Acemox

FDA-Approved Uses:

• Glaucoma: Chronic open-angle, secondary, and preoperative acute angle-closure.
• Edema: Associated with congestive heart failure or drug-induced causes.
• Seizure Disorders: Adjunctive treatment in centrencephalic epilepsies, including absence and myoclonic seizures.
• Acute Mountain Sickness (AMS): For prevention and treatment.
• Urinary Alkalinization: To enhance renal excretion of certain drugs/toxins.

Clinically Accepted Off-Label Uses:

• Idiopathic intracranial hypertension (pseudotumor cerebri).
• Periodic paralysis (hypokalemic and hyperkalemic forms).
• Central sleep apnea.
• Ménière’s disease.
• Prevention of contrast-induced nephropathy and methotrexate toxicity.
• Normal pressure hydrocephalus.
• Hemiplegic migraine.

Adults:

• Glaucoma: 250–1000 mg/day PO in divided doses every 6–12 hours. For acute cases, IV 500 mg followed by 125–250 mg PO every 4 hours.
• Edema: 250–375 mg PO once daily or every other day.
• Epilepsy: Start with 250 mg PO once or twice daily; may increase to a maximum of 1000 mg/day in divided doses.
• Acute Mountain Sickness: 125–250 mg PO every 12 hours, beginning 1–2 days before ascent and continuing during exposure.

Pediatrics (>12 years):

• Epilepsy/AMS: 8–30 mg/kg/day divided every 8–12 hours. Use with caution.

Elderly:

• Use lowest effective dose. Start at 125–250 mg PO once or twice daily, titrate based on tolerance and effect.

Renal Impairment:

• CrCl >50 mL/min: Usual dosing.
• CrCl 10–50 mL/min: Extend dosing interval (e.g., every 12 hours).
• CrCl <10 mL/min: Contraindicated.

Hepatic Impairment:

• Avoid in severe liver dysfunction or cirrhosis due to risk of hepatic encephalopathy.

IV Use:

• Reconstitute 500 mg vial with sterile water (minimum 5 mL). Administer over 3–5 minutes. Refrigerate after reconstitution and use within 12 hours.

Acetazolamide inhibits carbonic anhydrase, an enzyme that catalyzes the reversible hydration of carbon dioxide. This leads to decreased bicarbonate reabsorption in the proximal renal tubule, resulting in diuresis and metabolic acidosis. In the eye, it reduces aqueous humor formation, lowering intraocular pressure. In the CNS, acidosis may reduce seizure activity. In altitude sickness, induced acidosis enhances ventilation and improves oxygenation.

• Absorption: Rapid and nearly complete after oral administration.
• Protein Binding: 70–90%.
• Metabolism: Not significantly metabolized; remains as active parent compound.
• Half-life: 2–4 hours (therapeutic); longer in red blood cells (up to 50 hours).
• Excretion: ~90% excreted unchanged in urine via tubular secretion and filtration.

• Pregnancy: Category C. Animal studies show teratogenicity at high doses. Use only when potential benefits justify the risks.
• Lactation: Excreted in small amounts in breast milk. Generally considered safe at therapeutic doses, but caution is advised.

• Primary Class: Carbonic Anhydrase Inhibitor.
• Subclass: Sulfonamide derivative; non-bacteriostatic diuretic and ocular agent.

• Known hypersensitivity to acetazolamide or sulfonamides.
• Severe renal dysfunction (CrCl <10 mL/min).
• Severe hepatic impairment or cirrhosis.
• Adrenal insufficiency.
• Marked electrolyte imbalance (e.g., hyponatremia, hypokalemia).
• Hyperchloremic acidosis.
• Long-term use in acute angle-closure glaucoma.

• Metabolic Acidosis: Monitor bicarbonate and electrolytes. Risk increased in renal impairment and elderly.
• Severe Skin Reactions: Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) may occur.
• Hematologic Abnormalities: Risk of aplastic anemia, agranulocytosis—monitor CBC.
• CNS Effects: May cause drowsiness, confusion, and paresthesia—caution with activities requiring alertness.
• Sulfonamide Cross-Reactivity: Potential in sulfa-allergic patients.
• Aspirin Interaction: High-dose aspirin may increase risk of severe acidosis.

Common:

• Neurologic: Paresthesia, dizziness, drowsiness, fatigue.
• GI: Anorexia, nausea, vomiting, diarrhea, altered taste.
• Renal/Metabolic: Polyuria, hypokalemia, hyponatremia, metabolic acidosis, nephrolithiasis.
• ENT: Tinnitus.

Serious/Rare:

• Hematologic: Aplastic anemia, agranulocytosis, thrombocytopenia.
• Dermatologic: Stevens–Johnson syndrome, TEN, rash.
• Hepatic: Hepatic encephalopathy.
• Respiratory/Ocular: Non-cardiogenic pulmonary edema, choroidal effusion.

• Salicylates (e.g., aspirin): Increased risk of acidosis and toxicity.
• Lithium: Enhanced excretion—reduced therapeutic levels.
• Phenytoin/Primidone: May alter plasma levels; monitor for osteomalacia.
• Quinidine, Amphetamines: Reduced clearance—enhanced CNS effects.
• Cyclosporine: Possible increased serum concentrations.
• Methenamine: Reduced antimicrobial efficacy due to alkalinization of urine.
• Sodium Bicarbonate: Risk of nephrolithiasis due to increased urine alkalinity.

• Updated warnings include risks of choroidal effusion and non-cardiogenic pulmonary edema.
• Supported for use in pregnancy (after 20 weeks) for idiopathic intracranial hypertension.
• Maintained on WHO Essential Medicines List as of recent revisions.

• Oral Tablets/Capsules: Store at 20–25°C (68–77°F), protect from moisture and light.
• IV Powder: Store unreconstituted at room temperature. After reconstitution, refrigerate (2–8°C), and use within 12 hours.
• Do not freeze. Shake reconstituted solution gently before use. Inspect for particulate matter and discoloration prior to administration.