Carbonic Anhydrase Inhibiting Antiseizure Medicines

Carbonic anhydrase inhibiting antiseizure medicines reduce enzyme activity in brain and kidney, causing mild metabolic acidosis and altering neuronal excitability. The group includes acetazolamide, topiramate and zonisamide, with additional mechanisms for the last two.

Pharmacokinetics. Acetazolamide half life 6 to 9 hours. Topiramate is mainly renally cleared (half life 21 hours). Zonisamide half life is 63 hours.

• Acetazolamide 250 mg daily, increased to 500 to 1,000 mg daily in two or three doses.
• Topiramate 25 mg at night, increased by 25 mg weekly to 100 to 200 mg daily in two doses; maximum 400 mg daily.
• Zonisamide 100 mg once daily, increased by 100 mg every 2 weeks to 300 to 500 mg daily.

Differences. Topiramate also enhances GABA and blocks AMPA receptors. Zonisamide also blocks sodium and T-type calcium channels.

• Topiramate: broad spectrum adjunct for focal and generalised seizures; also migraine prevention (50 to 100 mg daily).
• Zonisamide: focal seizures and add-on in generalised epilepsy.
• Acetazolamide: catamenial epilepsy and short-term adjunct; also acute mountain sickness (125 to 250 mg twice daily, starting the day before ascent, relevant to climbs of Kilimanjaro and Mount Kenya), idiopathic intracranial hypertension (500 mg twice daily initially) and glaucoma.

Selection. Avoid topiramate in women of childbearing potential unless no alternative.

Contraindications. Sulphonamide hypersensitivity (zonisamide, acetazolamide), kidney stones, hyperchloraemic acidosis, severe liver or adrenal failure (acetazolamide).

Adverse effects. Metabolic acidosis, kidney stones, paraesthesia, cognitive slowing and word-finding difficulty, weight loss, acute angle-closure glaucoma with myopia within the first month, oligohidrosis and hyperthermia in children. Topiramate causes oral clefts and small-for-gestational-age babies. Zonisamide: irritability, psychosis, rash.

Interactions. Topiramate with valproate causes hyperammonaemic encephalopathy. Topiramate with metformin worsens acidosis. Topiramate at over 200 mg daily lowers oestrogen contraceptive efficacy. Enzyme inducers lower topiramate and zonisamide levels.

Special groups.

• Pregnancy: avoid topiramate and zonisamide; give folic acid 5 mg daily if exposed.
• Breastfeeding: avoid topiramate (infant diarrhoea and sedation).
• Children: zonisamide and topiramate by weight; risk of heat illness.
• Older adults: slower titration.
• Kidney impairment: halve topiramate when creatinine clearance is under 70 mL/min; avoid zonisamide under 20 mL/min.
• Liver impairment: use with care.

Monitoring. Serum bicarbonate at baseline and when unwell; kidney function; weight; mood; visual symptoms.

Referral and escalation. Sudden eye pain or visual loss needs same-day ophthalmology review and drug withdrawal. Persistent acidosis or recurrent stones need review.