Topiramate (Topamax)

Primer

Topiramate (Trade name: Topamax) is an anticonvulsant used to treat epilepsy and prevent migraines. It is also used in the treatment of alcohol use disorder.

Pharmacokinetics

Pharmacokinetics of Topiramate

Absorption
Distribution
Metabolism
Elimination
Half-life

Topiramate: Cytochrome P450 Metabolism

Substrate of (Metabolized by)
Induces
Inhibits

Pharmacodynamics

Mechanism of Action

  • Blocks Na+ channels
  • Increases GABA activity

Toxicity

Indications

  • Seizure disorders
  • Stimulant use disorder (cocaine and stimulant)
  • Possibly for aggression, alcoholism, anger, impulsivity (off-label)

Dosing

Dosing for Topiramate

Starting
Titration
Maximum
Taper

Formulations

  • Topiramate comes in

Monitoring

Contraindications

Absolute

Relative

Drug-Drug Interactions

Side Effects

  • Sedation, cognitive impairment can be significant (pejoratively called “Dopamax”)
  • Weight loss

Adverse Events

  • Topiramate increases the risk for nephrolithiasis (kidney stones) due to hypocitraturia and high urine pH[1][2]
    • However, it is not an absolute contraindication in patients with kidney stones[3]
  • Topiramate has been associated with glaucoma.[4]

Clinical Pearls

Special Populations

Geriatric

Pediatric

Obstetric and Fetal

  • Increases the risk for offspring to develop cleft palate in pregnancy

Medically Ill

Resources

References

1) Maalouf, N. M., Langston, J. P., Van Ness, P. C., Moe, O. W., & Sakhaee, K. (2011). Nephrolithiasis in topiramate users. Urological research, 39(4), 303-307.
2) Lamb, E. J., Stevens, P. E., & Nashef, L. (2004). Topiramate increases biochemical risk of nephrolithiasis. Annals of clinical biochemistry, 41(2), 166-169.
3) Jion, Y. I., Raff, A., Grosberg, B. M., & Evans, R. W. (2015). The risk and management of kidney stones from the use of topiramate and zonisamide in migraine and idiopathic intracranial hypertension. Headache: The Journal of Head and Face Pain, 55(1), 161-166.
4) Craig, J. E., Ong, T. J., Louis, D. L., & Wells, J. M. (2004). Mechanism of topiramate-induced acute-onset myopia and angle closure glaucoma. American journal of ophthalmology, 137(1), 193-195.