Acetazolamide Extended-release

Acetazolamide is a potent carbonic anhydrase inhibitor used to treat glaucoma, altitude sickness, and certain types of seizures. It works by reducing fluid pressure and adjusting electrolyte balance in the body.

The dosage of acetazolamide varies significantly based on the condition being treated. Your healthcare provider will determine the most appropriate dose for you.

• Glaucoma (Open-Angle): The standard dose is 250 mg taken one to four times daily. Doses in excess of 1,000 mg per day generally do not produce increased effect.
• Acute Mountain Sickness: The recommended dose is 500 mg to 1,000 mg daily, in divided doses. For prevention, it is best to start the medication 24 to 48 hours before reaching high altitude and continue for at least 48 hours while at the highest altitude.
• Edema in Heart Failure: The initial dose is usually 250 mg to 375 mg once daily in the morning. Note that acetazolamide works best for edema when given on alternate days or for two consecutive days followed by a day of rest.
• Epilepsy: The suggested total daily dose is 8 mg to 30 mg per kg of body weight in divided doses. The typical range is 375 mg to 1,000 mg daily.

Acetazolamide is used in children, but the dosage must be strictly calculated by a pediatrician based on the child's weight.

• Glaucoma: 8 mg to 30 mg/kg/day in divided doses every 6 to 8 hours.
• Epilepsy: similar weight-based dosing is used, typically starting at a lower range and titrating upward based on clinical response.
• Safety Note: Use in children requires frequent monitoring of electrolytes and growth parameters.

Renal Impairment

Because acetazolamide is cleared entirely by the kidneys, patients with reduced kidney function require lower doses. If the Glomerular Filtration Rate (GFR) is between 10-50 mL/min, the dosing interval is typically extended to every 12 hours. If the GFR is less than 10 mL/min, the medication is generally avoided.

Hepatic Impairment

Acetazolamide should be used with extreme caution in patients with liver disease. It can increase the risk of hepatic encephalopathy (brain dysfunction due to liver failure) because it reduces the clearance of ammonia.

Elderly Patients

Older adults often have decreased renal function and may be more sensitive to the electrolyte-depleting effects of the drug. Healthcare providers usually start at the lower end of the dosing range and monitor kidney function closely.

• Consistency: Take the medication at the same time each day to maintain steady levels in your blood.
• Food: You may take acetazolamide with or without food. If it causes stomach upset, taking it with a meal or milk may help.
• Extended-Release: If you are taking the Sequels (capsules), swallow them whole. Do not crush, chew, or open the capsules, as this destroys the slow-release mechanism.
• Hydration: Unless your doctor tells you otherwise, drink plenty of fluids to prevent dehydration and kidney stones.
• Storage: Store at room temperature (68°F to 77°F) away from moisture and heat.

If you miss a dose, take it as soon as you remember. However, if it is almost time for your next dose, skip the missed dose and return to your regular schedule. Do not double the dose to catch up.

Signs of overdose may include extreme drowsiness, tingling sensations (paresthesia), nausea, dizziness, and signs of electrolyte imbalance such as muscle weakness or confusion. If an overdose is suspected, contact a poison control center or seek emergency medical attention immediately. Treatment is generally supportive, focusing on restoring electrolyte and fluid balance.

> Important: Follow your healthcare provider's dosing instructions exactly. Do not adjust your dose or stop the medication without medical guidance, as this could lead to a rebound increase in eye pressure or seizure activity.

Acetazolamide is generally well-tolerated, but its unique mechanism of action leads to several predictable side effects. The most frequently reported side effect is paresthesia, which patients often describe as a 'pins and needles' tingling sensation in the fingers, toes, and sometimes around the mouth. This is due to the drug's effect on the nerves and electrolyte balance.

Another very common effect is polyuria (increased urination). Because the drug acts as a mild diuretic, you will likely find yourself needing to use the bathroom more frequently, especially during the first few days of treatment. Additionally, many patients report a distortion of taste (dysgeusia), specifically when consuming carbonated beverages. Sodas and beer may taste 'flat' or metallic because the drug inhibits the carbonic anhydrase enzyme in the taste buds, which is required to perceive the 'sting' of carbonation.

• Gastrointestinal Issues: Nausea, vomiting, diarrhea, and loss of appetite (anorexia) are common as the body adjusts to the medication.

Acetazolamide is a powerful medication that affects the entire body's acid-base balance. It is vital to understand that while it is effective, it requires careful medical supervision. Patients with a known allergy to sulfonamides (sulfa drugs) should be extremely cautious, as there is a risk of cross-reactivity. If you have ever had a severe reaction to a sulfa antibiotic, you must inform your doctor before starting acetazolamide.

No FDA black box warnings for Acetazolamide. However, the FDA does emphasize the risk of severe sulfonamide-type reactions, including Stevens-Johnson Syndrome.

• Allergic Reactions / Anaphylaxis Risk: Severe, sometimes fatal, reactions have occurred with sulfonamide derivatives. These can occur regardless of the route of administration. At the first sign of a skin rash or any sign of hypersensitivity, the medication must be discontinued.

There are certain medications that should never be used alongside acetazolamide due to the risk of severe toxicity:

• High-Dose Aspirin (Salicylates): This is a critical interaction. Acetazolamide can cause aspirin to accumulate to toxic levels in the brain, while aspirin can increase the blood levels of acetazolamide. This 'double-hit' can lead to severe metabolic acidosis, coma, and death. Even low-dose aspirin requires close monitoring.
• Methenamine: Acetazolamide makes the urine more alkaline. Methenamine requires acidic urine to work; therefore, acetazolamide renders methenamine ineffective for treating urinary tract infections.

• Lithium: Acetazolamide increases the excretion of lithium by the kidneys, which can significantly lower lithium levels in the blood and reduce its effectiveness in treating bipolar disorder.

Acetazolamide must NEVER be used in the following circumstances:

1. 1Depleted Sodium or Potassium Levels: If a patient already has low blood levels of sodium (hyponatremia) or potassium (hypokalemia), acetazolamide will dangerously worsen these imbalances, potentially leading to cardiac arrest or severe muscle paralysis.
2. 2Marked Kidney or Liver Disease: In severe renal failure, the drug cannot be excreted and will build up to toxic levels. In severe liver disease, the drug's effect on ammonia clearance can trigger a hepatic coma.
3. 3Adrenal Gland Failure (Addison's Disease): Patients with adrenal insufficiency cannot properly manage the electrolyte shifts caused by this medication.
4. 4

Acetazolamide is classified as FDA Pregnancy Category C. This means that animal studies have shown an adverse effect on the fetus (specifically limb defects in rodents), but there are no adequate and well-controlled studies in humans. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is generally avoided during the first trimester when organ development is most critical. If you are planning a pregnancy or become pregnant while taking this drug, notify your doctor immediately.

Acetazolamide is excreted into human breast milk in small amounts. While the levels are generally considered low, there is a theoretical risk of metabolic effects on the nursing infant. The American Academy of Pediatrics considers it usually compatible with breastfeeding, but the infant should be monitored for adequate weight gain and any signs of lethargy or diarrhea. Always consult your pediatrician before breastfeeding while on this medication.

Acetazolamide is approved for use in children for the treatment of glaucoma and epilepsy. However, long-term use in children can lead to chronic metabolic acidosis, which has been associated with

Acetazolamide is a potent inhibitor of the enzyme carbonic anhydrase (CA). This enzyme is a zinc-metalloprotein that catalyzes the reversible reaction involving the hydration of carbon dioxide and the dehydration of carbonic acid. By binding to the zinc atom at the active site of the enzyme, acetazolamide prevents this reaction.

In the proximal tubule of the kidney, this inhibition prevents the reabsorption of bicarbonate (HCO3-). As bicarbonate stays in the urine, it carries sodium and water with it, leading to diuresis. In the ciliary body of the eye, the inhibition of CA reduces the secretion of aqueous humor by approximately 50% to 60%. In the central nervous system, it slows the rate of cerebrospinal fluid production and increases the CO2 tension in the brain, which raises the seizure threshold.

• Onset of Action: For immediate-release tablets, the onset of the pressure-lowering effect in the eye occurs within 1 to 1.5 hours. For the diuretic effect, it begins within 2 hours.