Drug information of Acetazolamide

Mechanism of effect

Noncompetitive reversible inhibitor of the carbonic anhydrase enzyme.
Reduces the formation of hydrogen and bicarbonate ions from carbon dioxide and water, thereby reducing availability of these ions for active transport into secretions.

Pharmacodynamic

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.
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 .

Pharmacokinetics

Well absorbed from GI tract. Peak plasma concentrations attained within 1–4 or 3–6 hours following administration of conventional tablets or extended-release capsules, respectively. Distributed into erythrocytes, renal cortex, and aqueous humor of eye. Crosses the placenta.
Distributed into milk in dogs; not known whether distributed into human milk. Excreted principally in the urine as unchanged drug.

Drug indications

Seizures

Dosage

Adult
• Edema
Initial dose: 250 to 375 mg orally/IV once a day
-If after initial response there is a lack of response, hold therapy for a day
Maintenance dose: One dose every other day or once a day for 2 days alternating with a day of rest.
• Acute Mountain Sickness
500 to 1000 mg orally per day in divided doses.
Dosing should be to initiated 24 to 48 hours before ascent and continue for 48 hours while at high altitude, or longer as necessary to control symptoms.
• Glaucoma
Open-Angle Glaucoma: 250 to 1000 mg orally per day; amounts over 250 mg should be administered in divided doses
Preoperatively in Closed-Angle Glaucoma :
-Various regimens have been used including: 250 mg orally every 4 hours; 250 mg orally twice a day; OR 500 mg orally followed by 125 mg or 250 mg orally every 4 hours.
-In acute cases, IV therapy (at same oral dosage) has been used for rapid relief of ocular tension.
• Seizure Prophylaxis
Initial dose: 8 to 30 mg/kg orally/IV in divided doses
Range: 375 to 1000 mg per day
Initial dose for patients on other anticonvulsants: 250 mg orally/IV once a day.
Pediatric
• Acute Mountain Sickness
12 years or older:2.5 mg/kg orally every 12 hours
Maximum: 125 mg per dose
• Glaucoma
12 years or older: Extended-release (ER) capsules: 500 mg orally 2 times a day

Side effects

nausea , decreased appetite , dizziness , vomiting , Diarrhea , metabolic acidosis , tinnitus , polyuria

Interactions

Primidone , Sodium bicarbonate , Phenytoin , Aspirin , lithium , Methazolamide , Quinidine , Cyclosporine , ethacrynic acid , Ziprasidone , Dofetilide , Bendroflumethiazide , Methenamine , phenmetrazine , Methyl aminolevulinate , cyclopenthiazide , Florbetapir F18

Alerts

Fatalities have occurred, although rarely, due to severe reactions to sulfonamides including Stevens-Johnson syndrome, toxic epidermal necrolysis , fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias . Sensitizations may recur when a sulfonamide is readministered irrespective of the route of administration. If signs of hypersensitivity or other serious reactions occur, discontinue use of this drug. v Caution is advised for patients receiving concomitant high-dose aspirin and Acetazolamide , as anorexia, tachypnea , lethargy, coma and death have been reported. 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.

Points of recommendation

Some medical conditions may interact with acetazolamide. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you :
• if you are pregnant, planning to become pregnant, or are breast-feeding
• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement
• if you have allergies to medicines, foods, or other substances
• if you have kidney stones, a lung disease, glaucoma (eg, chronic non-congestive angle-closure glaucoma), diabetes, or difficulty breathing
• if you have had a severe allergic reaction (eg, a severe rash, hives, breathing difficulties, or dizziness) to any other sulfonamide medicine such as acetazolamide , celecoxib, certain diuretics (eg, hydrochlorothiazide), glyburide, probenecid, sulfamethoxazole, valdecoxib, or zonisamide.
Take acetazolamide by mouth with or without food. If stomach upset occurs, take with food to reduce stomach irritation. Drinking extra fluids while you are taking acetazolamide is recommended.
If a dose is missed, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Pregnancy level

C

Related drugs

Methazolamide , Brinzolamide , Dorzolamide