Davis's Drug Guide

acetaZOLAMIDE

General

Pronunciation:
a-seet-a-zole-a-mide


Trade Name(s)

  • Acetazolam [Canada]
  • Diamox
  • Diamox Sequels

Pregnancy Category
Category C

Ther. Class.
anticonvulsants
antiglaucoma agents
diuretics
ocular hypotensive agent

Pharm. Class.
carbonic anhydrase inhibitors

Indications

  • 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(s):

  • 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 Effect(s):

  • 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 m g/kg/day.

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

Protein Binding: 95%.

Metabolism and Excretion: Excreted mostly unchanged in urine.

Half-life: 2.4–5.8 hr.

TIME/ACTION PROFILE (lowering of intraocular pressure)

ROUTEONSETPEAKDURATION
PO1–1.5 hr2–4 hr8–12 hr
PO-ER2 hr8–18 hr18–24 hr
IV2 min15 min4–5 hr

Contraindication/Precautions

Contraindicated in:

  • Hypersensitivity or cross-sensitivity with sulfonamides may occur;
  • Hepatic disease or insufficiency;
  • 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.

Adverse Reactions/Side Effects

CNS: depression, fatigue, weakness, drowsiness

EENT: transient nearsightedness

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

GU: crystalluria, renal calculi

Derm: STEVENS-JOHNSON SYNDROME, rashes

Endo: hyperglycemia

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

Hemat: APLASTIC ANEMIA, HEMOLYTIC ANEMIA, LEUKOPENIA

Metabolic: weight loss, hyperuricemia

Neuro: paresthesias

Misc: ALLERGIC REACTIONS INCLUDING ANAPHYLAXIS

* CAPITALS indicate life-threatening.
Italics indicate most frequent.

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 q 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 q 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 q 6 hr, not to exceed 1 g/day. Edema– 5 mg/kg/dose once daily.

IV: Neonates Hydrocephalus– 5 mg/kg/dose q 6 hr ↑ by 25 mg/kg/day up to a maximum of 100 mg/kg/day.

Availability (generic available)

Tablets: 125 mg, 250 mg

Extended-release capsules: 500 mg

Powder for injection: 500 mg/vial

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.

Potential Diagnoses

Implementation

  • Do not confuse acetazolamide with acetohexamide. Do not confuse Diamox with Diabinese.
    • 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

  • pH: 9.2.
  • Direct IV: 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.
  • 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.