Acetazolamide

Pronunciation: (uh-seet-uh-ZOLE-uh-mide)Class: Anticonvulsant, Carbonic anhydrase inhibitor

Trade Names:Acetazolamide- Tablets 250 mg- Powder for injection, lyophilized 500 mg

Trade Names:Diamox Sequels- Capsules, sustained-release 500 mg

APO-Acetazolamide (Canada)

Pharmacology

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

Pharmacokinetics

Absorption

Sustained release (SR) T _max is 3 to 6 h. Immediate release (IR) T _max is 1 to 4 h.

Onset

SR is 2 h; IR is 1 to 1.5 h; IV is 2 min.

Peak

SR is 3 to 6 h; IR is 1 to 4 h; IV is 15 min.

Duration

SR is 18 to 24 h; IR is 8 to 12 h; IV is 4 to 5 h.

Indications and Usage

Prevention or lessening of symptoms associated with acute mountain sickness (tablet only); adjunctive treatment of chronic simple (open-angle) glaucoma and secondary glaucoma; preoperative treatment of acute congestive (closed-angle) glaucoma; adjunctive treatment of 1) edema caused by CHF or drug-induced edema and 2) centrencephalic epilepsies (eg, petit mal, generalized seizures).

Contraindications

Hypersensitivity to other sulfonamides; depressed sodium and/or potassium serum levels; marked kidney and liver disease or dysfunction; suprarenal gland failure; hyperchloremic acidosis; adrenocortical insufficiency; severe pulmonary obstruction with increased risk of acidosis; cirrhosis; long-term use in chronic noncongestive angle-closure glaucoma. Sustained release dosage form is not recommended for use as anticonvulsant or for treatment of edema caused by CHF or drug-induced edema.

Dosage and Administration

Acute Mountain SicknessAdults

PO 500 to 1,000 mg per day in divided doses.

Chronic Simple (Open-Angle) GlaucomaAdults

PO 250 mg to 1 g per day, usually in divided doses for amounts above 250 mg.

Diuresis in CHFAdults

PO/IV Initially 250 to 375 mg (5 mg/kg) every morning; then give on alternate days or for 2 days alternating with 1 day of rest.

Drug-Induced EdemaAdults

PO/IV 250 to 375 mg daily for 1 to 2 days, alternating with a day of rest.

EpilepsyAdults

PO/IV 8 to 30 mg/kg per day in divided doses; optimum range 375 to 1,000 mg/day. When drug is given in combination with other anticonvulsants, initial dosage is 250 mg daily.

Secondary Glaucoma/Preoperative Treatment of Closed-Angle GlaucomaAdults (short-term care)

PO 250 mg every  4 h or 250 mg twice daily.

Acute care

PO Initially 500 mg; then 125 to 250 mg every 4 h. IV therapy may be used for rapid relief of increased IOP. Direct IV administration is preferred because IM route is painful.

General Advice

• Powder for injection
• Direct IV administration is preferred because IM administration is painful due to alkaline pH of reconstituted solution. Not for intradermal, subcutaneous, or intra-arterial administration.
• Reconstitute following manufacturer's guidelines using at least 5 mL of sterile water for injection.
• Do not administer if particulate matter, cloudiness, or discoloration noted
• Discard any unused solution.

Storage/Stability

Store sustained-release capsules at controlled room temperature (68° to 77°F). Store tablets and powder for injection at ambient room temperature (59° to 86°F). Store reconstituted injectable solution in refrigerator (36° to 46°F) for up to 3 days or use within 12 h of reconstitution if stored at room temperature (59° to 86°F).

Drug Interactions

Diflunisal

May cause significant decrease in IOP.

Primidone

Primidone concentrations may be altered.

Quinidine

Quinidine serum levels may be increased.

Salicylates

May cause acetazolamide accumulation and toxicity, including CNS depression and metabolic acidosis.

Laboratory Test Interactions

False-positive urinary protein results may occur because of alkalinization of urine.

Adverse Reactions

CNS

Drowsiness; confusion; sensory disturbances, including paresthesia and loss of appetite; convulsions.

Dermatologic

Skin rash; urticaria.

EENT

Transient myopia; hearing disturbances; sore throat; tinnitus.

GI

Nausea; vomiting; diarrhea; melena; taste alterations.

Genitourinary

Polyuria; hematuria; glycosuria.

Hematologic

Blood dyscrasias, including agranulocytosis and aplastic anemia; unusual bleeding or bruising.

Hepatic

Hepatic insufficiency; fulminant hepatic necrosis.

Metabolic

Metabolic acidosis; electrolyte imbalance.

Miscellaneous

Flaccid paralysis; fever; flank or loin pain; severe adverse reactions associated with sulfonamides, including Stevens-Johnson syndrome and toxic epidermal necrolysis; photosensitivity.

Precautions

Monitor Adverse reactions Withhold drug and notify health care provider immediately if any of the following symptoms occur: sore throat, fever, pallor, purpura, hematuria, unusual bleeding or bruising. IOP measurements Ensure that for patient being treated for glaucoma that IOPs are measured and documented in the patient's record before starting therapy and periodically during therapy.

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Dose increases

Increasing dose does not augment diuresis but may increase drowsiness and paresthesias.

Pulmonary conditions

Use in pulmonary obstruction and emphysema may aggravate or precipitate acidosis.

Overdosage

Symptoms

Electrolyte imbalance, acidosis, CNS effects.

Patient Information

• Advise patient or caregiver that injection will be prepared and administered by a health care provider in a health care setting.
• Advise patient with glaucoma to continue to use other glaucoma medications prescribed by health care provider unless advised otherwise.
• Advise patient with epilepsy to continue to use other antiepileptic drugs prescribed by health care provider unless advised otherwise.
• Review dosing schedule with patient.
• Advise patient to take each dose with a full (8 oz) glass of water without regard to meals. Advise patient to take with food if stomach upset occurs.
• Advise patient using sustained-release capsules to swallow whole. Caution patient not to crush or chew capsule.
• Advise patient urine production may increase following the first few doses of the medication and that this is normal and of no concern. Advise patient to inform health care provider if excessive urine production occurs.
• Advise patient to drink fluids liberally (eg, eight 8 oz glasses of water daily) while taking this medication.
• Advise patient using medication for preventing symptoms of high altitude sickness that if rapid ascent produces symptoms of high altitude sickness, rapid descent is necessary.
• Advise patient to discontinue therapy and contact health care provider immediately if any of the following occur: rash, hives, itching, sore throat, unexplained fever, pallor, purple spots under the skin, unusual bleeding or bruising, blood in urine, tingling or tremors in hands or feet, ringing in ears or hearing changes, flank or loin pain.
• Advise patient to avoid unnecessary exposure to sunlight or tanning lamps and to use sunscreen and wear protective clothing to avoid photosensitivity reactions.
• Advise patient that drug may cause drowsiness and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.

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