Topiramate
Mechanism :
The precise mechanisms by which topiramate exerts its anticonvulsant and migraine prophylaxis effects are unknown; however, preclinical studies have revealed four properties that may contribute to topiramate's efficacy for epilepsy and migraine prophylaxis. Electrophysiological and biochemical evidence suggests that topiramate, at pharmacologically relevant concentrations, blocks voltage-dependent sodium channels, augments the activity of the neurotransmitter gamma-aminobutyrate at some subtypes of the GABA-A receptor, antagonizes the AMPA/kainate subtype of the glutamate receptor, and inhibits the carbonic anhydrase enzyme, particularly isozymes II and IV
Indication :
- Partial seizures
- Generalised tonic-clonic seizures
- Absence-Atonic seizures
- Lennox-Gastaut syndrome
- Migraine
Contraindications :
Contraindicated in patients with a history of hypersensitivity to any component of this product. Ensure adequate hydration to avoid nephrolithiasis. Acute myopia and glaucoma may occur rarely.
Dosing :
2 to <10 years:
25 mg (1-3 mg/kg/day) at bedtime for a week, orally. Increase dose by 1-3 mg/kg/day at 1-2 week intervals, divided 12 hourly to 5-9 mg/kg/day (Max: 250 mg/day in children weighing <11 kg, 300 mg/day in children between 12-22 kg, 350 mg/day in children weighing >23 kg).
>10 years:
200 mg/dose PO 12 hourly. Start with 25 mg PO BD and then increase weekly.
Adverse Effect :
Anorexia, somnolence, decrease in serum bicarbonate, nervousness, paresthesia, psychomotor slowing, abnormal vision, confusion, decreased memory, speech disorder, nausea, fatigue, ataxia. Chronic adverse effects include reduced appetite, anorexia and behavioural changes.
Interaction :
Phenytoin: May increase plasma phenytoin levels.
Digoxin: May decrease digoxin levels.
Oral Contraceptives: May decrease the effectiveness of oral contraceptives, advise patients to use other measures.
Carbamazepine and Phenytoin: may decrease topiramate levels.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | Migraine/epilepsy: Dose as in normal renal function |
| 10-20 | Migraine: Dose as in normal renal function Epilepsy: 50% of normal dose and increase according to response |
| <10 | Migraine: Dose as in normal renal function Epilepsy: 25–50% of normal dose and increase according to response |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Unknown dialysability. Dose as for GFR<10 mL/min |
| HD | Dialysed. Dose as for GFR<10 mL/min |
| HDF/High flux | Dialysed. Dose as for GFR<10 mL/min |
| CAV/VVHD | Unknown dialysability. Dose as for GFR=10–20 mL/min |
Hepatic Dose :
Dose reduction may be needed as drug is metabolised by liver. Plasma levels can be increased due to reduced clearance.