Acetazolamide

Acetazolamide is a carbonic anhydrase inhibitor. It lowers intraocular pressure in glaucoma, reduces cerebrospinal fluid production in idiopathic intracranial hypertension, prevents and treats acute mountain sickness, and corrects metabolic alkalosis. It causes a mild diuresis and metabolic acidosis. It is a sulphonamide and is cheap and widely available in East Africa.

Classification. Carbonic anhydrase inhibitor (sulphonamide); weak diuretic.

Mechanism. Inhibits carbonic anhydrase in the proximal renal tubule, ciliary body and choroid plexus, reducing bicarbonate reabsorption (alkaline diuresis and metabolic acidosis), aqueous humour production, and cerebrospinal fluid production.

Pharmacodynamics. Oral onset within 1 to 2 hours, peak at 2 to 4 hours, duration 6 to 12 hours. IV onset within 5 minutes, duration 4 to 5 hours. The diuretic effect fades over a few days as acidosis develops.

Pharmacokinetics. Oral bioavailability over 90%. Half life 6 to 9 hours. Not metabolised; about 90% excreted unchanged in urine by tubular secretion. Concentrates in red cells.

Chronic open angle glaucoma, adult. 250 to 1000 mg daily in 1 to 4 divided doses (usual 250 mg twice daily); maximum 1000 mg daily. Sustained release 500 mg once or twice daily.

Acute angle closure glaucoma, adult. 500 mg IV slowly, then 125 to 250 mg orally every 4 hours until the pressure is controlled; maximum 1000 mg daily.

Idiopathic intracranial hypertension, adult (specialist). Start 250 mg twice daily; increase by 250 to 500 mg every 1 to 2 weeks to a usual 1000 to 2000 mg daily in 2 divided doses; maximum 4000 mg daily if tolerated.

Acute mountain sickness, adult.

• Prevention: 125 to 250 mg twice daily, starting 1 day before ascent and continuing for 2 days after reaching the highest level.

• Treatment: 250 mg twice daily until symptoms resolve (usually 24 to 48 hours).

Epilepsy (adjunct, specialist), adult. 250 to 1000 mg daily in divided doses.

Metabolic alkalosis in heart failure or after diuretics, adult. 250 to 500 mg once or twice daily for 1 to 3 days, with IV 250 to 500 mg in intensive care.

Oedema, adult. 250 to 375 mg once daily in the morning on alternate days (the diuretic effect fades).

Children. Glaucoma: 5 to 10 mg/kg for each dose every 6 to 8 hours; maximum 1000 mg daily. Intracranial hypertension: 25 to 100 mg/kg daily in 3 or 4 divided doses (maximum 2000 mg daily). Mountain sickness prevention: 2.5 mg/kg every 12 hours (maximum 125 mg a dose).

Contraindications. Hypersensitivity to sulphonamides; hyponatraemia; hypokalaemia; hyperchloraemic acidosis; severe kidney impairment; severe hepatic impairment or cirrhosis (risk of hepatic encephalopathy); adrenocortical failure; long term use in chronic angle closure glaucoma.

Warnings. Metabolic acidosis; hypokalaemia; kidney stones; severe skin reactions (Stevens Johnson syndrome); blood dyscrasias; paraesthesia; reduced taste of carbonated drinks; drowsiness. In higher doses, tinnitus and confusion. Salicylate toxicity with high dose aspirin.

Adverse effects. Paraesthesia of fingers and toes, taste disturbance, nausea, diarrhoea, increased urination, drowsiness, headache, metabolic acidosis, hypokalaemia, kidney stones, rash.

Interactions. Aspirin and other salicylates: salicylate toxicity and acidosis. Topiramate and zonisamide: acidosis and kidney stones. Lithium: increased excretion. Phenytoin, carbamazepine: raised levels. Ciclosporin: raised levels. Quinidine and flecainide: raised levels. Metformin: acidosis risk. Corticosteroids and loop diuretics: more hypokalaemia.

Special groups.

• Pregnancy: avoid, especially in the first trimester; teratogenic in animals.

• Breastfeeding: small amounts in milk; acceptable with infant monitoring.

• Patients of African ancestry: no dose change; use with caution in sickle cell disease because acidosis can promote sickling.

• Older adults: start 125 mg twice daily; higher risk of acidosis and confusion.

• Kidney impairment: avoid with eGFR under 30 mL/min; reduce the dose or lengthen the interval (every 12 hours) with eGFR 10 to 50 mL/min.

• Liver impairment: avoid in cirrhosis.

Formulations. Tablets 250 mg; sustained release capsules 250 mg; powder for injection 500 mg.

Administration. Oral with food and plenty of fluid. IV: reconstitute 500 mg with 5 to 10 mL of water for injection; inject slowly over 3 to 5 minutes; do not give IM (painful and ineffective); use within 24 hours.

Baseline. Sodium, potassium, bicarbonate, creatinine and eGFR, full blood count, sulphonamide allergy history, pregnancy test.

Monitoring. Sodium, potassium, bicarbonate and creatinine at 1 to 2 weeks after starting, then every 3 to 6 months. Full blood count in prolonged use. Stop if bicarbonate falls below 18 mmol/L or potassium below 3.0 mmol/L despite replacement. Visual fields, intraocular pressure, or papilloedema as the condition requires.

Stopping. Taper where possible if used long term for intracranial hypertension; no taper for short courses.

Common prescribing errors. Giving to a patient with sulphonamide allergy; giving IM; using with high dose aspirin; starting 500 mg IV bolus in kidney impairment; using it for weeks for oedema when the effect has faded; continuing despite paraesthesia and acidosis.