46 mg daily, with potential escalation to 11.25 mg/69 mg daily and then 15 mg/92 mg daily for optimal efficacy 1.
• The medication should be taken early in the day to minimize the risk of insomnia, and patients should be advised to increase fluid intake to reduce the risk of kidney stones 1.

Comparison to Other Medications

• Phentermine-topiramate ER has been shown to be effective for weight loss, with a mean weight loss of 8.6-9.3% at 1 year and 8.7% at 2 years, compared to other medications such as orlistat, lorcaserin, and bupropion/naltrexone 1.
• The medication has a unique mechanism of action, targeting multiple signaling pathways involved in appetite and satiety regulation, and has been shown to be effective in patients with obesity and comorbidities such as type 2 diabetes 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Topamax Overview

• Topamax, also known as topiramate, is a broad-spectrum antiepileptic drug (AED) used in the treatment of epilepsy and migraine prophylaxis 2, 3, 4.
• It has established efficacy as monotherapy or adjunctive therapy in the treatment of adult and pediatric patients with various types of seizures, including generalized tonic-clonic seizures, partial seizures, and seizures associated with Lennox-Gastaut syndrome 2.

Mechanism of Action

• The anticonvulsant effect of topiramate is based on three mechanisms: modulating the blocking of Na channels, potentiation of GABAA-mediated inhibiting neurotransmission, and inhibition of excitatory neurotransmission by blocking AMPA glutamate receptors 3.
• Topiramate also has activity at multiple molecular targets, which may account for its effectiveness in migraine prophylaxis 4.

Efficacy and Safety

• Topiramate has been shown to reduce seizure frequency and improve quality of life in patients with epilepsy 2, 3.
• In migraine prophylaxis, topiramate reduces migraine frequency, acute medication use, and disability, and improves quality of life 4, 5.
• However, topiramate can cause adverse events, including CNS-related events, weight loss, renal calculi, and impairment of cognitive functions 2, 3, 4, 6.
• The incidence and severity of adverse events may be reduced through slow titration to effective and well-tolerated dosages 2.

Special Considerations

• Topiramate is associated with a risk of metabolic acidosis, elevated urine pH, reduced urine citrate, and hypercalciuria, which can increase the risk of calcium phosphate stone formation 6.
• Patients prescribed topiramate should be carefully monitored for metabolic derangements and may benefit from alkali supplementation or discontinuation of the drug in extreme cases 6.
• Topiramate is also associated with an increased risk of cleft lip with or without cleft palate in infants exposed to the drug during the first trimester of pregnancy 4, 5.