ACETAZOLAMIDE

(a-set-a-zole'a-mide)

Acetazolam

, Apo-Acetazolamide

, Diamox Sequels
ACETAZOLAMIDE SODIUM
(a-set-a-zole'a-mide)
Diamox Parenteral
Classifications: eye preparation; carbonic anhydrase inhibitor; diuretic; anticonvulsant;
Therapeutic: diuretic; anticonvulsant
Pregnancy Category: C

Availability

125 mg, 250 mg tablets; 500 mg sustained-release capsules; 500 mg powder for injection

Action

The mechanism of anticonvulsant action is unknown but thought to involve inhibition of CNS carbonic anhydrase, which retards abnormal transmission from CNS neurons. Diuretic effect is due to inhibition of carbonic anhydrase activity in proximal renal tubule, preventing formation of carbonic acid, and therefore the formation of H⁺ and HCO₃^–. Inhibition of carbonic anhydrase in eye reduces rate of aqueous humor formation with consequent lowering of intraocular pressure.

Therapeutic Effect

Reduces seizure activity and intraocular pressure. Additionally, it has a diuretic effect.

Uses

Treatment of seizures: absence or petit mal, generalized tonic-clonic (grand mal), and focal; reduction of intraocular pressure in open-angle glaucoma and secondary glaucoma; preoperative treatment of acute closed-angle glaucoma; drug-induced edema and as adjunct in treatment of edema due to congestive heart failure; acute high-altitude sickness.

Unlabeled Uses

Prevent uric acid or cystine renal calculi; to treat acute pancreatitis, premenstrual syndrome (PMS), metabolic alkalosis, and hypokalemic and hyperkalemic forms of familial periodic paralysis; to increase secretion of phenobarbital or lithium; hydrocephalus.

Contraindications

Hypersensitivity to carbonic anhydrase inhibitors, marked renal and hepatic disease; Addison's disease or other types of adrenocortical insufficiency; hyponatremia, hypokalemia, hyperchloremic acidosis; prolonged administration to patients with hyphema; chronic noncongestive angle-closure glaucoma; pregnancy (category C).

Cautious Use

Hypersensitivity to sulfonamides and derivatives (e.g., thiazides), history of hypercalciuria; diabetes mellitus, elderly, gout, patients receiving digitalis, obstructive pulmonary disease, respiratory acidosis.

Route & Dosage

Glaucoma
Adult: PO 250 mg 1–4 times/d, 500 mg sustained release b.i.d., up to 1 g/d IM/IV 500 mg, may repeat in 2–4 h
Child: PO 8–30 mg/kg/d in 3 doses IV 5–10 mg/kg q6h

Epilepsy
Adult/Child: PO 8–30 mg/kg/d in 1–4 doses

Edema
Adult: PO/IV 250–375 mg every a.m. (5 mg/kg); may be given every other day if condition improves
Child: PO/IV 5 mg/kg or 150 mg/m²/every a.m.

High Altitude Sickness
Adult: PO 250 mg q8–12h or 500 mg sustained release q12–24h, starting 24–48 h before climb and continuing for 48 h at high altitude

Treatment Hydrocephalus
Neonate/Infant: PO/IV 20 mg/kg/d in divided doses q8–12h (max: 100 mg/kg/d)

Renal Impairment
Cl_cr10–50 mL/min: extend interval to q12h; <10 mL/min: use not recommended
Hemodialysis: Administer post-dialysis

Administration

Oral

Administer diuretic dose in morning to avoid interrupted sleep.
Give with food or meals to minimize GI upset.
Note: If tablet(s) cannot be swallowed, soften tablet(s) (not sustained release form) in 2 tsp of hot water and add to 2 tsp of honey/syrup to disguise bitter taste; avoid syrups containing alcohol or glycerin, or crush tablet(s) and suspend in syrup (250–500 mg/5 mL syrup). Prepare just before administration. Drug does not dissolve in fruit juices.
Store oral preparations at 15°–30° C (59°–86° F) unless otherwise directed.

Intramuscular

Reconstitute as for IV administration. See PREPARE Direct.
Give IM for rapid lowering of intraocular pressure or in patients unable to take oral dosage.
Note: The intramuscular dosage is not the route of choice because the alkalinity of the solution makes the injection painful.

Intravenous

IV administration to neonates, infants, and children: Verify correct IV concentration and rate of infusion/injection with physician.

PREPARE: Direct: Reconstitute each 500 mg vial with at least 5 mL of sterile water for injection to yield approximately 100 mg/mL. IV Infusion: Reconstituted solution may be used as prepared or further diluted with DSW or NS. Use within 24 h of reconstitution.

ADMINISTER: Direct: Give at a rate of 500 mg or fraction thereof over 1 min. IV Infusion: Give as a continuous infusion over 4–8 h.

INCOMPATIBILITIES Solution/additive: Amino acid. Y-site: Diltiazem, TPN.

Adverse Effects (≥1%)

CNS: Paresthesias, sedation, malaise, disorientation, depression, fatigue, muscle weakness, flaccid paralysis. GI: Anorexia, nausea, vomiting, weight loss, dry mouth, thirst, diarrhea. Hematologic: Bone marrow depression with agranulocytosis, hemolytic anemia, aplastic anemia, leukopenia, pancytopenia. Metabolic: Increased excretion of calcium, potassium, magnesium, and sodium, metabolic acidosis, hyperglycemia, hyperuricemia. Ocular: transient myopia. Urogenital: Glycosuria, urinary frequency, polyuria, dysuria, hematuria, crystalluria. Other: Exacerbation of gout, hepatic dysfunction, Stevens-Johnson syndrome.

Diagnostic Test Interference

Monitor for false-positive urinary protein determinations; falsely high values for urine urobilinogen; depressed iodine uptake values (exception: hypothyroidism).

Interactions

Drug: Renal excretion of amphetamines, ephedrine, flecainide, quinidine, procainamide, tricyclic antidepressants may be decreased, thereby enhancing or prolonging their effects. Renal excretion of lithium is increased. Excretion of phenobarbital may be increased. Amphotericin B and corticosteroids may accelerate potassium loss. digitalis glycosides may predispose persons with hypokalemia to digitalis toxicity; puts patients on high doses of salicylates at high risk for salicylate toxicity.

Pharmacokinetics

Absorption: Well absorbed from GI tract. Onset: 1 h regular release; 2 h sustained release; 2 min IV. Peak: 2–4 h reg; 8–18 h sustained; 15 min IV. Duration: 8–12 h reg; 18–24 h sustained; 4–5 h IV. Distribution: Distributed throughout body, concentrating in RBCs, plasma, and kidneys; crosses placenta. Elimination: Primarily in urine. Half-Life: 2.4–5.8 h.

Nursing Implications

Assessment & Drug Effects

Establish baseline weight before initial therapy and weigh daily thereafter when used to treat edema.
Monitor for S&S of: mild to severe metabolic acidosis; potassium loss which is greatest early in therapy (see hypokalemia in Appendix F).
Monitor I&O especially when used with other diuretics.
Lab tests: Blood pH, blood gases, urinalysis, CBC, and serum electrolytes (initially and periodically during prolonged therapy or concomitant therapy with other diuretics or digitalis).

Patient & Family Education

Maintain adequate fluid intake (1.5–2.5 L/24 h; 1 liter is approximately equal to 1 quart) to reduce risk of kidney stones.
Report any of the following: numbness, tingling, burning, drowsiness, and visual problems, sore throat or mouth, unusual bleeding, fever, skin or renal problems.
Eat potassium-rich diet and take potassium supplement when taking this drug in high doses or for prolonged periods.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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