topiramate TOPAMAX

Class: AED/​Mood Stabilizer
FDA Indications: Adjunct Therapy For Partial Onset Seizures In Adults And Children Ages 2-16, Adjunct Therapy For Primary Generalized Tonic-clonic Seizures In Adults And Children Ages 2-16, Seizures Associated With Lennox-Gastaut Syndrome (ages 2 And Older), Migraine Prophylaxis
Off-Label Use: Bipolar Disorder, Binge Eating Disorder, PTSD, Drug-induced Weight Gain, Restless Leg Syndrome, Anxiety, Obesity, Stimulant Abuse, Alcohol Dependence
Prescribing
Forms: 25, 100, 200mg tablet; 15, 25mg sprinkle capsule
Dose Range: 50-300 mg/day
Starting: 50 mg bid; titrate up to 200-400 mg/day in two doses for epilepsy; 50-300 mg/day for adjunctive treatment of bipolar disorder
Stopping: Withdrawal should be done gradually
Monitoring: Baseline and periodic measurement of serum bicarbonate

NAMI drug fact sheet

Precautions
Contraindications: Use of additional carbonic anhydrase inhibitors, a ketogenic diet, or a family history of nephrolithiasis
Serious Side Effects: Metabolic acidosis, kidney stones, oligohidrosis and hyperthermia
Side Effects: sedation/somnolence, dizziness, confusion, ataxia, weakness, tremor, nausea, decreased appetite, weight loss, memory impairment, paresthesia, nervousness, nystagmus, speech and language difficulties
Pharmacodynamics
1° MOA: Blocks repetitive firing by acting on sodium channels, can enhance GABAA-mediated chloride flux, and appears to be an antagonist at the AMPA and KA receptors, thus blocking the effect of glutamate
Pharmacokinetics
t½: 21 (20-30)° TMAX: 1-4°
Substrate of: Renally cleared
Inhibits: 2C19; Induces: 3A4
Active Metabolites:
DDIs
  • - may interact with carbonic anhydrase inhibitors to increase risk of kidney stones
  • - may reduce effectiveness of oral contraceptives
  • - as a 2C19 inhibitor, can ↑ levels of co-prescribed 2C19 substrates as a 3A4 inducer, can ↓ levels of co-prescribed 3A4 substrates
Misc
  • - recently in combination with bupropion for weight loss in obesity (see: Contrave)
  • - weak inhibitor of carbonic anhydrase
  • - elimination kinetics are strictly linear & ∴ there is a linear relationship between maintenance dose and steady-state plasma levels
  • - excreted predominantly by the kidneys as unmetabolized drug
Special Populations

Category C

Limited data on 5 breastfeeding infants exposed to topiramate showed infant plasma topiramate levels equal to 10-20% of the maternal plasma level. The effects of this exposure on infants are unknown. Caution should be exercised when administered to a nursing woman.

Dosage adjustment may be necessary for elderly with impaired renal function

↓ dose by 50% in renally impaired patients (CrCl < than 70 mL/min/1.73 m2

In hepatically impaired patients, topiramate plasma concentrations may be increased.

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Last updated January 22 2018 19:18:05. Disclaimer: This website does not provide medical advice, nor is it a substitute for clinical judgment.