Topiramate

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Topiramate (Topamax) is an anticonvulsant (anti-epilepsy) drug.

It is used alone or with other medicines to treat seizures. Topiramate is also indicated to prevent migraine headaches in adults.

Contents

[edit] BRAND NAMES

[edit] STRUCTURE

Topiramate.jpg

[edit] MECHANISM OF ACTION

Topiramate reduces the frequency of action potentials by blocking sodium channels, increases GABA-induced chloride flux, antagonizes the AMPA/kainate subtype of the glutamate receptor, and inhibits the carbonic anhydrase enzyme, particularly isozymes II and IV.

[edit] INDICATIONS

  • Epilepsy:
    • Monotherapy epilepsy: Initial monotherapy in patients ≥ 2 years of age with partial onset or primary generalized tonic-clonic seizures
    • Adjunctive therapy epilepsy: Adjunctive therapy for adults and pediatric patients (2 to 16 years of age) with partial onset seizures or primary generalized tonic-clonic seizures, and in patients ≥ 2 years of age with seizures associated with Lennox-Gastaut syndrome (LGS)
  • Migraine: Treatment for adults for prophylaxis of migraine headache

[edit] DOSAGE


Initial Dose
Titration
Recommended Dose
Epilepsy monotherapy: children 2 to <10 years
25 mg/day administered nightly for the first week
The dosage should be titrated over 5–7 weeks
Daily doses in two divided doses based on weight
Epilepsy monotherapy: adults and pediatric patients ≥10 years
50 mg/day in two divided doses
The dosage should be increased weekly by increments of 50 mg for the first 4 weeks then 100 mg for weeks 5 to 6.
400 mg/day in two divided doses
Epilepsy adjunctive therapy: adults with partial onset seizures or LGS
25 to 50 mg/day
The dosage should be increased weekly to an effective dose by increments of 25 to 50 mg.
200–400 mg/day in two divided doses
Epilepsy adjunctive therapy: adults with primary generalized tonic-clonic seizures
25 to 50 mg/day
The dosage should be increased weekly to an effective dose by increments of 25 to 50 mg.
400 mg/day in two divided doses
Epilepsy adjunctive therapy: pediatric patients with partial onset seizures, primary generalized tonic-clonic seizures or LGS
25 mg/day (or less, based on a range of 1 to 3 mg/kg/day) nightly for the first week
The dosage should be increased at 1- or 2-week intervals by increments of 1 to 3 mg/kg/day (administered in two divided doses). Dose titration should be guided by clinical outcome.
5 to 9 mg/kg/day in two divided doses
Migraine
25 mg/day administered nightly for the first week
The dosage should be increased weekly by increments of 25 mg. Dose and titration should be guided by clinical outcome.
100 mg/day administered in two divided doses

[edit] CONTRAINDICATIONS

None

[edit] WARNINGS AND PRECAUTIONS

  • Acute myopia and secondary angle closure glaucoma: A syndrome consisting of acute myopia associated with secondary angle closure glaucoma has been reported in patients receiving Topiramate. Untreated elevated intraocular pressure can lead to permanent visual loss. The primary treatment to reverse symptoms is discontinuation of Topiramate as rapidly as possible
  • Oligohidrosis and hyperthermia: Monitor decreased sweating and increased body temperature, especially in pediatric patients )
  • Metabolic acidosis: Baseline and periodic measurement of serum bicarbonate is recommended. Consider dose reduction or discontinuation of Topiramate if clinically appropriate.
  • Suicidal behavior and ideation: Antiepileptic drugs increase the risk of suicidal behavior or ideation
  • Cognitive/neuropsychiatric: Topiramate may cause cognitive dysfunction. Patients should use caution when operating machinery including automobiles. Depression and mood problems may occur in epilepsy and migraine populations.
  • Fetal Toxicity: Topiramate use during pregnancy can cause cleft lip and/or palate
  • Withdrawal of antiepileptic drugs: Withdrawal of Topiramateshould be done gradually
  • Hyperammonemia and encephalopathy associated with or without concomitant valproic acid use: Patients with inborn errors of metabolism or reduced mitochondrial activity may have an increased risk of hyperammonemia. Measure ammonia if encephalopathic symptoms occur.
  • Kidney stones: Use with other carbonic anhydrase inhibitors, other drugs causing metabolic acidosis, or in patients on a ketogenic diet should be avoided
  • Hypothermia has been reported with and without hyperammonemia during topiramate treatment with concomitant valproic acid use

[edit] INTERACTIONS

  • Antiepileptic Drugs Decreased plasma concentrations of topiramate with concomitant administration of Carbamazepine, Valproic acid, phenytoin and Lamotrigine.
  • Effectiveness of oral contraceptives may be decreased, especially at doses greater than 200 mg/day
  • CNS Depressants:Concomitant administration of Topiramate and alcohol or other CNS depressant drugs may increase CNS depression as well as other cognitive and/or neuropsychiatric adverse reactions.
  • Concomitant administration of Carbonic anhydrase inhibitors (e.g., zonisamide, acetazolamide, or dichlorphenamide) may increase the risk of renal stone formation

[edit] PREGNANCY AND LACTATION

  • Pregnancy Category D (US). Topiramate can cause fetal harm when administered to a pregnant woman. Data from pregnancy registries indicate that infants exposed to topiramate in utero have an increased risk for cleft lip and/or cleft palate (oral clefts)
  • Nursing Mothers: 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.

[edit] SIDE EFFECTS

The most common adverse reactions in controlled, epilepsy clinical trials were paresthesia, anorexia, weight decrease, fatigue, dizziness, somnolence, nervousness, psychomotor slowing, difficulty with memory, difficulty with concentration/attention, cognitive problems, confusion, mood problems, fever, infection, and flushing.

The most common adverse reactions in controlled, migraine clinical trials were paresthesia and taste perversion

[edit] RELATED LINKS

Pharmacology of Antiepileptic Drugs

[edit] BIBLIOGRAPHY

http://www.topamax.com/sites/default/files/topamax.pdf

[edit] REFERENCES

Antimigraine preparations
5 HT1 agonists (Triptans) Almotriptan (Almogran, Axert)   Eletriptan (Relpax)   Frovatriptan (Frova, Migard, Menatriptan)   Rizatriptan (Maxalt)   Sumatriptan (Imigran)   Zolmitriptan (Zomig)
Ergot alkaloids Dihydroergotamine   Ergotamine
NSAIDs/ Analgesics Indometacin   Acetylsalicylic acid (Aspirin)   Diclofenac (Voltaren)   Ibuprofen (Advil, Brufen, Dolgit, Nurofen)   Ketorolac (Toradol)   Naproxen (Naprosyn, Aleve)   Nimesulide   Paracetamol (Efferalgan, Panadol...)
Prophylaxis Cinnarizine (Stugeron, Stugeron forte)   Flunarizine (Sibelium)   Nifedipine (Adalat)   Pizotifen   Propranolol (Inderal)   Topiramate (Topamax)