Topiramate: Drug Information
1. Drug Name
Generic Name
Topiramate
Brand Name(s)
- Pakistan: Topamax
- India: Topamac
- US: Topamax, Trokendi XR
- UK: Topamax
2. Pharmacological Class
Class
Anticonvulsant
Subclass
Sulfamate-substituted monosaccharide
3. Mechanism of Action
Topiramate enhances GABA activity, blocks voltage-dependent sodium channels, antagonizes AMPA/kainate glutamate receptors, and inhibits carbonic anhydrase enzymes. These actions contribute to its anticonvulsant and mood-stabilizing effects.
4. Indications
Primary Indications
- Epilepsy: Monotherapy or adjunctive therapy for partial onset seizures, primary generalized tonic-clonic seizures, and seizures associated with Lennox-Gastaut syndrome.
- Migraine: Prophylaxis of migraine headaches.
Off-label Uses
- Bipolar disorder
- Weight loss in obesity
- Neuropathic pain
- Post-traumatic stress disorder (PTSD)
5. Dosage and Administration
Standard Dosage
For epilepsy:
- Initial: 25-50 mg/day, increased weekly by 25-50 mg
- Maintenance: 200-400 mg/day in two divided doses
For migraine prophylaxis:
- Initial: 25 mg/day, increased weekly by 25 mg
- Maintenance: 100 mg/day in two divided doses
Route of Administration
Oral (tablets, sprinkle capsules, extended-release capsules)
Special Populations
- Pediatric: Safety and efficacy in children under 2 years of age for epilepsy have not been established.
- Geriatric: Dose adjustments may be necessary due to age-related renal function decline.
6. Pharmacokinetics
Absorption
Topiramate is rapidly absorbed with peak plasma concentrations occurring within 2 hours for immediate-release formulations and 24 hours for extended-release formulations.
Distribution
Topiramate is widely distributed with approximately 15-41% bound to plasma proteins.
Metabolism
Topiramate is partially metabolized in the liver, but a significant portion is excreted unchanged in the urine.
Excretion
Primarily excreted by the kidneys. Clearance is reduced in renal impairment.
Half-life
The elimination half-life of topiramate is approximately 21 hours.
7. Contraindications
- Hypersensitivity to topiramate or any of its components
8. Warnings and Precautions
- Increased risk of suicidal thoughts and behaviors
- May cause metabolic acidosis; monitor serum bicarbonate levels
- Use with caution in patients with renal or hepatic impairment
- May cause acute myopia and secondary angle closure glaucoma
- Avoid abrupt discontinuation to prevent seizure recurrence
9. Side Effects
Common Side Effects
- Paresthesia
- Fatigue
- Dizziness
- Weight loss
- Memory problems
Serious Side Effects
- Suicidal thoughts and behaviors
- Severe metabolic acidosis
- Kidney stones
- Severe allergic reactions
10. Drug Interactions
Major Interactions
- Metformin: Increased risk of metabolic acidosis
- Valproic acid: Increased risk of hyperammonemia and hypothermia
Moderate Interactions
- Oral contraceptives: Decreased efficacy of contraceptives
- Carbonic anhydrase inhibitors: Increased risk of kidney stones
Minor Interactions
- NSAIDs: Potential for increased side effects
11. Pregnancy and Lactation
Pregnancy Category
Category D - Positive evidence of risk. Topiramate can cause fetal harm when administered to pregnant women.
Breastfeeding Considerations
Topiramate is excreted in human milk. Caution is advised when administered to a nursing woman.
12. Patient Counseling Information
- Take topiramate exactly as prescribed and do not exceed the recommended dose.
- Topiramate may cause dizziness and drowsiness; avoid driving or operating heavy machinery until you know how it affects you.
- Inform your healthcare provider about all medications you are taking to avoid potential interactions.
- Do not stop taking topiramate abruptly without consulting your doctor.
- Stay hydrated to reduce the risk of kidney stones.
- Report any new or worsening symptoms,