Acetazolamide information from DrugsUpdate  

Pharmacodynamics

Inhibits carbonic anhydrase enzyme, reducing rate of aqueous humor formation and thus lowering IOP; produces diuretic effect; retards neuronal conduction in brain.

Pharmacokinetics

Acetazolamide specifically inhibits the enzyme carbonic anhydrase which catalyses the reversible reaction involving the hydration of CO2 and dehydration of carbonic acid. It increases the excretion of HCO3 ions and as well as Na and K leading to alkaline diuresis. Carbonic anhydrase is also inhibited in the CNS to retard abnormal and excessive discharge from neurons.

Onset
60-90 minutes (oral); 2 minutes (IV).

Duration
8-12 hours (oral); 4-5 hours (IV).

Absorption
Moderately rapid absorption from the GI tract; peak plasma concentrations after 2 hours (oral).

Distribution
Concentrates in the red blood cells and renal cortex; enters the breast milk. Protein-binding: High.

Excretion
Urine (as unchanged drug); 3-6 hours (elimination half-life).

Acetazolamide Indications / Acetazolamide Uses

Acetazolamide is a potent carbonic anhydrase inhibitor, effective in the control of fluid secretion (e.g., some types of glaucoma), in the treatment of certain convulsive disorders (e.g., epilepsy) and in the promotion of diuresis in instances of abnormal fluid retention (e.g., cardiac edema). Acetazolamide is not a mercurial diuretic. Rather, it is a nonbacteriostatic sulfonamide possessing a chemical structure and pharmacological activity distinctly different from the bacteriostatic sulfonamides. Acetazolamide is an enzyme inhibitor that acts specifically on carbonic anhydrase, the enzyme that catalyzes the reversible reaction involving the hydration of carbon dioxide and the dehydration of carbonic acid. In the eye, this inhibitory action of Acetazolamide decreases the secretion of aqueous humor and results in a drop in intraocular pressure, a reaction considered desirable in cases of glaucoma and even in certain nonglaucomatous conditions. Evidence seems to indicate that Acetazolamide has utility as an adjuvant in the treatment of certain dysfunctions of the central nervous system (e.g., epilepsy). Inhibition of carbonic anhydrase in this area appears to retard abnormal, paroxysmal, excessive discharge from central nervous system neurons. The diuretic effect of Acetazolamide is due to its action in the kidney on the reversible reaction involving hydration of carbon dioxide and dehydration of carbonic acid. The result is renal loss of HCO3 ion, which carries out sodium, water, and potassium. Alkalinization of the urine and promotion of diuresis are thus effected. Alteration in ammonia metabolism occurs due to increased reabsorption of ammonia by the renal tubules as a result of urinary alkalinization.

Acetazolamide Adverse Reactions / Acetazolamide Side Effects

Drowsiness, paraesthesia, ataxia, dizziness, thirst, anorexia, headache; confusion, malaise, depression; GI distress, metabolic acidosis, polyuria, hyperuricaemia, renal calculi, nephrotoxicity, hepatic dysfunction.

Potentially Fatal: Rarely, skin reactions or blood dyscrasias.

Precautions

Increasing the dose does not increase the diuresis and may increase the incidence of drowsiness and/or paresthesia. Increasing the dose often results in a decrease in diuresis. Under certain circumstances, however, very large doses have been given in conjunction with other diuretics in order to secure diuresis in complete refractory failure.

Overdosage
Symptoms may include electrolyte imbalance, acidotic state and central nervous effects. Monitor serum electrolyte levels (particularly potassium) and blood pH levels. Supportive measures are required to restore electrolyte and pH balance. Acidotic state can usually be corrected by the admin of bicarbonate.

Special Precautions

Potassium supplements may be required. Impaired hepatic or renal function; diabetes. Monitor plasma electrolytes and blood count regularly. IM route is not recommended. Caution when driving or operating machinery. Elderly.

Other Drug Interactions

Aids penetration of weakly acidic substances like sulphonamides across blood and CSF barrier. May inhibit renal excretion of basic drugs (e.g. quinidine, ephedrine, amphetamines) and promotes excretion of acidic drugs. May increase salicylate toxicity (acidosis). Hypokalaemia with corticosteroids and potassium-wasting diuretics. May increase excretion of lithium and primidone. May cause osteomalacia with anticonvulsants.

Potentially Fatal: May potentiate effect of folic acid antagonists, oral hypoglycaemic agents, oral anticoagulants and severe reactions to sulphonamides.

Other Interactions

Information Not Available

Dosage

Oral
Diuresis
Adult: 250-375 mg once daily or on alternate days. Intermittent treatment is needed for continued efficacy.

Oral
Preoperative management of angle-closure glaucoma
Adult: 250-1000 mg daily in divided doses.
Child: 1 month-12 years: 10-20 mg/kg daily. Max: 750 mg daily, in 2-4 divided doses.

Oral
Adjunct in open-angle glaucoma
Adult: 250-1000 mg daily in divided doses.
Child: 1 month-12 years: 10-20 mg/kg daily. Max: 750 mg daily, in 2-4 divided doses.

Oral
Epilepsy
Adult: Either alone or with other antiepileptics: 250-1000 mg daily in divided doses.
Child: Neonates and up to 12 years: Initially, 2.5 mg/kg bid-tid; maintenance: 5-7 mg/kg bid-tid. Max: 750 mg daily.

Oral
Prophylaxis of high-altitude disorders
Adult: 500-1000 mg daily in divided doses. Prompt descent is still advised if severe symptoms such as cerebral or pulmonary oedema occur.

Intravenous
Chronic open-angle glaucoma
Adult: As an adjunct, 0.25-1 g every 24 hours, usually in divided doses. Adjust dose according to symptomatology and ocular tension.

Intravenous
Acute closed angle glaucoma
Adult: 250-500 mg. may repeat 2-4 hours later if needed. Max: 1 g daily.

Intravenous
Epilepsy
Adult: 8-30 mg/kg daily in divided doses. Optimum dose: 375-1000 mg daily. When used with other anticonvulsants, initiate at 250 mg once daily in addition to existing medications and adjust accordingly.

Reconstitution
Reconstitute with at least 5 ml of sterile water for inj to produce a solution containing ≤ 100 mg/ml. Further dilute with 5% dextrose solution or normal saline for IV infusion.

Incompatibility
Admixture incompatibility: Multivitamins.

Food(before/after)

Should be taken with food.

Acetazolamide and Pregnancy

Contraindicated in pregnancy

Category C: Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Acetazolamide and Lactation

Contraindicated in lactation

Acetazolamide and Children

Although there is no specific information comparing use of carbonic anhydrase inhibitors in children with use in other age groups, these medicines are not expected to cause different side effects or problems in children than they do in adults.

Acetazolamide and Geriatic

Information Not Available

Acetazolamide and Other Contraindications

Hypersensitivity to sulphonamides; sodium or potassium depletion, hepatic insufficiency; hepatic cirrhosis; hyperchloraemic acidosis; severe renal impairment; severe pulmonary obstruction; chronic noncongestive angle-closure glaucoma; adrenocortical insufficiency. Pregnancy, lactation.

Storage

Intravenous
Store between 15-30°C (59-86°F).
Reconstituted solution may be stored at for 3 days at 2-8°C (36-46°C) or 12 hours at 15-30°C (59-86°F).

Oral
Store at 15-30°C.

Lab interference

Intravenous
Store between 15-30°C (59-86°F).
Reconstituted solution may be stored at for 3 days at 2-8°C (36-46°C) or 12 hours at 15-30°C (59-86°F).

Oral
Store at 15-30°C.