acetazolamide

REMS

Lowering of intraocular pressure in the treatment of glaucoma.
Management of acute altitude sickness.
Edema due to HF.
Adjunct to the treatment of refractory seizures.

Unlabeled Use:

Reduce cerebrospinal fluid production in hydrocephalus.
Prevention of renal calculi composed of uric acid or cystine.

Action ⬆ ⬇

Inhibition of carbonic anhydrase in the eye results in decreased secretion of aqueous humor.
Inhibition of renal carbonic anhydrase, resulting in self-limiting urinary excretion of sodium, potassium, bicarbonate, and water.
CNS inhibition of carbonic anhydrase and resultant diuresis may ↓ abnormal neuronal firing.
Alkaline diuresis prevents precipitation of uric acid or cystine in the urinary tract.

Therapeutic effects:

Lowering of intraocular pressure.
Control of some types of seizures.
Prevention and treatment of acute altitude sickness.
Diuresis and subsequent mobilization of excess fluid.
Prevention of uric acid or cystine renal calculi.

Pharmacokinetics ⬆ ⬇

Absorption: Dose dependent; erratic with doses >10 mg/kg/day.

Distribution: Crosses the placenta and blood-brain barrier; enters breast milk.

Protein Binding: 95%.

Metabolism/Excretion: Excreted mostly unchanged in urine.

Half-Life: 2.4–5.8 hr.

Time/Action Profile ⬆ ⬇

(lowering of intraocular pressure)

ROUTE	ONSET	PEAK	DURATION
PO	1–1.5 hr	2–4 hr	8–12 hr
PO-ER	2 hr	8–18 hr	18–24 hr
IV	2 min	15 min	4–5 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity or cross-sensitivity with sulfonamides may occur;
Hepatic impairment;
Concurrent use with ophthalmic carbonic anhydrase inhibitors (brinzolamide, dorzolamide) is not recommended;
OB: Avoid during first trimester of pregnancy.

Use Cautiously in:

Chronic respiratory disease;
Electrolyte abnormalities;
Gout;
Renal disease (dosage ↓ necessary for CCr <50 mL/min);
Diabetes mellitus;
OB: Use with caution during second or third trimester of pregnancy;
Lactation: Safety not established.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: rash, STEVENS-JOHNSON SYNDROME

EENT: transient nearsightedness

Endo: hyperglycemia

F and E: hyperchloremic acidosis, growth retardation (in children receiving chronic therapy), hypokalemia

GI: anorexia, metallic taste, melena, nausea, vomiting

GU: crystalluria, renal calculi

Hemat: APLASTIC ANEMIA, HEMOLYTIC ANEMIA, LEUKOPENIA

Metab: ↓weight, hyperuricemia

Neuro: depression, fatigue, paresthesias, weakness, drowsiness

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS)

Interactions ⬆ ⬇

Drug-drug:

Excretion of barbiturates, aspirin, and lithium is ↑ and may lead to ↓ effectiveness.
Excretion of amphetamine, quinidine, procainamide, and possibly tricyclic antidepressants is ↓ and may lead to toxicity.
May ↑ cyclosporine levels.

Route/Dosage ⬆ ⬇

PO (Adults ): Glaucoma (open angle): 250–1000 mg/day in 1–4 divided doses (up to 250 mg every 4 hr) or 500-mg extended-release capsules twice daily. Epilepsy: 4–16 mg/kg/day in 1–4 divided doses (maximum 30 mg/kg/day or 1 g/day). Altitude sickness: 250 mg 2–4 times daily started 24–48 hr before ascent, continued for 48 hr or longer to control symptoms. Antiurolithic: 250 mg at bedtime. Edema: 250–375 mg/day. Urine alkalinization: 5 mg/kg/dose repeated 2–3 times over 24 hr.
PO (Children ): Glaucoma: 8–30 mg/kg (300–900 mg/m²/day) in 3 divided doses (usual range 10–15 mg/kg/day). Edema: 5 mg/kg/dose once daily. Epilepsy: 4–16 mg/kg/day in 1–4 divided doses (maximum 30 mg/kg/day or 1 g/day).
PO (Neonates ): Hydrocephalus: 5 mg/kg/dose every 6 hr ↑ by 25 mg/kg/day up to a maximum of 100 mg/kg/day.
IV (Adults ): Glaucoma (closed angle): 250–500 mg, may repeat in 2–4 hr to a maximum of 1 g/day. Edema: 250–375 mg/day.
IV (Children ): Glaucoma: 5–10 mg/kg every 6 hr, not to exceed 1 g/day. Edema: 5 mg/kg/dose once daily.
IV (Neonates ): Hydrocephalus: 5 mg/kg/dose every 6 hr ↑ by 25 mg/kg/day up to a maximum of 100 mg/kg/day.

Availability ⬆ ⬇

(Generic available)

Extended-release capsules: 500 mg
Powder for injection: 500 mg/vial
Tablets: 125 mg; 250 mg

Assessment ⬆ ⬇

Observe for signs of hypokalemia (muscle weakness, malaise, fatigue, ECG changes, vomiting).
- Assess for allergy to sulfonamides.
Intraocular Pressure: Assess for eye discomfort or decrease in visual acuity.
Seizures: Monitor neurologic status in patients receiving acetazolamide for seizures. Initiate seizure precautions.
Altitude Sickness: Monitor for decrease in severity of symptoms (headache, nausea, vomiting, fatigue, dizziness, drowsiness, shortness of breath). Notify health care professional immediately if neurologic symptoms worsen or if patient becomes more dyspneic and rales or crackles develop.
Edema: Monitor intake and output ratios and daily weight during therapy.

Lab Test Considerations:

Serum electrolytes, complete blood counts, and platelet counts should be evaluated initially and periodically during prolonged therapy. May cause ↓ potassium, bicarbonate, WBCs, and RBCs. May cause ↑ serum chloride.
- May cause ↑ in serum and urine glucose; monitor serum and urine glucose carefully in diabetic patients.
- May cause false-positive results for urine protein and 17-hydroxysteroid tests.
- May cause ↑ blood ammonia, bilirubin, uric acid, urine urobilinogen, and calcium. May ↓ urine citrate.

Implementation ⬆ ⬇

Do not confuse acetazolamide with acetaminophen.
- Encourage fluids to 2000–3000 mL/day, unless contraindicated, to prevent crystalluria and stone formation.
- A potassium supplement without chloride should be administered concurrently with acetazolamide.
PO: Give with food to minimize GI irritation. Tablets may be crushed and mixed with fruit-flavored syrup to minimize bitter taste for patients with difficulty swallowing. Extended-release capsules may be opened and sprinkled on soft food, but do not crush, chew, or swallow contents dry. Extended-release capsules are only indicated for glaucoma and altitude sickness; do not use for epilepsy or diuresis.
IM: Extremely painful; avoid if possible.

IV Administration:

Reconstitute 500 mg of acetazolamide in at least 5 mL of sterile water for injection. Use reconstituted solution within 24 hr. Concentration: 100 mg/mL.
Rate: Not to exceed 500 mg/min.
Intermittent Infusion: Diluent: Further dilute in 50–100 mL of D5W, D10W, 0.45% NaCl, 0.9% NaCl, LR, or combinations of dextrose and saline or dextrose and LR solution.Concentration: 5–10 mg/mL.
Rate: Infuse over 15–30 min.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take as directed. Take missed doses as soon as possible unless almost time for next dose. Do not double doses. Patients on anticonvulsant therapy may need to gradually withdraw medication.
- Advise patient to report numbness or tingling of extremities, weakness, rash, sore throat, unusual bleeding or bruising, fever, or signs/symptoms of a sulfonamide adverse reaction (Stevens-Johnson syndrome [flu-like symptoms, spreading red rash, or skin/mucous membrane blistering], toxic epidermal necrolysis [widespread peeling/blistering of skin]) to health care professional. If hematopoietic reactions, fever, rash, hepatic, or renal problems occur, acetazolamide should be discontinued.
- May occasionally cause drowsiness. Caution patient to avoid driving and other activities that require alertness until response to the drug is known.
- Caution patient to use sunscreen and wear protective clothing to prevent photosensitivity reactions.
- Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
Intraocular Pressure: Advise patient of the need for periodic ophthalmologic exams; loss of vision may be gradual and painless.

Evaluation/Desired Outcomes ⬆ ⬇

Decrease in intraocular pressure when used for glaucoma. If therapy is not effective or patient is unable to tolerate one carbonic anhydrase inhibitor, using another may be effective and more tolerable.
Decrease in the frequency of seizures.
Reduction of edema.
Prevention of altitude sickness.
Prevention of uric acid or cystine stones in the urinary tract.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇