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+ | ====== Acetazolamide ====== | ||
+ | ===== Authorised indications ===== | ||
+ | |||
+ | **UK-SmPC: | ||
+ | **FDA-PI:** adjunctive treatment of centrencephalic epilepsies (petit mal, unlocalised seizures). | ||
+ | ===== Clinical applications ===== | ||
+ | |||
+ | Acetazolamide has limited use as an adjunctive therapy for a variety of seizures, but mainly absences | ||
+ | [(: | ||
+ | |||
+ | ===== Dosage and titration ===== | ||
+ | |||
+ | Adults: start treatment with 250 mg and increase to 500–750 mg. Children: 10–20 mg/day. Dosing: two or three times daily. Therapeutic drug monitoring (TDM): not needed. Reference range: 10–14 mg/l (400–700 μmol/l). | ||
+ | |||
+ | ===== Main ADRs ===== | ||
+ | |||
+ | Frequent and/or/or important: flushing, lethargy, anorexia, nausea, vomiting, paraesthesiae and increased diuresis. | ||
+ | |||
+ | Serious: idiosyncratic reactions, as with other sulfonamides (rash, aplastic anaemia, Stevens–Johnson synd rome), renal failure; nephrolithiasis in chronic treatment and metabolic acidosis, as with other carbonic anhydrase inhibitors (see also topiramate). | ||
+ | |||
+ | ===== Mechanism of action ===== | ||
+ | |||
+ | Acetazolamide is a carbonic anhydrase-inhibiting drug that reversibly catalyses the hydration of CO2 and the dehydration of carbonic acid. It blocks the action of brain carbonic anhydrase, resulting in an elevation of intracellular CO2, a decrease of intracellular pH and depression of neuronal activity. | ||
+ | |||
+ | ===== Pharmacokinetics ===== | ||
+ | |||
+ | Oral bioavailability: | ||
+ | |||
+ | ===== Drug interactions ===== | ||
+ | |||
+ | Not significant: | ||
+ | |||
+ | ===== Main disadvantages ===== | ||
+ | |||
+ | Unpredictable seizure efficacy, development of tolerance and idiosyncratic reactions that exceptionally may be fatal. | ||
+ | |||
+ | ===== Useful clinical notes ===== | ||
+ | |||
+ | * Risk of withdrawal seizures. | ||
+ | * Combination with carbamazepine or oxcarbazepine increases the risk of hyponatraemia. | ||
+ | * Avoid concurrent use with other carbonic anhydrase inhibitors (i.e. sulthiame, topiramate, zonisamide). | ||
+ | * It should be withdrawn prior to starting a ketogenic diet. | ||
+ | * Concurrent use with aspirin can lead to high plasma concentrations of acetazolamide and toxicity. | ||
+ | |||
+ | ===== References ===== | ||
+ | |||
+ | ~~REFNOTES cite~~ | ||
+ | {{tag> |